Acute cannabinoid intoxication (ACI) can cause symptoms like anxiety, panic attacks, tachycardia, and psychosis, primarily triggered by the activation of cannabinoid type 1 receptor (CB1) by Δ9-tetrahydrocannabinol (THC). Despite the rising cases of ACI, no approved treatments directly address its underlying cause.
The theory that a CB1 antagonist, which partially blocks the effects of an agonist like THC, or an inverse agonist, could counteract ACI symptoms seems logical. However, this approach has proven more complex than expected.
Take Rimonabant, for example. As a CB1 antagonist, it was initially believed to provide the opposite effects of THC, such as suppressing appetite instead of stimulating it (the “anti-munchies”). While this effect was sought to address metabolic syndrome and obesity, the drug also induced dysphoria, leading to its market withdrawal in 2008 due to concerns about suicidal ideation in patients.
Fast forward to 2025, and a recent study explored the potential of selonabant, another synthetic CB1 antagonist, for treating ACI. In a randomized, double-blind, placebo-controlled trial, selonabant successfully blocked the acute psychoactive effects of THC (up to 21 mg). Adverse effects, including dysphoria, were minimal, with no reports of suicidal ideation at the tested doses (A. Gorbenko et al., 2025).
This research highlights the potential of CB1 antagonists like selonabant in treating ACI. Another CB1 antagonist, the naturally occurring cannabinoid Tetrahydrocannabivarin (THCV), has shown promise in modulating THC effects, though it hasn’t been tested specifically for ACI. THCV acts as a CB1 antagonist at lower doses but can also be an agonist at higher doses, offering unique therapeutic possibilities. While research is ongoing, THCV may one day be part of the solution for cannabinoid-related toxicity, but further studies are needed.
