Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats.
Charlotte Klein, Emily Karanges, Adena Spiro, Alexander Wong, Jarrah Spencer, Thanh Huynh, Nathan Gunasekaran, Tim Karl, Leonora E Long, Xu-Feng Huang, Kelly Liu, Jonathon C Arnold, Iain S. Mcgregor
Psychopharmacology November 2011 DOI: 10.1007/s00213-011-2342-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adolescent rats |
| Interventions | THC CBD |
| Dose | THC 1 then 3 then 10 mg/kg daily over 21 days; CBD equivalent doses 20 min prior |
| Duration | 21 days of dosing |
| Topics | Cannabis CBD |
| Key findings | CBD pre-treatment potentiated THC's effects on body weight, anxiety, locomotion, and social interaction, and increased blood and brain THC levels while lowering THC metabolite levels, likely by inhibiting THC metabolism via CYP450 enzymes. |
Abstract
The interactions between Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) during chronic treatment, and at equivalent doses, are not well characterised in animal models. The aim of this study is to examine whether the behavioural effects of THC, and blood and brain THC levels are affected by pre-treatment with equivalent CBD doses. Adolescent rats were treated with ascending daily THC doses over 21 days (1 then 3 then 10 mg/kg). Some rats were given equivalent CBD doses 20 min prior to each THC injection to allow examination of possible antagonistic effects of CBD. During dosing, rats were assessed for THC and CBD/THC effects on anxiety-like behaviour, social interaction and place conditioning. At the end of dosing, blood and brain levels of THC, and CB(1) and 5-HT(1A) receptor binding were assessed. CBD potentiated an inhibition of body weight gain caused by chronic THC, and mildly augmented the anxiogenic effects, locomotor suppressant effects and decreased social interaction seen with THC. A trend towards place preference was observed in adolescent rats given CBD/THC but not those given THC alone. With both acute and chronic administration, CBD pre-treatment potentiated blood and brain THC levels, and lowered levels of THC metabolites (THC-COOH and 11-OH-THC). CBD co-administration did not alter the THC-induced decreases in CB(1) receptor binding and no drug effects on 5-HT(1A) receptor binding were observed. CBD can potentiate the psychoactive and physiological effects of THC in rats, most likely by delaying the metabolism and elimination of THC through an action on the CYP450 enzymes that metabolise both drugs.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 28
- Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Psychopharmacology May 1, 2019
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- Effects of Chronic Exposure to Low-Dose delta-9-Tetrahydrocannabinol in Adolescence and Adulthood on Serotonin/Norepinephrine Neurotransmission and Emotional Behavior The International Journal of Neuropsychopharmacology July 23, 2020
- Acute effects of different types of cannabis on young adult and adolescent resting-state brain networks Neuropsychopharmacology May 28, 2024
- Neurotoxic or Protective Cannabis Components: Delta-9-Tetrahydrocannabinol ( Δ9 THC) and Cannabidiol (CBD) Journal of Exploratory Research in Pharmacology July 12, 2023
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