How Does CBD Block Side Effects of THC? | Highs & Lows of Potent Cannabis Use. FPS #2

Evidence suggests that THC and CBD each act on specific receptors in the brain to cause different effects on Biomarkers, other neurotransmitter systems and molecular pathways. In fact, CBD can even prevent many of the side effects associated with potent cannabis (high THC cannabis) such as psychosis, paranoia, and in some cases can act as a treatment for those diagnosed with schizophrenia.

In this episode of First-Person Science, PhD Candidate & Vanier Scholar Roger Hudson speaks about his recently published manuscript in the Journal Of Neuroscience, discussing how THC causes adverse psychiatric side-effects in some users, and the science of how cannabidiol (CBD) can counteract these side effects.

“Cannabidiol (CBD) Counteracts the Psychotropic Side-Effects of Delta-9-Tetrahydrocannabinol (THC) in the Ventral Hippocampus through Bidirectional Control of ERK1–2 Phosphorylation”, published in The Journal of Neuroscience [2019 Oct;39(44):8762–8777] / DOI:10.1523/JNEUROSCI.0708-19.2019.


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ABSTRACT: Evidence suggests that the phytocannabinoids Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) differentially regulate salience attribution and psychiatric risk. The ventral hippocampus (vHipp) relays emotional salience via control of dopamine (DA) neuronal activity states, which are dysregulated in psychosis and schizophrenia. Using in vivo electrophysiology in male Sprague Dawley rats, we demonstrate that intra-vHipp THCstrongly increases ventral tegmental area (VTA)DAneuronal frequency and bursting rates, decreases GABA frequency, and amplifies VTA beta, gamma and epsilon oscillatory magnitudes via modulation of local extracellular signal-regulated kinase phosphorylation (pERK1–2). Remarkably, whereas intra-vHipp THC also potentiates salience attribution in morphine place-preference and fear conditioning assays, CBD coadministration reverses these changes by downregulating pERK1–2 signaling, as pharmacological reactivation of pERK1–2 blocked the inhibitory properties of CBD. These results identify vHipp pERK1–2 signaling as a critical neural nexus point mediating THC-induced affective disturbances and suggest a potential mechanism by which CBD may counteract the psychotomimetic and psychotropic side effects of THC.

Keywords: cannabidiol; delta-9-tetrahydrocannabinol; dopamine; extracellular signal-regulated kinase; ventral hippocampus; ventral tegmental area.

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