Impact of cyclooxygenase‐2 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers. (25th May 2022)

• Record Type: Journal Article
• Authors: Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D.; Herrmann, Evan S.; Reed, Stephanie Collins; Foltin, Richard W.; Kingsley, Philip J.; Marnett, Lawrence J.; Patel, Sachin
• Is Part Of: Addiction biology. Volume 27:Number 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-05-25
• Subjects: cannabis use disorder -- marijuana -- self‐administration; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.13183
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Attenuating enzymatic degradation of endocannabinoids (eCBs) by fatty acid amide hydrolase (FAAH) reduces cannabis withdrawal symptoms in preclinical and clinical studies. In mice, blocking cyclooxygenase‐2 (COX‐2) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo‐controlled study examined the effects of the FDA‐approved COX‐2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment‐seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11‐day study phases (separated by >14 days for medication clearance). In each phase, the effects of daily BID placebo (0 mg) or celecoxib (200 mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4 days of inactive cannabis self‐administration) and 'relapse' (3 days of active cannabis self‐administration following abstinence) were assessed. Outcome measures included mood, cannabis self‐administration, sleep, food intake, cognitive performance, tobacco cigarette use and circulating eCBs and related lipids. Under placebo maintenance, cannabis abstinence produced characteristic withdrawal symptoms (negative mood, anorexia and dreaming) relative to cannabis administration and was associated with increased OEA (a substrate of FAAH) and oleic acid (metabolite of OEA), with no change in eCB levels. Compared to placebo, celecoxib improved subjective (but not objective) measures of sleep and did not affect mood or plasma levels of eCBs or associated lipids and increased cannabis craving. The overall absence of effects on cannabis withdrawal symptoms, self‐administration or circulating eCBs relative to placebo, combined with an increase in cannabis craving, suggests celecoxib does not show promise as a potential pharmacotherapy for CUD. Abstract : Blocking cyclooxygenase‐2 (COX‐2) activity preclinically increases central endocannabinoid levels by inhibiting fatty acid degradation. This placebo‐controlled study examined the effects of the FDA‐approved COX‐2 selective inhibitor, celecoxib, on cannabis withdrawal, 'relapse', and circulating eCBs in a human laboratory model of cannabis use disorder. The results showed that celecoxib did not reduce cannabis withdrawal symptoms, cannabis self‐administration or affect circulating eCBs relative to placebo, suggesting celecoxib does not show promise as a potential pharmacotherapy for CUD.