Clinical TrialNeurocognitive DisordersPsilocybinRecruiting

Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

This open-label trial (n=24) will assess the feasibility of psilocybin therapy in patients with Amyotrophic Lateral Sclerosis (ALS) experiencing depressed mood. Participants will undergo an 8-week treatment course, including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments at 1, 3, and 6 months post-treatment.

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Target Enrollment
24 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

Proof-of-concept, single-group, open-label interventional trial of psilocybin in treatment-seeking patients with ALS and clinically significant depressive symptoms; primary aim is feasibility and secondary aims include depression, quality of life, hopelessness, and functional status.

Participants complete an 8-week course with two psilocybin dosing sessions (week 4: 15 mg; week 6: 15 or 25 mg) and follow-up visits at 1, 3, and 6 months to assess safety, mood, and function.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Psilocybin

experimental

Single-group, open-label psilocybin treatment arm with two dosing sessions embedded in an 8-week course.

Interventions

  • Psilocybin15 - 25 mg
    via Oral• two sessions• 2 doses total

    Session 1: 15 mg (week 4); Session 2: 15 mg or 25 mg (week 6). Psilocybin trihydrate tablets.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • 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

  • 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 Protocol, Arms & Participants

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Study Details

  • Status
    Recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment24 participants
  • Timeline
    Start: 2025-02-28
    End: 2026-07-01
  • Compound
    Psilocybin
  • Topic
    Neurocognitive Disorders

Study Team

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States

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