Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors
Hanna J Szkudlarek, Sagar Desai, Justine Renard, Brian J.g. Pereira, Christopher Norris, Christina E. L. Jobson, Nagalingam Rajakumar, Brian L. Allman, Steven R Laviolette
Neuropsychopharmacology November 27, 2018 DOI: 10.1038/s41386-018-0282-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | THC CBD |
| Duration | Acute |
| Topics | Anxiety Cannabis CBD |
| Keywords | Anxiogenic Prefrontal cortex Psychosis Cannabinoid Glutamatergic Cognition Schizophrenia object-oriented programming Pharmacology Anxiolytic Glutamate receptor |
| Citations | 63 |
| Key findings | Acute intra-PFC THC produces anxiogenic effects without impairing executive function, while intra-PFC CBD impairs attentional set-shifting and spatial working memory but reverses cognitive impairments from glutamatergic antagonism and blocks THC's anxiogenic properties. |
Abstract
The use of cannabis for therapeutic and recreational purposes is growing exponentially. Nevertheless, substantial questions remain concerning the potential cognitive and affective side-effects associated with cannabis exposure. In particular, the effects of specific marijuana-derived phytocannabinoids on neural regions such as the prefrontal cortex (PFC) are of concern, given the role of the PFC in both executive cognitive function and affective processing. The main biologically active phytocannabinoids, ∆-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), interact with multiple neurotransmitter systems important for these processes directly within the PFC. Considerable evidence has demonstrated that acute or chronic THC exposure may induce psychotomimetic effects, whereas CBD has been shown to produce potentially therapeutic effects for both psychosis and/or anxiety-related symptoms. Using an integrative combination of cognitive and affective behavioral pharmacological assays in rats, we report that acute intra-PFC infusions of THC produce anxiogenic effects while producing no impairments in executive function. In contrast, acute infusions of intra-PFC CBD impaired attentional set-shifting and spatial working memory, without interfering with anxiety or sociability behaviors. In contrast, intra-PFC CBD reversed the cognitive impairments induced by acute glutamatergic antagonism within the PFC, and blocked the anxiogenic properties of THC, suggesting that the therapeutic properties of CBD within the PFC may be present only during pathologically aberrant states within the PFC. Interestingly, the effects of PFC THC vs. CBD were found to be mediated through dissociable CB1 vs. 5-HT1A-dependent receptor signaling mechanisms, directly in the PFC.