Clinical trial NCT06816667: Safety, Tolerability, and Efficacy of Sublingual Microdoses of 5-MeO-DMT for Depression and Anxiety
Official title: A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability and Efficacy of Multiple Sublingual Microdoses of 5-MeO-DMT in Reducing Symptoms of Depression and/or Anxiety.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Biomind Labs Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hospital Descentralizado Dr. Marcial V. Quiroga
name: Universidad Católica de Cuyo
First posted: 2025-02-10
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse Events Coded by MedDRA Following Sublingual Administration of 5-MeO-DMT
timeFrame: Throughout the 6 weeks of the interventional study.
measure: Maximum Plasma Concentration (Cmax) following sublingual administration of 5-MeO-DMT.
timeFrame: From baseline at 0 minutes to 120 minutes following administration.
measure: Time to Maximum Plasma Concentration (Tmax) following sublingual administration of 5-MeO-DMT
timeFrame: From baseline at 0 minutes to 120 minutes following administration.
measure: Area Under the Curve (AUC) following sublingual administration of 5-MeO-DMT.
timeFrame: From baseline at 0 minutes to 120 minutes following administration.
measure: Elimination Half-life (t1/2) of 5-MeO-DMT.
timeFrame: From baseline at 0 minutes to 120 minutes following administration.
measure: Mystical Experience Questionnaire (MEQ) Assessment at 40 Minutes Post-Administration
timeFrame: 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.
measure: Peak Experience Scale (PES) Assessment at 40 Minutes Post-Administration
timeFrame: 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.
measure: Ego Dissolution Inventory (EDI) Assessment at 40 Minutes Post-Administration
timeFrame: 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:
measure: Mean change in Beck Depression Inventory II (BDI-II) from Baseline to Week 5
timeFrame: 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.
measure: Mean change in State-Trait Anxiety Inventory (STAI) from Baseline to Week 5
timeFrame: 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.
measure: Mean change in Depression, Anxiety, and Stress Scale (DASS-21) from Baseline to Week 5
timeFrame: 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.
measure: Change in Phonological Verbal Fluency Test (FAS) from Baseline to Week 5
timeFrame: 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.
measure: Change in Paced Auditory Serial Addition Test (PASAT) from Baseline to Week 5
timeFrame: 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.
measure: Change in Digit Span Scale (DSS) from Baseline to Week 5
timeFrame: The DSS will be administered at baseline (Week 0), during treatment (Weeks 1-4), and at follow-up (Week 5) to assess changes in attention and working memory following 5-MeO-DMT administration.
Other outcomes:
Locations:
city: San Juan
country: Argentina
facility: Hospital Descentralizado Dr. Marcial V. Quiroga.
state: Rivadavia
Study officials:
affiliation: Biomind Labs Inc.
name: Martin A. Bruno, PhD
role: PRINCIPAL_INVESTIGATOR
References: