Discriminative-stimulus effects of cannabidiol oil in Sprague-Dawley rats

Behav Pharmacol. 2024 Feb 1;35(1):36-46. doi: 10.1097/FBP.0000000000000762. Epub 2023 Dec 13.

Abstract

Cannabidiol (CBD) is one of the major centrally active phytocannabinoid components of cannabis, and has been approved by the FDA only for the treatment of seizures associated with three rare disorders. It has also been touted as a potential treatment for anxiety in place of more traditional treatments like benzodiazepines. Although there is some evidence of anxiolytic effects of CBD, its suitability as a substitute for benzodiazepines is unknown. This experiment was designed to assess the extent to which CBD shares interoceptive discriminative-stimulus properties with the anxiolytic drug chlordiazepoxide (CDP), a benzodiazepine. In the present experiment, a range of doses (0-1569 mg/kg) of over-the-counter CBD oil was administered (i.g.) in male Sprague-Dawley rats trained to discriminate 5.6 mg/kg CDP from saline. Due to the long time-course effects of CBD, generalization tests were conducted at 90 and 120 min post-CBD administration. The two highest doses of CBD tested (1064 and 1569 mg/kg) were found to partially substitute for 5.6 mg/kg CDP, with mean percent responding on the CDP-associated lever reaching above 20% at time 2 (120 min post-CBD administration), suggesting that high doses of the over-the-counter CBD oils used in this experiment share interoceptive discriminative-stimulus properties to some degree with CDP. These results are novel in comparison to existing research into stimulus effects of CBD, in which substitution for benzodiazepines has not previously been observed.

MeSH terms

  • Animals
  • Benzodiazepines / pharmacology
  • Cannabidiol* / pharmacology
  • Chlordiazepoxide / pharmacology
  • Discrimination Learning
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cannabidiol
  • Chlordiazepoxide
  • Benzodiazepines