Safety, Tolerability, and Efficacy of Sublingual Microdoses of 5-MeO-DMT for Depression and Anxiety

NCT06816667 | Completed Phase 1

• 1 other identifier: BMND08-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I/II clinical trial investigates the safety, tolerability, and potential therapeutic benefits of a novel sublingual formulation of 5-MeO-DMT. The study uses a randomized, double-blind, placebo-controlled design to evaluate the compound's effects on mood and overall well-being, focusing on participants with elevated symptoms of anxiety and depression. Study Design and Objectives: Participants are divided into four groups: one receiving a placebo and three receiving different doses of 5-MeO-DMT (6 mg, 9 mg, or 12 mg). Each group comprises 10 participants, totaling 40 individuals. The study administers one dose weekly for four weeks, with comprehensive monitoring at baseline and throughout the trial to track changes in emotional, cognitive, and physical well-being. Objectives: Assessing 5-MeO-DMT's impact on anxiety, depression, and emotional well-being. Understanding its pharmacokinetics (absorption, distribution, metabolism, and excretion). Evaluating its safety profile and identifying potential side effects, both mild and severe. Monitoring and Safety Participant safety is prioritized, with medical professionals conducting regular evaluations of vital signs, such as heart rate and blood pressure. Detailed tracking of mood, perception, and physical responses ensures any adverse reactions are documented and analyzed. Sublingual Administration The sublingual route is being studied for its rapid absorption into the bloodstream. Researchers will determine how efficiently the body processes 5-MeO-DMT, its duration in the bloodstream, and its influence on daily life. These findings will inform the practicality of this administration method in clinical settings. Significance of the Study This trial aims to establish a robust safety and tolerability profile for 5-MeO-DMT while exploring its effects on anxiety and depression. The results will also provide essential data to guide future studies into its therapeutic potential for improving mental health and overall quality of life. By addressing both the compound's safety and potential benefits, this research lays the groundwork for developing innovative mental health treatments.

Conditions

Healthy Volunteers

Keywords

5-MeO-DMT; Sublingual formulation; Safety; Tolerability; Pharmacokinetics; Psychedelics; Double blinded Placebo-controlled; Mood disorders; Phase I/II clinical trial; Efficacy; Anxiety; Depression

Outcome Measures

Primary Outcomes (8)

• Number of participants with Adverse Events Coded by MedDRA Following Sublingual Administration of 5-MeO-DMT

  Number of participants experiencing Adverse Events following the sublingual administration of 5-MeO-DMT, as assessed and coded by MedDRA.

  Throughout the 6 weeks of the interventional study.

• Maximum Plasma Concentration (Cmax) following sublingual administration of 5-MeO-DMT.

  Blood samples will be collected prior to and up to 120 minutes post-administration to determine the peak plasma concentration (Cmax) of 5-MeO-DMT.

  From baseline at 0 minutes to 120 minutes following administration.

• Time to Maximum Plasma Concentration (Tmax) following sublingual administration of 5-MeO-DMT

  Blood samples will be collected to assess the time taken to reach the maximum plasma concentration (Tmax) of 5-MeO-DMT.

  From baseline at 0 minutes to 120 minutes following administration.

• Area Under the Curve (AUC) following sublingual administration of 5-MeO-DMT.

  Blood samples will be analyzed to calculate the area under the plasma concentration-time curve (AUC), reflecting the overall drug exposure.

  From baseline at 0 minutes to 120 minutes following administration.

• Elimination Half-life (t1/2) of 5-MeO-DMT.

  Blood samples will be used to determine the elimination half-life (t1/2) of 5-MeO-DMT after sublingual administration.

  From baseline at 0 minutes to 120 minutes following administration.

• Mystical Experience Questionnaire (MEQ) Assessment at 40 Minutes Post-Administration

  The Mystical Experience Questionnaire (MEQ) is used to assess the subjective mystical experiences following psychedelic administration. It evaluates aspects such as feelings of unity, transcendence, and the sense of the sacred. The MEQ includes questions about altered perceptions of time, space, and self, as well as emotional and cognitive shifts. Higher scores indicate a stronger experience of mystical qualities.

  The MEQ will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to assess the subjective mystical experiences induced by sublingual 5-MeO-DMT.

• Peak Experience Scale (PES) Assessment at 40 Minutes Post-Administration

  The Peak Experience Scale (PES) is a tool for measuring the intensity and quality of peak experiences following psychedelic use. It includes items related to emotional intensity, personal insight, and transcendence. Participants rate the emotional and psychological impact of their experiences, with higher scores reflecting more intense peak experiences.

  The PES will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to capture the intensity and emotional impact of the 5-MeO-DMT experience.

• Ego Dissolution Inventory (EDI) Assessment at 40 Minutes Post-Administration

  The Ego Dissolution Inventory (EDI) assesses the extent to which participants experience a loss of ego boundaries or self-identity following psychedelic administration. It includes questions that explore the feeling of oneness with the environment, other people, or the universe, as well as the dissolution of self-related thoughts and ego. Higher scores indicate stronger experiences of ego dissolution.

  The EDI will be completed at 40 minutes post-administration during each dosing week (Weeks 1-4) to evaluate the degree of ego dissolution experienced after 5-MeO-DMT consumption.

Secondary Outcomes (6)

• Mean change in Beck Depression Inventory II (BDI-II) from Baseline to Week 5

  The BDI test will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess the impact of 5-MeO-DMT on the severity of depression.

• Mean change in State-Trait Anxiety Inventory (STAI) from Baseline to Week 5

  STAI evaluations will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess the impact of 5-MeO-DMT on anxiety levels.

• Mean change in Depression, Anxiety, and Stress Scale (DASS-21) from Baseline to Week 5

  DASS-21 will be conducted at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to evaluate the impact of 5-MeO-DMT on mood and stress.

• Change in Phonological Verbal Fluency Test (FAS) from Baseline to Week 5

  The FAS will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess changes in executive function during and after sublingual 5-MeO-DMT administration.

• Change in Paced Auditory Serial Addition Test (PASAT) from Baseline to Week 5

  The PASAT will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to evaluate the effects of 5-MeO-DMT on cognitive processing speed and attention.

Study Arms (4)

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration

EXPERIMENTAL

In this arm, participants will receive a sublingual dose of 6 mg of 5-MeO-DMT once a week for four consecutive weeks. This dosage is designed to evaluate the safety, tolerability, and potential efficacy of 5-MeO-DMT at a sub-psychedelic level. Comprehensive monitoring will include assessments of vital signs, adverse reactions, and overall well-being. Psychiatric evaluations, such as the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II), will measure changes in anxiety and depression symptoms. Neurocognitive tests will assess functions like attention, working memory, and executive function. EEG evaluations will explore potential changes in brain activity. The findings from this arm will provide critical insights into the effects of a 6 mg dose on emotional health and cognitive performance, contributing to the understanding of 5-MeO-DMT's therapeutic potential in mood and anxiety disorders without inducing a full psychedelic experience.

Drug: BMND08; Procedure: Brain electrical activity monitor; Diagnostic Test: Biochemical determinations; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

Arm 2: 9 mg 5-MeO-DMT Sublingual Administration

EXPERIMENTAL

In this arm, participants will receive a sublingual dose of 9 mg of 5-MeO-DMT once a week for four consecutive weeks. This dosage is chosen to evaluate the safety, tolerability, and pharmacokinetics of 5-MeO-DMT at a sub-psychedelic level. Participants will be closely monitored for adverse effects, changes in vital signs, and overall health during the treatment period. Assessments will include validated psychiatric evaluations, such as STAI and BDI-II, to measure changes in anxiety and depressive symptoms. Neurocognitive tests, including DSS, FAS and PASAT, will evaluate processing speed and executive function. EEG recordings will explore potential changes in brain activity. This arm will provide valuable insights into the emotional and cognitive effects of the 9 mg dose, offering critical information on its therapeutic potential for anxiety and depression while ensuring safety and tolerability without inducing full psychedelic experiences.

Drug: BMND08; Procedure: Brain electrical activity monitor; Diagnostic Test: Biochemical determinations; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

Arm 3: 12 mg 5-MeO-DMT Sublingual Administration

EXPERIMENTAL

In this arm, participants will receive a sublingual dose of 12 mg of 5-MeO-DMT once a week for four consecutive weeks. This higher dose is designed to evaluate the safety, tolerability, and pharmacokinetics of 5-MeO-DMT at a level that remains below the threshold for inducing full psychedelic experiences. Participants will be closely monitored for adverse effects, changes in vital signs, and overall health during the treatment period. Detailed psychiatric assessments, including the STAI, BDI-II and DASS-21 will be used to measure changes in anxiety, depression, and emotional well-being. Neurocognitive tests, such as the FAS, PASAT and Digit Symbol, to evaluate attention, working memory, and processing speed. Additionally, EEG evaluations will explore potential changes in brain activity. Data from this arm will provide critical insights into the therapeutic potential of the 12 mg dose for reducing mood and anxiety symptoms while ensuring safety and maintaining tolerability.

Drug: BMND08; Procedure: Brain electrical activity monitor; Diagnostic Test: Pharmacokinetic Study of Sublingually Administered Psychoactive Substance; Diagnostic Test: Biochemical determinations; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

Arm 4: Placebo Sublingual Administration

PLACEBO COMPARATOR

Participants in this arm will receive a placebo formulation administered sublingually once a week for four consecutive weeks. The placebo is designed to be indistinguishable from the active 5-MeO-DMT formulations in appearance, taste, and administration method, ensuring that both participants and investigators remain blinded to treatment allocations. Participants will undergo the same evaluations as those in the active treatment arms. These assessments include psychiatric evaluations (STAI, BDI-II, and DASS-21), and neurocognitive tests to measure attention, memory, and processing speed. EEG evaluations will also be performed to explore potential changes in brain activity. This arm serves as the baseline comparator, allowing for the differentiation of the specific therapeutic effects of 5-MeO-DMT from potential placebo effects. The findings will help establish the safety and efficacy of the active compound in reducing symptoms of anxiety and depression.

Drug: BMND08; Procedure: Brain electrical activity monitor; Diagnostic Test: Biochemical determinations; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

Interventions

BMND08 DRUG

Participants will receive a sublingual dose of 5-MeO-DMT once a week for four consecutive weeks. The intervention will be administered in the form of a sublingual tablet. The substance 5-MeO-DMT, a potent tryptamine, is known for its psychoactive properties but will be administered at a dose that does not induce a full psychedelic experience.

Also known as: Sublingual Administration of BMND08, 5 MeO-DMT, 5-Methoxy-N,N-dimethyltryptamine

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Brain electrical activity monitor PROCEDURE

EEG is a technique used to monitor brain electrical activity by recording brain waves through electrodes placed on the scalp. This procedure allows the assessment of brain waves such as delta, theta, alpha, and beta, specifically to evaluate the changes in brain activity following sublingual administration of 5-MeO-DMT.

Also known as: Electroencephalography (EEG)

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Pharmacokinetic Study of Sublingually Administered Psychoactive Substance DIAGNOSTIC_TEST

For pharmacokinetic analysis, approximately 6 mL of EDTA blood will be collected to assess the pharmacokinetics of a sublingual dose of 5-MeO-DMT. Samples will be obtained at baseline (pre-dose, 0 minutes) and at the following time points post-dose: 5, 10, 20, 30, 40, 50, 60, and 120 minutes.

Also known as: Pharmacokinetics

Arm 3: 12 mg 5-MeO-DMT Sublingual Administration

Biochemical determinations DIAGNOSTIC_TEST

Biochemical determinations will be performed to assess hematological, renal, hepatic, cardiac, and cellular lysis functions. The biochemical markers that will be measured include red blood cells, hematocrit, hemoglobin, glycated hemoglobin, white blood cells, microalbuminuria (urine albumin/creatinine ratio), and various serum markers such as cortisol, glucose, urea, serum creatinine, total cholesterol, HDL, LDL, triglycerides, AST, ALT, lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, and C-reactive protein.

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Acute Subjective Ratings of Psychedelic Effects DIAGNOSTIC_TEST

To determine the intensity of the acute effects experienced by subjects, retrospective ratings will be collected 1 hour after 5-MeO-DMT or placebo exposure. Subjective ratings will include the Peak Experience Scale (PES), the Ego Dissolution Inventory (EDI), and the Mystical Experiences Questionnaire (MEQ).

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

vital signs DIAGNOSTIC_TEST

Vital signs, including blood pressure, heart rate, oxygen saturation, respiration rate, body temperature, and electrocardiograms (ECGs), will be monitored over the six weeks of the treatment

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Cognitive Assessments DIAGNOSTIC_TEST

Cognitive assessments will evaluate the effects of sublingual 5-MeO-DMT on cognitive functions. Participants will undergo the Phonological Verbal Fluency Test (FAS) to assess executive function, the Paced Auditory Serial Addition Test (PASAT) to evaluate processing speed, and the Digit Span Scale (DSS) for attention span and working memory. These tests will be administered at baseline, during treatment, and post-treatment to assess any cognitive changes in response to the different doses of 5-MeO-DMT (6 mg, 9 mg, 12 mg) or placebo, helping to determine how the intervention may influence cognitive processing, memory, and attention.

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Psychiatric Assessments DIAGNOSTIC_TEST

Psychiatric evaluations will be conducted to assess the emotional and psychological effects of sublingual 5-MeO-DMT. Participants will complete the Beck Depression Inventory II (BDI II) to measure mood and depressive symptoms, the State-Trait Anxiety Inventory (STAI) to evaluate state anxiety, and the Depression, Anxiety, and Stress Scale (DASS-21) to assess stress levels. Additionally, the Suicidal Ideation Scale (SSI) will be used to monitor any changes in suicidal ideation throughout the study. These psychiatric assessments will be administered at multiple time points during the study to evaluate the potential therapeutic effects of 5-MeO-DMT in improving mood, anxiety, and overall psychological well-being.

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration; Arm 2: 9 mg 5-MeO-DMT Sublingual Administration; Arm 3: 12 mg 5-MeO-DMT Sublingual Administration; Arm 4: Placebo Sublingual Administration

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participants aged between 40 and 80 years, regardless of sex.
• Must provide written informed consent to participate in the study.
• Participants must exhibit moderate to high levels of anxiety and/or depression:
• Anxiety levels assessed using the State-Trait Anxiety Inventory (STAI):
• STAI-S (State) score of ≥20 for men and ≥23 for women
• STAI-T (Trait) score of ≥20 for men and ≥26 for women
• Depression levels assessed using the Beck Depression Inventory (BDI):
• BDI score of ≥21 indicating the presence of moderate to severe depressive symptoms.
• Participants may meet the criteria for either anxiety, depression, or both, as long as they meet the respective thresholds for each

You may not qualify if:

• Liver dysfunction
• Cardiovascular conditions, including: Uncontrolled hypertension, Angina, Clinically significant ECG abnormalities (e.g., atrial fibrillation), Transient ischemic attack (TIA) within the last 6 months.
• Stroke or peripheral/pulmonary vascular disease without active claudication.
• Blood pressure exceeding 140 mmHg systolic or 90 mmHg diastolic.
• Epilepsy or a history of seizures.
• Kidney failure.
• Insulin-dependent diabetes.
• Chronic obstructive pulmonary disease (COPD).
• Increased intracranial or cerebrospinal pressure
• Hyperthyroidism
• Psychotic symptoms or a family history of psychotic disorders
• Prodromal symptoms of schizophrenia or dissociative identity disorder.
• Severe symptoms of depression or anxiety requiring immediate treatment with antidepressants or daily anxiolytic medications, especially in cases involving suicidal ideation.
• Medications: Regular use of prescribed psychoactive medications, such as: Benzodiazepines, Medications affecting serotonin neurons (e.g., ondansetron), Monoamine oxidase inhibitors (MAOIs).
• Drug Interactions: Use of potent metabolic inducers or inhibitors, including: Inducers: Rifampicin (rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, phenobarbital), nevirapine, efavirenz, taxol, dexamethasone. or Inhibitors: All HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, and troleandomycin.

Sponsors & Collaborators

• Biomind Labs Inc.: lead
• Hospital Descentralizado Dr. Marcial V. Quiroga: collaborator
• Universidad Católica de Cuyo: collaborator

Study Sites (1)

Hospital Descentralizado Dr. Marcial V. Quiroga.

San Juan, Rivadavia, 5400, Argentina

Location

Related Publications (1)

• Bistue Millon MB, Noguera L, Bruno D, Vita L, Zanino M, Kassuha DE, Ortiz JE, Feresin GE, Diaz-Dellavalle P, Orosco L, Garces MA, Diez P, Albarracin SG, Bruno MA. Safety and tolerability of multiple sublingual microdoses of 5-MeO-DMT in adults with moderate symptoms of depression and/or anxiety: a randomized, double-blind, placebo-controlled study. Neuropsychopharmacology. 2025 Oct;50(11):1715-1723. doi: 10.1038/s41386-025-02167-3. Epub 2025 Jul 15.

  PMID: 40659913 DERIVED

Related Links

• Biomind Labs is developing the next generation of pharmaceuticals to treat patients suffering from neurological disorders. This unique approach targets the original and initial drivers of the diseases.

MeSH Terms

Conditions

Mood Disorders; Anxiety Disorders; Depression

Interventions

Methoxydimethyltryptamines; Pharmacokinetics; Vital Signs

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

N,N-Dimethyltryptamine; Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Bufotenin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Serotonin; Metabolism; Pharmacological and Toxicological Phenomena; Physiological Phenomena; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Martin A. Bruno, PhD

  Biomind Labs Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ThisPhase I/II clinical trial employs a randomized, double-blind, placebo-controlled design to evaluate the safety, pharmacokinetics, and therapeutic potential of sublingual 5-MeO-DMT. Forty healthy volunteers are randomized into four groups: placebo, or 5-MeO-DMT at doses of 6 mg, 9 mg, or 12 mg, receiving weekly doses for four weeks. Phase I focuses on safety and pharmacokinetics, monitoring vital signs, ECGs, and biochemical markers while analyzing parameters like Cmax, Tmax, and AUC. Phase II assesses efficacy in reducing anxiety and depression, measured through validated scales (STAI, BDI-II, DASS-21), alongside neurocognitive assessments (FAS, PASAT). This trial aims to provide comprehensive data on 5-MeO-DMT's safety, tolerability, and potential therapeutic effects for well being, mood and anxiety disorders.

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: February 10, 2025
• Study Start: October 21, 2024
• Primary Completion: February 14, 2025
• Study Completion: March 1, 2025
• Last Updated: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The individual participant data (IPD) and any supporting information will be made available starting 6 months after the publication of the study results. This will allow sufficient time for data analysis and the dissemination of primary findings. The data will remain available for at least 5 years following the publication, ensuring ample time for other researchers to access and utilize the data for further analysis or related studies. In case of any modifications to the availability period, these will be communicated clearly along with the reasons. This time frame is subject to ethical and regulatory requirements and may be adjusted if necessary.
• Access Criteria: Researchers seeking access to the individual participant data (IPD) and supporting information must submit a formal request outlining their proposed analyses. This proposal should detail the types of analyses, including the statistical methods to be used, which will be reviewed for scientific merit and methodological rigor. A signed data sharing agreement will be required, and the request must be submitted through the designated data sharing platform or by email to the study's data management team. Access to IPD will be granted based on ethical review and approval, ensuring that the proposed research aligns with the study's objectives and respects participant confidentiality. All requests will be reviewed by an independent committee responsible for overseeing data sharing, ensuring transparency, and safeguarding participant privacy.

Locations

AR (1)