Trial Outcomes & Findings for Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression (NCT NCT02914769)

Results Overview

changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing. Minimum and maximum scores are 0 and 50, respectively. Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2. Lower HAM-D score indicates less severe depression (better outcome). Usual cutoff points are a total score ranging from: 0 to 7 indicates that the patient is in the normal range (no depression); 8 to 16 indicates "mild depression"; 17 to 23 indicates "moderate depression"; a score of 24 and greater indicates "severe depression".

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

35 participants

Primary outcome timeframe

seven days after dosing

Results posted on

2025-04-06

Participant Flow

Patients were recruited from psychiatrist referrals at local outpatient psychiatric units or through media advertisements. All procedures took place at the Onofre Lopes University Hospital (HUOL), Natal-RN, Brazil.

From January 2014 to June 2016, we assessed 218 patients for eligibility, and 35 met criteria for the trial. 183 patients not met inclusion criteria for the trial, 26 declined to participate and 14 were not enrolled due to other reasons (several clinical conditions).

Participant milestones

Participant milestones
Measure	Placebo patients receiving a passive placebo placebo: patients will receive a single dose of a placebo.	Ayahuasca patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Overall Study STARTED	18	17
Overall Study COMPLETED	15	14
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo patients receiving a passive placebo placebo: patients will receive a single dose of a placebo.	Ayahuasca patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Overall Study Protocol Violation	3	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=15 Participants placebo: patients will receive a single dose of a placebo.	Ayahuasca n=14 Participants Ayahuasca: patients will receive a single dose of ayahuasca.	Total n=29 Participants Total of all reporting groups
Age, Continuous	39.71 years STANDARD_DEVIATION 11.26 • n=5 Participants	44.20 years STANDARD_DEVIATION 11.98 • n=7 Participants	41.95 years STANDARD_DEVIATION 11.62 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Brazil	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
MADRS	30.13 score STANDARD_DEVIATION 5.55 • n=5 Participants	36.14 score STANDARD_DEVIATION 6.12 • n=7 Participants	33.13 score STANDARD_DEVIATION 5.83 • n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: seven days after dosing

Population: A fixed-effects linear mixed model, with baseline scores as covariate, examined changes in HAM-D at D7. Herein we report mean HAM-D scores at D7.

changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing. Minimum and maximum scores are 0 and 50, respectively. Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine items are scored from 0-2. Lower HAM-D score indicates less severe depression (better outcome). Usual cutoff points are a total score ranging from: 0 to 7 indicates that the patient is in the normal range (no depression); 8 to 16 indicates "mild depression"; 17 to 23 indicates "moderate depression"; a score of 24 and greater indicates "severe depression".

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)	16.92 score on a scale Standard Deviation 7.36	9.72 score on a scale Standard Deviation 7.39

SECONDARY outcome

Timeframe: one, two and seven days after dosing

Population: Herein we report MADRS scores at D1, D2 and D7.

changes in depression severity, assessed by Montgomery-Asberg Depression Rating Scale (MADRS scale), from baseline to 1 day, 2 days, and 7 days after dosing. Lower MADRS score indicates less severe depression (better outcome). Minimum and maximum scores are 0 and 60, respectively. Usual cutoff points are a total score ranging from: 0 to 6 indicates that the patient is in the normal range (no depression); 7 to 19 indicates "mild depression"; 20 to 34 indicates "moderate depression"; a score of 35 and greater indicates "severe depression".

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7 MADRS Scores at D1	21.49 score on a scale Standard Deviation 10.90	12.65 score on a scale Standard Deviation 10.27
Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7 MADRS Scores at D2	19.09 score on a scale Standard Deviation 10.44	10.32 score on a scale Standard Deviation 10.44
Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7 MADRS Scores at D7	26.76 score on a scale Standard Deviation 10.11	11.58 score on a scale Standard Deviation 10.27

SECONDARY outcome

Timeframe: seven days after dosing

Population: Response rate

Response Rate:Number of Participants with reduction of 50% or more in Hamilton Depression Rating Scale (HAM-D) in baseline scores, assessed seven days after dosing.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Number of Participants With Reduction of 50% or More in Hamilton Depression Rating Scale(HAM-D) Scores at D7	3 Participants	8 Participants

SECONDARY outcome

Timeframe: one, two, and seven days after dosing

Population: Response rate

response rate: reduction of 50% or more in baseline scores, assessed at one day, two days and seven days after dosing by the MADRS scale.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D1	7 Participants	7 Participants
Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D2	10 Participants	11 Participants
Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D7	4 Participants	9 Participants

SECONDARY outcome

Timeframe: seven days after dosing

Population: Remission rate

Number of Participants With a score lower then or equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at seven days after dosing.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Number of Participants With a Score Lower Then or Equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at D7	2 Participants	6 Participants

SECONDARY outcome

Timeframe: one, two and seven days after dosing

Population: Remission rate

Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at one, two and seven days after dosing.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 Participants patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D1	7 Participants	6 Participants
Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D2	8 Participants	4 Participants
Number of Participants With a Score Lower Then or Equal to 10 in the Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7 D7	1 Participants	5 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Ayahuasca

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=15 participants at risk patients receiving a passive placebo placebo: patients will receive a single dose of a passive placebo.	Ayahuasca n=14 participants at risk patients receiving Ayahuasca Ayahuasca: patients will receive a single dose of ayahuasca.
Gastrointestinal disorders Nausea	26.7% 4/15 • One week. Definitions do not differ from the clinicaltrials.gov	71.4% 10/14 • One week. Definitions do not differ from the clinicaltrials.gov

Additional Information

Draulio Barros de Araujo

UFRN

Phone: +5584991225987

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place