Psilocybin-Assisted Psychotherapy in Treating Irritable Bowel Syndrome (IBS)
Triple-blind, placebo-controlled pilot RCT (n=10) assessing feasibility of psilocybin-assisted psychotherapy for severe IBS: single 25 mg oral psilocybin vs 100 mg niacin (active placebo) during guided psychotherapy with preparatory and integration sessions.
Detailed Description
Pilot randomized, parallel-group, triple-blind trial enrolling adults with severe IBS to assess feasibility and safety of psilocybin-assisted psychotherapy compared with an active placebo (niacin). Participants receive three preparatory therapy sessions, a medication-assisted psychotherapy session (psilocybin 25 mg or niacin 100 mg), and four integration sessions.
Outcomes include feasibility metrics, safety (labs, ECG, AEs), IBS symptom severity (IBS-SS), and other patient-reported measures; therapy is delivered by two licensed, trained psychedelic therapists who are present during sessions.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Psilocybin + PAP
experimentalSingle 25 mg oral psilocybin administered during a guided psychotherapy session with two therapists; includes preparatory and integration sessions.
Interventions
- Psilocybin25 mgvia Oral• single dose
Administered during the psychotherapy treatment session; two therapists present.
- Compoundvia Other• per protocol
Psychotherapy treatment sessions (3 preparation sessions, medication administration session, 4 integration sessions) provided by two licensed therapists.
Niacin + PAP
activeSingle 100 mg oral niacin (active placebo) administered during guided psychotherapy sessions; identical therapy schedule.
Interventions
- Placebo100 mgvia Oral• single dose
Niacin 100 mg as active placebo during the psychotherapy session.
- Compoundvia Other• per protocol
Psychotherapy treatment sessions (3 preparation sessions, medication administration session, 4 integration sessions) provided by two licensed therapists.
Participants
Inclusion Criteria
- Inclusion Criteria:
- Severe IBS patients meeting Rome IV criteria. Severe IBS is defined by IBS-SS >300, or one or more emergency room (ER) visit for abdominal pain in the last year.
- Experiencing persistent IBS symptoms despite pharmacologic therapy
- Have an identified support person
- Agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing
- Participants of childbearing potential must agree to practice an effective means of birth control throughout the duration of the study.
- Participants must agree to send outside medical records in order for the study team to verify eligibility.
Exclusion Criteria
- Exclusion Criteria:
- Unstable medical conditions or serious abnormalities on complete blood count, chemistries, or ECG that in the opinion of the study physician would preclude safe participation in the trial (examples include congestive heart failure; clinically significant arrhythmias or ECG abnormality such as corrected QT interval > 450; recent acute myocardial infarction or evidence of ischemia in the last year; malignant hypertension; congenital long QT syndrome; history of valvular heart disease; acute renal failure; moderate to severe hepatic impairment [Child Pugh class B and C]; respiratory failure; recent stroke < 1 year; laboratory abnormalities such as ALT ≥ 2X ULN, AST ≥ 2X ULN, hemoglobin <11.5, platelets <150, WBC >10, sodium >150, potassium <3.5 or >5.2).
- Abnormal and clinically significant results on physical examination (BP >139/89 mmHg), heart rate >90 bpm, history of pulmonary hypertension
- Significant central nervous system pathology (e.g., primary or secondary cerebral neoplasm, epilepsy, history of stroke, cerebral aneurysm, dementia, delirium)
- Primary psychotic or affective psychotic disorders (e.g., schizophrenia spectrum, schizoaffective disorder, bipolar I or II with psychotic features, substance-induced psychotic disorders, paranoid or delusional disorders, other psychotic illnesses)
- Family history of psychotic or serious bipolar spectrum illnesses (first-degree relative with schizophrenia spectrum disorder, schizoaffective disorder, bipolar I with psychotic features, or other psychotic illness)
- High risk of adverse emotional or behavioral reaction based on investigator assessment (examples: agitation, violent behaviour)
- Active substance use disorders (DSM-5 criteria for moderate or severe alcohol or drug use disorder within the past year; excludes caffeine and nicotine)
- Clinically significant suicidality or high risk of completed suicide as defined in protocol (see suicidality details)
- History of hallucinogen persisting perception disorder (HPPD)
- Pregnancy or lactation
- Cognitive impairment (MoCA < 23)
- Concurrent medications: antidepressants; centrally-acting serotonergic agents (e.g., MAOIs); antipsychotics; mood stabilizers (e.g., lithium, valproic acid); aldehyde dehydrogenase inhibitors (e.g., disulfiram); significant inhibitors of UGT1A0 or UGT1A10; niacin
- Subjects should not be taking serotonin-acting dietary supplements (e.g., 5-HTP, St. John's wort)
- Positive urine drug test for listed substances (amphetamines, barbiturates, buprenorphine, benzodiazepines, cocaine, methamphetamine, MDMA, methadone, opiates, PCP)
- Psychiatric condition incompatible with establishment of rapport with therapists or safe exposure to psilocybin
- Any psychological or physical symptom, medication or other finding prior to randomization that would make participant unsuitable per PI judgment
- Allergy or intolerance to psilocybin or niacin
- Enrolment in another clinical trial assessing interventions for anxiety, depression, or existential distress
- Unable or unwilling to provide external medical records
Study Details
- StatusNot yet recruiting
- PhasePhase I
- Typeinterventional
- DesignRandomizedtriple Blind
- Target Enrollment10 participants
- TimelineStart: 2025-01-01End: 2025-12-01
- Compounds
- Topic