Efficacy of Sublingual 5-MeO-DMT for Reducing Anxiety and Depression in MCI
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.
detailed description
This Phase I/II clinical trial is designed to rigorously evaluate the efficacy of a novel sublingual formulation of 5-MeO-DMT in reducing symptoms of anxiety, depression, and cognitive decline in individuals diagnosed with mild to moderate Alzheimer's disease. The trial will employ a randomized, double-blind, placebo-controlled design, considered the gold standard in clinical research, to ensure unbiased and reliable results. By blinding both participants and investigators to treatment allocations, the study aims to generate robust data on the therapeutic potential of 5-MeO-DMT in this specific patient population.
Participants will be randomly assigned to one the placebo group or to the groups receiving 6 mg 5-MeO-DMT. Each dose group will include 10 participants, with a total of 20 volunteers enrolled. The dosing regimen consists of one sublingual administration per week over four consecutive weeks, allowing the study to assess both immediate and cumulative effects of 5-MeO-DMT on cognitive, mood, and anxiety symptoms.
Outcome Measures and Assessments: The primary outcome measure will focus on evaluating changes in cognitive function, mood, and anxiety symptoms, using a comprehensive set of neuropsychological and psychiatric assessments at multiple time points throughout the trial. Key cognitive assessments will include the Clinical Dementia Rating (CDR), Activities of Daily Living Questionnaire (ADLQ), and the Addenbrooke's Cognitive Examination III (ACE-III). These scales will provide a detailed overview of cognitive decline and the ability of 5-MeO-DMT to potentially mitigate these effects. Additionally, the Ineco Frontal Screening (IFS) will be administered to assess frontal lobe functioning.
Key psychiatric assessments will include the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Suicidal Ideation Scale (SSI), which are validated tools for measuring anxiety, depression, and suicidal thoughts. These assessments will help evaluate the emotional and psychological impact of 5-MeO-DMT on participants with Alzheimer's-related cognitive impairment.
Neurocognitive Assessments: To further evaluate the impact of 5-MeO-DMT on cognitive function, a battery of neurocognitive tests will be conducted. These will include the Rey Auditory Verbal Learning Test (RAVLT) to assess episodic memory, the Trail Making Test (TMT) for attention and cognitive flexibility, and the Digit Span Subtests (DSS) to measure working memory and attention. These tests will be administered at baseline, during dosing, and at the conclusion of the study (week 5) to monitor changes in cognitive function across time.
official title
A Phase 1/2 Randomized, Double-Blind, Placebo-Controlled Trial of Multiple Sublingual 5-MeO-DMT Microdoses for Reducing Anxiety and/or Depression in Patients With Mild Cognitive Impairment.