Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.
Stephanie M Todd, Cilla Zhou, David J Clarke, Tariq W Chohan, Dilara Bahceci, Jonathon C Arnold
European Neuropsychopharmacology February 2017 DOI: 10.1016/j.euroneuro.2016.12.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical repeated-treatment study Peer reviewed |
|---|---|
| Population | Rodents (preclinical animal model) |
| Interventions | Cannabidiol (CBD) Δ9-tetrahydrocannabinol (THC) |
| Duration | 15 days of treatment |
| Topics | Cannabis CBD |
| Keywords | Behaviour Epigenetic Mesolimbic pathway Neuroadaption |
| Key points | CBD modestly reduced THC-induced rebound locomotor hyperactivity and slightly reduced THC's acute effects on sensorimotor gating at a 1:1 ratio, but did not alter THC-induced anxiety or tolerance. Repeated co-administration increased H3K9/14ac in the VTA and ΔFosB in the nucleus accumbens, suggesting complex, potentially supradditive long-term molecular actions. |
Abstract
The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 3
- Analysis of the Uptake, Metabolism, and Behavioral Effects of Cannabinoids on Zebrafish Larvae. Zebrafish August 2018
- Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC. European Neuropsychopharmacology December 2017
- Effect of prior foot shock stress and Δ9-tetrahydrocannabinol, cannabidiolic acid, and cannabidiol on anxiety-like responding in the light-dark emergence test in rats. Psychopharmacology July 2017
Cites 16
- Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. The Lancet Psychiatry March 1, 2016
- Hippocampal harms, protection and recovery following regular cannabis use. Translational Psychiatry January 12, 2016
- Neural correlates of interactions between cannabidiol and Δ(9) -tetrahydrocannabinol in mice: implications for medical cannabis. British Journal of Pharmacology January 2016
- Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. Pharmacological Research December 2015
- Sensorimotor gating, cannabis use and the risk of psychosis Schizophrenia Research May 1, 2015
and 11 more in the library