Christian D. Schubart

Cannabis with high cannabidiol content is associated with fewer psychotic experiences

OBJECTIVE Cannabis is associated with psychotic outcomes in numerous studies, an effect that is commonly attributed to Δ (9)-tetrahydrocannabinol (Δ 9-THC). An increasing number of authors identify cannabidiol, another component of the cannabis plant, as an antipsychotic agent. The objective of the current study is to investigate the role of cannabidiol content in the association between cannabis use and psychiatric symptoms in a large non-clinical population of cannabis users. METHODS In a web-based cross-sectional study we obtained detailed information about cannabis use and subclinical psychiatric experiences using the Community Assessment of Psychic Experiences (CAPE). Different types of cannabis (i.e. marijuana, hashish etc.) have distinctive proportions of Δ 9-THC and cannabidiol. Since average concentrations of Δ 9-THC and cannabidiol in the most popular types of cannabis sold on the Dutch market are annually measured, we were able to estimate exposure to Δ 9-THC and cannabidiol. RESULTS We included 1877 subjects (mean age 23, SD 6.0) who used the same type of cannabis in the majority of the occasions (in >60% of occasions). We found a significant inverse relationship (F(1,1877): 14.577, p<0.001) between cannabidiol content and self-reported positive symptoms, but not with negative symptoms or depression. The estimated effect size of cannabidiol content was small. CONCLUSION Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol.

Cannabis use at a young age is associated with psychotic experiences

BACKGROUND Cannabis use is associated with psychosis and a range of subclinical psychiatric symptoms. The strength of this association depends on dosage and age at first use. The current study investigates whether level of cannabis exposure and starting age are associated with specific profiles of subclinical symptoms. METHOD We collected cross-sectional data from a young adult population sample by administering an online version of the Community Assessment of Psychic Experiences (CAPE). Cannabis exposure was quantified as the amount of Euros spent on cannabis per week and the age of initial cannabis use. The primary outcome measure was the odds ratio (OR) to belong to the highest 10% of scores on the total CAPE and the positive-, negative- and depressive symptom dimensions. RESULTS In 17 698 adolescents (mean age 21.6, s.d.=4.2 years), cannabis use at age 12 years or younger was strongly associated with a top 10% score on psychotic experiences [OR 3.1, 95% confidence interval (CI) 2.1-4.3] and to a lesser degree with negative symptoms (OR 1.7, 95% CI 1.1-2.5). The OR of heavy users (>€25/week) for negative symptoms was 3.4 (95% CI 2.9-4.1), for psychotic experiences 3.0 (95% CI 2.4-3.6), and for depressive symptoms 2.8 (95% CI 2.3-3.3). CONCLUSIONS Early start of cannabis use is strongly associated with subclinical psychotic symptoms and to a lesser degree with negative symptoms, while smoking high amounts of cannabis is associated with increased levels of all three symptom dimensions: psychotic, negative and depressive. These results support the hypothesis that the impact of cannabis use is age specific.

The effect of childhood maltreatment and cannabis use on adult psychotic symptoms is modified by the COMT Val158Met polymorphism

BACKGROUND Cannabis use and childhood maltreatment are independent risk factors for the development of psychotic symptoms. These factors have been found to interact in some but not all studies. One of the reasons may be that childhood maltreatment and cannabis primarily induce psychotic symptoms in genetically susceptible individuals. In this context, an extensively studied psychosis vulnerability gene is catechol-methyl-transferase (COMT). Therefore, we aimed to examine whether the COMT Val(158)Met polymorphism (rs4680) moderates the interaction between childhood maltreatment and cannabis use on psychotic symptoms in the general population. METHOD The discovery sample consisted of 918 individuals from a cross-sectional study. For replication we used an independent sample of 339 individuals from the general population. RESULTS A significant three-way interaction was found between childhood maltreatment, cannabis use, and the COMT genotype (rs4680) in the discovery sample (P=0.006). Val-homozygous individuals displayed increased psychotic experiences after exposure to both cannabis use and childhood maltreatment compared to Met-heterozygous and Met-homozygous individuals. Supportive evidence was found in the replication sample with similar effect and direction even though the results did not reach statistical significance (P=0.25). CONCLUSIONS These findings suggest that a functional polymorphism in the COMT gene may moderate the interaction between childhood maltreatment and cannabis use on psychotic experiences in the general population. In conclusion, the COMT Val(158)Met polymorphism may constitute a genetic risk factor for psychotic symptoms in the context of combined exposure to childhood maltreatment and cannabis use.

Cigarette smoking and cannabis use are equally strongly associated with psychotic-like experiences: a cross-sectional study in 1929 young adults.

BACKGROUND Cannabis use is associated with increased risk for psychotic-like experiences (PLEs) and psychotic disorders. It remains unclear whether this relationship is causal or due to confounding. METHOD A total of 1929 young adults aged 18-30 years participated in a nationwide internet-based survey in The Netherlands and gave information on demographics, substance use and parental psychiatric illness and completed the Community Assessment of Psychic Experiences (CAPE). RESULTS Cigarette smoking and cannabis use were equally strongly associated with the frequency of PLEs in a fully adjusted model (β = 0.098 and 0.079 respectively, p < 0.05). Cannabis use was associated with distress from PLEs in a model adjusted for an elaborate set of confounders excluding smoking (β = 0.082, p < 0.05). However, when cigarette smoking was included in the model, cannabis use was not a significant predictor of distress from PLEs. Cigarette smoking remained associated with distress from PLEs in a fully adjusted model (β = 0.107, p < 0.001). CONCLUSIONS Smoking is an equally strong independent predictor of frequency of PLEs as monthly cannabis use. Our results suggest that the association between moderate cannabis use and PLEs is confounded by cigarette smoking.

Cannabis use as an indicator of risk for mental health problems in adolescents: a population-based study at secondary schools

BACKGROUND Although the association between cannabis use and a wide range of psychiatric symptoms is fairly well established, it is not clear whether cannabis use is also a risk factor for general mental health problems at secondary school. Method A total of 10 324 secondary school children aged 11-16 years, participating in an ongoing Public Health Service School Survey, gave information on demographics, substance use, school factors and stressful life events and completed the Strengths and Difficulties Questionnaire (SDQ). RESULTS Cannabis use in the past month was associated with a clinically relevant score on the SDQ [unadjusted odds ratio (OR) 4.46, 95% confidence interval (CI) 3.46-5.76]. Other risk factors associated with poor psychosocial functioning were: a low level of education, alcohol use, cigarette smoking, hard drug use, frequent truancy, an unfavourable school evaluation, feeling unsafe at school, being victimized, frequent absence due to illness, a mentally ill parent, molestation by a parent, financial problems and feeling distressed by an adverse event. In a full model adjusting for these risk factors, cannabis was not significantly associated with mental health problems, although an association at trend level was apparent. Of these risk factors, regular alcohol use, cigarette smoking, hard drug use, frequent truancy, an unfavourable school evaluation and frequent absence due to illness were also associated with cannabis use. CONCLUSIONS The association between cannabis use and poor psychosocial functioning in adolescence is due, at least in part, to confounding by other risk factors. Thus, cannabis use can best be viewed as an indicator of risk for mental health problems in adolescence.

Association between cannabis and psychiatric hospitalization

Schubart CD, Boks MPM, Breetvelt EJ, van Gastel WA, Groenwold RHH, Ophoff RA, Sommer IEC, Kahn RS. Association between cannabis and psychiatric hospitalization.

Change in cannabis use in the general population: A longitudinal study on the impact on psychotic experiences

OBJECTIVE To prospectively assess the relationship between cannabis use and psychotic experiences over time. METHOD In a longitudinal design, young adults aged 18-27years (N=705) gave online information on cannabis use and completed the Community Assessment of Psychic Experiences (CAPE). These measures were repeated after an interval ranging from six months to five years. RESULTS A decrease in cannabis use was associated with a decrease in total psychotic experiences (β=-0.096, p=0.01) after adjustment for a range of potential confounders. An increase in cannabis use was associated with increased positive symptoms at follow-up (β=0.07, p=0.02), but was not significantly associated with increases in Negative and Depression symptom scores, nor with the total number of psychotic experiences. CONCLUSION In the first study to the association of change in cannabis use and psychotic experiences over time in the general population, we found an association between changes in cannabis use and changes in the frequency of psychotic experiences. While this does not prove a causal relationship between cannabis use and psychosis, our findings are consistent with studies suggesting that cessation of cannabis use may be beneficial in terms of reducing psychotic experiences.

Advanced paternal age and vulnerability to psychotic-like experiences in the offspring

OBJECTIVE To investigate whether advanced paternal age is associated with increased psychotic-like experiences (PLEs) and increased sensitivity to Cannabis in the offspring. METHODS A cross-sectional population-based study in 1684 participants aged 18 to 25. RESULTS We found no association of paternal age with PLEs. Only the positive dimension subscale was associated to paternal age, but that could be largely contributed to outliers. Also no increased sensitivity to Cannabis smoking was apparent. CONCLUSION In the general population, we did not find robust support for an association between paternal age and vulnerability to PLEs in 18-25year old offspring.