Therapeutic effect of an ayahuasca analogue in clinically depressed patients: a longitudinal observational study

This observational study (n=20) assessed depressive symptomatology in clinically depressed patients, using the Beck Depression Inventory (BDI), before attending an ayahuasca ceremony, 1 day, 1 month, and 1 year after. The day after, 12/20 (60%) participants were in remission, which remained up to one year later. Three participants remained mildly depressed ever at 1-year follow-up, while two participants did not respond to treatment.

Abstract

“Rationale: Studies have suggested mental health improvements following the use of the psychotropic plant concoction ayahuasca in non-clinical and clinical samples.

Objectives: The present observational study assessed depressive symptomatology in 20 clinically depressed patients (symptom score > 13 on the Beck’s Depression Inventory) before attendance of an ayahuasca ceremony and 1 month and 1 year after. Secondary measures included ratings of altered states of consciousness and ego dissolution during the ayahuasca ceremony as well as global measures of mindfulness, satisfaction with life, depression, anxiety, and stress.

Results: Twenty participants completed baseline and 1-day follow-up, 19 completed measures at 1-month follow-up, and 17 completed measures at 1-year follow-up. BDI scores reduced from baseline (M = 22.7) to all post-ceremony measures (Ms 11.45, 12.89, and 8.88, for 1-day, 1-month, and 1-year follow-up, respectively). After 1 day, 12/20 participants were in remission (BDI < 13). Remission rates after 1 month and 1 year were 13/19 and 12/17, respectively. Three participants remained mildly depressed (BDI 14–19) at the 1-month and 1-year follow-up. Two participants did not respond and remained at a moderate/severe level of depression at 1-year follow-up. Reductions in the secondary mental health measures and increases in mindfulness and satisfaction with life were found up to 1-year post-ceremony. Improvements in clinical depression and mental health correlated with levels of experienced ego dissolution and oceanic boundlessness during the ceremony up to 1 month after the ceremony. Engagement in additional mental health treatments or use of another psychedelic during study participation may have contributed to improved mental health ratings at 1-year follow-up.

Conclusion: Ayahuasca produces long-term mental health improvements in clinically depressed patients, which highlights its therapeutic potential.”

Authors: Kim van Oorsouw, S. W. Toennes & Johannes G. Ramaekers

Summary

Studies have shown that ayahuasca improves mental health.

The present observational study assessed depressive symptomatology in 20 clinically depressed patients.

The study measured depression before and after an ayahuasca ceremony.

Ayahuasca ceremony reduces depression and anxiety in clinically depressed patients, and improves mental health up to 1 year after the ceremony. Engagement in additional mental health treatments or use of another psychedelic may have contributed to improved mental health ratings at 1-year follow-up.

Introduction

Ayahuasca is a hallucinogenic plant brew from the Amazon that contains N,N-dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAO-I). Ayahuasca analogues are plant combinations containing DMT and MAO-I that are used in Western countries because they produce similar effects but are cheaper and easier to access.

Ayahuasca is usually ingested in a group setting guided by a ceremonial leader. It is safe and non-addictive when taken in a supervised setting, yet some reports associate ayahuasca with higher risks of serious intoxication.

Observational studies in healthy volunteers and treatment-resistant depressed patients have demonstrated antidepressant, anxiolytic, and stress reducing properties of ayahuasca. Ayahuasca has also been shown to reduce anxiety, depression, and substance use disorder in first time ayahuasca users.

Ayahuasca may cause acute effects such as pharmacological changes in brain activity or altered states of consciousness, such as ego dissolution or oceanic boundlessness. These effects may also lead to long-term mental health outcomes.

Ayahuasca may improve mental health symptoms by improving mindfulness. Insights, a more positive life stance and changed worldview are commonly reported outcomes after ayahuasca intake.

The present study investigated the effects of an ayahuasca analogue on clinically depressed patients after a single ceremony. The results showed that participants showed improvements in all mental health variables, mindfulness, and satisfaction with life after intake.

Participants and procedure

Data were collected from 20 ayahuasca ceremony attendants in the Netherlands. The participants were screened for physical and mental capability to drink ayahuasca analogue and were instructed to stop any (non-prescribed) drugs at least 6 weeks before taking part in the ceremony.

All participants had suffered from chronic depression for more than 2 years and were receiving psychological treatment. Nineteen participants were new to drinking ayahuasca.

Participants completed an online 30-min survey before an ayahuasca ceremony, a 1-day post-ceremony survey, a 1-month post-ceremony survey, and a 1-year post-ceremony survey. The 1-year post-ceremony survey was completed within a range of 1 – 13 days and the 1-month post-ceremony assessment within a range of 31 – 70 days.

Ceremonial setting

Ayahuasca ceremonies were conducted in non-religious settings, and participants received extensive intake, coaching, and preparation guidelines. They were followed by two rounds of ayahuasca analogue and rituals that included burning herbs and/or tobacco, playing various musical instruments or recorded music, and singing healing songs.

Ayahuasca analogue

Participants were recruited via 3 different centers in the Netherlands that advertised with serving ayahuasca, but were actually using ayahuasca analogue brews. They received DMT and MAO-I in separate drinks within a 15-min interval, and the total dose was divided over 2 rounds of administration spaced about 2.5 h apart.

Measures

The Beck Depression Inventory (BDI) was used as the primary outcome measure, and a number of other questionnaires were used to assess mental health.

Beck’s Depression Inventory is a 21-item self-report rating scale that assesses affective, cognitive, somatic, and vegetative symptoms of depression. A score of 0 indicates no-minimal depression, 14 – 19 (mild depression), 20 – 28 (moderate depression), and 29 – 63 (severe depression). All participants with baseline scores > 13 were included in the present study. The primary outcome measure was the change in depression severity on BDI scores.

Follow‑up interviews

We used linear mixed model analysis with session as within subject factor to examine how the level of ego dissolution, oceanic boundlessness, and anxious ego dissolution were related to depression, mental health related measures, mindfulness, and satisfaction with life.

Results

A total of 20 participants completed the baseline, 1-day and 1-month post-ceremony surveys. Of those, 17 expected a beneficial outcome from participating in an ayahuasca ceremony, and 8 still received therapy and 3 started taking antidepressant medication.

Mental Health

Mixed model analysis revealed a significant session effect for BDI depression scores, and a significant reduction in BDI scores between baseline and all follow-up sessions. All but 2 participants showed a reduction in their depression ratings at 1 day, 1 month, and 1 year post-ceremony.

There was no correlation between BDI scores and the use of psychedelics or medication between 1 month and 1 year post-ceremony.

In a secondary analysis, baseline BDI score was included as a covariate to see if baseline scores affected any follow-up measures. High baseline scores were associated with a significant reduction in BDI scores.

DASS‑21

For depression and anxiety, a main session effect emerged, and for stress, a main session effect emerged, with significant reduction in self-reported stress between baseline and all follow-up sessions.

A significant session effect was found for ratings of BSI depression and anxiety, with significant reductions reported between baseline and all follow-up sessions. No significant session effect was found for somatization ratings.

SWLS

For mindful observing, mindful describing, and mindful non-judging, a main effect of session was found. Self-reported mindful observing and mindful describing increased from baseline to the day after the ceremony, and from baseline to the 1-year follow-up.

The psychedelic experience

The mean ratings on 5D-ASC dimensions varied between 16.75 and 45.55, with mean scores on OB and AED being 45.55 and 25.30, respectively. All participants experienced moderate levels of altered states of consciousness.

Relationship between the psychedelic experience and mental health changes

Pearson correlations were calculated between the level of experienced ego dissolution, oceanic boundlessness, and anxious ego dissolution and the primary outcome measure 1 day, 1 month, and 1 year post-ceremony. Higher levels of experienced ego dissolution were related to lower depression levels lasting until 1 month post-ceremony.

Follow‑up interviews

In the year between the 1-month and 1-year follow-ups, the percentage of remissions increased from 68 to 71%. Seven out of nine participants who took additional psychedelics reported that their experience had been beneficial, and three participants who were taking antidepressant medication reported their use had been beneficial.

Most participants reported making some changes in their lifestyle that affected their mental health. Meditation, breathwork, and regular walks in nature were the most prevalent measures.

Discussion

The present study evaluated the effect of a single ayahuasca ceremony on levels of depression, anxiety, stress, somatization, mindfulness, and satisfaction with life in 20 clinically depressed participants. The results showed that 71% of participants were in remission at 1 year post-ceremony.

The present findings are in line with reports on ayahuasca’s benefits for clinically depressed patients. Ayahuasca intake was observed to reduce depression symptoms in six clinically depressed patients and 17 patients with recurrent depression. Ayahuasca has an immediate and fast acting antidepressant effect, and its effects may last up to 1 year post-ceremony. Individuals with mild to moderate symptoms of depression were more likely to achieve remission than individuals with severe symptoms of depression.

Response rates were comparable to those reported in the ayahuasca group of Palhano Fontes and colleagues’ randomized clinical trial (RCT), even though current response rates were recorded at 1-month and 1-year follow-up. The average DMT dose was 1.25 mg/kg, divided over 2 dose administrations.

On the secondary measures, depression and stress ratings decreased significantly up to 1 year post-ceremony, and anxiety ratings decreased 1-day and 1 year post-ceremony. Also, participants reported significant increments in satisfaction with life and increases in mindfulness lasting up to 1 year post-ceremony.

Higher scores on the EDI and OB, two measures of spiritual insight and bliss, correlated with lower depression scores post-ceremony, in line with earlier reports in healthy samples. Several participants reported that 1 day after the ceremony, they realized how stuck they were in rigid, destructive thought patterns. However, 1 year after the ceremony, EDI and OB no longer correlated with BDI scores, suggesting that other factors may have contributed to the sustained relief of depressive symptoms.

Participants who were able to surrender to the psychedelic experience scored higher on the positive than on the challenging dimensions of the 5D-ASC, and were appreciative of the care and support that was provided, which may have created a positive setting in which positive ayahuasca experiences occurred.

A serious limitation of the present study is that there was no (treatment as usual) control group. A control group would have provided more insight on how expectations may have affected the improvement in mental health, as well as what the effect of the ritual and setting is in absence of a pharmacological agent. In the present study, an ayahuasca analogue was used, which is different from traditional ayahuasca concoctions. However, there is no agreement on a “standard recipe” for these brews. The current study had limitations, including the lack of control over additional mental health approaches to which some participants were exposed, and the lack of correlation between BDI scores and ayahuasca experience ratings at 1 year post-ceremony.

The current study suggests that ayahuasca can relieve depression in clinically depressed patients, reduce anxiety and stress, and increase mindfulness capacities and quality of life up to one year after participation.