Safety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine

Early Phase 1CompletedNCT05076370

Yale University7 enrolled

Overview

The overarching goal of this study is to evaluate the potential of Cannabidiol (CBD) as an adjunctive treatment for comorbid opioid use disorder (OUD) and chronic pain. This is a randomized, placebo-controlled, crossover human laboratory study investigating the dose-dependent safety and acute effects of CBD on measures of pain and opioid craving in outpatients with OUD receiving methadone or buprenorphine.

An initial safety pilot phase will recruit six participants: three receiving treatment with methadone and three receiving treatment with buprenorphine. If the results of the pilot study support the safety of CBD administration in this clinical sample, the general study will recruit participants with comorbid OUD and chronic pain, with half the subjects receiving methadone and half receiving buprenorphine. Both sub-studies will enroll participants who do not currently require an inpatient hospitalization.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Addiction

Interventions

CBD Day 1DRUG

CBD 400mg

CBD Day 2DRUG

CBD 800mg

CBD Day 3DRUG

CBD 1200mg

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women aged between 18 and 70 years old. * Diagnosed with OUD and currently enrolled in methadone or buprenorphine maintenance treatment. * Having chronic pain, uniformly operationalized as grade II (high-intensity) non- cancer pain for ≥ 6 months 49. * Capable of providing informed consent in English. * Compliant in opioid maintenance treatment and on a stable dose for four weeks or longer. * Not meeting DSM-5 criteria for substance use disorders other than OUD or tobacco use disorder within the last 12 months. * No current medical problems deemed contraindicated for participation by principal investigator. * For women, not pregnant as determined by pregnancy screening; not breast-feeding; using acceptable birth control methods. Acceptable contraception for women includes oral contraceptives, contraceptive depot injections, contraceptive subdermal implants, intrauterine devices, or surgical contraception methods. Acceptable contraception for men includes condoms or surgical contraception methods. Exclusion Criteria: * Other current major psychiatric disorders deemed clinically unstable by the principal investigator, such as severe depression and/or active suicidal ideation. * Having experienced major psychosocial stressors recently (≤ 6 weeks before enrollment), at the discretion of the principal investigator. * Methadone dose under 60mg or over 100mg * Buprenorphine over 24mg. * Having received inpatient psychiatric treatment recently (≤ 60 days before enrollment). * Candidates receiving products containing either THC or CBD will be excluded. * Current use regular use other prescription opioids, gabapentinoids (pregabalin, gabapentin), antidepressants (SSRIs, SNRIs, TCAs), benzodiazepines, platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor), or NSAIDs. * Current weight of less of 60 kg. * Allergy to sesame seed oil, which is an ingredient of the CBD formulation used. * Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator. * Participants who have elevation of liver enzymes (ALT and/or AST) 2x above the normal limit or higher.

Locations (1)

Veteran Affairs Hospital

West Haven, Connecticut, United States

Outcomes

Primary Outcomes

Agitation Calmness Evaluation Scale (ACES)

The ACES consists of a single item that rates overall agitation and sedation of the participant at the time of evaluation, where 1 indicates marked agitation; 2: moderate agitation; 3: mild agitation; 4: normal behavior; 5: mild calmness; 6: moderate calmness; 7: marked calmness; 8: deep sleep; and 9: unarousable. Clinically significant sedation was a priori defined as an ACES score of 7 (marked calmness) or higher at any point during the session. A score was averaged across all time intervals.

Time frame: Baseline (30 minutes before the administration of CBD), hourly for 4 hours after the administration of methadone (administered +210 minutes after CBD) and 3 hours after the administration of buprenorphine (administered +210 minutes after CBD)

Mini Mental Status Examination (MMSE)

The MMSE is a 30-point scale ranging from 0 to 30 that measures five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. Each scale is summed to compute a total score. The MMSE is used extensively in clinical and research settings to measure cognitive impairment. A score of 24 or higher is generally considered within the normal range, while lower scores suggest potential cognitive impairment. Scores are often interpreted as follows: 25-30 = normal cognition, 21-24 = mild impairment, 10-20 = moderate impairment, and below 10 = severe impairment.

Time frame: Baseline (30 minutes before the administration of CBD), hourly for 4 hours after the administration of methadone (administered +210 after CBD) and 3 hours after the administration of buprenorphine (administered +210 minutes after CBD)

Systematic Assessment of Side Effects (SAFTEE)

The SAFTEE is a multi-symptom checklist that has been used successfully in our previous studies to assess and monitor any adverse events and possible side effects of study medications. It includes information regarding the severity of any presenting symptoms (0= none, 1= mild, 2= moderate, and 3= severe), as well as the course of action taken by the study staff in response. The SAFTEE was administered before the administration of CBD at baseline, (timepoint -30 minutes) and 4.5 hours after the administration of CBD (timepoint +240 minutes) during each test session. Data presented here is the number of participants that reported symptoms on SAFTEE.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

Quantitative Sensory Testing (QST)- Threshold and Tolerance

Pain threshold and tolerance will be assessed using a comprehensive QST battery. This is a reliable, dynamic, and computerized method of quantifying distinct mechanisms of the pain experience. QST measures are sensitive to the effects of cannabinoids, important biomarkers of chronic pain, and predictors of the pain treatment response. Threshold: the temperature the participant first begins to feel pain (average pain threshold), and when the participant can no longer tolerate the stimuli (Tolerance). The temperature ranges from 37 degrees celsius to 50 degrees celsius. A lower temperature represents a lower pain threshold and a higher temperature represents a higher pain threshold. A lower temperature represents a lower pain tolerance and a higher temperature represents a higher pain tolerance.

Time frame: baseline, 2 hours and 4 hours after the administration of CBD.

Change in Quantitative Sensory Testing (QST) Conditioned Pain Modulation (CPM)

CPM indexes top-down pain inhibition, by leveraging the "pain inhibits pain phenomena". In CPM, a test stimulus is rated on a -100 to +100 Numeric Rating Scale (NRS) for pain both alone and during a concurrent conditioning stimulus applied elsewhere on the body. The CPM Score is the difference between these two ratings. CPM score is a Difference (Delta): Pain rating (test stimulus alone) - Pain rating (test stimulus with conditioning stimulus) Interpretation: Higher (more positive) values indicate greater pain inhibition.

Time frame: Baseline (-30 minutes), 2 hours (+120 minutes), and 4 hours (+240 minutes) after the administration of CBD.

Quantitative Sensory Testing (QST) Temporal Summation of Pain (TSP)

Pain will be assessed using a comprehensive QST battery. QST measures are sensitive to the effects of cannabinoids, important biomarkers of chronic pain, and predictors of the pain treatment response. TSP involves the repeated administration of noxious stimuli, indexing bottom-up pain facilitation. Therefore, TSP measures the increase in pain perception with repeated noxious stimuli, calculated as the area under the curve (AUC) of pain ratings over time during repeated stimulation. Higher TSP scores indicate worse outcomes (greater pain facilitation/central sensitization), while lower TSP scores indicate better outcomes (less pain facilitation/central sensitization). The TSP AUC values represent the cumulative pain experience during repeated stimulation (VAS units\*seconds), where larger values reflect greater temporal summation of pain, which is associated with central nervous system sensitization and chronic pain conditions.

Time frame: Baseline, 2 hours and 4 hours after the administration of CBD.