Psilocybin-Assisted Physical Therapy in Chronic Low Back Pain

NCT ID: NCT07306364

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-06-30

Study Completion Date

2029-06-30

Brief Summary

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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.

Detailed Description

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Preclinical and human studies suggest that psilocybin can temporarily disrupt rigid, maladaptive patterns of brain activity and promote longer-lasting changes in how the brain processes internal sensations. People with chronic pain who have used psilocybin qualitatively describe feeling more aware of their bodies, able to reinterpret pain sensations, and less distressed and disabled by their pain.

Building on these mechanistic insights, this randomized, double-blind, placebo-controlled trial will evaluate a single dose of low- (10 mg), moderate-dose (25 mg), or placebo (niacin) administered prior to a standardized course of physical therapy (PT) in adults with chronic low back pain (CLBP). Participants in both treatment groups will receive a course of PT that is consistent with what would be delivered outside of involvement in the research study. That is, the study is evaluating psilocybin as an adjunct to PT delivered in a community outpatient PT clinic. By testing whether psilocybin-induced recalibration of brain networks can enhance engagement with and outcomes of PT, this study aims to establish a novel, non-opioid integrative strategy to relieve CLBP and restore functional recovery.

Conditions

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Chronic Low Back Pain (CLBP) Physical Therapy Psilocybin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Low-dose psilocybin (10 mg)

Group Type ACTIVE_COMPARATOR

Psilocybin 10 mg

Intervention Type DRUG

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

Moderate-dose psilocybin (25 mg)

Group Type ACTIVE_COMPARATOR

Psilocybin 25 mg

Intervention Type 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.

Placebo (niacin).

Group Type PLACEBO_COMPARATOR

Niacin 100 mg

Intervention Type DRUG

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

Interventions

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Psilocybin 10 mg

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

Intervention Type DRUG

Psilocybin 25 mg

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

Intervention Type DRUG

Niacin 100 mg

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

Intervention Type DRUG

Eligibility Criteria

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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).
* 17\. Any other condition that, in the investigator's judgment, would compromise safety or ability to complete the study.
* 18\. Known or suspected cardiovascular disease, including but not limited to atrial fibrillation, coronary artery disease, history of myocardial infarction, structural heart disease, congestive heart failure, or uncontrolled hypertension.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Joao De Aquino

Assistant Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Joao De Aquino, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

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Connecticut Mental Health Center

New Haven, Connecticut, United States

Site Status

Countries

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United States

Central Contacts

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Julia Meyerovich, M.S.

Role: CONTACT

Phone: 203-932-5711

Email: [email protected]

Joao De Aquino, M.D.

Role: CONTACT

Phone: 203-974-7560

Email: [email protected]

Facility Contacts

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Thomas McMahon

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 34867525 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37392016 (View on PubMed)

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.

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PMID: 27208316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36065128 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29030624 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39020167 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38680011 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38627909 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34228959 (View on PubMed)

Other Identifiers

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2000041668

Identifier Type: -

Identifier Source: org_study_id