Combined THC and CBD for OUD and Chronic Pain

Официальное название

Combination of THC and CBD as Novel Treatment for Co-Occurring Opioid Use Disorder and Chronic Pain

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат CBD 600mg
  6 Nantheia™ (100mg) softgel capsules will be administered to participants on one of the three test session days.
• Препарат Placebo 0mg
  6 placebo (0 mg) softgel capsules will be administered to participants on one of the three test session days.

Первичные конечные точки

• Primary Outcome Variable #1: Pain Sensitivity [Срок оценки: Up to 8 hours]
• Primary Outcome Variable #2: Opioid Craving [Срок оценки: Baseline and +180 minutes post dose]

Вторичные конечные точки (6)

• Secondary Outcome Variable #1a: Cognitive/psychomotor effects (CPT) [Срок оценки: +180 minutes post dose]
• Secondary Outcome Variable #1b: Cognitive/psychomotor effects (HVLT) [Срок оценки: +180 minutes post dose]
• Secondary Outcome Variable #2a: Abuse potential of combined THC and CBD (MCP) [Срок оценки: +480 post dose]
• Secondary Outcome Variable #2b: Abuse potential of combined THC and CBD (DEQ) [Срок оценки: Up to 8 hours]
• Secondary Outcome Variable #3a: Monitor adverse events from the study medications (SAFTEE) [Срок оценки: Baseline ; +480 minutes post dose; One-week after last test session]
• Secondary Outcome Variable #3b: Monitor adverse events from the study medications (Cardiovascular) [Срок оценки: Up to 8 hours and One-week after last test session]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Meeting DSM-5 criteria for cannabis use disorder and/or substance use disorders (SUDs) within the last 3 months. Participants meeting DSM-5 criteria for OUD and/or tobacco use disorder, either currently or within the last 3 months, will not be excluded per this criterion.
• 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 ≤ 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Connecticut Mental Health Center — New Haven

Публикации

• Cooper ZD, Haney M. Sex-dependent effects of cannabis-induced analgesia. Drug Alcohol Depend. 2016 Oct 1;167:112-20. doi: 10.1016/j.drugalcdep.2016.08.001. Epub 2016 Aug 5. PMID 27522535
• 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. PMID 28811670
• Cooper ZD, Haney M. Investigation of sex-dependent effects of cannabis in daily cannabis smokers. Drug Alcohol Depend. 2014 Mar 1;136:85-91. doi: 10.1016/j.drugalcdep.2013.12.013. Epub 2014 Jan 3. PMID 24440051
• 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. PMID 30371854
• Turri M, Teatini F, Donato F, Zanette G, Tugnoli V, Deotto L, Bonetti B, Squintani G. Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX(R)) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials. Medicines (Basel). 2018 Jun 21;5(3):59. doi: 10.3390/medicines5030059. PMID 29933552
• Dunn KE, Bergeria CL, Huhn AS, Speed TJ, Mun CJ, Vandrey R, Campbell CM. Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model. Neuropsychopharmacology. 2021 Jul;46(8):1451-1459. doi: 10.1038/s41386-021-01007-4. Epub 2021 Apr 20. PMID 33879842
• Matheson J, Mann RE, Sproule B, Huestis MA, Wickens CM, Stoduto G, George TP, Rehm J, Le Foll B, Brands B. Acute and residual mood and cognitive performance of young adults following smoked cannabis. Pharmacol Biochem Behav. 2020 Jul;194:172937. doi: 10.1016/j.pbb.2020.172937. Epub 2020 May 1. PMID 32360692
• 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. PMID 33995015

Идентификаторы

NCT: NCT06544291 · 2000038372 · 1R01DA060066-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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