NCT06355414 · Johns Hopkins University
Psilocybin in Chronic Low Back Pain and Depression
What this study is about
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).
View original scientific description
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.
Interventions
DRUG
Psilocybin
Drug administration under supportive conditions
DRUG
Methylphenidate
Drug administration under supportive conditions
Primary outcome measures
Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- 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.
- Medical conditions contraindicated for methylphenidate administration:
- Concomitant use of Monoamine oxidase inhibitors (MAOIs), or use within 14 days of MAOI discontinuation
- Family history or diagnosis of Tourette's syndrome
- Known Fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose insufficiency
- Known hypersensitivity to methylphenidate
- Marked agitation, anxiety, and tension
- 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
Where
- Baltimore, Maryland
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Oct 14, 2025 · Source of record for eligibility and locations