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

BACKGROUND AND OBJECTIVES: Childhood trauma (CT) increases addiction vulnerability. We examined CT's impact on delta-9-tetrahydrocannabinol (THC) effects. METHODS: This is a post-hoc analysis of a randomized, placebo-controlled, crossover trial investigating the effects of oral THC (10, 20 mg) among 25 persons receiving methadone for opioid use disorder (OUD). RESULTS: Greater CT was associated with lower aversive effects from higher THC doses (20 mg) (p = .006). DISCUSSION AND CONCLUSIONS: CT may reduce the subjective aversive effects of THC, potentially leading to greater cannabis use in individuals with OUD. SCIENTIFIC SIGNIFICANCE: These findings offer insights into THC's risks versus benefits in OUD subgroups and emphasize assessing CT in OUD treatment and research.

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

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.