How might genetic variation contribute to different responses to medical cannabis?

Hryhorowicz S, Walcsak M, Zakerska-Banaszak O, Slomski R, Skrzypczak-Zielinska M. Pharmacogenetics of cannabinoids. Eur J Drug Metab Pharmacokinet 2018;43:1-2

Why was this study conducted?

Although there is growing interest in the use of cannabis to treat a number of medical conditions, different people can respond quite differently to it.  To date there is no means of determining who will benefit from cannabis or experience unwanted adverse effects such as cannabis use disorder or psychotic symptoms. In this article, the authors report on the research literature on genetic mutations that may be involved in how people react to cannabis.

What does this study add?

The authors reviewed the research on the effect of different mutations involved in the metabolism and effects of cannabis.  These mutations fell into four categories:

• cannabis receptor genes that enable cannabinoids to attach to cells or affect other aspects of neurotransmission (CNR1, CNR2, Trpv1, Gpr55, OPRM1 and GABRA2)
• transport and action genes (ABCB1, ABCG2, SLC6A4, and COMT), which affect the movement of substances in and out of cells and their action within the cells
• cannabinoid metabolism genes (CYPs and UGTs genes), that govern how cannabinoids are broken down by the body
• endocannabinoids biosynthesis and bioactivation genes associated with anadamide (AEA) and 2-arachidonoylglycerol (2-AG) (FAAH, MAGL, ABHD6, ABHD12, COX2, MAPK14, and NGR1), genes associated with the body’s natural endocannabinoid system.

Empirical evidence for systematic differences in reactions to cannabis based on variation in these genes remains at very early stages.

What does this study add?

Molecular genetic research suggests that genetic variation may affect the likelihood that people will have a positive or negative reaction to cannabis. This research is still in its early stages; in the future it may be possible to use genetic markers to personalize and optimize cannabinoid treatments.

Is there anything else I should know?

Currently, information on how genetic mutations affect the reaction to cannabis is in its early stages. Genetic mutations are not “on/off” switches but may be associated with difference in the likelihood of outcomes such as cannabis or substance abuse or psychotic symptoms. More research is needed to further our understanding of how various gene mutations act – both individually and in concert with other genes – to influence a person’s reaction to cannabis. This pertains to both medical and non-medical use.