Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

This study aims to study the feasibility of psilocybin therapy for patients with Amyotropic Lateral Sclerosis (ALS) with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Psilocybin

Detailed Description

The proposed research's primary objective is to study the feasibility of psilocybin therapy for patients with ALS with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population. The proposed proof-of-concept interventional trial will use a single-arm design. The study will be an open-label trial in a sample of up to 24 treatment-seeking patients with a diagnosis of ALS and depressed mood. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments 1, 3, and 6 months after the final psilocybin session.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Betsy Mosmiller; Phone Number: 410-502-0495; Email: emosmil1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins Center for Psychedelic and Consciousness Research
      • Contact: Ian Geithner, MPS; Phone Number: 410-550-0037; Email: igeithn1@jhmi.edu
      • Contact: Albert Garcia-Romeu, Ph.D.; Phone Number: 410-550-1972; Email: agarci33@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 18 years and older.
2. Patients must fulfill ALS El Escorial criteria for possible, probable, laboratory supported probable or definite ALS.
3. Patients with a pulmonary forced vital capacity (FVC) >60%. The investigators have chosen this measure of function to account for respiratory decompensation during the 6-month longitudinal portion of the study.
4. Patients with ability to swallow tablets by mouth. Participants may have a feeding tube, but must be able to swallow by mouth and cannot use the feeding tube to administer the psilocybin tablet.
5. Clinically significant depressive symptoms as evidenced by an Assessment of Depression Inventory (ADI)-12 score >22.

Exclusion Criteria:

1. Patients with severe speech impairments, including those who are nonverbal, require assisted speech devices, and those who can only communicate by writing or texting.
2. Patients who are unable to consent for themselves.
3. Patients with tracheostomy or continuous continuous positive airway pressure (CPAP) or BiPAP.
4. Known clinical evidence of frontotemporal dementia.
5. Cardiovascular conditions: corrected QT interval (QTc) >450 msec, uncontrolled hypertension (i.e., systolic blood pressure (SBP)> 139 mm Hg, diastolic blood pressure (DBP)> 89 mm Hg), resting heart rate (HR)> 90 beats per minute, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation), transient ischemic attack (TIA) in the last 6 months, stroke, peripheral or pulmonary vascular disease (no active claudication).
6. Epilepsy with history of seizures
7. Renal disease (creatinine clearance <40 ml/min using the Cockraft and Gault equation)
8. Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
9. Females who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control (i.e., intrauterine systems/devices, hormonal methods including implant, shot, patch, ring, or oral contraceptive, condom, diaphragm, sterilization, and abstinence).
10. Currently taking medications that interact with psilocybin on a regular (e.g., daily) basis: Atypical antidepressants, such as mirtazapine (Remeron), trazodone (Oleptro), vortioxetine (Brintellix), and vilazodone (Viibryd); Tricyclic antidepressants, such as amitriptyline, imipramine (Tofranil), nortriptyline (Pamelor), desipramine (Norpramin), doxepin, trimipramine (Surmontil), and protriptyline (Vivactil); and Monoamine oxidase inhibitors (MAOIs), such as Selegiline (Emsam), tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan).
11. Currently taking Nuedexta (dextromethorphan/quinidine combination), efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or UGT1A9 inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
12. Current or history of meeting Diagnostic and Statistical Manual (DSM)-5 criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I Disorder
13. Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Psilocybin; All subjects will be in the same, open label arm	Drug: Psilocybin; Psilocybin Trihydrate. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments 1, 3, and 6 months after the final psilocybin session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of psilocybin treatment as assessed by number of participants recruited, retained and adhere to treatment	feasibility will be assessed by participant recruitment, retention, and treatment adherence.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive symptoms as assessed by the Montgomery-Asberg Depression Rating Scale	Depressive symptoms from baseline at 1 week and 1 month after final psilocybin session measured by the Montgomery-Asberg Depression Rating Scale. Score range: 0-60; higher scores = worse outcome	Baseline, 1 week post psilocybin session, 1 month post psilocybin session
Depressive symptoms as assessed by the and ALS Depression Inventory	Depressive symptoms from baseline at 1 week and 1 month after final psilocybin session measured by the ALS Depression Inventory. Score ranges from 12 (best) to 48 (worst), with scores between 23 and 29 indicating mild depression and scores above 30 indicating severe depression.	Baseline, 1 week post psilocybin session, 1 month post psilocybin session
Impact of psilocybin treatment on quality of life as assessed by the EuroQoL 5-dimension, 3-level (EQ-5D-3L) 5-item ALS Assessment Questionnaire	Impact on quality of life measured by the 5-dimension, 3-level EuroQol, 5-item ALS Assessment Questionnaire. Score range 5-25; higher score more problems. The EQ-5D-3L also includes an EQ VAS, which is a vertical scale where respondents rate their health from "the best health you can imagine" to "the worst health you can imagine". The EQ-5D-3L index is calculated by subtracting the descriptive system values from 1, with 1 representing the best possible health status and a value below 0 representing the worst.	6 months
Impact of psilocybin treatment on hopelessness as assessed by the Beck Hopelessness Scale	Impact on hopelessness measured by the Beck Hopelessness Scale. Scores range from 0-20 with higher scores indicating a greater degree of hopelessness.	6 months
Impact of psilocybin treatment on function as assessed by the ALS Functional Rating Scale-Revised	Impact of function measured by the ALS Functional Rating Scale-Revised. Scale from 0 = can't do, to 4 = normal ability, with a total score range of 0- 52 points. Higher score better outcome.	6 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: United States Department of Defense; Congressionally Directed Medical Research Programs
• Investigators: Principal Investigator: Ambereen K Mehta, MD, MPH, FAAHPM, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 22, 2024
• First Posted (Actual): October 24, 2024

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: IRB00408938

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No