Evaluation of cannabimimetic effects of selected minor cannabinoids and Terpenoids in mice.
Jenny L Wiley, Julie A. Marusich, Bruce E. Blough, Ojas Namjoshi, Marcus Brackeen, Luli R Akinfiresoye, Teneille D Walker, Cassandra Prioleau, Daniel G Barrus, Thomas F Gamage
Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024 DOI: 10.1016/j.pnpbp.2024.110984 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical drug discrimination study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Δ9-THC cannabidiol (CBD) cannabinol (CBN) cannabichromene (CBC) cannabichromenevarin (CBCV) Δ8-tetrahydrocannabinol (Δ8-THC) (6aR 9R)-Δ10-tetrahydrocannabinol Δ9-tetrahydrocannabinol varin (THCV) β-caryophyllene (BC) β-caryophyllene oxide (BCO) |
| Topics | Cannabis CBD |
| Keywords | Drug discrimination Thcv Β-caryophyllene |
| Key points | Only Δ8-THC fully substituted for Δ9-THC in drug discrimination, while cannabinol and (6aR,9R)-Δ10-THC partially substituted; THCV and β-caryophyllene oxide did not alter Δ9-THC's discriminative stimulus effects. All minor cannabinoids showed measurable CB1 and CB2 receptor binding, with CBC, CBCV, and CBD showing the weakest CB1 affinity, while β-caryophyllene and its oxide had negligible affinity. The authors suggest that only four compounds tested [Δ9-THC, Δ8-THC, (6aR,9R)-Δ10-THC, and CBN] may possess cannabimimetic subjective effects. |
Abstract
The cannabis plant contains several cannabinoids, and many terpenoids that give cannabis its distinctive flavoring and aroma. Δ9-Tetrahydrocannabinol (Δ9-THC) is the plant's primary psychoactive constituent. Given the abuse liability of Δ9-THC, assessment of the psychoactive effects of minor cannabinoids and other plant constituents is important, especially for compounds that may be used medicinally. This study sought to evaluate select minor cannabinoids and terpenes for Δ9-THC-like psychoactivity in mouse Δ9-THC drug discrimination and determine their binding affinities at CB1 and CB2 receptors. Δ9-THC, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabichromenevarin (CBCV), Δ8-tetrahydrocannabinol (Δ8-THC), (6aR,9R)-Δ10-tetrahydrocannabinol [(6aR,9R)-Δ10-THC], Δ9-tetrahydrocannabinol varin (THCV), β-caryophyllene (BC), and β-caryophyllene oxide (BCO) were examined. All minor cannabinoids showed measurable cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor binding, with CBC, CBCV, and CBD, showing the weakest CB1 receptor binding affinity. BC and BCO exhibited negligible affinity for both CB1 and CB2 receptors. In drug discrimination, only Δ8-THC fully substituted for Δ9-THC, while CBN and (6aR,9R)-Δ10-THC partially substituted for Δ9-THC. THCV and BCO did not alter the discriminative stimulus effects of Δ9-THC. In summary, only some of myriad cannabinoids and other chemicals found in the cannabis plant bind potently to the identified cannabinoid receptors. Further, only four of the compounds tested herein [Δ9-THC, Δ8-THC, (6aR,9R)-Δ10-THC, and CBN] produced Δ9-THC-like discriminative stimulus effects, suggesting they may possess cannabimimetic subjective effects. Given that the medicinal properties of phytocannabinoids and terpenoids are being investigated scientifically, delineation of their potential adverse effects, including their ability to produce Δ9-THC-like intoxication, is crucial.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 3
- Cannabimimetic and discriminative stimulus effects of hexahydrocannabinols in mice. Journal of Psychopharmacology July 1, 2025
- Tolerance, physical dependence, and Δ9-THC-like interoceptive effects of cannabinol in mice. Drug and Alcohol Dependence September 1, 2026
- Effects of ketamine enantiomers on morphine and THC subjective effects in rats. Journal of Psychopharmacology December 26, 2025
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and 5 more in the library