Background: Cocaine use disorder has a detrimental impact on the individual, their families, and society. Psilocybin with psychological support, a synergistic combination of pharmacology and psychological support, is emerging as a multi-modal treatment paradigm that is showing therapeutic benefits for substance use disorders. Psilocybin activates cortical 5-HT2A receptors, induces transient alterations of brain connectivity in humans, and promotes synaptogenesis and neural plasticity in rodents. It is not yet known whether psilocybin with psychological support will play a therapeutic anti-addictive role in cocaine use disorder.
Aim: Assess trial procedures to inform a future definitive trial of psilocybin with psychological support for cocaine use disorder.
Methods: A 15-week randomised double-blind placebo-controlled pilot feasibility study of a single dose of oral psilocybin (25mg) or diphenhydramine 100mg (1:1) and 6 sessions of psychological support (3 preparation, 3 integration) will be conducted in 24 participants meeting DSM-5 criteria for cocaine use disorder (at least moderate severity) and who are seeking treatment. Participants will require a score of ≥4 on the Severity of Dependence Scale and self-reported cocaine use in the past month. Underpinned by the Medical Research Council Framework, the primary outcomes of this feasibility study will assess trial procedures to inform a definitive trial, determined by recruitment rates, adherence, retention, incidents/adverse events, and acceptability. Progression criteria, including a traffic light system of ‘stop’, ‘change‘ and ‘go’ thresholds will be used to facilitate decision-making for the definitive trial. The exploratory secondary outcomes will be cocaine use measured by the Timeline Follow-Back method (percentage days abstinent, complete/sustained abstinence, number of days to first use of cocaine after the drug administration session) verified by urine toxicology, self-reported cocaine craving assessed by the Cocaine Craving Questionnaire-Brief, and cocaine withdrawal using the Cocaine Selective Severity Assessment. Further exploratory measures will assess mood, anxiety, psychedelic experience, social connectedness and functionality using reliable and validated clinical measures.
Conclusion: We envisage that this study will provide the necessary information to launch a definitive trial to determine whether psilocybin with psychological support can reduce cocaine use and craving and improve outcomes in treatment seeking adults with moderate to severe DSM-5 cocaine use disorder.
