Trial Outcomes & Findings for Safety and Tolerability of Cannabidiol Among Persons With Opioid Use Disorder Receiving Methadone or Buprenorphine (NCT NCT05076370)

Participants were recruited through responses to fliers, craigslist, clinicaltrials.gov, BuildClinical and through local mental health and substance use disorder treatment facilities

Participants received buprenorphine or methadone.

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.

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.

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.

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.

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.

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.

The Heroin Craving Questionnaire - Short Form 14 (HCQ-SF-14) consists of 14 statements about the respondent's feelings and thoughts about using heroin as he or she is completing the questionnaire (i.e., right now). Each of the 14 items is scored on a scale from 1 (Strongly Disagree) to 7 (Strongly Agree). The HCQ-SF-14 score is obtained by adding the scores of all 14 statements and dividing the total by 14. Higher scores on the HCQ-SF-14 indicate a stronger craving for heroin. The HCQ-14 was administered before (+150 minutes) and after (+155 minutes) participants watched a cue-induced craving video. The difference of the two HCQ-14 scores (post - pre) will be used to index cue-elicited craving.