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



doi: 10.1097/j.pain.0000000000002902.


Online ahead of print.

Affiliations

Item in Clipboard

Rebecca M Craft et al.


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.

References

    1. Alkislar I, Miller AR, Hohmann AG, Sadaka AH, Cai X, Kulkami P, Ferris CF. Inhaled cannabis suppresses chemotherapy-induced neuropathic nociception by decoupling the raphe nucleus: a functional imaging study in rats. Biol Psychiatry 2020;6:479–89.

    1. Arout CA, Haney M, Herrmann ES, Bedi G, Cooper ZD. A placebo-controlled investigation of the analgesic effects, abuse liability, safety and tolerability of a range of oral cannabidiol doses in healthy humans. Br J Clin Pharmacol 2021;33:347–55.

    1. Atwal N, Casey SL, Mitchell VA, Vaughan CW. THC and gabapentin interactions in a mouse neuropathic pain model. Neuropharmacology 2019;144:115–21.

    1. Baglot SL, Hume C, Petrie GN, Aukema RJ, Lightfoot SHM, Grace LM, Zhou R, Parker L, Rho JM, Borgland SL, McLaughlin RJ, Brechenmacher L, Hill MN. Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Scientific Rep 2021;11:23990.

    1. Baker SL, Kentner AC, Konkle ATM, Santa-Maria Barbagallo L, Bielajew C. Behavioral and physiological effects of chronic mild stress in female rats. Physiol Behav 2006;87:314–22.

Read more here: Source link

Leave a Reply

Your email address will not be published. Required fields are marked *