Whole-mushroom psilocybin for obsessive-compulsive disorder.

A Randomized Double-masked Dose-controlled Trial to Assess the Tolerability, Safety, Subjective Experience, and Efficacy of Repeated Administration of Three Different Doses of Psilocybin Whole Mushroom for the Treatment of Obsessive-compulsive Disorder.

This trial tests whether different doses of whole psilocybin mushroom in chocolate can help adults with moderate-to-severe OCD who are not taking other psychoactive medications or street drugs.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Arizona (Academic / other)
• Locations: 1 site (Tucson, Arizona)
• Trial ID: NCT07347405 on ClinicalTrials.gov

What this trial studies

This phase 1 study enrolls 30 adults with DSM-5 OCD and Y-BOCS scores of at least 16 who have failed at least one guideline-concordant treatment. Participants are randomly assigned to low (10 mg), medium (20 mg), or high (30 mg) doses of whole psilocybin mushroom delivered in three chocolate pieces and receive four dosing sessions about three weeks apart. Each dosing visit includes a preparation session with a study therapist, monitoring by two staff with hourly vital sign checks during the session, and discharge with a responsible adult once effects have resolved. After the treatment phase, participants are contacted monthly for safety and symptom follow-up.

Who should consider this trial

Good fit: Ideal candidates are adults (18+) with DSM-5 diagnosed OCD of at least moderate severity (Y-BOCS ≥16), who have not responded to at least one adequate guideline-concordant treatment and who are willing and able to stop prohibited psychoactive medications and supplements before dosing.

Not a fit: People already well controlled on current treatments, those unable or unwilling to stop disallowed medications or supplements, or those with medical or psychiatric conditions making them unsafe for outpatient dosing are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could reduce OCD symptoms and provide a new treatment option for people who have not benefited from current therapies.

How similar studies have performed: Other small studies and case reports of psilocybin have shown promise for depression and anxiety, but controlled evidence specifically for OCD is limited and this approach remains relatively novel.

Eligibility criteria

Inclusion Criteria:

* Aged 18 years old, and older
* Have OCD (DSM-5) based on diagnostic interview using the Structured Clinical Interview for DSM-5 Research Version (SCID).
* At least moderate severity: Yale-Brown Obsessive Compulsive Scale (YBOCS) score ≥16.
* Failed at least one adequate trial of guideline concordant treatment.
* Considered safe for independent living
* Subjects must discontinue use of any of the following prescription or over the counter (OTC) products or nutritional supplements at least two weeks prior to initiating double-blind treatment:

  * Monoamine oxidase (MAOI), UGT1A10, and UGT1A9 inhibitors
  * Other active OCD treatments (cognitive behavioral therapy \[CBT\] or other psychotherapy; electrical or magnetic device treatments; pharmacological treatments such as antidepressant medications (e.g., SSRIs, SNRIs, MAOIs, TCAs, 5HT2 blockers, NERIs, etc.), lithium, antipsychotic drugs, 5-HT2 antagonists such as pimavanserin, and glutamatergic acting medications)

    \* Note that fluoxetine must be discontinued at least 6 weeks prior to initiating double-blind treatment.
  * 5HT2 agonists (e.g., efavirenz, lorcaserin), which may alter the response to psilocybin
  * Serotonin-acting dietary supplements (e.g., 5-hydroxy-tryptophan, St. John's wort) due to potential for interaction with psilocybin and increased safety risks

Exclusion Criteria:

* Concurrent active substance use disorder, or a personal history of psychosis.
* History of psychosis among first degree relatives as determined by the Family Interview for Genetic Studies (FIGS)32
* Medical illness based on physical examination and routine blood testing that may complicate cardiovascular safety or drug metabolism or excretion. Examples include: 1) Cardiovascular conditions: lifetime history of stroke, lifetime myocardial infarction, uncontrolled hypertension (resting blood pressure \>140/90 mmHg), tachycardia (resting heart rate \>100 beats per minute), elongated QT interval corrected by Fridericia's formula (QTcF; interval \>450 msec), participants with existing valvular heart disease, or clinically significant arrhythmia (\<1 year prior to signing the ICF); 2) Metabolic conditions: subjects with diabetes should have a stable diabetes treatment regimen and no history of diabetic ketoacidosis, hyperglycemic coma, or no hypoglycemic episodes with glucose below 54 mg/dL in the 3 months prior to baseline, and fasting glucose \>70 mg/dL at baseline; 3) Severe renal impairment: eGFR \<45 mL/min/1.73 m²); and Liver failure: Child-Pugh Classes B and C.
* Unstable Chronic Obstructive Pulmonary Disease (COPD) or severe sleep apnea
* Clinically significant renal or hepatic impairment, per clinical judgment of a study physician
* EKG QTc ≥ 450 msec
* Psychiatric comorbidity that may represent an acute risk to their own or other's safety, including history of bipolar disorder (I or II) in the participant or first degree relative, as well as any family history of psychosis.
* Subjects cannot require any sedative, narcotic, or neuroleptic medications on a regular basis. Any of these medications they have taken should have been stopped long enough in the past to allow for their elimination and safe withdrawal prior to starting administration of the study drug. The specific time required will be dependent on the medication the patient was previously receiving.
* Participants who are pregnant, breastfeeding, planning a pregnancy, or planning to donate sperm within three months post-last study drug administration.
* Participants of childbearing potential or participants with partners of childbearing potential who engage in intercourse which could result in pregnancy are unwilling/unable to practice medically acceptable highly effective birth control (double barrier, oral and injectable pharmacological contraceptives, or surgical such as vasectomy or bilateral tubal occlusion) during the study and up to three months after the last study drug administration.
* Suicide attempt within the 12 months prior to enrollment
* Any condition for which MRI is contraindicated, at the discretion of a study investigator or the MRI technician, including: Pacemakers and defibrillators; artificial heart valves which are not MRI safe; any metal in head, spinal cord, eyes or chest; any electrical devices such as cochlear implants, nerve stimulators, deep brain stimulators, gastric pacemaker, or insulin or pain pumps; aneurysm clips; ferrous (i.e. non titanium alloy) implants in any part of the body.
* Use within the week prior to screening of drugs of abuse as listed in the current US DOJ DEA Drugs of Abuse Resource Guide, including:

  * Cannabinoids (marijuana, synthetic cannabinoids)
  * Simulants (amphetamine, cocaine, methamphetamine, methylphenidate, modafinil)
  * Opioids (natural and synthetic),
  * Sedatives (benzodiazepines, barbiturates, GHB, zolpidem, zaleplon, zopiclone)
  * Hallucinogens (DMT, ibogaine, LSD, MDMA, psilocybin, psilocin, PSP)
* Weight below 45kg
* Allergy or significant intolerance to chocolate or cocoa

Where this trial is running

Tucson, Arizona

• The Clinical and Translational Sciences Research Center — Tucson, Arizona, United States (Recruiting)

Study contacts

• Principal investigator: Francisco Moreno, MD — University of Arizona
• Study coordinator: The clinical and translational research center

Conditions Obsessive-Compulsive Disorder