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ACI symptoms include anxiety, panic attacks, tachycardia, and psychosis, primarily mediated through cannabinoid type 1 receptor (CB<jats:sub>1<\/jats:sub>) agonism by \u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (THC). This phase II randomized, double\u2010blind, placebo\u2010controlled study assessed the potential of CB<jats:sub>1<\/jats:sub> receptor antagonist selonabant (ANEB\u2010001) to block THC\u2010induced effects in healthy adults. In Part A of the study, 10.5\u2009mg of THC was coadministered with 50\u2009mg (<jats:italic>N<\/jats:italic>\u2009=\u200920) or 100\u2009mg (<jats:italic>N<\/jats:italic>\u2009=\u200920) selonabant, or matching placebo (<jats:italic>N<\/jats:italic>\u2009=\u200920). In Part B, 21\u2010mg THC was coadministered with 30\u2009mg (<jats:italic>N<\/jats:italic>\u2009=\u20099) or 10\u2009mg (<jats:italic>N<\/jats:italic>\u2009=\u20097) selonabant, or matching placebo (<jats:italic>N<\/jats:italic>\u2009=\u20099). THC\u2010related effects were assessed using visual analogue scales (VAS) for feeling high and alertness, objective measures of postural stability, and heart rate and analyzed using a mixed effects model. Selonabant significantly reduced VAS \u201cFeeling High\u201d (up to \u221282.8% (95% CI: \u221291.0%, \u221267.2%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001) at 30\u2010mg selonabant) and increased VAS \u201cAlertness\u201d (up to 10.8\u2009mm (95% CI: 4.7, 16.8\u2009mm, <jats:italic>P<\/jats:italic>\u2009=\u20090.001) at 30\u2010mg selonabant) vs. placebo. Selonabant 10 and 30\u2009mg significantly reduced body sway (up to \u221230.6% (95% CI: \u221244.1%, \u221213.9%, <jats:italic>P<\/jats:italic>\u2009=\u20090.002) at 30\u2009mg selonabant) vs. placebo. Effects on heart rate were not significant. Selonabant was generally safe and no clinically meaningful changes in mood occurred. Nausea and vomiting occurred more frequently at high selonabant doses; 10\u2010mg selonabant was both well tolerated and efficacious. Present results support further development of selonabant for emergency treatment of ACI.<\/jats:p>","DOI":"10.1002\/cpt.3581","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T12:08:46Z","timestamp":1738584526000},"page":"1427-1436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>CB<sub>1<\/sub><\/scp> Receptor Antagonist Selonabant (<scp>ANEB<\/scp>\u2010001) Blocks Acute <scp>THC<\/scp> Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5917-7888","authenticated-orcid":false,"given":"Andriy A.","family":"Gorbenko","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Centre  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-5088","authenticated-orcid":false,"given":"Jules A. 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