Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
147 participants
INTERVENTIONAL
2024-10-22
2028-01-28
Brief Summary
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Detailed Description
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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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
OTHER
DOUBLE
Study Groups
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Dronabinol 5mg
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
CBD 300mg
3 Nantheia™ (100mg) softgel capsules and 3 placebo (0mg) softgel capsules will be administered to participants on one of the three test session days.
CBD 600mg
6 Nantheia™ (100mg) softgel capsules will be administered to participants on one of the three test session days.
Placebo 0mg
6 placebo (0 mg) softgel capsules will be administered to participants on one of the three test session days.
Dronabinol 10mg
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
CBD 300mg
3 Nantheia™ (100mg) softgel capsules and 3 placebo (0mg) softgel capsules will be administered to participants on one of the three test session days.
CBD 600mg
6 Nantheia™ (100mg) softgel capsules will be administered to participants on one of the three test session days.
Placebo 0mg
6 placebo (0 mg) softgel capsules will be administered to participants on one of the three test session days.
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
CBD 300mg
3 Nantheia™ (100mg) softgel capsules and 3 placebo (0mg) softgel capsules will be administered to participants on one of the three test session days.
CBD 600mg
6 Nantheia™ (100mg) softgel capsules will be administered to participants on one of the three test session days.
Placebo 0mg
6 placebo (0 mg) softgel capsules will be administered to participants on one of the three test session days.
Interventions
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CBD 300mg
3 Nantheia™ (100mg) softgel capsules and 3 placebo (0mg) softgel capsules will be administered to participants on one of the three test session days.
CBD 600mg
6 Nantheia™ (100mg) softgel capsules will be administered to participants on one of the three test session days.
Placebo 0mg
6 placebo (0 mg) softgel capsules will be administered to participants on one of the three test session days.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female aged 18-65 years.
4. 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).
5. 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.
6. Adherence to their clinically prescribed methadone therapy, on a stable dose (30-150 mg/day ≥ 3 weeks).
7. 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.
8. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
Exclusion Criteria
2. 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).
3. 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.
4. Contraindications for exposure to nociceptive stimuli, such as untreated hypertension, verbally noted by participant or verified during screening procedures.
5. Abnormal screening EKG (QTc interval \>450 ms), arrythmia, or vasospastic disease.
6. 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.
7. Currently lactating.
8. Male participants who plan to donate sperm starting at screening and through 90 days after final study drug administration.
9. Females who plan to donate ova starting at screening through 28 days after final study drug administration.
10. History of primary psychotic disorders or mood disorders with psychotic features.
11. Current suicidal ideation or related behavior.
12. 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.
13. Current, regular use of benzodiazepines, other prescription opioids, or platelet inhibitors (e.g., clopidogrel, apixaban, ticagrelor).
14. Allergy or serious adverse reaction to cannabis or its constituent cannabinoid.
15. Allergy or serious adverse reaction to sesame oil or seeds.
16. Allergy or serious adverse reaction to Butylated Hydroxytoluene (BHT).
17. Unable to swallow or have difficulty swallowing capsules.
18. 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 ≤ 150 mg/mL. If a participant tests greater than ≤ 150 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.
18 Years
65 Years
ALL
No
Sponsors
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National Institute on Drug Abuse (NIDA)
NIH
National Institutes of Health (NIH)
NIH
Yale University
OTHER
Responsible Party
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Joao De Aquino
Assistant Professor of Psychiatry
Principal Investigators
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Joao P. De Aquino, M.D.
Role: PRINCIPAL_INVESTIGATOR
Yale University
Locations
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Connecticut Mental Health Center
New Haven, Connecticut, United States
Countries
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Central Contacts
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Facility Contacts
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Thomas McMahon
Role: primary
References
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Cooper ZD, Craft RM. Sex-Dependent Effects of Cannabis and Cannabinoids: A Translational Perspective. Neuropsychopharmacology. 2018 Jan;43(1):34-51. doi: 10.1038/npp.2017.140. Epub 2017 Jul 17.
Smith MT Jr, Remeniuk B, Finan PH, Speed TJ, Tompkins DA, Robinson M, Gonzalez K, Bjurstrom MF, Irwin MR. Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption: implications for sex differences in chronic pain. Sleep. 2019 Feb 1;42(2):zsy209. doi: 10.1093/sleep/zsy209.
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Leweke FM, Rohleder C, Gerth CW, Hellmich M, Pukrop R, Koethe D. Cannabidiol and Amisulpride Improve Cognition in Acute Schizophrenia in an Explorative, Double-Blind, Active-Controlled, Randomized Clinical Trial. Front Pharmacol. 2021 Apr 29;12:614811. doi: 10.3389/fphar.2021.614811. eCollection 2021.
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Morean ME, de Wit H, King AC, Sofuoglu M, Rueger SY, O'Malley SS. The drug effects questionnaire: psychometric support across three drug types. Psychopharmacology (Berl). 2013 May;227(1):177-92. doi: 10.1007/s00213-012-2954-z. Epub 2012 Dec 28.
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Georgopoulos V, Akin-Akinyosoye K, Zhang W, McWilliams DF, Hendrick P, Walsh DA. Quantitative sensory testing and predicting outcomes for musculoskeletal pain, disability, and negative affect: a systematic review and meta-analysis. Pain. 2019 Sep;160(9):1920-1932. doi: 10.1097/j.pain.0000000000001590.
Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012 Jun;153(6):1193-1198. doi: 10.1016/j.pain.2012.02.021. Epub 2012 Apr 3.
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De Aquino JP, Meyerovich J, Xie CZ, Ranganathan M, Compton P, Pittman B, Rogan M, Sofuoglu M. Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study. Addict Biol. 2023 Sep;28(9):e13317. doi: 10.1111/adb.13317.
De Aquino JP, Bahji A, Gomez O, Sofuoglu M. Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies. Drug Alcohol Depend. 2022 Dec 1;241:109702. doi: 10.1016/j.drugalcdep.2022.109702. Epub 2022 Nov 18.
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Other Identifiers
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2000038372
Identifier Type: -
Identifier Source: org_study_id