Psilocybin in Chronic Low Back Pain and Depression

Phase 1

Recruiting

• Conditions: Chronic Low-back Pain; Depression
• Interventions: Drug: Psilocybin; Drug: Methylphenidate

• Registration Number: NCT06355414
• Lead Sponsor: Johns Hopkins University

Brief Summary

This study seeks to provide insight on psilocybin's effects on mechanisms of chronic pain among patients with co-morbid chronic low back pain and depression (CLBP+D).

Participants will receive either a single high-dose of psilocybin (25mg absolute dose) or methylphenidate (40mg absolute dose). Participants will be asked to complete assessments of pain, depressive symptoms, and more general questionnaires regarding the participants experiences during the experimental sessions and the associated enduring effects.

Detailed Description

This study will investigate the effects of a single experimental psilocybin (25 mg fixed dose) administration compared to a dose of methylphenidate (40 mg fixed dose). Assessments will be conducted during screening visits, before and after the drug session, at follow up visits up to 1-month after the drug session, as well as periodically throughout study participation via a multi-time-per-day survey application. Forty participants will complete all study visits including follow-up visits.

Primary objectives:

1. Investigate the feasibility, safety, and acceptability of psilocybin for CLBP+D

2. Investigate the effect of psilocybin on self-report of positive affect, negative affect, and pain catastrophizing

3. Investigate the effect of psilocybin on a behavioral task called positive affective pain inhibition

Secondary objectives:

1. Investigate the durability (1-month follow-up) effects of psilocybin on self-report of positive affect, negative affect, and pain catastrophizing

2. Investigate the effect of psilocybin on dynamic associations between affective measures, pain, and function on a moment-to-moment basis.

Study Timeline

• Study First Submitted: 2024-03-26
• Study First Submitted QC: 2024-04-04
• Study First Posted: 2024-04-09
• Study Start: 2024-04-22
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-24
• Last Update Posted: 2024-10-26
• Primary Completion: 2026-07-30
• Study Completion: 2026-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 21 to 80 years old
• Have given written informed consent
• Report low back pain as ongoing problem ≥ 3 months and any low back pain on at least half of the days over the past 6 months (consistent with NIH Consensus Recommendations for defining CLBP; other chronic pain problems can be present, but CLBP must be reported as primary)
• Report at least moderate depression symptoms Grid-Hamilton Depression Rating Scale (GRID-HAMD) ≥ 17
• Fluent in English
• At least high school level of education
• Agree to abstain from any psychoactive drugs on the day prior to and the day of the drug administration session
• Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control must agree to practice an effective means of birth control throughout the duration of the study
• Be judged by study team clinicians to be at low risk for suicidality
• Concurrent psychotherapy or pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs), serotonin and norephinephrine reuptake inhibitors (SNRIs), and/or bupropion (< 300 mg bupropion) is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
• Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study
• Be otherwise medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests; CBC, comprehensive metabolic panel (CMP), urine beta-human chorionic gonadotropin (HCG), urine toxicology screen.
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
• Agree not to take any as needed (PRN) medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration
• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
• Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)

Exclusion Criteria

• Lifetime history of serious psychiatric (other than depression) or neurological disorders, including bipolar disorder, psychosis, or seizure disorder

• Lifetime history of severe substance use disorder or current (past six months) substance use disorder of moderate severity

• Clinically significant suicidal ideation (e.g. with strong intent or means) within past 6 months or lifetime history of suicide attempt

• Medical condition incompatible with psilocybin administration (e.g., cardiovascular)

• On unstable/changing dose of opioid, benzodiazepine or other psychoactive or pain medication within 4 weeks prior to enrollment and/or unable to abstain from medication on drug administration day

• Current use/positive toxicology for illicit drugs or positive breath alcohol test at screening and prior to each drug administration session.

• Clinically significant transaminitis- aspertate aminotransferase (AST) or alanine aminotransferase (ALT) greater than two times normal value).

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing;

• Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control.

• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (QTc) interval (i.e., QTc > 450 msec), heart valve, or transient ischemic attack (TIA) in the past year.

• History of seizures and/or epilepsy with history of seizures.

• Type 1 diabetes.

• BMI < 18

• Medical conditions contraindicated for methylphenidate administration:

  1. Concomitant use of Monoamine oxidase inhibitors (MAOIs), or use within 14 days of MAOI discontinuation
  2. Family history or diagnosis of Tourette's syndrome
  3. Known Fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose insufficiency
  4. Glaucoma
  5. Known hypersensitivity to methylphenidate
  6. Marked agitation, anxiety, and tension
  7. Motor tics

• Currently taking on a regular (e.g., daily) basis any antidepressant medications other than SSRIs, SNRIs, or bupropion, or any other medications that have a primary centrally-acting serotonergic effect, including MAOIs. Bupropion dosage must be < 300 mg in order to be included. For individuals who have intermittent or PRN use of such medications and/or who taper off such medications after regular use, psilocybin sessions will not be conducted until at least 14 days or 5 half-lives (whichever is greater) of the agent have elapsed after the last dose.

• Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a psilocybin session day

• Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Psilocybin	Psilocybin	This arm will receive a single, absolute dose (25 mg) of psilocybin.
Methylphenidate	Methylphenidate	This arm will receive a single, absolute dose (40 mg) of methylphenidate.

Primary Outcome Measures

Name	Time	Method
Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA Post-drug Session (1-day through 1-week after drug session) relative to Baseline (beginning the day after baseline visit is complete)	Discrete positive affect items: joy, love, hope, contentment. Positive affect will be assessed by asking participants to rate the intensity of four discrete positive emotions (joy, love, hope, contentment) on a 5-point Likert scale from 1-5 ("Very slightly or not at all" to "Extremely") and averaging those discrete items. Positive Affect scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Higher Positive Affect scores represent higher levels of positive affect.; A separate set of linear mixed-effects models (LMERs) will be utilized for each primary endpoint (aggregated averages of momentary positive affect), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in Pain Catastrophizing as assessed by the Pain Catastrophizing Scale and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA Post-drug Session (1-day through 1-week after drug session) relative to Baseline (beginning the day after baseline visit is complete)	Pain catastrophizing will be assessed with three items taken from the Pain Catastrophizing Scale that have been specifically validated for use in Ecological Momentary Assessment (EMA) studies of patients with chronic pain. Items will be administered via EMA and scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Each item is on a 5-point Likert scale (ranging from 0, "Not at all", to 4, "All the time"). Higher scores on each of these items indicates increased pain catastrophizing.; A separate set of LMERs will be utilized for each primary endpoint (aggregated averages of momentary pain catastrophizing), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in negative affect as assessed by discrete negative affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA Post-drug Session (1-day through 1-week after drug session) relative to Baseline (beginning the day after baseline visit is complete)	Discrete negative emotion items: depressed, angry, frustrated, and worried. Negative affect will be assessed by asking participants to rate the intensity of four discrete negative emotions (depressed, angry, frustrated, and worried) on a 5-point Likert scale from 1-5 ("Very slightly or not at all" to "Extremely") and averaging those discrete items. Negative Affect scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Lower Negative Affect scores represent lower levels of negative affect.; A separate set of LMERs will be utilized for each primary endpoint (aggregated averages of momentary negative affect), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in Positive Affective Pain Inhibition (Quantitative Sensory Testing)	Baseline, 1-week follow-up	Positive Affective Pain Inhibition will be assessed using quantitative sensory testing at baseline, 1-week post-drug-administration, and 1-month post-drug-administration. Positive affective pain inhibition is measured as the difference in pain ratings to noxious stimuli administered during the presentation of positive/rewarding stimuli relative to neutral or negative stimuli.; A separate set of LMERs will be utilized for each primary endpoint (index of Positive Affective Pain Inhibition), with a primary LMER estimating the difference between Baseline and Week 1. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the primary endpoint differs between Baseline and Week 1, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Secondary Outcome Measures

Name	Time	Method
Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA 1-month Post-drug (7 days leading up to 1-month follow-up) relative to Baseline (beginning the day after baseline visit is complete)	Discrete positive affect items: joy, love, hope, contentment. Positive affect will be assessed by asking participants to rate the intensity of four discrete positive emotions (joy, love, hope, contentment) on a 5-point Likert scale from 1-5 ("Very slightly or not at all" to "Extremely") and averaging discrete items. Positive Affect scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Higher Positive Affect scores represent higher levels of positive affect.; A separate set of LMERs will be utilized for each endpoint (aggregated averages of momentary positive affect), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in negative affect as assessed by discrete negative affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA 1-month Post-drug (7 days leading up to 1-month follow-up) relative to Baseline (beginning the day after baseline visit is complete)	Discrete negative emotion items: depressed, angry, frustrated, and worried. Negative affect will be assessed by asking participants to rate the intensity of four discrete negative emotions (depressed, angry, frustrated, and worried) on a 5-point Likert scale from 1-5 ("Very slightly or not at all" to "Extremely") and averaging discrete items. Negative Affect scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Lower Negative Affect scores represent lower levels of negative affect.; A separate set of LMERs will be utilized for each endpoint (aggregated averages of momentary negative affect), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in Pain Catastrophizing as assessed by the Pain Catastrophizing Scale and averaged over 7-day periods of Ecological Momentary Assessment (EMA)	7-day period of EMA 1-month Post-drug (7 days leading up to 1-month follow-up) relative to Baseline (beginning the day after baseline visit is complete)	Pain catastrophizing will be assessed with three items taken from the Pain Catastrophizing Scale that have been specifically validated for use in Ecological Momentary Assessment (EMA) studies of patients with chronic pain. Items will be administered via EMA and scores will be aggregated over 7-day EMA periods at baseline, post-session, and 1-month follow-up. Each item is on a 5-point Likert scale (ranging from 0, "Not at all", to 4, "All the time"). Higher scores on each of these items indicates increased pain catastrophizing.; A separate set of LMERs will be utilized for each endpoint (aggregated averages of momentary pain catastrophizing), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.
Changes in Positive Affective Pain Inhibition (Quantitative Sensory Testing)	Baseline, 1-Month follow-up	Positive Affective Pain Inhibition will be assessed using quantitative sensory testing at baseline, 1-week post-drug-administration, and 1-month post-drug-administration. Positive affective pain inhibition is measured as the difference in pain ratings to noxious stimuli administered during the presentation of positive/rewarding stimuli relative to neutral or negative stimuli.; A separate set of LMERs will be utilized for each endpoint (index of Positive Affective Pain Inhibition), with a secondary LMER estimating the difference between Baseline and 1-Month. The Time x Group interaction will be the primary focus of interest, and we aim to evaluate 1) the extent to which the secondary endpoint differs between Baseline and 1-Month, and 2) the extent to which that difference varies between the Psilocybin and Control groups.

Trial Locations

Locations (1)

Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States