PET Synaptogenesis After Psilocybin In DEpression Recovery

Participants with depression will be given a single dose of psilocybin and supportive psychotherapy before, during, and after drug administration. Participants will undergo positron emission tomography (PET) imaging before and one week after psilocybin using a marker of synaptic density. This design allows us to assess the relationship between neurotrophic, and antidepressant effects produced by psilocybin.

Inclusion Criteria:Men and women between 18 and 65 years of age;Able to provide informed consentWomen of childbearing age must agree to be on two forms of contraception and men are required to utilize at least one form of contraceptionWillingness to comply and be available for all study requirements, including psychological, cognitive, and imaging for the duration of the studyMeeting DSM-5 criteria for major depressive disorder and current depressive episodeSnaith-Hamilton Anhedonia Pleasure Scale (SHAPS) ≥ 6 pointsWilling and able to taper and/or discontinue current psychotropic medicationsExclusion Criteria:Women who are pregnant or who intend to become pregnant or nurse during the study duration.Presence of psychiatric conditions that are contraindications to psilocybin exposure (e.g., personal or first degree relative with history of schizophrenia spectrum or bipolar disorder);Use of psychotropic medication that may interact with psilocybin (TCA, MAOi, antipsychotic/neuroleptics, anti-epileptic/mood stabilizer, lithium, SSRI, SNRI, Mirtazapine, Buproprion, Vortioxetine).Recent use of psychedelics (psilocybin, LSD, ayahuasca, mescaline; past 5 years); or prior severe adverse reactions to psychedelicsActive suicidal ideation or history of a suicide attempt.Presence of medical conditions that are contraindications to psilocybin exposure (e.g., neurological conditions or severe hypertension, severe and/or unstable metabolic or cardiovascular conditions);Current medical conditions that are known to increase risk of severe coronavirus infection or deemed by a study physician to put an individual at high risk (i.e., cancer, COPD, obesity, immunosuppression, type 2 diabetes, serious heart conditions, sickle cell disease, asthma);Presence of contraindications to PET or MRI scanning (renal disease, implantable devices, bone hardware, some IUDs);Body mass index >30 (due to MRI confounds).