I reviewed a research study last fall examining a Dutch study of cannabis use and psychotic symptoms. That post is linked here. In summary, the study suggested cannabis probably does not produce psychotic symptoms in the majority of users. However, if you have a family member with a psychotic disorder (suggesting you may have a genetic risk for psychosis) you may be more likely to experience psychotic symptoms (i.e. hallucinations/delusions) with cannabis use. This risk may be increased with higher potency cannabis formulations.
Now two additional research publications weigh in on this issue. Both were published in the February 2011 issue of Archives of General Psychiatry. Both studies come from the Genetic Risk and Outcome of Psychosis (GROUP) study sample.
The first manuscript summarized the results of study using a sibling-control and cross-sibling comparison. Eleven hundred twenty subjects with a psychotic disorder were compared to 1057 siblings and 590 controls. In summary the results of this study were:
- You were much more likely to report psychotic symptoms (both positive and negative psychotic symptoms) with cannabis use if you had a sibling with psychosis
- Siblings using cannabis resembled psychotic siblings in their ratings much more than siblings not using cannabis
- The statistical analysis of the relationship pointed to a familial risk increasing cannabis sensitivity, rather than familial risk increasing use of cannabis
So this finding in in line with the original study. Families may resemble each other in the way they respond to cannabis. Some families may be particularly more likely to have psychotic symptoms in the context of cannabis use.
The second study takes another step to try to explain this relationship. Can candidate genes be identified that are linked to this cannabis-linked psychosis effect? If so, do these genes make biological sense or do they seem to just likely be random associations.
The answers proposed by the GROUP investigators are intriguing.
- Sixteen single nucleotide proteins (SNPs) showed significant interactions
- The AKT1 gene status (C/C genotype) increased risk of psychosis after cannabis use
- AKT1 gene status explained 19% of the variance of psychotic symptoms in siblings with recent cannabis use
- The AKT1 gene is regulated by endogenous cannabanoid signaling
- This signal is downstream from the dopamine D2 receptor--a receptor known to be involving in psychosis and the target of antipsychotic drugs
The authors note that their proposed mechanism explains two commonly clinical findings:
- antipsychotic drugs do not block the psychotic effect of THC in those that experience psychosis with the drug
- substance abusing patients with schizophrenia respond more poorly to antipsychotic treatment
The explanation would be the endocannabanoid AKT1 effect is downstream from the D2 receptor. Blocking the D2 receptor would have limited effects downstream from the receptor.
These two studies add to support for a role for cannabis to be a potential risk factor for some forms of psychosis and schizophrenia. The genetic and molecular correlations in this study a mutually supportive. So the take home message seems to be the same--there just seems to be more support the message is research based. Some individuals may have a genetic risk for psychotic symptoms related to cannabis use. This is not a trivial risk. If you have a sibling or other relative with psychosis, or if you experience psychotic symptoms with cannabis use, don't use cannabis.
Photo of Back Yard Blue Jay in Tulsa after Snowfall Courtesy of Yates Photography
van Winkel, R., , ., Kahn, R., Linszen, D., van Os, J., Wiersma, D., Bruggeman, R., Cahn, W., de Haan, L., Krabbendam, L., & Myin-Germeys, I. (2010). Family-Based Analysis of Genetic Variation Underlying Psychosis-Inducing Effects of Cannabis: Sibling Analysis and Proband Follow-up Archives of General Psychiatry, 68 (2), 148-157 DOI: 10.1001/archgenpsychiatry.2010.152
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