Psilocybin-Assisted Treatment of Cocaine Use Disorder - ABSTRACT: Cocaine use disorder (CocUD) imposes significant medical, economic, and psychosocial burdens globally. Here we propose to explore the potential efficacy and safety of psilocybin, a serotonergic hallucinogenic compound found in psychedelic mushrooms, as a possible treatment for addiction to cocaine, which is a form of stimulant use disorder, but which we refer to herein as CocUD. Psychedelics are being explored as a novel therapy for mood, anxiety, and addictive disorders due to their ability to induce acute perceptual changes (i.e., a psychedelic effect). Studies suggest psychedelics may have lasting effects on behavior after only one or two doses. Psychedelics are generally safe and well-tolerated in human subjects, especially when used under medical supervision. Psilocybin may reduce cocaine consumption, potentially through emotional modulation, attentional bias alteration, and craving reduction via interactions with serotonin receptors and subsequent induction of neural plasticity. Our research will evaluate the treatment effects of psilocybin combined with psychedelic integrative therapy and cognitive behavioral therapy (Psy+T) for CocUD. The initial phase will involve a proof-of-concept randomized controlled trial focusing on safety, tolerability, a comparison of two doses (25mg and 40mg), and potential efficacy. If we are successful in reaching all milestone goals of the initial UG3 pilot study, we will progress to a larger trial (UH3) that aims to demonstrate efficacy and explore possible reasons for some patients responding better than others. Understanding how psilocybin influences attentional bias, craving, emotional states, mystical experience, and metacognition may lead to more effective personalized CocUD treatment strategies. We will use resting state and task-based functional Magnetic Resonance Imaging to explore ways to eventually personalize and optimize the treatment with precision.
