This cohort study uses Danish national registry data to examine associations between parental psychiatric disease and risks of attempted suicide and violent offending among offspring.
This cohort study examines the precise nature of the association between continued cannabis use after the onset of psychosis and risk of relapse of psychosis.
This longitudinal study examines the association of long-term marijuana use in young adults with the response of the nucleus accumbens to award anticipation.
This 38-year longitudinal study of a representative birth cohort (the Dunedin Multidisciplinary Health and Development Study of New Zealand) tests associations between cannabis use over 20 years and a variety of physical health indexes at early midlife.
This genome-wide association study assesses analyses from 3 studies of substance use disorder genetics to identify DSM-IV criteria for cannabis dependence in a large African American and European American cohort.
This cohort study uses national survey data to examine associations between cannabis use and risk of mental health and substance use disorders in the general US adult population.
This review article summarizes what is known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis.
This study compares prevalence and trends in marijuana use and marijuana use disorder from the National Epidemiologic Survey of Alcohol and Related Conditions with those from the National Survey on Drug Use and Health.
This cross-sectional study using a sample of twins/siblings reports that differences in amygdala volume in cannabis users are attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences of cannabis use.
This observational study investigates whether cannabis use during early adolescence is associated with variations in male brain maturation as a function of genetic risk for schizophrenia in 3 samples of adolescents who underwent magnetic resonance imaging and risk evaluation.
Allsop et al evaluate the safety and efficacy of nabiximols treating cannabis withdrawal with use of a 6-day regimen of nabiximols or placebo with standardized psychosocial interventions during a 9-day admission.
A number of studies have found that the use of cannabis and other psychoactive substances is associated with an earlier onset of psychotic illness.
To establish the extent to which use of cannabis, alcohol, and other psychoactive substances affects the age at onset of psychosis by meta-analysis.
Peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non–substance-using groups were located using searches of CINAHL, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science.
Studies in English comparing the age at onset of psychosis in cohorts of patients who use substances with age at onset of psychosis in non–substance-using patients. The searches yielded 443 articles, from which 83 studies met the inclusion criteria.
Information on study design, study population, and effect size were extracted independently by 2 of us.
Meta-analysis found that the age at onset of psychosis for cannabis users was 2.70 years younger (standardized mean difference = −0.414) than for nonusers; for those with broadly defined substance use, the age at onset of psychosis was 2.00 years younger (standardized mean difference = −0.315) than for nonusers. Alcohol use was not associated with a significantly earlier age at onset of psychosis. Differences in the proportion of cannabis users in the substance-using group made a significant contribution to the heterogeneity in the effect sizes between studies, confirming an association between cannabis use and earlier mean age at onset of psychotic illness.
The results of meta-analysis provide evidence for a relationship between cannabis use and earlier onset of psychotic illness, and they support the hypothesis that cannabis use plays a causal role in the development of psychosis in some patients. The results suggest the need for renewed warnings about the potentially harmful effects of cannabis.
Individual differences in cannabis sensitivity may be associated with genetic risk for psychotic disorder.
To demonstrate and replicate, using 2 conceptually different genetic epidemiological designs, that (familial) liability to psychosis is associated with sensitivity to cannabis.
Sibling-control and cross-sibling comparisons using samples of patients with a psychotic disorder (n = 1120), their siblings (n = 1057), and community controls (n = 590) in the Netherlands and Flanders.
Positive and negative schizotypy using the Structured Interview for Schizotypy–Revised (for siblings and controls) and self-reported positive and negative psychotic experiences using the Community Assessment of Psychic Experiences (for siblings and patients). Cannabis use was assessed as current use (by urinalysis) and lifetime frequency of use (by Composite International Diagnostic Interview).
In the sibling-control comparison, siblings displayed more than 15 times greater sensitivity to positive schizotypy associated with particularly current cannabis use by urinalysis (adjusted B = 0.197, P < .001) than controls (adjusted B = 0.013, P = .86) (P interaction = .04) and a similar difference in sensitivity to its effect on negative schizotypy (siblings: adjusted B = 0.120, P < .001; controls: B = −0.008, P = .87; P interaction = .03). Similarly, siblings exposed to cannabis resembled their patient relative nearly 10 times more closely in the positive psychotic dimension of the Community Assessment of Psychic Experiences (adjusted B = 0.278, P < .001) compared with nonexposed siblings (adjusted B = 0.025, P = .12) (P interaction < .001). No significant effect was apparent for the Community Assessment of Psychic Experiences negative domain, although the association was directionally similar (2 times more resemblance; P interaction = .17). Cross-sibling, cross-trait analyses suggested that the mechanism underlying these findings was moderation (familial risk increasing sensitivity to cannabis) rather than mediation (familial risk increasing use of cannabis).
Genetic risk for psychotic disorder may be expressed in part as sensitivity to the psychotomimetic effect of cannabis. Cannabis use may synergistically combine with preexisting psychosis liability to cause positive and negative symptoms of psychosis.
Individual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive.
To investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use.
Interactions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with psychosis to examine genetic moderation of the association between Structured Interview for Schizotypy–Revised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder.
The Netherlands and Flanders, Belgium.
Eight hundred one patients with psychosis and their 740 unaffected siblings.
Significant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, case-sibling, and case-control analyses.
In the unaffected siblings, 16 SNPs in 12 genes showed significant interaction at P < .05, 3 of which survived correction for multiple testing (P < .0003), situated in AKT1 (rs2494732 and rs1130233) and LRRTM1 (rs673871). Follow-up analysis supported AKT1 rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis. In the unaffected siblings, the AKT1 × cannabis interaction explained 2.2% additional variance in schizotypy in the whole sample and 19.0% additional variance in the exposed siblings with recent cannabis use.
Genetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D2 receptor.