PSILOCYBIN AND IBOGAINE FACILITATE EXTINCTION OF COCAINE SEEKING WITH LIMITED EFFECTS ON CUE-INDUCED REINSTATEMENT

Psychedelics are being explored as potential therapeutics for substance use disorders, yet preclinical validation in stimulant models remains limited. Here, a clinically inspired dose-escalation protocol of psilocybin and ibogaine was tested for effects on extinction learning and cue-induced reinstatement of cocaine seeking in male Wistar rats following intravenous cocaine self-administration (IVSA). Rats acquired IVSA under a fixed-ratio 1 schedule using dose escalation (0.25 mg/kg/infusion followed by 0.5 mg/kg/infusion). After acquisition, animals were randomized into treatment groups and underwent 10 days of extinction. Psilocybin (1.25 mg/kg on extinction day 1, and 5 mg/kg on day 5, subcutaneous) or ibogaine (10 mg/kg on day 1 and 40 mg/kg on day 5, intraperitoneal) was administered during extinction. Cue-induced reinstatement was assessed five days after the final treatment. Psilocybin significantly reduced active lever pressing on extinction day 6 (t(28) = 2.36, p = 0.026), with an early trend after the first treatment (t(28) = 1.32, p = 0.098), while cue-induced reinstatement was not significantly altered (t(28) = 0.83, p = 0.20). Ibogaine significantly reduced responding on extinction day 2 (t(22) = 1.73, p = 0.049) and day 6 (t(22) = 2.59, p = 0.016), with no effect on reinstatement (t(22) = -0.14, p = 0.56). Open field testing 24 hours after each administration indicated no treatment-related changes in locomotion or emotionality, supporting behavioral specificity. Together, these results show that psilocybin and ibogaine can facilitate extinction of cocaine seeking in this IVSA model, whereas effects on cue-driven relapse-like behavior were limited under the present conditions.