Highs & Lows of Marijuana: How CBD Blocks Schizophrenia – Like Side Effects of THC. FPS #2

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In this episode of First-Person Science, Thomas Lapointe speaks with Roger Hudson about his recently published manuscript in the Journal Of Neuroscience, discussing how the main psychoactive ingredient in cannabis, THC, causes adverse psychiatric side-effects in some users, and the science of how cannabidiol, or 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.
https://www.ncbi.nlm.nih.gov/pubmed/31570536

1:10–2:00: General context (psychological side effects of THC, how THC may cause these side-effects, how CBD works)
2:22-4:28: ERK explained, how its modulated, and its role in the effects of THC+CBD
4:42-7:05: How THC acts on CB1 receptors and how this modulates GABA and glutamate neurotransmission, leading to alterations in salience attribution
7:06-8:36: General methodology
8:37-10:59: Results figure 1 (pERK expression)
11:00-16:37: Results figure 2 (anxiety tests: open field and light/dark test)
16:38-19:08: Methodology: difference between context dependent and context independent tasks
19:09-21:10: Results figure 3 (aversive learning: context dependent/independent fear conditioning
21:11-22:22: Interpretations figure 3
22:23-26:47: Results figure 3 (appetitive learning: conditioned place preference and sucrose preference)
27:04-35:36: Results figure 4, 5 ,6 (electrophysiology)

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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-vHippTHCstrongly 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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