Safety, Tolerability and Antidepressant Effects of DMT in Patients With Depression

An Open Label Trial of Inhaled N,N-Dimethyltryptamine in Patients With Partial Response in Depression.

This study aims to evaluate the acute and subacute effects of an inhaled N, N-Dimethyltryptamine (DMT) in patients with partial response in depression.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Depression, Unipolar
• Intervention / Treatment: Drug: N,N-Dimethyltryptamine

Detailed Description

This is a phase II open-label, single-ascending, fixed-order study to assess the feasibility and efficacy of inhaled N, N-Dimethyltryptamine (DMT) in patients with partial response in depression.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • RN
    • Natal, RN, Brazil, 59012300
      • Hospital Universitário Onofre Lopes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients in current treatment for depression with a partial response.

Exclusion Criteria:

• heart failure
• liver failure
• kidney failure
• uncontrolled high blood pressure
• history of heart rhythm disorders
• history of valvular heart disease
• history of chronic obstructive pulmonary disease (COPD)
• active or in treatment for bronchial asthma
• severe obesity
• coagulation disorders
• clinical evidence or history of increased intracranial
• clinical evidence or history of cerebrospinal pressure
• history or reports of epilepsy
• severe neurological disease
• pregnancy
• reported or clinically recognized thyroid disorders
• diagnosis or family suspicion of genetic monoamine deficiency oxidase
• previous adverse response to psychedelic substances
• symptoms or family members with a present or past psychotic disorder
• dissociative identity disorder
• bipolar affective disorder
• prodromal symptoms of schizophrenia
• problematic use or abuse of alcohol or other psychoactive substances (except tobacco)
• acute or subacute risk of suicide
• acute flu symptoms
• symptoms of airway infection
• contact with a confirmed case of COVID-19 (SARS-CoV-2) in the last 7 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N,N-Dimethyltryptamine; Administration of up to 2 inhaled doses of DMT within a single day (15 mg, followed by 60 mg) with a 1-hour dose interval.	Drug: N,N-Dimethyltryptamine; DMT will be administered using a vaporizer device in an ascending fixed-order of 15mg and 60mg.; Other Names: DMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MADRS scores	Change in MADRS scores from baseline to 7 days after the dosing session. The Montgomery and Asberg Depression Rating Scale (MADRS) is in portuguese and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PHQ-9 scores	Change in PHQ-9 scores from baseline to 7 days after the dosing session. The Patient Health Questionnaire-9 (PHQ-9) is a questionnaire self-reported assessing the severity of the depression. The scale was in french and has 9 items, with an overall score ranging from 0 to 27 points. Higher score indicates more severe depression.	7 days
Change in BSI scores.	Change in BSI scores from baseline to 1 day after the dosing session. The Beck rating scale for suicidal ideation (BSI) is a 21-item self-report questionnaire. Each item is rated on a scale from 0 to 2, resulting in a total score ranging from 0 to 38.	1 day
Change in MADRS scores 14 days	Change in MADRS scores from baseline to 14 day after the dosing session. The Montgomery and Asberg Depression Rating Scale (MADRS) is in portuguese and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.	14 days
Change in MADRS scores 1 month	Change in MADRS scores from baseline to one month after the dosing session. The Montgomery and Asberg Depression Rating Scale (MADRS) is in portuguese and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.	1 month
Change in MADRS scores 3 months	Change in MADRS scores from baseline to three months after the dosing session. The Montgomery and Asberg Depression Rating Scale (MADRS) is in portuguese and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	Assessed 7 times on each session	up to 2 hours
Diastolic Blood Pressure	Assessed 7 times on each session	up to 2 hours
Heart rate	Assessed 7 times on each session	up to 2 hours
Respiratory rate	Assessed 7 times on each session	up to 2 hours
Oxygen saturation	Assessed 7 times on each session	up to 2 hours
Plasma level of glucose	Assessed 2 times on each session	up to 2 hours
Plasma level of total cholesterol	Assessed 2 times on each session	up to 2 hours
Plasma level of C-reactive protein (CRP)	Assessed 2 times on each session	up to 2 hours
Plasma level of urea	Assessed 2 times on each session	up to 2 hours
Plasma level of creatinine	Assessed 2 times on each session	up to 2 hours
Plasma level of aspartate transaminase (AST)	Assessed 2 times on each session	up to 2 hours
Plasma level of alanine transaminase (ALT)	Assessed 2 times on each session	up to 2 hours
Plasma level of cortisol	Assessed 2 times on each session	up to 2 hours
Plasma level of brain derived neurotrophic factor	Assessed 2 times on each session	up to 2 hours
Evaluate the subjective effects of DMT	Assessment of the acute subjective effects of DMT, by 5D-ASC (5 Dimensions - Altered States of consciousness). Scores range from 0 to 94, where higher scores indicate more intense psychedelic subjective effects.	up to 2 hours
Evaluate the mystical effects of DMT	Assessment of the acute subjective effects of DMT, by MEQ (Questionnaire of Mystical Experiences). Scores range from 0 to 150, where higher scores indicate more intense psychedelic subjective effects.	up to 2 hours
Evaluate the influence of expectations on improvement in depressive symptoms	Assessment of the influence of patient's expectations on improvement in depressive symptoms as measured by a 5 point likert scale range from: nothing to extreme.	up to 0.5 hours
Evaluate the influence of personality trait, by BFI (Big Five Inventory)	Assessment of the influence of personality trait assessed by the 44-item Big Five Inventory that measures an individual on the Big Five Factors (dimensions) of personality on depressive symptoms. The 5 dimensions are: Extraversion vs. introversion; Agreeableness vs. antagonism; Conscientiousness vs. lack of direction; Neuroticism vs. emotional stability; Openness vs. closedness to experience.	up to 3 months

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio Grande do Norte
• Investigators: Principal Investigator: Draulio Araujo, Ph.D, Universidade Federal do Rio Grande do Norte; Study Director: Marcelo Falchi, M.D., Universidade Federal do Rio Grande do Norte; Study Director: Fernanda Palhano-Fontes, Ph.D, Universidade Federal do Rio Grande do Norte

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2023
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): March 30, 2024

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: DMTPRD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No