Evaluating Potential Anxiolytic Effects of Minor Cannabinoids and Terpenes After Acute and Chronic Oral Administration in Rats.
Bryan W Jenkins, Catherine F Moore, Dan Covey, Jacob D McDonald, Timothy W Lefever, Marcel O Bonn-Miller, Elise M Weerts
Cannabis and Cannabinoid Research September 2023 DOI: 10.1089/can.2023.0083 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult male Sprague Dawley rats |
| Interventions | tetrahydrocannabivarin cannabidiolic acid cannabidivarin cannabigerol D-limonene bisabolol ethyl alcohol |
| Dose | D8-THC 10 mg/kg; tetrahydrocannabivarin 32 mg/kg; cannabidiolic acid 32 mg/kg; cannabidivarin 32 mg/kg; cannabigerol 100 mg/kg; D-limonene 17 mg/kg; alpha-pinene 100 mg/kg; alpha-terpineol 10 mg/kg; bisabolol 100 mg/kg; beta-caryophyllene 17 mg/kg |
| Duration | Experiment 1: acute administration with testing 30 minutes post-administration. Experiment 2: once-daily dosing for 21 days with assessment after 7, 14, and 21 days. |
| Measures | marble burying test, three-chamber social interaction test, novelty-induced hypophagia test |
| Topics | Anxiety |
| Keywords | Monoterpenes Phytocannabinoids Terpenoid |
| Key findings | Acute bisabolol and D-limonene increased food intake, and bisabolol, D-limonene, alpha-pinene, and beta-caryophyllene reduced outer-zone time in the novelty-induced hypophagia test, which the authors suggest indicates anxiolytic effects. Only ethanol increased social interaction. D8-THC showed anxiogenic effects acutely in the marble burying test and chronically in the novelty-induced hypophagia test; the other cannabinoids and terpenes showed no anxiolytic or anxiogenic effects at the doses and times tested. |
Abstract
Background: Cannabis and its primary psychoactive constituent delta-9-tetrahydrocannabinol (D9-THC) produce biphasic, dose-dependent effects on anxiety. In addition to D9-THC, cannabis contains other "minor" cannabinoids and terpenes with purported therapeutic potential for the treatment of anxiety. Empirical data on potential therapeutic effects of these compounds is limited. The current study evaluated the effects of selected minor cannabinoids and terpenes in a battery of tests sensitive to anxiolytic and anxiogenic drugs.
Methods: In Experiment 1, adult male Sprague Dawley rats (N=7-8/group) were administered acute oral doses of one of five minor cannabinoids: delta-8-tetrahydrocannabinol (D8-THC; 10 mg/kg), tetrahydrocannabivarin (32 mg/kg), cannabidiolic acid (32 mg/kg), cannabidivarin (32 mg/kg), and cannabigerol (100 mg/kg), or one of five terpenes: D-limonene (17 mg/kg), ⍺-pinene (100 mg/kg), ⍺-terpineol (10 mg/kg), bisabolol (100 mg/kg), and β-caryophyllene (17 mg/kg), or vehicle (medium-chain triglycerides [MCT] oil). Ethyl alcohol was tested as an active comparator. Thirty minutes post-administration, the marble burying test, the three-chamber social interaction test, and the novelty-induced hypophagia test were completed; motor activity was assessed throughout testing. Experiment 2 examined the potential anxiolytic effects of minor cannabinoids when administered chronically; rats administered MCT oil or minor cannabinoids in Experiment 1 continued receiving once-daily doses for 21 days and were assessed using the same test battery after 7, 14, and 21 days of administration. Results and
Conclusions: When compared to vehicle, acute administration of bisabolol and D-limonene increased the amount of food consumed and bisabolol-, D-limonene-, ⍺-pinene-, and β-caryophyllene decreased percent time spent in the outer zone in the novelty-induced hypophagia test, suggestive of an anxiolytic effect. Only ethanol increased social interaction. After acute administration, anxiogenic effects in the marble burying test were observed for D8-THC, but not for other minor cannabinoids and terpenes. Throughout chronic administration, only D8-THC displayed anxiogenic effects in the novelty-induced hypophagia test. The other cannabinoids did not show anxiolytic or anxiogenic effects in any of the tests at the doses or times tested. The minor cannabinoids and terpenes did not impair or stimulate general motor activity. These data provide a foundation for future studies investigating cannabinoid/terpene interactions.