Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression a SPECT study

This open-label study (n=17) found that a single dose of ayahuasca (100-200ml) had significant antidepressant effects up to 21 days later (MADRS-scale and others).

Abstract

“Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT_2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.”

Authors: Rafael F. Sanches, Flávia de Lima Osório, Rafael G. dos Santos, Ligia R. H. Macedo, João P. Maia-de-Oliveira, Lauro Wichert-Ana, Draulio Barros de Araujo, Jordi Riba, José Alexandre S. Crippa & Jaime E. C. Halla

Notes

Further analysis of the data on suicidality was done by Zeifman and colleagues (2020).

Dos Santos and colleagues (2018) did a five-year qualitative follow-up study with 8 participants from this study.

Summary

Ayahuasca is a botanical brew made by de-coctioning the bark of Banisteriopsis caapi and the leaves of Psychotria viridis. It contains -carboline alkaloids and DMT, which act together to produce hallucinogenic effects.

Ayahuasca may have antidepressive properties, and administration to patients with recurrent major depressive disorder (MDD) was associated with fast-acting and enduring antidepressive effects.

Volunteers

Seventeen volunteers with recurrent MDD were recruited through local advertisement and referrals from private psychiatric clinics. They were invited to participate in an experimental study investigating the antidepressive properties of ayahuasca, which is relatively well known in Brazil because of syncretic religions.

Volunteers received detailed information regarding the effects of ayahuasca and gave their written consent to participate. The study was approved by the local Ethics Committee.

Drug

Ayahuasca, obtained from the Brazilian religious organization Santo Daime, contained 0.8 mg/mL DMT, 0.21 mg/mL harmine, and no harmaline as measured by GC/MS. Each patient drank a single dose of 120 to 200 mL.

Medical Interview and Laboratory Tests

A general clinical examination, laboratory work-up, electrocardiogram, and clinical interview were performed to confirm the diagnosis of MDD.

Assessment of Ayahuasca Effects on Psychiatric Symptoms

Depressive symptoms, maniac symptoms, general psychiatric symptoms, and dissociative symptoms were assessed before, 40, 80, 140, and 180 minutes after ayahuasca administration.

Assessment of Ayahuasca Effects on Regional Cerebral Blood Flow

Ayahuasca effects on regional cerebral blood flow were assessed by single photon emission tomography (SPECT) imaging performed before drug intake and eight hours after treatment.

Experimental Procedure

In an open-label trial, volunteers were admitted to an inpatient psychiatric unit for two weeks prior to ayahuasca administration. There was no formal preparation sessions prior to drug administration, and no psychological intervention was included after drug effects had subsided.

Ayahuasca Effects on Psychiatric Symptoms

Ayahuasca administration was associated with significant decreases in HAM-D and MADRS scores and increases in CADSS scores from 40 to 80 minutes after ayahuasca intake, while no significant changes were observed in the YMRS score.

Ayahuasca Effects on Blood Perfusion

Ayahuasca administration was associated with significant activation of the left nucleus accumbens, right insula, and left subgenual area.

Tolerability

Ayahuasca was well tolerated, and only vomiting was reported. The volunteers considered the ayahuasca session as a pleasant experience.

DISCUSSION

Administration of ayahuasca was associated with rapid and sustained antidepressive effects, including improvements in depressed mood, sadness, anxiety, feelings of guilt, suicidal ideation, difficulties at work/activities, pessimistic thinking, and difficulty concentrating.

Ayahuasca intake did not affect YMRS or Activation BPRS subscale scores, suggesting that maniac-like effects were absent. However, patients with bipolar disorder should be cautious when using ayahuasca.

After ayahuasca intake, blood perfusion in the subgenual area, nucleus accumbens, and insula was increased. This effect was not observed in healthy volunteers.

Ayahuasca may have antidepressant effects by activating 5-HT1A/2A/2C receptors and decreasing activity in the default mode network (DMN), which is associated with self-perception. This may explain why fMRI studies show inconsistent results with SPECT/PET studies.

Ayahuasca was well tolerated, and the only adverse effect was vomiting. The psychoactive effects were mild and short-lived, and volunteers considered it a pleasant experience.

Although the results are promising, they should be replicated in randomized, double-blind, placebo-controlled trials, and future research should investigate how a ceremonial/ritual context may impact therapeutic outcomes.