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In mice, blocking cyclooxygenase\u20102 (COX\u20102) activity increases central eCB levels by inhibiting fatty acid degradation. This placebo\u2010controlled study examined the effects of the FDA\u2010approved COX\u20102 selective inhibitor, celecoxib, on cannabis withdrawal, \u2018relapse\u2019, and circulating eCBs in a human laboratory model of cannabis use disorder. Daily, nontreatment\u2010seeking cannabis smokers (12M, 3F) completed a crossover study comprising two 11\u2010day study phases (separated by &gt;14\u2009days for medication clearance). In each phase, the effects of daily BID placebo (0\u00a0mg) or celecoxib (200\u2009mg) on cannabis (5.3% THC) intoxication, withdrawal symptoms (4\u00a0days of inactive cannabis self\u2010administration) and \u2018relapse\u2019 (3\u00a0days of active cannabis self\u2010administration following abstinence) were assessed. Outcome measures included mood, cannabis self\u2010administration, 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\u2010administration 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.<\/jats:p>","DOI":"10.1111\/adb.13183","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T06:18:10Z","timestamp":1653545890000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of cyclooxygenase\u20102 inhibition on cannabis withdrawal and circulating endocannabinoids in daily cannabis smokers"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-9528","authenticated-orcid":false,"given":"Margaret","family":"Haney","sequence":"first","affiliation":[{"name":"New York State Psychiatric Institute  New York New York USA"},{"name":"Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6718-0099","authenticated-orcid":false,"given":"Gillinder","family":"Bedi","sequence":"additional","affiliation":[{"name":"Centre for Youth Mental Health The University of Melbourne and Substance Use Research Group, Orygen  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziva D.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Los Angeles Cannabis Research Initiative, Jane &amp; Terry Semel Institute for Neuroscience &amp; Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan S.","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Division of Therapeutics and Medical Consequences National Institute on Drug Abuse  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Collins","family":"Reed","sequence":"additional","affiliation":[{"name":"New York State Psychiatric Institute  New York New York USA"},{"name":"Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Foltin","sequence":"additional","affiliation":[{"name":"New York State Psychiatric Institute  New York New York USA"},{"name":"Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Kingsley","sequence":"additional","affiliation":[{"name":"A.B. 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