Ignite Creation Date:
2025-12-24 @ 10:54 PM
Ignite Modification Date:
2026-01-02 @ 12:30 PM
Study NCT ID:
NCT02914769
Status:
COMPLETED
Last Update Posted:
2025-04-06
First Post:
2016-09-21
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003865', 'term': 'Depressive Disorder, Major'}, {'id': 'D003863', 'term': 'Depression'}], 'ancestors': [{'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D013812', 'term': 'Therapeutics'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'draulio@neuro.ufrn.br', 'phone': '+5584991225987', 'title': 'Draulio Barros de Araujo', 'organization': 'UFRN'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'One week.', 'description': 'Definitions do not differ from the clinicaltrials.gov', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.', 'otherNumAtRisk': 15, 'otherNumAffected': 4, 'seriousNumAtRisk': 15, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.', 'otherNumAtRisk': 14, 'otherNumAffected': 10, 'seriousNumAtRisk': 14, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 14, 'numAffected': 10}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'categories': [{'measurements': [{'value': '16.92', 'spread': '7.36', 'groupId': 'OG000'}, {'value': '9.72', 'spread': '7.39', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'seven days after dosing', 'description': 'changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing.\n\nMinimum 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.\n\nLower 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".', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '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.'}, {'type': 'SECONDARY', 'title': 'Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'title': 'MADRS Scores at D1', 'categories': [{'measurements': [{'value': '21.49', 'spread': '10.90', 'groupId': 'OG000'}, {'value': '12.65', 'spread': '10.27', 'groupId': 'OG001'}]}]}, {'title': 'MADRS Scores at D2', 'categories': [{'measurements': [{'value': '19.09', 'spread': '10.44', 'groupId': 'OG000'}, {'value': '10.32', 'spread': '10.44', 'groupId': 'OG001'}]}]}, {'title': 'MADRS Scores at D7', 'categories': [{'measurements': [{'value': '26.76', 'spread': '10.11', 'groupId': 'OG000'}, {'value': '11.58', 'spread': '10.27', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'one, two and seven days after dosing', 'description': '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).\n\nMinimum 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".', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Herein we report MADRS scores at D1, D2 and D7.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Reduction of 50% or More in Hamilton Depression Rating Scale(HAM-D) Scores at D7', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'seven days after dosing', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Response rate'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'title': 'D1', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}]}, {'title': 'D2', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}]}, {'title': 'D7', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'one, two, and seven days after dosing', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Response rate'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Score Lower Then or Equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at D7', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'seven days after dosing', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Remission rate'}, {'type': 'SECONDARY', 'title': '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', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '14', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a passive placebo.'}, {'id': 'OG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'classes': [{'title': 'D1', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'D2', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'D7', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'one, two and seven days after dosing', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Remission rate'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'patients receiving a passive placebo\n\nplacebo: patients will receive a single dose of a placebo.'}, {'id': 'FG001', 'title': 'Ayahuasca', 'description': 'patients receiving Ayahuasca\n\nAyahuasca: patients will receive a single dose of ayahuasca.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '17'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '14'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': '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.', 'preAssignmentDetails': '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).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'placebo: patients will receive a single dose of a placebo.'}, {'id': 'BG001', 'title': 'Ayahuasca', 'description': 'Ayahuasca: patients will receive a single dose of ayahuasca.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '39.71', 'spread': '11.26', 'groupId': 'BG000'}, {'value': '44.20', 'spread': '11.98', 'groupId': 'BG001'}, {'value': '41.95', 'spread': '11.62', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Brazil', 'categories': [{'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'MADRS', 'classes': [{'categories': [{'measurements': [{'value': '30.13', 'spread': '5.55', 'groupId': 'BG000'}, {'value': '36.14', 'spread': '6.12', 'groupId': 'BG001'}, {'value': '33.13', 'spread': '5.83', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'This scale measures depression severity. Each item yields a score of 0 to 6; the overall score thus ranges from 0 to 60. Higher MADRS score indicates more severe depression.\n\nUsual 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".', 'unitOfMeasure': 'score', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': '218 patients were assessed for eligibility, and 35 met criteria for the trial. Six subjects had to be excluded: five no longer met criteria for depression in the day of dosing, and one dropped out before dosing.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 35}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-04', 'studyFirstSubmitDate': '2016-09-21', 'resultsFirstSubmitDate': '2023-06-04', 'studyFirstSubmitQcDate': '2016-09-23', 'lastUpdatePostDateStruct': {'date': '2025-04-06', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-04-04', 'studyFirstPostDateStruct': {'date': '2016-09-26', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2025-04-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Hamilton Depression Rating Scale (HAM-D) Effect Seven Days After Dosing (D7)', 'timeFrame': 'seven days after dosing', 'description': 'changes in depression severity, assessed by the Hamilton Depression Rating Scale (HAM-D) scale, from baseline to 7 days after dosing.\n\nMinimum 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.\n\nLower 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".'}], 'secondaryOutcomes': [{'measure': 'Montgomery-Asberg Depression Rating Scale (MADRS) Effect at D1, D2 and D7', 'timeFrame': 'one, two and seven days after dosing', 'description': '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).\n\nMinimum 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".'}, {'measure': 'Number of Participants With Reduction of 50% or More in Hamilton Depression Rating Scale(HAM-D) Scores at D7', 'timeFrame': 'seven days after dosing', 'description': '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.'}, {'measure': 'Number of Participants With Reduction of 50% or More in Montgomery-Asberg Depression Rating Scale (MADRS) at D1, D2 and D7', 'timeFrame': 'one, two, and seven days after dosing', 'description': '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.'}, {'measure': 'Number of Participants With a Score Lower Then or Equal to 7 in the Hamilton Depression Rating Scale (HAM-D) at D7', 'timeFrame': 'seven days after dosing', 'description': '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.'}, {'measure': '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', 'timeFrame': 'one, two and seven days after dosing', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Depression', 'Ayahuasca', 'Psychedelics'], 'conditions': ['Major Depression']}, 'referencesModule': {'references': [{'pmid': '26650973', 'type': 'BACKGROUND', 'citation': 'Sanches RF, de Lima Osorio F, Dos Santos RG, Macedo LR, Maia-de-Oliveira JP, Wichert-Ana L, de Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study. J Clin Psychopharmacol. 2016 Feb;36(1):77-81. doi: 10.1097/JCP.0000000000000436.'}, {'pmid': '25806551', 'type': 'BACKGROUND', 'citation': 'Osorio Fde L, Sanches RF, Macedo LR, Santos RG, Maia-de-Oliveira JP, Wichert-Ana L, Araujo DB, Riba J, Crippa JA, Hallak JE. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report. Braz J Psychiatry. 2015 Jan-Mar;37(1):13-20. doi: 10.1590/1516-4446-2014-1496.'}, {'pmid': '31798447', 'type': 'DERIVED', 'citation': 'Zeifman RJ, Palhano-Fontes F, Hallak J, Arcoverde E, Maia-Oliveira JP, Araujo DB. The Impact of Ayahuasca on Suicidality: Results From a Randomized Controlled Trial. Front Pharmacol. 2019 Nov 19;10:1325. doi: 10.3389/fphar.2019.01325. eCollection 2019.'}, {'pmid': '31231276', 'type': 'DERIVED', 'citation': 'de Almeida RN, Galvao ACM, da Silva FS, Silva EADS, Palhano-Fontes F, Maia-de-Oliveira JP, de Araujo LB, Lobao-Soares B, Galvao-Coelho NL. Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial. Front Psychol. 2019 Jun 4;10:1234. doi: 10.3389/fpsyg.2019.01234. eCollection 2019.'}, {'pmid': '29903051', 'type': 'DERIVED', 'citation': 'Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, Pessoa JA, Mota-Rolim SA, Osorio FL, Sanches R, Dos Santos RG, Tofoli LF, de Oliveira Silveira G, Yonamine M, Riba J, Santos FR, Silva-Junior AA, Alchieri JC, Galvao-Coelho NL, Lobao-Soares B, Hallak JEC, Arcoverde E, Maia-de-Oliveira JP, Araujo DB. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019 Mar;49(4):655-663. doi: 10.1017/S0033291718001356. Epub 2018 Jun 15.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of the present trial is to test the efficacy of Ayahuasca in treatment-resistant depression. Ayahuasca is a decoction of two plants, long used by Amazonian Amerindians. Traditionally, it is prepared by decoction of a bush (Psychotria viridis) with a liana (Banisteriopsis caapi). P. viridis is a rich source of N,N-dimethyltryptamine (DMT), a serotonergic agonist, and B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A), such as harmine, harmaline. The study is designed as a randomized placebo controlled trial with two parallel arms, and it will also evaluate changes of different biomarkers of depression including anatomical and functional Magnetic Resonance Imaging (MRI), serum levels of BDNF, TNF-a, cortisol, IL-6, and IL-10, polysomnography, neuropsychological, psychiatric scales and questionnaires.', 'detailedDescription': '1\\) Background\n\nThe therapeutic effectiveness of currently available antidepressant is low. Less than 50% of the patients achieve remission after single treatment, and about 30% after four different treatments. Besides low response rates, pharmacological treatment are associated with several side effects and response onset is usually long (\\~2-3 weeks). Thus, great effort has been made to the development of alternative antidepressants. For instance, ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and potent antidepressant effects in treatment of major depressive and bipolar disorders.\n\nThis proposal aims at testing the antidepressant effects of Ayahuasca, traditionally prepared by decoction of two plants: Psychotria viridis and Banisteriopsis caapi, long used by Amazonian Amerindians. P. viridis is a rich source of the serotonergic agonist N,N-dimethyltryptamine (DMT), whereas B. caapi contains potent monoamine oxidase-A inhibitors (MAOi-A) such as harmine, harmaline, and tetrahydroharmine, a serotonin reuptake inhibitor.\n\nCommon effects of Ayahuasca include sedation, gastrointestinal distress, changes of spatiotemporal scaling, dissociation, sense of well-being, insights, feelings of apprehension, increased interoceptive attention and sensory pseudo-hallucinations. Effects begin at 30-40 min after oral intake, and last up to 4 hours. Previous studies suggest the absence of psychological, neuropsychological or psychiatric harm caused by prolonged Ayahuasca consumption, and it is not addictive, on the contrary, it also shows promise in treating addiction.\n\nRecently, two preliminary open label studies have tested tolerability, safety and the antidepressant effect of Ayahuasca in treatment-resistant depression. In the first study, six patients were recruited, in the second, 17 patients. The results show significant decrease in depression severity (HAM-D \\& MADRS scales) already at 2 hours after intake, which lasted for 21 days. Although the results are promising, they must be considered with caution, specially due to the lack of control of the placebo effect, which is generally high in clinical trials.\n\nThus, the present study is a randomized placebo-controlled trial in 50 patients with treatment resistant depression. Besides the Antidepressant effects of Ayahuasca, this study will also evaluate different biomarkers of depression, including anatomical and functional Magnetic Resonance Imaging (MRI), serum levels of BDNF, TNF-a, cortisol, IL-6, and IL-10, polysomnography, neuropsychological and psychiatric scales and questionnaires.\n\n2\\. Methods\n\nAll 50 patients will undergo routine evaluation, including complete blood testing for individual glycemic profile, serum cholesterol and triglyceride, plasma sodium and potassium, urea and creatinine.\n\nPatients will undergo a wash-out period, between 7 and 14 days prior to the experimental session, depending on the lifetime of the antidepressant in use. Experiments will take place at the Hospital Universitário Onofre Lopes, a tertiary university hospital affiliated to the Universidade Federal do Rio Grande do Norte (UFRN), Brazil.\n\nIn the treatment session, 25 patients will drink Ayahuasca, 25 will drink an inert placebo. Psychiatric scales (HAM-D, MADRS, BPRS, CADSS and YMRS) will be completed during treatment session, day one before (-D1), one day after (+D1), two days (+D2), seven days (+D7), fourteen days (+D14), one month (+M1), and up to six months (+M6) following the treatment session. The following exams will also be conducted at D-1 and D+1: neuropsychological tests (watch test, trail test, and N-back), structural and functional MRI, polysomnography and blood testing (BDNF, TNF-a, cortisol, oxytocin, IL-6, and IL-10).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age: 18-60 years old;\n* Diagnostic of major depressive disorder (DSM-IV);\n* At least two previous unsuccessful antidepressant medications;\n* Current depressive episode (HAM-D \\>= 17).\n\nExclusion Criteria:\n\n* History of psychosis;\n* Present or past history of bipolar disorder or schizophrenia;\n* Diagnosis of current clinical disease, based on history, physical examination and routine hematologic and biochemical tests;\n* Serious and imminent suicidal risk;\n* Pregnancy, current drug or alcohol dependence;\n* Previous experience with ayahuasca.'}, 'identificationModule': {'nctId': 'NCT02914769', 'briefTitle': 'Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression', 'organization': {'class': 'OTHER', 'fullName': 'Universidade Federal do Rio Grande do Norte'}, 'officialTitle': 'Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression', 'orgStudyIdInfo': {'id': 'CNPq-466760/2014-0'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'placebo', 'description': 'patients receiving a passive placebo', 'interventionNames': ['Drug: placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Ayahuasca', 'description': 'patients receiving Ayahuasca', 'interventionNames': ['Drug: Ayahuasca']}], 'interventions': [{'name': 'Ayahuasca', 'type': 'DRUG', 'otherNames': ['treatment'], 'description': 'patients will receive a single dose of ayahuasca.', 'armGroupLabels': ['Ayahuasca']}, {'name': 'placebo', 'type': 'DRUG', 'description': 'patients will receive a single dose of a passive placebo.', 'armGroupLabels': ['placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '59012-300', 'city': 'Natal', 'state': 'Rio Grande do Norte', 'country': 'Brazil', 'facility': 'Draulio B de Araujo', 'geoPoint': {'lat': -5.795, 'lon': -35.20944}}], 'overallOfficials': [{'name': 'Draulio B de Araujo, Ph.D', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Brain Institute - UFRN'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Universidade Federal do Rio Grande do Norte', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Sao Paulo', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Draulio Barros de Araujo', 'investigatorAffiliation': 'Universidade Federal do Rio Grande do Norte'}}}}