Combined THC and CBD for OUD and Chronic Pain
- Conditions
- Opioid Use DisorderChronic Pain
- Interventions
- Registration Number
- NCT06544291
- Lead Sponsor
- Yale University
- Brief Summary
The primary objective of this phase 2 study is to investigate the therapeutic potential of orally administered combined delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in relieving both pain and cue-induced opioid craving in people with co-occurring opioid use disorder (OUD) and chronic pain who are undergoing methadone therapy.
- Detailed Description
This phase 2 study will utilize a rigorous double-blind, placebo-controlled, crossover experimental design. We will enroll 147 participants with co-occurring OUD and chronic pain who are receiving methadone maintenance treatment and randomize them into three groups (n=49). Across three test sessions, each group will receive single doses of THC (5 mg, 10 mg, or placebo) and CBD (300 mg, 600 mg, or placebo) in a 3x3 design, with THC dose as a between-subject (parallel-group) factor and CBD dose as within-subject (crossover) factor. All three groups will undergo otherwise identical procedures to ensure internal validity.
Our central hypothesis posits that, combined, THC and CBD will be more effective in alleviating pain and cue-induced opioid craving than either drug alone. While THC's analgesic effects may benefit those with co-occurring OUD and chronic pain, its abuse potential and cognitive/psychomotor deficits require careful dose consideration. Combining THC with non-hedonic and neuroprotective CBD could offer a compelling two-pronged approach to alleviate both pain and opioid craving. This study will also explore if sex influences the responses to THC and CBD, given the growing evidence indicating sex-specific effects of cannabinoids and pain responses. If our hypothesis is confirmed, selected THC/CBD doses may serve as a novel, dual-action therapy to alleviate both pain and opioid craving in co-occurring OUD and chronic pain.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 147
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female aged 18-65 years.
- Co-occurring OUD (meeting DSM-5 criteria) and chronic pain (uniformly operationalized as high-impact [occurring most days, limiting life or work activities] non-cancer low back pain for ≥ 3 months).
- Prior exposure to cannabis or its constituent cannabinoids at least once in the last 10 years, 1-10 times in the last 20 years, or more than 20 times in lifetime.
- Adherence to their clinically prescribed methadone therapy, on a stable dose (30-150 mg/day ≥ 3 weeks).
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 2 weeks after the last test session.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
- Meeting DSM-5 criteria for cannabis use disorder and/or substance use disorders (SUDs) other than OUD or tobacco use disorder, within the last 12 months.
- Clinically significant medical disorders as noted by the participant or through study screening procedures (e.g. liver dysfunction, as indicated by ALT and/or AST > 1.5 times the normal limit).
- Neurological conditions that may change the response to nociceptive stimuli (e.g., stroke, neuropathy), or that lead to loss of balance, evidenced by a neuro-sensory exam during screening.
- Contraindications for exposure to nociceptive stimuli, such as untreated hypertension, verbally noted by participant or verified during screening procedures.
- Abnormal screening EKG (QTc interval >450 ms), arrythmia, or vasospastic disease.
- Positive urine pregnancy test, or lack of birth control measures in women of childbearing potential. For males of reproductive potential refusal to use condoms or other methods to ensure effective contraception with partner.
- Currently lactating.
- Male participants who plan to donate sperm starting at screening and through 90 days after final study drug administration.
- Females who plan to donate ova starting at screening through 28 days after final study drug administration.
- History of primary psychotic disorders or mood disorders with psychotic features.
- Current suicidal ideation or related behavior.
- A physician will carefully evaluate participants for use of over-the-counter or prescription psychoactive drugs known to affect pain threshold or pain tolerance (including NSAIDS, serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g. venlafaxine, duloxetine), gabapentinoids, tricyclic antidepressants (e.g., nortriptyline, amitriptyline), anticonvulsant medications (e.g., topiramate, carbamazepine). Only participants who are on stable doses (i.e., consistent daily administration of the medication for at least three months at the same dose following the last dose change, either increase or decrease) of these medications, and whose dosing schedules allow participation in the study visits, thus excluding instances of single-dose or temporary dosing of the medication, will be eligible as determined by the sponsor-investigator. If possible, the morning dose will be administered after the study visit.
- Current, regular use of benzodiazepines, other prescription opioids, or platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor).
- Allergy or serious adverse reaction to cannabis or its constituent cannabinoid.
- Allergy or serious adverse reaction to sesame oil or seeds.
- Allergy or serious adverse reaction to Butylated Hydroxytoluene (BHT).
- Unable to swallow or have difficulty swallowing capsules.
- Prior to receiving the study medication on the first test session, participants' cannabinoid use will be assessed using a quantitative point-of-care urine 11-nor-9-carboxy-THC concentration test with a cut-off of ≤ 50 mg/mL. If a participant tests greater than ≤ 50 mg/mL, they will be asked to abstain for an additional 7 to 14 days. If 14 days after their initial THC concentration test the participant continues to test positive, they will not be allowed to participate in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Dronabinol 10mg CBD 600mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 10 mg Dronabinol across all three test sessions Placebo 0mg CBD 600mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 0 mg Dronabinol across all three test sessions Dronabinol 10mg CBD 300mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 10 mg Dronabinol across all three test sessions Placebo 0mg CBD 300mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 0 mg Dronabinol across all three test sessions Dronabinol 5mg CBD 300mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 5 mg Dronabinol across all three test sessions Dronabinol 5mg CBD 600mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 5 mg Dronabinol across all three test sessions Dronabinol 5mg Placebo 0mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 5 mg Dronabinol across all three test sessions Dronabinol 10mg Placebo 0mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 10 mg Dronabinol across all three test sessions Placebo 0mg Placebo 0mg Participants will be randomized to which dronabinol (or placebo) dose they receive. The fixed dose they receive will be administered across all three test sessions. Therefore, participants may receive a single capsule of 0 mg Dronabinol across all three test sessions
- Primary Outcome Measures
Name Time Method Primary Outcome Variable #1: Pain Sensitivity Up to 8 hours We will measure pain sensitivity using a comprehensive QST battery at baseline and approximately hourly for 8 hours. The battery includes several nociceptive modalities such as pressure, mechanical, heat, and cold stimuli. The main outcome will be a composite pain sensitivity measure, integrating data from the QST battery.
Primary Outcome Variable #2: Opioid Craving Baseline and +180 minutes post dose We will measure opioid craving using the short form Heroin Craving Questionnaire (HCQ-14) given to participants before and after a watching a visual probe task used to induce craving.
- Secondary Outcome Measures
Name Time Method Secondary Outcome Variable #3b: Monitor adverse events from the study medications (Cardiovascular) Up to 8 hours and One-week after last test session To monitor cardiovascular effects from the study medications, heart rate and blood pressure will be measured at baseline and every 30 minutes during the experimental sessions, and at the one-week follow-up.
Secondary Outcome Variable #1a: Cognitive/psychomotor effects (CPT) +180 minutes post dose The cognitive/psychomotor effects of THC and CBD will be assessed using the Continuous Performance Test (CPT). For the CPT, the primary outcome will be the throughput score, which indexes attention/working memory accuracy (i.e. percent of correct responses) and speed (i.e. reaction time).
Secondary Outcome Variable #1b: Cognitive/psychomotor effects (HVLT) +180 minutes post dose The cognitive/psychomotor effects of THC and CBD will be assessed using the Hopkins Verbal Learning Test (HVLT). The primary outcome for the HVLT will be immediate and delayed recall, which index verbal memory.
Secondary Outcome Variable #2a: Abuse potential of combined THC and CBD (MCP) +480 post dose The abuse potential of combined THC and CBD will be assessed using a modified Multiple-Choice Procedure (MCP) at the end of each test session. The primary outcome for the MCP is the crossover point (i.e., the value at which participants choose money over the study medication).
Secondary Outcome Variable #2b: Abuse potential of combined THC and CBD (DEQ) Up to 8 hours The abuse potential of combined THC and CBD will be assessed using the Drug Effects Questionnaire (DEQ) administered at baseline and every 30 minutes. The primary DEQ outcome is the Stimulatory Effects subscale, obtained by averaging participants responses to the items: "Feel High"; "Feel Stimulated"; and "Feel the Drug Strength".
Secondary Outcome Variable #3a: Monitor adverse events from the study medications (SAFTEE) Baseline ; +480 minutes post dose; One-week after last test session To monitor adverse events from the study medications, the Systematic Assessment for Treatment Emergent Events (SAFTEE) will be administered before and after each experimental session and during the one-week follow-up. This is a symptom checklist that has been used successfully in our previous studies to assess possible side effects of study medications. It includes information regarding severity of any presenting side effects, as well as the course of action taken by study staff in response.
Trial Locations
- Locations (1)
Connecticut Mental Health Center
🇺🇸New Haven, Connecticut, United States