Cannabis Genetics Research

The genetics of cannabis lifetime use.

Bright, Uri · 2026

11 independent genome-wide significant variants for cannabis lifetime use, most prominently CADM2*rs7609594 (p=7.4×10⁻²⁰); genetic correlations with risk-taking, openness, and substance use; bidirectional causal relationships via Mendelian randomization; distinct from CUD genetic architecture..

DNA methylation profiles of long-term cannabis users in midlife: a comprehensive evaluation of published cannabis-associated methylation markers in a representative cohort.

Meier, Madeline H · 2025

Analysis of the Dunedin Multidisciplinary Health and Development Study revealed that decades of cannabis use was associated with specific DNA methylation changes, a type of epigenetic modification that can alter gene expression without changing the DNA sequence itself..

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Noble, Alexandra J · 2025

Prenatal cannabis exposure was associated with genome-wide significant DNA methylation differences at birth, 7 years, 15-17 years, and 27 years.

Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use.

Fang, Fang · 2024

Four CpG sites were significantly associated with lifetime cannabis use independent of smoking: cg22572071 (near ADGRF1), cg15280358 (in ADAM12), cg00813162 (in ACTN1), and cg01101459 (near LINC01132).

Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits.

Galimberti, Marco · 2024

CUD showed significant causal effects on all analyzed substance use traits: opioid use disorder (IVW beta 0.925), problematic alcohol use (0.443), smoking initiation (0.405), drinks per week (0.182), nicotine dependence (0.183), and cigarettes per day (0.150).

Genome-wide DNA methylation analysis of cannabis use disorder in a veteran cohort enriched for posttraumatic stress disorder.

Garrett, Melanie E · 2024

Four CpGs were associated with lifetime CUD after smoking adjustment: AHRR cg05575921, LINC00299 cg23079012, VWA7 cg22112841, and FAM70A cg08760398.

The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study.

Cheng, Weiqiu · 2023

Genome-wide genetic correlations between psychotic disorders and cannabis phenotypes ranged from 0.22-0.35.

Comorbidity and Coaggregation of Major Depressive Disorder and Bipolar Disorder and Cannabis Use Disorder in a Controlled Family Study.

Quick, Courtney R · 2022

CUD in probands was associated with increased CUD in relatives (aOR 2.64).

Genome-wide identification of the shared genetic basis of cannabis and cigarette smoking and schizophrenia implicates NCAM1 and neuronal abnormality.

Song, Weichen · 2022

A common genetic factor of cannabis and cigarette smoking explained 8.6% of schizophrenia heritability.

The Effects of Alcohol and Cannabis Use on the Cortical Thickness of Cognitive Control and Salience Brain Networks in Emerging Adulthood: A Co-twin Control Study.

Harper, Jeremy · 2021

Greater alcohol misuse was linked to thinner cortex in prefrontal, temporal, insula, and parietal regions, predominantly right-lateralized.

No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder.

Hjorthøj, Carsten · 2021

Schizophrenia polygenic risk scores did not predict CUD in controls (HR=1.16, not significant) or in patients with other psychiatric disorders.

The relationship between cannabis and schizophrenia: a genetically informed perspective.

Johnson, Emma C · 2021

Genetic liability to CUD predicted schizophrenia (beta=0.29, p=0.001) even after accounting for cannabis ever-use, tobacco smoking, and nicotine dependence.

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Munn-Chernoff, Melissa A · 2021

Significant positive genetic correlations emerged between anorexia nervosa and cannabis initiation (rg = 0.23), and between anorexia nervosa with binge eating and cannabis use disorder (rg = 0.27).

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Quattrone, Diego · 2021

Schizophrenia polygenic risk score (SZ-PRS) was associated with both negative (B=0.18) and positive (B=0.19) symptom dimensions in 617 first-episode patients, regardless of diagnostic category.

Adolescent cannabis use and adult psychoticism: A longitudinal co-twin control analysis using data from two cohorts.

Schaefer, Jonathan D · 2021

In 1,544 twins, both cumulative adolescent cannabis use and cannabis use disorder were associated with higher adult Psychoticism scores, but comparing twins within pairs (where one used more cannabis) showed no within-pair difference, pointing to familial confounds rather than causal effects..

Investigating causality between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization.

Treur, Jorien L · 2021

Genetic liability to ADHD increased the likelihood of smoking initiation, heavier smoking, difficulty quitting smoking, and cannabis initiation.

Cannabis, schizophrenia genetic risk, and psychotic experiences: a cross-sectional study of 109,308 participants from the UK Biobank.

Wainberg, Michael · 2021

Cannabis ever-use was associated with 67% greater adjusted odds of delusions of reference among individuals in the top fifth of schizophrenia polygenic risk, but only 7% greater adjusted odds among the bottom fifth.

A large-scale genome-wide association study meta-analysis of cannabis use disorder.

Johnson, Emma C · 2020

This GWAS meta-analysis identified 22 genome-wide significant loci associated with cannabis use disorder, with SNP-based heritability estimated at 11%.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

Murray, R M · 2020

In 410 first-episode psychosis patients and 370 controls in South London, approximately 25% of new psychosis cases were attributable to high-potency cannabis use.

Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.

Soler Artigas, María · 2020

Using GWAS data from 53,293 ADHD and 32,330 cannabis use subjects, genetic correlation between ADHD and lifetime cannabis use was r2=0.29 (p=1.63×10-5).

Cannabinoid receptor CNR1 expression and DNA methylation in human prefrontal cortex, hippocampus and caudate in brain development and schizophrenia.

Tao, Ran · 2020

CNR1 expression is high in fetal prefrontal cortex and hippocampus, then drops dramatically after birth.

Genome-wide association study implicates CHRNA2 in cannabis use disorder.

Demontis, Ditte · 2019

A variant (rs56372821) near the CHRNA2 gene reached genome-wide significance for cannabis use disorder risk (P = 9.31 x 10^-12) and replicated independently (P = 3.27 x 10^-3).

Risk factors and peripheral biomarkers for schizophrenia spectrum disorders: an umbrella review of meta-analyses.

Belbasis, L · 2018

Researchers conducted an umbrella review, a review of reviews, to systematically evaluate all published meta-analyses of non-genetic risk factors and biomarkers for schizophrenia spectrum disorders.

Associations between childhood ADHD, gender, and adolescent alcohol and marijuana involvement: A causally informative design.

Elkins, Irene J · 2018

Researchers studied 3,762 twins (64% identical) to determine whether childhood ADHD causally leads to adolescent substance use or whether shared genetic and environmental factors explain the link. Children with more severe ADHD symptoms initiated alcohol and marijuana use earlier, escalated to frequent or heavy use faster, and developed more symptoms of substance use problems by age 17. Females with more hyperactivity-impulsivity had higher alcohol consumption and progressed further toward daily marijuana use than males with similar symptoms. The critical test: when identical twins who differed in ADHD severity were compared, the twin with more severe ADHD did not have significantly worse substance outcomes than their co-twin.

Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design.

Hines, Lindsey A · 2018

Researchers used data from 3,303 Australian twins to decompose the genetic and environmental contributions to three stages of cannabis involvement: opportunity to use, frequency of use, and cannabis abuse/dependence. All three stages were substantially heritable: opportunity (64%), frequency (74%), and abuse/dependence (78%).

Genome-wide association meta-analysis of age at first cannabis use.

Minică, Camelia C · 2018

Researchers conducted the largest genome-wide association study of age at first cannabis use to date. Twin analysis (8,055 twins from three cohorts) estimated heritability at 38% (95% CI 19-60%).

Cannabis consumption and psychosis or schizophrenia development.

Ortiz-Medina, María Bettina · 2018

Researchers reviewed 66 papers examining the relationship between cannabis use and psychosis in people without pre-existing schizophrenia. The main conclusion: cannabis use doubles the risk of developing psychosis in vulnerable individuals. Additional findings: - A dose-response relationship exists: heavier cannabis use is associated with greater psychosis risk. - Age of first use matters: earlier initiation is associated with higher risk. - Gene-environment interactions modulate the association, meaning genetic susceptibility influences how much cannabis increases individual psychosis risk. The evidence was drawn from 23 cohort studies (which follow people over time) and 43 reviews, representing a substantial evidence base accumulated over decades of research..

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Pasman, Joëlle A · 2018

In the largest GWAS of lifetime cannabis use to date, researchers analyzed 184,765 individuals and identified eight genome-wide significant SNPs in six genomic regions. All measured genetic variants combined explained 11% of the variance in cannabis use. Gene-based tests revealed 35 significant genes in 16 regions.

Major depressive disorder, suicidal thoughts and behaviours, and cannabis involvement in discordant twins: a retrospective cohort study.

Agrawal, Arpana · 2017

Among nearly 14,000 twins from the Australian Twin Registry, the identical twin who used cannabis frequently (100+ times) was significantly more likely to report major depressive disorder (odds ratio 1.98) and suicidal ideation (odds ratio 2.47) compared to their genetically identical co-twin who used less. These associations persisted even after adjusting for early alcohol and nicotine use, early mood symptoms, conduct disorder, and childhood sexual abuse.

Genetic and Environmental Contributions to the Association Between Cannabis Use and Psychotic-Like Experiences in Young Adult Twins.

Nesvåg, Ragnar · 2017

This twin study of 2,793 young adults disentangled the genetic and environmental contributions to the cannabis-psychosis relationship. Cannabis use disorder symptoms were strongly associated with psychotic-like experiences, with an incidence rate ratio of 6.3.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Stringer, S · 2016

The International Cannabis Consortium pooled genetic data from 13 cohorts totaling 32,330 participants.

Protein kinase B (AKT1) genotype mediates sensitivity to cannabis-induced impairments in psychomotor control.

Bhattacharyya, S · 2014

In a double-blind study, healthy occasional cannabis users received either THC or placebo and performed a response inhibition task during brain imaging.

Decline in genetic influence on the co-occurrence of alcohol, marijuana, and nicotine dependence symptoms from age 14 to 29.

Vrieze, Scott I · 2012

Researchers followed twins from age 11 through 29, measuring nicotine, alcohol, and marijuana dependence symptoms at six timepoints.

Common genetic contributions to alcohol and cannabis use and dependence symptomatology.

Sartor, Carolyn E · 2010

Researchers analyzed data from 6,257 Australian twins aged 24 to 36 to understand genetic and environmental contributions to alcohol and cannabis use and dependence. Genetic factors accounted for over 60% of variance in alcohol consumption, cannabis use, and cannabis dependence symptoms.

Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies.

Verweij, Karin J H · 2010

Researchers conducted a meta-analysis of 28 twin studies on cannabis initiation and 24 on problematic use, weighting results by sample size. For cannabis use initiation, genetics explained 48% of variance in males and 40% in females.

Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use.

Lynskey, Michael T · 2004

Among 277 twin pairs discordant for cannabis dependence, the cannabis-dependent twin had 2.5 to 2.9 times higher odds of suicidal ideation and suicide attempt compared to their non-dependent co-twin.

Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins.

Kendler, K S · 2000

Researchers interviewed 1,198 male-male twin pairs (708 identical, 490 fraternal) from a population registry about lifetime use, heavy use, abuse, and dependence on six drug classes including cannabis. Twin resemblance was consistently greater in identical twins than fraternal twins across all measures.

Cannabis use, abuse, and dependence in a population-based sample of female twins.

Kendler, K S · 1998

Researchers interviewed 1,934 women from female twin pairs, including 485 identical (monozygotic) and 335 fraternal (dizygotic) pairs, about their lifetime cannabis use. Nearly half (47.9%) had used cannabis at least once.

Education shares distinct genetic influences with substance use and disorder.

Davis, Christal N · 2026

Education shared 84% of causal genetic variants with cannabis use disorder (CUD) but only 48% with cannabis use.

Comparing random forest and elastic net models to predict substance use disorder transitions in participants with cannabis and stimulant use: Evidence from the All of Us cohort.

Zamora, Gabriel · 2026

For cannabis users, both elastic net and random forest models achieved AUC of about 0.74 (no significant difference).

Investigating the polygenic relationship between heavy cannabis use and schizophrenia in the All of Us Research Program.

Austin-Zimmerman, Isabelle · 2025

The association between heavy cannabis use and schizophrenia has been documented for decades, but a fundamental question remains: does cannabis cause psychosis, does genetic vulnerability to psychosis drive cannabis use, or both? This study used polygenic scores — genetic risk calculators derived from large genome-wide association studies — to test these pathways in real individuals with data on both genetics and diagnoses. Using the All of Us Research Program (a diverse U.S.

Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

Cupertino, Renata Basso · 2025

Higher genetic risk for CUD was associated with greater cannabis exposure, more novelty/sensation seeking, higher impulsivity, and lower white matter integrity from age 14.

Methylomic signature of current cannabis use in two first-episode psychosis cohorts.

Dempster, Emma L · 2025

Current cannabis use was associated with differential methylation at a site in the CAVIN1 gene, independent of tobacco effects.

Smoking initiation as a mediator: investigating the causal relationship between sedentary lifestyles and cannabis use disorder through Mendelian randomization.

Meng, Deyu · 2025

Using Mendelian randomization, leisure screen time was causally linked to a 43% increased risk of cannabis use disorder (OR=1.43).

The Relationship of glutamate signaling to cannabis use and schizophrenia.

Niznikiewicz, Margaret · 2025

The review synthesizes three lines of evidence: cannabis is associated with psychosis in a subset of users, glutamate dysregulation is a feature of schizophrenia, and cannabis affects the glutamate system.

Intergenerational Transmission of Cannabis Use: Testing Genetic Risk and the Mitigating Influences of Parent Positive Behavior Support in Early Childhood.

Ostner, Savannah G · 2025

Parent cannabis use significantly predicted offspring cannabis use at age 18, while polygenic risk scores for CUD did not.

Mental Health, Substance Use, and Related Factors Associated with Recent Use of Cannabis for Sleep: A Co-Twin Control Study.

Panchal, Zoë · 2025

In co-twin control analyses that account for genetic and shared environmental factors, using cannabis for sleep remained significantly associated with more cannabis use problems, higher cannabis frequency, worse sleep quality, and more frequent use of alcohol and sleep medications.

Cannabis use and psychotic-like experiences: A systematic review of biological vulnerability, potency effects, and clinical trajectories.

Ricci, Valerio · 2025

Across 38 studies, four major risk factor categories emerged for psychotic-like experiences (PLEs) in non-clinical populations: biological vulnerabilities (metabolic profiles, genetics, neurobiology), substance use patterns (especially high-potency cannabis), socio-demographic factors (digital media, ethnic density, gender), and downstream consequences (suicidal behavior, cognitive impairment).

Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First Episode Study.

Rodriguez, Victoria · 2025

In 573 first-episode psychosis cases and 1,005 controls, polygenic risk for schizophrenia was the strongest genetic predictor of schizophrenia-spectrum disorders, with a notably larger effect in people not exposed to strong environmental risks like frequent cannabis use (OR 2.43 unexposed vs 1.35 exposed).

A Meta-Narrative Review of Channelopathies and Cannabis: Mechanistic, Epidemiologic, and Forensic Insights into Arrhythmia and Sudden Cardiac Death.

Šoša, Ivan · 2025

Cannabinoids affect calcium and potassium currents through both receptor-dependent and -independent pathways, alter autonomic regulation, and promote oxidative stress and inflammation in heart tissue.

Polygenic Risk for Substance Use Disorders as Predictors of Substance Use Initiation Among African American Youth.

Sosnowski, David W · 2025

Cannabis use disorder and nicotine dependence polygenic risk scores were not associated with initiation of these substances.

Associations between cannabis use frequency and suicidal thoughts and behaviors: A clinical longitudinal sibling study.

Stern, Elisa F · 2025

Cannabis use was not associated with suicidality (all p's > 0.05) in cross-sectional or prospective models accounting for within-family clustering.

Decoding the genetic links between substance use disorder and cancer vulnerability.

Su, Xin · 2025

No significant causal relationship was found between CUD and any cancer type (all P>0.05).

Methylation Status of the DAT1 Dopamine Transporter Gene in Individuals With Cannabis Use Disorder: Associations With Personality Traits.

Suchanecka, Aleksandra · 2025

Individuals with CUD showed altered DAT1 methylation levels compared to controls.

The influence of genetics on the endocannabinoid system gene expression and relevance for targeting reproductive conditions.

Tanaka, Keisuke · 2025

In 31,684 participants from eQTLGen, 22,020 genetic variants (eQTLs) influenced 43 of 70 selected ECS genes.

The endocannabinoid system's genetic polymorphisms in sickle cell anemia patients.

Berti, Amanda Cristina Meneguetti · 2024

Sickle cell anemia (SCA) is a genetic blood disorder that causes a range of severe complications, including priapism — prolonged, painful erections caused by sickled red blood cells blocking penile blood vessels.

DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?

Di Bartolomeo, Martina · 2024

DNA methylation at CNR1 and DRD2 genes was significantly higher in psychotic subjects than healthy controls, and the two genes' methylation levels were directly correlated.

Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis.

Amir, Carolyn M · 2023

CHR-P youth had significantly higher substance use across tobacco, alcohol, and cannabis compared to controls, while 22qDel carriers had significantly lower use.

Impact of tobacco, alcohol, and marijuana on genome-wide DNA methylation and its relationship with hypertension.

Carreras-Gallo, Natàlia · 2023

Three epigenome-wide association studies in the same cohort found 2,569 CpG sites differentially methylated by alcohol and 528 by tobacco.

Genetic support of a causal relationship between cannabis use and educational attainment: a two-sample Mendelian randomization study of European ancestry.

Chen, Dongze · 2023

Bidirectional Mendelian randomization found genetic liability to cannabis use disorder was associated with 1.2 fewer months of education (P=0.0008).

Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults.

Nannini, Drew R · 2023

At examination year 15 (n = 1,023), 22 and 31 methylation markers were associated with recent and cumulative marijuana use.

Clinical Epigenomic Explanation of the Epidemiology of Cannabinoid Genotoxicity Manifesting as Transgenerational Teratogenesis, Cancerogenesis and Aging Acceleration.

Reece, Albert Stuart · 2023

Longitudinal epigenome-wide association studies showed cannabinoid exposure disrupts chromosomal segregation, DNA repair, methylation machinery, and telomerase function.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Segura, Alex G · 2023

Current cannabis use was associated with increased positive symptoms.

Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.

Shorey-Kendrick, Lyndsey E · 2023

Prenatal THC exposure was associated with differential methylation at 581 CpGs, with 573 (98%) in placenta.

Molecular Insights into Epigenetics and Cannabinoid Receptors.

Basavarajappa, Balapal S · 2022

Epigenetic mechanisms including DNA methylation, histone protein modifications, and RNA regulatory networks significantly influence cannabinoid receptor (CB1 and CB2) gene expression, contributing to both normal function and disease states..

Association of cannabis use disorder with cardiovascular diseases: A two-sample Mendelian randomization study.

Chen, Miao · 2022

Genetic liability to cannabis use disorder was associated with higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke in both univariable and multivariable MR analyses adjusting for smoking, alcohol, BMI, lipids, diabetes, hypertension, and depression.

Association between Polymorphism rs1799732 of DRD2 Dopamine Receptor Gene and Personality Traits among Cannabis Dependency.

Chmielowiec, Jolanta · 2022

Cannabis-dependent individuals scored significantly higher on neuroticism, openness, state anxiety, and trait anxiety, and lower on extraversion, agreeableness, and conscientiousness compared to controls.

Cannabis, Intraocular Pressure, and the Growth Arrest-Specific 7 (GAS7) Gene: A Retrospective Analysis.

Lehrer, Steven · 2022

Carriers of the GAS7 gene variant (rs9913911 minor allele G) showed lower intraocular pressure with increased cannabis use (P<0.001).

Associations between cognition and polygenic liability to substance involvement in middle childhood: Results from the ABCD study.

Paul, Sarah E · 2022

Polygenic risk for lifetime cannabis use was positively associated with all three cognitive facets: general ability, executive function, and learning/memory (Bs ≥ 0.045, qs ≤ 0.044).

Shared Genetic Etiology between Cortical Brain Morphology and Tobacco, Alcohol, and Cannabis Use.

Rabinowitz, Jill A · 2022

Eight significant negative genetic correlations were found between brain measures and substance use, including between alcohol consumption and cortical thickness.

Genomic relationships across psychiatric disorders including substance use disorders.

Abdellaoui, Abdel · 2021

Alcohol and nicotine dependence showed significant genetic correlations with multiple psychiatric disorders including ADHD, schizophrenia, and major depression.

An Examination of Risk Factors for Tobacco and Cannabis Smoke Exposure in Adolescents Using an Epigenetic Biomarker.

Andersen, Allan · 2021

Increasing proportions of students tested positive for cotinine (5-16%), THC (3-10%), and the epigenetic biomarker (5-7%) from 10th to 12th grade.

Typologies of illicit drug use in mid-adulthood: a quasi-longitudinal latent class analysis in a community-based sample of twins.

Dash, Genevieve F · 2021

Five drug use classes emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%).

Cannabis alters epigenetic integrity and endocannabinoid signalling in the human follicular niche.

Fuchs Weizman, Noga · 2021

6.4% of patients tested positive for cannabis in follicular fluid.

Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization.

Hatoum, Alexander S · 2021

The genetic correlation between CUD and COVID-19 hospitalization was 0.423 (p = 1.33 x 10^-6).

Bipolar disorder and cannabis use: A bidirectional two-sample Mendelian randomization study.

Jefsen, Oskar Hougaard · 2021

Genetic liability to bipolar disorder was significantly associated with increased risk of lifetime cannabis use across all three MR methods (inverse variance weighted, weighted median, and Egger regression).

Experimentally exploring the potential behavioral effects of personalized genetic information about marijuana and schizophrenia risk.

Lebowitz, Matthew S · 2021

Participants told they had a genetic predisposition for marijuana to increase schizophrenia risk rated the likelihood and importance of avoiding marijuana as significantly higher than controls.

Epigenome-wide analysis uncovers a blood-based DNA methylation biomarker of lifetime cannabis use.

Markunas, Christina A · 2021

Researchers identified a replicated association between lifetime cannabis use and DNA methylation at site cg15973234 in the CEMIP gene (combined P = 3.3 x 10^-8).

Risk and protective factors for cannabis, cocaine, and opioid use disorders: An umbrella review of meta-analyses of observational studies.

Solmi, Marco · 2021

Of 19 associations between 12 risk/protective factors and substance use disorders, none reached "convincing" evidence.

Genetic overlap and causality between substance use disorder and attention-deficit and hyperactivity disorder.

Vilar-Ribó, Laura · 2021

The study confirmed a common genetic background between ADHD and SUD using both clinical (n=989) and population GWAS data.

Cannabis Use and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study.

Zhao, Jianqiang · 2021

Standard MR analysis showed no causal effects of cannabis use on coronary artery disease, myocardial infarction, stroke subtypes, atrial fibrillation, or heart failure.

Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene.

Boks, Marco P · 2020

A SNP in the P2RX7 gene (rs7958311) was associated with increased psychotic-like experiences in regular cannabis users (p = 1.10 x 10^-7) and was replicated in the IMAGEN cohort (p = 0.020).

Neuronal nicotinic acetylcholine receptors mediate ∆9 -THC dependence: Mouse and human studies.

Donvito, Giulia · 2020

Alpha3beta4 nAChR antagonist/partial agonist reduced THC withdrawal signs.

Contribution of Dopamine Transporter Gene Methylation Status to Cannabis Dependency.

Grzywacz, Anna · 2020

No overall difference in DAT1 gene promoter methylation was found between groups.

Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.

Scherma, Maria · 2020

Adolescent rats pre-exposed to the synthetic cannabinoid WIN showed cross-sensitization to cocaine, correlating with histone hyperacetylation and decreased HDAC6 in the prefrontal cortex.

Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.

Schrott, Rose · 2020

THC exposure via oral gavage altered DNA methylation at seven neurodevelopmentally active genes in rat sperm.

Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.

Schrott, Rose · 2020

Using RRBS, cannabis use was associated with significant hypomethylation of the autism-linked gene DLGAP2 in human sperm.

Exploring Phenotypic and Genetic Overlap Between Cannabis Use and Schizotypy.

Vaissiere, James · 2020

Positive phenotypic correlations (range 0.05-0.18) were found between 11 of 12 cannabis use and schizotypy trait pairs in UK Biobank.

Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis.

Bioque, Miquel · 2019

The FAAH rs2295633 genetic polymorphism interacted with cannabis use to dramatically increase psychosis risk.

Acute effects of ∆9-tetrahydrocannabinol (THC) on resting state brain function and their modulation by COMT genotype.

Bossong, Matthijs G · 2019

THC increased perfusion in bilateral insula, medial superior frontal cortex, and left orbital frontal gyrus.

Tobacco and cannabis use in college students are predicted by sex-dimorphic interactions between MAOA genotype and child abuse.

Fite, Paula J · 2019

In female students, high-activity MAOA alleles combined with physical and emotional abuse predicted lifetime tobacco and cannabis use.

Genetic and environmental risk factors in the non-medical use of over-the-counter or prescribed analgesics, and their relationship to major classes of licit and illicit substance use and misuse in a population-based sample of young adult twins.

Gillespie, Nathan A · 2019

NMUA heritability was 46%.

Cannabis and Psychosis: Are We any Closer to Understanding the Relationship?

Hamilton, Ian · 2019

The evidence for cannabis as a direct cause of schizophrenia has not been established.

Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons.

Miller, Michael L · 2019

THC exposure disrupted normal PFC development by inducing premature spine pruning and dendritic atrophy.

Highs and lows of cannabinoid-dopamine interactions: effects of genetic variability and pharmacological modulation of catechol-O-methyl transferase on the acute response to delta-9-tetrahydrocannabinol in humans.

Ranganathan, Mohini · 2019

Val/Val individuals showed the greatest THC-induced working memory and attention deficits.

Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. 'cannabinoid exposure and altered DNA methylation in rat and human sperm' epigenetics 2018; 13: 1208-1221.

Reece, Albert Stuart · 2019

Building on the Murphy et al.

Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis.

Rojnic Kuzman, Martina · 2019

Carriers of the CNR1 rs7766029 CC genotype showed significantly greater improvement in verbal memory (Wechsler, Wechsler 30') and attention (Digit span F).

Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.

Aas, M · 2018

Researchers assigned schizophrenia polygenic risk scores to 381 schizophrenia spectrum patients, 220 bipolar disorder spectrum patients, and 415 healthy controls.

The effect of interactions between genetics and cannabis use on neurocognition. A review.

Cosker, E · 2018

Researchers systematically reviewed 13 studies examining how genetic variations influence the cognitive effects of cannabis use.

Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence.

Hiemstra, Marieke · 2018

Researchers followed 372 adolescents from the RADAR-Y study, tracking substance use from ages 13-20 while measuring each participant's genetic vulnerability to schizophrenia using polygenic risk scores. High schizophrenia genetic vulnerability was specifically associated with a stronger increase in cannabis use during ages 16-20.

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Murphy, Susan K · 2018

Researchers compared DNA methylation in sperm from human cannabis users versus non-users, and from THC-exposed versus unexposed rats. In human sperm, cannabis users differed from non-users by at least 10% methylation at 3,979 CpG sites. Pathway analysis identified Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02).

High times for cannabis: Epigenetic imprint and its legacy on brain and behavior.

Szutorisz, Henrietta · 2018

Cannabinoid exposure during critical developmental periods creates epigenetic changes (modifications to how genes are read) that persist long after exposure ends.

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4.

Fransquet, Peter D · 2017

Among 804 neonates whose mothers provided detailed trimester-by-trimester drug use information, 44 were exposed to maternal cannabis use during pregnancy.

Heavy cannabis use prior psychosis in schizophrenia: clinical, cognitive and neurological evidences for a new endophenotype?

Mallet, Jasmina · 2017

This study compared 34 schizophrenia patients who reported heavy cannabis use before their first psychotic episode with 27 patients who did not. The results were counterintuitive: heavy pre-psychosis cannabis users showed significantly fewer neurological soft signs (subtle neurological abnormalities considered markers of early neurodevelopmental impairment) and better cognitive functioning across multiple domains including reaction time, episodic memory, and visuoconstructive abilities. These findings held after controlling for alcohol and tobacco use.

Cannabis use, COMT, BDNF and age at first-episode psychosis.

Mané, Anna · 2017

This study investigated whether cannabis use and two genes (COMT Val158Met and BDNF Val66Met) interact to influence when psychosis first appears. Among 260 Caucasian first-episode psychosis patients, two factors independently predicted younger age at psychosis onset: early cannabis use and carrying the met-allele of the BDNF Val66Met polymorphism. The BDNF finding is significant because BDNF (brain-derived neurotrophic factor) is critical for brain development and neural plasticity.

Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement.

Carey, Caitlin E · 2016

Researchers tested whether genetic risk for five psychiatric disorders (ADHD, autism, bipolar disorder, depression, and schizophrenia) predicted involvement with five substances (alcohol, cannabis, cocaine, nicotine, and opioids) in 2,573 European-American participants. A combined cross-disorder psychiatric risk score significantly predicted general substance involvement, explaining about 1.1% of variance.

Cannabis Involvement and Nonsuicidal Self-Injury: A Discordant Twin Approach.

Few, Lauren R · 2016

Researchers studied nearly 10,000 Australian twins to untangle whether cannabis use leads to nonsuicidal self-injury (NSSI) or whether both behaviors stem from shared genetic and environmental factors. Lifetime cannabis use was associated with a 2.84 times higher odds of self-injury.

Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.

Ramaekers, J G · 2016

Researchers gave 122 regular drug users acute doses of cannabis, cocaine, and placebo and measured cognitive impulsivity and brain connectivity.

Epigenetic Effects of Cannabis Exposure.

Szutorisz, Henrietta · 2016

This review examined the emerging field of cannabis epigenetics, where researchers study how cannabis exposure changes gene expression without altering the DNA sequence itself. Accumulating evidence from both human and animal studies showed that cannabinoids can modify epigenetic marks, including DNA methylation and histone modifications, in brain tissue and peripheral cells.

The complex etiology of schizophrenia - general state of the art.

Hosák, Ladislav · 2015

This review synthesized the complex, multi-factorial etiology of schizophrenia.

A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

Kendler, Kenneth S · 2015

Researchers analyzed registry data from nearly 80,000 Swedish male twin and sibling pairs to understand whether genetic risk for drug abuse is substance-specific or shared across drug types. The total heritability for cannabis, stimulant, and sedative abuse ranged from 64-70%.

Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence.

Palmer, Rohan H C · 2015

Researchers analyzed genetic data from 2,596 individuals in the Study of Addiction: Genetics and Environment to estimate how much common genetic variation contributes to drug dependence vulnerability. Common single nucleotide polymorphisms (SNPs) explained 25-36% of the variance across three measures of drug problems.

Psychotic experiences are linked to cannabis use in adolescents in the community because of common underlying environmental risk factors.

Shakoor, Sania · 2015

Researchers used data from 4,830 twin pairs (aged 16) to determine whether the cannabis-psychosis association is driven by genetics, shared environment, or unique environment. Cannabis use was modestly heritable (37%) with strong shared environmental influence (55%).

Initial reactions to tobacco and cannabis smoking: a twin study.

Agrawal, Arpana · 2014

In a study of female twins, researchers examined how initial reactions to tobacco and cannabis (the first time each was used) related to later development of DSM-IV diagnoses.

ADHD symptoms, autistic traits, and substance use and misuse in adult Australian twins.

De Alwis, Duneesha · 2014

In a study of 3,080 young adult Australian twins, researchers examined how ADHD symptoms and autistic traits independently related to substance use.

Stability and change of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis DSM-IV dependence symptoms.

Palmer, R H C · 2013

Researchers studied 2,361 adolescents across two assessment waves to examine the stability of genetic and environmental influences on substance dependence liability.

A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5.

Verweij, K J H · 2013

In a study of 2,276 Australian twins who had used cannabis at least once, 11.9% met criteria for DSM-5 cannabis withdrawal.

The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation.

Verweij, Karin J H · 2013

Researchers conducted a meta-analysis of two genome-wide association studies (GWAS) involving more than 10,000 individuals to identify genetic variants associated with initiating cannabis use.

Borderline personality traits and substance use: genetic factors underlie the association with smoking and ever use of cannabis, but not with high alcohol consumption.

Distel, Marijn A · 2012

Researchers studied 5,638 Dutch and Belgian twins aged 21-50 from 3,567 families.

An Australian twin study of cannabis and other illicit drug use and misuse, and other psychopathology.

Lynskey, Michael T · 2012

Researchers interviewed 3,824 young adult twins born 1972-1979 about cannabis and other drug use.

Genetic etiology of the common liability to drug dependence: evidence of common and specific mechanisms for DSM-IV dependence symptoms.

Palmer, Rohan H C · 2012

Using data from 2,484 twins, researchers found that dependence symptoms for alcohol, tobacco, and cannabis loaded onto a single underlying trait, suggesting a common vulnerability.

No association of candidate genes with cannabis use in a large sample of Australian twin families.

Verweij, Karin J H · 2012

Researchers used a large Australian twin family sample to test whether 10 genes previously reported to be associated with cannabis use actually replicated.

Age moderates non-genetic influences on the initiation of cannabis use: a twin-sibling study in Dutch adolescents and young adults.

Distel, Marijn A · 2011

Researchers examined 6,208 twins and 1,545 siblings from 3,503 Dutch families to understand how the genetic-environmental balance for cannabis initiation changed with age. At the median age of 16.5, genetic factors explained 40% of individual differences in cannabis initiation.

Heritability of cannabis initiation in Dutch adult twins.

Vink, Jacqueline M · 2010

Researchers examined cannabis initiation in 3,115 Dutch twins with a mean age of 27.4 years.

Candidate genes for cannabis use disorders: findings, challenges and directions.

Agrawal, Arpana · 2009

This review synthesized the genetic research on cannabis use disorders, covering both linkage studies (mapping chromosomal regions) and candidate gene association studies. Four linkage studies identified regions on chromosomes 1, 3, 4, 9, 14, 17, and 18.

Developing a quantitative measure of alcohol consumption for genomic studies on prospective cohorts.

Agrawal, Arpana · 2009

Researchers developed a quantitative alcohol consumption factor score using four measures: maximum typical consumption, maximum drinks in 24 hours, frequency of 5+ drinks per day, and frequency of intoxication. The composite score showed good psychometric properties: factor loadings of 0.60-0.90, measurement invariance across two samples and genders, and 50% heritability.

Subjective effects to cannabis are associated with use, abuse and dependence after adjusting for genetic and environmental influences.

Scherrer, Jeffrey F · 2009

Using data from 464 cannabis-using offspring of twins from the Vietnam Era Twin Registry, researchers identified four classes of subjective response to cannabis: high responders (39%), positive responders (28%), mixed/relaxed (22%), and low responders (11%). Compared to low responders, all other groups used more heavily (odds ratios 3.0 to 11.8).

Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample.

Agrawal, Arpana · 2008

Using large multi-generational families from the COGA study, researchers scanned the genome for regions linked to substance dependence using 1,717 genetic markers. For alcohol dependence, significant linkage signals appeared on chromosomes 1, 2, and 10 (highest LOD score 3.7 on chromosome 10).

The association between conduct problems and the initiation and progression of marijuana use during adolescence: a genetic analysis across time.

Shelton, Katherine · 2007

Using data from 1,088 adolescent twin pairs in Wales and England, researchers examined how genetic and environmental factors influence the path from childhood conduct problems to adolescent marijuana use. Marijuana use initiation (whether someone tried it) was influenced by genetic factors, shared environment, and unique environment.

The genetic epidemiology of cannabis use, abuse and dependence.

Agrawal, Arpana · 2006

This review examined twin, family, and adoption studies investigating genetic and environmental influences on cannabis use.

Illicit psychoactive substance use, abuse and dependence in a population-based sample of Norwegian twins.

Kendler, Kenneth S · 2006

Researchers assessed lifetime use, abuse, and dependence across five illicit drug categories (cannabis, stimulants, opiates, cocaine, psychedelics) in 1,386 young adult Norwegian twin pairs.

Genetic and environmental vulnerabilities underlying adolescent substance use and problem use: general or specific?

Young, Susan E · 2006

Researchers studied 645 monozygotic twin pairs, 702 dizygotic twin pairs, 429 biological sibling pairs, and 96 adoptive sibling pairs, all aged 12-18 years.

Evolutionary origins of the endocannabinoid system.

McPartland, John M · 2006

By searching for endocannabinoid system genes across twelve species spanning the tree of life, McPartland and colleagues traced the evolutionary origins of every major ECS component.

Cannabis and other illicit drugs: comorbid use and abuse/dependence in males and females.

Agrawal, Arpana · 2004

Using data from 1,191 male and 934 female same-sex twin pairs, researchers tested 13 genetically informative models of comorbidity between cannabis and other illicit drug use.

Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: contribution of antisocial personality disorder in men.

Fu, Qiang · 2002

Among male veteran twins, the heritability estimates were 69% for antisocial personality disorder, 56% for alcohol dependence, 50% for marijuana dependence, and 40% for major depression.

Cannabis use in the last year in a US national sample of twin and sibling pairs.

Kendler, K S · 2002

Twin and sibling resemblance for cannabis use in the past year was substantial.

Sex-Dependent Effects of MAOA Genotypes on the Relations Between Childhood Sexual Abuse, Aggression, and Cannabis Use in Emerging Adults.

Fite, Paula J · 2025

Among 498 emerging adults, males with the low-activity MAOA gene variant (MAOA-L) who experienced childhood sexual abuse and used cannabis reported using it specifically for coping at higher rates than other groups.

COMT Genetic Variants and BDNF Level Associations with Cannabinoid Plasma Exposure: A Preliminary Study.

Manca, Alessandra · 2025

The COMT 680 T>C genetic variant significantly influenced plasma levels of THC (p = 0.017).

Association of cannabinoid gene polymorphism with neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) in type 2 diabetes mellitus with chronic kidney disease.

Mohammed, Maryam Z · 2025

This study explored whether genetic variations in the cannabinoid receptor 1 (CNR1) gene—part of the endocannabinoid system—are associated with kidney damage in people with type 2 diabetes. The researchers genotyped 120 subjects divided into three groups: 40 diabetic patients with chronic kidney disease (CKD), 40 diabetic patients without CKD, and 40 healthy controls.

Association of Cannabinoid CB2 Receptor Q63R Variant With Rheumatoid Arthritis in an Iranian Cohort.

Nateghi, Ali · 2025

Logistic regression revealed significant associations between the Q63R polymorphism in the CNR2 gene and rheumatoid arthritis under codominant, dominant, and additive inheritance models.

Genetic characterization of the endocannabinoid system and psychiatric features in patients with migraine and medication overuse headache.

Romozzi, Marina · 2025

FAAH (fatty acid amide hydrolase), the enzyme that breaks down the endocannabinoid anandamide, showed significantly lower gene expression in medication overuse headache (MOH) patients compared to episodic migraine (EM) patients.

Genetic Insights into Cannabis-induced Psychosis: Role of CNR1 Gene Mutation (rs1049353) and Implications- A Cross-sectional Study.

Sahoo, Sujata · 2025

Not everyone who uses cannabis develops psychosis, and not everyone with schizophrenia has used cannabis.

Hypothesized pharmacogenomic and medication influences on tetrahydrocannabinol and cannabidiol metabolism in a cohort of unselected oral cannabis users.

Wright, Jessica A · 2025

Why do two people taking the same cannabis product at the same dose sometimes have dramatically different responses? This study points to genetics as a major factor. The researchers reviewed charts of 71 patients who had both pharmacogenomic testing and reported oral cannabis use.

Epigenetic effects of cannabis: A systematic scoping review of behavioral and emotional symptoms associated with cannabis use and exocannabinoid exposure.

Machado, Ana Sofia · 2024

Across 37 included studies, cannabis exposure was most consistently associated with global hypomethylation and changes at specific genes related to dopamine signaling (DRD2, COMT), cellular function (AKT1, STAT3), and neural development (NCAM1, DLGAP2).

Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis.

Bortoletto, Riccardo · 2022

Cannabis exposure in autistic individuals may exert disruptive epigenetic effects on brain regions critical to schizophrenia pathophysiology.

Regulation of DNA Methylation by Cannabidiol and Its Implications for Psychiatry: New Insights from In Vivo and In Silico Models.

Domingos, Luana B · 2022

CBD appears to regulate DNA methylation both directly, by binding to methylation enzymes (DNMTs), and indirectly, through neurotransmitter-mediated signaling pathways.

Cannabis significantly alters DNA methylation of the human ovarian follicle in a concentration-dependent manner.

Fuchs Weizman, Noga · 2022

Among 14 matched case-control patients, cannabis-exposed ovarian follicle cells showed 3,679 differentially methylated DNA sites, with two-thirds affecting coding genes.

The Cannabis-Induced Epigenetic Regulation of Genes Associated with Major Depressive Disorder.

Mohammad, Guldar Sayed · 2022

Cross-referencing cannabis methylation studies with the largest depression GWAS revealed that multiple depression-associated genes are epigenetically regulated by cannabis exposure.

Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation.

Russo, Ethan B · 2022

CHS patients showed significantly elevated mutations in COMT (OR 12.0), ABCA1 (OR 8.4), CYP2C9 (OR 7.8), DRD2 (OR 6.2), and TRPV1 (OR 5.8) compared to cannabis-using controls without CHS.

Cannabis alters DNA methylation at maternally imprinted and autism candidate genes in spermatogenic cells.

Schrott, Rose · 2022

In an in vitro human spermatogenesis model, cannabis exposure significantly altered DNA methylation at maternally imprinted genes (SGCE, GRB10, PEG3) and autism candidate genes (HCN1, NR4A2) in spermatogonial stem cell-like and spermatid-like cells..

Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring.

Schrott, Rose · 2022

Cannabis extract exposure caused 3,321 differentially methylated sites in rat sperm, some of which persisted after a washout period.

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

Smith, Robert C · 2022

The 13.4% THC group showed significantly increased CB2 and DNMT3A mRNA levels at 4 hours post-smoking compared to placebo.

DNA methylation changes associated with cannabis use and verbal learning performance in adolescents: an exploratory whole genome methylation study.

Wiedmann, Melina · 2022

Six CpG methylation sites showed reduced methylation associated with the extent of chronic cannabis use.

Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions.

Zuo, Yanning · 2022

THC-treated mice showed memory and social behavior changes in late adolescence.

Epigenetic Mediation of AKT1 rs1130233's Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing.

Blest-Hopley, Grace · 2021

The number of A alleles at AKT1 rs1130233 and methylation percentage at the CpG11-12 site independently predicted greater THC effects on parahippocampal/amygdala activation during fear processing.

Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences.

Clark, Shaunna L · 2021

45 significant methylation sites were identified in whole blood, plus 32 additional in cell-type analyses.

Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts.

Elkrief, Laurent · 2021

Two SNPs were significantly associated with positive AUDIT screens after correction: rs9353525 in CNR1 (OR=0.73) and rs507961 in MGLL (OR=0.78).

Adolescent cannabinoid exposure modulates the vulnerability to cocaine-induced conditioned place preference and DNMT3a expression in the prefrontal cortex in Swiss mice.

Gobira, P H · 2021

Adolescent WIN55,212-2 exposure did not alter anxiety or depression in adulthood.

Reelin deficiency contributes to long-term behavioral abnormalities induced by chronic adolescent exposure to Δ9-tetrahydrocannabinol in mice.

Iemolo, Attilio · 2021

Heterozygous Reeler mice (reduced Reelin) treated with THC during adolescence showed impaired social behaviors, elevated disinhibitory phenotypes, and increased stress reactivity compared to wild-type mice given the same THC treatment.

Differential Methylation Pattern of Schizophrenia Candidate Genes in Tetrahydrocannabinol-Consuming Treatment-Resistant Schizophrenic Patients Compared to Non-Consumer Patients and Healthy Controls.

Jahn, Kirsten · 2021

In the NRXN1 gene promoter, THC-consuming schizophrenia patients had nearly double the methylation rate compared to non-consuming patients.

Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.

Schrott, Rose · 2021

Whole-genome bisulfite sequencing identified 163 CpG sites with significantly altered DNA methylation in cannabis users' sperm, concentrated at genes involved in cardiogenesis and neurodevelopment, and many of these changes were reversed after one spermatogenic cycle (77 days) of abstinence..

Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice.

Wanner, Nicole M · 2021

F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory in a sex-specific manner.

Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug-Drug Interactions.

Brown, Joshua D · 2020

This review mapped out the pharmacological interactions between THC and other medications, revealing a more complex picture than most cannabis users — or their doctors — appreciate.

Endocannabinoid genetic variation enhances vulnerability to THC reward in adolescent female mice.

Burgdorf, Caitlin E · 2020

Adolescent female FAAHC/A mice (but not males) showed enhanced mesolimbic dopamine circuitry from VTA to nucleus accumbens, altered CB1 receptor levels at inhibitory and excitatory terminals in the VTA, and increased THC conditioned place preference that persisted into adulthood..

Paternal factors in neurodevelopmental toxicology: THC exposure of male rats causes long-lasting neurobehavioral effects in their offspring.

Holloway, Zade R · 2020

Offspring of THC-exposed fathers showed adolescent hyperactivity (at 2 mg/kg dose), faster decline in novel object interest (at 2 mg/kg), and delayed radial-arm maze learning (at 4 mg/kg).

Response to cannabidiol in epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations: An open-label, prospective, interventional study.

Poisson, Kelsey · 2020

Three patients with EIMFS secondary to KCNT1 mutations received pharmaceutical-grade CBD.

CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim.

Sales, Amanda J · 2020

CBD (10 mg/kg) produced antidepressant-like behavior in the forced swim test.

Subacute cannabidiol alters genome-wide DNA methylation in adult mouse hippocampus.

Wanner, Nicole M · 2020

CBD-treated mice had 3,323 differentially methylated loci with a slight skew toward global hypomethylation.

Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways.

Al-Ghezi, Zinah Zamil · 2019

THC+CBD combination (10 mg/kg each) attenuated experimental autoimmune encephalomyelitis in mice by reducing brain-infiltrating inflammatory T cells and pro-inflammatory molecules while increasing anti-inflammatory markers.

The epigenetic modulation of alcohol/ethanol and cannabis exposure/co-exposure during different stages.

Dobs, Yasminah Elsaadany · 2019

Both alcohol and cannabis independently modulate the epigenome through chromatin modification and remodeling, affecting gene activation and silencing.

Paternal activation of CB2 cannabinoid receptor impairs placental and embryonic growth via an epigenetic mechanism.

Innocenzi, Elisa · 2019

JWH-133 (CB2 agonist) exposure in male mice decreased sperm count, impaired placental development, and reduced offspring growth.

Adolescent Δ9-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic Vulnerability Converge on Nuclear Factor-κB-Cyclooxygenase-2 Signaling to Impair Memory in Adulthood.

Jouroukhin, Yan · 2019

Astrocyte-specific expression of DN-DISC1 combined with adolescent THC synergistically impaired recognition memory in adult mice.

Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring.

Levin, Edward D · 2019

Paternal THC exposure (2 mg/kg/day for 12 days) did not affect litter size, sex ratio, birth weight, or survival, but caused significant, long-lasting impairment in attentional performance and increased habituation of locomotor activity in adult offspring..

The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users.

Batalla, Albert · 2018

Researchers examined hippocampal brain structure in 59 young men aged 18-30, including 30 chronic cannabis users who started regular use before age 16 and 29 controls.

Gene variants and educational attainment in cannabis use: mediating role of DNA methylation.

Gerra, Maria Carla · 2018

Researchers compared genetic variants and DNA methylation patterns between 40 cannabis users and 96 control subjects. A variant in the CNR1 gene (which codes for the CB1 cannabinoid receptor) was significantly associated with cannabis use (p=0.01).

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

Kasten, Chelsea R · 2018

Researchers selectively bred mice for sensitivity or resistance to the locomotor effects of a single THC dose (10 mg/kg) during adolescence. THC-locomotor sensitivity proved to be moderately heritable, with the strongest heritability estimates seen in females from the F2 to S3 generations. An important correlated trait emerged: mice selected for THC-locomotor sensitivity also showed increased anxiety-like activity in the open field test, suggesting shared genetic factors between THC sensitivity and anxiety. This is the first demonstration that adolescent THC-locomotor sensitivity can be influenced through selective breeding, establishing a genetic basis for individual differences in cannabis response..

Developmentally Specific Associations Between CNR1 Genotype and Cannabis Use Across Emerging Adulthood.

Ashenhurst, James R · 2017

Using latent growth curve modeling across 10 waves of data from ages 18 to 24, one variant in the cannabinoid receptor gene CNR1 (rs806374) was significantly associated with cannabis use frequency.

The clinical impact of a positive family history of psychosis or mental illness in psychotic and non-psychotic mentally ill adolescents.

Paruk, Saeeda · 2017

Researchers compared 45 adolescents with first-episode early-onset psychosis (EOP) to 45 age- and gender-matched adolescents with non-psychotic mental illness.

Cannabinoid receptor 1 (CNR1) gene variant moderates neural index of cognitive disruption during nicotine withdrawal.

Evans, D E · 2016

Researchers tested whether genetic variation in the cannabinoid receptor 1 gene (CNR1) affected how much nicotine withdrawal disrupted cognitive function, as measured by resting brainwave (EEG) patterns. Seventy-three Caucasian smokers (15+ cigarettes/day) completed two lab sessions: one after smoking nicotine cigarettes and one after smoking placebo cigarettes following overnight deprivation.

Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

Ballinger, Michael D · 2015

Researchers studied mice carrying a mutation in the DISC1 gene (disrupted in schizophrenia 1) to test whether adolescent THC exposure interacts with genetic vulnerability to worsen adult brain function.

Strain dependence of adolescent Cannabis influence on heroin reward and mesolimbic dopamine transmission in adult Lewis and Fischer 344 rats.

Cadoni, Cristina · 2015

Researchers tested the "gateway hypothesis" by exposing adolescent rats of two genetically distinct strains (Lewis and Fischer 344) to THC and measuring heroin-related behaviors in adulthood.

Cold acclimation induces distinctive changes in the chromatin state and transcript levels of COR genes in Cannabis sativa varieties with contrasting cold acclimation capacities.

Mayer, Boris F · 2015

Researchers tested nine Cannabis sativa varieties for their ability to survive freezing after a cold acclimation period.

Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure.

Watson, Corey T · 2015

Researchers examined whether THC exposure during adolescence could produce epigenetic changes that pass to the next generation.

Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring.

Zumbrun, Elizabeth E · 2015

This review examined evidence from animal studies on how prenatal exposure to cannabinoids affects the developing immune system and whether those effects persist into adulthood or pass to future generations. Animal models showed that in-utero cannabinoid exposure resulted in significant T cell dysfunction and weakened immune responses to viral antigens in offspring.

Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation.

Szutorisz, Henrietta · 2014

Adult offspring of rats exposed to THC during adolescence displayed multiple abnormalities despite having no direct THC exposure.

St8sia2 deficiency plus juvenile cannabis exposure in mice synergistically affect higher cognition in adulthood.

Tantra, Martesa · 2014

Juvenile THC treatment (7 mg/kg every other day for 3 weeks) had no appreciable effect on cognition in normal (wildtype) mice.

Catechol-O-methyltransferase gene methylation and substance use in adolescents: the TRAILS study.

van der Knaap, L J · 2014

In 463 adolescents (mean age 16), methylation of the membrane-bound COMT (MB-COMT) promoter was associated with non-daily smoking (OR=1.82, p=0.03), but not with daily smoking or alcohol use. A gene-epigenetic interaction was found for cannabis use: adolescents with the Met/Met genotype (associated with higher dopamine levels) and high MB-COMT promoter methylation were less likely to be high-frequency cannabis users compared to those with Val/Val or Val/Met genotypes.

Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring.

Euser, Anja S · 2013

Researchers compared error-processing brain activity (ERN) between 28 high-risk adolescents (children of parents with substance use disorders) and 40 normal-risk controls during a flanker task.

A preliminary examination of how serotonergic polymorphisms influence brain response following an adolescent cannabis intervention.

Feldstein Ewing, Sarah W · 2012

This preliminary study examined whether genetic variations in the serotonin system moderated brain responses to psychosocial treatment for adolescent cannabis use disorders.

Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability.

Tomasiewicz, Hilarie C · 2012

Researchers demonstrated a direct causal chain linking adolescent THC exposure to adult heroin vulnerability.

A genome-wide association study of DSM-IV cannabis dependence.

Agrawal, Arpana · 2011

Researchers conducted the first genome-wide association study (GWAS) specifically targeting DSM-IV cannabis dependence.

Association between a cannabinoid receptor gene (CNR1) polymorphism and cannabinoid-induced alterations of the auditory event-related P300 potential.

Stadelmann, Andreas M · 2011

Twenty healthy volunteers received oral THC, cannabis extract (THC + CBD), or placebo in a controlled study.

Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues.

Filbey, Francesca M · 2010

Thirty-seven regular marijuana users who had been abstinent for 3 days underwent fMRI while exposed to marijuana cues.

Catechol-O-Methyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications.

Pelayo-Terán, José María · 2010

Researchers examined 169 patients with first-episode schizophrenia spectrum disorders, looking at how the COMT gene (which regulates dopamine) interacted with cannabis use to affect when psychosis first appeared. Cannabis users had significantly earlier onset of psychosis compared to non-users.

Genetic influences for distinct impulsivity domains are differentially associated with early substance use initiation: Results from the ABCD Study.

Kinstler, Ethan · 2025

Among 4,808 adolescents in the ABCD Study, sensation-seeking polygenic scores significantly predicted any substance use initiation (OR > 1.10) and alcohol use initiation by age 15.

The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies.

Austin-Zimmerman, Isabelle · 2024

In the EU-GEI study, daily use of high-potency cannabis had OR 5.09 (95% CI 3.08-8.43) for psychotic disorder even after adjusting for schizophrenia polygenic risk score (PRS).

Cannabinoid hyperemesis syndrome: genetic susceptibility to toxic exposure.

Russo, Ethan B · 2024

Five genetic mutations distinguish CHS patients from asymptomatic heavy cannabis users: mutations in TRPV1 receptor, two dopamine genes, the CYP2C9 enzyme (which metabolizes THC), and the ATP-binding cassette transporter.

Common liability to addiction and "gateway hypothesis": theoretical, empirical and evolutionary perspective

Vanyukov MM · 2012

The gateway hypothesis is unfalsifiable, empirically contradicted by variable international drug sequencing patterns, and unsupported by genetics.

Escalation of drug use in early-onset cannabis users vs co-twin controls

Lynskey MT · 2003

In 311 Australian twin pairs discordant for early cannabis use, the twin who used cannabis before age 17 was 2.1-5.2 times more likely to subsequently use other illicit drugs and develop drug dependence, even after controlling for shared genetics, environment, and established risk factors.