Banca de DEFESA: FERNANDA PALHANO XAVIER DE FONTES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : FERNANDA PALHANO XAVIER DE FONTES
DATA : 28/07/2017
HORA: 14:00
LOCAL: INSTITUTO DO CEREBRO
TÍTULO:

The antidepressant effects of ayahuasca, its neural bases and relation with the psychedelic experience.

PALAVRAS-CHAVES:

psychedelics, ayahuasca, treatment-resistant depression, randomized clinical trial, fMRI

PÁGINAS: 155
GRANDE ÁREA: Ciências Biológicas
ÁREA: Fisiologia
RESUMO:

Recent open label trials show that psychedelics hold promise as fast-onset antidepressants in treatment resistant depression. In Brazil, a psychedelic substance worth mentioning is the ayahuasca. This brew composed by the psychedelic N,N-dimethyltryptamine (DMT), a serotonin and sigma-1 receptors agonist, and reversible monoamine oxidase A inhibitors, such as harmine, harmaline, and tetrahydroharmine, causes changes in perception, emotion and cognition. Preliminary results from our group suggest its antidepressant potential, in addition to demonstrating its safety and tolerability. Although promising, none of these studies have controlled for the placebo effect, which is high in clinical trials for depression. To address this issue, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 35 patients with treatment-resistant depression. A healthy control group of 50 volunteers was also examined. Patients received a single dose of either ayahuasca or placebo. One day before dosing, and one day after dosing patients were enrolled in a series of tests and assessments, including psychometric scales and fMRI, conducted in the course of a four-day experimental session, to assess changes in different markers of depression. Two clinical scales for depression assessed changes in depression severity: the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at 1, 2 and 7 days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all endpoints. MADRS scores were significantly lower in the ayahuasca group, compared to placebo. Likewise, HAM-D scores were significantly different at D7. Between-group effect sizes increased from D1 to D7. Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group at D7. Remission rate was marginally significant at D7. In addition, we examined the relationship between the antidepressant and acute psychedelic effects of ayahuasca. The psychedelic effects were assessed using the Hallucinogen Rating Scale (HRS) and the Mystical Experience Questionnaire (MEQ30) after the dosing session. We found that higher psychedelic effects measured by both HRS and MEQ30 correlated with improvements in clinical outcome at D7. Finally, to investigate the neural bases of the antidepressant effects of ayahuasca, we used fMRI data through an emotional and resting state protocols at baseline, and one day after dosing. We observed changes in key limbic regions, such as subgenual cingulate cortex, amygdala and insula in ayahuasca group when compared to placebo. To our knowledge this is the first controlled trial to test a psychedelic substance in treatment resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

MEMBROS DA BANCA:
Presidente - 1243905 - DRAULIO BARROS DE ARAUJO
Interno - 1721223 - ADRIANO BRETANHA LOPES TORT
Interno - 2394627 - EDUARDO BOUTH SEQUERRA
Externo à Instituição - ANDERSON MARCELO WINKLER - HIAE
Externo à Instituição - JOSE NEANDER SILVA ABREU - UFBA