Clinical TrialNeurodegenerative Disorders5-MeO-DMTPlaceboCompleted

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

This Phase I/II randomised, triple-blind, placebo-controlled trial (n=20) will study the effects of sublingual 5-MeO-DMT (6 mg, administered weekly for four weeks) on anxiety, depression, and cognitive function in individuals with mild to moderate Alzheimer's disease.

Target Enrollment
20 participants
Study Type
Phase I/II interventional
Design
Randomized, triple Blind

Detailed Description

Randomized, triple-blind, placebo-controlled Phase I/II trial in participants with mild to moderate Alzheimer's disease or MCI (n=20). Participants are assigned 1:1 to sublingual 5-MeO-DMT 6 mg or matched placebo, administered once weekly for four weeks.

Primary assessments include cognitive measures (ACE-III, CDR, IFS, RAVLT, TMT, PASAT, DSS) and psychiatric inventories (BDI-II, STAI, SSI); safety monitoring comprises vital signs, ECGs, biochemical panels, and adverse-event tracking.

The study evaluates short-term and cumulative effects of low-dose sublingual 5-MeO-DMT on cognition, anxiety, and depressive symptoms in older adults, with EEG and subjective psychedelic-effect ratings captured acutely.

Study Protocol

Preparation

sessions

Dosing

4 sessions

Integration

sessions

Study Arms & Interventions

5-MeO-DMT 6 mg

experimental

Sublingual 6 mg once weekly for four weeks.

Interventions

  • 5-MeO-DMT6 mg
    via Sublingual• weekly• 4 doses total

    Sublingual administration once weekly for four consecutive weeks.

Placebo

inactive

Placebo sublingual formulation once weekly for four weeks.

Interventions

  • Placebo
    via Sublingual• weekly• 4 doses total

    Placebo matched to appearance and administration of active arm.

Participants

Ages
40 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 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

Exclusion Criteria

  • Exclusion Criteria:
  • 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.

Study Details

Locations

Hospital Descentralizado Dr. Marcial V. Quiroga. — San Juan, Rivadavia, Argentina

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