1. Introduction

Drug misuse is a significant global issue. Statistics indicate that in 2021, approximately 5.8% of individuals aged 15–64 had engaged in drug use within the preceding 12 months. This number increased from 240 million in 2011 to 296 million in 2021, affecting health, particularly mental well-being and safety. Furthermore, stigma and discrimination often hinder individuals with drug-related challenges from seeking help, with less than 20% receiving treatment, and access to treatment varies greatly [1].

The substance use disorder spectrum includes both people who use one particular drug and individuals who use and/or abuse more than one, that is, “polysubstance users”. Polysubstance use disorders are more difficult to treat than single SUDs and are associated with more serious substance use, mental health, and physical health outcomes [2]. People with wide-ranging polysubstance use are more likely to experience additional clinical complexities than single substance users, including psychosis [2].

1.1. Psychoactive Substances and Addiction

According to the DSM substance use disorder definition, a “substance” has the main characteristic of activating the brain’s reward system, leading people to neglect normal activities in favor of taking the said substance [3]. This category, therefore, includes such substances as alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants (including amphetamine-type substances, cocaine, and other stimulants), and tobacco.

For the purpose of this review, we are taking into consideration only the substances that are culturally and most commonly referred to as “drugs”, which are natural or chemical substances known to have significant effects on human consciousness, decision-making processes, quality of life, as well as craving, tolerance, hazardous use, social and interpersonal problems, physical and psychological problems. In this perspective, the term “drugs” includes cannabis, hallucinogens (MDMA), opioids (heroin), hypnotics, and stimulants (cocaine and amphetamines).

These substances can also lead to addiction, especially in younger people. It was proved that those who start smoking, drinking, and taking drugs before the age of 18 are more likely to develop addictive behaviors toward these and other substances [4].

Marijuana is among the most often used illegal psychotropic substances internationally. According to the World Drug Report 2023, led by the United Nations Office on Drugs and Crime, cannabis continues to be the most used drug, with an estimated 219 million users (4.3 percent of the global adult population) in 2021. According to current trends, there is a noticeable increase in both the use of marijuana and hospitalizations linked to marijuana, particularly among young people [1].

Hallucinogens can be divided into three groups: classical hallucinogens, which include substances like D-lysergic acid diethylamide (LSD), psilocybin, mescaline, DMT, and 251-NBOMe; dissociative hallucinogens, such as Phencyclidine (PCP), ketamine, dextromethorphan, and Salvia divinorum; other hallucinogens, such as MDMA, ibogaine, and salvia [5]. These substances are predominantly used for recreational purposes. In fact, data from 2020 indicates that 7.5% of adolescents have used hallucinogens at least once in their lives [6].

Opioids are used both medically and recreationally. In 2021, an estimated 60 million individuals engaged in non-medical opioid use, with 31.5 million using opiates, primarily heroin. Additionally, opioids continue to be the leading cause of fatal overdoses, accounting for nearly 70% of the 128,000 deaths attributed to drug use disorders in 2019 [1]. In Europe, heroin is the substance most closely related to crime. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), in its annual report based on information provided by the EU law enforcement agencies, points out that five percent of seizures involve heroin [7].

Stimulants such as cocaine are powerfully addictive stimulant drugs derived from the leaves of the coca plant exported from South America [8]. In 2020, 0.4% of the global population aged 15–64 used cocaine. The highest prevalence was in North America (2.5%), Oceania (1.9%), and Western and Central Europe (1.5%). The U.S. had the most users (6.5 million), but Colombia had the highest prevalence rate (3.4%) [9].

1.2. Gender Differences

Although substance use disorder is most frequently reported by males, evidence can be found that drug abuse is a widespread issue involving both men and women, with some peculiar differences [10]. Previous research indicated a notable gender disparity in SUDs, with a higher prevalence observed among men. However, recent studies suggest that this gender gap has significantly narrowed. Interestingly, women tend to escalate their drug consumption more rapidly than men once they initiate use, leading to more pronounced negative health and social consequences [11]. According to the World Drug Report 2023, in 2021, the majority of women were found to use amphetamine-type stimulants (45% of users) and engage in non-medical use of pharmaceuticals (with 45–49% of users being women), whereas men comprised the highest percentage of users in opiates (75%) and cocaine (73%) [1].

1.3. Age Differences

The use of cannabis among 15–16-year-olds varies by region, from less than 3 percent in Asia to over 17 percent in Oceania, but in most regions, the proportion of adolescents using the drug is higher than in the general population aged 15–64 [1].

Younger patients were more likely to report using cocaine and cannabis, violating lockdown rules, experiencing deteriorated family relationships, and facing reduced incomes. In contrast, older patients more frequently reported maintaining abstinence [12].

1.4. Comorbidity with Psychiatric Symptoms

SUDs frequently co-occur with other mental health conditions, especially among polysubstance users. Comorbidities observed during treatment are varied, with mood, anxiety, eating, and post-traumatic stress disorders (PTSDs) being the most common. Additionally, there is a notable prevalence of positive psychotic symptoms and schizophrenia. The connection between mental health and SUDs works both ways, with various mental health symptoms being linked to the use of different clusters of substances to achieve desired effects, such as intoxication, energy, or relief from distress [2].

Psychiatric symptoms and/or psychopathological behaviors are not only related to the development of a SUD; in fact, authors have found significant correlations between some psychiatric symptoms and various phases of drug addiction, e.g., abstinence [13] or craving [14].

1.5. Aim of this Study

This review aims to analyze the main factors contributing to the development and maintenance of SUD and its co-occurring psychiatric symptoms. We believe that, especially in cases of dual diagnosis, it is important to understand what factors can lead to a concerning phenomenon such as drug abuse. The purpose is multiple: on the one hand, we aim to provide scientific data to help project and implement effective prevention plans; on the other hand, we aim to understand what role psychiatric symptoms play in a substance abuse disorder. That is, whether the presence of psychiatric symptoms can be a cause of the disorder or whether it is a direct consequence of it and, in either case, to what extent it is possible to understand which case one is facing. In doing so, we will first analyze biological, psychological, and social factors that contribute to developing a SUD; then, we will study both progression patterns and characteristics that represent potential risk or protection factors in relation to this disorder; last, attention will be given to the interaction between the various factors emerged in the previous paragraphs to give a better overview on the prodromal stages of SUD.

2. Materials and Methods

This review, while not a systematic review in the traditional sense, has implemented systematic search methods to ensure maximum transparency and rigor in the selection of included papers. The systematic search was conducted in January 2024, using Primo VE Discovery as a tool for aggregating results across several databases: PubMed; PubMed Central; Health & Medical Collection; ScienceDirect Freedom Collection; Wiley Online Library. Our selection of articles was obtained using four different search strings:

1. (((substance use disorder) OR (addiction)) AND (psychiatric symptoms)) AND ((neurobiological factors) OR (genetic influences) OR (pharmacological factors));

2. (((substance use disorder) OR (addiction)) AND (psychiatric symptoms)) AND ((mental health) OR (psychological factors) OR (cognitive processes));

3. (((substance use disorder) OR (addiction)) AND (psychiatric symptoms)) AND ((family dynamics) OR (peer influence) Or (cultural norms));

4. (((substance use disorder) OR (addiction)) AND (development) OR (progression patterns) OR (risk and protective factors)).

The choice of the search keywords was related to the main topics of our paper, that is to say, how biological, psychological, and social factors singularly contribute to the development and maintenance of substance use disorder (SUD), as well as how they interact with each other in individuals who show such disease; moreover, we intend to analyze which individual and social factors prevent or increase the possibility of developing a SUD and its co-occurring psychiatric symptoms.

This review includes the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram [15] to describe the research methodology and selection of articles included.

While this review does not include certain features typically associated with systematic reviews, such as a meta-analysis or a risk of bias assessment, the systematic search methods employed ensure a comprehensive and transparent approach to the identification and selection of relevant studies. This approach enhances the reliability and validity of the findings presented in this review. It is important to note that the absence of these features does not undermine the value of the review but rather reflects the specific aims and scope of this particular piece of research.

Eligibility Criteria

We included articles that met the following criteria:

• All studies and reviews were published in indexed journals such as PubMed, PubMed Central, Health & Medical Collection, ScienceDirect Freedom Collection 2021, Wiley Online Library;

• Studies that included the keywords used and/or related to their topic;

• Studies that were published from the year 2022 on. The year 2022 was selected to provide sources as recent as possible that could include, but were not exclusively focused on, elements related to the COVID-19 pandemic lapse.

3. Results

Characteristics of Included Studies

This literature review examines sixty full-text articles to analyze the biological, psychological, and social factors influencing the development and persistence of SUD and its concurrent psychiatric symptoms (see flow diagram, Figure 1). Articles were selected based on their relevance to understanding the interaction among these factors, as well as identifying risk and protective factors useful for designing prevention strategies and treatment recommendations. The reviewed studies conducted between 2022 and 2024 were diverse in terms of geographic location, including Italy, India, Australia, Norway, Spain, Switzerland, and the United States. Methodologies employed varied, encompassing cross-sectional, longitudinal, and randomized controlled trial designs. Collectively, these studies offer comprehensive insights into contemporary SUD manifestations, their biological, psychological, and social etiology, the interplay among these factors, and the key determinants influencing treatment outcomes.

Figure 1. PRISMA 2020 flow diagram for new systematic reviews, which included searches of databases, registers, and other sources [15] generated using Haddaway and colleagues’ online generator [16].

4. Biological Factors

Throughout the years, several studies have been interested in investigating the biological factors that might underlie the development and maintenance of addictions to substances.

While a causal link between the presence of certain biological factors and the development of addiction has not yet been established with certainty, the results of some studies are interesting and promising in this regard, paving the way for subsequent insights that could deeply change the treatment perspectives of addiction and SUD [17].

A significant implication of neurotransmitter systems in substance addiction has been observed. A particularly relevant role seems to be played by the endocannabinoid and dopaminergic systems: substances bind to these systems and/or alter their neurotransmitter actions, leading to changes in a specific brain area activity. In these areas, there is a massive presence of receptors belonging to these two systems, such as the prefrontal cortex (PFC), the inferior cingulate gyrus (ICG) and anterior cingulate gyrus (ACG), the striatum, the thalamus, the nucleus accumbens (NAcc), the Ventral Tegmental Area (VTA) and the amygdala [17]. Activation of these brain areas is responsible for the feeling of gratification experienced by individuals with substance addictions, as they are brain regions responsible for regulating emotions, decision-making processes, and impulse control [17].

In the following sections, we will analyze which and how biological factors intervene for each class of drugs.

4.1. Cannabis Addiction

Genetic and Neurobiological Factors

Genetic variants of several elements of the endocannabinoid system have been suggested as possible risk factors for cannabis dependence [17]. Specifically, polymorphism of specific SNPs of the CNR1 gene, G allele, was associated with increased withdrawal and craving after brief cannabis abstinence and more significant responses in several brain areas, such as the OFC, the ICG, and the ACG [17]. In a study by Schacht et al., it was found that cannabis users carrying the G allele have a reduced hippocampal volume, and this could be due to the interaction of cannabis with the CB1 receptor altered by the polymorphism, which would act in a way that goes to alter the volume of the hippocampus [18]. Most recently, the CNR2 gene has been linked to an elevated risk of developing schizophrenia in patients with CUD (Cannabis Use Disorder) [19].

Studies have highlighted how alleles A and C are also strongly involved in cannabis addiction, as these alleles have been observed to correlate with increased activity and reactivity of specific brain areas closely related to gratification [17].

A recent study showed structural brain alterations in cannabis-dependent patients that appeared to be significantly associated with regional differences in the expression of MAGL, an enzyme responsible for the degradation of endocannabinoids [20].

Bhattacharyya et al. conducted a research study to evaluate the effect of THC on anxiety and amygdala response, from which they found that anxiety-induced THC intake modulated amygdala activation and increased CB1 cannabinoid receptor availability [21].

4.2. Opioid Addiction

Genetic and Neurobiological Factors

There is a lack of information about the polymorphism of the endocannabinoid system related to opioid addiction.

Similar to cannabis addiction, the involvement of specific genes and alleles, such as the C allele, can also be traced to opioid addiction. One study evaluated the association between CNR1 and the development of major depression and/or suicidal behaviors in opioid-dependent outpatients undergoing skilled methadone treatment. This work found that the C allele of CNR1 was closely correlated with a lower prevalence of lifelong major depression but not with suicidal behaviors [17]. There are numerous studies of the biological effects of opioids carried out using the animal model. In a significant study by Viganò et al., rats were chronically treated with morphine and CB1R binding, and levels of eCBs (endocannabinoids) were assessed. Morphine-tolerant rats showed reduced CB1R binding in the cerebellum and hippocampus and reduced CB1R functions in the NAcc [22].

4.3. Stimulant Addiction

Cocaine is a substance of abuse that destroys mesolimbic dopaminergic neurons, inhibiting dopamine uptake and leading to compulsive behavior and relapse.

Methamphetamine, on the other hand, induces specific damage to the dopaminergic neurotransmitter system and is associated with cell death. A single intake of methamphetamine alters concentrations of certain endocannabinoids in the striatum of adult male mice, suggesting that the endocannabinoid system may be involved in brain responses to these drugs [17].

Alterations at central and peripheral levels have been found in individuals exposed to psychostimulants such as amphetamines and cocaine [17]. Specific polymorphisms of the CNR1 gene have been associated with the development of stimulant dependence. Furthermore, numerous changes in the targets of the endocannabinoid system have been traced mainly from cocaine studies, revealing the importance of this system in regulating different aspects of stimulant addiction, such as gratification, motivation, withdrawal, or relapse [17].

Genetic and Neurobiological Factors

Several studies highlight the functional importance of the endocannabinoid system in regulating the actions produced by psychostimulant substances, such as cocaine and amphetamine.

To this date, it has been confirmed that some genetic variant contributes to the vulnerability to relapse of stimulant-dependent individuals. Indeed, it has been found that two independent variants of CNR1, the G allele genotype and the T/T genotype, had a significant effect on the risk of cocaine addiction in Euro-Americans as well as in African-Americans with these genotypes [23].

The importance of the dopaminergic system should also not be underestimated. Indeed, D1 receptors are crucial in mediating the action of cocaine, the search for the substance leading to self-administration and cocaine-related effects in gene expression in the striatum [24]. D2 receptor levels, on the other hand, predict the “liking” effects of psychostimulants such as methylphenidate. Chronic cocaine use or abuse attenuates the availability of D2/D3 receptors in the striatum and abrupt dopaminergic responses to the administration of psychostimulants [24].

4.4. Hallucinogens Addiction

Genetic and Neurobiological Factors

Several studies have evaluated the effects of dissociative drugs on the cannabis and endogenous systems. Subchronic administration of ketamine in mice increased endocannabinoid concentrations in the CPU, amygdala, and hippocampus [25].

Although limited information is currently available on the subject, most authors support the potential usefulness of identifying changes in cannabinoid receptors, ligands, or enzymes as biomarkers to improve the diagnostic classification of patients with SUD and increase the success of their drug treatment [17].

4.5. Pharmacology and Treatment Insights on SUD

Despite extensive investigations, the field of pharmacotherapy for SUDs remains relatively uncharted. While significant progress has been made in understanding the neurobiology and behavioral aspects of addiction, the development of targeted medications has proven challenging. So far, there is no drug treatment approved by the FDA (Food and Drug Administration) or EMA (European Medicines Agency) for most substance use disorders, except for AUD (Alcohol Use Disorder), NUD (Nicotine Use Disorder), and OUD (Opioid Use Disorder) [26].

Since GABAergic system dysfunction is associated with substance use, a number of studies have also been conducted on the efficacy of antiepileptic drugs [27] and combination therapies [28]. Another treatment strategy is to target the endophenotypes associated with SUDs. For example, using cognitive enhancers to improve decision-making, planning, or impulse control may be a useful strategy [29]. Several pharmacological studies are currently underway [28].

In addition to new pharmacological perspectives, alternative therapies, such as psychotherapy (including drug-supported), mindfulness-based interventions (MBI), and the use of virtual reality (VR) techniques can be considered [28]. Table 1 presents an overview of biological factors associated with various types of substance addiction, including cannabis, opioids, stimulants, and hallucinogens.

Table 1. Table showing biological factors associated with various types of substance addiction, including cannabis, opioids, stimulants, and hallucinogens. This table summarizes genetic variants, structural brain alterations, and involvement of neurotransmitter systems, highlighting key factors influencing addiction development and maintenance.

5. Psychological Factors

5.1. Complex Entanglement: Substance Use Disorder; Personality; and Psychopathology

Substance use disorder can be viewed as a complex intertwining of behavior, personality, and psychopathology. The co-occurrence of substance use and psychopathology (dual diagnosis) can be explained by shared risk factors such as socioeconomic status and personality traits [30,31,32]. Many people with SUDs show psychiatric comorbidity, personality, mood, and anxiety disorders [12,30,31,32,33], especially in cases of poly-drug use, where eating disorders, psychotic symptoms, schizophrenia [2], and PTSD (Post-Traumatic Stress Disorder) [4,34] can also be found; in some cases, the dual diagnosis of SUD and ASD (Autism Spectrum Disorder) is also found [35].

According to several surveys, approximately 10–20% of the population suffers from an addiction-related problem [31], and half of the people with a substance use disorder experience other mental disorders during their lifetime, and vice versa [36], as the relationship between the two would appear to be bidirectional [2]. A positive association was found between anxiety, depression, and craving intensity. In addition, time of abstinence could influence the association between craving and psychiatric symptoms [13].

5.2. Mental Health Conditions

5.2.1. Personality Factors and Addiction

Temperament and personality traits represent crucial factors that contribute to the development and persistence of addiction-related behaviors [31,32]. Among these traits, disinhibition and lack of self-control, which are intended to be the ability to regulate one’s behavior, emotions, and cognition, represent key elements. Self-control is considered a transdiagnostic dimension; its absence can manifest in both externalized behaviors, as in substance-related disorders and Attention Deficit Hyperactivity Disorder (ADHD), and internalizing behaviors, as in mood or anxiety disorders [31]. In addition, high levels of behavioral activation (BAS) and low levels of self-control (EC) have been associated with Cluster B of personality disorders, while high levels of behavioral inhibition (BIS) and low levels of self-control (EC) have been linked to Cluster C. As for Cluster A, a mixed pattern of BAS and BIS has been observed [31,32].

The development of clinical symptoms, especially anxiety and depression, and the manifestation of personality disorders both correlated with low levels of self-control (effortful control—EC) and high levels of behavioral inhibition (BIS) in people with SUD [31,32]. Hence, there is a greater inclination to neuroticism, which is considered an additional personality trait that represents a vulnerability factor for the development and persistence of SUD [30].

Several studies indicate that low self-esteem is frequently observed in patients with SUD. However, in contrast to this perspective, other studies that have examined the relationship between SUD and self-esteem have found high levels of self-esteem [37].

In the following section, we will briefly analyze the psychological factors that are most found in comorbidity with SUDs.

5.2.2. Anxiety and Addiction

Anxiety disorders are frequently found in patients diagnosed with substance use disorder (SUD) [31,36], and research also shows a strong correlation with craving intensity [13]. Anxiety symptoms reveal a strong association with substance use and addiction severity [30]. In addition, stress has been observed to have a positive correlation with craving intensity in opiate and methamphetamine use.

5.2.3. Mood Disorders and Addiction

Mood disorders are commonly found in comorbidity both with SUD [31,36] and craving intensity [13]. In particular, depression was proved to have a positive correlation with craving intensity for heroin in patients receiving methadone maintenance treatment [13]. Interestingly, although substance use may impair brain function and cause depressive or anxiety symptoms, people may use substances more frequently as a form of “self-medication” to manage such symptoms [30].

5.2.4. ADHD and SUD

Attention-deficit hyperactivity disorder (ADHD) is found in around 25% of people with SUD [36]. ADHD is also considered an important risk factor for the development of SUD, as it promotes early use of illicit substance use, thus being an important predictor of the development of substance use disorder [38]. According to some data, the presence of an ADHD disorder would increase an individual’s vulnerability to developing a psychoactive substance abuse disorder by a factor of two [33]. Conversely, addiction exerts a negative impact on the course of ADHD by exacerbating cognitive and memory impairment. The course of SUD is found to be more severe in patients with comorbidity with ADHD than in those with SUD alone [33].

5.2.5. Traumatic Events, PTSD, and SUD

Post-Traumatic Stress Disorder (PTSD) is frequently found in comorbidity with SUD [2,34], and both disorders tend to occur commonly during adolescence. According to some theories, the experience of traumatic events in adolescence might promote the development of SUD, in turn facilitating the onset of PTSD. Other hypotheses state that the coexistence of the two disorders could result from the adoption of substance use as a coping strategy to mitigate the effects of symptoms associated with PTSD [34].

It appears that some substances are able to influence the immediate experience of PTSD symptoms, predisposing to a subsequent inclination to use such substances [34]. A history of trauma is a significant risk factor for violent and suicidal behavior in individuals with SUD. This suggests the need to carefully consider the psychological and trauma context in the assessment and treatment of patients with SUD.

An additional study examined the co-occurrence of Sexual Compulsive Behavior Disorder (CSBD) and tendencies for risky sexual actions among women with SUD [11]. The results indicate that women with SUD manifest more pronounced symptoms of CSBD and show a greater propensity for risky sexual behavior than controls. In this context, it appears that CSBD plays a mediating role in the association between substance use and risky sexual behaviors.

In addition, it was found that addictive behaviors were related to emotional abuse during childhood but were not associated with other types of abuse [11].

5.2.6. SUD and ASD

SUD and Autism Spectrum Disorder (ASD) are often found in comorbidity with each other, resulting in a dual diagnosis; in most of these cases, people use substances as a means to manage high levels of anxiety, stress, and social difficulties, including perceived social rejection [35]. The cause of this phenomenon seems mainly neurobiological, although its interaction with psychological aspects will be explored in depth in another paragraph.

5.2.7. Self-Harm and Suicide Risk in People with SUD

Individuals suffering from chronic pain or mood disorders often find themselves disproportionately prescribed opioid medications. This subgroup faces a greater risk of suicide. Numerous studies have explored the potential connections between suicidal symptoms and SUD. Some findings suggest that a diagnosis of any SUD amplifies the likelihood of suicide, and conversely, an increased suicide risk is associated with SUDs. In-depth research comparing the impact of specific substances has highlighted that opioids, in particular, exhibit a stronger correlation with suicidal ideation and attempts compared to substances like cocaine and cannabis. The intricate interplay between chronic pain, mood disorders, opioid use, and the heightened risk of suicide underscores the complexity of these issues and the need for comprehensive and multifaceted care approaches [39]. For research purposes, it is essential to consider comorbid disorders alongside substance use disorders (SUDs), which may include mood and personality disorders. Additionally, assessing anxiety and depression symptoms is crucial to providing personalized treatments to individuals at risk of suicidal ideation [40]. Table 2 presents a summary of psychological factors related to substance addiction, including complex entanglement with behavior, personality, and psychopathology, as well as specific psychological factors such as anxiety, mood disorders, ADHD, PTSD, ASD, and the risk of self-harm and suicide.

Table 2. Table summarizing psychological factors associated with substance addiction, including complex entanglement with behavior, personality, and psychopathology, as well as specific psychological factors such as anxiety, mood disorders, ADHD, PTSD, ASD, and the risk of self-harm and suicide. References are provided for each factor.

6. Social Factors

SUD is a complex condition that is influenced by a multitude of factors, including social ones. Social factors play a significant role in both the development and maintenance of SUD. Social determinants of health (SDoH) are referred to as the conditions in which individuals are born, grow, live, work, and age [41]. These circumstances are influenced by the distribution of financial resources, power, and assets at global, national, and local scales [41]. In the following paragraph, we will analyze social factors that contribute to the development and maintenance of SUD.

6.1. Childhood

To understand how an addiction can seep into a person’s life, we need to start by examining the context in which the individual grew up, starting right from childhood. The parental style with which the child is raised and the resulting family dynamics play a very important role in both the development of the individual and the development of addiction. Children raised with an authoritarian parenting style characterized by demanding, strict, and firm parents who show little affection, warmth, and involvement will tend to be more likely to use alcohol and other substances. In contrast, an authoritative parenting style, characterized by high demands and responsiveness, has been found to have positive results, decreasing the likelihood of children’s use of alcohol, cigarettes, and cannabis. The neglectful parenting style with low demand and responsiveness is most likely to be associated with substance use; finally, although to a lesser extent, the permissive parenting style, with low demand and high responsiveness, was also found to be related to substance use [42].

In addition, traumas experienced in childhood (physical or emotional abuse, neglect), even occurring only once [43,44], lead to adverse physiological consequences and poor health outcomes, causing, for example, increased cortisol levels that subsequently increase the risk of substance use [42]. This could explain the relationship between the mechanisms involved in coping with trauma and those that lead to substance use, putting stress at the center of the relationship: while milder forms can result in positive behavioral effects, severe or chronic levels can cripple it, so that the individual will try to cope with it by taking substances that can quell perceived stress and anxiety, increasing the likelihood of developing an addiction [44].

6.2. Adolescence

As widely known, adolescence is a crucial period for biological, psychological, and social development, but it is also a sensitive time when one is particularly susceptible to substance use, its negative effects, and subsequent addictions [44,45]. Early encounters with substances increase the likelihood of future problems (physical, behavioral, social, and health) but also raise the risk of addiction if you start before age 18 [44]. Adolescents may start experimenting with substances out of simple curiosity, boredom, rebellion, societal pressure, relationship breakdown, or to improve concentration, physical endurance, learning difficulties, and gain a sense of identity. Students who use them are also the ones who commit more crimes, such as bullying or violent behavior, with insignificant psychological, behavioral, and sociocultural consequences [44].

In this scenario, studies have found that parental support is a protective factor against the onset of SUD: adolescents aged 9 to 18 years with positive parental relationships, characterized by emotional closeness and supervision, are less likely to try alcohol, marijuana, and cigarettes; conversely, lower levels of family functioning increase the likelihood of these behaviors being enacted [46]. This is a very interesting result when compared with peer support, as opposite effects are obtained: peer support is correlated with higher alcohol consumption. Both the subject’s perceived rejection of parents and peers and loneliness are associated with alcohol consumption [4,42,46]. Social support is the most effective tool used to aid in the disorder’s resolution; it encompasses a variety of behaviors ranging from simply being present, listening, and sharing problems to providing concrete help. Offering this support can be family, friends, and professionals, and it is important because addiction requires much more support than physical illness, as it is characterized by withdrawal and severing ties with toxic friendships [47].

The relationship between social conditions and drug use is two-way. In parallel with what has been said so far, SUD adversely affects social behavior, leading the individual to avoid social situations so that he or she has more time to spend on drug taking rather than on rewarding social situations, thus entering a vicious cycle in which the individual begins to take drugs more often, thus increasing his or her isolation. This phenomenon has increased in recent years due to the lockdown, which has forced young people to stay at home for long periods of time. In fact, it has been found that COVID-19 contributed to the increase in overdoses and social isolation [44].

6.3. Adulthood

As they age, individuals with AUD report having had a family characterized by less cohesion and expressiveness and more conflict: these are risk factors for alcohol use, disguised by the individual’s justifications for why they use (e.g., alcohol makes me worry less) [46]. Increasing levels of loneliness, also experienced during COVID-19, are related to increased alcohol use and anxiety [46]. Lack of social support, medical complications, and confrontation with bereavement are features of older age that could contribute to the onset of SUD or AUD [42]. This increases the likelihood of premature mortality, impacting healthy aging and increasing health risks: alcohol consumption impacts higher rates of dementia and vulnerability to negative withdrawal symptoms due to their frailty and the presence of comorbidities [42].

An interesting aspect emerging from research is the incidence of SUDs in young adults aged 18 to 25. Approximately 21% of young adults meet the diagnostic criteria for SUDs, a stark contrast to the 9% prevalence in 12–17-year-olds and 7% in individuals aged 26 and above [48]. These data could be explained by many factors. For instance, difficulties that people aged 18–25 face in successfully adapting to this transitional phase could lead them to turn to substance use as a coping mechanism. Furthermore, there is evidence indicating that early manifestations of delinquency or aggression are correlated with substance use in young adults [48].

6.4. Social Background

The social context in which an individual grows up and lives has a crucial role in the development of certain addictions. One research study found that most addicts ignore the idea of marriage so they can devote their time to addictive behaviors without having responsibility or being criticized by their spouse. More than half of the sample was male and came from urban areas, easily accessible for drug cultivation and dealing, with many security and surveillance problems [47]. Another study found that disorder in the neighborhood, such as the presence of graffiti, noise nuisance, and crime, was associated with alcohol use more prominently in women but not in men, for whom, instead, a risk factor was social cohesion, defined as feelings of attachment to the neighborhood, relationships and solidarity with neighbors, and the neighborhood in general [46]. Table 3 presents a summary of social factors related to substance addiction, including influences from childhood, adolescence, adulthood, and social background, with corresponding references.

Table 3. Table summarizing social factors associated with substance addiction, including influences from childhood, adolescence, adulthood, and social background. Each factor is described along with relevant references.

7. Progression Patterns and Factors of Risk and Protection

Understanding how addictions develop and persist is crucial for adopting the most effective prevention and intervention strategies. This paragraph aims to examine both the patterns of progression in substance use and the related risk and protective factors in order to provide a comprehensive framework for the complexity of this phenomenon.

7.1. Risk and Protection Factors

7.1.1. Impaired Illness Awareness

Impaired illness awareness of addiction to recreational or pharmaceutical substances is an understudied construct that impacts intervention adoption, treatment-seeking behaviors, and retention in treatment [49]. In substance use disorder, the term illness awareness refers to one’s subjective recognition of having a problem with substance use. It also includes one’s acceptance of the need for treatment and the negative consequences that arise from substance use [49].

Individuals with impaired illness awareness in substance use disorder are less likely to utilize clinical services and more likely to drop out of treatment despite the severity of the use. On the other hand, higher levels of illness awareness in substance use disorder are associated with better treatment engagement and adherence and improved clinical outcomes [49].

7.1.2. Transitional Age Youth (TAY)

A narrative review shows a strong connection between mental disorders and SUD in TAY, the span period that encompasses adolescence and emerging adulthood, approximately between 15 and 25 years of age. Initiation of drug use peaks in adolescence, but in many cases, drug use gradually decreases after this period [50]. Most adolescents do not show problematic use patterns, and this spike can be considered experimental drug use [50].

All children entering adolescence are at risk for adverse health outcomes related to alcohol or other drug use. Substance misuse increases markedly from mid to late adolescence [51]. For adolescents, any level of SU is risky and can result in negative developmental outcomes, including disruption of brain development, educational underachievement, behavioral consequences (e.g., driving, sexual behavior), and injury, as well as the potential for inducing or exacerbating mental comorbidities and progression to SUD [6,51]. Furthermore, early-onset substance use is associated with increased psychosocial problems and problematic substance use later in life [52].

7.1.3. Preexisting Mental Disorders

It has been found that preexisting mental disorders represent risk factors for the emergence and progression of SUD [50]. A narrative review highlights a common comorbidity between mental disorders and SUD among adolescents and young adults [50]. According to the authors, the two issues negatively influence each other. A study of juvenile detainees [53] demonstrated that substance use, behavioral disorders, and internalizing disorders predict the development of SUD. This underlines the importance of treating childhood/adolescent disorders to reduce the emergence of secondary SUD [50].

7.1.4. Socioeconomic Position

Emerging evidence shows that low Socioeconomic Position (SEP) is an important determinant of many mental disorders, including substance use disorders [54,55,56]. In a cohort study involving 1.6 million individuals in the Stockholm region [54], alcohol and drug use disorders were more common among individuals with lower levels of education compared to those with higher levels of education, both in males and females.

7.1.5. Physical Activity and Peer Interactions

Peer interactions are often enmeshed within physical activities in adolescence, and physical activity is broadly (positively) related to mental health via psychosocial, behavioral, and physiological mechanisms [52]. Two studies that examined pairs of discordant twins on physical activity found that physical inactivity in adolescence was associated with increased consumption of alcohol, drugs, and smoking in young adulthood [52].

Peer interactions are often linked to physical activities during adolescence. Across adolescence, peer relationships become more important as friends increasingly become a source of social support and influence on developing adaptive and maladaptive behaviors [52]. In the context of substance use disorders, observational studies on adolescents have yielded conflicting results depending on the type of physical activity and substances under examination [52]. Factors such as rejection and loneliness may increase the risk of substance-related issues in adolescence and early adulthood. Social integration may lead to greater access to substances, as well as friendship with deviant peers. Conversely, friendship with peers who do not use substances may serve as a protective factor [52]. This study employed a co-twin control design to explore participation in sports, physical activity, and friendship quality as predictors of substance use. The results indicate that participation in sports and positive friendship quality were associated with the increased likelihood of substance use [52].

In a longitudinal study [57], participants (N = 2880) completed four annual surveys during late adolescence and the transition to young adulthood as part of an ongoing longitudinal study. Results highlight key individual and community-level protective factors that decrease the risk of opioid use [57].

7.1.6. Use Aimed at Increasing Sexual Performance

While long-term use of alcohol, opioids, or sedatives is often associated with impaired sexual function, the use of alcohol, cannabis, cocaine, amphetamines, or hallucinogens may increase sexual arousal in the short term [58]. This may lead to performance-enhancing use.

Several studies have investigated the association between prevalent SUD and hypersexuality. The targeted use of drugs to evoke specific physical and/or psychological effects during sexual activity (e.g., to increase sexual performance or achieve sexual disinhibition) is termed chemsex [58].

7.1.7. Media Representation of Drugs

Media representation about substances and alcohol (TV shows and movies that display people openly using drugs and/or alcohol) has a strong impact on the ideas children and adolescents will have about them. They are also more likely to start to use them and, therefore, develop SUDs [45]. The power of the media should be used to positively influence opinions and beliefs about drugs and alcohol, given its power in teens’ lives.

7.1.8. Correlation between Risk and Protection Factors

Risk factors often exhibit positive correlations with each other and negative associations with protective factors [59]. Essentially, individuals with certain risk factors are more likely to encounter additional risks, while protective factors tend to be less prevalent. Furthermore, the cumulative impact of these factors significantly influences the development or prevention of behavioral health issues. Young people with multiple risk factors face a higher likelihood of experiencing conditions affecting their physical or mental well-being, whereas those with multiple protective factors are at a reduced risk [59].

8. Interactions between Psychological, Social, and Biological Factors

In the previous paragraphs of this article, we analyzed the extent to which individual factors (biological, psychological, and social) contributed to the development and maintenance of substance use disorder. However, these factors rarely have a significant influence if taken individually; it is, therefore, important to acknowledge the co-presence of these factors and pay attention to how they interact with each other in a person’s life.

In this section, we will examine how, collectively, these factors interact with each other in individuals with SUD.

8.1. A Biopsychosocial Model for Understanding Addiction

Substance addiction is a bio-psychosocial phenomenon. Psychosocial factors are multidimensional constructs pertaining to two different domains: psychological, which include factors such as depression, anxiety, distress, self-esteem, and satisfaction; and social (related to socioeconomic status, employment, religion, physical attributes, family, relationship with others, locality). These factors contribute to the development of mental and physical disorders [3]. In fact, drug use is frequently correlated with negative outcomes in people’s lives in various aspects. On the one hand, SUDs can lead to adverse physical, mental, and social consequences, including addiction, substance-induced disorders, neurological complications, cognitive impairment, unemployment, incarceration, and suicidal behavior [2]. On the other hand, stigma and discrimination make it less likely that people who use drugs will receive the help they need. Fewer than 20 percent of people with drug use disorders are in treatment, and access is highly unequal. Out of the approximately 39.5 million individuals globally diagnosed with drug use disorders in 2021, only one in five received treatment [1].

The importance of considering a biopsychosocial model in examining influences on the development of substance dependence disorder was confirmed by a 2020 study conducted at the Department of Health and Environmental Engineering at the Johns Hopkins Bloomberg School of Public Health and the Multidisciplinary Center for Health Equity Research at Texas A&M University [60]. The biopsychosocial model of addiction, in understanding the development and progression of substance use problems, emphasizes biological factors such as genetic predisposition, psychological and cognitive factors such as self-efficacy, outcome expectations, and readiness to change, and social factors such as family, peer, and partner influence. Therefore, understanding the interconnectedness of these factors could be an effective strategy in substance use prevention programs [61].

Substance use disorder involves a variety of neurobiological processes, including the brain reward system. This system, also known as the dopaminergic system, is crucial in sending behavioral responses related to pleasure and gratification. Thus, a key role in understanding how an SUD develops is played by the interaction between social environment, individual functioning, and family history.

8.2. Family History, Role Models, and Psychological Factors

Starting with the family during childhood, young people become involved in multiple activities when they enter school; especially during middle school, peers become increasingly important and are a factor influencing the individual’s development [62]. In adolescence, and more so in the transition to adulthood, romantic relationships become additional agents of socialization and represent, along with the peer group, an element of the reward system [63].

Family members serve as role models for children, as shown in research conducted by the University of Washington and the University of Southern California [64] involving 808 participants of different ethnicities and genders and ages from 10 to 33. The results showed that positive social and family environments create a positive model for future interactions. In contrast, a family history of depression may negatively influence mental health functioning during adulthood: the family environment characterized by chronic stress, conflict, or other forms of dysfunction influences the reward system, increasing sensitivity to rewarding stimuli and leading to greater reliance on substances that provide temporary relief. In addition, if there are substance use behaviors in the family, children may perceive such behaviors as acceptable, and this may trigger an approach to a range of substance-focused social contexts as they grow up. The authors found that some psychological factors, such as the presence of generalized anxiety disorder or panic disorder or the experience of childhood trauma, are related to substance use. Psychological factors such as childhood trauma may modulate social perceptions and adaptation to stressful life contexts, which may promote the approach to substance use [4].

Other social factors, frequently associated with the development of psychopathological symptoms, are also linked to the development of SUD. According to research conducted in Stockholm, a low level of education increases the risk of substance use disorders and self-harm; furthermore, an association between low educational attainment and various mental disorders, such as schizophrenia, depression, anxiety, ADHD, and behavioral disorders, is highlighted [54].

8.3. Neurological Factors, Genetic Predispositions, and Personality Traits

Genetic predisposition can affect the brain’s response to opioids and its ability to regulate the impulse for substance use on the one hand and affect an individual’s vulnerability to developing psychological disorders such as anxiety or depression, which, in turn, are strongly linked to the risk of addiction [35]. For example, some theories suggest that individuals with autism spectrum disorder may possess dopaminergic differences in the fronto-cortical cortex, making them susceptible to repetitive pleasurable sensation seeking, with the risk of easily translating into addictive behaviors. In addition, there appears to be a common dysregulation of the limbic system in individuals with SUD and ASD [35].

In a systematic review exploring the impact of both PTSD and SUDs on uncontrolled craving for substances, it was found that post-traumatic stress disorder was significantly associated with increased levels of craving among patients with alcohol, cannabis, cocaine, tobacco, and other substance use disorders [65]. Some studies have also observed a correlation between the severity of post-traumatic stress disorder symptoms and craving intensity, as substance use is a means of alleviating traumatic symptoms. The underlying mechanisms refer to negative emotional states, and emotional dysregulation plays a role in eliciting craving after traumatic exposure. Psychological, social, and biological factors may interact synergistically in craving and substance use. PTSD symptoms can trigger emotions that, in turn, would increase craving for substances, and similarly, exposure to traumatic environments can act as a trigger for craving.

8.4. Psychological Factors and Treatment Success Expectations

Working on addiction, we must also consider factors such as self-efficacy (confidence in one’s ability to succeed without the substance) and motivation (desire to change one’s behavior), which are positively correlated with treatment success and in direct relation to each other: lower self-efficacy influences motivation to seek positive social supports, and fewer social supports decrease self-efficacy [44].

9. Discussion

The development and maintenance of substance use disorders involve a complex interplay of biological, psychological, and social factors.

In the biological realm, the endocannabinoid and dopaminergic systems, along with genetic variants in CNR1 and CNR2, contribute to specific pathways in cannabis, opioid, and stimulant addiction [17]. Psychological aspects reveal the significance of personality traits, such as disinhibition and low self-esteem, in addiction vulnerability [30]. The coexistence of anxiety, mood disorders, and addiction, coupled with the strong correlation between traumatic events and substance use, further emphasizes the importance of considering psychological dimensions [34]. Social elements, encompassing family background, parental styles, neighborhood characteristics, and peer support, significantly shape addiction patterns, while addiction, in turn, disrupts social behaviors, leading the individual to isolation [44]. The intricate interconnection of these factors underscores the multifaceted nature of addiction and the importance of comprehensive approaches in prevention and treatment strategies.

9.1. Future Research

There are several avenues for future research that could enhance our understanding of SUD and its co-occurring psychiatric symptoms. Firstly, longitudinal studies tracking individuals from adolescence to adulthood could provide valuable insights into the long-term impact of early substance use on mental health outcomes and addiction trajectories. Understanding how factors, such as childhood trauma, parental styles, and peer influences, interact over time to shape substance use behaviors is crucial for developing targeted prevention and intervention strategies. Secondly, investigating the role of genetic influences and neurobiological factors in predisposing individuals to specific types of substance addictions could offer a more nuanced understanding of addiction vulnerability. By exploring the genetic markers associated with different substance use disorders and their interactions with environmental factors, researchers can identify potential biomarkers for early detection and personalized treatment approaches. Furthermore, exploring the impact of social determinants such as socioeconomic status, access to healthcare, and community support on SUD outcomes is essential for addressing disparities in addiction treatment and recovery. Research focusing on how social factors influence treatment engagement, retention, and outcomes can inform the development of more effective and equitable interventions for individuals with SUD. Lastly, investigating the impact of emerging trends, such as the use of digital technologies and social media on substance use behaviors, could provide valuable insights into novel risk factors for addiction. Understanding how online platforms influence substance-related attitudes, behaviors, and perceptions among different age groups can inform targeted prevention efforts in the digital age.

By addressing these research gaps and exploring the complex interplay of biological, psychological, and social factors influencing SUD, future studies can contribute to more effective prevention strategies, personalized treatment approaches, and improved outcomes for individuals struggling with addiction and co-occurring psychiatric symptoms.

9.2. Limitations

While this review provides valuable insights into the complex interplay of biological, psychological, and social factors contributing to SUD and co-occurring psychiatric symptoms, several limitations should be acknowledged. Firstly, the generalizability of the findings may be constrained by the geographic diversity of the included studies, which spanned various countries. This diversity could introduce cultural nuances that impacted the interpretation of results and the generalizability of the findings. The wide variation in cultural insights featured in this paper may result in a lack of overall consistency. Secondly, the methodologies employed in the reviewed studies varied, encompassing cross-sectional, longitudinal, and randomized controlled trial designs. Variability in study designs may affect the comparability and synthesis of results. Additionally, the reliance on published articles from indexed journals may introduce publication bias, potentially excluding valuable data from unpublished sources; therefore, we’ve incorporated the grey literature, including technical reports [5,6,8], organizational documents [1,9], blog posts [41], and theses [48], providing a more balanced and inclusive perspective. Finally, while efforts were made to include a comprehensive range of factors influencing SUD, there may exist additional variables not covered in this review that could contribute to a more holistic understanding of substance addiction.

10. Conclusions

The findings in the present review underscore the importance of considering a biopsychosocial model when understanding addiction, emphasizing the significant role played by neurotransmitter systems such as the endocannabinoid and dopaminergic systems in substance addiction. Moreover, this review highlights the impact of media representation on substance use behaviors among children and adolescents, emphasizing the need for positive messaging to counteract negative influences. Furthermore, awareness of the risks associated with substance use is particularly important from a prevention perspective.

Introduction

Drug misuse represents a significant global health and safety concern. In 2021, an estimated 296 million individuals aged 15–64 engaged in drug use, an increase from 240 million in 2011, indicating a growing public health challenge. This issue negatively impacts overall health, particularly mental well-being, and compromises safety. Social stigma and discrimination frequently deter individuals with drug-related challenges from seeking necessary assistance, with less than 20% receiving treatment and significant disparities in access.

The spectrum of substance use disorders (SUDs) encompasses both single-substance and polysubstance use. Polysubstance use disorders are often more challenging to treat and are associated with more severe outcomes in terms of substance use patterns, mental health, and physical health. Individuals engaging in widespread polysubstance use are also more likely to experience additional clinical complexities, including psychosis.

Psychoactive Substances and Addiction

According to established diagnostic criteria for substance use disorder, a "substance" is characterized primarily by its ability to activate the brain’s reward system, leading individuals to prioritize substance intake over typical activities. This category includes a range of substances such as alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants (including amphetamine-type substances and cocaine), and tobacco.

For a focused examination, the current discussion considers substances commonly referred to as "drugs," which are natural or chemical compounds known to significantly affect human consciousness, decision-making, and quality of life. These substances can induce cravings, tolerance, hazardous use, and contribute to social, interpersonal, physical, and psychological problems. Specifically, the term "drugs" in this context includes cannabis, hallucinogens (such as MDMA), opioids (such as heroin), hypnotics, and stimulants (such as cocaine and amphetamines).

Such substances possess the potential for addiction, especially in younger populations. Research indicates that initiation of smoking, drinking, and drug use prior to age 18 correlates with an increased likelihood of developing addictive behaviors towards these and other substances. Marijuana remains among the most frequently used illicit psychotropic substances globally, with an estimated 219 million users in 2021. Current trends suggest an increase in both cannabis use and associated hospitalizations, particularly among young individuals.

Hallucinogens are broadly categorized into classical hallucinogens (e.g., LSD, psilocybin), dissociative hallucinogens (e.g., PCP, ketamine), and other hallucinogens (e.g., MDMA). These substances are primarily used for recreational purposes, with data from 2020 indicating that 7.5% of adolescents had used hallucinogens at least once. Opioids are utilized for both medical and recreational purposes; in 2021, approximately 60 million individuals engaged in non-medical opioid use. Opioids continue to be the leading cause of fatal overdoses, accounting for nearly 70% of drug use disorder-related deaths in 2019. In Europe, heroin is most frequently linked to criminal activity, with five percent of seizures involving this substance.

Stimulants such as cocaine, derived from the coca plant, are powerfully addictive. In 2020, 0.4% of the global population aged 15–64 used cocaine, with the highest prevalence observed in North America (2.5%), Oceania (1.9%), and Western and Central Europe (1.5%). The United States reported the highest number of users, while Colombia exhibited the highest prevalence rate.

Gender Differences

While substance use disorder is more commonly reported by males, evidence indicates that drug misuse is a widespread issue affecting both men and women, albeit with distinct patterns. Historically, a greater prevalence of SUDs was observed among men; however, recent studies suggest a narrowing of this gender gap. Interestingly, women tend to escalate their drug consumption more rapidly than men once use begins, leading to more pronounced negative health and social consequences. In 2021, women constituted a higher proportion of users of amphetamine-type stimulants and non-medical pharmaceuticals, whereas men comprised the largest percentage of users of opiates and cocaine.

Age Differences

Cannabis use among 15–16-year-olds varies regionally, ranging from less than 3% in Asia to over 17% in Oceania. In most regions, the proportion of adolescents using cannabis exceeds that of the general population aged 15–64. Younger patients are more likely to report cocaine and cannabis use, violations of lockdown rules, deteriorated family relationships, and reduced incomes. Conversely, older patients more frequently report maintaining abstinence.

Comorbidity with Psychiatric Symptoms

Substance use disorders frequently co-occur with other mental health conditions, particularly among polysubstance users. Common comorbidities observed during treatment include mood, anxiety, eating, and post-traumatic stress disorders (PTSDs). A notable prevalence of positive psychotic symptoms and schizophrenia is also observed. The relationship between mental health and SUDs is bidirectional, with various mental health symptoms linked to the use of different substance clusters to achieve desired effects, such as intoxication, energy, or distress relief. Psychiatric symptoms and psychopathological behaviors are not only related to the development of SUD but also exhibit significant correlations with various phases of drug addiction, such as abstinence or craving.

Aim of this Study

This review aims to analyze the primary factors contributing to the development and maintenance of substance use disorder and its co-occurring psychiatric symptoms. In cases of dual diagnosis, understanding the factors that can lead to drug misuse is crucial. The purpose is multifaceted: to provide scientific data for the projection and implementation of effective prevention plans, and to understand the role psychiatric symptoms play in substance use disorder. This involves examining whether the presence of psychiatric symptoms is a cause or a direct consequence of the disorder and, if so, to what extent distinguishing between these cases is possible. The discussion first analyzes biological, psychological, and social factors contributing to SUD development. Subsequently, progression patterns and characteristics representing potential risk or protective factors are explored. Finally, attention is given to the interaction among these various factors to provide a comprehensive overview of the prodromal stages of SUD.

Materials and Methods

This review, while not a systematic review in the traditional sense, employed systematic search methods to ensure transparency and rigor in article selection. The systematic search was conducted in January 2024, utilizing Primo VE Discovery to aggregate results from several databases, including PubMed, PubMed Central, Health & Medical Collection, ScienceDirect Freedom Collection, and Wiley Online Library. Article selection was based on four distinct search strings.

The keywords for the search strings were chosen to align with the paper's main topics: how biological, psychological, and social factors individually contribute to the development and maintenance of substance use disorder (SUD), and how these factors interact in individuals with SUD. Additionally, the search aimed to analyze individual and social factors that prevent or increase the likelihood of developing SUD and its co-occurring psychiatric symptoms.

This review incorporates the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram to describe the research methodology and selection of included articles. Although this review does not include features typically associated with systematic reviews, such as a meta-analysis or risk of bias assessment, the systematic search methods employed ensure a comprehensive and transparent approach to identifying and selecting relevant studies. This approach enhances the reliability and validity of the findings. The absence of certain features reflects the specific aims and scope of this research.

Eligibility Criteria

Articles meeting the following criteria were included:

• Studies and reviews published in indexed journals (e.g., PubMed, PubMed Central, Health & Medical Collection, ScienceDirect Freedom Collection 2021, Wiley Online Library).

• Studies that included the specified keywords and/or were relevant to their topic.

• Studies published from the year 2022 onward, selected to provide the most recent sources, including, but not exclusively focused on, elements related to the COVID-19 pandemic.

Characteristics of Included Studies

This literature review examined sixty full-text articles to analyze the biological, psychological, and social factors influencing the development and persistence of SUD and its concurrent psychiatric symptoms. Articles were selected based on their relevance to understanding the interaction among these factors, as well as identifying risk and protective factors useful for designing prevention strategies and treatment recommendations. The reviewed studies, conducted between 2022 and 2024, varied geographically, including locations such as Italy, India, Australia, Norway, Spain, Switzerland, and the United States. Methodologies employed were diverse, encompassing cross-sectional, longitudinal, and randomized controlled trial designs. Collectively, these studies offer comprehensive insights into contemporary SUD manifestations, their biological, psychological, and social origins, the interplay among these factors, and the key determinants influencing treatment outcomes.

Biological Factors

Over the years, numerous studies have investigated the biological factors that may underlie the development and maintenance of substance addictions. While a definitive causal link between the presence of specific biological factors and the development of addiction remains unestablished, existing research offers promising insights. These findings pave the way for further investigation that could significantly alter treatment perspectives for addiction and SUD.

A significant involvement of neurotransmitter systems in substance addiction has been observed. The endocannabinoid and dopaminergic systems appear to play a particularly relevant role. Substances bind to these systems or alter their neurotransmitter actions, leading to changes in the activity of specific brain areas. These areas, including the prefrontal cortex (PFC), inferior cingulate gyrus (ICG), anterior cingulate gyrus (ACG), striatum, thalamus, nucleus accumbens (NAcc), Ventral Tegmental Area (VTA), and amygdala, have a high concentration of receptors belonging to these two systems. Activation of these brain regions is responsible for the feeling of gratification experienced by individuals with substance addictions, as these areas regulate emotions, decision-making, and impulse control.

The subsequent sections analyze how specific biological factors intervene for each class of drugs.

Cannabis Addiction

Genetic variants of several components of the endocannabinoid system have been proposed as potential risk factors for cannabis dependence. Specifically, polymorphism of certain single nucleotide polymorphisms (SNPs) within the CNR1 gene, particularly the G allele, has been associated with increased withdrawal symptoms and craving after brief cannabis abstinence. This genetic variant is also linked to more significant responses in brain areas such as the orbitofrontal cortex (OFC), the ICG, and the ACG. One study found that cannabis users carrying the G allele exhibited reduced hippocampal volume, potentially due to the interaction of cannabis with the CB1 receptor, which is altered by this polymorphism. More recently, the CNR2 gene has been linked to an elevated risk of developing schizophrenia in patients with Cannabis Use Disorder (CUD). Alleles A and C are also strongly implicated in cannabis addiction, correlating with increased activity and reactivity of specific gratification-related brain areas. A recent study demonstrated structural brain alterations in cannabis-dependent patients, which were significantly associated with regional differences in the expression of MAGL, an enzyme responsible for endocannabinoid degradation. Research has also explored the effect of THC on anxiety and amygdala response, finding that anxiety-induced THC intake modulated amygdala activation and increased CB1 cannabinoid receptor availability.

Opioid Addiction

Information regarding polymorphism of the endocannabinoid system specifically related to opioid addiction is limited. However, similar to cannabis addiction, the involvement of specific genes and alleles, such as the C allele, can be traced to opioid addiction. One study investigated the association between CNR1 and the development of major depression or suicidal behaviors in opioid-dependent outpatients undergoing methadone treatment. This work found that the C allele of CNR1 was closely correlated with a lower prevalence of lifelong major depression but not with suicidal behaviors. Numerous studies on the biological effects of opioids have utilized animal models. For example, in a significant study, rats chronically treated with morphine showed reduced CB1R binding in the cerebellum and hippocampus and diminished CB1R functions in the NAcc.

Stimulant Addiction

Cocaine, a substance of abuse, damages mesolimbic dopaminergic neurons by inhibiting dopamine uptake, which contributes to compulsive behavior and relapse. Methamphetamine, conversely, causes specific damage to the dopaminergic neurotransmitter system and is associated with cell death. Even a single intake of methamphetamine can alter concentrations of certain endocannabinoids in the striatum of adult male mice, suggesting the involvement of the endocannabinoid system in the brain's response to these drugs. Alterations at both central and peripheral levels have been observed in individuals exposed to psychostimulants such as amphetamines and cocaine. Specific polymorphisms of the CNR1 gene have been associated with the development of stimulant dependence. Furthermore, numerous changes in the targets of the endocannabinoid system have been primarily identified in cocaine studies, highlighting the importance of this system in regulating various aspects of stimulant addiction, including gratification, motivation, withdrawal, and relapse.

Several studies emphasize the functional importance of the endocannabinoid system in modulating the effects produced by psychostimulant substances. It has been confirmed that some genetic variants contribute to the vulnerability to relapse in stimulant-dependent individuals. Two independent variants of CNR1, the G allele genotype and the T/T genotype, showed a significant effect on the risk of cocaine addiction in both Euro-Americans and African-Americans with these genotypes. The importance of the dopaminergic system should also be acknowledged. D1 receptors are crucial in mediating cocaine's action, substance-seeking leading to self-administration, and cocaine-related effects on gene expression in the striatum. D2 receptor levels, on the other hand, predict the "liking" effects of psychostimulants such as methylphenidate. Chronic cocaine use or abuse attenuates the availability of D2/D3 receptors in the striatum and reduces acute dopaminergic responses to psychostimulant administration.

Hallucinogens Addiction

Several studies have evaluated the effects of dissociative drugs on the cannabis and endogenous cannabinoid systems. Subchronic administration of ketamine in mice, for instance, increased endocannabinoid concentrations in the caudate putamen (CPU), amygdala, and hippocampus. Although limited information is currently available on the subject, most researchers support the potential utility of identifying changes in cannabinoid receptors, ligands, or enzymes as biomarkers. Such biomarkers could improve the diagnostic classification of patients with SUD and enhance the success of their drug treatment.

Pharmacology and Treatment Insights on SUD

Despite extensive investigations, the field of pharmacotherapy for SUDs remains relatively underexplored. While significant progress has been made in understanding the neurobiology and behavioral aspects of addiction, the development of targeted medications has proven challenging. Currently, no drug treatment has received approval from the FDA (Food and Drug Administration) or EMA (European Medicines Agency) for most substance use disorders, with the exceptions of Alcohol Use Disorder (AUD), Nicotine Use Disorder (NUD), and Opioid Use Disorder (OUD). Given that GABAergic system dysfunction is associated with substance use, various studies have also explored the efficacy of antiepileptic drugs and combination therapies. Another treatment strategy involves targeting endophenotypes associated with SUDs; for example, using cognitive enhancers to improve decision-making, planning, or impulse control may be a useful approach. Several pharmacological studies are presently underway. In addition to new pharmacological perspectives, alternative therapies such as psychotherapy (including drug-supported), mindfulness-based interventions (MBI), and the use of virtual reality (VR) techniques are also considered.

Psychological Factors

Substance use disorder can be conceptualized as a complex interplay of behavior, personality, and psychopathology. The co-occurrence of substance use and psychopathology (dual diagnosis) can be explained by shared risk factors such as socioeconomic status and personality traits. Many individuals with SUDs exhibit psychiatric comorbidity, including personality, mood, and anxiety disorders, particularly in cases of poly-drug use, where eating disorders, psychotic symptoms, schizophrenia, and post-traumatic stress disorder (PTSD) may also be found. In some instances, a dual diagnosis of SUD and Autism Spectrum Disorder (ASD) is also observed.

Approximately 10–20% of the population experiences an addiction-related problem, and half of those with a substance use disorder also experience other mental disorders during their lifetime, and vice versa. The relationship between the two appears to be bidirectional. A positive association has been identified between anxiety, depression, and craving intensity. Moreover, the duration of abstinence can influence the association between craving and psychiatric symptoms.

Temperament and personality traits are crucial factors contributing to the development and persistence of addiction-related behaviors. Among these traits, disinhibition and a lack of self-control—defined as the ability to regulate one's behavior, emotions, and cognition—represent key elements. Self-control is considered a transdiagnostic dimension; its absence can manifest in both externalized behaviors, such as substance-related disorders and Attention Deficit Hyperactivity Disorder (ADHD), and internalizing behaviors, such as mood or anxiety disorders. High levels of behavioral activation (BAS) and low levels of self-control (EC) have been associated with Cluster B personality disorders, while high levels of behavioral inhibition (BIS) and low levels of self-control (EC) have been linked to Cluster C. For Cluster A, a mixed pattern of BAS and BIS has been observed. The development of clinical symptoms, particularly anxiety and depression, and the manifestation of personality disorders, both correlate with low levels of self-control (effortful control—EC) and high levels of behavioral inhibition (BIS) in individuals with SUD. This suggests a greater inclination toward neuroticism, which is considered an additional personality trait serving as a vulnerability factor for the development and persistence of SUD. While some studies indicate low self-esteem in patients with SUD, others examining the relationship between SUD and self-esteem have found high levels.

Anxiety disorders are frequently observed in patients diagnosed with SUD, and research demonstrates a strong correlation with craving intensity. Anxiety symptoms exhibit a significant association with substance use and addiction severity. Furthermore, stress has been positively correlated with craving intensity in opiate and methamphetamine use. Mood disorders are commonly comorbid with SUD and craving intensity. Depression, in particular, shows a positive correlation with heroin craving intensity in patients undergoing methadone maintenance treatment. While substance use may impair brain function and induce depressive or anxiety symptoms, individuals may also use substances as a form of "self-medication" to manage such symptoms.

Attention-deficit hyperactivity disorder (ADHD) is present in approximately 25% of individuals with SUD. ADHD is considered an important risk factor for SUD development, promoting early illicit substance use and serving as a predictor of substance use disorder. Data suggest that the presence of ADHD doubles an individual's vulnerability to developing a psychoactive substance use disorder. Conversely, addiction negatively impacts the course of ADHD by exacerbating cognitive and memory impairment. The course of SUD is often more severe in patients with comorbid ADHD than in those with SUD alone.

Post-Traumatic Stress Disorder (PTSD) frequently co-occurs with SUD, and both disorders commonly manifest during adolescence. Some theories propose that traumatic experiences in adolescence may promote SUD development, which in turn facilitates PTSD onset. Other hypotheses suggest that the coexistence of these disorders could result from adopting substance use as a coping strategy to mitigate PTSD symptoms. Certain substances appear capable of influencing the immediate experience of PTSD symptoms, predisposing individuals to subsequent substance use. A history of trauma is a significant risk factor for violent and suicidal behavior in individuals with SUD, highlighting the need to consider psychological and trauma contexts in assessment and treatment. An additional study examined the co-occurrence of Sexual Compulsive Behavior Disorder (CSBD) and risky sexual actions among women with SUD. Results indicate that women with SUD exhibit more pronounced CSBD symptoms and a greater propensity for risky sexual behavior than control groups, with CSBD appearing to mediate the association between substance use and risky sexual behaviors. Furthermore, addictive behaviors have been linked to emotional abuse during childhood but not to other forms of abuse.

SUD and Autism Spectrum Disorder (ASD) often present as comorbidities, leading to dual diagnoses. In most such cases, individuals use substances to manage high levels of anxiety, stress, and social difficulties, including perceived social rejection. The primary cause of this phenomenon appears neurobiological, though its interaction with psychological aspects warrants further exploration. Individuals suffering from chronic pain or mood disorders are often disproportionately prescribed opioid medications, increasing their risk of suicide. Research has explored connections between suicidal symptoms and SUD, finding that any SUD diagnosis amplifies suicide likelihood, and conversely, increased suicide risk is associated with SUDs. In-depth research highlights opioids, in particular, as exhibiting a stronger correlation with suicidal ideation and attempts compared to substances like cocaine and cannabis. The intricate interplay of chronic pain, mood disorders, opioid use, and heightened suicide risk underscores the complexity of these issues and the necessity for comprehensive, multifaceted care. For research purposes, it is essential to consider comorbid disorders alongside SUDs, including mood and personality disorders, and to assess anxiety and depression symptoms to provide personalized treatments to individuals at risk of suicidal ideation.

Social Factors

Substance use disorder is a complex condition influenced by numerous factors, including social ones. Social factors play a significant role in both the development and maintenance of SUD. Social determinants of health (SDoH) refer to the conditions in which individuals are born, grow, live, work, and age. These circumstances are shaped by the distribution of financial resources, power, and assets at global, national, and local levels. The following discussion analyzes social factors contributing to the development and maintenance of SUD.

Childhood

Understanding the pathways to addiction necessitates examining the individual's upbringing environment, starting from childhood. The parenting style and resulting family dynamics play a crucial role in both individual development and the development of addiction. Children raised with an authoritarian parenting style, characterized by demanding, strict, and firm parents who display little affection, warmth, or involvement, tend to exhibit a higher likelihood of alcohol and other substance use. Conversely, an authoritative parenting style, marked by high demands and responsiveness, has been associated with positive outcomes, decreasing the likelihood of children's use of alcohol, cigarettes, and cannabis. The neglectful parenting style, with low demand and responsiveness, is most strongly associated with substance use. Finally, to a lesser extent, the permissive parenting style, characterized by low demand and high responsiveness, also shows a correlation with substance use.

Additionally, traumas experienced in childhood, such as physical or emotional abuse or neglect, even isolated incidents, can lead to adverse physiological consequences and poor health outcomes. For example, such experiences may result in increased cortisol levels, which subsequently elevate the risk of substance use. This could explain the relationship between coping mechanisms for trauma and those leading to substance use, placing stress at the center of the dynamic. While milder forms of stress can yield positive behavioral effects, severe or chronic stress can be debilitating, prompting individuals to cope by taking substances that can alleviate perceived stress and anxiety, thereby increasing the likelihood of developing an addiction.

Adolescence

Adolescence is a critical period for biological, psychological, and social development, but it is also a sensitive time during which individuals are particularly susceptible to substance use, its negative effects, and subsequent addictions. Early encounters with substances increase the likelihood of future problems (physical, behavioral, social, and health) and raise the risk of addiction if use begins before age 18. Most adolescents do not exhibit problematic use patterns, and this initial spike in use can often be considered experimental. For adolescents, any level of substance use carries risks and can result in negative developmental outcomes, including disrupted brain development, educational underachievement, behavioral consequences (e.g., impaired driving, risky sexual behavior), and injury, as well as the potential for inducing or exacerbating mental comorbidities and progressing to SUD. Furthermore, early-onset substance use is associated with increased psychosocial problems and problematic substance use later in life.

In this context, studies have found that parental support serves as a protective factor against SUD onset. Adolescents aged 9 to 18 years with positive parental relationships, characterized by emotional closeness and supervision, are less likely to experiment with alcohol, marijuana, and cigarettes. Conversely, lower levels of family functioning increase the likelihood of these behaviors. This finding is particularly interesting when compared with peer support, as opposite effects are observed: peer support correlates with higher alcohol consumption. Both perceived rejection from parents and peers, and loneliness, are associated with alcohol consumption. Social support is considered the most effective tool in aiding disorder resolution, encompassing behaviors ranging from simple presence, listening, and problem-sharing to providing concrete assistance. Support can come from family, friends, and professionals, and it is crucial because addiction requires extensive support, often involving withdrawal and severing ties with detrimental friendships.

The relationship between social conditions and drug use is bidirectional. In parallel with the aforementioned points, SUD adversely affects social behavior, leading individuals to avoid social situations to dedicate more time to drug taking rather than engaging in rewarding social interactions. This creates a vicious cycle where increased drug use leads to greater isolation. This phenomenon has intensified in recent years due to lockdowns, which compelled young people to remain at home for extended periods. It has been observed that the COVID-19 pandemic contributed to increases in overdoses and social isolation.

Adulthood

As individuals age, those with Alcohol Use Disorder (AUD) often report growing up in families characterized by less cohesion and expressiveness and more conflict. These are identified risk factors for alcohol use, often masked by the individual's justifications for their consumption (e.g., alcohol reduces worry). Increasing levels of loneliness, also experienced during the COVID-19 pandemic, are related to increased alcohol use and anxiety. Lack of social support, medical complications, and confronting bereavement are features of older age that could contribute to the onset of SUD or AUD. This, in turn, increases the likelihood of premature mortality, impacts healthy aging, and heightens health risks. Alcohol consumption correlates with higher rates of dementia and increased vulnerability to negative withdrawal symptoms due to the frailty of older adults and the presence of comorbidities.

An interesting aspect emerging from research is the incidence of SUDs in young adults aged 18 to 25. Approximately 21% of young adults meet the diagnostic criteria for SUDs, a significant contrast to the 9% prevalence in 12–17-year-olds and 7% in individuals aged 26 and above. These data could be attributed to various factors. For instance, difficulties that individuals aged 18–25 face in successfully adapting to this transitional phase could lead them to turn to substance use as a coping mechanism. Furthermore, evidence indicates a correlation between early manifestations of delinquency or aggression and substance use in young adults.

Social Background

The social context in which an individual grows up and lives plays a crucial role in the development of certain addictions. One research study found that most individuals with addiction problems tend to disregard the idea of marriage to dedicate their time to addictive behaviors without responsibility or spousal criticism. More than half of the sample in this study were male and originated from urban areas, which are often easily accessible for drug cultivation and dealing, and present numerous security and surveillance issues. Another study revealed that neighborhood disorder, such as the presence of graffiti, noise nuisance, and crime, was more prominently associated with alcohol use in women. For men, conversely, social cohesion—defined as feelings of attachment to the neighborhood, relationships and solidarity with neighbors, and the neighborhood in general—was identified as a risk factor.

Progression Patterns and Factors of Risk and Protection

Understanding how addictions develop and persist is crucial for adopting the most effective prevention and intervention strategies. This discussion examines both the patterns of progression in substance use and the related risk and protective factors to provide a comprehensive framework for the complexity of this phenomenon.

Risk and Protection Factors

Impaired illness awareness of addiction to recreational or pharmaceutical substances is an understudied construct that impacts the adoption of interventions, treatment-seeking behaviors, and retention in treatment. In substance use disorder, the term illness awareness refers to an individual's subjective recognition of having a problem with substance use. It also includes an individual's acceptance of the need for treatment and the negative consequences arising from substance use. Individuals with impaired illness awareness in SUD are less likely to utilize clinical services and more likely to drop out of treatment, despite the severity of their substance use. Conversely, higher levels of illness awareness in SUD are associated with better treatment engagement and adherence, and improved clinical outcomes.

A narrative review demonstrates a strong connection between mental disorders and SUD in Transitional Age Youth (TAY), the period encompassing adolescence and emerging adulthood, approximately between 15 and 25 years of age. Initiation of drug use typically peaks in adolescence, but in many cases, drug use gradually decreases after this period. Most adolescents do not exhibit problematic use patterns, and this spike can be considered experimental drug use. All children entering adolescence are at risk for adverse health outcomes related to alcohol or other drug use, with substance misuse increasing markedly from mid to late adolescence. For adolescents, any level of substance use is risky and can result in negative developmental outcomes, including disruption of brain development, educational underachievement, behavioral consequences (e.g., related to driving, sexual behavior), and injury, as well as the potential for inducing or exacerbating mental comorbidities and progression to SUD. Furthermore, early-onset substance use is associated with increased psychosocial problems and problematic substance use later in life.

Preexisting mental disorders are identified as risk factors for the emergence and progression of SUD. A narrative review highlights a common comorbidity between mental disorders and SUD among adolescents and young adults. According to the authors, these two issues negatively influence each other. A study of juvenile detainees demonstrated that substance use, behavioral disorders, and internalizing disorders predict the development of SUD. This underscores the importance of treating childhood and adolescent disorders to reduce the emergence of secondary SUD.

Emerging evidence indicates that low Socioeconomic Position (SEP) is an important determinant of many mental disorders, including substance use disorders. In a cohort study involving 1.6 million individuals in the Stockholm region, alcohol and drug use disorders were more common among individuals with lower levels of education compared to those with higher levels of education, in both males and females.

Peer interactions are often intertwined with physical activities during adolescence, and physical activity is broadly and positively related to mental health through psychosocial, behavioral, and physiological mechanisms. Two studies examining pairs of discordant twins on physical activity found that physical inactivity in adolescence was associated with increased consumption of alcohol, drugs, and smoking in young adulthood. Throughout adolescence, peer relationships gain importance as friends increasingly become a source of social support and influence on developing adaptive and maladaptive behaviors. In the context of substance use disorders, observational studies on adolescents have yielded conflicting results depending on the type of physical activity and substances under examination. Factors such as rejection and loneliness may increase the risk of substance-related issues in adolescence and early adulthood. Social integration may lead to greater access to substances, as well as friendship with deviant peers. Conversely, friendship with peers who do not use substances may serve as a protective factor. One study employed a co-twin control design to explore participation in sports, physical activity, and friendship quality as predictors of substance use. The results indicated that participation in sports and positive friendship quality were associated with an increased likelihood of substance use. In a longitudinal study, participants completed four annual surveys during late adolescence and the transition to young adulthood. Results highlighted key individual and community-level protective factors that decrease the risk of opioid use.

While long-term use of alcohol, opioids, or sedatives is often associated with impaired sexual function, the short-term use of alcohol, cannabis, cocaine, amphetamines, or hallucinogens may increase sexual arousal. This can lead to use aimed at enhancing performance. Several studies have investigated the association between prevalent SUD and hypersexuality. The targeted use of drugs to evoke specific physical or psychological effects during sexual activity (e.g., to increase sexual performance or achieve sexual disinhibition) is termed chemsex.

Media representation of substances and alcohol, such as TV shows and movies openly displaying drug and alcohol use, significantly impacts children's and adolescents' perceptions. Exposure increases the likelihood of young people initiating use and subsequently developing SUDs. The influence of media should therefore be harnessed to positively shape opinions and beliefs about drugs and alcohol, given its considerable power in the lives of teenagers. Risk factors often exhibit positive correlations with each other and negative associations with protective factors. Essentially, individuals with certain risk factors are more likely to encounter additional risks, while protective factors tend to be less prevalent. Furthermore, the cumulative impact of these factors significantly influences the development or prevention of behavioral health issues. Young people with multiple risk factors face a higher likelihood of experiencing conditions affecting their physical or mental well-being, whereas those with multiple protective factors are at a reduced risk.

Interactions between Psychological, Social, and Biological Factors

In previous sections, the individual contributions of biological, psychological, and social factors to the development and maintenance of substance use disorder were analyzed. However, these factors rarely exert a significant influence in isolation. It is therefore crucial to acknowledge their co-presence and understand how they interact within an individual's life. This section examines the collective interaction of these factors in individuals with SUD.

A Biopsychosocial Model for Understanding Addiction

Substance addiction is a biopsychosocial phenomenon. Psychosocial factors are multidimensional constructs spanning psychological domains (e.g., depression, anxiety, distress, self-esteem, satisfaction) and social domains (e.g., socioeconomic status, employment, religion, physical attributes, family, relationships with others, locality). These factors contribute to the development of mental and physical disorders. Indeed, drug use is frequently correlated with negative outcomes across various aspects of an individual's life. SUDs can lead to adverse physical, mental, and social consequences, including addiction, substance-induced disorders, neurological complications, cognitive impairment, unemployment, incarceration, and suicidal behavior. Conversely, stigma and discrimination reduce the likelihood that individuals who use drugs will receive necessary help. Fewer than 20 percent of people with drug use disorders are in treatment, and access is highly unequal. Of the approximately 39.5 million individuals globally diagnosed with drug use disorders in 2021, only one in five received treatment.

The importance of considering a biopsychosocial model in examining influences on the development of substance dependence disorder was confirmed by a 2020 study conducted by the Johns Hopkins Bloomberg School of Public Health and Texas A&M University. The biopsychosocial model of addiction, in understanding the development and progression of substance use problems, emphasizes biological factors such as genetic predisposition, psychological and cognitive factors such as self-efficacy, outcome expectations, and readiness to change, and social factors such as family, peer, and partner influence. Consequently, comprehending the interconnectedness of these factors could be an effective strategy in substance use prevention programs. Substance use disorder involves a variety of neurobiological processes, including the brain reward system. This system, also known as the dopaminergic system, is crucial in transmitting behavioral responses related to pleasure and gratification. Thus, the interaction between social environment, individual functioning, and family history plays a key role in understanding SUD development.

Family History, Role Models, and Psychological Factors

Starting with the family during childhood, young people engage in multiple activities upon entering school; especially during middle school, peers gain increasing importance and influence individual development. In adolescence, and more so during the transition to adulthood, romantic relationships become additional agents of socialization and, along with the peer group, represent an element of the reward system. Family members serve as role models for children, as demonstrated in research involving participants aged 10 to 33. The results showed that positive social and family environments create a positive model for future interactions. In contrast, a family history of depression may negatively influence mental health functioning during adulthood. Family environments characterized by chronic stress, conflict, or other forms of dysfunction influence the reward system, increasing sensitivity to rewarding stimuli and leading to greater reliance on substances that provide temporary relief. Additionally, if substance use behaviors are present in the family, children may perceive such behaviors as acceptable, potentially triggering an approach to various substance-focused social contexts as they mature. The authors found that some psychological factors, such as generalized anxiety disorder, panic disorder, or the experience of childhood trauma, are related to substance use. Psychological factors like childhood trauma may modulate social perceptions and adaptation to stressful life contexts, potentially promoting substance use. Other social factors frequently associated with the development of psychopathological symptoms are also linked to SUD development. According to research conducted in Stockholm, a low level of education increases the risk of substance use disorders and self-harm. Furthermore, an association between low educational attainment and various mental disorders, such as schizophrenia, depression, anxiety, ADHD, and behavioral disorders, is highlighted.

Neurological Factors, Genetic Predispositions, and Personality Traits

Genetic predisposition can influence the brain's response to opioids and its ability to regulate the impulse for substance use. It can also affect an individual's vulnerability to developing psychological disorders such as anxiety or depression, which are strongly linked to addiction risk. For example, some theories suggest that individuals with autism spectrum disorder may possess dopaminergic differences in the fronto-cortical cortex, making them susceptible to repetitive pleasurable sensation-seeking, with the risk of easily translating into addictive behaviors. Additionally, a common dysregulation of the limbic system appears to exist in individuals with SUD and ASD. In a systematic review exploring the impact of both PTSD and SUDs on uncontrolled craving for substances, post-traumatic stress disorder was significantly associated with increased levels of craving among patients with alcohol, cannabis, cocaine, tobacco, and other substance use disorders. Some studies have also observed a correlation between the severity of post-traumatic stress disorder symptoms and craving intensity, as substance use serves as a means of alleviating traumatic symptoms. The underlying mechanisms involve negative emotional states, and emotional dysregulation plays a role in eliciting craving after traumatic exposure. Psychological, social, and biological factors may interact synergistically in craving and substance use. PTSD symptoms can trigger emotions that, in turn, increase craving for substances, and similarly, exposure to traumatic environments can act as a trigger for craving.

Psychological Factors and Treatment Success Expectations

When addressing addiction, factors such as self-efficacy (confidence in one's ability to succeed without the substance) and motivation (desire to change one's behavior) must be considered. These factors are positively correlated with treatment success and directly related to each other: lower self-efficacy influences motivation to seek positive social supports, and fewer social supports decrease self-efficacy.

Discussion

The development and maintenance of substance use disorders involve a complex interplay of biological, psychological, and social factors. In the biological realm, the endocannabinoid and dopaminergic systems, along with genetic variants, contribute to specific pathways in cannabis, opioid, and stimulant addiction. Psychological aspects reveal the significance of personality traits, such as disinhibition and low self-esteem, in addiction vulnerability. The coexistence of anxiety, mood disorders, and addiction, coupled with the strong correlation between traumatic events and substance use, further emphasizes the importance of considering psychological dimensions. Social elements, encompassing family background, parental styles, neighborhood characteristics, and peer support, significantly shape addiction patterns, while addiction, in turn, disrupts social behaviors, leading the individual to isolation. The intricate interconnection of these factors underscores the multifaceted nature of addiction and the importance of comprehensive approaches in prevention and treatment strategies.

Future Research

Several avenues for future research could enhance the understanding of SUD and its co-occurring psychiatric symptoms. Firstly, longitudinal studies tracking individuals from adolescence to adulthood could provide valuable insights into the long-term impact of early substance use on mental health outcomes and addiction trajectories. Understanding how factors such as childhood trauma, parental styles, and peer influences interact over time to shape substance use behaviors is crucial for developing targeted prevention and intervention strategies. Secondly, investigating the role of genetic influences and neurobiological factors in predisposing individuals to specific types of substance addictions could offer a more nuanced understanding of addiction vulnerability. By exploring genetic markers associated with different substance use disorders and their interactions with environmental factors, researchers can identify potential biomarkers for early detection and personalized treatment approaches. Furthermore, exploring the impact of social determinants such as socioeconomic status, access to healthcare, and community support on SUD outcomes is essential for addressing disparities in addiction treatment and recovery. Research focusing on how social factors influence treatment engagement, retention, and outcomes can inform the development of more effective and equitable interventions for individuals with SUD. Lastly, investigating the impact of emerging trends, such as the use of digital technologies and social media on substance use behaviors, could provide valuable insights into novel risk factors for addiction. Understanding how online platforms influence substance-related attitudes, behaviors, and perceptions among different age groups can inform targeted prevention efforts in the digital age. By addressing these research gaps and exploring the complex interplay of biological, psychological, and social factors influencing SUD, future studies can contribute to more effective prevention strategies, personalized treatment approaches, and improved outcomes for individuals struggling with addiction and co-occurring psychiatric symptoms.

Limitations

While this review offers valuable insights into the complex interplay of biological, psychological, and social factors contributing to SUD and co-occurring psychiatric symptoms, several limitations should be acknowledged. Firstly, the generalizability of the findings may be constrained by the geographic diversity of the included studies, which spanned various countries. This diversity could introduce cultural nuances that impacted the interpretation of results and the generalizability of the findings. The wide variation in cultural insights featured in this paper may result in a lack of overall consistency. Secondly, the methodologies employed in the reviewed studies varied, encompassing cross-sectional, longitudinal, and randomized controlled trial designs. Variability in study designs may affect the comparability and synthesis of results. Additionally, the reliance on published articles from indexed journals may introduce publication bias, potentially excluding valuable data from unpublished sources; therefore, grey literature, including technical reports, organizational documents, blog posts, and theses, has been incorporated to provide a more balanced and inclusive perspective. Finally, while efforts were made to include a comprehensive range of factors influencing SUD, additional variables not covered in this review may exist that could contribute to a more holistic understanding of substance addiction.

Conclusions

The findings presented in this review underscore the importance of considering a biopsychosocial model for understanding addiction. The significant role played by neurotransmitter systems, such as the endocannabinoid and dopaminergic systems, in substance addiction is emphasized. Moreover, this review highlights the impact of media representation on substance use behaviors among children and adolescents, underscoring the need for positive messaging to counteract negative influences. Furthermore, awareness of the risks associated with substance use is particularly important from a prevention perspective.

Introduction

Drug misuse represents a major global challenge. In 2021, about 5.8% of individuals aged 15–64 used drugs in the previous year. This number increased from 240 million in 2011 to 296 million in 2021, impacting overall health, especially mental well-being and safety. People facing drug-related issues often experience stigma and discrimination, which prevents them from seeking help. Less than 20% receive treatment, and access to care varies widely.

Substance use disorder (SUD) includes those who use one drug and those who use multiple drugs, known as "polysubstance users." Polysubstance use disorders are generally more difficult to treat than single SUDs and are linked to more severe substance use, mental health, and physical health problems. Individuals who use a wide range of substances often experience additional clinical complications, such as psychosis.

Psychoactive Substances and Addiction

According to the diagnostic criteria for substance use disorder, a "substance" is primarily characterized by its ability to activate the brain's reward system, causing individuals to neglect normal activities in favor of using the substance. This category includes substances like alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics or anxiolytics, stimulants (including amphetamine-type substances, cocaine, and other stimulants), and tobacco.

For discussion purposes, this review focuses on substances commonly referred to as "drugs." These are natural or chemical substances known to significantly affect human consciousness, decision-making, quality of life, and cause cravings, tolerance, hazardous use, social and interpersonal problems, and physical and psychological issues. From this perspective, "drugs" encompass cannabis, hallucinogens (such as MDMA), opioids (like heroin), hypnotics, and stimulants (such as cocaine and amphetamines).

These substances can lead to addiction, particularly in younger individuals. Research shows that those who begin smoking, drinking, and using drugs before age 18 are more likely to develop addictive behaviors toward these and other substances.

Marijuana is among the most frequently used illicit psychoactive substances globally. The World Drug Report 2023, published by the United Nations Office on Drugs and Crime, indicates that cannabis remained the most used drug in 2021, with an estimated 219 million users (4.3% of the global adult population). Current trends show an increase in both marijuana use and related hospitalizations, especially among young people.

Hallucinogens are categorized into three main groups: classical hallucinogens (e.g., LSD, psilocybin, mescaline, DMT, 251-NBOMe), dissociative hallucinogens (e.g., PCP, ketamine, dextromethorphan, Salvia divinorum), and other hallucinogens (e.g., MDMA, ibogaine, salvia). These substances are primarily used for recreational purposes. In 2020, data indicated that 7.5% of adolescents had used hallucinogens at least once in their lives.

Opioids are used for both medical and recreational purposes. In 2021, an estimated 60 million individuals engaged in non-medical opioid use, with 31.5 million using opiates, mainly heroin. Opioids remain the leading cause of fatal overdoses, accounting for nearly 70% of the 128,000 deaths attributed to drug use disorders in 2019. In Europe, heroin is the substance most frequently linked to crime, with five percent of seizures involving it, according to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).

Stimulants like cocaine are highly addictive drugs derived from the coca plant, exported from South America. In 2020, 0.4% of the global population aged 15–64 used cocaine. North America (2.5%), Oceania (1.9%), and Western and Central Europe (1.5%) reported the highest prevalence. The United States had the most users (6.5 million), while Colombia had the highest prevalence rate (3.4%).

Gender Differences

While substance use disorder is more commonly reported in males, evidence indicates that drug misuse affects both men and women, with distinct differences. Earlier research showed a significant gender gap in SUDs, with a higher prevalence among men. However, recent studies suggest this gap has narrowed considerably. Women tend to increase their drug consumption more quickly than men once they start, leading to more pronounced negative health and social outcomes. In 2021, the World Drug Report found that women comprised the majority of users of amphetamine-type stimulants (45% of users) and non-medical pharmaceutical use (45–49% of users), whereas men accounted for the highest percentage of opiate (75%) and cocaine (73%) users.

Age Differences

Cannabis use among 15–16-year-olds varies regionally, from less than 3% in Asia to over 17% in Oceania. In most regions, the proportion of adolescents using the drug is higher than in the general population aged 15–64.

Younger patients were more likely to report using cocaine and cannabis, violating lockdown rules, experiencing worsened family relationships, and facing reduced incomes. In contrast, older patients more often reported maintaining abstinence.

Comorbidity with Psychiatric Symptoms

Substance Use Disorders (SUDs) frequently co-occur with other mental health conditions, particularly among polysubstance users. Common co-occurring conditions observed during treatment include mood, anxiety, eating, and post-traumatic stress disorders (PTSDs). There is also a notable prevalence of positive psychotic symptoms and schizophrenia. The relationship between mental health and SUDs is often bidirectional, meaning that various mental health symptoms can be linked to the use of different substances to achieve desired effects, such as intoxication, energy, or relief from distress.

Psychiatric symptoms and psychopathological behaviors are not only related to the development of an SUD but also show significant correlations with various phases of drug addiction, such as abstinence or craving.

Aim of this Study

This review aims to analyze the primary factors contributing to the development and continuation of SUD and its co-occurring psychiatric symptoms. The review emphasizes the importance of understanding these factors, especially in cases of dual diagnosis, to address the concerning phenomenon of drug misuse. The goals are multifaceted: to provide scientific data for designing and implementing effective prevention plans, and to understand the role psychiatric symptoms play in substance use disorder—whether they cause the disorder or are a direct consequence of it, and to what extent one can determine this relationship. The review first analyzes biological, psychological, and social factors that contribute to SUD development. It then examines progression patterns and characteristics that act as potential risk or protective factors. Finally, attention is given to the interaction among these various factors to offer a comprehensive overview of the early stages of SUD.

Materials and Methods

This review employed systematic search methods to ensure transparency and rigor in selecting included papers, though it is not a systematic review in the traditional sense. The systematic search took place in January 2024, using Primo VE Discovery to aggregate results from several databases: PubMed, PubMed Central, Health & Medical Collection, ScienceDirect Freedom Collection, and Wiley Online Library. Articles were selected using four different search strings focusing on substance use disorder/addiction, psychiatric symptoms, and biological, psychological, and social factors.

The chosen keywords aligned with the main topics of this paper: how biological, psychological, and social factors individually contribute to the development and maintenance of substance use disorder (SUD), and how they interact in individuals with the condition. The review also aimed to analyze individual and social factors that prevent or increase the likelihood of developing an SUD and its co-occurring psychiatric symptoms.

This review includes the PRISMA 2020 flow diagram to describe the research methodology and article selection process. While this review does not include features typical of systematic reviews, such as meta-analysis or risk of bias assessment, the systematic search methods employed ensure a comprehensive and transparent approach to identifying and selecting relevant studies. This approach enhances the reliability and validity of the findings presented, with the absence of certain features reflecting the specific aims and scope of this particular research.

Eligibility Criteria

Included articles met the following criteria:

• All studies and reviews were published in indexed journals such as PubMed, PubMed Central, Health & Medical Collection, ScienceDirect Freedom Collection 2021, and Wiley Online Library.

• Studies included keywords used and/or were related to the topics of interest.

• Studies were published from the year 2022 onward, selected to provide the most recent sources, potentially including elements related to the COVID-19 pandemic period.

Results

Characteristics of Included Studies

This literature review examined sixty full-text articles to analyze the biological, psychological, and social factors influencing the development and persistence of Substance Use Disorder (SUD) and its concurrent psychiatric symptoms. Articles were selected based on their relevance to understanding the interaction among these factors, as well as identifying risk and protective factors useful for designing prevention strategies and treatment recommendations. The reviewed studies, conducted between 2022 and 2024, showed geographic diversity, with origins including Italy, India, Australia, Norway, Spain, Switzerland, and the United States. Various methodologies were employed, such as cross-sectional, longitudinal, and randomized controlled trial designs. Collectively, these studies offer comprehensive insights into current SUD manifestations, their biological, psychological, and social origins, the interplay among these factors, and the key determinants influencing treatment outcomes.

Biological Factors

Numerous studies have investigated the biological factors that may contribute to the development and continuation of substance addiction. While a definitive causal link between specific biological factors and addiction development has not been fully established, current findings are promising and could significantly influence future addiction treatment approaches.

Neurotransmitter systems, particularly the endocannabinoid and dopaminergic systems, appear to play a significant role in substance addiction. Substances interact with these systems or alter their neurotransmitter actions, leading to changes in the activity of specific brain areas. These areas, including the prefrontal cortex (PFC), inferior cingulate gyrus (ICG) and anterior cingulate gyrus (ACG), striatum, thalamus, nucleus accumbens (NAcc), Ventral Tegmental Area (VTA), and amygdala, contain a high concentration of receptors for these two systems. The activation of these brain regions is responsible for the feeling of reward experienced by individuals with substance addictions, as these areas regulate emotions, decision-making processes, and impulse control.

Cannabis Addiction

Genetic variants within the endocannabinoid system have been suggested as potential risk factors for cannabis dependence. Specifically, a polymorphism of certain single nucleotide polymorphisms (SNPs) in the CNR1 gene, the G allele, has been linked to increased withdrawal symptoms and craving after brief cannabis abstinence, as well as heightened responses in brain areas like the orbitofrontal cortex (OFC), ICG, and ACG. One study found that cannabis users with the G allele have reduced hippocampal volume, possibly due to the interaction of cannabis with a modified CB1 receptor. More recently, the CNR2 gene has been associated with an increased risk of developing schizophrenia in patients with Cannabis Use Disorder (CUD). Alleles A and C are also strongly involved in cannabis addiction, correlating with increased activity and reactivity in brain areas linked to gratification. A recent study observed structural brain alterations in cannabis-dependent patients, which were significantly associated with regional differences in the expression of MAGL, an enzyme that degrades endocannabinoids. Another research study found that anxiety-induced THC intake modulated amygdala activation and increased CB1 cannabinoid receptor availability.

Opioid Addiction

Information regarding endocannabinoid system polymorphisms related to opioid addiction is limited. However, like cannabis addiction, specific genes and alleles, such as the C allele, may be involved in opioid addiction. One study found that the C allele of CNR1 correlated with a lower lifetime prevalence of major depression in opioid-dependent outpatients undergoing methadone treatment, but not with suicidal behaviors. Many studies of the biological effects of opioids have used animal models. For example, in one study, rats chronically treated with morphine showed reduced CB1R binding in the cerebellum and hippocampus, and diminished CB1R functions in the NAcc.

Stimulant Addiction

Cocaine, a substance of abuse, damages mesolimbic dopaminergic neurons, inhibiting dopamine reuptake and leading to compulsive behavior and relapse. Methamphetamine causes specific damage to the dopaminergic neurotransmitter system and is linked to cell death. A single dose of methamphetamine can alter concentrations of certain endocannabinoids in the striatum of adult male mice, suggesting the endocannabinoid system's involvement in the brain's response to these drugs. Alterations at both central and peripheral levels have been observed in individuals exposed to psychostimulants like amphetamines and cocaine. Specific CNR1 gene polymorphisms have been linked to the development of stimulant dependence. Furthermore, numerous changes in the targets of the endocannabinoid system, primarily from cocaine studies, reveal this system's importance in regulating various aspects of stimulant addiction, including gratification, motivation, withdrawal, or relapse.

Several studies highlight the endocannabinoid system's functional importance in regulating the actions of psychostimulant substances, such as cocaine and amphetamine. It has been confirmed that some genetic variants contribute to the vulnerability of stimulant-dependent individuals to relapse. For instance, two independent CNR1 variants, the G allele genotype and the T/T genotype, showed a significant effect on the risk of cocaine addiction in both Euro-Americans and African-Americans with these genotypes. The dopaminergic system's importance should not be underestimated. D1 receptors are crucial in mediating cocaine's action, substance-seeking behavior, and cocaine-related effects on gene expression in the striatum. D2 receptor levels predict the "liking" effects of psychostimulants like methylphenidate. Chronic cocaine use or abuse reduces the availability of D2/D3 receptors in the striatum and blunts dopaminergic responses to psychostimulant administration.

Hallucinogens Addiction

Several studies have evaluated the effects of dissociative drugs on the cannabis and endogenous systems. Subchronic administration of ketamine in mice increased endocannabinoid concentrations in the CPU, amygdala, and hippocampus. While limited information is currently available, most researchers support the potential utility of identifying changes in cannabinoid receptors, ligands, or enzymes as biomarkers to improve the diagnostic classification of patients with SUD and enhance the success of their drug treatment.

Pharmacology and Treatment Insights on SUD

Despite extensive research, the field of pharmacotherapy for Substance Use Disorders (SUDs) remains relatively underdeveloped. While significant progress has been made in understanding the neurobiology and behavioral aspects of addiction, developing targeted medications has proven challenging. Currently, there are no drug treatments approved by the FDA (Food and Drug Administration) or EMA (European Medicines Agency) for most substance use disorders, with the exceptions of Alcohol Use Disorder (AUD), Nicotine Use Disorder (NUD), and Opioid Use Disorder (OUD).

Since GABAergic system dysfunction is associated with substance use, various studies have investigated the effectiveness of antiepileptic drugs and combination therapies. Another treatment strategy involves targeting endophenotypes associated with SUDs. For example, using cognitive enhancers to improve decision-making, planning, or impulse control may be a beneficial approach. Several pharmacological studies are currently underway. In addition to new pharmacological perspectives, alternative therapies such as psychotherapy (including drug-supported), mindfulness-based interventions (MBI), and virtual reality (VR) techniques are also being considered.

Psychological Factors

Complex Entanglement: Substance Use Disorder, Personality, and Psychopathology

Substance Use Disorder (SUD) can be understood as a complex interplay of behavior, personality, and mental health conditions. The co-occurrence of substance use and psychopathology (referred to as dual diagnosis) can be explained by shared risk factors such as socioeconomic status and certain personality traits. Many individuals with SUDs exhibit co-occurring psychiatric conditions, including personality, mood, and anxiety disorders, particularly in cases of poly-drug use. In these situations, eating disorders, psychotic symptoms, schizophrenia, and Post-Traumatic Stress Disorder (PTSD) can also be present. In some instances, a dual diagnosis of SUD and Autism Spectrum Disorder (ASD) is also observed.

Approximately 10–20% of the population experiences an addiction-related problem, and half of individuals with a substance use disorder also experience other mental disorders during their lifetime, and vice versa. The relationship between the two appears to be bidirectional. A positive association has been found between anxiety, depression, and craving intensity. Additionally, the duration of abstinence can influence the relationship between craving and psychiatric symptoms.

Mental Health Conditions

Temperament and personality traits are crucial factors contributing to the development and persistence of addiction-related behaviors. Key elements among these traits include disinhibition and a lack of self-control, referring to the ability to regulate one's behavior, emotions, and cognition. Self-control is considered a transdiagnostic dimension; its absence can manifest as externalized behaviors, seen in substance-related disorders and Attention Deficit Hyperactivity Disorder (ADHD), and internalizing behaviors, as in mood or anxiety disorders. High levels of behavioral activation (BAS) and low levels of self-control (EC) have been linked to Cluster B personality disorders, while high levels of behavioral inhibition (BIS) and low levels of self-control (EC) have been associated with Cluster C. For Cluster A, a mixed pattern of BAS and BIS has been observed.

The development of clinical symptoms, particularly anxiety and depression, and the manifestation of personality disorders, have both been correlated with low levels of self-control (effortful control—EC) and high levels of behavioral inhibition (BIS) in individuals with SUD. This suggests a greater inclination toward neuroticism, considered an additional personality trait that acts as a vulnerability factor for the development and persistence of SUD. Several studies indicate that low self-esteem is frequently observed in patients with SUD. However, some studies examining the relationship between SUD and self-esteem have reported high levels of self-esteem in some cases.

Anxiety disorders are frequently found in individuals diagnosed with Substance Use Disorder (SUD), and research also shows a strong correlation with craving intensity. Anxiety symptoms exhibit a strong association with substance use and addiction severity. Additionally, stress has been observed to have a positive correlation with craving intensity in opiate and methamphetamine use. Mood disorders are commonly found alongside SUD and correlate with craving intensity. Specifically, depression has a positive correlation with heroin craving intensity in patients receiving methadone maintenance treatment. While substance use may impair brain function and cause depressive or anxiety symptoms, individuals may use substances more frequently as a form of "self-medication" to manage such symptoms.

Attention-deficit hyperactivity disorder (ADHD) is found in approximately 25% of individuals with SUD. ADHD is considered a significant risk factor for SUD development, promoting early use of illicit substances and serving as an important predictor of the disorder. Some data suggest that ADHD doubles an individual's vulnerability to developing a psychoactive substance use disorder. Conversely, addiction negatively impacts the course of ADHD by worsening cognitive and memory impairment. The course of SUD is often more severe in patients with co-occurring ADHD than in those with SUD alone.

Post-Traumatic Stress Disorder (PTSD) frequently co-occurs with SUD, and both disorders commonly begin in adolescence. Some theories propose that traumatic experiences in adolescence may promote SUD development, which in turn facilitates PTSD onset. Other hypotheses suggest that the coexistence of the two disorders could result from using substances as a coping strategy to mitigate PTSD symptoms. It appears that certain substances can influence the immediate experience of PTSD symptoms, predisposing individuals to later substance use. A history of trauma is a significant risk factor for violent and suicidal behavior in individuals with SUD, highlighting the need to carefully consider psychological and trauma contexts in SUD assessment and treatment. An additional study examined the co-occurrence of Sexual Compulsive Behavior Disorder (CSBD) and tendencies for risky sexual actions among women with SUD. Results indicate that women with SUD exhibit more pronounced CSBD symptoms and a greater propensity for risky sexual behavior than controls. In this context, CSBD appears to mediate the association between substance use and risky sexual behaviors. Furthermore, addictive behaviors were found to be related to emotional abuse during childhood but not to other types of abuse.

SUD and Autism Spectrum Disorder (ASD) often co-occur, leading to a dual diagnosis. In most such cases, individuals use substances to manage high levels of anxiety, stress, and social difficulties, including perceived social rejection. The primary cause of this phenomenon appears to be neurobiological, although its interaction with psychological aspects is also important.

Individuals suffering from chronic pain or mood disorders are often disproportionately prescribed opioid medications, and this subgroup faces a greater risk of suicide. Numerous studies have explored potential connections between suicidal symptoms and SUD. Some findings suggest that any SUD diagnosis increases the likelihood of suicide, and conversely, an increased suicide risk is associated with SUDs. In-depth research comparing the impact of specific substances indicates that opioids, in particular, show a stronger correlation with suicidal ideation and attempts compared to substances like cocaine and cannabis. The intricate interplay between chronic pain, mood disorders, opioid use, and the heightened risk of suicide underscores the complexity of these issues and the need for comprehensive and multifaceted care approaches. For research purposes, it is essential to consider co-occurring disorders alongside SUDs, including mood and personality disorders. Additionally, assessing anxiety and depression symptoms is crucial for providing personalized treatments to individuals at risk of suicidal ideation.

Social Factors

SUD is a complex condition influenced by numerous social factors, which play a significant role in both its development and maintenance. Social determinants of health (SDoH) refer to the conditions in which individuals are born, grow, live, work, and age. These circumstances are shaped by the distribution of financial resources, power, and assets at global, national, and local levels.

Childhood Influences

To understand how addiction can become embedded in a person's life, it is necessary to examine the individual's upbringing, starting from childhood. Parental style and the resulting family dynamics play a crucial role in both individual development and addiction development. Children raised with an authoritarian parenting style—characterized by demanding, strict, and firm parents who show little affection, warmth, and involvement—tend to be more likely to use alcohol and other substances. In contrast, an authoritative parenting style, marked by high demands and responsiveness, has positive outcomes, decreasing the likelihood of children using alcohol, cigarettes, and cannabis. The neglectful parenting style, with low demand and responsiveness, is most strongly associated with substance use; finally, though to a lesser extent, the permissive parenting style, with low demand and high responsiveness, also shows a connection to substance use.

Furthermore, traumas experienced in childhood (physical or emotional abuse, neglect), even if occurring only once, can lead to adverse physiological consequences and poor health outcomes, such as increased cortisol levels that subsequently elevate the risk of substance use. This could explain the relationship between mechanisms involved in coping with trauma and those that lead to substance use, placing stress at the center of this connection: while milder forms of stress can result in positive behavioral effects, severe or chronic stress can overwhelm an individual, leading them to cope by taking substances that can quell perceived stress and anxiety, thereby increasing the likelihood of developing an addiction.

Adolescent Influences

Adolescence is a critical period for biological, psychological, and social development, but it is also a sensitive time when individuals are particularly susceptible to substance use, its negative effects, and subsequent addictions. Early encounters with substances increase the likelihood of future problems (physical, behavioral, social, and health) and raise the risk of addiction if use begins before age 18. Most adolescents do not exhibit problematic use patterns, and this initial spike in use can be considered experimental. Any level of substance use during adolescence is risky and can lead to negative developmental outcomes, including disruption of brain development, educational underachievement, behavioral consequences (e.g., related to driving, sexual behavior), and injury, as well as the potential to induce or worsen mental comorbidities and progress to SUD. Additionally, early-onset substance use is associated with increased psychosocial problems and problematic substance use later in life.

In this scenario, studies have found that parental support acts as a protective factor against SUD onset: adolescents aged 9 to 18 years with positive parental relationships, characterized by emotional closeness and supervision, are less likely to try alcohol, marijuana, and cigarettes. Conversely, lower levels of family functioning increase the likelihood of these behaviors. This finding is particularly interesting when compared with peer support, as opposite effects are observed: peer support correlates with higher alcohol consumption. Both perceived rejection from parents and peers, and loneliness, are associated with alcohol consumption. Social support is the most effective tool in resolving the disorder; it encompasses various behaviors, from simply being present, listening, and sharing problems to providing concrete help. This support can come from family, friends, and professionals, and it is crucial because addiction requires more support than physical illness, often involving withdrawal and severing ties with harmful friendships.

The relationship between social conditions and drug use is reciprocal. In parallel with previous points, SUD negatively affects social behavior, causing individuals to avoid social situations in favor of drug use, thus entering a vicious cycle where increased drug use leads to greater isolation. This phenomenon has intensified in recent years due to lockdowns, which confined young people at home for extended periods. It has been observed that COVID-19 contributed to an increase in overdoses and social isolation.

Adult Influences

As individuals age, those with Alcohol Use Disorder (AUD) often report having grown up in families characterized by less cohesion and expressiveness and more conflict. These are risk factors for alcohol use, often masked by the individual’s justifications for their use (e.g., alcohol reduces worry). Increasing levels of loneliness, also experienced during COVID-19, are linked to increased alcohol use and anxiety. A lack of social support, medical complications, and confronting bereavement are characteristics of older age that could contribute to the onset of SUD or AUD. This increases the likelihood of premature mortality, impacting healthy aging and elevating health risks: alcohol consumption is associated with higher rates of dementia and vulnerability to negative withdrawal symptoms due to the fragility and co-occurrence of other health conditions in older adults.

An interesting aspect emerging from research is the incidence of SUDs in young adults aged 18 to 25. Approximately 21% of young adults meet the diagnostic criteria for SUDs, a significant contrast to the 9% prevalence in 12–17-year-olds and 7% in individuals aged 26 and above. These data could be explained by many factors. For instance, difficulties young adults aged 18–25 face in successfully adapting to this transitional phase could lead them to turn to substance use as a coping mechanism. Furthermore, evidence indicates that early manifestations of delinquency or aggression correlate with substance use in young adults.

Social Background Factors

The social context in which an individual grows up and lives plays a crucial role in the development of certain addictions. One research study found that most individuals with addiction disregard the idea of marriage to dedicate their time to addictive behaviors without responsibility or criticism from a spouse. More than half of the sample were male and came from urban areas, which are easily accessible for drug cultivation and dealing, often presenting security and surveillance issues. Another study found that neighborhood disorder, such as graffiti, noise nuisance, and crime, was associated with alcohol use more prominently in women but not in men. For men, instead, social cohesion—defined as feelings of attachment to the neighborhood, relationships and solidarity with neighbors, and the neighborhood in general—was a risk factor.

Progression Patterns and Risk and Protection Factors

Understanding how addictions develop and persist is crucial for adopting the most effective prevention and intervention strategies. This section examines both the patterns of progression in substance use and the related risk and protective factors to provide a comprehensive framework for this complex phenomenon.

Impaired awareness of illness related to addiction to recreational or pharmaceutical substances is an understudied concept that affects whether individuals adopt interventions, seek treatment, and remain in treatment. In substance use disorder, illness awareness refers to one's subjective recognition of having a substance use problem. It also includes accepting the need for treatment and understanding the negative consequences of substance use. Individuals with impaired illness awareness in substance use disorder are less likely to use clinical services and more likely to drop out of treatment, regardless of the severity of their use. Conversely, higher levels of illness awareness in substance use disorder are associated with better treatment engagement, adherence, and improved clinical outcomes.

A narrative review indicates a strong connection between mental disorders and SUD in Transitional Age Youth (TAY), the period spanning adolescence and emerging adulthood, approximately between 15 and 25 years of age. The initiation of drug use peaks in adolescence, but in many cases, drug use gradually decreases after this period. Most adolescents do not show problematic use patterns, and this spike can be considered experimental drug use. All children entering adolescence are at risk for adverse health outcomes related to alcohol or other drug use. Substance misuse significantly increases from mid to late adolescence. For adolescents, any level of substance use is risky and can result in negative developmental outcomes, including disruption of brain development, educational underachievement, behavioral consequences (e.g., related to driving, sexual behavior), and injury, as well as the potential for inducing or exacerbating mental comorbidities and progression to SUD. Furthermore, early-onset substance use is associated with increased psychosocial problems and problematic substance use later in life.

Preexisting mental disorders are known risk factors for the emergence and progression of SUD. A narrative review highlights a common co-occurrence between mental disorders and SUD among adolescents and young adults. According to the authors, these issues negatively influence each other. A study of juvenile detainees demonstrated that substance use, behavioral disorders, and internalizing disorders predict the development of SUD. This underscores the importance of treating childhood/adolescent disorders to reduce the emergence of secondary SUD.

Emerging evidence shows that a low Socioeconomic Position (SEP) is an important determinant of many mental disorders, including substance use disorders. In a cohort study involving 1.6 million individuals in the Stockholm region, alcohol and drug use disorders were more common among individuals with lower levels of education compared to those with higher levels of education, in both males and females.

Peer interactions are often intertwined with physical activities during adolescence, and physical activity is broadly (positively) related to mental health through psychosocial, behavioral, and physiological mechanisms. Two studies examining pairs of discordant twins on physical activity found that physical inactivity in adolescence was associated with increased consumption of alcohol, drugs, and smoking in young adulthood. Peer relationships become more important during adolescence, serving increasingly as a source of social support and influence on developing adaptive and maladaptive behaviors. In the context of substance use disorders, observational studies on adolescents have yielded conflicting results depending on the type of physical activity and substances examined. Factors such as rejection and loneliness may increase the risk of substance-related issues in adolescence and early adulthood. Social integration may lead to greater access to substances, as well as friendship with deviant peers. Conversely, friendship with peers who do not use substances may serve as a protective factor. This study used a co-twin control design to explore participation in sports, physical activity, and friendship quality as predictors of substance use. The results indicate that participation in sports and positive friendship quality were associated with an increased likelihood of substance use. In a longitudinal study, participants (N = 2880) completed four annual surveys during late adolescence and the transition to young adulthood. Results highlighted key individual and community-level protective factors that decrease the risk of opioid use.

While long-term use of alcohol, opioids, or sedatives is often associated with impaired sexual function, the use of alcohol, cannabis, cocaine, amphetamines, or hallucinogens may increase sexual arousal in the short term. This can lead to use aimed at enhancing performance. Several studies have investigated the association between prevalent SUD and hypersexuality. The targeted use of drugs to evoke specific physical and/or psychological effects during sexual activity (e.g., to increase sexual performance or achieve sexual disinhibition) is termed chemsex.

Media representation of substances and alcohol (TV shows and movies that depict people openly using drugs and/or alcohol) significantly impacts the ideas children and adolescents form about them. Young people are also more likely to begin using them and, consequently, develop SUDs. The power of the media should be harnessed to positively influence opinions and beliefs about drugs and alcohol, given its influence in teenagers' lives.

Risk factors often show positive correlations with each other and negative associations with protective factors. Essentially, individuals with certain risk factors are more likely to encounter additional risks, while protective factors tend to be less prevalent. Furthermore, the cumulative impact of these factors significantly influences the development or prevention of behavioral health issues. Young people with multiple risk factors face a higher likelihood of experiencing conditions affecting their physical or mental well-being, whereas those with multiple protective factors are at a reduced risk.

Interactions Between Psychological, Social, and Biological Factors

Previous sections of this article analyzed the extent to which individual biological, psychological, and social factors contribute to the development and maintenance of substance use disorder. However, these factors rarely have a significant influence when considered in isolation; therefore, it is important to acknowledge their co-presence and pay attention to how they interact in a person's life. This section examines how these factors collectively interact in individuals with SUD.

A Biopsychosocial Model for Understanding Addiction

Substance addiction is a biopsychosocial phenomenon. Psychosocial factors are multidimensional constructs spanning two domains: psychological, which includes factors such as depression, anxiety, distress, self-esteem, and satisfaction; and social, relating to socioeconomic status, employment, religion, physical attributes, family, relationships with others, and locality. These factors contribute to the development of mental and physical disorders. Drug use is frequently associated with negative outcomes across various aspects of an individual's life. SUDs can lead to adverse physical, mental, and social consequences, including addiction, substance-induced disorders, neurological complications, cognitive impairment, unemployment, incarceration, and suicidal behavior. Additionally, stigma and discrimination reduce the likelihood of individuals who use drugs receiving needed help. Fewer than 20 percent of people with drug use disorders are in treatment, and access is highly unequal. Out of approximately 39.5 million individuals globally diagnosed with drug use disorders in 2021, only one in five received treatment.

The importance of considering a biopsychosocial model in examining influences on the development of substance dependence disorder was confirmed by a 2020 study conducted by the Department of Health and Environmental Engineering at the Johns Hopkins Bloomberg School of Public Health and the Multidisciplinary Center for Health Equity Research at Texas A&M University. The biopsychosocial model of addiction, in understanding the development and progression of substance use problems, emphasizes biological factors such as genetic predisposition, psychological and cognitive factors such as self-efficacy, outcome expectations, and readiness to change, and social factors such as family, peer, and partner influence. Therefore, understanding the interconnectedness of these factors could be an effective strategy in substance use prevention programs. Substance use disorder involves a variety of neurobiological processes, including the brain reward system. This system, also known as the dopaminergic system, is crucial in sending behavioral responses related to pleasure and gratification. Thus, a key role in understanding how an SUD develops is played by the interaction between the social environment, individual functioning, and family history.

Family History, Role Models, and Psychological Aspects

Beginning with the family during childhood, young people become involved in multiple activities when they enter school; especially during middle school, peers become increasingly important and influence individual development. In adolescence, and even more so in the transition to adulthood, romantic relationships become additional agents of socialization and, along with the peer group, represent an element of the reward system.

Family members serve as role models for children, as shown in research conducted by the University of Washington and the University of Southern California involving 808 participants of different ethnicities, genders, and ages from 10 to 33. The results showed that positive social and family environments create a positive model for future interactions. In contrast, a family history of depression may negatively influence mental health functioning during adulthood: a family environment characterized by chronic stress, conflict, or other forms of dysfunction influences the reward system, increasing sensitivity to rewarding stimuli and leading to greater reliance on substances that provide temporary relief. Additionally, if substance use behaviors exist in the family, children may perceive such behaviors as acceptable, potentially triggering an approach to various substance-focused social contexts as they grow up. The authors found that some psychological factors, such as the presence of generalized anxiety disorder or panic disorder or the experience of childhood trauma, are related to substance use. Psychological factors like childhood trauma may modulate social perceptions and adaptation to stressful life contexts, which can promote substance use. Other social factors, frequently associated with the development of psychopathological symptoms, are also linked to the development of SUD. According to research conducted in Stockholm, a low level of education increases the risk of substance use disorders and self-harm; furthermore, an association between low educational attainment and various mental disorders, such as schizophrenia, depression, anxiety, ADHD, and behavioral disorders, is highlighted.

Neurological Factors, Genetic Predispositions, and Personality Traits

Genetic predisposition can affect the brain's response to opioids and its ability to regulate the impulse for substance use. It can also influence an individual's vulnerability to developing psychological disorders such as anxiety or depression, which are strongly linked to the risk of addiction. For example, some theories suggest that individuals with autism spectrum disorder may possess dopaminergic differences in the fronto-cortical cortex, making them susceptible to repetitive pleasure-seeking, with the risk of easily translating into addictive behaviors. Additionally, a common dysregulation of the limbic system appears to exist in individuals with SUD and ASD.

A systematic review exploring the impact of both PTSD and SUDs on uncontrolled craving for substances found that post-traumatic stress disorder was significantly associated with increased levels of craving among patients with alcohol, cannabis, cocaine, tobacco, and other substance use disorders. Some studies have also observed a correlation between the severity of post-traumatic stress disorder symptoms and craving intensity, as substance use is a means of alleviating traumatic symptoms. The underlying mechanisms relate to negative emotional states, and emotional dysregulation plays a role in eliciting craving after traumatic exposure. Psychological, social, and biological factors may interact synergistically in craving and substance use. PTSD symptoms can trigger emotions that, in turn, increase craving for substances, and similarly, exposure to traumatic environments can act as a trigger for craving.

Psychological Factors and Treatment Success Expectations

When addressing addiction, factors such as self-efficacy (confidence in one's ability to succeed without the substance) and motivation (desire to change one's behavior) must be considered. These factors are positively correlated with treatment success and directly related to each other: lower self-efficacy influences motivation to seek positive social supports, and fewer social supports decrease self-efficacy.

Discussion

The development and maintenance of substance use disorders involve a complex interplay of biological, psychological, and social factors. In the biological realm, the endocannabinoid and dopaminergic systems, along with genetic variants, contribute to specific pathways in cannabis, opioid, and stimulant addiction. Psychological aspects reveal the significance of personality traits, such as disinhibition and low self-esteem, in addiction vulnerability. The co-occurrence of anxiety, mood disorders, and addiction, coupled with the strong correlation between traumatic events and substance use, further emphasizes the importance of considering psychological dimensions. Social elements, encompassing family background, parental styles, neighborhood characteristics, and peer support, significantly shape addiction patterns, while addiction, in turn, disrupts social behaviors, leading to isolation. The intricate interconnection of these factors underscores the multifaceted nature of addiction and the importance of comprehensive approaches in prevention and treatment strategies.

Future Research

Several avenues for future research could enhance understanding of SUD and its co-occurring psychiatric symptoms. Longitudinal studies tracking individuals from adolescence to adulthood could provide valuable insights into the long-term impact of early substance use on mental health outcomes and addiction trajectories. Understanding how factors such as childhood trauma, parental styles, and peer influences interact over time to shape substance use behaviors is crucial for developing targeted prevention and intervention strategies. Investigating the role of genetic influences and neurobiological factors in predisposing individuals to specific types of substance addictions could offer a more nuanced understanding of addiction vulnerability. By exploring genetic markers associated with different substance use disorders and their interactions with environmental factors, researchers can identify potential biomarkers for early detection and personalized treatment approaches. Furthermore, exploring the impact of social determinants such as socioeconomic status, access to healthcare, and community support on SUD outcomes is essential for addressing disparities in addiction treatment and recovery. Research focusing on how social factors influence treatment engagement, retention, and outcomes can inform the development of more effective and equitable interventions for individuals with SUD. Finally, investigating the impact of emerging trends, such as the use of digital technologies and social media on substance use behaviors, could provide valuable insights into novel risk factors for addiction. Understanding how online platforms influence substance-related attitudes, behaviors, and perceptions among different age groups can inform targeted prevention efforts in the digital age. By addressing these research gaps and exploring the complex interplay of biological, psychological, and social factors influencing SUD, future studies can contribute to more effective prevention strategies, personalized treatment approaches, and improved outcomes for individuals struggling with addiction and co-occurring psychiatric symptoms.

Limitations

While this review provides valuable insights into the complex interplay of biological, psychological, and social factors contributing to SUD and co-occurring psychiatric symptoms, several limitations should be acknowledged. The generalizability of the findings may be constrained by the geographic diversity of the included studies, which spanned various countries. This diversity could introduce cultural nuances that impacted the interpretation of results and the generalizability of the findings, potentially leading to a lack of overall consistency. The methodologies employed in the reviewed studies varied, encompassing cross-sectional, longitudinal, and randomized controlled trial designs. Variability in study designs may affect the comparability and synthesis of results. Additionally, reliance on published articles from indexed journals may introduce publication bias, potentially excluding valuable data from unpublished sources. To mitigate this, grey literature, including technical reports, organizational documents, blog posts, and theses, was incorporated, providing a more balanced and inclusive perspective. Finally, while efforts were made to include a comprehensive range of factors influencing SUD, additional variables not covered in this review might contribute to a more holistic understanding of substance addiction.

Conclusions

The findings in this review emphasize the importance of considering a biopsychosocial model when understanding addiction, highlighting the significant role played by neurotransmitter systems such as the endocannabinoid and dopaminergic systems in substance addiction. Moreover, the review underscores the impact of media representation on substance use behaviors among children and adolescents, stressing the need for positive messaging to counteract negative influences. Furthermore, awareness of the risks associated with substance use is particularly important from a prevention perspective.

Introduction

Drug misuse represents a significant global challenge. In 2021, an estimated 296 million people, or about 5.8% of adults aged 15–64, had used drugs in the past year. This widespread issue negatively impacts health, particularly mental well-being and safety. Unfortunately, many individuals facing drug-related problems do not seek help due to stigma and discrimination; less than 20% receive treatment, and access to care varies widely. It is important to note that substance use disorder can involve a single drug or multiple drugs (polysubstance use), with polysubstance use often being more difficult to treat and linked to more severe health issues, including psychosis.

A substance is defined as anything that activates the brain's reward system, causing individuals to prioritize its use over daily activities. This category includes alcohol, caffeine, cannabis, hallucinogens, opioids, and stimulants like cocaine and amphetamines. These substances can lead to addiction, especially for those who begin using them before age 18. Cannabis remains the most commonly used illegal substance globally, with 219 million users in 2021, and its use, particularly among young people, is increasing.

Hallucinogens, such as LSD and MDMA, are mainly used for recreation, with a notable percentage of adolescents having tried them. Opioids, like heroin, are used both medically and recreationally, and accounted for nearly 70% of drug-related deaths in 2019. Stimulants such as cocaine are highly addictive, with millions of users worldwide, particularly in North America, Oceania, and Western Europe.

While drug use disorders are more commonly reported by men, the issue affects both genders, with distinct patterns. Women tend to increase their drug consumption more quickly than men once they start, leading to more severe health and social problems. In 2021, women were the majority of users for amphetamine-type stimulants and non-medical pharmaceuticals, while men accounted for most opiate and cocaine users. Age also plays a role, with cannabis use among 15–16-year-olds often higher than in the general adult population. Younger individuals with substance use disorders are more likely to use cocaine and cannabis, violate rules, and experience strained family relationships, while older individuals more often maintain abstinence.

Substance use disorders frequently co-occur with other mental health conditions, especially in polysubstance users. Common co-occurring conditions include mood, anxiety, eating, and post-traumatic stress disorders (PTSDs), as well as psychotic symptoms and schizophrenia. The relationship between mental health symptoms and substance use is often a two-way street; mental health symptoms can be linked to substance use as a way to achieve desired effects or find relief, and substance use can also worsen mental health. This review aims to analyze the main factors contributing to the development and continuation of substance use disorders and their co-occurring mental health symptoms, providing data for prevention plans and understanding the role of psychiatric symptoms.

Materials and Methods

This review, though not a systematic review in the traditional sense, used structured search methods to ensure transparency in selecting articles. The search was conducted in January 2024 using Primo VE Discovery, which combines results from databases like PubMed, PubMed Central, and ScienceDirect. The selection of articles used four main search terms related to substance use disorder, addiction, psychiatric symptoms, and biological, psychological, or social factors.

The chosen keywords directly relate to the study's aim: to analyze how biological, psychological, and social factors individually contribute to and interact in the development and maintenance of substance use disorder (SUD) and its co-occurring psychiatric symptoms. The review also aimed to identify individual and social factors that either prevent or increase the likelihood of developing SUD.

Articles included in the review met specific criteria: they were published in indexed journals such as PubMed or ScienceDirect, contained or related to the chosen keywords, and were published from 2022 onwards to ensure the most recent information, including data related to the COVID-19 pandemic.

Results

This literature review analyzed sixty full-text articles to understand the biological, psychological, and social factors that influence the development and continuation of substance use disorder (SUD) and its related mental health symptoms. Articles were chosen based on their relevance to how these factors interact, as well as their usefulness in identifying risk and protective factors for prevention and treatment. The studies, conducted between 2022 and 2024, came from various countries including Italy, India, Australia, Norway, Spain, Switzerland, and the United States. Researchers used different methods, such as cross-sectional, longitudinal, and randomized controlled trial designs. Together, these studies offer extensive insights into current patterns of SUD, its biological, psychological, and social origins, how these factors interact, and what influences treatment success.

Biological Factors

Researchers have long investigated the biological factors that may contribute to the development and continuation of substance addiction. While a direct cause-and-effect link between specific biological factors and addiction has not been definitively proven, current research offers promising insights that could change how addiction is treated. A key finding is the involvement of neurotransmitter systems, especially the endocannabinoid and dopaminergic systems. Psychoactive substances interact with these systems, altering brain activity in areas like the prefrontal cortex, striatum, and amygdala. These brain regions are crucial for regulating emotions, decision-making, and impulse control, and their activation produces the feelings of pleasure experienced by individuals with substance addictions.

Genetic factors also play a role in the risk of addiction. For cannabis dependence, variations in genes like CNR1 and CNR2 have been linked to increased withdrawal symptoms, craving, and brain changes. Studies show that specific gene variations can lead to altered brain volumes and increased activity in reward-related brain areas for cannabis users. For opioid addiction, similar genetic factors, such as specific alleles of the CNR1 gene, have been correlated with mental health conditions like major depression. Research using animal models has also shown how morphine treatment can reduce specific receptor functions in brain areas associated with pleasure and reward.

Stimulant addictions, like those to cocaine and methamphetamine, also involve changes in the brain's reward system. Cocaine affects dopamine levels, leading to compulsive behavior and relapse, while methamphetamine causes damage to the dopamine system and cell death. The endocannabinoid system appears to be involved in the brain's response to these drugs, with specific genetic variations linked to vulnerability to stimulant dependence and relapse. Dopamine receptors, especially D1 and D2, are critical in mediating cocaine's effects and predicting how a person experiences psychostimulants.

For hallucinogens, such as ketamine, studies suggest that these drugs can alter endocannabinoid concentrations in various brain regions. While information on the genetic factors specifically related to hallucinogen addiction is limited, many researchers believe that identifying changes in cannabinoid receptors or related enzymes could serve as important indicators to improve diagnosis and treatment success for individuals with substance use disorders.

Despite ongoing research into the neurobiology and behavioral aspects of addiction, the development of specific medications for substance use disorders remains challenging. Currently, few drug treatments are approved by major health agencies for most substance use disorders, with exceptions for alcohol, nicotine, and opioid use disorders. Future treatment strategies are exploring various approaches, including targeting underlying brain dysfunctions, using anti-epileptic drugs, or combining different therapies. Additionally, non-pharmacological methods like psychotherapy, mindfulness-based interventions, and virtual reality techniques are being considered to support recovery.

Psychological Factors

Substance use disorder (SUD) is deeply connected with an individual's behavior, personality, and other mental health conditions. Many people with SUD also experience other mental health challenges, such as personality disorders, mood disorders, and anxiety. This overlap, often called a "dual diagnosis," can be explained by shared risk factors like economic status and certain personality traits. For example, half of those with SUD will experience another mental disorder in their lifetime, and vice versa, suggesting a two-way relationship where each condition can influence the other.

Personality traits significantly contribute to the development and continuation of addictive behaviors. Key traits include a lack of self-control and disinhibition, which is the inability to manage one's own behavior, emotions, and thoughts. Low self-control is linked to various issues, from substance use to ADHD and mood disorders. Individuals with low self-control and high behavioral inhibition (a tendency to avoid new experiences) are more prone to anxiety and depression when experiencing SUD. While some studies link low self-esteem to SUD, others surprisingly find high self-esteem in these patients.

Anxiety disorders are very common in individuals with SUD and are strongly linked to the intensity of drug cravings. Similarly, mood disorders, especially depression, are frequently seen with SUD and can increase cravings for certain substances. Some individuals may use substances as a form of "self-medication" to cope with anxiety or depressive symptoms, even though substance use can worsen these mental health issues.

Attention-deficit hyperactivity disorder (ADHD) is present in about 25% of people with SUD and is a major risk factor for early substance use and the development of SUD, potentially doubling an individual's vulnerability. Conversely, addiction can worsen ADHD symptoms, leading to more severe cognitive and memory problems. Post-Traumatic Stress Disorder (PTSD) is also frequently linked with SUD, particularly starting in adolescence. One theory suggests that traumatic events in youth might lead to SUD, which then facilitates PTSD, or that substance use becomes a coping mechanism for PTSD symptoms. Trauma history is also a significant risk factor for violent and suicidal behaviors in individuals with SUD, highlighting the need for comprehensive care. Additionally, studies show a connection between SUD and problematic sexual behaviors, often mediated by sexual compulsive behavior. Emotional abuse in childhood has also been specifically linked to addictive behaviors.

Individuals with both SUD and Autism Spectrum Disorder (ASD) often use substances to manage high levels of anxiety, stress, and social difficulties. The underlying causes appear to be neurobiological, interacting with psychological factors. For people suffering from chronic pain or mood disorders, who are often prescribed opioids, there is a higher risk of suicide. Research consistently shows that any SUD increases the likelihood of suicide, with opioids showing a particularly strong link to suicidal thoughts and attempts. It is crucial to consider co-occurring mood and personality disorders, along with anxiety and depression symptoms, when assessing and treating individuals with SUD who may be at risk for self-harm or suicide.

Social Factors

Substance use disorder (SUD) is greatly shaped by social factors throughout a person's life. These social determinants of health, which include the conditions in which individuals are born, grow, live, work, and age, significantly influence both the start and continuation of SUD. How financial resources, power, and other assets are distributed globally, nationally, and locally also impacts these circumstances.

Early life experiences, especially during childhood, play a crucial role. The way a child is raised and family dynamics have a major impact on their development and risk of addiction. Children with authoritarian parents (demanding, strict, little affection) are more likely to use alcohol and other substances. In contrast, authoritative parenting (high demands, high responsiveness) is linked to lower rates of substance use. Neglectful parenting (low demand, low responsiveness) is most strongly associated with substance use, followed by permissive parenting. Childhood traumas, such as physical or emotional abuse, also increase the risk of substance use by causing adverse physiological effects, like elevated stress hormones, which can lead individuals to use substances to cope.

Adolescence is a sensitive period for substance use because of significant biological, psychological, and social development. Starting substance use early increases the risk of future physical, behavioral, social, and health problems, and raises the likelihood of addiction if initiated before age 18. Adolescents may experiment due to curiosity, boredom, peer pressure, or to cope with difficulties. Parental support and close family relationships are protective factors against SUD in adolescents, reducing the likelihood of alcohol, marijuana, and cigarette use. Conversely, low family functioning increases these behaviors. Peer support, however, can have opposite effects; while beneficial in general, it is correlated with higher alcohol consumption among peers. Loneliness and feeling rejected by parents or peers are also linked to increased alcohol use.

In adulthood, individuals with alcohol use disorder often report less family cohesion and more conflict in their backgrounds, which are risk factors. Increased loneliness, highlighted during the COVID-19 pandemic, is associated with higher alcohol use and anxiety. Older adults may face new challenges like lack of social support, medical complications, and bereavement, which can trigger or worsen SUD. This can lead to increased health risks, including higher rates of dementia and vulnerability to severe withdrawal symptoms due to their overall frailty and other existing health conditions. A significant number of young adults aged 18-25 meet the criteria for SUDs, possibly due to difficulties adapting to this transitional life stage and using substances as a coping mechanism.

The broader social environment also impacts addiction. Research shows that addicts may avoid marriage to maintain their addictive behaviors without judgment. Studies have found that male addicts often come from urban areas with easy access to drugs, while for women, neighborhood disorder (graffiti, noise, crime) is a stronger risk factor for alcohol use. For men, social cohesion—a sense of attachment and solidarity with their neighborhood—is important.

Progression Patterns and Factors of Risk and Protection

Understanding how addictions develop and continue is essential for effective prevention and treatment. Various factors influence this progression, acting as either risks that increase vulnerability or protections that reduce it.

One critical factor is impaired illness awareness, which refers to a person's recognition of their substance use problem, their acceptance of treatment needs, and understanding of the negative consequences. Individuals with poor awareness are less likely to seek or stay in treatment, despite the severity of their substance use. Conversely, greater awareness is linked to better engagement with treatment and improved outcomes.

Transitional Age Youth (TAY), typically aged 15 to 25, face a significant risk period. Drug use peaks during adolescence, though for many, this is experimental and decreases later. However, any substance use during adolescence is risky, potentially disrupting brain development, impacting education, leading to behavioral problems, and worsening or causing mental health issues. Early substance use is also linked to greater psychosocial problems and more severe substance use later in life.

Preexisting mental disorders are major risk factors for developing and worsening SUD. There is a common overlap between mental disorders and SUD in adolescents and young adults, with each issue negatively influencing the other. For example, childhood behavioral and internalizing disorders can predict the development of SUD, emphasizing the importance of treating these early-life conditions to prevent later SUD.

A person's socioeconomic position (SEP) also plays a significant role. Emerging evidence shows that lower SEP is linked to many mental disorders, including SUD. Studies indicate that individuals with less education are more likely to experience alcohol and drug use disorders compared to those with higher education levels.

Peer interactions, often tied to physical activities during adolescence, become increasingly influential. While physical activity is generally positive for mental health, its specific link to substance use varies. For instance, some studies on twins suggest that physical inactivity in adolescence is associated with increased alcohol, drug, and smoking use in young adulthood. Peer relationships are a major source of social support and influence. While social integration might lead to greater access to substances or friendships with peers who use drugs, having friends who do not use substances can be a protective factor. Loneliness and rejection can increase the risk of substance-related issues.

The use of substances to enhance sexual performance is another specific risk factor. While long-term use of certain substances can impair sexual function, others like alcohol, cannabis, cocaine, amphetamines, or hallucinogens may temporarily increase sexual arousal, leading to "chemsex" behaviors. Media representation of drugs and alcohol also significantly impacts the beliefs and behaviors of children and adolescents, potentially increasing their likelihood of substance use and addiction. Therefore, media has a powerful role in positively influencing perceptions of drugs and alcohol.

Finally, risk factors often go hand-in-hand and are negatively associated with protective factors. This means that individuals with one risk factor are more likely to encounter others, while protective factors tend to be less common. The combined effect of these factors significantly influences whether a person develops behavioral health issues. Young people with multiple risk factors face a higher chance of developing problems, whereas those with multiple protective factors have a lower risk.

Interactions between Factors

Substance addiction is a complex problem influenced by biological, psychological, and social factors working together. These "psychosocial" elements cover a wide range of issues, from mental states like depression, anxiety, and self-esteem to social aspects like economic status, family, and community relationships. These factors collectively contribute to both mental and physical health issues. Drug use often leads to negative consequences in many areas of life, including physical, mental, and social problems like addiction, brain damage, job loss, and suicidal behavior. Additionally, the stigma attached to drug use prevents many from getting the help they need; in 2021, only one in five people diagnosed with a drug use disorder received treatment.

The importance of considering this biopsychosocial model for understanding substance dependence was supported by research from Johns Hopkins Bloomberg School of Public Health. This model highlights biological factors such as genetic predisposition, psychological factors like self-efficacy and readiness to change, and social factors like family, peer, and partner influences. Understanding how these factors are connected is a vital strategy for effective substance use prevention programs. The brain's reward system, particularly the dopamine system, plays a key role in the pleasure and gratification associated with substance use. Therefore, the development of a substance use disorder is largely shaped by the interplay between a person's social environment, individual functioning, and family history.

Starting in childhood, family members act as role models. As individuals attend school and enter adolescence, friends become increasingly influential, along with romantic relationships in early adulthood, all contributing to the reward system. A family history of depression, for instance, can negatively affect mental health in adulthood, as a family environment marked by chronic stress or conflict can alter the brain's reward system. This increases a person's sensitivity to rewarding stimuli, leading to a greater reliance on substances for temporary relief. If substance use is common in the family, children may view it as acceptable, which can lead them towards social circles centered around drugs as they grow up. Psychological factors like anxiety, panic disorder, or childhood trauma are also linked to substance use. Childhood trauma, for example, can affect how a person perceives social situations and adapts to stress, potentially encouraging substance use. Other social factors, such as a low level of education, also increase the risk of both substance use disorders and various mental health conditions like schizophrenia, depression, and ADHD.

Genetic predispositions can influence how a person's brain responds to drugs and how well they can control impulses. Genes can also make someone more vulnerable to psychological disorders like anxiety or depression, which are strongly linked to addiction risk. For example, individuals with autism spectrum disorder might have differences in their brain's dopamine system, making them more prone to seeking repetitive pleasurable sensations, which can lead to addictive behaviors. A systematic review found that Post-Traumatic Stress Disorder (PTSD) is significantly associated with increased drug cravings across various substance use disorders. The severity of PTSD symptoms can correlate with craving intensity, as individuals may use substances to alleviate traumatic symptoms. The interplay of psychological, social, and biological factors can increase cravings and substance use, with traumatic experiences or environments acting as triggers.

For successful treatment, psychological factors like self-efficacy (belief in one's ability to succeed without the substance) and motivation (desire to change) are crucial. These factors are positively related to treatment success and influence each other: lower self-efficacy can reduce motivation to seek positive social support, and less social support can, in turn, decrease self-efficacy.

Discussion

The development and continuation of substance use disorders involve a complex interaction of biological, psychological, and social factors. In terms of biology, the endocannabinoid and dopaminergic systems, along with specific genetic variations, contribute to the pathways of cannabis, opioid, and stimulant addiction. Psychologically, personality traits like disinhibition and low self-control increase vulnerability. The common co-occurrence of anxiety, mood disorders, and addiction, alongside the strong link between traumatic events and substance use, highlights the importance of psychological considerations. Social elements, including family background, parenting styles, neighborhood characteristics, and peer influence, significantly shape addiction patterns. In turn, addiction disrupts social behaviors, leading to isolation. The intricate connection of these factors emphasizes the complex nature of addiction and the need for comprehensive prevention and treatment strategies.

Future Research

Further research could enhance our understanding of substance use disorder (SUD) and its co-occurring mental health issues. Long-term studies tracking individuals from adolescence to adulthood would provide valuable insights into how early substance use affects mental health and addiction pathways over time. Understanding how factors like childhood trauma, parenting, and peer influence interact throughout life is crucial for developing targeted prevention and treatment. Investigating the role of genetic and brain-related factors in predisposing individuals to specific addictions could offer a more detailed understanding of addiction vulnerability. By exploring genetic markers and their interaction with environmental factors, researchers could identify early detection tools and personalized treatments.

It is also essential to explore the impact of social determinants such as economic status, healthcare access, and community support on SUD outcomes. Research focusing on how social factors influence engagement and retention in treatment can lead to more effective and fair interventions. Lastly, studying the impact of new trends, such as the use of digital technologies and social media on substance use, could reveal novel risk factors for addiction. Understanding how online platforms influence attitudes and behaviors related to substances across different age groups can help shape targeted prevention efforts in the digital age. By addressing these research gaps and exploring the complex interplay of biological, psychological, and social factors, future studies can contribute to more effective prevention strategies, tailored treatment approaches, and improved outcomes for individuals dealing with addiction and related mental health conditions.

Limitations

While this review offers valuable insights into the complex interplay of biological, psychological, and social factors contributing to substance use disorder (SUD) and co-occurring mental health symptoms, it has several limitations. First, the findings' broad applicability may be limited by the diverse geographic locations of the included studies, which could introduce cultural differences affecting interpretation. The wide variation in cultural insights in this paper might lead to some inconsistencies. Second, the studies reviewed used various methodologies, including cross-sectional, longitudinal, and randomized controlled trial designs. This variability in study designs can make it difficult to compare and combine results effectively. Additionally, relying solely on articles from indexed journals might introduce publication bias, potentially excluding important information from unpublished sources. However, to mitigate this, grey literature, such as technical reports, organizational documents, blog posts, and theses, was also included to provide a more balanced and complete perspective. Lastly, while efforts were made to cover a comprehensive range of factors influencing SUD, other variables not included in this review could contribute to a more complete understanding of substance addiction.

Conclusions

The findings in this review highlight the importance of using a biopsychosocial model to understand addiction, emphasizing the key role played by brain systems such as the endocannabinoid and dopaminergic systems in substance addiction. Furthermore, the review underscores how media representation influences substance use behaviors in children and adolescents, pointing to the need for positive messaging to counter harmful influences. Lastly, being aware of the risks associated with substance use is especially crucial for effective prevention efforts.

Introduction

Drug misuse is a big problem around the world. In 2021, nearly 6 out of 100 people aged 15 to 64 had used drugs in the past year. This number went up from 240 million people in 2011 to 296 million in 2021. Drug use can hurt a person's health, especially their mental well-being, and their safety.

Often, people with drug problems do not get help because others judge them. Less than 20 out of 100 people with drug use problems get treatment, and it is not easy for everyone to get it. Some people use only one drug, while others use more than one. When people use more than one drug, it is often harder to treat, and it can cause more serious health problems, both mental and physical. People who use many different drugs may also have more complex health issues, like seeing things that are not there.

Types of Substances and Addiction

A "substance" that can lead to a drug use problem makes the brain feel good. This can cause people to stop doing normal things so they can use the substance instead. Examples of such substances are alcohol, caffeine, cannabis, drugs that make one see things (hallucinogens), things people breathe in (inhalants), pain relievers (opioids), calming drugs (sedatives), sleeping pills (hypnotics), anxiety medicine (anxiolytics), energy drugs (stimulants like amphetamines and cocaine), and tobacco.

For this study, the word "drugs" means natural or man-made substances that greatly change how a person thinks, makes choices, lives, and feels. These substances can cause strong cravings, lead to needing more for the same effect, cause dangerous use, create problems with family and friends, and harm a person's body and mind. This includes cannabis, hallucinogens (like MDMA), opioids (like heroin), hypnotics, and stimulants (like cocaine and amphetamines).

These substances can also lead to addiction, especially for younger people. Studies show that people who start smoking, drinking, or using drugs before age 18 are more likely to become addicted to these or other substances.

Marijuana is one of the most used illegal mind-altering drugs worldwide. In 2021, about 219 million people used cannabis. This number is 4.3 out of every 100 adults around the world. There is now more marijuana use and more people going to the hospital because of it, especially young people.

Hallucinogens can be put into three groups: classic ones like LSD and psilocybin; drugs that make a person feel separate from their body, like PCP and ketamine; and other types like MDMA. Most people use these drugs for fun. In 2020, about 7.5 out of 100 teenagers had used hallucinogens at least once.

Opioids are used both as medicine and for fun. In 2021, about 60 million people used opioids when they were not supposed to. Most of these people, about 31.5 million, used opiates like heroin. Opioids are also the main cause of deadly overdoses. They were linked to almost 70 out of every 100 drug-related deaths in 2019. In Europe, heroin is the drug most linked to crime.

Stimulants like cocaine are very addictive drugs that come from the coca plant. In 2020, about 0.4 out of 100 people aged 15 to 64 used cocaine around the world. North America had the most users, then Oceania, and then Western and Central Europe. The U.S. had the highest number of users, but Colombia had the highest rate of use compared to its population size.

Differences by Gender

Even though drug use problems are reported more often by men, both men and women have drug problems, but with some differences. In the past, more men had drug use problems. But recent studies show that this gap is much smaller now. Women tend to increase their drug use faster than men once they start, which leads to more serious health and social problems for them. In 2021, more women used stimulants like amphetamines and misused prescription drugs. Men made up most of the users for opiates and cocaine.

Differences by Age

Cannabis use among 15- to 16-year-olds changes depending on the area. In most places, more teenagers use the drug than adults aged 15 to 64.

Younger patients were more likely to use cocaine and cannabis. They were also more likely to break lockdown rules, have worse family relationships, and earn less money. Older patients, however, were more likely to stay away from drugs.

Mental Health and Drug Use

Drug use problems often happen with other mental health conditions, especially when a person uses more than one drug. Common mental health issues seen during treatment include problems with mood, anxiety, eating, and PTSD (Post-Traumatic Stress Disorder). Seeing things that are not there and schizophrenia are also common. Mental health and drug use are connected in two ways: mental health problems can lead to drug use, and drug use can cause mental health problems. People may use drugs to feel good, get energy, or ease their worries.

Mental health issues and behaviors are not only linked to starting a drug problem. They are also connected to different stages of drug addiction, like when a person stops using drugs or has strong cravings for them.

About This Study

This study looked at what main things cause drug use problems to start and continue, and how they relate to mental health issues. It is important to know what causes drug problems, especially when someone also has a mental health condition. The study aims to provide facts to help create good ways to prevent drug use. It also aims to understand how mental health problems play a role in drug use. This means finding out if mental health problems cause drug use, or if drug use causes mental health problems, and how to tell the difference. To do this, the study first looked at body, mind, and social factors that lead to drug use problems. Then, it looked at how drug use gets worse and what helps or harms. Last, it focused on how all these different factors work together to show how drug use problems might begin.

How This Study Was Done

This study used careful search methods to find and pick the right papers, even though it is not a traditional full review. The search was done in January 2024, using a tool that looked through many different research databases.

The study looked for papers that had certain main words related to how body, mind, and social factors lead to drug use problems and how these factors work together. It also looked at what individual and social things stop or increase the chance of drug use problems and related mental health issues.

This study included a chart to show how the research was done and how papers were picked. While this study did not do some things typical for full reviews, like a deep analysis of numbers or checking for study flaws, the careful search methods help make sure the findings are reliable. Not having these extra steps does not mean the study is not helpful; it just means it has a clear purpose and focus.

What Papers Were Included

The study included papers that met these rules:

• All studies and reviews were in well-known science journals.

• Studies used the search words or were about the same topics.

• Studies were published from 2022 onward. This was to make sure the information was as new as possible, including things related to the COVID-19 pandemic.

What Was Found

Details of Studies Used

This study looked at 60 full papers to learn about the body, mind, and social factors that cause drug use problems and ongoing mental health issues. Papers were chosen based on how well they helped understand how these factors work together, and how to find helpful or harmful things for planning ways to prevent and treat drug use. The studies looked at were done between 2022 and 2024 in many different places, like Italy, India, Australia, Norway, Spain, Switzerland, and the United States. They used different ways of studying, like looking at groups at one time, watching groups over time, or doing tests where people were put into groups by chance. Together, these studies give a full picture of modern drug use problems, their causes in the body, mind, and society, how these factors mix, and what helps people get better.

Body Factors

Over the years, many studies have tried to find out what body factors might cause and keep drug addictions going.

It is not yet known for sure if certain body factors directly cause addiction. However, some study results are interesting and show promise. They could greatly change how addiction is treated.

Scientists have seen that certain brain systems are very important in drug addiction. Two of these, the endocannabinoid and dopamine systems, seem to play a very big role. Drugs connect to these systems or change how they work. This leads to changes in how certain parts of the brain act. These brain areas have a lot of receptors from these two systems. They include the front part of the brain, parts involved in feelings, and parts that help with rewards and decision-making. When these brain areas are active, people with drug addictions feel a sense of pleasure. This is because these brain parts help control feelings, make choices, and stop sudden urges.

The next parts will look at how different body factors play a part for each type of drug.

Cannabis Addiction

Genetics and brain factors may play a role. Certain differences in genes related to the endocannabinoid system might make it more likely for someone to become dependent on cannabis. For example, a specific gene change was linked to more withdrawal symptoms and cravings after a short time without cannabis. It also caused more activity in certain brain areas. In one study, cannabis users with a certain gene change had a smaller part of their brain called the hippocampus. This might happen because cannabis affects a brain receptor that is changed by this gene. More recently, another gene has been linked to a higher chance of schizophrenia in people with cannabis use disorder.

Studies have also shown how other gene types are strongly involved in cannabis addiction. These gene types have been linked to more activity in brain areas related to pleasure.

A recent study showed that people dependent on cannabis had changes in their brain structure. These changes seemed to be linked to how much of an enzyme (a body chemical) that breaks down certain brain chemicals was present in different brain regions.

One research study looked at how THC (a chemical in cannabis) affects worry and a brain area called the amygdala. They found that when people were worried, taking THC changed how the amygdala reacted and increased the number of certain brain receptors available.

Opioid Addiction

There is not much information about gene differences in the endocannabinoid system linked to opioid addiction.

Like cannabis addiction, certain genes and gene types can also be linked to opioid addiction. One study looked at how a specific gene type was linked to major depression or thoughts of suicide in people getting treatment for opioid addiction. This study found that a certain gene type was strongly linked to a lower chance of having major depression in their lifetime, but not to suicidal thoughts. Many studies on how opioids affect the body have been done using animals. In one important study, rats were given morphine for a long time. They showed fewer of certain brain receptors and less of certain brain chemicals in parts of the brain that control pleasure.

Stimulant Addiction

Cocaine is a drug that harms brain cells that release dopamine, which is a chemical that makes people feel good. It stops the brain from taking back dopamine, which leads to strong urges and falling back into old habits.

Methamphetamine, another stimulant, damages the dopamine system and causes brain cells to die. Just one use of methamphetamine changes the amounts of certain brain chemicals in mice. This suggests that the endocannabinoid system might be involved in how the brain reacts to these drugs.

Changes in the body and brain have been found in people who use stimulants like amphetamines and cocaine. Specific gene differences have been linked to developing a dependence on stimulants. Also, many changes in the endocannabinoid system's targets have been found, mainly from cocaine studies. This shows how important this system is in controlling different parts of stimulant addiction, like feeling good, wanting more, withdrawal, or falling back into old habits.

Genes and brain factors are very important. Many studies show how important the endocannabinoid system is in controlling what stimulants like cocaine and amphetamine do.

It has been confirmed that some genetic differences make people more likely to fall back into stimulant use. Two different gene changes were found to greatly increase the risk of cocaine addiction in both white and Black people with these gene types.

The importance of the dopamine system should not be forgotten. Certain brain receptors are key in how cocaine works. They are involved in seeking the drug, giving it to oneself, and how cocaine affects gene activity in the brain. Other brain receptor levels can predict how much someone likes stimulants. Using or misusing cocaine for a long time lowers the number of these receptors and lessens the brain's quick responses to stimulants.

Hallucinogens Addiction

Some studies have looked at how drugs that cause visions affect the cannabis and brain's natural systems. Giving ketamine to mice for a short time increased brain chemical levels in certain brain areas.

Even though there is little information right now, most experts believe it would be helpful to find changes in brain receptors, chemicals, or enzymes. This could help doctors better identify people with drug use problems and make their drug treatment more successful.

Treatment Ideas

Even after many studies, treating drug use problems with medicine is still a new area. While much progress has been made in understanding how addiction affects the brain and behavior, it has been hard to create specific medicines. So far, no drug treatments have been approved by major health groups for most drug use problems, except for alcohol use disorder, nicotine use disorder, and opioid use disorder.

Since problems with a certain brain system are linked to drug use, many studies have also looked at how well anti-seizure medicines work and how well using a mix of treatments works. Another treatment idea is to focus on specific problems related to drug use. For example, using medicines to help with decision-making, planning, or stopping sudden urges might be helpful. Many medicine studies are happening now.

Besides new medicine ideas, other treatments can be considered. These include talking therapy (sometimes with drug support), mind-training exercises, and using virtual reality. A table lists body factors linked to different drug addictions like cannabis, opioids, stimulants, and hallucinogens. This table sums up gene differences, brain changes, and how brain chemical systems are involved, showing key things that affect addiction.

Mind Factors

Drug Use, Personality, and Mental Health

Drug use problems can be seen as a complex mix of behavior, personality, and mental health issues. Drug use and mental health problems often happen together because they share common causes like a person's money situation and personality traits. Many people with drug use problems also have mental health issues, personality problems, mood problems, and anxiety problems, especially if they use more than one drug. In these cases, eating problems, seeing things that are not there, schizophrenia, and PTSD (Post-Traumatic Stress Disorder) can also be found. Sometimes, a drug use problem and autism are found together.

Studies show that about 10 to 20 out of 100 people have a problem related to addiction. Half of the people with a drug use problem also have other mental problems in their lives, and the same is true the other way around. The two seem to affect each other. There was a link found between worry, sadness, and how strong cravings were. Also, how long someone had stopped using drugs could affect the link between cravings and mental health problems.

Personality and Addiction

A person's natural qualities and personality traits are very important in causing and keeping addiction-related behaviors going. Among these traits, not being able to control oneself is key. Self-control means being able to manage one's own actions, feelings, and thoughts. Not having self-control can show up in outward behaviors, like drug use problems and ADHD, or in inward feelings, like mood or anxiety problems. High levels of seeking rewards and low self-control have been linked to certain personality problems. High levels of avoiding problems and low self-control have been linked to other personality problems. For another group of personality problems, there is a mix of seeking rewards and avoiding problems.

Having mental health problems, especially worry and sadness, and showing personality disorders were both linked to low self-control and high levels of avoiding problems in people with drug use problems. This means there is a greater chance of being a worried person, which is another personality trait that makes a person more likely to develop and keep a drug use problem.

Some studies show that low self-worth is common in people with drug use problems. However, other studies looking at drug use problems and self-worth have found high levels of self-worth.

The next part will briefly look at the mental factors most often seen with drug use problems.

Anxiety and Addiction

Anxiety problems are often found in people with drug use problems. Research also shows a strong link with how strong cravings are. Anxiety symptoms are clearly connected to drug use and how serious the addiction is. Also, stress has been seen to be linked to how strong cravings are for opiates and methamphetamine.

Mood Disorders and Addiction

Mood problems are commonly found with drug use problems and strong cravings. In particular, sadness was found to be linked to strong cravings for heroin in patients getting methadone treatment. It is interesting that even though drug use can harm brain function and cause sadness or worry, people might use drugs more often to "self-medicate" or manage these feelings.

ADHD and Drug Use

Attention-deficit hyperactivity disorder (ADHD) is found in about 25 out of 100 people with drug use problems. ADHD is also seen as a big risk factor for developing drug use problems because it makes people start using illegal drugs earlier. This makes it an important sign of future drug use problems. Some information suggests that having ADHD makes someone twice as likely to develop a drug use problem. On the other hand, addiction makes ADHD worse by hurting thinking and memory. Drug use problems are more serious in people who have both ADHD and drug use problems than in those who only have drug use problems.

Traumatic Events, PTSD, and Drug Use

Post-Traumatic Stress Disorder (PTSD) is often found with drug use problems, and both problems often start in teenage years. Some ideas suggest that experiencing upsetting events in teenage years might lead to drug use problems, which then makes PTSD more likely. Other ideas say that having both problems might come from using drugs to cope with PTSD symptoms.

It seems that some drugs can change how someone experiences PTSD symptoms right away, which then makes them more likely to use those drugs later. A history of upsetting events is a big risk for violent and suicidal behavior in people with drug use problems. This means that doctors need to carefully think about a person's mental state and past upsetting events when checking and treating patients with drug use problems.

One study looked at sexual actions that are hard to control and risky sex habits among women with drug use problems. The results show that women with drug use problems had more signs of sexual actions that are hard to control and were more likely to have risky sex than women without drug use problems. In this case, actions that are hard to control seemed to play a role in the link between drug use and risky sex.

Also, it was found that addictive behaviors were linked to emotional harm during childhood but not to other types of harm.

Drug Use and Autism

Drug use problems and Autism Spectrum Disorder (ASD) are often found together, leading to a "dual diagnosis." In most of these cases, people use drugs to manage high levels of worry, stress, and social problems, including feeling left out by others. The main cause of this seems to be related to the brain, though how it mixes with mental factors will be looked at more in other studies.

Self-Harm and Suicide Risk in People with Drug Use Problems

People who have ongoing pain or mood problems often get too many opioid pain medicines. This group of people has a higher risk of suicide. Many studies have looked at the possible links between thoughts of suicide and drug use problems. Some findings suggest that having any drug use problem makes suicide more likely, and in turn, a higher risk of suicide is linked to drug use problems. Detailed research comparing the effect of specific drugs has shown that opioids, in particular, have a stronger link to thoughts and attempts of suicide compared to drugs like cocaine and cannabis. The complex way that ongoing pain, mood problems, opioid use, and the higher risk of suicide are connected shows how complicated these issues are. It also shows the need for full and many-sided ways of care. For research, it is important to think about other health problems along with drug use problems, such as mood and personality problems. Also, checking for worry and sadness symptoms is key to giving special treatments to people at risk of thinking about suicide. A table sums up mental factors linked to drug addiction, including how it mixes with behavior, personality, and mental health issues, as well as specific mental factors like worry, mood problems, ADHD, PTSD, autism, and the risk of self-harm and suicide.

Life and Social Factors

Drug use problems are complex and are affected by many things, including social ones. Social factors play a big part in both starting and continuing drug use problems. Social influences on health are the living conditions people are born into, grow up in, live in, work in, and age in. These conditions are shaped by how money, power, and assets are shared around the world, in countries, and in local areas. The next part will look at social factors that cause and keep drug use problems going.

How Childhood Can Affect Drug Use

To understand how addiction can get into a person's life, one must start by looking at where the person grew up, right from childhood. The way parents raise a child and the family life that comes from it play a very important part in both how a person grows and how addiction starts. Children raised by very strict parents who demand a lot but show little love or care are more likely to use alcohol and other substances. On the other hand, parents who demand a lot but also respond to their child's needs have positive results, making it less likely for children to use alcohol, cigarettes, and cannabis. Parents who do not demand much and do not respond much are most likely to be linked to drug use. Lastly, parents who do not demand much but respond a lot were also linked to drug use, though to a smaller degree.

Also, upsetting events in childhood (like physical or emotional harm, or not being cared for), even if they happened only once, can lead to bad health effects. For example, they can cause higher levels of a stress hormone. This then increases the risk of drug use. This might explain why coping with upsetting events is linked to drug use. Stress is at the center of this link. While small amounts of stress can have good effects on behavior, serious or long-lasting stress can make a person unable to cope. Then, the person might try to deal with it by taking substances that calm stress and worry, making them more likely to develop an addiction.

How Teenage Years Can Affect Drug Use

It is widely known that teenage years are a very important time for body, mind, and social growth. But it is also a sensitive time when a person can easily be affected by drug use, its bad effects, and later addictions. Starting to use drugs early makes it more likely to have problems in the future (body, behavior, social, and health problems). It also raises the risk of addiction if drug use starts before age 18. Most teenagers do not have serious drug use problems, and this early use can be seen as trying drugs out.

All children entering their teenage years are at risk for bad health outcomes from alcohol or other drug use. Drug misuse greatly increases from mid to late teenage years. For teenagers, any drug use is risky and can lead to bad things happening as they grow, like harming brain growth, doing poorly in school, bad behaviors (like unsafe driving or sex), and injuries. It can also cause or make worse mental health problems and lead to a drug use disorder. Also, starting drug use early is linked to more social and mental problems and more serious drug use later in life.

In this situation, studies have found that parent support helps protect against drug use problems. Teenagers aged 9 to 18 who have good relationships with their parents, where there is emotional closeness and oversight, are less likely to try alcohol, marijuana, and cigarettes. But, less strong family life increases the chance of these behaviors happening. This is interesting when compared to friend support, as it has opposite effects: friend support is linked to more alcohol use. Both feeling rejected by parents and friends, and feeling alone, are linked to alcohol use. Social support is the best way to help solve the problem. It includes many behaviors, from just being there, listening, and sharing problems to giving real help. This support can come from family, friends, and professionals. It is important because addiction needs much more support than a physical sickness. This is because it causes people to withdraw and break ties with bad friends.

The link between social situations and drug use goes both ways. Along with what has been said, drug use problems harm social behavior. They make a person avoid social situations so they can spend more time on drug use instead of on rewarding social times. This creates a bad cycle where the person starts using drugs more often, which makes them feel more alone. This has happened more in recent years because of lockdowns, which made young people stay home for long times. In fact, it has been found that COVID-19 led to more overdoses and feeling alone.

How Adult Life Can Affect Drug Use

As they get older, people with alcohol use problems say their family had less closeness and openness and more fighting. These are risks for alcohol use, hidden by the person's reasons for using (for example, "alcohol makes me worry less"). Growing feelings of loneliness, also felt during COVID-19, are linked to more alcohol use and worry. Not having social support, health problems, and dealing with loss are common in older age that could lead to a drug or alcohol use problem. This increases the chance of dying too soon, hurting healthy aging, and raising health risks. Alcohol use is linked to higher rates of memory loss and being more open to bad withdrawal symptoms because older people are weaker and have other health problems.

An interesting point from research is how many young adults, aged 18 to 25, have drug use problems. About 21 out of 100 young adults meet the signs for drug use problems. This is a big difference from the 9 out of 100 for 12- to 17-year-olds and 7 out of 100 for people aged 26 and older. These numbers could be because of many things. For example, problems people aged 18-25 face in dealing with this change in life could lead them to use drugs to cope. Also, there is proof that early signs of bad behavior or aggression are linked to drug use in young adults.

Where Someone Lives and Grew Up

The social setting where a person grows up and lives plays a very important part in whether they develop certain addictions. One study found that most people with addictions ignore the idea of marriage so they can spend their time on addictive behaviors without having duties or being criticized by a spouse. More than half of the people in the study were men and came from city areas that were easy to access for growing and selling drugs, and had many safety and watching problems. Another study found that problems in the neighborhood, like spray paint, loud noises, and crime, were linked to alcohol use more often in women than in men. For men, a risk factor was social closeness, which means feeling connected to the neighborhood, having relationships and unity with neighbors, and the neighborhood in general. A table sums up social factors linked to drug addiction, including influences from childhood, teenage years, adulthood, and social background.

How Drug Use Gets Worse and What Helps or Harms

Understanding how addictions start and continue is very important for finding the best ways to prevent and treat them. This part aims to look at how drug use gets worse and what helps or harms, to give a full picture of how complex this problem is.

Not Knowing One Has a Problem

Not knowing one has a problem with using drugs, either for fun or as medicine, is a little-studied idea. But it affects whether someone gets help, seeks treatment, and stays in treatment. For drug use problems, "illness awareness" means a person's own understanding that they have a problem with drug use. It also includes whether they accept needing treatment and the bad things that happen because of drug use.

People who do not know they have a drug use problem are less likely to use health services and more likely to quit treatment, even if their drug use is very serious. But, people who are more aware of their drug use problem are more likely to stay in and stick with treatment, and they have better outcomes.

Transitional Age Youth (TAY)

A study review shows a strong link between mental problems and drug use problems in Transitional Age Youth (TAY), which means teenagers and young adults, roughly between 15 and 25 years old. Drug use starts most often in teenage years, but for many, drug use slowly goes down after this time. Most teenagers do not show problem use, and this peak can be seen as trying drugs.

All children entering their teenage years are at risk for bad health outcomes related to alcohol or other drug use. Drug misuse greatly increases from mid to late teenage years. For teenagers, any drug use is risky and can lead to bad things happening as they grow, like harming brain growth, doing poorly in school, bad behaviors (like unsafe driving or sex), and injuries. It can also cause or make worse mental health problems and lead to a drug use disorder. Also, starting drug use early is linked to more social and mental problems and more serious drug use later in life.

Preexisting Mental Disorders

It has been found that having mental problems already makes it more likely for drug use problems to start and get worse. A study review points out a common link between mental problems and drug use problems among teenagers and young adults. The study says that the two problems make each other worse. A study of young people in jail showed that drug use, bad behaviors, and internalizing problems (like sadness or worry) lead to drug use problems. This shows how important it is to treat childhood and teenage problems to lower the chance of drug use problems starting later.

Socioeconomic Position

New information shows that a low social and money position is an important cause of many mental problems, including drug use problems. In a study of 1.6 million people, alcohol and drug use problems were more common among people with less schooling compared to those with more schooling, for both men and women.

Physical Activity and Peer Interactions

Friend interactions often happen during physical activities in teenage years. Physical activity is generally linked to better mental health through social, behavior, and body reasons. Two studies that looked at twin pairs who were different in how much physical activity they did found that not being active in teenage years was linked to more alcohol, drug, and smoking use in young adulthood.

Friend interactions are often linked to physical activities during teenage years. As teenagers grow, friendships become more important. Friends increasingly become a source of support and influence on good and bad behaviors. In the case of drug use problems, studies on teenagers have shown different results depending on the type of physical activity and the drugs being looked at. Things like feeling rejected and alone might increase the risk of drug-related problems in teenage years and early adulthood. Being part of a social group might mean more access to drugs, as well as friendships with friends who do bad things. On the other hand, being friends with people who do not use drugs can help protect against drug use. This study used a design that compared twins to look at joining sports, physical activity, and how good friendships were as signs of drug use. The results show that joining sports and having good friendships were linked to a higher chance of drug use.

In a study over time, people took part in four yearly surveys during late teenage years and into young adulthood. The results highlight key individual and community factors that protect against opioid use.

Use Aimed at Increasing Sexual Performance

While using alcohol, opioids, or calming drugs for a long time often leads to problems with sexual function, using alcohol, cannabis, cocaine, amphetamines, or hallucinogens can increase sexual excitement for a short time. This might lead to using drugs to improve performance.

Several studies have looked at the link between drug use problems and having too much sexual behavior. Using drugs on purpose to get specific body and/or mind effects during sex (for example, to improve sexual performance or act without restraint) is called "chemsex."

Media Representation of Drugs

How drugs and alcohol are shown in the media (TV shows and movies that show people openly using drugs and/or alcohol) has a strong effect on what children and teenagers will think about them. They are also more likely to start using them and, because of that, develop drug use problems. The power of the media should be used to positively change opinions and beliefs about drugs and alcohol, given how much power it has in teenagers' lives.

How Harm and Help Factors Work Together

Harmful factors often are linked to each other and are linked negatively to helpful factors. Basically, people with some harmful factors are more likely to face more harm, while helpful factors tend to be less common. Also, how all these factors add up greatly affects whether mental health problems start or are stopped. Young people with many harmful factors are more likely to have problems with their body or mind. But those with many helpful factors are less at risk.

How Body, Mind, and Life Factors Work Together

In the parts before this, the study looked at how single factors (body, mind, and social) caused and kept drug use problems going. But these factors rarely have a big effect by themselves. So, it is important to know that these factors are often present together and to pay attention to how they work with each other in a person's life.

This part will look at how all these factors together work in people with drug use problems.

All Factors Work Together

Drug addiction involves the body, mind, and social life. Social-mind factors are many-sided ideas that belong to two different areas: mental, which includes things like sadness, worry, stress, self-worth, and feeling happy; and social (related to money situation, job, religion, body looks, family, relationships with others, and where one lives). These factors lead to mental and physical problems. In fact, drug use is often linked to bad outcomes in many parts of people's lives. Drug use problems can lead to bad body, mind, and social problems, including addiction, drug-caused problems, brain problems, thinking problems, no job, jail, and thinking about suicide. On the other hand, judgment and unfair treatment make it less likely that people who use drugs will get the help they need. Fewer than 20 out of 100 people with drug use problems are in treatment, and getting help is very unfair. Out of about 39.5 million people worldwide who had drug use problems in 2021, only one in five got treatment.

A study in 2020 confirmed how important it is to look at a body-mind-social model when thinking about what causes drug dependence. This model for addiction, when trying to understand how drug use problems start and get worse, focuses on body factors like genes that make someone more likely to have a problem, mind and thinking factors like belief in oneself, what one expects to happen, and readiness to change, and social factors like the influence of family, friends, and partners. So, understanding how these factors are connected could be a good plan for programs that prevent drug use.

Drug use problems involve many brain processes, including the brain's reward system. This system, also called the dopamine system, is key in sending out behaviors related to pleasure and feeling good. So, a main part of understanding how a drug use problem starts is how the social world, a person's own actions, and family history work together.

Family, Role Models, and Mind Factors

Starting with the family during childhood, young people get involved in many activities when they start school. Especially during middle school, friends become more and more important and influence how a person grows. In teenage years, and even more so when becoming an adult, romantic relationships become another way people learn social behavior. They are, along with friend groups, part of the reward system.

Family members act as role models for children. Research involving many different people showed that good social and family settings create a good model for future interactions. But, a family history of sadness can hurt mental health in adulthood. Family life with ongoing stress, fighting, or other problems affects the brain's reward system. This makes a person more sensitive to things that feel good, leading them to rely more on drugs that give quick relief. Also, if there is drug use in the family, children might think such behaviors are okay. This might make them go towards social groups that focus on drugs as they grow up. The study found that some mental factors, like having generalized worry or panic attacks, or having upsetting events in childhood, are linked to drug use. Mental factors like upsetting childhood events might change how someone sees social situations and how they handle stressful life events, which could make them more likely to use drugs.

Other social factors, often linked to developing mental health symptoms, are also tied to developing drug use problems. According to research in Stockholm, having less schooling increases the risk of drug use problems and self-harm. Also, a link between less schooling and various mental problems, like schizophrenia, sadness, worry, ADHD, and behavior problems, is shown.

Brain, Genes, and Personality

Genes can affect how the brain reacts to pain relievers and its ability to control the urge to use drugs. They can also make a person more likely to develop mental problems like worry or sadness, which are strongly linked to the risk of addiction. For example, some ideas suggest that people with autism might have differences in a brain chemical called dopamine in the front part of their brain. This could make them more likely to seek enjoyable feelings over and over, with the risk of easily turning this into addictive behaviors. Also, there seems to be a common problem with how the brain's emotion system works in people with drug use problems and autism.

A review that looked at how both PTSD and drug use problems affect uncontrollable cravings for drugs found that PTSD was strongly linked to higher levels of craving among patients with alcohol, cannabis, cocaine, tobacco, and other drug use problems. Some studies have also seen a link between how serious PTSD symptoms are and how strong cravings are, because drug use is a way to ease upsetting symptoms. The reasons behind this involve bad feelings, and not being able to control emotions plays a role in causing cravings after an upsetting event. Mental, social, and body factors can work together to cause cravings and drug use. PTSD symptoms can trigger feelings that, in turn, increase cravings for drugs. Likewise, being in upsetting environments can act as a trigger for cravings.

Getting Better

When working on addiction, one must also think about things like self-belief (trusting one's ability to succeed without the drug) and desire (wanting to change one's behavior). These are positively linked to successful treatment and directly related to each other: lower self-belief affects the desire to find good social support, and less social support lowers self-belief.

Talking About the Findings

Drug use problems start and continue because many body, mind, and social factors work together in a complex way.

In the body, the endocannabinoid and dopamine systems, along with gene differences, play a part in cannabis, opioid, and stimulant addiction. From a mind standpoint, personality traits like not being able to control oneself and low self-worth are important in how likely someone is to become addicted. Having worry, mood problems, and addiction together, along with the strong link between upsetting events and drug use, shows how important mental factors are. Social elements, like family background, parenting styles, neighborhood traits, and friend support, greatly shape addiction patterns. In turn, addiction breaks up social behaviors, making a person feel alone. The complex way these factors are connected shows how many parts addiction has and how important it is to have full plans for preventing and treating it.

What More Needs to Be Studied

There are several ways future studies could help us understand drug use problems and related mental health issues better. First, studies that follow people from teenage years to adulthood could give important information about how early drug use affects mental health over time and how addiction develops. Understanding how things like childhood upsetting events, parenting styles, and friends' influence work together over time to shape drug use behaviors is very important for making specific prevention and help plans. Second, looking into how genes and brain factors make people more likely to have certain types of drug addictions could help us understand addiction better. By looking at gene markers linked to different drug use problems and how they mix with things in the environment, researchers can find possible signs for early detection and special treatment plans. Also, looking at how social factors like money situation, access to health care, and community support affect drug use outcomes is key to fixing unfairness in addiction treatment and recovery. Research on how social factors affect whether someone gets into treatment, stays in it, and gets better can help make more effective and fair treatments for people with drug use problems. Last, looking into new trends, like how digital technology and social media affect drug use behaviors, could give important information about new risk factors for addiction. Understanding how online places affect attitudes, behaviors, and ideas about drugs among different age groups can help with prevention efforts in the digital world.

By looking at these knowledge gaps and how body, mind, and social factors work together in drug use problems, future studies can lead to better prevention plans, special treatment methods, and improved results for people struggling with addiction and related mental health issues.

What This Study Could Not Do

While this study gives important information about how body, mind, and social factors combine in drug use problems and related mental health issues, some limits should be known. First, what was found might not apply to everyone because the studies came from different countries. This difference could mean that local cultures changed how results were understood, making it hard to apply them everywhere. Second, the ways the studies were done varied, including looking at groups at one time, watching groups over time, and doing tests where people were put into groups by chance. These different study types might make it hard to compare and put results together. Also, relying only on published articles might mean missing valuable information from studies that were not published. To fix this, the study included other sources like reports, official papers, blog posts, and student papers, which gives a more balanced and complete view. Finally, while efforts were made to include many factors that affect drug use problems, there might be other things not covered in this study that could help us understand drug addiction more fully.

Main Ideas

The findings in this study show how important it is to think about how the body, mind, and social life are all connected when understanding addiction. They point out the big role played by brain chemical systems in drug addiction. Also, this study shows how media images of drugs affect drug use behaviors in children and teenagers, stressing the need for good messages to balance out bad influences. Knowing the risks that come with drug use is especially important for preventing it.