Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

NCT06656702 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: IRB00408938
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Depressive symptoms as assessed by the Montgomery-Asberg Depression Rating Scale

  Baseline, 1 week post psilocybin session, 1 month post psilocybin session

• Depressive symptoms as assessed by the and ALS Depression Inventory

  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

  6 months

• Impact of psilocybin treatment on hopelessness as assessed by the Beck Hopelessness Scale

  6 months

• Impact of psilocybin treatment on function as assessed by the ALS Functional Rating Scale-Revised

  6 months

Study Arms (1)

Psilocybin

OTHER

All subjects will be in the same, open label arm

Drug: Psilocybin

Interventions

Psilocybin DRUG

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.

Psilocybin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years and older.
• Patients must fulfill ALS El Escorial criteria for possible, probable, laboratory supported probable or definite ALS.
• 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.
• 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.
• Clinically significant depressive symptoms as evidenced by an Assessment of Depression Inventory (ADI)-12 score \>22.

You may not qualify if:

• Patients with severe speech impairments, including those who are nonverbal, require assisted speech devices, and those who can only communicate by writing or texting.
• Patients who are unable to consent for themselves.
• Patients with tracheostomy or continuous continuous positive airway pressure (CPAP) or BiPAP.
• Known clinical evidence of frontotemporal dementia.
• 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).
• Epilepsy with history of seizures
• Renal disease (creatinine clearance \<40 ml/min using the Cockraft and Gault equation)
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• 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).
• 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).
• 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.
• 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
• Have a first degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I disorder.

Sponsors & Collaborators

• United States Department of Defense: collaborator
• Congressionally Directed Medical Research Programs: collaborator
• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Ambereen K Mehta, MD, MPH, FAAHPM

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Betsy Mosmiller

CONTACT

410-502-0495; emosmil1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 24, 2024
• Study Start: April 9, 2025
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)