Efficacy of Sublingual 5-MeO-DMT for Reducing Anxiety and Depression in MCI

NCT06812221 | Completed Phase 1

• 1 other identifier: BMND08-03
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I/II clinical trial aims to test the effectiveness of a new sublingual formulation of 5-MeO-DMT in reducing symptoms of anxiety, depression, and cognitive decline in individuals with mild to moderate Alzheimer's disease. The study will include participants who have a Clinical Dementia Rating (CDR) score between 0.5 and 1, indicating mild to moderate cognitive impairment, and who meet specific educational and cognitive criteria. Participants must have an ACE-III score of ≤86 for individuals with a high level of education (≥12 years) or \<62 for those with a low educational level (≤12 years). Additionally, participants must show moderate to high levels of anxiety, as indicated by the State-Trait Anxiety Inventory (STAI), with STAI-S (State) scores ≥20 for men and ≥23 for women, and STAI-T (Trait) scores ≥20 for men and ≥26 for women. Participants also need to exhibit moderate to severe depressive symptoms, as indicated by a Beck Depression Inventory (BDI) score of ≥21. To ensure that participants are cognitively functional but showing signs of impairment, they are assessed with the CDR and ADLQ scales to confirm they can maintain independence in daily activities. All participants must have scores above the threshold on cognitive screening tests like the ACE III and IFS, ensuring no significant cognitive impairment at the baseline. The study will measure the effects of 5-MeO-DMT through a range of cognitive and psychiatric assessments: Cognitive Assessments: These include the Rey Auditory Verbal Learning Test (RAVLT) for episodic memory, the Trail Making Test (TMT) for attention and cognitive flexibility, the Semantic and Phonological Fluency Test (SFT-FAS) for verbal fluency, the Paced Auditory Serial Addition Test (PASAT) for processing speed, and the Digit Span Subtests (DSS) for attention and working memory. These tests will provide valuable insights into how 5-MeO-DMT affects cognitive functions. Psychiatric Assessments: These will assess symptoms of suicidal ideation (SSI), mood (BDI II), anxiety (STAI), and mindfulness (FFMQ), as well as self-reported cognitive complaints (CQC). These evaluations will help determine the psychological and emotional impact of 5-MeO-DMT on participants. In addition, the study will include biochemical assessments such as microalbuminuria, blood glucose levels, liver and kidney function, cholesterol, and several biomarkers of inflammation. Cardiovascular evaluations will also be conducted during the trial, ensuring comprehensive monitoring of potential side effects. This structured approach will help researchers assess the cognitive and psychological effects of 5-MeO-DMT in individuals with mild to moderate Alzheimer's disease. By focusing on participants with elevated anxiety, depression, and early cognitive decline, this trial aims to provide insights into the therapeutic potential of 5-MeO-DMT for neurodegenerative conditions.

Conditions

Mild Cognitive Impairment; Anxiety State; Depression Anxiety Disorder

Keywords

double blind placebo-controlled; Phase I/II clinical trial; ramdomized; sublingual administration; 5-MeO.DMT; anxiety; Depression; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (6)

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

  The Phonological Verbal Fluency Test (FAS) measures executive function by assessing a participant's ability to generate words within a specific time limit, categorized by a starting letter. The task is designed to evaluate verbal memory, cognitive flexibility, and processing speed. A higher score indicates better performance.

  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 Paced Auditory Serial Addition Test (PASAT) is a cognitive test used to measure processing speed and attention. Participants are presented with a sequence of numbers and must add each new number to the previous one as quickly as possible. Performance is scored based on the number of correct responses within a given time. A higher score reflects better cognitive processing and attention.

  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.

• Change in Digit Span Scale (DSS) from Baseline to Week 5

  The Digit Span Scale (DSS) is used to assess attention span and working memory. In this test, participants must repeat a series of numbers either in the same order (forward) or in reverse (backward). The DSS measures short-term memory and cognitive flexibility. A higher score indicates better working memory and attention capacity.

  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.

• 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 (3)

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

  The BDI-II 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.

Study Arms (2)

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

EXPERIMENTAL

In this arm, participants will receive a single sublingual dose of 6 mg of 5-MeO-DMT once a week for four consecutive weeks. This dosage aims to assess the potential therapeutic effects of 5-MeO-DMT in reducing anxiety and depression symptoms in individuals with Mild Cognitive Impairment (MCI). The 6 mg dose is selected to avoid inducing strong psychedelic effects, focusing on emotional well-being improvement. Participants will undergo standardized psychiatric assessments, such as STAI and BDI II, to measure changes in mood and anxiety levels. Additionally, neurocognitive assessments, including the Phonological Verbal Fluency Test (FAS), Paced Auditory Serial Addition Test (PASAT), and Digit Span Scale (DSS), will evaluate cognitive effects on executive function, processing speed, and working memory. Participants will be monitored closely for any adverse effects, changes in vital signs, and alterations in emotional or cognitive states throughout the study.

Drug: Sublingual administration; Procedure: Electroencephalography; Diagnostic Test: Biochemical mesurements; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: Vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

: Arm 2: Placebo Sublingual Administration

EXPERIMENTAL

Participants will receive a placebo formulation that mirrors the appearance, taste, and administration method of the 5-MeO-DMT doses but contains no active ingredient. This group will serve as the comparator, allowing the effects of the active 5-MeO-DMT treatment to be evaluated. Participants will undergo the same psychiatric and neurocognitive assessments as those in the experimental arm, including the STAI, BDI II, DASS-21, and cognitive tests. The placebo group will provide essential baseline data on mood, anxiety, and cognitive function, helping to determine whether observed changes in the experimental arms are due to the active drug. Monitoring for adverse events and changes in emotional or cognitive states will also be conducted in this group. The differences between this group and the 5-MeO-DMT arms will help establish the efficacy of 5-MeO-DMT for improving mood and cognitive function in individuals with MCI.

Drug: Sublingual administration; Procedure: Electroencephalography; Diagnostic Test: Biochemical mesurements; Diagnostic Test: Acute Subjective Ratings of Psychedelic Effects; Diagnostic Test: Vital signs; Diagnostic Test: Cognitive Assessments; Diagnostic Test: Psychiatric Assessments

Interventions

Sublingual administration DRUG

Participants will receive a sublingual dose of 5-MeO-DMT or placebo, once a week for four consecutive weeks.

: Arm 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration

Electroencephalography PROCEDURE

Conducting baseline electroencephalography and during the consumption of the corresponding dose.

: Arm 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration

Biochemical mesurements 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 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT 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 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT 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 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT Sublingual Administration

Cognitive Assessments DIAGNOSTIC_TEST

Cognitive assessments will evaluate the effects of sublingual 5-MeO-DMT on cognitive functions. Participants will complete 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) to measure attention span and working memory. These tests will be administered at baseline, during treatment, and post-treatment to monitor any cognitive changes in response to either a 6 mg dose of 5-MeO-DMT or placebo. This will help determine how the intervention may affect cognitive processing, memory, and attention.

: Arm 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT 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 2: Placebo Sublingual Administration; Experimental: Arm 1: 6 mg 5-MeO-DMT 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:

• Adults aged 40 to 80 years
• Diagnosis of mild to moderate Alzheimer's disease
• Clinical Dementia Rating (CDR) score between 0.5 and 1
• ACE-III score ≤ 86 for individuals with high educational levels (≥12 years of schooling)
• ACE-III score \< 62 for individuals with low educational levels (≤12 years of schooling)
• Moderate to high levels of anxiety, as defined by:
• State-Trait Anxiety Inventory (STAI-S) State score ≥20 for men, ≥23 for women
• STAI-Trait score ≥20 for men, ≥26 for women
• Mild to moderate depressive symptoms, as indicated by a Beck Depression Inventory (BDI) score ≥21
• Must provide written informed consent to participate in the study

You may not qualify if:

• Liver dysfunction
• Cardiovascular conditions (e.g., uncontrolled hypertension, angina, significant ECG abnormalities, recent transient ischemic attack or stroke, peripheral/pulmonary vascular disease without active claudication).
• Blood pressure \>140 mmHg systolic or \>90 mmHg diastolic
• Epilepsy or history of seizures
• Kidney failure
• Insulin-dependent diabetes
• Chronic obstructive pulmonary disease (COPD)
• Increased intracranial or cerebrospinal pressure
• Hyperthyroidism
• Psychotic symptoms or family history of psychotic disorders
• Prodromal symptoms of schizophrenia or dissociative identity disorder
• Severe depression or anxiety requiring immediate treatment with antidepressants or daily anxiolytics, particularly in cases with suicidal ideation
• Medications: Regular use of psychoactive medications, including benzodiazepines, serotonin-active medications (e.g., ondansetron), or monoamine oxidase inhibitors (MAOIs)
• Drug Interactions: Use of potent metabolic inducers or inhibitors, such as: Inducers: rifampicin, anticonvulsants (e.g., carbamazepine, phenytoin), nevirapine, efavirenz, taxol, dexamethasone. Inhibitors: HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, 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 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

Cognitive Dysfunction; Anxiety Disorders; Depression

Interventions

Administration, Sublingual; Vital Signs

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Administration, Oral; Drug Administration Routes; Drug Therapy; Therapeutics; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Martin A. Bruno, PhD

  Biomind Labs Inc.

  STUDY CHAIR

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: This Phase I/II clinical trial uses a randomized, double-blind, placebo-controlled design to evaluate the effects of 6 mg sublingual 5-MeO-DMT on individuals with Mild Cognitive Impairment (MCI). Participants will be randomly assigned to either the active treatment group or the placebo group, each consisting of 10 participants. The trial will last 4 weeks, with weekly doses administered under supervision. Primary outcomes include assessments of cognitive function (via ACE III and IFS) and mood (via BDI II and STAI). Safety will be closely monitored through regular checks on vital signs, ECGs, biochemical markers, and psychological evaluations. The goal is to assess the cognitive and psychological effects of 5-MeO-DMT, contributing to the understanding of its potential as a treatment for MCI-related symptoms.

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: February 6, 2025
• Study Start: December 15, 2024
• Primary Completion: February 15, 2025
• Study Completion: March 15, 2025
• Last Updated: April 9, 2025

Record last verified: 2024-11

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)