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Psilocybin for Chronic Low Back Pain and Depression

This study is looking into how psilocybin affects chronic low back pain and depression. Researchers want to see if psilocybin can help improve your mood and reduce how much you focus on pain. You might be able to join if you are 21 to 80 years old, have had low back pain for at least three months, and also experience moderate depression. Participants will receive either a single dose of psilocybin (25mg) or methylphenidate (40mg). The study will measure changes in your positive and negative feelings, and how you think about your pain, within a week after the drug session.

Study design
This interventional study plans to enroll 40 participants. It compares the effects of a single dose of psilocybin to a single dose of methylphenidate.
What's involved
You will have screening visits, a drug session, and follow-up visits for up to one month after the drug session. You will also complete surveys multiple times a day throughout the study.
Compensation
Not stated in the trial record.
Follow-up
Participants will be followed for up to one month after the drug session.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06355414

Psilocybin in Chronic Low Back Pain and Depression

Recruiting
PHASE1Ages 21–80InterventionalTreatment
Johns Hopkins University
~40 participants
Updated 2026-07-24 on ClinicalTrials.gov
What's tested:PsilocybinMethylphenidate

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
Measured over 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)
+3 more outcomes measured

Conditions

Chronic Low-back Pain
Depression

Explore related trials

Chronic low back painDepression

Where it's being run

1 sites across 1 states
Maryland1

Study leadership

  • David B Yaden, PhD · PRINCIPAL_INVESTIGATOR · Johns Hopkins University

Who to contact

Arozo Azimi, BA
[email protected]
410-550-1140
Email the study team

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Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

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Eligibility criteria

Inclusion

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

Lifetime history of serious psychiatric (other than depression) or neurological disorders, including bipolar disorder, psychosis, or seizure disorder
History (past 2 years) 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 history (past 5 years) 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:
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

What this trial measures

  • 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 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 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 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.