Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain

NCT07306364 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000041668
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Low Back Pain (CLBP); Physical Therapy; Psilocybin

Outcome Measures

Primary Outcomes (3)

• Change in interoceptive awareness as measured by the Multidimensional Assessment of Interoceptive Awareness-2 from 4 weeks post-dose to 8 weeks post dose

  The Multidimensional Assessment of Interoceptive Awareness-2 (MAIA-2) is a validated 37-item, self-report instrument assessing mind-body connections (i.e., interoceptive awareness). MAIA-2 scoring involves rating the 37 items on a 0 (never) to 5 (always) Likert scale, resulting in scores for eight subscales (Noticing, Not-distracting, Not-worrying, Attention regulation, Emotional awareness, Self-regulation, Body Listening, Trusting). Scores for each of the 8 scales are averaged (sum of items divided by number of subscale items). Higher scores indicate better interoceptive awareness. Change = (8-week post-dose score - 4-week post-dose score).

  4 weeks post dose, 8 weeks post-dose

• Change in Pain, Enjoyment, and General Activity (PEG) total score at 8 weeks post dose

  The Pain, Enjoyment, General Activity (PEG) Scale is a 3-item questionnaire used to measure how chronic pain affects a person's life, focusing on average pain intensity (P), interference with enjoyment (E), and interference with general activity (G) using 0-10 Likert scale for each item. The final PEG score is calculated by adding the three scores and dividing by three. Scores range from 0-10, with higer scores indicating higher pain impact. Change= (8-week post-dose score - 4-week post-dose score).

  4 weeks post-dose, 8 weeks post-dose

• Change in functional disability measured by the Oswestry Disability Index (ODI) from baseline to 8 weeks post-dose.

  The Oswestry Disability Index (ODI) is a widely used, 10-question self-report questionnaire that measures functional disability and quality of life for people with low back pain, assessing activities like walking, sitting, sleeping, and pain intensity, with scores ranging from 0-100% categorized into minimal (0-20%), moderate (21-40%), severe (41-60%), crippled (61-80%), and bed-bound (81-100%) disability. Change = (8-week post-dose score - baseline \[day 0\] score)

  Baseline (Day 0), 8 weeks post-dose

Secondary Outcomes (12)

• Physical activity measured by average daily step count via daily Experience Sampling Monitoring (ESM)

  Daily for approximately 28 days post-dose

• Change in functional mobility from 4 weeks post-dose to 8 weeks post-dose measured by the 10-Meter Walk Test (10MWT)

  4 weeks post-dose, 8 weeks post-dose

• Change in functional mobility from 4 weeks post-dose to 8 weeks post-dose measured by the 30-Second Sit to Stand (30STS)

  4 weeks post-dose, 8 weeks post-dose

• Change in back-specific strength from 4 weeks post-dose to 8 weeks post-dose, measured by myotomal dynamometry spanning vertebrae L2 to S2 using an isometric deadlift test.

  4 weeks post-dose, 8 weeks post-dose

• Nociceptive sensitivity assessed by a composite multimodal Quantitative Sensory Testing (QST) battery

  4 weeks post-dose, 8 weeks post-dose

Other Outcomes (4)

• Peak Plasma Concentration (Cmax) of Psilocybin

  30 minutes pre-dose; 60, 120, 240, and 360 minutes post-dose

• Area Under the Plasma Concentration-Time Curve from 0 to 6 Hours (AUC0-6h) of Psilocybin

  30 minutes pre-dose; 60, 120, 240, and 360 minutes post-dose

• Peak Plasma Concentration (Cmax) of Psilocin

  30 minutes pre-dose; 60, 120, 240, and 360 minutes post-dose

Study Arms (3)

Low-dose psilocybin (10 mg)

ACTIVE COMPARATOR

Drug: Psilocybin 10 mg

Moderate-dose psilocybin (25 mg)

ACTIVE COMPARATOR

Drug: Psilocybin 25 mg

Placebo (niacin).

PLACEBO COMPARATOR

Drug: Niacin 100 mg

Interventions

Psilocybin 10 mg DRUG

Two 5 mg psilocybin capsuels will be administered to participants randomized into the low-dose psilocybin group.

Low-dose psilocybin (10 mg)

Psilocybin 25 mg DRUG

One 25 mg psilocybin capsuel and one 100 mg niacin (placebo) capsuel will be administered to participants radomized into the moderate-dose psilocybin group.

Moderate-dose psilocybin (25 mg)

Niacin 100 mg DRUG

Two 100 mg niacin capsuels will be adminstered to participants randomized to the placebo group.

Placebo (niacin).

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Ability to provide informed consent in English.
• \. Provision of signed and dated informed consent form.
• \. Stated willingness to comply with all study procedures and availability for the duration of the study.
• \. Male and female participants aged 18-65 years.
• \. 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.
• \. At least moderate pain-related disability as measured by a total score on the ODI ≥ 15.
• \. 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.
• \. 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.
• \. Resting blood pressure ≤ 140/90 mmHg (average of three screenings) and resting heart rate 60-100 bpm.
• \. Normal screening EKG: QTcF \< 450 ms; no clinically significant arrhythmias, ischemia, or bundle branch block.
• \. Hepatic and renal function within acceptable limits: AST/ALT ≤ 2× ULN; bilirubin ≤ 1.5× ULN; eGFR ≥ 50 mL/min/1.73 m².
• \. Ability to safely ingest oral capsules for the dosing visit.
• \. Safe transportation plan after the dosing session (e.g., designated driver).

You may not qualify if:

• \. Hallucinogen Use Disorder or Hallucinogen Persisting Perceptual Disorder.
• \. 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.
• \. Active suicidal ideation or behavior in the past 3 months, as indicated on the C-SSRS.
• \. 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.
• \. 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).
• \. Total score on the ODI ≥ 35, indicating an individual is "completely disabled."
• \. 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.
• \. 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).
• \. Neurological conditions altering nociceptive response (e.g., stroke, neuropathy) or history of seizure/head injury with \> 30 minutes loss of consciousness.
• \. Contraindications to nociceptive testing (e.g., untreated hypertension \> 140/90 mmHg).
• \. Current use of serotonergic medications (e.g., SSRIs, SNRIs, TCAs).
• \. Current regular use of medications affecting pain (e.g., opioids, gabapentinoids, cyclobenzaprine).
• \. Current regular use of inhibitors of UGT1A9, UGT1A10, MAO and aldehyde or alcohol dehydrogenase.
• \. Major neurocognitive disorders (e.g., dementia) or any cognitive deficit impairing consent/participation.
• \. Abnormal EKG findings (e.g., ischemia, infarct patterns, bundle branch block, atrial fibrillation, QTcF ≥ 450 ms).

Sponsors & Collaborators

• Yale University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, United States

Location

Related Publications (9)

• Bornemann J, Close JB, Spriggs MJ, Carhart-Harris R, Roseman L. Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research. Front Psychiatry. 2021 Nov 12;12:735427. doi: 10.3389/fpsyt.2021.735427. eCollection 2021.

  PMID: 34867525 BACKGROUND

• Skosnik PD, Sloshower J, Safi-Aghdam H, Pathania S, Syed S, Pittman B, D'Souza DC. Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms. J Psychopharmacol. 2023 Jul;37(7):687-697. doi: 10.1177/02698811231179800. Epub 2023 Jun 30.

  PMID: 37392016 BACKGROUND

• Anderson SM, Raghinaru D, Pinsker JE, Boscari F, Renard E, Buckingham BA, Nimri R, Doyle FJ 3rd, Brown SA, Keith-Hynes P, Breton MD, Chernavvsky D, Bevier WC, Bradley PK, Bruttomesso D, Del Favero S, Calore R, Cobelli C, Avogaro A, Farret A, Place J, Ly TT, Shanmugham S, Phillip M, Dassau E, Dasanayake IS, Kollman C, Lum JW, Beck RW, Kovatchev B; Control to Range Study Group. Multinational Home Use of Closed-Loop Control Is Safe and Effective. Diabetes Care. 2016 Jul;39(7):1143-50. doi: 10.2337/dc15-2468. Epub 2016 Apr 13.

  PMID: 27208316 BACKGROUND

• Barba T, Buehler S, Kettner H, Radu C, Cunha BG, Nutt DJ, Erritzoe D, Roseman L, Carhart-Harris R. Effects of psilocybin versus escitalopram on rumination and thought suppression in depression. BJPsych Open. 2022 Sep 6;8(5):e163. doi: 10.1192/bjo.2022.565.

  PMID: 36065128 BACKGROUND

• Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJ. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017 Oct 13;7(1):13187. doi: 10.1038/s41598-017-13282-7.

  PMID: 29030624 BACKGROUND

• Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, Reneau TR, Metcalf NV, Chacko RV, Gratton C, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J, Yacoub E, Nelson SM, Vizioli L, Fair DA, Lenze EJ, Carhart-Harris R, Raison CL, Raichle ME, Snyder AZ, Nicol GE, Dosenbach NUF. Psilocybin desynchronizes the human brain. Nature. 2024 Aug;632(8023):131-138. doi: 10.1038/s41586-024-07624-5. Epub 2024 Jul 17.

  PMID: 39020167 BACKGROUND

• Zhao X, Du Y, Yao Y, Dai W, Yin Y, Wang G, Li Y, Zhang L. Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice. J Psychopharmacol. 2024 May;38(5):489-499. doi: 10.1177/02698811241249436. Epub 2024 Apr 28.

  PMID: 38680011 BACKGROUND

• Weleff J, Nunes JC, Costa GPA, Sofuoglu M, MacLean RR, De Aquino JP. From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder. Br J Clin Pharmacol. 2024 Dec;90(12):3036-3053. doi: 10.1111/bcp.16045. Epub 2024 Apr 16.

  PMID: 38627909 BACKGROUND

• Shao LX, Liao C, Gregg I, Davoudian PA, Savalia NK, Delagarza K, Kwan AC. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron. 2021 Aug 18;109(16):2535-2544.e4. doi: 10.1016/j.neuron.2021.06.008. Epub 2021 Jul 5.

  PMID: 34228959 BACKGROUND

MeSH Terms

Interventions

Psilocybin; Niacin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Joao De Aquino, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Meyerovich, M.S.

CONTACT

203-932-5711; julia.meyerovich@yale.edu

Joao De Aquino, M.D.

CONTACT

203-974-7560; joao.deaquinolima@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: Adults with CLBP beginning a course of PT will be allocated equally into three parallel arms. Participants will receive a single oral dose of either low-dose psilocybin (10 mg), moderate-dose psilocybin (25 mg), or placebo (niacin). All three groups will follow identical study procedures.

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: December 29, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)