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New Psilocybin Study Beginning

Compass Pathways will sponsor the study run by Anthony Rothschild, M.D.

Date Posted: Monday, October 02, 2023
By: Bennett Wechsler, M.D.

We are excited to announce that the Center for Psychopharmacologic Research and Treatment in the UMass Chan Department of Psychiatry, under the direction of Anthony Rothschild, M.D., was chosen as a site for a Compass Pathways sponsored phase 3 trial to evaluate the efficacy of psilocybin for treatment resistant depression.

This study will involve the administration of psilocybin in a controlled and comfortable setting, with substantial psychological support administered by trained therapists.  The dosing session will last for 8 hours, have accompanying therapy, and will be proceeded by several preparatory sessions with a lead and assistant therapist.  Integration sessions will occur after the dosing session, with the goal of consolidating insights learned during the experience. 

Psilocybin is a tryptamine alkaloid found in several species of psilocybin mushrooms and has shown promise in helping those with treatment resistant depression (TRD).  Unlike traditional antidepressants, psilocybin is thought to act via serotonin-2A agonism, producing a psychedelic experience that can elicit profound shifts in perception and emotional processing.  Psilocybin has also been observed to induce mystical experiences and can trigger new ways of processing long held beliefs and behavioral patterns.  This can be particularly helpful in those with TRD who have inflexible ways of thinking and emoting.  Because of the psychologically challenging content that can arise during the experience, treatment with psilocybin is accompanied by psychotherapy in research trials.

In addition to the subjective effects of psilocybin, neuroimaging results show decreased activity in the default mode network (DMN) in patients taking the compound.  The DMN is a brain network comprised of the anterior cingulate cortex, medial prefrontal cortex, posterior cingulate, and is highly involved in rumination.  The DMN has increased activity in those with depression, and the extent of symptom reduction after psilocybin administration is inversely correlated with subjective effects of the drug.  Psilocybin is associated with increased Brain Derived Neurotrophic Factor and neurogenesis in animal models, further supporting the theory that the compound may be associated with a neurological and psychological critical period.

Psilocybin is a schedule I substance and has been classified as such since 1970. However, it has been given breakthrough therapy designation for treatment resistant depression by the FDA since 2018 after promising research results.  Psilocybin has shown potential efficacy in aiding anxiety and depressive symptoms in those diagnosed with cancer and receiving end of life treatment.  Pilot studies have demonstrated that psilocybin was at least as effective as escitalopram in treating the symptoms of major depressive disorder.  And most recently, the results of phase 2 trials from COMPASS evaluating the use of psilocybin in treatment resistant depression were published in the New England Journal of Medicine, showing statistically significant decreases in depressive symptoms when compared to placebo.

If you have patients interested in participating in this study, please contact Michelangela Yusif at 774-455-4136.

Bennett Wechsler, M.D. is Medical Director of the Med-Psych Unit 8E at UMass Memorial Medical Center.