Citation

Martin EL, Baker NL, Sempio C, Christians U, Klawitter J, McRae-Clark AL. Addict. Biol. 2023; 28(10): e13337.

Copyright

(Copyright © 2023, John Wiley and Sons)

DOI

10.1111/adb.13337

PMID

37753564

Abstract

Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate-to-severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in-person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N-arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [β = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [β = 0.22 (SE = 0.13)] and 2-arachidonoylglycerol (2-AG) [β = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB-based interventions may produce differential effects by sex.

Language: en

Keywords

Adult; Humans; Female; Male; Pilot Projects; sex differences; *Cannabis; *Marijuana Abuse; *Substance Withdrawal Syndrome; *Substance-Related Disorders; Caffeine; Cannabinoid Receptor Agonists; cannabis use disorder; endocannabinoid; Endocannabinoids; Sex Characteristics; withdrawal