INTRODUCTION

The U.S. Surgeon General reported that in 2015, 27.1 million adolescents and adults used illicit drugs or misused prescription drugs. Recent estimations suggest that the annual cost for an individual with substance or alcohol use disorder can range from $2600 in agriculture to more than $13 000 in the information and communications sectors. Prevalence and frequencies of cocaine or methamphetamine have increased over the past 5 years, with overdose deaths involving psychostimulants increasing by as much as 180%. Similarly, risk perception and use patterns for cannabis have changed dramatically following a wave of legalization across the U.S. Yet, despite these rising rates of substance use and the associated consequences, our understanding of the disease processes underlying the development and maintenance of substance use remains elusive. It is clear that the cause of substance use develops over time and across multiple levels of influence, for example biological, such as genetic or neural circuits, individual, for example temperamental factors or behaviour patterns, and social, for example the influence of parental or peer attitudes. There is emerging consensus among neuroimaging studies suggesting that the prefrontal cortex in assigning excessive salience to drug over nondrug-related processes, which leads to lapses in self-control, and deficits in reward-related decision-making and insight into illness. This review provides some of the recent developments and insights that focuses on novel case–control findings (for a predictive overview see Fig. 1), the emerging of prediction of different aspects of substance use, associations between substance use and different constructs, emerging longitudinal results, meta-analyses and review, and new emerging constructs.

FIGURE 1.

_{Axial slices of prospective meta-analysis using neuroquery.org, indicating the predicted activations to the keywords ‘neuroimaging, substance use, addiction’. The colour codes represent threshold (at 3.0) z-values (positive ¼ red, negative ¼ blue).}

CASE–CONTROL STUDIES

Case–control studies tend to be dominated by small samples, which helps to understand why – sometimes – there are contradictory findings. In general, there is strong evidence for subcortical disease from both structural and functional neuroimaging studies that seem to occur in individuals with all substance use disorders. The differences in other parts of the brain are more variable and depend on the type of construct that is being examined. Comparing individuals with cannabis user disorder relative to comparison individuals, researchers found lower resting-state functional connectivity within the dorsal attention network, which was associated with more severe cannabis use measures, including increased lifetime cannabis use, shorter length of abstinence and more severe cannabis use disorder symptoms. On the one hand, in participants with heroin use disorder, there appears to be a marked decrease in resting-state functional connectivity between interhemispheric dorsolateral prefrontal cortex. On the other hand, others have been unable to find reliable univariate between-group differences in cortical structure or edgewise resting state functional connectivity in prescription opioid users. Structural neuroimaging approaches have shown that relative to comparison participants, individuals with substance use disorder have smaller left nucleus accumbens, right thalamus, right hippocampus, left caudal anterior cingulate cortex (ACC) volume and larger right caudal ACC volume, and right caudal ACC, right caudal middle frontal gyrus (MFG) and right posterior cingulate cortex (PCC) surface than Healthy Comparison. Some have speculated that these differences are both due to preexisting factors and the influence of recent substance. Taken together, resting-state functional connectivity studies support some but not for all substances of abuse and disruption in executive control. In comparison, structural neuroimaging findings point towards reduced subcortical volumes, which may emerge as an interaction between preexisting factors and recent substance use.

PREDICTION

There is an increasingly sophisticated approach to building prediction models, some of which focus on group membership and others on continued abstinence. These models take a pragmatic approach, that is they focus on obtaining robust test parameters without focusing on the process that is being used to generate the prediction. There is evidence from several studies that neuroimaging provides some predictive utility; however, the current approaches are still insufficient to generate robust individual-level predictions with clinical utility. In a recent study, using the physiological response to smoking-related stimuli, investigators build a classification algorithm that was able to identify smokers who were nearly 2.5 times more likely to be abstinent. Others have developed a sophisticated connectome-based predictive modelling (CPM) approach to predict abstinence during treatment, which involves measuring the connectivity between cognitive/executive control regions and those brain areas involved in reward responsiveness. Using a risk model approach, participants who initiated cannabis use by 15 years of age had activation differences characterized by increases in frontoparietal and decreases in visual association regions. A meta-analysis using an activation likelihood estimation approach showed that not only the right putamen and claustrum, but also rostral-ventral anterior cingulate cortex was associated with relapse resilience. Taken together, although there are initial and intriguing results from both individual studies and meta-analyses that neuro-prediction is possible, these findings are still based on relatively small, single-site studies.

ASSOCIATION

Studies examining the association between a particular construct that is relevant for the initiation or maintenance of drug use and substance use find synergistic effects for some of the brain structures that have been associated with substance use disorder. Specifically, subcortical disease in terms of both structure and function is also affected by stress, impulsivity, externalizing disease and paternal substance use. Thus, there appears to be a common neural pathway that involves constructs that often co-occur with substance use and imaging findings observed with substance use disorder individuals. Specifically, individuals with adverse childhood experiences and substance use show decreased gray matter or activation in regions of executive functioning, the hippocampal complex and the supplementary motor area, as well as altered activation in anterior cingulate cortex, caudate and amygdala during a stress-induction paradigm. Others reported that higher motor impulsivity was positively correlated with right nucleus accumbens volume, but those with greater resting-state functional connectivity between the right nucleus accumbens and bilateral superior frontal gyrus showed lower motor impulsivity. Similarly, substance use individuals with higher nonplanning impulsivity and affect-based impulsivity showed changes in structure and function of the medial orbitofrontal-striatal system and hyperexcitability of dopamine receptors in this network. This connectivity also seems to be modulated by a family history of substance use. Finally, externalizing disorders also show structural and functional changes in the basal ganglia and prefrontal cortex. Taken together, these association studies further support dysregulation of prefrontal-subcortical processing but extend these findings to constructs that are relevant to substance use such as impulsivity and externalizing disease.

LONGITUDINAL

Longitudinal studies of two kinds have emerged. First, studies examine the effect of abstinence on brain structure and functioning and, second, cohort studies investigate the role of brain structure and function as a risk or resilience factor for developing problems with substance use. Interestingly, both types of studies identify a diverse set of neural structures that are not necessarily consistent with those that have been identified in case–control studies. Several cortical brain regions seem to play a role in both increasing the risk and acting as protection from transition to use. The relatively sparse neuroimaging literature based on exposure cohort studies suggests that the neurocognitive deficits in substance-exposed children persist into adulthood. On the contrary, most longitudinal studies following individuals into recovery support the notion that there is a partial neurobiological recovery with abstinence, which includes structures such as frontal cortical regions, the insula, hippocampus and cerebellum Several longitudinal cohorts examining cannabis use have found that extended use is associated with smaller hippocampal volume and cerebellar changes. There is some evidence that frontostriatal, frontolimbic and frontocerebellar systems are altered as a consequence of use. Others have reported increasing risk-related insular cortex activation with prolonged substance use. Using longitudinal cohorts to predict the emergence of substance use, investigators reported that both decreased anterior cingulate cortex volume and blunted orbitofrontal cortex activation during reward outcome predicted greater risk for substance and alcohol use initiation. Taken together, the small but developing literature of longitudinal studies implicate some of the same core brain structures as well as their function that have also been identify via case–control studies.

REVIEW OR META-ANALYSES

Over the past years, there have been several important reviews and meta-analysis attempting to synthesize the fast-growing literature on neuroimaging and substance use. These publications have focused on a diverse set of themes. A commonly emerging aspect of these reviews is that despite voluminous literature on the topic, definitive statements are hard to come by. There are several reasons for this. First, most imaging studies are cross-sectional, which makes causal inference impossible. Second, the size of an individual study tends to be small, which results in large errors around the point estimate. Third, there are few multicentre studies, which make it difficult to extrapolate from one finding whether this will hold in other populations. Meta-analyses of individuals with cannabis use disorder point towards reductions in amygdala, accumbens and hippocampus volumes. In addition, these individuals also show lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region. Others have not only reported functional and structural alterations in frontoparietal, fronto-limbic, fronto-striatal and cerebellar regions among adolescent cannabis users, but also subcortical structures during reward-related processing. Examining studies focusing on the emergence of substance, investigators found that altered neural structure and function of regions in reward processing, cognitive control and impulsivity can predate substance use initiation, escalation and disorder. Individuals with smaller fronto-parietal and amygdala volume and larger ventral striatal volume are more likely to engage in prospective substance misuse. Importantly, some of these effects in the striatum, hippocampus, amygdala, insula and corpus collosum might also be sex-specific. Interestingly, similar structures such as anterior cingulate cortex, inferior frontal gyrus, among others, showed consistent brain-behaviour associations with treatment-outcome variables. Several reviews and meta-analyses have been conducted with a focus on delay discounting, that is the degree to which future rewards (or punishments) are appraised as less salient than current rewards (or punishments) of the same magnitude. The ventromedial prefrontal cortex and ventral striatum have been implicated in evaluating reward values, whereas the anterior cingulate cortex has been linked to cognitive control, and the middle temporal gyrus has been associated with predictions. Attenuated activation in these structures has been associated with differences in delayed discounting. Among individuals with substance use disorders, there is evidence of greater neural activity in the executive control network during choices for larger-delayed rewards relative to choices for smaller-immediate rewards in cognitive control areas such as the dorsolateral prefrontal cortex. These studies support the emergence of dysregulation of cortical control over subcortical salience processing, but the degree to which this imbalance precedes the emergence of substance use and the degree to which it can heal after cessation of use is still very much unclear.

NEW APPROACHES

Given the limited advance in better understanding the processes and neural substrates that contribute to the development and maintenance of substance use disorder despite the growing number of neuroimaging publications with SUD individuals, it should not be surprising that there have been initiatives to examine novel constructs that might provide further insights into the pathology of this disorder. Computational psychiatry approaches are foremost among them. These approaches use a mathematical model underlying the observed behaviour to extract parameters that can be related to specific processes and can be associated with brain activation. The goal is to improve ‘carve nature at its joints’. For example, using a computational approach, investigators have reported that evidence accumulation may provide a process that indicates risk for substance use in youth. Deficits in this process are consistent with other findings, suggesting that substance use individuals fail to adequately compute the probability for engaging inhibitor control. Others have suggested that increased variables or decreased consistency in processing as measured by increased inter-trial variability of electrophysiological markers might contribute to these deficits. Lastly, novel brain areas have emerged as potential targets of dysfunction in substance users. Specifically, the periaqueductal gray has been a core substrate to interact with the ventral tegmental area, extended amygdala, medial prefrontal cortex, pontine nucleus, bed nucleus of the stria terminalis and hypothalamus to integrate responses to the physical discomfort associated with drug withdrawal. These approaches point towards novel directions, which may help to further elucidate the difficult task to delineate the processes that lead to and maintain substance use disorders.

NEUROLOGICAL DISORDERS AND SUBSTANCE USE

There has been an interesting association between Parkinson's disease and substance use disorder. Evidence over the past decade has shown that dopaminergic medication can induce severe addictive behaviours in susceptible Parkinson's disease patients. Imaging studies suggest that medication-induced downregulation of frontostriatal connections and upregulation of striatum might combine to induce impulsive behaviour. Recent reviews of the literature show inconsistent findings for the domains of reward and punishment learning, reflection impulsivity and disadvantageous decision-making. In comparison, there is emerging consensus of dopaminergic agents altering motor or cognitive/attentional control, thereby increasing choice impulsivity. Thus, impulse control problems such as substance use occur in a subset of susceptible patients with Parkinson's disease with dopamine replacement therapy, which may be due to deficits in dopaminergic receptor expression, connectivity patterns in cortico-striatal circuitry and exaggerated neural responses to cue exposure. Those Parkinson disease individuals who report greater levels of depression and show a nontremor phenotype seem to be susceptible to boosting of reward-versus punishment-based choice by medication, which may reflect an underlying dysregulation of the mesolimbic dopamine system. Taken together, preexisting conditions such as an imbalance between executive control processing and incentive salience processing that involve brain areas such as the prefrontal cortex versus subcortical striatum may put Parkinson's disease patients at risk for substance use when exposed to dopaminergic replacement treatment.

CONCLUSION

There continues to be vigorous progress in neuroimaging research focused on substance use disorders, yet there are several issues that are noteworthy. First, most studies still focus on case–control designs and are unable to draw causal conclusions from the neuroimaging data. However, this is changing with the emergence of large consortium studies such as the Adolescent Brain Cognitive Development study. Nevertheless, as these studies will take years to collect data, results are not yet available. Second, there is clear evidence from several studies that associations between brain and behaviour are weak and that even large-scale studies only show modest correlations between psychopathology and structural or functional brain characteristics. Therefore, it is unlikely that neuroimaging studies will be able to find substantial associations of behavioural or clinical characteristics. Lastly, there is likely to be significant heterogeneity among substance users in terms of the predisposing factors as well as the substance-related changes that result in a complex mixture of brain phenotypes, which contributes to the difficulty in delineating a core neural substrate underlying substance use disorders.

INTRODUCTION

Substance use and misuse significantly impact public health and the economy. In recent years, there has been a notable increase in the prevalence of illicit drug use and prescription drug misuse, leading to substantial societal and individual costs. For instance, psychostimulant-related overdose deaths have risen sharply. Understanding the complex origins and persistence of substance use disorders (SUDs) is crucial, as they stem from a combination of biological, individual, and social influences. Neuroimaging research suggests that the prefrontal cortex plays a key role, contributing to impaired self-control and altered decision-making in individuals with SUDs. This review explores recent advancements and insights from neuroimaging studies concerning substance use.

CASE–CONTROL STUDIES

Research comparing individuals with substance use disorders to control groups frequently identifies alterations in brain structure and function, particularly within subcortical regions. These changes are observed across various substance use disorders. For instance, findings include altered resting-state functional connectivity in cannabis users and reduced connectivity in the prefrontal cortex among individuals with heroin use disorder. Structural imaging often reveals smaller volumes in key areas like the nucleus accumbens, thalamus, and hippocampus. These differences are believed to arise from a combination of pre-existing vulnerabilities and the impact of substance use. Longitudinal studies further contribute to understanding these neurobiological changes. Some research indicates that abstinence can lead to a partial recovery in brain structures, including frontal cortical regions. Other studies highlight that prolonged substance use, such as cannabis use, is associated with specific changes like reduced hippocampal volume. Importantly, factors such as stress, impulsivity, and a family history of substance use also influence these same brain structures, suggesting common neural pathways that contribute to the development and maintenance of substance use disorders.

PREDICTION

Increasingly sophisticated approaches are being developed to predict various aspects of substance use, including group membership and continued abstinence. Neuroimaging shows promise in predictive utility, though current methods are not yet robust enough for widespread individual-level clinical predictions. Studies have utilized physiological responses to stimuli, and connectome-based predictive modeling has been developed to forecast abstinence during treatment by measuring connectivity between cognitive control and reward regions. Risk models also demonstrate activation differences in individuals who initiate cannabis use early. Initial findings from individual studies and meta-analyses suggest that neuro-prediction is possible, but these results typically stem from relatively small, single-site investigations. Novel research initiatives are also exploring new constructs to enhance understanding of substance use disorder pathology. Computational psychiatry, for example, uses mathematical models to link observed behaviors with specific brain processes and activations. Deficits in processes like evidence accumulation are being investigated as potential indicators of risk. Furthermore, specific brain areas, such as the periaqueductal gray, are emerging as key targets of dysfunction, given their role in integrating responses to drug withdrawal discomfort. These new directions offer potential for a more detailed understanding of the processes underlying substance use disorders.

REVIEW OR META-ANALYSES

Despite a growing body of neuroimaging literature on substance use, definitive conclusions remain challenging due to several factors. Most studies are cross-sectional, preventing causal inference. Individual study sample sizes tend to be small, leading to less precise estimates. Additionally, a scarcity of multi-center studies limits the generalizability of findings across diverse populations. Meta-analyses of individuals with cannabis use disorder frequently point to reduced volumes in areas like the amygdala, accumbens, and hippocampus, and reduced cortical thickness in frontal regions. Functional and structural changes are also observed in frontoparietal, fronto-limbic, and cerebellar regions among adolescent cannabis users. Importantly, altered neural structure and function in regions associated with reward processing, cognitive control, and impulsivity can predate the initiation and escalation of substance use. Some effects, particularly in the striatum, hippocampus, amygdala, insula, and corpus callosum, may also be sex-specific. Current research supports the concept of dysregulation in cortical control over subcortical salience processing in substance use disorders. However, whether this imbalance precedes substance use and the extent to which it can recover after cessation remain unclear. Overall, despite significant progress, neuroimaging research continues to grapple with the complexity and heterogeneity of substance use disorders, making it difficult to pinpoint a singular core neural substrate.

NEUROLOGICAL DISORDERS AND SUBSTANCE USE

An interesting association exists between Parkinson's disease and substance use disorder. Over the past decade, evidence indicates that dopaminergic medication used to treat Parkinson's can induce severe addictive behaviors in susceptible patients. Imaging studies suggest that medication-induced changes in frontostriatal connections and dopamine receptor expression may contribute to impulsive behaviors. Individuals with Parkinson's disease who experience greater levels of depression and exhibit a non-tremor phenotype appear more susceptible to medication-induced choices favoring reward over punishment. This suggests a pre-existing imbalance between executive control and incentive salience processing, involving areas like the prefrontal cortex and subcortical striatum, may predispose these patients to substance use when exposed to dopaminergic treatment.

INTRODUCTION

In 2015, the U.S. Surgeon General reported that over 27 million adults and adolescents used illicit drugs or misused prescription drugs. The annual cost for an individual with substance or alcohol use disorder can range from approximately $2,600 to more than $13,000, depending on the industry. Over the past five years, the use of cocaine and methamphetamine has risen, with overdose deaths involving stimulants increasing by up to 180%. Similarly, attitudes towards cannabis and its use patterns have significantly changed following widespread legalization across the U.S. Despite these increases in substance use and their consequences, a complete understanding of how substance use disorders develop and continue remains unclear. It is recognized that the causes of substance use emerge over time from multiple interacting factors, including biological elements like genetics and brain circuits, individual aspects like personality and behavior, and social influences such as parental or peer attitudes. Neuroimaging studies increasingly suggest that the prefrontal cortex in the brain may assign too much importance to drug-related cues over other processes, leading to difficulties with self-control, poor decision-making regarding rewards, and limited insight into the illness. This review highlights recent findings and insights from studies focusing on new observations from specific cases, the ability to predict various aspects of substance use, connections between substance use and different concepts, emerging long-term study results, summaries from meta-analyses, and new theoretical ideas.

CASE–CONTROL STUDIES

Case-control studies often involve small groups of participants, which can contribute to inconsistent findings. Generally, strong evidence suggests subcortical brain issues in individuals with all types of substance use disorders, based on both structural and functional brain imaging. Differences in other parts of the brain are more varied and depend on the specific brain function or structure being examined. For instance, individuals with cannabis use disorder show less resting-state functional connectivity within their dorsal attention network compared to others. This reduction is linked to more severe cannabis use. In contrast, participants with heroin use disorder often exhibit a notable decrease in resting-state functional connectivity between the two halves of the dorsolateral prefrontal cortex. However, other studies have not found consistent differences in brain structure or resting-state functional connectivity in individuals who misuse prescription opioids.

Structural neuroimaging approaches show that individuals with substance use disorder, when compared to control groups, tend to have smaller volumes in several brain areas, including the left nucleus accumbens, right thalamus, right hippocampus, and left caudal anterior cingulate cortex (ACC). They also show larger volumes and surface areas in the right caudal ACC, right caudal middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC). Some researchers believe these differences result from both pre-existing conditions and the effects of recent substance use. Overall, resting-state functional connectivity studies support some, but not all, disruptions in executive control related to substance use. Meanwhile, structural neuroimaging points to reduced subcortical brain volumes, which may arise from an interaction between prior vulnerabilities and recent drug use.

PREDICTION

Methods for building prediction models are becoming more sophisticated, with some focusing on identifying group membership and others on predicting continued abstinence. These models take a practical approach, aiming for reliable prediction results without necessarily focusing on the exact processes that generate the prediction. Several studies indicate that neuroimaging can offer some predictive value; however, current methods are not yet robust enough to make reliable individual-level predictions for clinical use. One study used physiological responses to smoking-related cues to develop a classification algorithm, which identified smokers who were nearly 2.5 times more likely to remain abstinent. Other researchers have created a complex connectome-based predictive modeling (CPM) approach to forecast abstinence during treatment, which measures the connections between brain regions involved in cognitive control and those related to reward.

A risk model approach found that individuals who began using cannabis by age 15 had distinct brain activation patterns, including increased activity in frontoparietal regions and decreased activity in visual association areas. A meta-analysis using an activation likelihood estimation approach showed that the right putamen and claustrum, as well as the rostral-ventral anterior cingulate cortex, were linked to resilience against relapse. Although these initial findings from individual studies and meta-analyses are promising for neuro-prediction, they are still primarily based on relatively small, single-site studies.

ASSOCIATION

Studies examining the connection between specific factors relevant to starting or maintaining drug use and substance use often reveal combined effects on brain structures linked to substance use disorder. Specifically, subcortical brain regions, in terms of both their structure and function, are also affected by stress, impulsivity, externalizing disorders (like ADHD or conduct disorder), and parental substance use. This suggests a common brain pathway that involves factors often co-occurring with substance use and the brain changes observed in individuals with substance use disorder. For example, individuals with adverse childhood experiences and substance use show less gray matter or activation in executive functioning areas, the hippocampal complex, and the supplementary motor area. They also show altered activity in the anterior cingulate cortex, caudate, and amygdala during stress.

Other research indicates that higher motor impulsivity is positively linked to the volume of the right nucleus accumbens. However, individuals with stronger resting-state functional connectivity between the right nucleus accumbens and the bilateral superior frontal gyrus tend to show lower motor impulsivity. Similarly, individuals with substance use disorders who exhibit higher non-planning impulsivity and impulsivity driven by emotions show changes in the structure and function of the medial orbitofrontal-striatal system and increased excitability of dopamine receptors in this network. This connectivity also appears to be influenced by a family history of substance use. Lastly, externalizing disorders also involve structural and functional changes in the basal ganglia and prefrontal cortex. Collectively, these association studies further support the idea of dysregulation in prefrontal-subcortical processing, extending these findings to related factors such as impulsivity and externalizing disorders.

LONGITUDINAL

Two types of longitudinal studies have emerged. First, some studies examine how abstinence affects brain structure and function. Second, cohort studies investigate the role of brain structure and function as factors that either increase risk or provide resilience against developing substance use problems. Interestingly, both types of studies identify a diverse range of brain structures that are not always consistent with those found in case-control studies. Several cortical brain regions appear to play a role in both increasing the risk for substance use and protecting against transitioning to use. The relatively limited neuroimaging literature from exposure cohort studies suggests that neurocognitive deficits in children exposed to substances persist into adulthood.

Conversely, most longitudinal studies tracking individuals into recovery support the idea that partial neurobiological recovery occurs with abstinence. This recovery involves structures such as frontal cortical regions, the insula, hippocampus, and cerebellum. Several longitudinal studies on cannabis use have found that extended use is linked to smaller hippocampal volume and changes in the cerebellum. There is some evidence that frontostriatal, frontolimbic, and frontocerebellar systems are altered as a result of substance use. Other researchers have reported increased risk-related activation in the insular cortex with prolonged substance use. Using longitudinal cohorts to predict the emergence of substance use, investigators found that both decreased anterior cingulate cortex volume and blunted activation in the orbitofrontal cortex during reward outcomes predicted a greater risk for initiating substance and alcohol use. Overall, the small but growing body of longitudinal studies points to some of the same core brain structures and their functions that have also been identified through case-control studies.

REVIEW OR META-ANALYSES

In recent years, several important reviews and meta-analyses have aimed to summarize the rapidly growing literature on neuroimaging and substance use. These publications have explored various themes. A common theme emerging from these reviews is that despite a large amount of research, definitive statements are difficult to make. There are several reasons for this: most imaging studies are cross-sectional, which makes it impossible to determine cause and effect. Second, individual studies tend to have small sample sizes, leading to large uncertainties in their findings. Third, few multi-center studies exist, making it challenging to confirm whether findings from one group will apply to other populations.

Meta-analyses of individuals with cannabis use disorder indicate reductions in the volume of the amygdala, accumbens, and hippocampus. Additionally, these individuals show thinner cortex in frontal regions, particularly the medial orbitofrontal area. Other analyses have reported functional and structural alterations in frontoparietal, fronto-limbic, fronto-striatal, and cerebellar regions among adolescent cannabis users, as well as in subcortical structures during reward processing. Studies focusing on the emergence of substance use found that altered brain structure and function in regions involved in reward processing, cognitive control, and impulsivity can exist before the initiation, escalation, and development of substance use disorder. Individuals with smaller fronto-parietal and amygdala volumes and larger ventral striatal volumes are more likely to engage in future substance misuse. Importantly, some of these effects in the striatum, hippocampus, amygdala, insula, and corpus callosum might also be sex-specific.

Interestingly, similar structures like the anterior cingulate cortex and inferior frontal gyrus show consistent brain-behavior links with treatment outcomes. Several reviews and meta-analyses have focused on "delay discounting," which is how much future rewards (or punishments) are valued less than immediate ones of the same size. The ventromedial prefrontal cortex and ventral striatum are involved in evaluating reward values, while the anterior cingulate cortex is linked to cognitive control, and the middle temporal gyrus is associated with predictions. Reduced activity in these structures has been connected to differences in delay discounting. Among individuals with substance use disorders, there is evidence of greater neural activity in the executive control network, specifically in cognitive control areas like the dorsolateral prefrontal cortex, when choosing larger-delayed rewards over smaller-immediate ones. These studies support the idea of a dysregulation where cortical control over subcortical reward processing is impaired, but it remains unclear whether this imbalance precedes substance use and how much it can recover after cessation of use.

NEW APPROACHES

Given the limited progress in better understanding the processes and brain structures that contribute to the development and maintenance of substance use disorder, despite the increasing number of neuroimaging publications involving individuals with SUD, it is not surprising that initiatives have begun to examine new concepts that might offer further insights into the disorder's pathology. Computational psychiatry approaches are prominent among these. These methods use mathematical models of observed behavior to extract parameters that can be linked to specific processes and associated with brain activation. The goal is to more accurately "carve nature at its joints"—meaning to better define fundamental processes.

For example, using a computational approach, researchers have reported that "evidence accumulation" may indicate a risk for substance use in youth. Deficits in this process align with other findings suggesting that individuals with substance use problems fail to adequately calculate the likelihood of successfully using inhibitory control. Others have proposed that increased variability or decreased consistency in processing, measured by increased variation in electrophysiological markers between trials, might contribute to these deficits. Lastly, new brain areas have emerged as potential sites of dysfunction in substance users. Specifically, the periaqueductal gray has been identified as a key structure that interacts with areas like the ventral tegmental area, extended amygdala, medial prefrontal cortex, pontine nucleus, bed nucleus of the stria terminalis, and hypothalamus to integrate responses to the physical discomfort associated with drug withdrawal. These approaches point towards novel directions that may help further clarify the complex task of defining the processes that lead to and maintain substance use disorders.

NEUROLOGICAL DISORDERS AND SUBSTANCE USE

An interesting connection has been observed between Parkinson's disease and substance use disorder. Over the past decade, evidence has shown that dopaminergic medication, used to treat Parkinson's, can induce severe addictive behaviors in vulnerable patients. Brain imaging studies suggest that medication-induced downregulation of frontostriatal connections (reduced activity) and upregulation of the striatum (increased activity) might combine to cause impulsive behavior. Recent reviews of the literature show inconsistent findings regarding reward and punishment learning, reflection impulsivity, and disadvantageous decision-making.

In contrast, there is increasing agreement that dopaminergic agents alter motor or cognitive/attentional control, thereby increasing "choice impulsivity." Thus, impulse control problems like substance use occur in a subset of susceptible Parkinson's disease patients receiving dopamine replacement therapy. This may be due to deficits in dopamine receptor expression, altered connectivity patterns in cortico-striatal brain circuits, and exaggerated neural responses to drug cues. Those Parkinson's disease patients who report higher levels of depression and exhibit a non-tremor form of the disease seem particularly susceptible to medication boosting reward-based choices over punishment-based ones. This might reflect an underlying dysregulation of the mesolimbic dopamine system. Overall, pre-existing conditions, such as an imbalance between executive control processing and incentive salience processing involving brain areas like the prefrontal cortex versus the subcortical striatum, may put Parkinson's disease patients at risk for substance use when exposed to dopaminergic replacement treatment.

CONCLUSION

Significant progress continues in neuroimaging research focused on substance use disorders, but several important issues remain. First, most studies still rely on case-control designs, which prevent drawing conclusions about cause and effect from neuroimaging data. However, this is changing with the emergence of large collaborative studies, such as the Adolescent Brain Cognitive Development study. Nevertheless, as these studies will take years to collect data, results are not yet widely available. Second, clear evidence from several studies shows that associations between brain characteristics and behavior are weak. Even large-scale studies only demonstrate modest correlations between mental health issues and structural or functional brain features. Therefore, it is unlikely that neuroimaging studies alone will find substantial associations with behavioral or clinical characteristics. Lastly, there is likely considerable variation among individuals who use substances in terms of their predisposing factors and the substance-related changes that occur. This leads to a complex mix of brain phenotypes, which contributes to the difficulty in identifying a core neural substrate underlying substance use disorders.

INTRODUCTION

In 2015, reports from the U.S. Surgeon General showed that 27.1 million adolescents and adults used illegal drugs or misused prescription medications. Recent estimates suggest that the annual cost for an individual with a substance or alcohol use disorder can range from $2,600 in some fields to more than $13,000 in others, such as information and communication. Over the past five years, the frequency and commonness of cocaine or methamphetamine use have increased, with overdose deaths involving stimulant drugs rising by as much as 180%.

Similarly, how people view the risks of cannabis and their patterns of use have changed significantly following a wave of legalization across the U.S. Despite these rising rates of substance use and their associated problems, a clear understanding of how substance use disorders develop and continue remains difficult to grasp.

It is clear that the causes of substance use emerge over time and are influenced by many factors. These include biological factors, such as genetics or brain pathways; individual factors, such as personality traits or behavior patterns; and social factors, like the influence of parents or friends. Brain imaging studies are increasingly agreeing that the front part of the brain, known as the prefrontal cortex, plays a role by giving too much importance to drugs compared to other things. This can lead to poor self-control, problems making decisions about rewards, and a lack of insight into one's own condition. This review highlights some of the recent developments and insights from studies, focusing on new findings from different types of research.

CASE–CONTROL STUDIES

Case-control studies often involve small groups, which can lead to conflicting results. Generally, there is strong evidence from both structural and functional brain imaging studies pointing to problems in deeper brain areas, which seem to occur in individuals with all types of substance use disorders. Differences in other parts of the brain are more varied and depend on the specific brain function being examined.

When comparing individuals with cannabis use disorder to those without, researchers found lower communication between brain areas within the dorsal attention network when at rest. This was linked to more severe cannabis use measures, including greater lifetime use, shorter periods of abstinence, and more severe symptoms. In individuals with heroin use disorder, there appears to be a notable decrease in resting communication between the outer, front parts of both sides of the brain. However, other studies have not found clear differences in the brain's outer structure or in resting communication patterns in people who misuse prescription opioids.

Structural brain imaging has shown that compared to healthy individuals, those with substance use disorder have smaller volumes in several key brain regions, including the left nucleus accumbens, right thalamus, right hippocampus, and left anterior cingulate cortex (ACC). They also have larger volumes in the right ACC, and larger surfaces in the right ACC, right middle frontal gyrus (MFG), and right posterior cingulate cortex (PCC). Some experts believe these differences result from a combination of pre-existing factors and the effects of recent substance use. Overall, studies on resting brain communication support some, but not all, substances causing disruption in the brain's ability to manage thoughts and actions. Structural imaging findings suggest reduced volumes in deep brain areas, which might emerge from an interaction between existing vulnerabilities and recent substance use.

PREDICTION

There is an increasingly sophisticated approach to building prediction models, some of which focus on predicting group membership and others on predicting continued abstinence. These models take a practical approach, aiming for strong, reliable predictions without focusing on the exact process used to generate them. Several studies show that brain imaging offers some ability to predict outcomes. However, current methods are still not strong enough to create reliable individual predictions that can be used in patient care.

In a recent study, researchers used a person's physical response to smoking-related cues to develop a system that could identify smokers who were nearly 2.5 times more likely to remain abstinent. Other researchers have developed an advanced brain connectivity modeling approach to predict abstinence during treatment. This involves measuring communication between brain regions involved in thinking and self-control, and those areas responsible for responding to rewards. Using a risk model, individuals who started using cannabis by age 15 showed changes in brain activity, with more activity in areas for planning and less in areas for vision.

A meta-analysis using a method to combine findings from multiple studies showed that the right putamen, claustrum, and a specific part of the anterior cingulate cortex were linked to the ability to avoid returning to substance use. In summary, while there are initial and intriguing results from individual studies and meta-analyses suggesting that brain imaging can predict outcomes, these findings are still based on relatively small, single-site studies.

ASSOCIATION

Studies examining the connection between certain factors, relevant for starting or continuing drug use, and substance use, find combined effects for some of the brain structures linked to substance use disorder. Specifically, problems in deep brain regions, regarding both structure and function, are also affected by stress, impulsivity, outwardly expressed behavioral problems, and parental substance use. This suggests a shared brain pathway involving factors that often occur alongside substance use and the brain imaging findings observed in individuals with substance use disorder.

Specifically, individuals with adverse childhood experiences and substance use show decreased brain tissue or activity in regions related to executive functioning, memory, and movement. They also show changed activity in the anterior cingulate cortex, caudate, and amygdala during stressful situations. Other studies reported that higher impulsivity related to movement was positively connected with the volume of the right nucleus accumbens. However, those with greater resting communication between the right nucleus accumbens and the superior frontal gyrus on both sides of the brain showed lower motor impulsivity. Similarly, individuals with substance use who showed higher impulsivity from poor planning and strong emotions had changes in the structure and function of the medial orbitofrontal-striatal system and overly active dopamine receptors in this network. This brain communication also seems to be influenced by a family history of substance use. Finally, outwardly expressed behavioral problems also show structural and functional changes in the basal ganglia and prefrontal cortex.

Taken together, these association studies further support an imbalance in how the front part of the brain controls deeper brain areas. They also extend these findings to factors relevant to substance use, such as impulsivity and outwardly expressed behavioral problems.

LONGITUDINAL

Two types of longitudinal studies have emerged. First, studies examine the effect of stopping substance use on brain structure and function. Second, cohort studies investigate the role of brain structure and function as a risk or protective factor for developing problems with substance use. Interestingly, both types of studies identify a variety of brain structures, which do not always match what is found in case-control studies. Several outer brain regions (cortical areas) seem to play a role in both increasing the risk and acting as protection against developing substance use.

The relatively limited brain imaging research from studies that follow groups exposed to substances suggests that brain and thinking problems in children exposed to substances continue into adulthood. In contrast, most longitudinal studies that follow individuals into recovery support the idea that there is some recovery of brain function and structure when individuals stop using substances. This recovery includes structures such as frontal cortical regions, the insula, hippocampus, and cerebellum. Several longitudinal studies examining cannabis use have found that extended use is associated with smaller hippocampal volume and changes in the cerebellum. There is some evidence that brain systems connecting the front of the brain with other parts like the striatum, limbic system, and cerebellum are altered as a consequence of substance use. Others have reported increased activity in the insular cortex, linked to risk-taking, with prolonged substance use.

Using longitudinal groups to predict the emergence of substance use, researchers reported that both decreased volume in the anterior cingulate cortex and reduced activity in the orbitofrontal cortex during reward outcomes predicted a greater risk for starting substance and alcohol use. In summary, the small but growing body of longitudinal studies points to some of the same main brain structures and their functions as identified in case-control studies.

REVIEW OR META-ANALYSES

Over the past years, several important reviews and meta-analyses have attempted to bring together the rapidly growing research on brain imaging and substance use. These publications have focused on a diverse set of themes. A commonly emerging aspect of these reviews is that despite a large amount of research on the topic, it's difficult to make firm conclusions. There are several reasons for this.

First, most imaging studies are like a snapshot in time, which means they cannot determine cause and effect. Second, the size of individual studies tends to be small, which means results can vary widely. Third, there are few studies involving multiple centers, making it difficult to know if findings from one group apply to others. Meta-analyses of individuals with cannabis use disorder point towards smaller volumes in brain areas like the amygdala, accumbens, and hippocampus. Additionally, these individuals also show thinner outer brain layers in the frontal regions, particularly the medial orbitofrontal area.

Other studies have reported not only functional and structural changes in regions connecting the front of the brain with other parts like the parietal lobe, limbic system, striatum, and cerebellum among adolescent cannabis users, but also in deeper brain structures when processing rewards. Examining studies focusing on the emergence of substance use, researchers found that altered brain structure and function in regions involved in reward processing, cognitive control, and impulsivity can exist before someone starts using substances, uses more, or develops a disorder. Individuals with smaller fronto-parietal and amygdala volumes and larger ventral striatal volumes are more likely to engage in future substance misuse. Importantly, some of these effects in the striatum, hippocampus, amygdala, insula, and corpus callosum might also be different for males and females. Interestingly, similar structures such as the anterior cingulate cortex and inferior frontal gyrus, among others, showed consistent links between brain activity and treatment outcomes.

Several reviews and meta-analyses have focused on "delay discounting," which describes how much future rewards (or punishments) are valued less than immediate ones of the same size. The ventromedial prefrontal cortex and ventral striatum have been implicated in evaluating reward values, while the anterior cingulate cortex has been linked to cognitive control, and the middle temporal gyrus has been associated with predictions. Reduced activity in these structures has been connected with differences in delayed discounting. Among individuals with substance use disorders, there is evidence of greater neural activity in the brain network for self-control when choosing larger-delayed rewards compared to smaller-immediate rewards, especially in cognitive control areas like the dorsolateral prefrontal cortex. These studies support the emergence of an imbalance where the brain's outer layer struggles to control the importance given to things by deeper brain areas. However, whether this imbalance happens before substance use starts or how much it can improve after someone stops using substances is still very unclear.

NEW APPROACHES

Despite a growing number of brain imaging studies on substance use disorders, understanding how these conditions develop and continue is still limited. This has led to initiatives to examine new ideas that might provide further insights into the pathology of this disorder. Computational psychiatry is a leading new approach. These methods use mathematical models to understand the numbers that drive observed behaviors and relate them to specific brain processes or activity. The goal is to better define and understand the underlying mechanisms.

For example, using a computational approach, researchers have reported that how the brain gathers information to make decisions may indicate risk for substance use in youth. Problems in this process are consistent with other findings, suggesting that individuals with substance use disorders fail to adequately use self-control. Others have suggested that more variation or less consistency in how the brain processes information, seen in brainwave patterns, might contribute to these problems. Lastly, new brain areas have emerged as potential targets of dysfunction in substance users. Specifically, the periaqueductal gray has been identified as a key brain area that interacts with other regions like the ventral tegmental area, extended amygdala, medial prefrontal cortex, and hypothalamus, to combine responses to the physical discomfort associated with drug withdrawal. These approaches point towards new directions that may help clarify the complex task of defining the processes that lead to and maintain substance use disorders.

NEUROLOGICAL DISORDERS AND SUBSTANCE USE

There has been an interesting association between Parkinson's disease (PD) and substance use disorder. Evidence over the past decade has shown that medication that affects dopamine can cause severe addictive behaviors in Parkinson's disease patients who are vulnerable. Brain imaging studies suggest that medication may lead to reduced activity in connections between the frontal lobe and striatum, and increased activity in the striatum, which could combine to cause impulsive behavior. Recent reviews of the literature show conflicting results regarding how individuals learn from rewards or punishments, how they think before acting, and how they make risky decisions.

In contrast, there is increasing agreement that dopamine-affecting drugs can alter motor control or thinking/attention, thereby leading to more impulsive choices. Thus, impulse control problems like substance use occur in a subset of susceptible Parkinson's disease patients who are on dopamine replacement therapy. This may be due to problems with dopamine receptors, brain circuit connections, and overly strong brain reactions to drug-related cues.

Parkinson's disease individuals who report greater levels of depression and show a type of Parkinson's disease without tremors seem to be susceptible to medication making reward-based choices more appealing than punishment-based ones. This may reflect an underlying imbalance in the brain's reward system. In summary, pre-existing conditions, such as an imbalance between self-control (involving the prefrontal cortex) and the brain's strong focus on rewards (involving the striatum), may put Parkinson's disease patients at risk for substance use when exposed to dopamine replacement treatment.

CONCLUSION

Active development continues in brain imaging research focused on substance use disorders; however, several important points are worth noting. First, most studies still use case-control designs and cannot determine cause and effect from the brain imaging data. This is changing with the emergence of large collaborative studies, such as the Adolescent Brain Cognitive Development study. Nevertheless, as these studies will take years to collect data, results are not yet available.

Second, there is clear evidence from several studies that links between the brain and behavior are weak, and even large-scale studies show only small connections between mental health conditions and brain characteristics. Therefore, it is unlikely that brain imaging studies will find strong links between brain features and how people behave or their clinical symptoms.

Lastly, there is likely a lot of variety among individuals who use substances, both in what makes them vulnerable and how substances change their brains. This leads to a complex mix of brain characteristics, which contributes to the difficulty in identifying a core brain basis for substance use disorders.

INTRODUCTION

Many adults used illegal drugs or misused prescription drugs in 2015. It costs a lot of money each year to help someone with a drug or alcohol problem. This cost can be different depending on where a person works.

More people are using drugs like cocaine and methamphetamine now than five years ago. Deaths from these drugs have also gone up significantly. Also, how people think about and use cannabis (marijuana) has changed a lot as it has become legal in many parts of the U.S.

Even with more people using drugs and facing problems from it, doctors and scientists still do not fully understand why drug use starts and continues. It is clear that drug use problems grow over time. Many things play a part, like a person's genes and brain, their behavior and feelings, and even what their family and friends do or think.

Brain studies often show that a part of the brain, called the prefrontal cortex, starts to care too much about drugs and not enough about other things. This can make it hard for people to control themselves, make good choices, or see that they have a problem. This paper will look at new ideas and studies about drug use. It will cover topics like comparing people who use drugs to those who do not, trying to guess who might use drugs, how drug use connects to other issues, studies that follow people over time, summaries of many studies, and new ideas in this area.

CASE–CONTROL STUDIES

Studies that compare people who use drugs to those who do not often have small groups of people. This can make some study results seem to go against each other. Generally, there is strong proof that drug use changes the brain in important inner parts. This seems to happen in people with all kinds of drug use problems.

Changes in other parts of the brain are not always the same and depend on what is being studied. For example, people who use cannabis daily have less brain connection in a certain network, which is linked to more serious cannabis use. In people who use heroin, there is a clear drop in brain connections between specific brain areas. However, other studies have not found clear differences in brain structure or connections in people who misuse prescription opioids.

Brain scans have shown that people with drug use problems have smaller parts in some brain areas, like the nucleus accumbens, thalamus, and hippocampus. They may also have larger parts in other areas. Some experts think these differences are both there before drug use starts and are changed by recent drug use. Overall, studies show that drug use can harm a person's ability to control their actions. Also, structural brain studies show smaller brain parts deep inside, which may come from a mix of things that were already there and recent drug use.

PREDICTION

Scientists are getting better at building models to guess who might have drug problems or who might stay sober. These models focus on getting good predictions, not so much on how the prediction works. Brain imaging can help guess who might have problems, but current methods are not yet good enough to help individual patients in a strong way.

One study found that by looking at how a smoker's body reacted to smoking-related sights and smells, scientists could guess who was almost 2.5 times more likely to quit. Other studies have looked at how different brain parts connect to predict if someone will stay sober during treatment. People who started using cannabis by age 15 had different brain activity, showing more activity in some areas and less in others. A study that combined many brain scans found that certain brain parts were linked to staying free from drug use.

Overall, there are interesting first results that show brain scans can help predict drug use. However, these findings come from smaller studies done in only one place.

ASSOCIATION

Studies that look at how drug use is connected to other issues often find that certain brain parts are affected. For example, problems in deep brain areas (both how they are built and how they work) are also affected by stress, acting without thinking, other mental problems, and if a parent used drugs. This suggests a common brain pathway that connects drug use to other problems that often happen at the same time.

Specifically, people who had bad experiences as children and also use drugs show changes in their brain's gray matter or activity in areas that help with thinking, memory, and movement. Other studies found that acting without thinking was linked to the size of a certain brain area. But people with stronger connections in that area had less impulsive behavior. Similarly, people who use drugs and act without thinking, or make choices based on feelings, showed changes in how parts of their brain work. Family history of drug use also seems to affect these connections. Finally, other mental problems also show changes in brain structure and function.

All these studies support the idea that the brain's control system and its deeper parts are not working well together. They also show how this problem connects to other issues like acting without thinking and other mental problems.

LONGITUDINAL

Two main types of studies have looked at brain changes over time. First, some studies look at how staying sober affects the brain's structure and how it works. Second, other studies follow groups of people to see if certain brain structures or functions make them more likely to develop drug problems or protect them from it.

It is interesting that both types of studies find different brain areas involved than those found in studies that just compare users to non-users at one time. Some outer brain areas seem to both increase the risk of drug use and protect against it. Studies of children exposed to drugs before birth suggest that their brain problems can last into adulthood. However, most studies that follow people into recovery show that the brain can partly heal with sobriety, especially areas like the front of the brain, the insula, and the hippocampus.

Some long-term studies of cannabis use found that continued use is linked to a smaller hippocampus and changes in the cerebellum. There is some proof that systems connecting the front of the brain to other areas are changed by drug use. Others have seen that a part of the brain called the insular cortex becomes more active with longer drug use, which is linked to risk. When scientists followed groups of people to predict drug use, they found that smaller parts of the brain and less activity in certain areas during rewards predicted a greater risk for starting drug and alcohol use.

Overall, the small but growing number of long-term studies show that some of the same main brain parts and their functions are involved, just like in the comparison studies.

REVIEW OR META-ANALYSES

In recent years, many important reviews and studies that combine results from many papers have tried to make sense of the fast-growing information on brain imaging and drug use. These papers have looked at many different topics. A common idea from these reviews is that even with a lot of studies, it is hard to make clear statements. There are several reasons for this.

First, most brain imaging studies look at people at only one point in time. This means they cannot prove that one thing causes another. Second, individual studies are often small, which can lead to results that are not very precise. Third, there are few studies done in many different places, which makes it hard to know if a finding will be true for other groups of people.

Studies that combine results from many papers on cannabis use problems show smaller amygdala, accumbens, and hippocampus sizes. Also, these people show thinner outer brain layers in the front, especially in the medial orbitofrontal area. Other studies have found changes in brain function and structure in different areas, including deeper brain parts, in young people who use cannabis.

Looking at studies that focus on the start of drug use, scientists found that changes in brain structure and function in areas for reward, control, and impulsivity can happen before drug use starts, gets worse, or becomes a disorder. People with smaller front brain areas and amygdala, and larger ventral striatum, are more likely to misuse drugs. Importantly, some of these effects in parts of the brain like the striatum and hippocampus might also be different for males and females.

Interestingly, similar brain areas like the anterior cingulate cortex were linked to how well people did in drug treatment. Many reviews have looked at "delay discounting," which is how much people value rewards now compared to rewards in the future. Specific brain areas are involved in valuing rewards and in controlling thoughts. Less activity in these areas has been linked to differences in delay discounting.

Among people with drug use problems, there is more brain activity in areas that help with control when they choose bigger rewards that come later, compared to smaller rewards that come right away. These studies show that the brain's control center may not be working well with the parts that feel pleasure. However, it is still not clear if this problem starts before drug use or if it can heal after someone stops using drugs.

NEW APPROACHES

Even though many brain imaging studies have been done on people with drug use problems, it is still hard to fully understand what causes and keeps these problems going. Because of this, new ways of thinking and new studies have started to look at different ideas that might help understand the disorder better.

One new approach uses math models to study behavior. These models help scientists understand what is happening in the brain that leads to certain actions. The goal is to better understand how the brain works. For example, using a math approach, scientists have found that how a person collects information might show a risk for drug use in young people. Problems with this process fit with other findings that people who use drugs do not correctly figure out if they should stop themselves from doing something.

Others have suggested that more changes or less steadiness in how the brain processes information might lead to these problems. Finally, new brain areas have been found as possible problem spots in people who use drugs. One area, the periaqueductal gray, works with other brain parts to deal with the pain of drug withdrawal. These new ways of studying point to new directions that may help explain why drug use problems start and continue.

NEUROLOGICAL DISORDERS AND SUBSTANCE USE

There is an interesting link between Parkinson's disease and drug use problems. Over the past ten years, studies have shown that medicines for Parkinson's disease can cause strong drug-seeking behaviors in some patients. Brain imaging suggests that these medicines might change how brain areas connect, leading to impulsive behavior.

Recent reviews of studies show mixed results about reward and punishment learning, thinking before acting, and making bad choices. However, there is growing agreement that Parkinson's medicines change how the brain controls movement or attention, which makes people act more impulsively. So, impulse control problems like drug use happen in some Parkinson's patients who take certain medicines. This might be because of problems with brain receptors, connections in certain brain circuits, and a stronger brain reaction to drug cues.

Parkinson's patients who feel more sadness and have certain symptoms seem more likely to choose rewards over punishments when taking medicine. This might show a problem in a specific brain system. All in all, existing problems, like a poor balance between brain control and reward feelings, might put Parkinson's patients at risk for drug use when they take certain medicines.

CONCLUSION

There continues to be good progress in brain imaging research on drug use problems. However, there are a few important things to note. First, most studies still compare people who use drugs to those who do not. This means they cannot prove that one thing causes another based on the brain scan data. But this is changing with big studies that follow young people over many years. Still, it will take years to get results from these studies.

Second, there is clear proof from several studies that links between the brain and behavior are weak. Even very large studies only show small connections between mental health problems and brain features. So, it is not likely that brain imaging studies will find very strong links to behavior or health issues. Lastly, people who use drugs are likely very different from each other in what made them start and how drugs changed their brains. This leads to many different brain patterns, which makes it hard to find one main brain problem behind drug use disorders.