Although some die-hard believers in the medicinal benefits of marijuana will argue this truth to no end, plenty of evidence already exists showing cannabis can be addictive 1.
Now researchers have identified specific alleles on the human genome that are associated with cannabis dependence risk, and have shown “evidence of genetic overlap between cannabis dependence and schizophrenia and major depressive disorder,” according to a paper published online March 30 in JAMA Psychiatry 2.
Doctors from Yale University and the Veterans Affairs Connecticut Healthcare Center analyzed genetic molecular data from almost 15,000 study participants enrolled in three different substance dependence trials: The Yale-Penn Study, Study of Addiction: Genetics and Environment (SAGE), and International Consortium on the Genetics of Heroin Dependence. The research was led by biomedical genetics scientist Richard Sherva.
The subjects had been referred and recruited from their communities and substance abuse centers. The sample included 6,000 African American and 8,754 European American participants.
Study Builds on Previous Genetic Research
Previous research had shown that cannabis addiction could be inherited 3, and this study sought to determine whether those with inherited cannabis addiction also were afflicted with co-occurring inherited mental disorders, as often is the case with alcoholism.
“We were surprised to find a genetic risk overlap between cannabis dependence and major depression,” lead author Dr. Joel Gelernter, Foundations Fund professor of psychiatry at Yale, as well as a professor of genetics and neuroscience, said in a Yale News release. 4
According to the paper, cannabis dependence was “significantly associated with major depressive disorder in African American participants, but not schizophrenia, bipolar affective disorder, attention-deficit/hyperactivity disorder, or autism spectrum disorder. Cannabis disorder was not associated with any of these disorders in European American participants.”
The definition of cannabis disorder was based on the criteria used by DSM-IV, the diagnostic manual of mental health professionals.
Cannabis Dependence Ranged from 18 to 36 Percent
Overall, between 18 percent and 36 percent of the sample met the DSM criteria for cannabis dependence. Three regions were identified in the 1,000 genome reference panel that offered hints about the biology of cannabis dependence, including an inflammatory component, which has been linked to both depression and schizophrenia.
The other regions included a potential member of what is known as the drug/metabolite transporter superfamily and an area that includes growth cones of developing nervous system neurons called CSMDI.
Schizophrenia already has been associated with different variations on the CSMDI gene, and a link between cannabis use and schizophrenia (although not necessarily genetic) already has been established. “Thus, CSMDI is the second gene to be implicated in both disorders (the first was a gene called NRGI) and may explain at least part of their shared genetic susceptibility,” the authors wrote.
Accompanying Editorial Critical of Findings
An accompanying editorial printed alongside the JAMA article by James T.R. Walters and Michael J. Owen, scientists in Wales, was critical of the findings. “A related and relevant feature of the study by Sherva and colleagues is that it combines data from three studies, each of which recruited individuals principally on the basis of dependence to other substances (alcohol, nicotine and cocaine). Although there is genetic overlap between use of different substances, it remains to be seen whether the results in the samples studies will generalize to wider populations of cannabis users.” 5
Walters and Owens also argued that the discovery of a schizophrenia sample in the study was contradictory with previous studies. “It is important to resolve these uncertainties about the nature and degree of genetic overlap between cannabis use and schizophrenia given that this will inform debate about causation.”
Still, Sherva and colleagues believe their work is important in an era of increasing acceptance and decriminalization of marijuana use, which they say in their paper “is based on the erroneous perception that it is relatively harmless.”
They admit more research is necessary to build on their findings, but say such research is crucial as the push to increase the drug’s availability continues.
“These findings will lead our understanding of genetic vulnerability to cannabis dependence in new directions that can inform our understanding of the biology of cannabis dependence,” the authors concluded. “We obtained entirely novel evidence of genetic overlap between cannabis dependence and major depressive disorder and conclude that CSMDI may be a candidate gene that affects the risk for cannabis dependence and schizophrenia, a topic of considerable research interest. These results also suggest that common pathways (nervous system development, inflammation and ion homeostasis) mediate the risk for multiple psychiatric disorders and dependence on multiple substances, including cannabis.”
1.Weinstein, A., et al. Pharmacological treatment of cannabis dependence. Curr Pharm Des. 2011;17(14):1351-1358. Retrieved April 2, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/21524266
2.Sherva, R. et al. Genome-wide Association Study of Cannabis Dependence Severity, Novel Risk Variants, and Shared Genetic Risks. JAMA Psychiatry. 2016 (March 30). Retrieved April 2, 2016, from http://archpsyc.jamanetwork.com/article.aspx?articleid=2504223
3.Verweij, K., et al. Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies. Addiction. 2010;105(3):417-430. Retrieved April 2, 2016, from http://www.ncbi.nlm.nih.gov/pubmed/20402985
4.Hathaway, B. Study links gene to marijuana use and major depression. Yale News. 2016 (March 30). Retrieved April 2, 2016, from http://news.yale.edu/2016/03/30/study-links-genes-marijuana-dependence-and-major-depression
5.Walters, J. et al. Genome-wide Significant Associations for Cannabis Dependence Severity. JAMA Psychiatry. 2016 (March 30). Retrieved April 2, 2016, from http://archpsyc.jamanetwork.com/article.aspx?articleid=2504221
Wriiten by David Heitz