Dextromethorphan (DXM) / Anhedonia in Healthy Volunteers / Psilocybin (drug) · Phase 1 Trial

A Study of Psychedelics in Healthy Older Adults With Low Well-being

ClinicalTrials.gov · September 9, 2026

Preliminary Why this matters to you Expert discussion

Early or partial results. Treat as a signal, not a conclusion.

AI Summary

This is a registered Phase 1 study examining acute electroencephalographic and inflammatory biomarker responses to psilocybin versus dextromethorphan in older adults (50–90 years) with anhedonia. No results have been posted; the record describes the planned protocol only and should not be interpreted as yielding any evidence of efficacy or safety.

What was studied

Phase 1, Interventional, Randomized, Parallel, Triple masking, Treatment purpose. Anhedonia in Healthy Volunteers, Older Adults (50-90 Years); age from 50 Years; to 85 Years; accepts healthy volunteers. Intervention: A low-to-moderate dose of Psilocybin (5-10 mg); A moderate-to-high dose of Psilocybin (25-30 mg); A low-to-moderate dose of Dextromethorphan (30-60 mg); A moderate-to-high dose of Dextromethorphan (80-90 mg). Compared with: Dextromethorphan (active control) at matched dose ranges.. n = 80. 1 site: United States.

Key findings

Safety

Primary outcome is an acute neurophysiological surrogate (EEG complexity); clinical benefit or safety is not addressed in this protocol.

Who this may help

The source did not state who this applies to in practice.

Plain-language summary

Phase 1 study registration with no reported results; early-stage investigation of psilocybin's acute neurophysiological effects in a novel population using surrogate endpoints (EEG complexity, biomarkers).

Study design

As stated by the source record.

MethodsPrimary outcome measure: Acute changes in EEG-based ESBA (assessed at Pre- to post-dose two hours later)

DesignPhase 1, Interventional, Randomized, Parallel, Triple masking, Treatment purpose

PopulationAnhedonia in Healthy Volunteers, Older Adults (50-90 Years); age from 50 Years; to 85 Years; accepts healthy volunteers

Sample size80

InterventionA low-to-moderate dose of Psilocybin (5-10 mg); A moderate-to-high dose of Psilocybin (25-30 mg); A low-to-moderate dose of Dextromethorphan (30-60 mg); A moderate-to-high dose of Dextromethorphan (80-90 mg)

ComparatorDextromethorphan (active control) at matched dose ranges.

Setting1 site: United States

Reported figures

Quoted from the source exactly as published.

Planned enrollment80

Study phasePHASE 1

Primary outcome measureAcute changes in EEG-based ESBA, pre- to post-dose two hours later

Psilocybin dose range (low-to-moderate)5–10 mg

Psilocybin dose range (moderate-to-high)25–30 mg

Study durationUp to 3 months

Caveats

This is a registry record only; no results, outcomes, or efficacy data have been reported.
Blinding, randomisation method, and allocation concealment not described in the registry text.
Per-arm sample sizes not specified; four drug arms across 80 participants may yield underpowered comparisons.
Primary outcome is an acute neurophysiological surrogate (EEG complexity); clinical benefit or safety is not addressed in this protocol.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

moderate

Phase 1 with active comparator (DXM); cross-arm design but no results posted.

Directness

limited

Primary outcomes are acute EEG changes and plasma neuroinflammation markers, not clinical endpoints.

Consistency

insufficient

No results reported; consistency cannot be assessed from registry record alone.

Risk of bias

insufficient

Study protocol registered but no methods detail on blinding, allocation concealment, or analysis plan.

Sample adequacy

limited

80 participants estimated across four drug arms; small per-arm sample for Phase 1 mechanistic work.

What is missing. This record has no key findings. That is a gap in the analysis, not a judgement about the study.

Source abstract

Registry record from ClinicalTrials.gov (NCT07386730). This is a study registration, not published results. Lead sponsor: Jennifer Mitchell. Recruitment status: RECRUITING. Phase: PHASE1. Study type: INTERVENTIONAL. Enrollment: 80 participants (ESTIMATED). Conditions: Anhedonia in Healthy Volunteers, Older Adults (50-90 Years). Interventions: DRUG: Psilocybin (drug); DRUG: Dextromethorphan (DXM). Primary outcome measures: Acute changes in EEG-based ESBA , Pre- to post-dose two hours later. Brief summary: This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being. The main questions it aims to answer are, does psilocybin: 1. Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology. 2. Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology. 3. Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below. Researchers will compare participants who receive the following drug options: * A low-to-moderate dose of Psilocybin (5-10 mg) * A moderate-to-high dose of Psilocybin (25-30 mg) * A low-to-moderate dose of Dextromethorphan (30-60 mg) * A moderate-to-high dose of Dextromethorphan (80-90 mg)

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Dextromethorphan (DXM)Anhedonia in Healthy VolunteersJennifer MitchellNCT07386730Psilocybin (drug)Older Adults (50 90 Years)