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

B

Biomind Labs

Status and phase

Completed
Phase 2
Phase 1

Conditions

Healthy Volunteers

Treatments

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

Study type

Interventional

Funder types

Industry
Other

Identifiers

NCT06816667
BMND08-01

Details and patient eligibility

About

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.

Full description

This Phase I/II clinical trial employs a rigorous, randomized, double-blind, placebo-controlled design to evaluate the safety, tolerability, pharmacokinetics, and efficacy of a novel sublingual formulation of 5-MeO-DMT. The trial focuses on understanding the compound's effects in healthy volunteers and those with elevated symptoms of anxiety and depression, aiming to build a comprehensive profile of its potential therapeutic and pharmacological properties.

Study Objectives

The Phase I component emphasizes:

  • Safety and Tolerability: Assessing physiological responses, including vital signs (heart rate, blood pressure, respiration rate, temperature) and cardiac function (ECGs). Biochemical markers of renal, hepatic, and hematological health will be monitored to detect potential adverse effects.
  • Pharmacokinetics: Evaluating how 5-MeO-DMT is absorbed, distributed, metabolized, and eliminated through blood sampling at multiple time points. Key metrics include peak plasma concentration (Cmax), time to peak (Tmax), and overall exposure (AUC).

The Phase II component explores the efficacy of 5-MeO-DMT in reducing symptoms of anxiety and depression and enhancing emotional well-being.

Participants and Dosing Regimen The trial enrolls 40 participants aged 40-80, divided into four groups: one placebo group and three active treatment groups receiving sublingual doses of 6 mg, 9 mg, or 12 mg of 5-MeO-DMT. A single weekly dose is administered over four weeks, enabling the evaluation of immediate and cumulative effects.

Recruitment will target healthy volunteers who meet specific anxiety and mood criteria. Notably, participants will be screened to exclude individuals with previous psychedelic experiences involving tryptamines, ergolines, or phenethylamines, those with contraindications to the use of psychedelics, and those currently taking prescribed psychoactive medications. This includes serotonin reuptake inhibitors, benzodiazepines, medications primarily affecting serotonin neurons (e.g., ondansetron), and MAO inhibitors.

Neurocognitive and Psychological Assessments

Participants undergo validated assessments to evaluate changes in:

  • Mood and Anxiety: Tools include the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory II (BDI-II), Depression, Anxiety, and Stress Scale (DASS-21), and Suicidal Ideation Scale (SSI).
  • Cognitive Function: Neurocognitive tests like the Phonological Verbal Fluency Test (FAS), Paced Auditory Serial Addition Test (PASAT), and Digit Span Scale (DSS) assess executive function, working memory, and attention.

Validated instruments will be employed to evaluate mood, anxiety levels, cognitive function, and any perceptual or psychological effects experienced by participants. These assessments will be conducted at baseline (Week 0), during each dosing week (Weeks 1-4), and at the end of the study (Week 5). By measuring these parameters, the trial aims to identify the effects of sub-psychedelic doses of 5-MeO-DMT on cognitive processes and emotional states.

Safety Protocols The study complies with Good Clinical Practice (GCP) and ethical standards, including approval from the CEI of the Ministry of Health of San Juan, Argentina. Informed consent is obtained from all participants, who are screened to exclude individuals with prior psychedelic experiences, contraindications, or concurrent use of psychoactive medications.

The trial prioritizes participant safety with continuous monitoring and immediate medical response protocols for any adverse events.

Expected Outcomes This study aims to generate a comprehensive dataset on the safety, pharmacokinetics, and potential efficacy of sublingual 5-MeO-DMT, providing a clear and detailed understanding of its safety and tolerability profile under controlled conditions.

The findings are expected to inform future research into the therapeutic potential of 5-MeO-DMT for anxiety, depression, and other mental health disorders, offering critical insights into its clinical applications. By advancing the understanding of psychedelic compounds, this study represents a pivotal step toward developing innovative, evidence-based treatments for mental health challenges.

Enrollment

40 patients

Sex

All

Ages

40 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • 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

Exclusion criteria

  • 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

40 participants in 4 patient groups, including a placebo group

Arm 1: 6 mg of 5-MeO-DMT Sublingual Administration
Experimental group
Description:
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.
Treatment:
Diagnostic Test: vital signs
Diagnostic Test: Biochemical determinations
Diagnostic Test: Psychiatric Assessments
Drug: BMND08
Diagnostic Test: Cognitive Assessments
Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects
Procedure: Brain electrical activity monitor
Arm 2: 9 mg 5-MeO-DMT Sublingual Administration
Experimental group
Description:
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.
Treatment:
Diagnostic Test: vital signs
Diagnostic Test: Biochemical determinations
Diagnostic Test: Psychiatric Assessments
Drug: BMND08
Diagnostic Test: Cognitive Assessments
Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects
Procedure: Brain electrical activity monitor
Arm 3: 12 mg 5-MeO-DMT Sublingual Administration
Experimental group
Description:
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.
Treatment:
Diagnostic Test: Pharmacokinetic Study of Sublingually Administered Psychoactive Substance
Diagnostic Test: vital signs
Diagnostic Test: Biochemical determinations
Diagnostic Test: Psychiatric Assessments
Drug: BMND08
Diagnostic Test: Cognitive Assessments
Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects
Procedure: Brain electrical activity monitor
Arm 4: Placebo Sublingual Administration
Placebo Comparator group
Description:
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.
Treatment:
Diagnostic Test: vital signs
Diagnostic Test: Biochemical determinations
Diagnostic Test: Psychiatric Assessments
Drug: BMND08
Diagnostic Test: Cognitive Assessments
Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects
Procedure: Brain electrical activity monitor

Trial contacts and locations

1

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Central trial contact

Maria B. Bistue Millon, PhD; Maria L. Noguera Roberto, PhD

Data sourced from clinicaltrials.gov

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