Marijuana, or cannabis, was considered an illicit drug for decades. However, in many parts of the world, cannabis has been legalized for medical use or decriminalized for recreational or medicinal applications. This shift in attitude has resulted in a rapid increase in its use. It has been estimated that ≈183 million people in the world used marijuana in 2014¹ and that 22 million met criteria for cannabis use disorder in 2016.² In addition, according to the 2002 to 2019 National Survey on Drug Use and Health, the proportion of the US population >12 years of age who used marijuana in the past year increased gradually from 11% in 2002 to 18% in 2019.³ The use of marijuana has gained popularity, particularly among adolescents and young adults, with ≈36% of 12th graders and 43% of college students reporting having used it in the past year.⁴ In parallel, evidence suggests that the potency of cannabis products in the United States, measured by the concentration of the primary psychoactive constituent of marijuana, Δ⁹-tetrahydrocannabinol (THC), has gradually increased from ≈4% in 1995 to 15% in 2018.⁵

Cannabinoid receptors are expressed in high density in areas of the brain involved in executive function and memory such as the hippocampus, amygdala, and prefrontal cortex (PFC), particularly during periods of active brain development.⁶ Acute intoxication with cannabinoids can impair memory and behavioral inhibition.⁷ Cannabinoids also regulate anxiety and can produce psychosis-like effects.⁶ Evidence shows that age at exposure may influence the effect of cannabinoids on cognitive function. For example, the prenatal, perinatal, and adolescent periods may be particularly sensitive to these compounds.⁸ Data obtained in preclinical models have shown that cannabis and its associated signaling pathways regulate neurotransmission and play an active role in key cerebral processes, including neuroinflammation, neurogenesis, neural migration, synaptic pruning, and white matter development.^6,9 Furthermore, experimental data show that cannabinoids can regulate the functioning of different cytochrome-P450 isoforms and uridine 5′-diphospho-glucuronosyltransferases. Thus, there is a potential risk for drug-to-drug interactions with medications commonly used by the elderly such as warfarin, antiarrhythmic agents, sedatives, and anticonvulsants.¹⁰

These factors have raised concerns about the potential effect of cannabis on cognitive vitality. The goal of this scientific statement is to critically appraise the safety of cannabis use from the perspective of brain health.

Cannabis and Endocannabinoids

Anandamide and 2-arachidonoyl-glycerol are endogenous bioactive lipids that activate 2 G-protein–coupled receptors designated as cannabinoid receptor type 1 (CB1) and 2 (CB2). These lipids, called endocannabinoids, are not stored in vesicles but are synthesized on demand. The system formed by the cannabinoid receptors CB1 and CB2, endogenous ligands, and enzymes involved in their production and degradation is known as the endocannabinoid system (ECS). A detailed description of the composition and regulation of the ECS is beyond the scope of this publication; this topic has been reviewed extensively elsewhere.^9,11,12

Phytocannabinoids are exogenous cannabinoids extracted from flowering plants from the cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Whether these are species or subspecies is a matter of debate. More than 100 phytocannabinoids have been extracted from these plants, with THC and cannabidiol (CBD) being the most abundant. The relative concentration of THC and CBD in these strains is variable. In general, cannabis cultivars can be classified according to the cannabinoid produced as chemotype I (THC rich), II (THC/CBD balanced), III (CBD rich), IV (cannabigerol rich), or V (cannabinoid free).¹³

THC is a psychoactive alkaloid that signals through CB1 and CB2 receptors. Cannabinoid receptor type 1 is expressed abundantly in peripheral and central neural cells. In the periphery, CB1 localizes to sympathetic nerve terminals and sensory neurons. In the central nervous system, it is expressed mainly in presynaptic membranes of excitatory and inhibitory neurons, where it regulates the vesicular release of dopamine, GABA, and glutamate. In comparison, CB2 is expressed mainly in immune cells, including microglia.⁹

CBD is a nonpsychoactive cannabinoid that has antioxidant and anti-inflammatory properties. It is thought that CBD exerts some of the beneficial effects that phytocannabinoids have in Dravet syndrome and Lennox-Gastaut syndrome. Furthermore, studies done in preclinical models suggest that CBD is beneficial in Alzheimer disease, cerebral ischemia, multiple sclerosis, and other neurologic disorders.^9,14 The therapeutic potential of CBD is being investigated in different clinical trials. Compared with THC, CBD signals through different pathways but does not activate CB1 and CB2. At low concentration, CBD blocks the orphan G-protein–coupled receptor-55, the equilibrative nucleoside transporter 1, and the transient receptor potential of melastatin type 8 channel. It also activates the serotonin (5-hydroxytryptamine) 1A receptor, the transient receptor potential of ankyrin type 1 channel, and α3 and α1 glycine receptors. At high concentration, CBD activates the nuclear peroxisome proliferator-activated receptor γ and the transient receptor potential of vanilloid types 1 and 2.^12,14

Several cannabinoids have received approval in different countries for the treatment of specific medical conditions. In addition, high-potency synthetic cannabimimetics such as Spice are available in the illegal market (Table 1).^15–17

Neurobiological Actions of Cannabis in Animal Models

Molecular and cellular mechanisms underlying the effects of cannabis on the developing brain are inferred mainly from preclinical studies that permit controlling for social and environmental factors that could influence outcomes of interest. In addition, animal models allow the investigation of a range of human age-related behavioral factors (eg, novelty and sensation seeking, impulsivity, risk-taking behaviors) and key stages of neurodevelopment that are conserved across many mammalian species. However, many individual (eg, species, strain, age) and experimental (eg, design, drug, dose, delivery, regimen) variables, along with objective end points (eg, behavioral paradigm, experimental technique), have contributed to equivocal findings across studies. Nonetheless, experimental animal models of prenatal and adolescent cannabis exposure have proved fundamental in disclosing the underlying neurobiological mechanisms that might explain several clinical neuropsychiatric outcomes outlined here.

Animal models have been used to examine the role of the ECS in the modulation of synaptic plasticity, a process that allows the brain to change and adapt to new information.¹⁸ The ECS modulates synaptic plasticity by affecting the strength of interneuronal connections and, ultimately, the functioning of neuronal networks. From the mechanistic standpoint, THC activates cannabinoid receptors in the brain, thus interfering with physiological actions of endocannabinoids. Spatial and time resolution of endocannabinoid production is pivotal for correct processing of different brain functions such as higher-order cognition, memory, reward, mood, and stress sensitivity.^8,19,20 Consequently, THC, activating nonspecifically CB1 receptors in the brain, disrupts the fine-tuning of synaptic activity exerted by endocannabinoids, eventually impairing connectivity of neuronal networks and brain functionality.

Although incompletely understood, the way in which THC disrupts memory and learning may be through its differential effect on neurotransmitter release and binding to CB1 receptors.¹⁹ For example, THC activates CB1 receptors located on GABAergic interneurons, which represent nearly three-quarters of the brain CB1 receptors, and astrocytes, resulting in the release of hippocampal glutamate. Concomitantly, THC affects the transmission of other neurotransmitters involved in the modulation of memory such as acetylcholine, adenosine, and serotonin.^19,20 Furthermore, THC activation of CB1 receptors present on mitochondria leads to decreased cellular respiration and ATP supply.¹⁹ ATP is fundamental in maintaining and regulating neurotransmission, and its reduction might contribute to THC-induced cognitive deficits.

Repeated exposure to cannabis, especially during the adolescent developmental period, may be especially harmful to brain health and cause structural, molecular, and functional alterations of brain circuits, particularly in the PFC and hippocampus.^8,21,22 Long-term THC exposure induces CB1 receptor downregulation and desensitization that appear more intense and widespread after adolescent exposure as opposed to adulthood exposure.²² Data obtained in experimental models showed that these effects could have implications for neurodevelopmental processes in which the ECS plays a role. Accordingly, long-term THC exposure during adolescence may disrupt dynamic changes occurring in glutamatergic and GABAergic systems, leading to excessive synaptic pruning (ie, loss of synaptic contacts), long-term dysfunction in prefrontal excitatory/inhibitory balance, and desynchronization of PFC neuronal networks, which also dysregulate the mesolimbic dopaminergic pathway (Figure).²³ These changes may represent the molecular underpinnings of cognitive deficits and altered emotional reactivity and social behavior observed long after adolescent long-term THC exposure.²² Long-term changes in brain functionality induced by THC exposure during adolescence might also arise from epigenetic modifications with a marked reprogramming of the transcriptome, affecting mainly genes related to synaptic plasticity processes.^8,19 These effects have not been reported after adult THC exposure.¹⁹

In addition to the effects on neuron cellular and subcellular components, recent evidence suggests that alterations in glial cells have a key role in the actions of THC.²⁴ Long-term THC exposure activates microglia and astrocytes to produce inflammatory cytokines. For example, long-term administration of THC during adolescence increased the microglial expression of the proinflammatory mediators tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 by 60%, 130%, and 80%, respectively, and reduced the expression of the anti-inflammatory cytokine interleukin-10 by 30% in the PFC. The resulting neuroinflammatory response was associated with memory impairment during adulthood.²⁵

Dose constitutes an additional important variable to consider. Most studies describe detrimental effects of THC in models of heavy cannabis use in middle adolescence. However, even lower doses may produce these same effects when administered earlier in adolescence.²²

Effect of Prenatal Exposure to Cannabinoid Agonists

A recent study examined associations between prenatal cannabis exposure (PCE) and various indicators of mental and neurocognitive health in a sample of 11 489 youth.²⁶ Self-report of maternal cannabis use during pregnancy was associated with various adverse outcomes among youth at 9 to 10 years of age, including poorer performance on tests of neurocognitive functioning and total intracranial volumes, even after controlling for potential confounders. Several reviews describe PCE sequelae in preclinical models.^8,24,27–30 Here, we focus on mechanistic insights inferred from animal studies recapitulating the neuropsychiatric features of clinical outcomes.³¹ The detrimental effect of PCE on cognitive processing and emotional regulation of the progeny has been ascribed to changes in intrinsic and synaptic properties and plasticity of cortical (eg, PFC), limbic (eg, amygdala, hippocampus), and midbrain (eg, ventral tegmentum) regions. Changes in the balance of excitatory and inhibitory input strength, along with alterations in how principal neurons and interneurons receive, integrate, and convey information, have been observed in these neuroanatomic areas (Figure).^8,24,27–30 Aberrant glutamatergic function is a common hallmark, as indexed by changes in the expression and function of ionotropic and metabotropic receptors and in dynamic regulation of glutamate levels by glutamate transporters at both synaptic cleft and extrasynaptic spaces. These changes depend largely on the alterations of endocannabinoid signaling pathways caused by exogenous cannabinoids during development and throughout ontogenesis (eg, neural proliferation, survival, directional axonal growth).^8,24,27–30 Defects in ECS function also may account for the interneuronopathy observed in many brain regions of PCE offspring, a phenomenon often more prominent in female than in male animals.^8,27–29 In the PFC, this persistent inhibitory circuit deficit also is associated with a delayed switch of GABA from its excitatory role early in development to a classic inhibitory function exerted throughout the central nervous system later in life.^8,29 This is particularly relevant because the GABA switch represents a critical milestone during neurodevelopment. Any alteration in the normal and predictable temporal sequence of these periods such as delays, stalls, or accelerations imposed by PCE may lead to perturbations of offspring cognitive processing and emotional behavior.^8,29

It was observed that marijuana use leads to dysregulation of monoaminergic pathways and stress response systems.^8,27–29 PCE hampers the maturation of monoamines, which also exert trophic actions on target neurons and afferent terminals. This phenomenon may depend on epigenetic modifications and may be implicated in aberrant reward signaling. Furthermore, PCE is associated with an endophenotype in the offspring, which displays protracted dysregulation of stress responsivity that is not explained by glucocorticoid levels. A susceptibility to acute and chronic stress is tied to many psychiatric disorders, ranging from depressed mood and psychosis to substance use disorders and anxiety. A deeper understanding of how PCE interferes with endocannabinoid signaling during neurodevelopment would allow us to explore potential interventions aimed at restoring or reprogramming the hierarchical progression of developmental milestones.

Effects of Marijuana Use on Human Cognition

Acute intoxication from marijuana is associated with impairment of working and episodic memory, behavioral disinhibition, and impulsivity, which can affect performance in real-world activities.⁶ For example, a meta-analysis from 2016 showed that the odds of being involved in a motor vehicle accident was increased 36% in cannabis users relative to nonusers.³² In addition, a crossover clinical trial published in 2020 investigated the effect of different cannabis products in relation to on-road driving tests. The SD of lateral position, a measure of lane weaving, swerving, and overcorrection, was 20.29 cm at 40 to 100 minutes after inhalation of THC-dominant cannabis and 21.09 cm after inhalation of a mixture of THC and CBD. It is interesting to note that the SD of lateral position after inhalation of CBD-dominant cannabis was similar to that in the placebo group (18.21 cm versus 18.26 cm).³³ These observations illustrate the differential short-term effect of THC and CBD on cognition. Evidence also suggests that the short-term effects of cannabinoids are transient and can be influenced by the development of tolerance and the use of other drugs.

The long-term effect of cannabis on cognition, however, is less well established. Recent meta-analyses report residual effects of cannabis use on neurocognition, consistent with prior research.³⁴ A meta-analysis by Lovell et al³⁵ in 2020 focused on adult near-daily cannabis use for >2 years and found global neurocognition among users (n=849) to be about one-quarter of an SD worse than that of nonusers (n=764). Four of the 7 domains investigated (decision-making, verbal learning, retention, executive function) showed significant effect sizes ranging from Hedges g=−0.52 to −0.18. A meta-analysis of cannabis users <26 years of age (n=2152) and nonusers (n=6575) also showed a one-quarter of an SD difference in global neurocognitive performance but with more specific domains affected,³⁶ albeit with smaller effect size compared with that found by Lovell et al.³⁵ Both lacked support for worse neurocognition in early adolescence in that neither found that age at onset of cannabis use influenced the association between exposure and cognitive performance.

In contrast to these meta-analyses, large longitudinal studies provide stronger causal inferences by examining change over time. In the CARDIA study (Coronary Artery Risk Development in Young Adults), 3385 participants 18 to 30 years of age were followed up longitudinally. Marijuana use was assessed periodically in the 25-year follow-up. In addition, cognitive assessment was completed 25 years after inception. In this study, cumulative years of exposure to marijuana was associated with worse verbal memory (0.13 lower SD in the verbal memory test for each additional 5 years of exposure to marijuana).³⁷ Longitudinal co-twin studies use a research design that additionally controls for shared variance from genetic and environmental factors. Two large longitudinal twin studies (n=3066) with neurocognitive measures collected before (at 9–12 years of age) and after (17–20 years of age) cannabis exposure reported that declines in vocabulary and general knowledge were associated with being a cannabis user but not with amount of cannabis consumed.³⁸ Twins discordant for cannabis use showed no differences in IQ declines. Thus, differences were likely caused by shared risk factors. Using a similar design, Meier et al³⁹ reported that lower IQ predated cannabis use with no evidence of actual IQ declines among 1989 twins assessed at 5, 12, and 18 years of age. Ross et al⁴⁰ evaluated other aspects of neurocognition among 856 individual twins and reported only 1 within-family effect of 70 tested. Specifically, frequency of cannabis use at 17 years of age was associated with poorer executive functioning at 23 years of age, but executive functioning problems predating cannabis use could not be ruled out.

Magnetic resonance imaging (MRI) techniques demonstrate differential associations of cannabis use with brain structure and function. In terms of brain structure, alterations related to cannabis use have been mixed. In a longitudinal study including 1598 MRIs done in adolescents at baseline and the 5-year follow-up, a dose-dependent association was observed between cannabis use and PFC thinning.⁴¹ On the other hand, although a meta-analysis found that regular cannabis consumption was associated with smaller hippocampal (standardized mean difference, 0.14 [95% CI, 0.02–0.27]), medial orbitofrontal cortex (standardized mean difference, 0.30 [95% CI, 0.15–0.45]), and lateral orbitofrontal cortex (standardized mean difference, 0.19 [95% CI, 0.07–0.32]) volumes relative to nonuse, brain volumes were not associated with cannabis use duration and dosage.⁴² Other large studies have reported null effects. In 2 large twin samples from the United States (n=474) and Australia (n=622), cannabis use was unrelated to volumes of the thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens.⁴³ A multisite study of cortical surface measures (n=262) reported no difference in cortical thickness, surface area, and gyrification index in cannabis users versus nonusers, in cannabis dependence versus nondependence versus nonusers, and in early adolescent versus late adolescent onset of cannabis use versus nonuse.⁴⁴ Thus, brain structural abnormalities related to cannabis use are inconsistent.

Functional MRI studies report more robust effects, particularly after prolonged cannabis use. A meta-analysis of task-based functional MRI studies in current adult and adolescent users found abnormalities in activation in both age groups. Relative to nonusing control subjects, adult cannabis users had greater brain activation in the superior (seed-based d mapping [SDM-Z], 1.561; P<0.002) and posterior (SDM-Z, 1.479; P<0.003) transverse temporal and inferior frontal gyri (SDM-Z, 1.568; P<0.002) and less activation in the striatum (SDM-Z, −1.843; P<0.001), insula (SDM-Z, −1.637; P<0.001), and middle frontal gyrus across different tasks. Adolescent cannabis users also had greater activation in the inferior parietal gyrus (SDM-Z, 1.06; P<0.001) and putamen (SDM-Z, 1.008; P<0.001) compared with nonusers across various tasks, suggesting compensatory neuroadaptive mechanisms.⁴⁵ These functional abnormalities persist despite cessation of cannabis use and beyond the period when THC metabolites are detectable. A meta-analysis of the same adolescent studies found that >25-day abstinent adolescent cannabis users exhibited greater activation in the right inferior frontal gyrus in addition to other areas relevant for executive functioning and self-regulatory mechanisms.⁴⁶

Several recent studies examined cannabis effects in populations with premorbid clinical risk factors and those using medical marijuana. A meta-analysis focused only on cannabis users with psychosis <25 years of age (n=529) and nonusing control subjects with psychosis (n=901). In this study, there were significant differences in 3 of 11 domains assessed (premorbid IQ, Hedges g=0.40 [standardized effect size]; current IQ, Hedges g=−0.17; working memory, Hedges g=−0.76).⁴⁷ Among a sample of 215 adult patients with chronic pain provided daily herbal cannabis containing 12.5% THC for 1 year, no significant neurocognitive differences were found compared with 216 control subjects.⁴⁸ This is in line with a study of patients with multiple sclerosis in response to oral dronabinol that found no significant differences in MRI-derived measures, including annual percentage of brain volume change and occurrence of new lesions, after 12 months of use.⁴⁹ These clinical trials suggest no significant adverse effect of THC on neurocognitive symptoms in specific clinical populations.

Cerebrovascular Risk and Disease

Cerebrovascular Risk Factors

Similar to the literature linking marijuana use with cardiovascular outcomes,¹⁰ evidence that marijuana consumption increases the prevalence of specific cerebrovascular risk factors and disease is limited by a preponderance of observational studies, cross-sectional studies, case reports, and case series prone to potential publication and other biases. Postulated adverse effects of marijuana use may include sympathetic nervous system activation, blood pressure changes, platelet activation, and electrophysiological effects.^50–52 Concomitant tobacco smoking and other substance use and abuse possibly contribute to these effects, which may be short term and have been studied mostly in low-risk populations such as younger adults. These factors may explain why many longitudinal studies linking marijuana use and cardiovascular or metabolic risk factors have been negative after multivariable adjustment for unhealthy behaviors such as diet and tobacco smoking.^53–55

Hypertension, in particular, is an important risk factor for ischemic stroke, hemorrhagic stroke, and subarachnoid hemorrhage. With marijuana use, the most common acute reaction in humans is a decrease in blood pressure resulting from cannabinoid effects on the vasculature and autonomic nervous system.⁵² Despite this physiological reaction, limited studies using the National Health and Nutrition Examination Survey showed a modest association of recent cannabis use with higher systolic blood pressure and higher prevalence of hypertension among current users 30 to 59 years of age.⁵⁶ Heavy users, defined as use of marijuana or hashish in >20 of the past 30 days, had higher odds of abnormal blood pressure compared with never-users. Although this difference remained statistically significant after adjustment for age, sex, race, ethnicity, body mass index, education, and survey year, it was no longer statistically significant after additional adjustment for current tobacco and binge alcohol use (adjusted odds ratio, 1.47 [95% CI, 0.99–2.16]).⁵⁷ The relationship between marijuana use and elevated blood pressure, especially among heavy users, may drive longer-term associations with cerebrovascular outcomes, although this mechanism remains to be studied.

Prior cardiovascular disease such as myocardial infarction (MI) or atrial fibrillation (AF) is also an important risk factor for stroke.⁵⁸ Case reports of MI after marijuana use are mainly among young adults who lack vascular risk factors, with onset of MI shortly after use.⁵⁹ Risk of MI was elevated 4.8-fold within an hour after smoking marijuana compared with periods of nonuse. This association demonstrates the potential role of marijuana as an acute trigger for cardiovascular disease.⁶⁰ Over 25 years of follow-up, among 5113 adult participants in the Coronary Artery Risk Development in Young Adults study, cumulative or recent marijuana use was not associated with coronary heart disease, stroke, or cardiovascular disease mortality.⁶¹ This finding contrasts with a population-based, multi-institutional database study that observed an increased risk of 3-year cumulative incidence of MI among marijuana users compared with control subjects (1.37% vs 0.54%; relative risk, 2.54 [95% CI, 2.45–2.61]).⁶²

Similarly, marijuana use appears to be a trigger for AF. Data from the Nationwide Inpatient Sample show that the percentage of individuals with cannabis use disorder discharged in the postlegalization period (2010–2014) with the diagnosis of arrhythmia increased 31%.⁶³ However, in a study of patients hospitalized for heart failure, marijuana users had a reduced odds of AF compared with nonusers (adjusted odds ratio, 0.87 [95% CI, 0.77–0.98]).⁵⁰ Simultaneous use of cocaine, stimulants, and other drugs may be responsible for observations of AF among marijuana users, although this remains to be fully studied outside of observational and cross-sectional reports.

Risk of Stroke and Transient Ischemic Attack

Several case reports and case series mostly in young individuals suggest a relationship between recent and heavy cannabis use and risk of stroke.^64–66 In contrast, and as reviewed below, findings among case-control studies,⁶⁷ population-based studies,⁶⁸ and studies conducted using outpatient^69,70 or inpatient^71,72 national databases or hospital electronic health records⁷³ have been equivocal, depending on the study design, covariates considered in the analysis, and source of the population being studied. Inconsistent associations also can be attributable to the presence of comparison groups and whether adjustment of other important risk factors was considered, along with attention to potential confounding by other risk factor and lifestyle features between cannabis users and nonusers.

In 1 case-control study using cannabis urine screens to identify cannabis users, the authors found an association between cannabis use and the risk of ischemic stroke and transient ischemic attack, but the association was not significant when tobacco use was included as a covariate (adjusted odds ratio, 1.59 [95% CI, 0.71–3.70]) among subjects 18 to 55 years of age with and without stroke.⁶⁷ Similarly, after adjustment for cigarette smoking and alcohol use, another study found no association between cannabis use in young adulthood and the occurrence of fatal and nonfatal stroke later in life among Swedish men in up to 38 years of follow-up.⁶⁸

Data from studies that have examined more specifically the dose or amount of cannabis consumed within a designated time frame suggest that regular cannabis use may increase the risk of stroke. Using data from population-based surveys, investigators have reported that when no cannabis use was compared with heavy cannabis use in the past year, cannabis use was associated with an increased risk for the occurrence of nonfatal stroke and transient ischemic attack.⁷⁰ Similarly, another study found that recent (within the past 30 days) and frequent (>10 d/mo) cannabis use was associated with increased risk for the occurrence of stroke compared with nonuse, whereas less frequent cannabis use (≤10 d/mo or less than weekly in the past year) was not associated with increased risk.^69,70

Using several International Classification of Diseases, Ninth Revision, Clinical Modification codes for marijuana use, a Nationwide Inpatient Sample study found that cannabis use among men and women hospitalized between 2004 and 2011 was associated with a 17% increased relative risk for acute ischemic stroke in a multivariable-adjusted analysis. Concomitant use of tobacco with cannabis increased the risk to 31%.⁷¹ Similarly, a separate study using the Nationwide Inpatient Sample but between 2009 and 2010 observed a higher odds of stroke among cannabis users (odds ratio, 1.24 [95% CI, 1.14–1.34]).⁷² In contrast, investigators using electronic health record data from patients admitted to a single center between 2015 and 2017 found that testing positive for cannabis use was not associated with the risk of ischemic stroke compared with testing negative, even after adjustment for numerous confounders, including age, cigarette smoking, and comorbidities.⁷³

There may be certain populations or scenarios in which cannabis use can be meaningfully linked to stroke. A study of a large longitudinal cohort of Canadian pregnant women that included >1 million participants between 1989 and 2019 with follow-up at 30 years observed that cannabis use disorder was associated with a doubling of risk for hemorrhagic stroke (hazard ratio, 2.08 [95% CI, 1.07–4.05]) but no increased risk for ischemic or other cerebrovascular disease.⁷⁴ Because of the theoretical vasoactive effect of cannabis, its use has been implicated in some cases of reversible cerebral vasoconstriction syndrome, with 6 of 24 nonidiopathic reversible cerebral vasoconstriction syndrome cases at a Colorado stroke center attributed to marijuana use.⁷⁵ In addition, an elevated risk of stroke from intracranial arterial stenosis has been described among young cannabis users 18 to 45 years of age wherein vasospasm or reversible cerebral vasoconstriction syndrome may be a potential mechanism.⁷⁶ Studies done in experimental models have shown that cannabinoids exert complex effects on cardiac contractility, vascular tone, and atherogenesis. Both vasodilatation and vasoconstriction responses were observed, depending on the experimental model and cannabinoid used. CB1 activation promotes inflammation, upregulates the production of reactive oxygen species, and activates proapoptotic pathways in endothelial cells and cardiomyocytes. In addition, it induces endothelial dysfunction and vascular smooth muscle cell proliferation and migration. These processes have been linked to cardiac dysfunction and the development of atherosclerosis.⁵² This is in contrast to the atheroprotective role associated with CB2.

Acute cardiovascular events and stroke also have been reported in patients using synthetic cannabinoids.⁷⁷ Spice is associated with idiopathic thrombocytopenic purpura, which increases the risk of major hemorrhage.⁷⁸ In addition, intracranial hemorrhage in Spice users has been linked to the presence of brodifacoum, an adulterant considered a superwarfarin.⁷⁹

Education and Future Directions

Our understanding of the ramifications of cannabis consumption on brain health is limited but rapidly evolving. Observational studies have produced conflicting results in relation to the effect of marijuana on different outcomes of interest, including hypertension, AF, MI, and cognition. Several methodological factors may explain these apparent contradictions. First, given its historical classification as an illicit drug, the use of marijuana has been underreported for generations. The inclusion of marijuana users in the control group of observational studies that rely on self-reported use could underestimate its effect on brain health. Second, several behaviors such as smoking and alcohol use are associated with marijuana consumption and can influence stroke risk and brain connectivity.^80,81 The often missing information on frequency of exposure to these factors limits our ability to determine with accuracy the independent effect of marijuana. Third, the time of exposure, frequency of use, and bioavailability of marijuana, which is affected by the route of administration, diet, and concomitant use of medications that may affect its metabolism, are reported inconsistently.¹⁰ Fourth, THC and CBD have different pharmacological effects. Although the use of THC has been associated with detrimental effects, CBD appears to have therapeutic potential in some neurologic disorders.⁹ The absolute and relative concentrations of these compounds differ according to the strain of cannabis plant and the methodology used to extract the active ingredients.⁸² Fifth, the gradual increase in the potency of marijuana used recreationally limits the relevance of older studies.⁵ Sixth, different factors impede the development of long-term placebo-controlled studies, including ethical reasons and the psychotropic effect of THC, which cannot be blinded.

Social media may emphasize a beneficial role for marijuana, and the general population may perceive it as a harmless drug. However, the emerging evidence linking marijuana use to cardiovascular events and stroke, as well as the potential and demonstrated drug-to-drug interactions between marijuana and medications commonly used in the general population, calls for caution and highlights the potential importance of active surveillance programs.^10,83 In addition, the high density of cannabinoid receptors in areas involved in executive function and memory, the dose-dependent detrimental effect of THC on working and episodic memory, and the role of cannabinoid-associated biochemical pathways on synaptic plasticity and neuronal development raise concern that long-term exposure to marijuana may affect brain health. There is lack of agreement on whether the effects of marijuana resolve completely after months of abstinence. However, the disruption of endocannabinoid signaling pathways during the prenatal and perinatal periods and in adolescence may be detrimental to neurodevelopment.^6,8,9 Key points discussed in this scientific statement are summarized in Table 2. It should be noted that the overarching goal of this scientific statement was to discuss mechanisms by which marijuana use could influence brain health. However, as the field is developing, several important aspects require additional research. As an example, there is limited information comparing the differential effect of recreational, illicit, and medicinal uses of marijuana, as well as the type of cannabis product consumed. Similarly, the modulatory effects of social determinants of health and race and ethnicity on the interaction of brain health and marijuana use are largely unexplored. The latter area of research may be particularly important because communities of color in the United States may be disproportionately affected by natural and synthetic cannabinoids in relation to use and exposure and the legal implications of criminalization of marijuana.⁸⁴

Public health efforts should be considered to raise awareness about the potential negative effects associated with the use of marijuana in the general population. Possible strategies include the use of standardized concentrations of biologically active components and health warning labels on available formulations. In addition, the use of marijuana should be individualized and closely monitored. Health care professionals and patients should receive unbiased education about the potential consequences of medicinal, recreational, and illicit marijuana use on brain health, particularly when the exposure occurs during vulnerable vital periods. It also may be important for professionals to monitor cognitive performance of marijuana users and to review their medications to identify potential drug-to-drug interactions. Knowledgeable health care professionals will be able to properly educate potential or active marijuana users about its possible adverse effects, empowering them to make an informed decision that is based on unbiased data.

Article Information

Published online February 10, 2022.

The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists.

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 29, 2021, and the American Heart Association Executive Committee on September 5, 2021. A copy of the document is available at https://professional.heart.org/statements by using either “Search for Guidelines & Statements” or the “Browse by Topic” area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com

Summary

For decades, cannabis, also known as marijuana, was classified as an illegal drug. However, many regions globally have legalized cannabis for medical purposes or decriminalized it for recreational and medicinal uses. This change has led to a rapid increase in its consumption. Estimates suggest approximately 183 million people used marijuana in 2014, with 22 million meeting the criteria for cannabis use disorder in 2016. In the United States, the proportion of individuals over 12 years of age who used marijuana in the past year rose from 11% in 2002 to 18% in 2019. Its popularity has grown, particularly among adolescents and young adults, with about 36% of 12th graders and 43% of college students reporting past-year use. Concurrently, the potency of cannabis products, measured by Δ9-tetrahydrocannabinol (THC) concentration, has significantly increased from around 4% in 1995 to 15% in 2018.

Cannabinoid receptors are highly concentrated in brain areas vital for executive function and memory, such as the hippocampus, amygdala, and prefrontal cortex, especially during critical periods of brain development. Acute intoxication with cannabinoids can impair memory and behavioral inhibition. Cannabinoids also influence anxiety levels and can induce psychosis-like effects. Evidence suggests that the age of exposure can impact how cannabinoids affect cognitive function, with prenatal, perinatal, and adolescent periods being particularly vulnerable. Preclinical studies indicate that cannabis and its related signaling pathways regulate neurotransmission and are involved in crucial brain processes, including neuroinflammation, neurogenesis, neural migration, synaptic pruning, and white matter development. Furthermore, cannabinoids can regulate the function of certain enzymes (cytochrome-P450 isoforms and uridine 5′-diphospho-glucuronosyltransferases), raising concerns about potential drug interactions with medications commonly used by older adults, such as warfarin, antiarrhythmic agents, sedatives, and anticonvulsants.

These factors raise concerns about the potential impact of cannabis on cognitive vitality. The objective of this scientific statement is to critically evaluate the safety of cannabis use concerning brain health.

Cannabis and Endocannabinoids

Anandamide and 2-arachidonoyl-glycerol are naturally occurring lipids in the body that activate two G-protein-coupled receptors known as cannabinoid receptor type 1 (CB1) and type 2 (CB2). These lipids, called endocannabinoids, are produced as needed rather than stored. The system comprising CB1 and CB2 receptors, their natural ligands, and the enzymes involved in their production and breakdown is known as the endocannabinoid system (ECS).

Phytocannabinoids are cannabinoids obtained from cannabis plants, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Over 100 phytocannabinoids have been identified from these plants, with THC and cannabidiol (CBD) being the most common. The levels of THC and CBD vary among different strains, allowing for classification into chemotypes based on their cannabinoid profiles (e.g., THC-rich, CBD-rich, or balanced).

THC is a psychoactive compound that interacts with both CB1 and CB2 receptors. CB1 receptors are highly present in neural cells throughout the body and brain. In the central nervous system, CB1 receptors on presynaptic membranes regulate the release of important neurotransmitters like dopamine, GABA, and glutamate. In contrast, CB2 receptors are mainly found in immune cells, including microglia.

CBD is a non-psychoactive cannabinoid known for its antioxidant and anti-inflammatory properties. It is believed to contribute to the beneficial effects of phytocannabinoids in certain medical conditions like Dravet syndrome and Lennox-Gastaut syndrome. Preclinical research also suggests CBD may be beneficial in Alzheimer's disease, cerebral ischemia, multiple sclerosis, and other neurological disorders. CBD's therapeutic potential is currently being investigated in clinical trials. Unlike THC, CBD does not activate CB1 and CB2 receptors but interacts through other pathways. At low concentrations, CBD blocks certain receptors and transporters, while at higher concentrations, it activates other nuclear and transient receptor potential pathways.

Neurobiological Actions of Cannabis in Animal Models

Preclinical studies using animal models are crucial for understanding the molecular and cellular ways cannabis affects the developing brain, as these studies allow for control over social and environmental factors that might influence outcomes. Animal models also enable the investigation of age-related behaviors and key stages of neurodevelopment consistent across many mammalian species. Despite variations in individual and experimental variables leading to some inconsistent findings, these models have been fundamental in revealing neurobiological mechanisms that may explain various clinical neuropsychiatric outcomes.

Animal models have demonstrated the endocannabinoid system's role in modulating synaptic plasticity, which is the brain's ability to change and adapt to new information. The ECS influences synaptic plasticity by altering the strength of connections between neurons, thereby affecting neuronal network function. From a mechanistic perspective, THC activates cannabinoid receptors in the brain, interfering with the natural actions of endocannabinoids. The precise timing and location of endocannabinoid production are essential for proper brain functions, including higher-order cognition, memory, reward, mood, and stress sensitivity. Consequently, THC, by broadly activating CB1 receptors in the brain, disrupts the delicate balance of synaptic activity maintained by endocannabinoids, potentially impairing neuronal network connectivity and overall brain function.

The mechanisms by which THC disrupts memory and learning may involve its varied effects on neurotransmitter release and its binding to CB1 receptors. For instance, THC activates CB1 receptors located on GABAergic interneurons and astrocytes, leading to the release of hippocampal glutamate. Additionally, THC affects the transmission of other neurotransmitters involved in memory modulation, such as acetylcholine, adenosine, and serotonin. Furthermore, THC's activation of CB1 receptors on mitochondria results in reduced cellular respiration and ATP (energy) supply. A reduction in ATP, which is essential for maintaining neurotransmission, may contribute to THC-induced cognitive deficits.

Repeated exposure to cannabis, particularly during adolescence, can be especially harmful to brain health, causing structural, molecular, and functional changes in brain circuits, notably in the prefrontal cortex and hippocampus. Long-term THC exposure leads to CB1 receptor downregulation and desensitization, effects that appear more pronounced after adolescent exposure compared to adult exposure. Experimental models indicate that these effects could impact neurodevelopmental processes where the ECS plays a vital role. Accordingly, prolonged THC exposure during adolescence may disrupt the dynamic changes in glutamatergic and GABAergic systems, leading to excessive synaptic pruning (loss of synaptic connections), long-term dysfunction in the prefrontal excitatory/inhibitory balance, and desynchronization of prefrontal cortex neuronal networks, which also affects the mesolimbic dopaminergic pathway. These changes may underlie the cognitive deficits and altered emotional reactivity and social behavior observed long after adolescent THC exposure. Such long-term functional brain changes from adolescent THC exposure might also stem from epigenetic modifications that reprogram gene expression, particularly affecting genes related to synaptic plasticity. These specific effects have not been reported after adult THC exposure.

Beyond neuronal effects, recent evidence suggests that alterations in glial cells play a key role in THC's actions. Long-term THC exposure can activate microglia and astrocytes to produce inflammatory cytokines. For example, prolonged THC administration during adolescence increased microglial expression of pro-inflammatory mediators and reduced an anti-inflammatory cytokine in the prefrontal cortex. This resulting neuroinflammatory response was linked to memory impairment in adulthood. The dose of cannabis is another important variable; most studies describe harmful effects with heavy cannabis use in mid-adolescence, but even lower doses can produce these same effects when administered earlier in adolescence.

Effect of Prenatal Exposure to Cannabinoid Agonists

A recent study examined the relationship between prenatal cannabis exposure (PCE) and various indicators of mental and neurocognitive health in a sample of over 11,000 youth. The mothers' self-reported cannabis use during pregnancy was associated with several negative outcomes in their children at 9 to 10 years of age, including poorer performance on neurocognitive tests and reduced total intracranial volumes, even after accounting for other influencing factors. Several reviews detail the consequences of PCE in preclinical models, and this discussion focuses on the insights gained from animal studies that mirror clinical neuropsychiatric features.

The harmful effects of PCE on offspring cognitive processing and emotional regulation have been attributed to changes in the intrinsic and synaptic properties and plasticity of brain regions like the prefrontal cortex, amygdala, hippocampus, and ventral tegmentum. Alterations in the balance of excitatory and inhibitory input strength, along with changes in how neurons process and transmit information, have been observed in these areas. A common finding is aberrant glutamatergic function, indicated by changes in the expression and function of glutamate receptors and in the dynamic regulation of glutamate levels at synapses. These changes largely depend on alterations to endocannabinoid signaling pathways caused by external cannabinoids during development, affecting processes like neural proliferation, survival, and axonal growth.

Defects in endocannabinoid system function may also explain the observed interneuronopathy (abnormalities in interneurons) in many brain regions of PCE offspring, a phenomenon often more pronounced in female animals. In the prefrontal cortex, this persistent inhibitory circuit deficit is also linked to a delayed switch of GABA (a neurotransmitter) from its excitatory role early in development to its typical inhibitory function later in life. This is particularly significant because the GABA switch is a critical milestone in neurodevelopment. Any disruption to the normal timing of these developmental periods, such as delays or accelerations caused by PCE, can lead to disturbances in the offspring's cognitive processing and emotional behavior.

Marijuana use has been observed to lead to the dysregulation of monoaminergic pathways and stress response systems. PCE hinders the maturation of monoamines, which also play a role in nourishing target neurons. This phenomenon may involve epigenetic modifications and could be related to abnormal reward signaling. Furthermore, PCE is associated with an enduring dysregulation of stress responsiveness in offspring, a condition not fully explained by glucocorticoid levels. A heightened susceptibility to acute and chronic stress is linked to numerous psychiatric disorders, including depression, psychosis, substance use disorders, and anxiety. A deeper understanding of how PCE interferes with endocannabinoid signaling during neurodevelopment could facilitate the development of interventions aimed at restoring or reprogramming the normal progression of developmental milestones.

Effects of Marijuana Use on Human Cognition

Acute intoxication from marijuana is linked to impairments in working and episodic memory, along with behavioral disinhibition and impulsivity, which can impact performance in real-world activities. For instance, a 2016 meta-analysis indicated that cannabis users had a 36% higher likelihood of being involved in a motor vehicle accident compared to non-users. A 2020 clinical trial investigating the effect of different cannabis products on driving performance found that inhalation of THC-dominant cannabis or a THC and CBD mixture increased lane weaving and overcorrection, whereas CBD-dominant cannabis had a similar effect to placebo. These observations highlight the differing short-term cognitive effects of THC and CBD. Evidence also suggests that the short-term effects of cannabinoids are temporary and can be influenced by developing tolerance and the use of other drugs.

The long-term effects of cannabis on cognition are less definitively established. Recent meta-analyses report residual neurocognitive effects from cannabis use, consistent with earlier research. One 2020 meta-analysis focused on adults who used cannabis near-daily for over two years, finding their global neurocognition was approximately one-quarter of a standard deviation worse than non-users. Four of seven cognitive domains examined (decision-making, verbal learning, retention, executive function) showed significant negative effects. Another meta-analysis of cannabis users under 26 years old and non-users also showed a similar difference in global neurocognitive performance, though with specific affected domains. Neither study found that the age at which cannabis use began influenced the association between exposure and cognitive performance.

In contrast to these meta-analyses, large longitudinal studies provide stronger insights into causality by examining changes over time. In the CARDIA study (Coronary Artery Risk Development in Young Adults), which followed over 3,000 participants for 25 years, cumulative years of marijuana exposure were associated with worse verbal memory. Longitudinal co-twin studies, which control for shared genetic and environmental factors, have yielded mixed results. Two large twin studies reported that declines in vocabulary and general knowledge were associated with being a cannabis user, but not with the amount consumed, and twins differing in cannabis use showed no differences in IQ declines, suggesting that shared risk factors were likely the cause. Other studies using similar designs have reported that lower IQ often predated cannabis use, with no evidence of actual IQ declines among users. One study found that the frequency of cannabis use at age 17 was associated with poorer executive functioning at age 23, but the possibility of pre-existing executive functioning problems could not be ruled out.

Magnetic resonance imaging (MRI) techniques show varying associations between cannabis use and brain structure and function. Structural brain alterations related to cannabis use have been inconsistent. A longitudinal study of adolescents found a dose-dependent link between cannabis use and thinning of the prefrontal cortex. However, while one meta-analysis found regular cannabis use was associated with smaller volumes in certain brain areas (hippocampus, orbitofrontal cortex), these volumes were not linked to the duration or dosage of cannabis use. Other large studies have reported no effects on brain volumes. A multi-site study of cortical measures found no differences in cortical thickness, surface area, or gyrification index between cannabis users and non-users, or based on dependence or age of onset. Thus, findings on brain structural abnormalities related to cannabis use are not consistent.

Functional MRI studies, however, report more robust effects, particularly after prolonged cannabis use. A meta-analysis of task-based functional MRI studies in current adult and adolescent users revealed abnormal brain activation patterns. Compared to non-using control subjects, adult cannabis users exhibited greater brain activation in certain temporal and frontal gyri but less activation in the striatum, insula, and middle frontal gyrus across various tasks. Adolescent cannabis users also showed greater activation in the inferior parietal gyrus and putamen, suggesting potential compensatory neuroadaptive mechanisms. These functional abnormalities can persist even after cannabis use has ceased and after THC metabolites are no longer detectable.

Several recent studies have examined cannabis effects in populations with pre-existing clinical risk factors and among those using medical marijuana. A meta-analysis focusing on cannabis users with psychosis under 25 years of age found significant differences in premorbid IQ, current IQ, and working memory compared to non-using control subjects with psychosis. In a study of adult patients with chronic pain who received daily herbal cannabis containing 12.5% THC for one year, no significant neurocognitive differences were observed compared to control subjects. Similarly, a study of multiple sclerosis patients using oral dronabinol found no significant differences in MRI measures, including annual brain volume change or new lesion occurrence, after 12 months. These clinical trials suggest no significant adverse neurocognitive effects of THC in these specific clinical populations.

Cerebrovascular Risk and Disease

Cerebrovascular Risk Factors

Similar to the literature linking marijuana use with cardiovascular outcomes, evidence that marijuana consumption increases the prevalence of specific cerebrovascular risk factors and disease is limited. This is due to a dominance of observational studies, cross-sectional studies, case reports, and case series, which are susceptible to potential biases. Postulated adverse effects of marijuana use may include activation of the sympathetic nervous system, changes in blood pressure, platelet activation, and electrophysiological effects. Concurrent tobacco smoking and other substance use may contribute to these effects, which are often short-term and have primarily been studied in younger, low-risk populations. These factors might explain why many longitudinal studies connecting marijuana use with cardiovascular or metabolic risk factors have yielded negative results after adjusting for unhealthy behaviors like diet and tobacco smoking.

Hypertension, a significant risk factor for various types of stroke, warrants particular attention. While the most common acute human reaction to marijuana use is a decrease in blood pressure, resulting from cannabinoid effects on the vasculature and autonomic nervous system, limited studies using the National Health and Nutrition Examination Survey showed a modest association between recent cannabis use and higher systolic blood pressure, as well as a higher prevalence of hypertension among current users aged 30 to 59 years. Heavy users, defined as using marijuana or hashish on more than 20 of the past 30 days, had higher odds of abnormal blood pressure compared to non-users. Although this difference remained statistically significant after adjusting for age, sex, race, ethnicity, body mass index, education, and survey year, it was no longer statistically significant after further adjustment for current tobacco and binge alcohol use. The relationship between marijuana use and elevated blood pressure, especially among heavy users, could potentially drive longer-term associations with cerebrovascular outcomes, though this mechanism requires further study.

Prior cardiovascular diseases, such as myocardial infarction (MI) or atrial fibrillation (AF), are also important risk factors for stroke. Case reports of MI following marijuana use primarily involve young adults without other vascular risk factors, with MI onset shortly after use. The risk of MI was elevated 4.8-fold within an hour after smoking marijuana compared to periods of non-use, indicating marijuana's potential role as an acute trigger for cardiovascular disease. However, in a 25-year follow-up of over 5,000 adult participants in the Coronary Artery Risk Development in Young Adults study, cumulative or recent marijuana use was not associated with coronary heart disease, stroke, or cardiovascular disease mortality. This contrasts with a population-based, multi-institutional database study that observed an increased 3-year cumulative incidence of MI among marijuana users compared to control subjects.

Similarly, marijuana use appears to be a trigger for AF. Data from the Nationwide Inpatient Sample show that the percentage of individuals diagnosed with cannabis use disorder who were discharged with an arrhythmia diagnosis increased by 31% during the post-legalization period (2010–2014). However, in a study of heart failure patients, marijuana users had reduced odds of AF compared to non-users. The concurrent use of cocaine, stimulants, and other drugs may explain observations of AF among marijuana users, although this requires further study beyond observational and cross-sectional reports.

Risk of Stroke and Transient Ischemic Attack

Several case reports and case series, mostly involving young individuals, suggest a link between recent and heavy cannabis use and the risk of stroke. Conversely, findings from case-control studies, population-based studies, and studies using national databases or hospital electronic health records have been inconsistent. This variability depends on the study design, covariates included in the analysis, and the source of the study population. Inconsistent associations can also be attributed to the presence of comparison groups and whether adjustments were made for other important risk factors and lifestyle differences between cannabis users and non-users.

In one case-control study that used cannabis urine screens to identify users, an association was found between cannabis use and the risk of ischemic stroke and transient ischemic attack, but this association was not statistically significant when tobacco use was included as a covariate among subjects aged 18 to 55 with and without stroke. Similarly, another study found no association between cannabis use in young adulthood and the occurrence of fatal and nonfatal stroke later in life among Swedish men, after adjusting for cigarette smoking and alcohol use, over up to 38 years of follow-up.

Data from studies that have more specifically examined the dose or amount of cannabis consumed within a given timeframe suggest that regular cannabis use may increase the risk of stroke. Using data from population-based surveys, researchers have reported that heavy cannabis use in the past year, compared to no use, was associated with an increased risk for nonfatal stroke and transient ischemic attack. Similarly, another study found that recent (within the past 30 days) and frequent (more than 10 days per month) cannabis use was associated with an increased risk for stroke, whereas less frequent cannabis use (10 days or less per month or less than weekly in the past year) was not associated with an increased risk.

Using diagnostic codes for marijuana use, one Nationwide Inpatient Sample study found that cannabis use among men and women hospitalized between 2004 and 2011 was associated with a 17% increased relative risk for acute ischemic stroke in a multivariable-adjusted analysis. Concurrent tobacco use with cannabis increased this risk to 31%. Similarly, a separate study using the Nationwide Inpatient Sample between 2009 and 2010 observed a higher odds of stroke among cannabis users. In contrast, researchers using electronic health record data from patients admitted to a single center between 2015 and 2017 found that testing positive for cannabis use was not associated with the risk of ischemic stroke compared to testing negative, even after adjusting for numerous confounding factors, including age, cigarette smoking, and comorbidities.

Certain populations or scenarios may show a more meaningful link between cannabis use and stroke. A study of a large longitudinal cohort of Canadian pregnant women, with over one million participants followed for 30 years, observed that cannabis use disorder was associated with a doubled risk for hemorrhagic stroke but no increased risk for ischemic or other cerebrovascular disease. Due to the theoretical vasoactive effect of cannabis, its use has been implicated in some cases of reversible cerebral vasoconstriction syndrome (RCVS), with some cases at a Colorado stroke center attributed to marijuana use. Additionally, an elevated risk of stroke from intracranial arterial stenosis has been described among young cannabis users, where vasospasm or RCVS may be a potential mechanism. Experimental models have shown that cannabinoids have complex effects on cardiac contractility, vascular tone, and atherogenesis. Both vasodilation and vasoconstriction responses have been observed, depending on the experimental model and cannabinoid used. CB1 activation promotes inflammation, increases reactive oxygen species, and activates proapoptotic pathways in endothelial cells and cardiomyocytes. It also induces endothelial dysfunction and vascular smooth muscle cell proliferation and migration. These processes have been linked to cardiac dysfunction and the development of atherosclerosis, in contrast to the atheroprotective role associated with CB2.

Acute cardiovascular events and stroke have also been reported in patients using synthetic cannabinoids. "Spice" has been linked to idiopathic thrombocytopenic purpura, increasing the risk of major hemorrhage. Furthermore, intracranial hemorrhage in Spice users has been associated with the presence of brodifacoum, an adulterant considered a "superwarfarin."

Education and Future Directions

The current understanding of how cannabis consumption affects brain health is limited but rapidly evolving. Observational studies have produced conflicting results regarding marijuana's impact on various outcomes, including hypertension, atrial fibrillation, myocardial infarction, and cognition. Several methodological factors may account for these apparent contradictions. Historically, as an illicit drug, marijuana use has often been underreported, which can lead to underestimation of its effects on brain health if users are inadvertently included in control groups of observational studies relying on self-reported data. Additionally, behaviors such as smoking and alcohol use are frequently associated with marijuana consumption and can influence stroke risk and brain connectivity. The common lack of information on the frequency of exposure to these confounding factors limits the accurate determination of marijuana's independent effect.

Furthermore, details such as the time of exposure, frequency of use, and bioavailability of marijuana are often reported inconsistently. Bioavailability is affected by the route of administration, diet, and concurrent use of medications that might influence its metabolism. Moreover, THC and CBD possess distinct pharmacological effects; while THC use has been linked to detrimental outcomes, CBD appears to offer therapeutic potential in certain neurological disorders. The absolute and relative concentrations of these compounds vary significantly based on the cannabis strain and the extraction methods used for active ingredients. The gradual increase in the potency of recreationally used marijuana also limits the relevance of older studies. Ethical considerations and the psychotropic effects of THC, which make blinding difficult, impede the development of long-term placebo-controlled studies.

Emerging evidence links marijuana use to cardiovascular events and stroke, along with demonstrated drug-to-drug interactions with medications commonly used by the general population. This calls for caution and emphasizes the importance of active surveillance programs. The high density of cannabinoid receptors in brain regions involved in executive function and memory, the dose-dependent harmful effects of THC on working and episodic memory, and the role of cannabinoid-associated biochemical pathways in synaptic plasticity and neuronal development all raise concerns that long-term marijuana exposure may negatively affect brain health. There is no consensus on whether the effects of marijuana fully resolve after months of abstinence. However, disruption of endocannabinoid signaling pathways during the prenatal, perinatal, and adolescent periods can be particularly detrimental to neurodevelopment. Key points are often summarized in scientific statements. As the field develops, several important areas require further research, including comparing the differential effects of recreational, illicit, and medicinal uses of marijuana, as well as the specific types of cannabis products consumed. Similarly, the modulating effects of social determinants of health and race and ethnicity on the interaction between brain health and marijuana use are largely unexplored. This latter area of research may be especially important given that communities of color in the United States may be disproportionately affected by natural and synthetic cannabinoids concerning both use and exposure, and the legal implications of marijuana's criminalization.

Public health initiatives should aim to increase awareness about the potential negative effects associated with marijuana use in the general population. Potential strategies include the use of standardized concentrations of biologically active components and health warning labels on available formulations. Additionally, marijuana use should be individualized and closely monitored. Healthcare professionals and patients should receive unbiased education about the potential consequences of medicinal, recreational, and illicit marijuana use on brain health, particularly when exposure occurs during vulnerable life stages. It may also be important for professionals to monitor the cognitive performance of marijuana users and review their medications to identify potential drug-to-drug interactions. Knowledgeable healthcare professionals can properly educate current or potential marijuana users about its possible adverse effects, enabling them to make informed decisions based on unbiased data.

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Marijuana, or cannabis, was long considered an illegal substance. However, many regions worldwide have now legalized or decriminalized its use for medical or recreational purposes, leading to a significant increase in its consumption. For instance, global marijuana use was estimated at 183 million people in 2014, with 22 million experiencing cannabis use disorder by 2016. In the United States, annual marijuana use among individuals over 12 years old rose from 11% in 2002 to 18% in 2019, with notable popularity among adolescents and young adults. Concurrently, the potency of the main psychoactive compound, THC, increased from roughly 4% in 1995 to 15% in 2018.

Cannabinoid receptors are highly concentrated in brain areas crucial for executive function and memory, especially during brain development. Acute cannabis use can impair memory and behavioral control, and it may influence anxiety and cause psychosis-like effects. Early life exposure, such as during prenatal, perinatal, and adolescent periods, appears especially sensitive to these compounds. Research also indicates that cannabis can affect brain processes like inflammation and neuron development, and it may interfere with common medications, posing a risk for older adults. These factors raise concerns about cannabis's impact on brain health, which is the focus of this scientific statement.

Cannabis and Endocannabinoids

The body naturally produces substances called endocannabinoids, like anandamide and 2-arachidonoyl-glycerol, which activate cannabinoid receptors (CB1 and CB2). These endocannabinoids are made on demand and, along with their receptors and enzymes, form the endocannabinoid system (ECS). This system plays a crucial role in various bodily functions.

Phytocannabinoids are compounds found in cannabis plants such as Cannabis sativa. Over 100 types exist, with Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most common. THC is the psychoactive component, acting primarily through CB1 receptors located in the brain and peripheral nervous system, where it influences the release of neurotransmitters. CBD, on the other hand, is non-psychoactive and is known for its antioxidant and anti-inflammatory effects. Research suggests CBD may offer benefits in conditions like Dravet syndrome, Lennox-Gastaut syndrome, Alzheimer's disease, and multiple sclerosis, acting through different pathways than THC. Some cannabinoids are also approved medications for specific health issues.

Neurobiological Actions of Cannabis in Animal Models

Animal models are vital for understanding how cannabis affects the developing brain, allowing researchers to control variables and study neurodevelopmental stages relevant to humans. These studies suggest that the endocannabinoid system (ECS) influences synaptic plasticity, which is the brain's ability to adapt and change connections. THC interferes with the natural function of endocannabinoids by activating cannabinoid receptors in the brain, disrupting this fine-tuning and potentially impairing how neuronal networks function.

Specifically, THC's impact on memory and learning may stem from its effects on neurotransmitter release, such as glutamate, acetylcholine, and serotonin. It can also reduce the brain's energy supply, further contributing to cognitive issues. Repeated exposure to cannabis, especially during adolescence, is particularly concerning. This period of rapid brain development can lead to long-lasting changes in brain circuits, including the prefrontal cortex and hippocampus. Such exposure can result in excessive loss of synaptic connections, imbalances in brain signaling, and altered neuronal networks, which are thought to contribute to long-term cognitive and emotional problems. These severe effects are more pronounced with adolescent exposure compared to adult exposure and can even involve changes to gene expression.

Furthermore, studies show that long-term THC use activates brain immune cells (microglia and astrocytes), causing inflammation that can impair memory. The dosage of cannabis also plays a role, with even lower doses potentially having harmful effects if administered earlier in adolescence.

Effect of Prenatal Exposure to Cannabinoid Agonists

Studies have investigated the impact of prenatal cannabis exposure (PCE) on development. One large study of nearly 11,500 children found that maternal cannabis use during pregnancy was linked to poorer neurocognitive function and smaller total brain volumes in children aged 9-10, even after accounting for other factors. Preclinical animal studies further explore the underlying mechanisms of these observations.

Research in animal models indicates that PCE can negatively affect cognitive processing and emotional regulation in offspring. These effects are attributed to changes in critical brain regions like the prefrontal cortex, amygdala, and hippocampus, specifically altering how neurons communicate and adapt. Disruptions in the balance of excitatory and inhibitory signals, as well as abnormal glutamate function, are common findings. These issues often arise from the interference of cannabis compounds with the endocannabinoid system's crucial role in brain development, including neuron growth and migration.

Additionally, PCE can lead to issues with brain interneurons, sometimes more noticeably in female animals. It can also delay a critical developmental shift in the brain's GABA signaling, potentially impacting cognitive and emotional behavior later in life. PCE has also been observed to disrupt brain pathways involved in reward and stress response, suggesting a long-term susceptibility to stress-related psychiatric conditions. Understanding these interferences is essential for developing interventions.

Effects of Marijuana Use on Human Cognition

Acute cannabis intoxication can impair working and episodic memory, reduce behavioral inhibition, and increase impulsivity, affecting daily activities. For example, a 2016 meta-analysis found a 36% increased risk of motor vehicle accidents among cannabis users. A 2020 study on driving performance showed that THC-dominant cannabis significantly increased lane weaving, while CBD-dominant cannabis had effects similar to a placebo, highlighting the different short-term impacts of these compounds. These immediate effects are generally temporary and can be influenced by tolerance or other drug use.

The long-term cognitive effects of cannabis are less clear. Recent meta-analyses indicate some lasting neurocognitive effects. One analysis of adults using cannabis almost daily for over two years found slightly worse overall cognitive performance compared to non-users, particularly in areas like decision-making, verbal learning, and executive function. Another meta-analysis of younger users (under 26) showed a similar overall cognitive difference. However, neither study found that the age at which cannabis use began influenced these cognitive associations.

Longitudinal studies offer a stronger view of causality. The CARDIA study, tracking young adults for 25 years, linked cumulative marijuana exposure to poorer verbal memory. Co-twin studies, which help control for genetic and environmental factors, have yielded mixed results. Some found vocabulary and general knowledge declines associated with cannabis use but no differences in IQ between twins with differing cannabis use, suggesting shared underlying factors might be at play. Other studies indicated that lower IQ often predated cannabis use, rather than being caused by it.

Brain imaging studies using MRI have shown inconsistent findings regarding structural changes. Some studies reported dose-dependent thinning of the prefrontal cortex in adolescents, and a meta-analysis found smaller volumes in some brain regions. However, many large studies found no significant differences in brain volumes or cortical measures between cannabis users and non-users. In contrast, functional MRI (fMRI) studies consistently show altered brain activation patterns in both adult and adolescent cannabis users, suggesting the brain may adapt in response to chronic use. These functional changes can persist even after individuals stop using cannabis.

Cerebrovascular Risk and Disease

The link between marijuana use and cerebrovascular risks, such as stroke, is still being clarified, often limited by the nature of available observational studies. Potential adverse effects of marijuana may involve changes in the nervous system, blood pressure, and blood clotting, although these are often short-term and can be influenced by co-occurring behaviors like tobacco and alcohol use.

Regarding specific risk factors, while marijuana's immediate effect often lowers blood pressure, some studies show a modest association between recent cannabis use and higher blood pressure, particularly among heavy users. However, this link often becomes statistically insignificant when accounting for tobacco and alcohol use. Similarly, for other cardiovascular diseases, some case reports suggest an increased risk of heart attack shortly after marijuana use, especially in young adults without other risk factors. Yet, large longitudinal studies have not always found a long-term association between cumulative marijuana use and heart disease, stroke, or cardiovascular mortality, contrasting with some database studies that report an increased risk of heart attacks. Marijuana use has also been implicated as a trigger for irregular heart rhythms, though the role of other substance use needs further investigation.

Evidence for a direct link between cannabis use and stroke or transient ischemic attack (TIA) is mixed. While some case reports suggest a connection, especially with recent and heavy use in young individuals, larger studies relying on population data or hospital records have produced inconsistent results. These variations often depend on study design, how other risk factors are controlled for, and the specific populations examined. Some studies indicate that regular or frequent cannabis use might increase the risk of nonfatal stroke or TIA, with some finding a 17% to 24% increased risk for acute ischemic stroke, which rises further with concomitant tobacco use. However, other single-center studies found no such association. In specific contexts, such as pregnant women with cannabis use disorder, a doubled risk for hemorrhagic stroke has been observed. Additionally, cannabis use has been linked to conditions like reversible cerebral vasoconstriction syndrome and intracranial arterial stenosis, possibly through its effects on blood vessel constriction. Experimental models suggest that THC can promote inflammation and other processes that might contribute to heart dysfunction and atherosclerosis, while CBD may offer some protective effects.

Education and Future Directions

Current understanding of cannabis's impact on brain health is still developing, and observational studies often show conflicting results regarding its effects on conditions like hypertension, heart issues, and cognition. These inconsistencies can be attributed to several factors: cannabis use has historically been underreported due to its illegal status, and its effects are often intertwined with other behaviors like tobacco and alcohol use, which are not always fully accounted for. Furthermore, variations in dosage, frequency of use, and the differing effects of THC and CBD, whose potencies have changed over time, make comparisons difficult. Ethical considerations also limit comprehensive long-term placebo-controlled studies.

Despite common perceptions, emerging evidence connects marijuana use to cardiovascular events and stroke, as well as potential interactions with medications, emphasizing the need for caution. The concentration of cannabinoid receptors in brain areas vital for memory and executive function, along with THC's dose-dependent impact on these functions and the role of cannabinoids in brain development, raise significant concerns about long-term brain health. The disruption of the body's endocannabinoid system during critical developmental stages, such as prenatal, perinatal, and adolescence, appears particularly detrimental.

Further research is needed to differentiate the effects of recreational, illicit, and medicinal cannabis, and to understand how different product types impact health. The influence of social factors, race, and ethnicity on brain health in relation to marijuana use also remains largely unexplored, which is crucial given the disproportionate impact of cannabis criminalization on certain communities.

Public health initiatives should focus on raising awareness about the potential negative effects of marijuana. This could involve standardizing active components and adding health warning labels to products. Cannabis use should be personalized and closely monitored. Healthcare professionals and patients require accurate, unbiased information on the potential consequences of all forms of marijuana use, especially when exposure occurs during vulnerable life stages. Professionals should also monitor cognitive function in users and check for potential drug interactions to help individuals make informed decisions.

Article Information

This document is a scientific statement published online, affirmed by the American Academy of Neurology and approved by the American Heart Association's Science Advisory and Coordinating Committee and Executive Committee. It reflects efforts to avoid conflicts of interest among its authors.

Marijuana, also known as cannabis, was considered an illegal drug for many years. However, attitudes have changed, and in many parts of the world, cannabis is now legal for medical use or has been decriminalized for both recreational and medicinal purposes. This shift has led to a quick rise in its use. It is estimated that about 183 million people globally used marijuana in 2014, and 22 million were diagnosed with cannabis use disorder in 2016. In the United States, the number of people over 12 years old who used marijuana in the past year steadily increased from 11% in 2002 to 18% in 2019. Marijuana use has become more common, especially among teenagers and young adults, with about 36% of 12th graders and 43% of college students reporting use in the past year. At the same time, the strength of cannabis products in the U.S., measured by the amount of THC (the main active chemical), has increased from about 4% in 1995 to 15% in 2018.

Cannabinoid receptors are highly concentrated in brain areas that handle thinking skills and memory, such as the hippocampus, amygdala, and prefrontal cortex, especially when the brain is still developing. Being acutely under the influence of cannabinoids can harm memory and control over one's behavior. Cannabinoids also affect anxiety and can cause effects similar to psychosis. Research suggests that the age when someone first uses cannabinoids might change how they affect brain function. For example, periods before birth, around birth, and during adolescence might be especially sensitive to these compounds. Studies in animal models show that cannabis and its related pathways affect how brain signals are sent and play a role in key brain processes like inflammation, new brain cell growth, nerve cell migration, and the development of white matter. Also, research indicates that cannabinoids can affect how certain enzymes work, which means there is a potential risk for interactions with medicines commonly used by older adults, such as blood thinners, heart rhythm medications, sedatives, and seizure medications.

These factors have raised worries about how cannabis might affect brain health. The purpose of this scientific statement is to carefully evaluate the safety of cannabis use in terms of brain health.

Cannabis and Endocannabinoids

Anandamide and 2-arachidonoyl-glycerol are natural fats in the body that activate two types of cannabinoid receptors, called CB1 and CB2. These fats, known as endocannabinoids, are not stored but are made when needed. The system involving CB1 and CB2 receptors, these natural compounds, and the enzymes that make and break them down is called the endocannabinoid system (ECS). A detailed explanation of the ECS is outside the scope of this document, but it has been widely reviewed elsewhere.

Phytocannabinoids are cannabinoids taken from flowering cannabis plants, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis. It is debated whether these are separate species or sub-species. More than 100 phytocannabinoids have been found in these plants, with THC and cannabidiol (CBD) being the most common. The amounts of THC and CBD in different cannabis types vary. Generally, cannabis plants can be grouped by the main cannabinoid they produce: chemotype I (high THC), II (balanced THC/CBD), III (high CBD), IV (high cannabigerol), or V (no cannabinoids).

THC is a chemical that affects the mind and works by signaling through CB1 and CB2 receptors. CB1 receptors are found in large numbers in nerve cells throughout the body and brain. In the body, CB1 is found in nerve endings for sympathetic and sensory nerves. In the brain, it is mainly found on the connections (presynaptic membranes) of nerve cells that either excite or calm other nerve cells. Here, it helps control the release of important brain chemicals like dopamine, GABA, and glutamate. In contrast, CB2 receptors are mostly found in immune cells, including microglia (brain immune cells).

CBD is a cannabinoid that does not affect the mind and has properties that can reduce inflammation and act as an antioxidant. It is believed that CBD provides some of the benefits seen with phytocannabinoids in certain seizure disorders like Dravet syndrome and Lennox-Gastaut syndrome. Additionally, animal studies suggest that CBD may be helpful in conditions such as Alzheimer's disease, stroke, multiple sclerosis, and other neurological problems. The possible medical uses of CBD are currently being studied in clinical trials. Unlike THC, CBD works through different pathways and does not activate CB1 and CB2 receptors. At low amounts, CBD blocks certain receptors and transporters. At higher amounts, it activates other specific receptors.

Several cannabinoids have been approved in various countries for treating certain medical conditions. Also, very strong artificial cannabinoids, like Spice, are available illegally.

Neurobiological Actions of Cannabis in Animal Models

Our understanding of how cannabis affects the developing brain at a molecular and cellular level mainly comes from animal studies. These studies allow scientists to control social and environmental factors that might affect the results. Animal models also help investigate human age-related behaviors (like seeking new experiences, impulsivity, and taking risks) and important stages of brain development that are similar across many mammal species. However, many individual differences (such as species, age) and experimental factors (like study design, drug dose, and how it's given) have led to mixed findings in different studies. Still, experimental animal models of cannabis exposure before birth and during adolescence have been crucial in revealing the brain mechanisms that may explain various mental health outcomes seen in humans.

Animal models have been used to study how the ECS helps change and adapt the brain (a process called synaptic plasticity). The ECS adjusts synaptic plasticity by influencing the strength of connections between nerve cells, which then affects how nerve networks function. From a scientific viewpoint, THC activates cannabinoid receptors in the brain, which interferes with the normal actions of endocannabinoids. The precise timing and location of endocannabinoid production are essential for the brain to properly handle functions like higher-level thinking, memory, reward, mood, and stress response. Therefore, when THC activates CB1 receptors in the brain broadly, it disrupts the careful control of nerve cell activity that endocannabinoids usually provide. This can lead to problems with how nerve networks connect and how the brain functions.

Although not fully understood, THC may disrupt memory and learning because it affects how neurotransmitters are released and how they bind to CB1 receptors. For example, THC activates CB1 receptors on certain nerve cells and support cells (astrocytes), leading to the release of glutamate in the hippocampus (a memory area). At the same time, THC affects other neurotransmitters involved in memory, such as acetylcholine, adenosine, and serotonin. Furthermore, when THC activates CB1 receptors found on mitochondria (the energy powerhouses of cells), it reduces cellular breathing and energy supply. This reduction in energy is crucial for maintaining and regulating nerve signal transmission and may contribute to the memory problems caused by THC.

Repeated exposure to cannabis, especially during adolescence when the brain is developing, can be particularly harmful to brain health. It may cause changes in the structure, molecules, and function of brain circuits, especially in the prefrontal cortex and hippocampus. Long-term THC use causes CB1 receptors to become less sensitive and fewer in number, and these effects appear stronger and more widespread after exposure during adolescence compared to adulthood. Data from animal models show that these effects could impact brain development processes where the ECS plays a role. Consequently, long-term THC exposure during adolescence may disrupt the natural changes happening in nerve chemical systems, leading to excessive "synaptic pruning" (loss of nerve connections), long-term problems with brain balance, and disrupted communication in certain brain networks. These changes may explain the thinking problems, altered emotional reactions, and social behavior issues seen long after adolescent THC exposure. Long-term changes in brain function caused by THC exposure during adolescence might also come from epigenetic changes, which involve significant reprogramming of genes related to synaptic plasticity. These specific effects have not been reported after THC exposure in adults.

In addition to affecting nerve cell parts, recent evidence suggests that changes in glial cells (brain support cells) play a key role in THC's actions. Long-term THC exposure activates microglia and astrocytes (types of glial cells) to produce inflammatory chemicals. For example, long-term THC use during adolescence increased the expression of inflammation-causing substances by microglia and reduced an anti-inflammatory chemical in the prefrontal cortex. This resulting brain inflammation was linked to memory problems in adulthood.

The amount of cannabis used is another important factor. Most studies describe harmful effects of THC in models of heavy cannabis use in mid-adolescence. However, even lower doses may cause these same effects if given earlier in adolescence.

Effect of Prenatal Exposure to Cannabinoid Agonists

A recent study examined connections between cannabis exposure before birth (PCE) and various measures of mental and brain health in nearly 11,500 young people. Mothers who reported using cannabis during pregnancy had children who, at ages 9-10, performed worse on brain function tests and had smaller overall brain volumes, even when other influencing factors were considered. Several reviews describe the long-term effects of PCE in animal models. This document focuses on insights from animal studies that mirror the mental health issues seen in clinical outcomes.

The harmful effect of PCE on a child's thinking and emotional control has been linked to changes in the properties and adaptability of nerve cells and connections in areas of the brain such as the prefrontal cortex, amygdala, hippocampus, and ventral tegmentum. Changes have been observed in the balance of exciting and calming signals, as well as how main nerve cells receive, combine, and send information in these brain regions. Problems with the function of glutamate, a key brain chemical, are a common sign, shown by changes in its receptors and how its levels are controlled. These changes largely depend on how natural cannabinoid signaling pathways are altered by external cannabinoids during development and throughout life (e.g., nerve cell growth, survival, and direction of nerve connections).

Defects in the ECS function may also explain the problems observed in certain nerve cells (interneurons) in many brain regions of offspring exposed to cannabis before birth, a phenomenon often more pronounced in female than in male animals. In the prefrontal cortex, this ongoing problem with calming signals is also linked to a delayed switch in GABA's role from exciting nerve cells early in development to its typical calming function later in life. This is especially important because this GABA switch is a critical step in brain development. Any changes to the normal and expected timing of these periods, such as delays or accelerations caused by PCE, may lead to problems with the child's thinking and emotional behavior.

Marijuana use has been observed to cause imbalances in brain chemical pathways and stress response systems. PCE hinders the full development of monoamines (a type of brain chemical), which also have growth-promoting effects on nerve cells. This phenomenon may depend on changes at the gene level and might be involved in abnormal reward signaling. Furthermore, PCE is linked to a pattern in offspring that shows long-lasting problems with how they respond to stress, which is not fully explained by hormone levels. A susceptibility to acute and chronic stress is connected to many mental health conditions, from depression and psychosis to substance use disorders and anxiety. A deeper understanding of how PCE interferes with endocannabinoid signaling during brain development would allow researchers to explore possible ways to intervene and restore the normal progression of developmental milestones.

Effects of Marijuana Use on Human Cognition

Acute intoxication from marijuana is linked to problems with working memory and episodic memory, as well as impulsive behavior, which can affect performance in everyday activities. For example, a 2016 review of studies found that cannabis users were 36% more likely to be involved in a car accident compared to non-users. Additionally, a 2020 study using driving tests showed that after inhaling cannabis with a lot of THC, drivers had more trouble staying in their lane. It is important to note that when cannabis with mostly CBD was inhaled, driving performance was similar to that of the placebo group. These observations highlight the different short-term effects of THC and CBD on thinking. Evidence also suggests that the short-term effects of cannabinoids are temporary and can be influenced by developing a tolerance or using other drugs.

The long-term effects of cannabis on thinking, however, are less clear. Recent reviews of studies report that some lingering effects of cannabis use on brain function exist, which aligns with earlier research. A 2020 review focusing on adults who used cannabis nearly every day for more than two years found that their overall brain function was about one-quarter of a standard deviation worse than non-users. Four out of seven areas tested (decision-making, verbal learning, memory recall, and executive function) showed significant differences. Another review of cannabis users under 26 years old also found a similar difference in overall brain function, but with different specific areas affected. Neither of these reviews found that the age at which cannabis use began affected the link between exposure and thinking performance.

Unlike these reviews, large long-term studies provide stronger insights by looking at changes over time. In the CARDIA study, which followed over 3,300 participants for 25 years, more years of marijuana exposure were linked to worse verbal memory. Additionally, studies on twins, which help control for shared genetic and environmental factors, have shown mixed results. Some twin studies found that declines in vocabulary and general knowledge were linked to being a cannabis user, but not to the amount used, and that differences were likely due to shared risk factors. Other twin studies reported that lower IQ scores happened before cannabis use, with no actual IQ decline among cannabis users.

Brain imaging techniques (MRI) show varied links between cannabis use and brain structure and function. In terms of brain structure, findings related to cannabis use have been inconsistent. One long-term study with adolescents found that more cannabis use was linked to thinning of the prefrontal cortex. However, a review of studies found that while regular cannabis use was linked to smaller volumes in certain brain areas, brain volumes were not linked to the length or amount of cannabis use. Other large studies have found no link. For example, two large twin studies found no connection between cannabis use and the size of several brain structures. Similarly, a study across multiple sites found no differences in brain thickness, surface area, or folding patterns between cannabis users and non-users, or based on when cannabis use began. Therefore, structural brain abnormalities linked to cannabis use are not consistently reported.

Functional MRI studies, which look at brain activity, report more consistent effects, especially after long-term cannabis use. A review of functional MRI studies in current adult and adolescent users found abnormal brain activity in both age groups. Compared to non-users, adult cannabis users showed more activation in certain brain areas and less activation in others, suggesting the brain might be trying to compensate. Adolescent cannabis users also showed increased activation in certain areas, which might indicate the brain is adapting. These functional brain abnormalities continue even after cannabis use stops and after THC is no longer detectable. Another review focusing on abstinent adolescent cannabis users found increased activation in areas important for executive function and self-control.

Several recent studies have looked at the effects of cannabis in people with existing health risks or those using medical marijuana. One review of cannabis users with psychosis found significant differences in pre-illness IQ, current IQ, and working memory. However, in a study of over 200 chronic pain patients given daily herbal cannabis with THC for one year, no significant differences in brain function were found compared to a control group. This aligns with a study of multiple sclerosis patients using an oral cannabinoid medication, which found no significant differences in brain MRI measures after 12 months of use. These clinical trials suggest that THC may not have significant negative effects on brain function in specific patient groups.

Cerebrovascular Risk and Disease

Understanding the link between marijuana use and specific risk factors for brain blood vessel diseases (cerebrovascular disease) is limited. Most of the evidence comes from observational studies, single case reports, and small case series, which can be prone to bias. Potential negative effects of marijuana use may include increased activity in the nervous system, changes in blood pressure, increased platelet activity, and effects on the heart's electrical signals. Using tobacco and other substances at the same time likely adds to these effects, which might be temporary and have mostly been studied in younger, low-risk groups. These factors might explain why many long-term studies linking marijuana use to heart and metabolic risk factors have found no clear connection after adjusting for unhealthy habits like diet and tobacco smoking.

High blood pressure, in particular, is a major risk factor for different types of stroke. While marijuana use commonly causes a temporary drop in blood pressure due to its effects on blood vessels and the nervous system, some limited studies have shown a small link between recent cannabis use and higher systolic blood pressure and more common high blood pressure in current users aged 30 to 59. Heavy users (more than 20 days of use in the past month) had a higher chance of abnormal blood pressure compared to those who never used. Although this difference remained statistically significant after adjusting for age, sex, and other factors, it became less significant when also adjusting for current tobacco and heavy alcohol use. The relationship between marijuana use and elevated blood pressure, especially among heavy users, might lead to long-term brain blood vessel problems, but this needs more study.

Previous heart diseases, like heart attacks or irregular heartbeats (atrial fibrillation), are also significant risk factors for stroke. Case reports of heart attacks after marijuana use are mainly among young adults without other heart risk factors, with the heart attack occurring soon after use. The risk of a heart attack was nearly five times higher within an hour of smoking marijuana compared to periods of non-use, suggesting marijuana can be an immediate trigger for heart problems. However, in a 25-year study of over 5,000 adults, cumulative or recent marijuana use was not linked to coronary heart disease, stroke, or death from heart disease. This contrasts with a study using a large patient database, which observed an increased risk of heart attack over three years among marijuana users compared to control subjects.

Similarly, marijuana use appears to be a trigger for atrial fibrillation. Data from a national hospital database showed that the percentage of people with cannabis use disorder who were hospitalized with an arrhythmia diagnosis increased by 31% after legalization (2010–2014). However, in a study of heart failure patients, marijuana users had a reduced chance of atrial fibrillation compared to non-users. Simultaneous use of cocaine, stimulants, and other drugs may explain some observations of atrial fibrillation among marijuana users, though this needs more study beyond observational reports.

Several case reports and small studies, mostly in young people, suggest a link between recent and heavy cannabis use and the risk of stroke. In contrast, findings from other types of studies, such as those comparing cases to controls, population-based studies, and studies using national patient databases or hospital records, have been inconsistent. This inconsistency depends on the study design, other factors considered in the analysis, and the population being studied. Mixed associations can also be due to whether comparison groups were used, if other important risk factors were adjusted for, and if other risk and lifestyle factors between cannabis users and non-users were taken into account.

Studies that have looked more closely at the dose or amount of cannabis consumed within a certain time frame suggest that regular cannabis use may increase the risk of stroke. Data from population surveys have shown that heavy cannabis use in the past year was linked to an increased risk for non-fatal stroke and transient ischemic attack, compared to no cannabis use. Similarly, another study found that recent (within 30 days) and frequent (more than 10 days per month) cannabis use was linked to an increased risk for stroke, while less frequent use was not.

Using patient codes for marijuana use, one national hospital database study found that cannabis use among men and women hospitalized between 2004 and 2011 was linked to a 17% increased risk for acute ischemic stroke after adjusting for other factors. Using tobacco with cannabis further increased this risk to 31%. Another study using a national hospital database observed a higher chance of stroke among cannabis users. In contrast, researchers using electronic health records from a single hospital found that a positive cannabis test was not linked to the risk of ischemic stroke, even after adjusting for many other factors like age, smoking, and other health conditions.

There may be specific groups or situations where cannabis use can be clearly linked to stroke. A study of over a million Canadian pregnant women found that cannabis use disorder was linked to a doubling of risk for hemorrhagic stroke but no increased risk for ischemic or other cerebrovascular diseases. Because cannabis can affect blood vessels, its use has been implicated in some cases of reversible cerebral vasoconstriction syndrome, where blood vessels in the brain temporarily narrow. Additionally, an increased risk of stroke from narrowing of brain arteries has been described among young cannabis users, where temporary blood vessel spasms might be a cause. Animal studies have shown that cannabinoids have complex effects on heart muscle contraction, blood vessel tension, and the development of hardened arteries. Both widening and narrowing of blood vessels have been observed depending on the study and cannabinoid used. Activation of CB1 receptors promotes inflammation, increases harmful chemicals, and activates cell death pathways in blood vessel lining cells and heart muscle cells. It also causes blood vessel problems and the growth and movement of smooth muscle cells in blood vessels. These processes have been linked to heart problems and the development of hardened arteries. This is different from CB2, which is associated with protecting against hardened arteries.

Acute heart events and stroke have also been reported in patients using synthetic cannabinoids. These substances are linked to a blood disorder that increases the risk of major bleeding. Additionally, brain bleeding in users of synthetic cannabis has been linked to the presence of brodifacoum, a strong type of blood thinner used as a rodenticide.

Education and Future Directions

Our understanding of how cannabis use affects brain health is still limited but is quickly growing. Studies have produced conflicting results regarding the effects of marijuana on various outcomes, including high blood pressure, atrial fibrillation, heart attack, and thinking abilities. Several issues with research methods may explain these contradictions. First, because marijuana was historically an illegal drug, its use has been underreported for generations. Including marijuana users in the control group of studies that rely on self-reported use could make the negative effects on brain health seem smaller than they are. Second, behaviors like smoking and alcohol use are often linked with marijuana use and can influence stroke risk and brain connectivity. Often, information on how frequently people are exposed to these other factors is missing, which makes it hard to accurately determine the independent effect of marijuana. Third, details like how long someone has used marijuana, how often they use it, and how much of the active ingredients the body absorbs (which depends on how it is used, diet, and other medications) are reported inconsistently. Fourth, THC and CBD have different effects on the body. While THC has been linked to harmful effects, CBD appears to have potential medical benefits in some neurological conditions. The exact amounts and ratios of these compounds vary depending on the cannabis plant strain and how the active ingredients are extracted. Fifth, the increasing strength of recreationally used marijuana makes older studies less relevant. Sixth, different factors prevent long-term studies where some people get a placebo, including ethical reasons and the mind-altering effects of THC, which cannot be hidden from participants.

Social media may highlight only the positive aspects of marijuana, leading the general public to see it as a harmless drug. However, growing evidence links marijuana use to heart events and stroke, and there are known potential drug interactions between marijuana and common medications. This calls for caution and emphasizes the importance of active monitoring programs. Additionally, the high concentration of cannabinoid receptors in brain areas involved in thinking and memory, the dose-dependent harmful effect of THC on working and episodic memory, and the role of cannabinoid-related pathways in nerve cell development raise concerns that long-term marijuana exposure may affect brain health. There is no clear agreement on whether the effects of marijuana fully go away after months of not using it. However, disruptions to the natural cannabinoid signaling pathways during periods before birth, around birth, and in adolescence may be harmful to brain development. The main goal of this scientific statement was to discuss how marijuana use might affect brain health. However, as this field of study develops, several important areas need more research. For example, there is limited information comparing the different effects of recreational, illegal, and medicinal uses of marijuana, as well as the types of cannabis products consumed. Similarly, how social factors, race, and ethnicity affect the relationship between brain health and marijuana use is largely unexplored. This last area of research may be especially important because certain communities in the United States may be more affected by natural and synthetic cannabinoids in terms of use and exposure, as well as the legal consequences of marijuana being a criminalized substance.

Public health efforts should aim to raise awareness about the potential negative effects linked to marijuana use in the general population. Possible strategies include requiring standard concentrations of active ingredients and health warning labels on available products. Additionally, marijuana use should be tailored to individuals and closely monitored. Healthcare professionals and patients should receive fair, unbiased information about the possible consequences of medicinal, recreational, and illegal marijuana use on brain health, especially when exposure happens during sensitive developmental periods. It may also be important for professionals to monitor the thinking abilities of marijuana users and to check their medications for possible drug interactions. Knowledgeable healthcare professionals will be able to properly educate potential or active marijuana users about its possible harmful effects, enabling them to make informed decisions based on accurate data.

Here is the rewritten content at a 5th-grade reading level for adult audiences:

Marijuana, also called cannabis, was seen as an illegal drug for many years. Now, in many parts of the world, cannabis is allowed for medical use or has less strict laws for general use. Because of this change, more people are using it. About 183 million people worldwide used marijuana in 2014, and 22 million had a cannabis use problem in 2016.

In the United States, the number of people over 12 years old who used marijuana in the past year slowly went up from 11% in 2002 to 18% in 2019. It has become very popular, especially among teens and young adults. For example, about 36% of 12th graders and 43% of college students said they used it in the past year. Also, the strength of cannabis products in the U.S. has grown stronger over time. The main active chemical, THC, went from about 4% in 1995 to 15% in 2018.

Special spots in the brain called cannabinoid receptors are found in areas that handle thinking and memory. These areas include the hippocampus and the prefrontal cortex, which are very active when the brain is still growing. Using cannabis can quickly make memory and self-control worse. It can also affect worry and sometimes cause mind-altering effects. Research shows that a person's age when first exposed to cannabis can change how it affects their thinking. Times before and just after birth, and during the teenage years, may be especially sensitive.

Studies on animals show that cannabis affects how brain cells talk to each other. It plays a role in brain processes like swelling in the brain, making new brain cells, and how brain connections are formed. Research also shows that cannabis can affect how the body breaks down other medicines. This means there is a chance it could cause problems with common medicines used by older adults, such as blood thinners or seizure medicines.

These points lead to worries about how cannabis might affect brain health over time. This report aims to carefully look at how safe cannabis use is for the brain.

Cannabis and Natural Body Chemicals

The body makes its own natural chemicals called endocannabinoids, like anandamide and 2-arachidonoyl-glycerol. These chemicals work with two special spots in the body, called cannabinoid receptor type 1 (CB1) and 2 (CB2). These natural chemicals are made when needed and are not stored. This system of receptors, natural chemicals, and the body's ways of making and breaking them down is known as the endocannabinoid system (ECS).

Plant-based cannabinoids come from cannabis plants like Cannabis sativa. There are more than 100 plant-based cannabinoids. The most common ones are THC and CBD. The amount of THC and CBD in different types of cannabis plants can change. Generally, cannabis plants are sorted by the main cannabinoid they make, such as those rich in THC, those balanced with THC and CBD, or those rich in CBD.

THC is a chemical that affects the mind and works with CB1 and CB2 receptors. The CB1 receptor is found in many nerve cells both in the body and brain. In the body, it is in nerve endings and sensing nerves. In the brain, it is mainly in spots where brain cells send messages, helping to control chemicals like dopamine and glutamate. The CB2 receptor is mostly found in immune cells, including some brain cells called microglia.

CBD is a cannabinoid that does not affect the mind. It has properties that help fight damage and swelling in the body. It is believed that CBD helps with certain medical problems like severe epilepsy. Also, studies in animals suggest that CBD could help with conditions such as Alzheimer's disease and multiple sclerosis. Doctors are still studying how CBD might help in different health trials. Unlike THC, CBD works through different paths in the body and does not activate CB1 and CB2 receptors.

Some cannabinoids are approved in different countries to treat certain health issues. Also, very strong man-made versions of cannabis, like Spice, can be found illegally.

How Cannabis Affects Animal Brains

Scientists use animal studies to learn how cannabis affects the growing brain. These studies help understand how the brain changes and adapts to new information, known as synaptic plasticity. The ECS helps control this brain plasticity by changing how strong connections between brain cells are. THC acts on cannabinoid receptors in the brain, getting in the way of how the body's natural endocannabinoids work. The careful timing of when endocannabinoids are made is key for many brain functions like thinking, memory, mood, and dealing with stress. So, when THC turns on these CB1 receptors too much, it can mess up this careful balance, harming how brain cells connect and how the brain works.

Scientists are still learning how THC harms memory and learning. It might change how brain chemicals are released and how they connect to CB1 receptors. For example, THC turns on CB1 receptors on certain brain cells, which can cause the release of a chemical called glutamate in the hippocampus, a part of the brain important for memory. THC also affects other brain chemicals important for memory, like acetylcholine and serotonin. Furthermore, when THC activates CB1 receptors on parts of brain cells that make energy, it can lower the energy supply, which may also lead to problems with thinking.

Repeated cannabis use, especially during the teenage years, can harm brain health. It can cause changes in the structure, chemistry, and function of brain parts, especially those for thinking and memory. Studies also suggest that THC affects glial cells, which are important helper cells in the brain, leading to swelling in the brain. This brain swelling was linked to memory problems later in adulthood in animal studies.

The amount of cannabis used also matters. Most studies show bad effects from heavy cannabis use in middle to late teenage years. But even smaller amounts can cause the same problems if used earlier in the teenage years.

Effects of Cannabis Exposure Before Birth

A recent study looked at how cannabis exposure before birth was linked to brain and thinking skills in over 11,000 children. The study found that mothers who said they used cannabis during pregnancy had children who performed worse on thinking tests and had smaller overall brain sizes at ages 9 to 10. This was true even after controlling for other things that could confuse the results.

Research from animal studies suggests that cannabis exposure before birth can harm a child's thinking and feelings later in life. This harm comes from changes in how brain cells work and connect in important areas for thinking, memory, and emotions. These changes affect how brain cells receive, process, and send information. Problems with a brain chemical called glutamate are often seen, affecting how it is used in the brain. These changes depend on how cannabinoids from outside the body affect the endocannabinoid system during brain development.

Scientists have also seen that cannabis use can mess with how certain brain chemicals (monoamines) work and how the body handles stress. Cannabis exposure before birth can stop these chemicals from growing properly, which may affect how the brain handles rewards. It is also linked to offspring being more sensitive to stress, which can lead to problems like sadness, mind-altering effects, or substance use issues. Learning how cannabis exposure before birth affects the brain's natural chemical system could help find ways to fix or adjust these important developmental steps.

How Marijuana Affects Human Thinking

Being high right after using marijuana can make it hard to remember things, control actions, and stop sudden urges. This can affect daily activities. For example, a study showed that cannabis users were 36% more likely to be in a car crash than non-users. Another study in 2020 looked at how different cannabis products affected driving. It found that using cannabis with a lot of THC made people weave more in their lane. But using cannabis with mostly CBD had no more effect on driving than using a placebo. These findings show how THC and CBD affect thinking differently in the short term. It also appears that these short-term effects can change as people get used to cannabis or use other drugs.

The long-term effects of cannabis on thinking are not as clear. Some studies that combine many reports show lasting effects on brain function. For example, one large study found that adults who used cannabis almost daily for over two years performed slightly worse on overall thinking tests than non-users. Specific areas like decision-making, learning new words, remembering things, and executive function were more affected. Other large studies that follow people over time give a clearer picture. One study found that more years of marijuana use were linked to poorer verbal memory. However, other studies looking at twins found that lower thinking ability often came before cannabis use, rather than being caused by it. These results suggest that shared risk factors, like genes or environment, might be at play.

Brain scans (MRI) show mixed results for changes in brain structure from cannabis use. Some studies found that regular cannabis use in teens was linked to thinning in a part of the brain important for thinking. Other studies found smaller sizes in certain brain areas, but these were not linked to how long someone used cannabis or how much. However, other large studies found no changes in brain size in areas like the hippocampus. This means that structural changes in the brain related to cannabis use are not always consistent in studies.

But scans looking at how the brain works often show clearer effects, especially after long-term use. A study combining many functional MRI reports found that both adult and teenage cannabis users showed different brain activity compared to non-users. This suggests the brain might be trying to make up for changes. These brain function changes can last even after people stop using cannabis for a while.

Several recent studies looked at how cannabis affects people who already have health issues or use medical marijuana. One study found that young cannabis users with psychosis showed differences in thinking skills and working memory compared to those with psychosis who did not use cannabis. However, a study of adult patients with long-term pain who used medical cannabis daily for a year showed no major thinking differences compared to a group who did not use cannabis. These studies suggest that the effects of cannabis on thinking might vary depending on the person's health condition.

Cannabis, Brain Blood Flow, and Disease

Risk Factors for Brain Blood Vessel Issues

Similar to how marijuana use is linked to heart problems, there is limited proof that it increases the risk of certain brain blood vessel issues. Studies linking marijuana use to heart and brain vessel problems are often based on observations or single cases, which can sometimes be biased. Some possible harmful effects of marijuana use include changes in blood pressure, effects on blood clotting, and heart rhythm changes. Other things like tobacco smoking or using other drugs at the same time might also cause these effects. These issues might be short-term and are mostly studied in young adults who generally have low health risks. This may explain why many long-term studies did not find a clear link between marijuana use and heart or body health risks after considering other unhealthy habits.

High blood pressure is a major risk factor for different kinds of strokes. When people use marijuana, the most common immediate effect is a drop in blood pressure. However, some studies showed a small link between recent cannabis use and higher blood pressure in adults aged 30 to 59. Heavy users (those who used marijuana more than 20 days a month) had a higher chance of abnormal blood pressure. This link was less clear after accounting for tobacco and heavy alcohol use. More research is needed to see if this link between marijuana use and higher blood pressure, especially for heavy users, leads to long-term brain blood vessel problems.

Having heart conditions like a heart attack or an irregular heartbeat (atrial fibrillation) also increases the risk of stroke. Some reports show heart attacks in young adults shortly after using marijuana, even if they had no other risk factors. The risk of a heart attack went up by 4.8 times within an hour of smoking marijuana. This suggests marijuana can trigger immediate heart problems. However, a long-term study following adults for 25 years found no link between regular marijuana use and coronary heart disease, stroke, or heart-related deaths. But another study that looked at many patient records found a higher risk of heart attack over three years in marijuana users compared to non-users.

Similarly, marijuana use seems to trigger irregular heartbeats. Data from hospitals showed that the number of people with cannabis use disorder who were also diagnosed with irregular heartbeats went up by 31% after marijuana laws became less strict. However, one study of heart failure patients found that marijuana users had a lower chance of irregular heartbeats than non-users. Sometimes, using other drugs like cocaine or stimulants at the same time might explain the irregular heartbeats seen in marijuana users. More research is needed to fully understand this.

Risk of Stroke and Mini-Stroke

Some individual reports and small studies, mostly in young people, suggest that recent and heavy cannabis use might increase the risk of stroke. However, studies that compare groups of people or use large patient databases have shown mixed results. These differences might depend on how the study was set up, what other factors were considered, and who was included in the study.

For example, one study found a link between cannabis use and the risk of stroke, but this link was not significant when tobacco use was also considered. Similarly, another study found no link between cannabis use in young adulthood and fatal or non-fatal stroke later in life among Swedish men, after accounting for cigarette smoking and alcohol use.

However, other studies that looked more closely at the amount or frequency of cannabis use suggest that regular use might increase stroke risk. Some population surveys reported that heavy cannabis use in the past year was linked to a higher risk of non-fatal stroke and mini-stroke. Also, frequent cannabis use (more than 10 days a month) was linked to an increased risk of stroke, while less frequent use was not.

Using hospital records, one study found that men and women admitted to the hospital with cannabis use were 17% more likely to have an acute stroke. If they also used tobacco, the risk went up to 31%. Another study using hospital data found a higher chance of stroke among cannabis users. In contrast, a study using patient records from a single hospital found no link between testing positive for cannabis use and the risk of stroke, even after considering many other factors.

There might be specific groups or situations where cannabis use is clearly linked to stroke. A large study of over 1 million pregnant women in Canada found that a cannabis use disorder doubled the risk for a bleeding stroke, but not for other types of stroke. Because cannabis can affect blood vessels, it has also been linked to a rare condition called reversible cerebral vasoconstriction syndrome, which can cause strokes. Also, a higher risk of stroke from narrowed brain arteries has been seen in young cannabis users. Studies in animals show that cannabinoids can have complex effects on the heart and blood vessels, sometimes causing blood vessels to widen or narrow. They can also lead to swelling and damage in blood vessel cells, which is linked to heart problems and hardened arteries.

Serious heart events and strokes have also been reported in people using man-made cannabinoids like Spice. Spice has been linked to a blood disorder that increases the risk of major bleeding. Also, bleeding in the brain in Spice users has been connected to a chemical called brodifacoum, which is a strong blood thinner sometimes found in these illegal products.

What We Are Learning and Future Steps

Our understanding of how cannabis affects brain health is still growing and changing quickly. Studies that just observe people have shown mixed results regarding marijuana's effects on blood pressure, irregular heartbeats, heart attacks, and thinking. Many things can explain these mixed findings. First, since marijuana was illegal for so long, people might not have always said if they used it. This could make it seem like its effects are smaller than they are. Second, other habits like smoking and drinking alcohol often go along with marijuana use and can affect the risk of stroke and brain connections. We often lack enough information on how often people do these other things, making it hard to know marijuana's exact effect by itself.

Third, how often someone uses marijuana, how much they use, and how the body takes it in (which depends on how it is used, diet, and other medicines) are often not reported clearly. Fourth, THC and CBD have different effects. While THC has been linked to harmful effects, CBD may help with some brain problems. The exact amounts of these chemicals are different in various cannabis plants and how they are processed. Fifth, the strength of recreational marijuana has increased over time, making older studies less relevant today. Lastly, it is hard to do long-term studies where some people get a real drug and others get a fake one (placebo). This is due to ethical concerns and because THC affects the mind in ways that cannot be hidden from users.

Social media may highlight only the good parts of marijuana, making many people think it is harmless. However, new evidence linking marijuana use to heart attacks and strokes, plus the possible problems with common medicines, means people should be careful. It is important to have programs that watch for these effects. Also, there should be clear health warnings on cannabis products. Each person's marijuana use should be looked at carefully by health professionals. Doctors and patients should get truthful information about the possible harms of medical, recreational, and illegal marijuana use on brain health, especially when used during important times of growth. It might also be important for doctors to check the thinking skills of marijuana users and review their medicines to find any possible bad interactions. Well-informed health care workers can teach people about the possible harms, helping them make smart choices based on real facts.