Grant: Operating Grant: Psilocybin-assisted Psychotherapy - Substance Use Disorders

There is growing interest in using psychedelic drugs such as psilocybin to treat various psychiatric disorders. For instance, a very recent clinical trial reported that psilocybin administered in the context of supportive, motivation-focused therapy can reduce heavy drinking in patients with an alcohol use disorder (AUD). This is encouraging, as alcohol-related problems are of the most costly to society and current treatment options are inadequate. However, like in nearly all trials involving psilocybin, patients were able to figure out if received psilocybin or the control compound. This makes it difficult to determine if the effects on alcohol consumption are due to the pharmacological effects of psilocybin or what people expect psilocybin to do. This is becoming an increasing concern in psychedelic trials due to the growing positive media coverage (or "hype") around psychedelic drugs. In this study, we plan to begin addressing this issue of expectancies by giving all 128 AUD patients psilocybin, but varying the dose so that half receive the active treatment dose (25mg) and the other half get a smaller active control dose (1mg). The active control dose is just enough for participants to feel short-lived drug effects during the session, likely preventing them from easily determining if they are in the active or control group, but not enough to produce long-lasting effects on behavior. If it is only the expectations that drive effects, we will see no difference between groups. However, if the pharmacological effects of psilocybin are indeed driving the reduction in drinking, then we will see greater improvements in individuals receiving the active 25mg dose. We will also measure how psilocybin-assisted psychotherapy influences behavioral and brain metrics related to alcohol consumption. Together, we will determine if psilocybin-assisted psychotherapy can reduce alcohol consumption, an if so, what mechanisms may be supporting this change in behavior.