Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: An Open-Label SPECT Neuroimaging Study

Open-label inpatient pilot study (Brazil; collaborating institutions include Universidade de São Paulo–Ribeirão Preto and Universidade Federal do Rio Grande do Norte) of a single oral dose of ayahuasca in 17 adults with recurrent MDD (14 women; mean age 42.7 ± 12.11 years) who had an inadequate response to their current antidepressant and were undergoing a planned medication change. Three participants had a mild current episode, 13 moderate, and one severe. After a 2-week washout, participants underwent medical screening (clinical examination, laboratory tests, ECG) and a structured diagnostic interview (SCID-IV). Exclusion criteria: bipolar or psychotic disorder, active psychotic symptoms, pregnancy, history of antidepressant- or substance-induced mania/hypomania. Primary objective: characterise changes in regional cerebral blood flow using single-photon emission computed tomography (SPECT) neuroimaging. Secondary outcomes: Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) assessed at baseline and multiple post-dosing time points including 80 minutes, 24 hours, 48 hours, 72 hours, and 21 days. Study preceded the randomized placebo-controlled RCT by the same group (NCT02914769, UFRN, n=35, started 2014), which cites this open-label pilot as background. Approved by a local ethics committee. No trial registration number reported; study pre-dates routine REBEC registration requirements for open-label pilot work and was classified as a single-arm neuroimaging study.