Psilocybin-Assisted Physical Therapy in Chronic... — Clinical Trial Details

Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain

This Phase II, randomised, quadruple-masked, placebo-controlled, parallel-group trial (n=45) will assess whether a single administration of psilocybin (10 mg or 25 mg) given prior to a course of physical therapy can improve interoceptive awareness and thereby reduce pain and disability in adults aged 18–65 with chronic low back pain. The trial's primary aims are supportive care: to evaluate change in interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness-2), change in pain (Pain, Enjoyment, and General Activity [PEG] score) and change in functional disability (Oswestry Disability Index) up to 8 weeks post-dose. Participants will be randomised to one of three parallel arms: low-dose psilocybin 10 mg (two 5 mg oral capsules), moderate-dose psilocybin 25 mg (one 25 mg psilocybin capsule plus one 100 mg niacin capsule), or placebo (two 100 mg niacin capsules). The single oral dose is administered prior to a standardised course of outpatient community physical therapy delivered as the real-world adjunct being evaluated. Key outcomes are assessed at baseline (Day 0) and at 4 and 8 weeks post-dose, with the primary endpoint timing focused on 8 weeks; estimated enrolment is 45 and the study is planned from June 2026 to June 2029.

Detailed Description

The purpose of this research study is to investigate whether a single administration of psilocybin can improve interoceptive awareness (awareness of bodily sensations) in individuals with chronic low back pain undergoing physical therapy, and whether these improvements are linked to pain relief and better physical therapy outcomes.

Participants

Ages

18 – 65

Sexes

Male & Female

BMI

Psychosis History

Inclusion Criteria

1\. Ability to provide informed consent in English.
2\. Provision of signed and dated informed consent form.
3\. Stated willingness to comply with all study procedures and availability for the duration of the study.
4\. Male and female participants aged 18-65 years.
5\. CLBP, uniformly defined as high-impact or bothersome non-cancer low back pain lasting ≥ three months that occurs most days and limits life or work activities.
6\. At least moderate pain-related disability as measured by a total score on the ODI ≥ 15.
7\. For women of childbearing potential, must have a negative urine pregnancy test at screening and immediately before dose administration.
* Negative urine pregnancy test at screening and immediately before dose administration.
* Use of one highly effective contraception (e.g., IUD, barrier method) for ≥ 1 month prior to screening.
8\. Participants are required to commit to employing dual contraceptive methods throughout the study and to abstain from sperm or egg donation during the study period and for 28 days following the final drug dose for ova, and for 90 days following the final drug dose for sperm. Dual contraceptive methods encompass the use of a barrier contraceptive, such as condoms, coupled with another effective method capable of preventing pregnancy, such as oral or parenteral contraceptives, intrauterine devices, spermicide, and the like.
9\. Resting blood pressure ≤ 140/90 mmHg (average of three screenings) and resting heart rate 60-100 bpm.
10\. Normal screening EKG: QTcF \< 450 ms; no clinically significant arrhythmias, ischemia, or bundle branch block.
11\. Hepatic and renal function within acceptable limits: AST/ALT ≤ 2× ULN; bilirubin ≤ 1.5× ULN; eGFR ≥ 50 mL/min/1.73 m².
12\. Ability to safely ingest oral capsules for the dosing visit.
13\. Safe transportation plan after the dosing session (e.g., designated driver).
14\. Signed medical release permitting the study team to communicate with outside providers for medication/therapy history or crisis management.
15\. Designation of an adult emergency contact (relative, spouse, close friend) willing to monitor for mood/behavior changes post-dose and provide transportation if needed.
16\. Agreement to attend preparatory and integration sessions, follow-up visits, and to respond to telephone/email contacts.

Exclusion Criteria

1\. Hallucinogen Use Disorder or Hallucinogen Persisting Perceptual Disorder.
2\. Personal or family history of schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder with psychotic features; any history of substance-induced psychosis or current psychotic symptoms at Screening per the Brief Psychiatric Rating Scale.
3\. Active suicidal ideation or behavior in the past 3 months, as indicated on the C-SSRS.
4\. Lifetime use of classic psychedelics (5-HT2A agonists) within the preceding 12 months, or unwillingness to abstain from their use for up to 4 weeks post-dose.
5\. Current moderate or severe depression, as indicated by a score of ≥ 3 on the depression subscale (items 1 and 2) of the Patient Health Questionnaire-4 (PHQ-4).
6\. Total score on the ODI ≥ 35, indicating an individual is "completely disabled."
7\. Meeting DSM-5 criteria for alcohol or substance use disorders (other than tobacco use disorder) within the last year; use of THC-containing products \> 2×/week over the past 30 days or unwillingness to abstain for at least 1 week pre-dose through 4 weeks post-dose. Abstinence will be confirmed via point-of-care urine 11-nor-9-carboxy-THC testing with a cut-off ≤ 50 ng/mL.
8\. Clinically significant medical disorders (e.g., moderate-to-severe hepatic impairment \[Child-Pugh B/C\], AST/ALT \> 2× ULN, bilirubin \> 1.5× ULN, eGFR \< 50 mL/min/1.73 m², diabetes, uncontrolled thyroid disease).
9\. Neurological conditions altering nociceptive response (e.g., stroke, neuropathy) or history of seizure/head injury with \> 30 minutes loss of consciousness.
10\. Contraindications to nociceptive testing (e.g., untreated hypertension \> 140/90 mmHg).
11\. Current use of serotonergic medications (e.g., SSRIs, SNRIs, TCAs).
12\. Current regular use of medications affecting pain (e.g., opioids, gabapentinoids, cyclobenzaprine).
13\. Current regular use of inhibitors of UGT1A9, UGT1A10, MAO and aldehyde or alcohol dehydrogenase.
14\. Major neurocognitive disorders (e.g., dementia) or any cognitive deficit impairing consent/participation.
15\. Abnormal EKG findings (e.g., ischemia, infarct patterns, bundle branch block, atrial fibrillation, QTcF ≥ 450 ms).
16\. Resting QTcF prolongation or other torsades de pointes risk factors (uncontrolled electrolyte disturbances, family history of sudden death, torsadogenic medications).

Company

Product

Legal

Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain

Detailed Description

Study Arms & Interventions

Low-dose psilocybin (10 mg)

Interventions

Moderate-dose psilocybin (25 mg)

Interventions

Placebo (niacin).

Locations

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators