Isis Koutrouli
Charles University, Czech RepublicPresentation Title:
Psychedelics in a(ddi)ction: Behavioral insights from cocaine-seeking rats
Abstract
Psychedelic substances are increasingly being considered as novel therapeutics for psychiatric conditions, including substance use disorders. Human studies have indicated that a single administration of psilocybin or ibogaine can have long-lasting effects. However, preclinical evidence supporting their role in modulating cocaine-seeking behavior remains limited. In this study, we employed an established intravenous self-administration (IVSA) model in rats to assess the effects of psilocybin and ibogaine on cocaine-seeking and relapse-like behavior. Animals underwent a dose-escalation paradigm of cocaine intake (0.25 mg/kg/infusion for 1 week, followed by 0.5 mg/kg/infusion for another week) to simulate the transition from controlled use to compulsive intake.
After this acquisition phase, animals underwent 10 days of extinction training. Psilocybin (1.25 mg/kg on day 1, 5 mg/kg on day 5) or ibogaine (20 mg/kg on day 1, 40 mg/kg on day 5) were administered intraperitoneally during the extinction phase. A cue-induced reinstatement test was performed five days after the final treatment to assess the impact of treatment on relapse-like behavior. Although no statistically significant differences were observed during reinstatement, both treatments consistently showed a trend toward reduced lever pressing compared to controls, suggesting a potential enhancement of extinction learning. Open Field testing indicated no changes in locomotor activity or emotionality, ruling out general behavioral suppression. As an exploratory follow-up, additional reinstatement tests were conducted to probe potential acute and delayed treatment effects, as well as possible differences across relapse paradigms. While no statistically significant effects emerged, a consistent trend toward reduced drug-seeking persisted in the psychedelic-treated groups.
These results suggest that psilocybin and ibogaine may facilitate extinction learning and modestly attenuate cocaine-seeking behavior. Further investigation into optimal timing, dose, and mechanisms is warranted to inform clinical translation in stimulant use disorders.
Keywords: Psychedelics; Cocaine addiction; Extinction learning; Psilocybin; Ibogaine.
Biography
Isis Koutrouli, MSc, is a 2nd year PhD student in Neurosciences at the 3rd Faculty of Medicine, Charles University, conducting research at the Psychedelic Research Center (National Institute of Mental Health), under the supervision of Dr. Tomáš Páleníček. She holds a BSc in Biology and an MSc in Neurosciences, with a strong background in cellular signalling and molecular pharmacology, particularly in opioid and cannabinoid systems. Her research focuses on investigating the therapeutic mechanisms of psychedelic substances in drug addiction. She independently carries out all experimental work, including stereotactic surgery, electrophysiology, jugular catheterization, behavioral assessments, and data analysis. She coordinates internal data meetings and supports the organization of workshops and conferences. Her earlier work as a medical advisor in the pharmaceutical industry provided a translational perspective to her current academic path. Isis is an active member of the uniMIND journal club in Prague and participant in psychedelic communities, where she contributes to discussions bridging neuroscience research and emerging topics in psychedelic science.
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