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CB Receptor Antagonist Selonabant (ANEB-001) Blocks Acute THC Effects in Healthy Volunteers: A Phase II Randomized Controlled Trial.

2 May 2025. doid: 10.1002/cpt.3581

Gorbenko AA, Heuberger JAAC, Juachon M, Klaassen E, Tagen M, Lawler JF, Schneeberger D, Cundy KC, Klumpers LE, Groeneveld GJ

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Emergency department visits due to cannabinoid-induced toxicity, including acute cannabinoid intoxication (ACI) have increased worldwide as more states have liberalized cannabis policy. ACI symptoms include anxiety, panic attacks, tachycardia, and psychosis, primarily mediated through cannabinoid type 1 receptor (CB) agonism by Δ-tetrahydrocannabinol (THC). This phase II randomized, double-blind, placebo-controlled study assessed the potential of CB receptor antagonist selonabant (ANEB-001) to block THC-induced effects in healthy adults. In Part A of the study, 10.5 mg of THC was coadministered with 50 mg (N = 20) or 100 mg (N = 20) selonabant, or matching placebo (N = 20). In Part B, 21-mg THC was coadministered with 30 mg (N = 9) or 10 mg (N = 7) selonabant, or matching placebo (N = 9). THC-related 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 was generally safe and no clinically meaningful changes in mood occurred. Nausea and vomiting occurred more frequently at high selonabant doses; 10-mg selonabant was both well tolerated and efficacious. Present results support further development of selonabant for emergency treatment of ACI.

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