A new class of iboga alkaloids, called oxa-iboga, was created by modifying the iboga skeleton to include a benzofuran group. These compounds act as potent kappa opioid receptor agonists but show atypical behavioral effects compared to standard kappa psychedelics. Oxa-noribogaine, a key oxa-iboga compound, demonstrated greater therapeutic efficacy in rat models of opioid use than noribogaine, with no cardiac pro-arrhythmic potential. A single dose produced long-lasting suppression of morphine and fentanyl intake, and a short treatment regimen persistently reduced morphine intake and reinforcing efficacy. It also suppressed drug seeking in relapse models and elevated neurotrophin proteins in brain regions linked to addiction, suggesting targeted neuroplasticity. Oxa-iboga compounds are candidates for a novel pharmacotherapy for opioid use disorder.
A single intravenous dose of GM-2505, a novel 5-HT2A receptor agonist, was safe and well tolerated in 48 healthy volunteers at doses up to 20 mg. The drug produced mild, transient increases in blood pressure and pulse, no significant electrocardiograph changes, and a half-life of 40–50 minutes. Dose-dependent effects appeared on neuroendocrine hormones, neuropsychological and neurophysiological measures, subjective drug effects, and resting-state electroencephalography, with decreased theta and alpha power and increased slow and fast gamma power. These pharmacodynamic effects resembled those of other 5-HT2A agonists, but GM-2505's shorter duration of cardiovascular and subjective effects than psilocybin and longer than DMT suggests a more practical temporal profile for supervised clinical use, with an optimal dose range of 10–15 mg IV.