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Here, we investigated the effects of a clinically inspired dose\u2010escalation protocol of psilocybin and ibogaine on extinction and cue\u2010induced reinstatement in Wistar male rats following intravenous cocaine self\u2010administration (IVSA). Rats were trained on a fixed ratio 1 (FR1) schedule with cocaine dose\u2010escalation during the acquisition phase (0.25\u2009mg\/kg\/infusion, followed by 0.5\u2009mg\/kg\/infusion). Following acquisition, animals were randomised into treatment groups and then subjected to 10\u2009days of extinction. Psilocybin (1.25\u2009mg\/kg and 5\u2009mg\/kg) or ibogaine (10\u2009mg\/kg and 40\u2009mg\/kg) was administered subcutaneously and intraperitoneally, respectively, on extinction days 1 and 5. A cue\u2010induced reinstatement test was conducted 6\u2009days after the last treatment. Both treatments significantly modulated behaviour during extinction; psilocybin reduced active lever pressing 1\u2009day 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\u2010like behaviour, as measured in the open field test 24\u2009h 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.<\/jats:p>","DOI":"10.1111\/adb.70111","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:41:42Z","timestamp":1773013302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Psilocybin and Ibogaine in Cocaine\u2010Seeking: Extinction Enhancement Without Relapse Prevention"],"prefix":"10.1111","volume":"31","author":[{"given":"Isis\u00a0Rita\u00a0Anzel","family":"Koutrouli","sequence":"first","affiliation":[{"name":"Psychedelic Research Centre National Institute of Mental Health  Klecany Czech Republic"},{"name":"3rd Faculty of Medicine Charles University  Prague Czech 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