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Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta\u20109\u2010tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within\u2010subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20\u2009mg, administered as dronabinol) or placebo, during three separate 5\u2010h test sessions. Measures of experimental and self\u2010reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed\u2010effects models examined the main effects of THC dose and interactions between THC (10 and 20\u2009mg) and methadone doses (low\u2010dose methadone defined as &lt;90\u2009mg\/day; high dose defined as &gt;90\u2009mg\/day). Results demonstrated that, for self\u2010reported rather than experimental pain sensitivity measures, 10\u00a0mg THC provided greater relief than 20\u2009mg THC, with no substantial evidence of abuse potential, and inconsistent dose\u2010dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk\u2013benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.<\/jats:p>","DOI":"10.1111\/adb.13317","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T06:08:50Z","timestamp":1690783730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Delta\u20109\u2010tetrahydrocannabinol\u00a0modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within\u2010subject, randomized, placebo\u2010controlled laboratory study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7357-8215","authenticated-orcid":false,"given":"Joao P.","family":"De Aquino","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale 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