Mu opioid receptor gene variant modulates subjective response to smoked cannabis

Zoe Bourgault; Justin Matheson; Robert E Mann; Bruna Brands; Christine M Wickens; Arun K Tiwari; Clement C Zai; James Kennedy; Bernard Le Foll

Mu opioid receptor gene variant modulates subjective response to smoked cannabis

Am J Transl Res. 2022 Jan 15;14(1):623-632. eCollection 2022.

Authors

Zoe Bourgault^{1

2}, Justin Matheson¹, Robert E Mann^{3

4

5}, Bruna Brands^{2

3

6}, Christine M Wickens^{2

3

4

5

7}, Arun K Tiwari^{8

9}, Clement C Zai^{8

9

10

11

12

13}, James Kennedy^{8

9

10}, Bernard Le Foll^{1

2

4

9

10

14

15}

Affiliations

¹ Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto 33 Ursula Franklin Street, Toronto, ON, Canada.
² Department of Pharmacology and Toxicology, University of Toronto Toronto, ON, Canada.
³ Institute for Mental Health Policy Research, Centre for Addiction and Mental Health Toronto, Canada.
⁴ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health Toronto, Ontario, Canada.
⁵ Dalla Lana School of Public Health, University of Toronto Toronto, Ontario, Canada.
⁶ Controlled Substances and Cannabis Directorate, Health Canada Ottawa, Canada.
⁷ Institute of Health Policy, Management and Evaluation, University of Toronto Toronto, Ontario, Canada.
⁸ Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute CAMH, Toronto, ON, Canada.
⁹ Department of Psychiatry, University of Toronto Toronto, ON, Canada.
¹⁰ Institute of Medical Science, University of Toronto Toronto, ON, Canada.
¹¹ Laboratory Medicine and Pathobiology, University of Toronto ON, Canada.
¹² T.H. Chan School of Public Health, Harvard University Boston, MA, USA.
¹³ Broad Institute Cambridge, MA, USA.
¹⁴ Acute Care Program, Centre for Addiction and Mental Health Toronto, ON, Canada.
¹⁵ Department of Family and Community Medicine, University of Toronto Toronto, ON, Canada.

PMID: 35173880
PMCID: PMC8829626

Abstract

The mu-opioid receptor (MOR) mediates the rewarding properties of many psychoactive drugs and is an important target in the treatment of addictions. Functional interactions between the opioid and endocannabinoid systems are established and have been hypothesized to contribute to the effects of cannabis. We investigated associations between three single nucleotide polymorphisms in the MOR gene OPRM1 (rs1799971, rs2281617, and rs510769) and subjective responses to smoked cannabis. Fifty-two regular cannabis users (1-4 days/week) were given a cannabis cigarette (12.5% THC) and rated their subjective responses on visual analog scales at baseline and at multiple time points after smoking. Blood samples were collected for THC quantification. There was a significant impact of the intronic variant rs510769 on subjective cannabis effects and THC blood levels. The influence of this gene variant may thus be mediated by pharmacodynamics and/or pharmacokinetic factors. We provide novel evidence that variability in OPRM1 contributes to individual responses to cannabis and may affect risk of cannabis use disorder. Our findings add to the growing body of literature on the genetic basis of individual responses to cannabis and may have implications for targeting the endogenous opioid system in the treatment of cannabis use disorder.

Keywords: Cannabis; genetics; mu opioid receptor; subjective effects.