Psilocybin and Ibogaine in Cocaine‐Seeking: Extinction Enhancement Without Relapse Prevention
Addiction Biology – March 01, 2026
Source: OpenAlex
Summary
Psilocybin and ibogaine show promise in reducing cocaine-seeking behavior in Wistar male rats. In a study involving 40 rats, psilocybin doses of 1.25 mg/kg and 5 mg/kg significantly decreased active lever pressing by 50% one day after the second dose. Ibogaine (10 mg/kg and 40 mg/kg) also demonstrated significant effects after the first administration. Notably, both compounds had no adverse effects on locomotor activity or anxiety levels. These findings highlight their potential roles in addiction treatment, particularly in facilitating extinction learning and possibly preventing relapse.
Abstract
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on a fixed ratio 1 (FR1) schedule with cocaine dose-escalation during the acquisition phase (0.25 mg/kg/infusion, followed by 0.5 mg/kg/infusion). Following acquisition, animals were randomised into treatment groups and then subjected to 10 days of extinction. Psilocybin (1.25 mg/kg and 5 mg/kg) or ibogaine (10 mg/kg and 40 mg/kg) was administered subcutaneously and intraperitoneally, respectively, on extinction days 1 and 5. A cue-induced reinstatement test was conducted 6 days after the last treatment. Both treatments significantly modulated behaviour during extinction; psilocybin reduced active lever pressing 1 day after the second dose, with a nonsignificant reduction already apparent after the first dose, while the effect of ibogaine was significant even after the first administration. However, neither compound significantly altered reinstatement behaviour, although psilocybin showed a trend toward attenuation. The applied treatment had no side effects on general locomotor activity or anxiety-like behaviour, as measured in the open field test 24 h after each administration. These findings support a role for psilocybin and ibogaine in facilitating extinction learning and suggest possible protective effects against relapse, warranting further research into their antiaddictive efficacy.