Clinical trial NCT06355414: Psilocybin in Chronic Low Back Pain and Depression
Official title: Psilocybin and Affective Function in Chronic Lower Back Pain Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Low-back Pain
Depression
Keywords: Psilocybin
Chronic Low-back Pain
Depression
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2024-04-09
Enrollment: 40
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, active control study comparing the effects of psilocybin (25mg fixed dose) and methylphenidate (40mg fixed dose)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in negative affect as assessed by discrete negative affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in Pain Catastrophizing as assessed by the Pain Catastrophizing Scale and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in Positive Affective Pain Inhibition (Quantitative Sensory Testing)
timeFrame: Baseline, 1-week follow-up
Secondary outcomes:
measure: Changes in positive affect as assessed by discrete positive affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in negative affect as assessed by discrete negative affect items and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in Pain Catastrophizing as assessed by the Pain Catastrophizing Scale and averaged over 7-day periods of Ecological Momentary Assessment (EMA)
timeFrame: 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)
measure: Changes in Positive Affective Pain Inhibition (Quantitative Sensory Testing)
timeFrame: Baseline, 1-Month follow-up
Other outcomes:
measure: Pain as assessed by discrete pain items assessed via EMA
timeFrame: 7-day periods of EMA at 1-week follow-up and 1-month follow-up, each relative to Baseline
measure: Dynamic association between affect and pain using micro-longitudinal EMA data of affective variables (positive, negative affect outcomes) and pain outcomes
timeFrame: 7-day periods of EMA at: Baseline (beginning the day after baseline visit is complete), Post-drug Session (beginning the day after drug session), and 1-month follow-up (the seven days leading up to the 1-month follow-up visit)
measure: Changes in mood as measured by a selection of discrete items derived from the Positive and Negative Affect Schedule- Expanded Form (PANAS-X).
timeFrame: 7-day periods of EMA at: Baseline (beginning the day after baseline visit is complete), Post-drug Session (beginning the day after drug session), and 1-month follow-up (the seven days leading up to the 1-month follow-up visit)
measure: Changes in self-reported Pain Impact as measured by Pain intensity (P), interference with Enjoyment of life (E), and interference with General activity (G) Scale (PEG)
timeFrame: 7-day periods of EMA at: Baseline (beginning the day after baseline visit is complete), Post-drug Session (beginning the day after drug session), and 1-month follow-up (the seven days leading up to the 1-month follow-up visit)
measure: Changes in Pressure Pain Threshold (Quantitative Sensory Testing)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Changes in Conditioned Pain Modulation (Quantitative Sensory Testing)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Chronic Pain Exacerbation as measured by the Graded Chronic Pain Scale- Revised (GCPS-R)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Changes in neuropathic pain features as assessed by the painDETECT questionnaire (PDQ)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Changes in CLBP-related disability as measured by the Oswestry Disability Index (ODI)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Change in Emotion Regulation as assessed by the Difficulties in Emotion Regulation Scale (DERS)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Pain intensity and related dimensions of health (i.e., sleep) as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29 v2.0).
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Psychological Inflexibility in Pain as measured by the Psychological Inflexibility in Pain Scale (PIPS)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Personal values and the degree of success in following those values as measured by the Chronic Pain Values Inventory (CPVI).
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Dispositional tendencies to feel positive emotions towards others in daily life as measured by the Dispositional Positive Emotion Scale (DPES)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Mindfulness as measured by the Five Facet Mindfulness Questionnaire (FFMQ-15)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
measure: Subjective experiences: Awe Experience Scale (AWE-S)
timeFrame: post drug administration up to 8 hours, 1-week follow-up, 1-month follow-up
measure: Subjective experiences: Mystical Experience Questionnaire (MEQ30)
timeFrame: post drug administration up to 8 hours, 1-week follow-up, 1-month follow-up
measure: Subjective experiences: Challenging Experience Questionnaire (CEQ)
timeFrame: post drug administration up to 8 hours, 1-week follow-up, 1-month follow-up
measure: Subjective experiences: Altered States of Consciousness Questionnaire (5D-ASC)
timeFrame: post drug administration up to 8 hours, 1-week follow-up, 1-month follow-up
measure: Subjective experiences: Psychological Insight Questionnaire (PIQ)
timeFrame: post drug administration up to 8 hours, 1-week follow-up, 1-month follow-up
measure: Changes in basic beliefs about the world as measured by the Primals Inventory (PI-6)
timeFrame: Baseline, 1-week follow-up, 1-month follow-up
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: David B Yaden, PhD
role: PRINCIPAL_INVESTIGATOR
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