Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis

Inclusion criteria

• 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.

Exclusion criteria

• 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.