Psilocybin therapy for patients with ALS and depression

Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

This study is testing if psilocybin therapy can help people with ALS who are also feeling depressed.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06656702 on ClinicalTrials.gov

What this trial studies

This research investigates the feasibility of psilocybin therapy in patients diagnosed with Amyotrophic Lateral Sclerosis (ALS) who also experience depressed mood. The trial is designed as a proof-of-concept, open-label, single-arm study involving up to 24 participants. Over an 8-week period, patients will undergo two psilocybin sessions, with follow-up assessments to evaluate changes in depression, quality of life, hopelessness, and functional status. The study aims to provide insights into the therapeutic potential of psilocybin for this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a diagnosis of ALS and clinically significant depressive symptoms.

Not a fit: Patients with severe speech impairments or those unable to consent for themselves may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could improve mood and quality of life for patients suffering from ALS-related depression.

How similar studies have performed: While psilocybin therapy is a novel approach in this context, other studies have shown promising results in treating depression with psychedelics.

Eligibility 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:

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.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Ambereen K Mehta, MD, MPH, FAAHPM — Johns Hopkins University
• Study coordinator: Betsy Mosmiller

Conditions Amyotrophic Lateral Sclerosis