Psilocybin in Chronic Low Back Pain: An Integrative Study of Lab-Based Mechanisms and Real-World Physical Therapy Outcomes
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Change in interoceptive awareness as measured by the Multidimensional Assessment of Interoceptive Awareness-2 from 4 weeks post-dose to 8 weeks post dose
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 ≥
- •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.
排除标准
- •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.
研究组 & 干预措施
Moderate-dose psilocybin (25 mg)
干预措施: Psilocybin 25 mg (Drug)
Placebo (niacin).
干预措施: Niacin 100 mg (Drug)
Low-dose psilocybin (10 mg)
干预措施: Psilocybin 10 mg (Drug)
结局指标
主要结局
Change in interoceptive awareness as measured by the Multidimensional Assessment of Interoceptive Awareness-2 from 4 weeks post-dose to 8 weeks post dose
时间窗: 4 weeks post dose, 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).
Change in Pain, Enjoyment, and General Activity (PEG) total score at 8 weeks post dose
时间窗: 4 weeks post-dose, 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).
Change in functional disability measured by the Oswestry Disability Index (ODI) from baseline to 8 weeks post-dose.
时间窗: Baseline (Day 0), 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)
次要结局
- 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)
- Fear of movement measured using the physical activity subscale of the Fear Avoidance Beliefs Questionnaire (FABQ-PA) mean score(4 weeks post-dose, 8 weeks post-dose)
- Pain catastrophizing measured by the Pain Catastrophizing Scale (PCS-6) and Situational Catastrophizing Questionnaire (SCQ) mean score(4 weeks post-dose, 8 weeks post-dose)
- Situational pain catastrophizing measured by the Situational Catastrophizing Questionnaire (SCQ) mean score(4 weeks post-dose, 8 weeks post-dose)
- Daily pain intensity/interference measured by the Pain, Enjoyment, General Activity (PEG) Scale via daily Experience Sampling Monitoring (ESM) mean score(Daily for approximitely 28 days post-dose)
- Daily pain affect measured by the Positive and Negative Affect Schedule (PANAS) via daily Experience Sampling Monitoring (ESM) mean score(Daily for approximitely 28 days post-dose)
- Psychedelic-related adverse events will be measured by the Swiss Psychedelic Side Effect Inventory (SPSI)(8 hours post-dose)
- Subjective psychedelic effects will be measured by the 5-Dimensional Altered States of Consciousness Scale (5D-ASC) mean score(8 hours post-dose)
研究者
Joao De Aquino
Assistant Professor of Psychiatry
Yale University