Vaporized cannabis extract-induced antinociception in male vs female rats with persistent inflammatory pain.

ABSTRACT: Although preclinical studies generally report robust antinociceptive effects of cannabinoids in rodent persistent pain models, randomized controlled trials in chronic pain patients report limited pain relief from cannabis/cannabinoids. Differences between animal and human studies that may contribute to these discrepant findings include route of cannabis/cannabinoid administration, type of cannabis/cannabinoid, and how pain is measured. To address these factors, rats with complete Freund adjuvant (CFA)-induced hind paw inflammation were exposed acutely or repeatedly to vaporized cannabis extract that was either tetrahydrocannabinol (THC) or cannabidiol (CBD)dominant. One measure of evoked pain (mechanical threshold), 2 functional measures of pain (hind paw weight-bearing, and locomotor activity), and hind paw edema were assessed for up to 2 hours after vapor exposure. Acute exposure to vaporized THC-dominant extract (200 or 400 mg/mL) decreased mechanical allodynia and hind paw edema and increased hind paw weight-bearing and locomotor activity, with no sex differences. After repeated exposure to vaporized THC-dominant extract (twice daily for 3 days), only the antiallodynic effect was significant. Acute exposure to vaporized CBD-dominant cannabis extract (200 mg/mL) did not produce any effects in either sex; repeated exposure to this extract (100, 200, or 400 mg/mL) decreased mechanical allodynia in male rats only. Sex differences (or lack thereof) in the effects of vaporized cannabis extracts were not explained by sex differences in plasma levels of THC, CBD, or their major metabolites. These results suggest that although vaporized THC-dominant extract is likely to be modestly effective against inflammatory pain in both male and female rats, tolerance may develop, and the CBD-dominant extract may be effective only in male rats.

Adolescent THC exposure: effects on pain-related, exploratory, and consummatory behaviors in adult male vs. female rats.

RATIONALE: Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids. OBJECTIVE: To determine whether adolescent Δ9-tetrahydrocannabinol (THC) exposure alters pain-related behaviors before and after induction of persistent inflammatory pain, and whether it influences antinociceptive of THC, in adult rats, and to compare the impact of adolescent THC exposure on pain to its effects on known DA-dependent behaviors such as exploration and consumption of a sweet solution. METHODS: Vehicle or THC (2.5 to 10 mg/kg s.c.) was administered daily to male and female rats on post-natal day (PND) 30-43. In adulthood (PND 80-88), sensitivity to mechanical and thermal stimuli before and after intraplantar injection of complete Freund's adjuvant (CFA) was determined. Antinociceptive, exploratory, and consummatory effects of 2.0 mg/kg THC were then examined. RESULTS: Adolescent THC exposure did not significantly alter adult sensitivity to non-noxious or noxious stimuli either before or after CFA injection, nor did it alter the antinociceptive effect of THC. In contrast, adolescent THC exposure altered adult exploratory and consummatory behaviors in a sex-dependent manner: when tested as adults, adolescent THC-treated males showed less hedonic drinking than adolescent vehicle-treated males, and females but not males that had been THC-exposed as adolescents showed reduced sensitivity to THC-induced suppression of activity and THC-induced hedonic drinking as adults. CONCLUSIONS: Adolescent THC exposure that altered both exploratory and consummatory behaviors in adults did not alter pain-related behaviors either before or after induction of inflammatory pain, suggesting that cannabinoid exposure during adolescence is not likely to substantially alter pain or cannabinoid analgesia in adulthood.

Cannabis use moderates the relationship between pain and negative affect in adults with opioid use disorder.

INTRODUCTION: Adults in Medication-Assisted Treatment (MAT) for opioid addiction are at risk for substance use relapse and opioid overdose. They often have high rates of cannabis use and comorbid symptoms of pain, depression, and anxiety. Low levels of self-efficacy (confidence that one can self-manage symptoms) are linked to higher symptom burdens and increased substance use. The effects of cannabis use on symptom management among adults with MAT are currently unclear. Therefore, the primary purpose of this study is to examine whether cannabis use moderates the relationships between pain and negative affect (i.e., depression and anxiety) and whether self-efficacy influences these interactions. METHODS: A total of 150 adults receiving MAT and attending one of two opioid treatment program clinics were administered a survey containing measures of pain, depression, anxiety, self-efficacy, and cannabis use. RESULTS: Cannabis use frequency moderated the relationships between pain and depression as well as pain and anxiety. Specifically, as cannabis use frequency increased, the positive relationships between pain and depression and pain and anxiety grew stronger. However, cannabis use was no longer a significant moderator after controlling for self-efficacy. CONCLUSIONS: Results suggest that cannabis use strengthens, rather than weakens, the relationships between pain and depression and pain and anxiety. These effects appear to be driven by decreased self-efficacy in cannabis users. It is important to understand how self-efficacy can be improved through symptom self-management interventions and whether self-efficacy can improve distressing symptoms for people in MAT.