Delta‐9‐tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within‐subject, randomized, placebo‐controlled laboratory study

Abstract

The opioid and cannabinoid receptor systems are inextricably linked—overlapping at the anatomical, functional and behavioural levels. Preclinical studies have reported that cannabinoid and opioid agonists produce synergistic antinociceptive effects. Still, there are no experimental data on the effects of cannabinoid agonists among humans who receive opioid agonist therapies for opioid use disorder (OUD). We conducted an experimental study to investigate the acute effects of the delta‐9‐tetrahydrocannabinol (THC) among persons receiving methadone therapy for OUD. Using a within‐subject, crossover, human laboratory design, 25 persons on methadone therapy for OUD (24% women) were randomly assigned to receive single oral doses of THC (10 or 20 mg, administered as dronabinol) or placebo, during three separate 5‐h test sessions. Measures of experimental and self‐reported pain sensitivity, abuse potential, cognitive performance and physiological effects were collected. Mixed‐effects models examined the main effects of THC dose and interactions between THC (10 and 20 mg) and methadone doses (low‐dose methadone defined as <90 mg/day; high dose defined as >90 mg/day). Results demonstrated that, for self‐reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose‐dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses. Collectively, these results provide valuable insights for future studies aiming to evaluate the risk–benefit profile of cannabinoids to relieve pain among individuals receiving opioid agonist therapy for OUD, a timely endeavour amidst the opioid crisis.

The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder

“…The authors of this latter study also attempted to test 40 mg of dronabinol, but found that this dosage induced sinus tachycardia, anxiety and panic resulting in discontinuation. Interestingly, further research has suggested a potential biphasic effect of THC, with lower doses producing anxiolysis and analgesia and conversely, higher doses able to increase pain sensitivity and anxiety [ 62 ]. De Aquino et al investigated the effect of varying doses of dronabinol (10 mg and 20 mg) on pain sensitivity among participants receiving methadone therapy for OUD and found that while both doses lead to lower total pain scores than placebo, 10 mg was more effective than 20 mg in this regard [ 62 ].…”

“…Interestingly, further research has suggested a potential biphasic effect of THC, with lower doses producing anxiolysis and analgesia and conversely, higher doses able to increase pain sensitivity and anxiety [ 62 ]. De Aquino et al investigated the effect of varying doses of dronabinol (10 mg and 20 mg) on pain sensitivity among participants receiving methadone therapy for OUD and found that while both doses lead to lower total pain scores than placebo, 10 mg was more effective than 20 mg in this regard [ 62 ]. It may be that dronabinol has a narrow therapeutic window for mediating withdrawal symptoms without producing troublesome adverse effects.…”

Brief report: The influence of childhood trauma on the effects of delta‐9‐tetrahydrocannabinol in persons with opioid use disorder

“…Patients receiving benzodiazepines or testing positive for substances other than methadone and cannabinoids were excluded. Further details on the inclusion and exclusion criteria are discussed in De Aquino et al 7…”

“…Approximately 68% of participants self-identified as White, 6% as African American or Black, and 8% as Hispanic or Latin-American. More details on participant demographics can be found in De Aquino et al 7…”

“…Test sessions took place at the laboratory located in the West Haven VA, CT VA Healthcare System Campus and began at 8 a.m. A series of assessments were conducted to measure the analgesic (Cold Pressor Test, CPT), subjective (Drug Effects Questionnaire, DEQ), and cognitive effects (Hopkins Verbal Learning Task, HVLT, and continuous performance test) of THC. For a comprehensive description of study procedures, please refer to De Aquino et al7 Statistical analysisThe independent and interactive effects of THC dose (placebo, 10 mg THC, 20 mg THC; within-subjects predictor) and CT (continuous) on the CPT, DEQ (10 question version; subscores of Stimulatory, Aversive, and Pleasurable Effects), continuous performance test, and HVLT outcomes were assessed using linear mixed models. All analyses were conducted using data collected 180 min post-THC administration to capture peak effects.…”