THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways.
Hanna J Szkudlarek, Mar Rodríguez-ruiz, Roger Hudson, Marta De Felice, Tony Jung, Walter J Rushlow, Steven R Laviolette
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2021 DOI: 10.1016/j.pnpbp.2020.110029 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Sprague Dawley rats |
| Interventions | THC CBD |
| Topics | Cannabis CBD |
| Keywords | Cannabinoids Latent inhibition Panic Prefrontal cortex |
| Key findings | Intra-PFC THC induces panic-like behavior via ERK1/2 phosphorylation, while CBD impairs latent inhibition and perceptive functions via 5-HT1A receptor activation and reduced p70S6K phosphorylation, and CBD counteracts THC-induced panic. |
Abstract
Clinical and pre-clinical evidence demonstrates divergent psychotropic effects of THC vs. CBD. While THC can induce perceptual distortions and anxiogenic effects, CBD displays antipsychotic and anxiolytic properties. A key brain region responsible for regulation of cognition and affect, the medial prefrontal cortex (PFC), is strongly modulated by cannabinoids, suggesting that these dissociable THC/CBD-dependent effects may involve functional and molecular interplay within the PFC. The primary aim of this study was to investigate potential interactions and molecular substrates involved in PFC-mediated effects of THC and CBD on differential cognitive and affective behavioural processing. Male Sprague Dawley rats received intra-PFC microinfusions of THC, CBD or their combination, and tested in the latent inhibition paradigm, spontaneous oddity discrimination test, elevated T-maze and open field. To identify local, drug-induced molecular modulation in the PFC, PFC samples were collected and processed with Western Blotting. Intra-PFC THC induced strong panic-like responses that were counteracted with CBD. In contrast, CBD did not affect panic-like behaviours but blocked formation of associative fear memories and impaired latent inhibition and oddity discrimination performance. Interestingly, these CBD effects were dependent upon 5-HT1A receptor transmission but not influenced by THC co-administration. Moreover, THC induced robust phosphorylation of ERK1/2 that was prevented by CBD, while CBD decreased phosphorylation of p70S6K, independently of THC. These results suggest that intra-PFC infusion of THC promotes panic-like behaviour associated with increased ERK1/2 phosphorylation. In contrast, CBD impairs perceptive functions and latent inhibition via activation of 5-HT1A receptors and reduced phosphorylation of p70S6K.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 4
- Opposite Roles for Cannabidiol and δ-9-Tetrahydrocannabinol in Psychotomimetic Effects of Cannabis Extracts Journal of Clinical Psychopharmacology August 20, 2021
- The Relationship Between Cannabis, Cognition, and Schizophrenia: It’s Complicated Current Topics in Behavioral Neurosciences 2022
- The Effects of Cannabidiol and δ-9-Tetrahydrocannabinol in Social Cognition: A Naturalistic Controlled Study Cannabis and Cannabinoid Research July 26, 2022
- Adolescent female rats are resistant to the affective and cognitive impacts of Δ9-tetrahydrocannabinol exposure despite long-lasting molecular and neuronal disturbances in the hippocampal-hypothalamic network. Psychopharmacology November 1, 2025
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