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This study tested the potential efficacy and tolerability of a daily bedtime administration of the FDA\u2010approved \u03b12a\u2010adrenergic agonist, guanfacine, in a human laboratory model of cannabis use disorder. Daily, nontreatment\u2010seeking cannabis smokers (13M, 2F) completed a within\u2010subject study comprising two 9\u2010day inpatient study phases. Each phase tested the effects of daily placebo or immediate\u2010release guanfacine (2\u00a0mg) on cannabis intoxication (5.6 percent THC; 2\u00a0days), withdrawal (4\u00a0days of abstinence) and subsequent \u2018relapse\u2019 (3\u00a0days of cannabis self\u2010administration). Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor performance and cannabis self\u2010administration were assessed. An outpatient phase preceded each inpatient phase for medication clearance or dose induction. Under placebo medication conditions, cannabis abstinence produced significant withdrawal, including irritability, sleep disruption and anorexia. Guanfacine reduced ratings of irritability and improved objective measures of sleep during cannabis withdrawal relative to placebo but did not reduce cannabis self\u2010administration. Guanfacine was well tolerated with little evidence of fatigue and only small decreases in blood pressure: no dose was held due to hypotension. Thus, a single daily administration of guanfacine at bedtime improved sleep and mood during cannabis withdrawal relative to placebo. This positive signal supports further studies varying the guanfacine dose, formulation or frequency of administration, or combining it with other medications to increase the likelihood of having an impact on cannabis use.<\/jats:p>","DOI":"10.1111\/adb.12621","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T13:25:42Z","timestamp":1523885142000},"page":"707-716","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Guanfacine decreases symptoms of cannabis withdrawal in daily cannabis smokers"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-9528","authenticated-orcid":false,"given":"Margaret","family":"Haney","sequence":"first","affiliation":[{"name":"Division on Substance Use Disorders, New York State Psychiatric Institute and Department of Psychiatry Columbia University Medical Center New York NY 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