THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways

Szkudlarek, Hanna; Rodríguez-Ruiz, Mar; Hudson, Roger; Felice, Marta De; Jung, Tony; Rushlow, Walter; Laviolette, Steven R.

doi:10.1016/j.pnpbp.2020.110029

Cited by 16 publications

(8 citation statements)

References 77 publications

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“…); CBD (5–400 mg/kg·bw, i.p.) CBD had a significant effect on reducing seizures 24 , 43 Depression CBC used in combination with CBD (0.2 ng/nL, intracranial infusions) or THC (0.2 ng/nL, intracranial infusions) improve insomnia and antidepressants 49 , 50 CBD anti-depression and anxiolytic 51 Sleep disorders CBD inhibit FAAH to increase the level of AEA to promote sleep 59 AEA sleep-promoting effect △ 9 -THC activate CB1 receptor to promote sleep Stroke AEA and 2-AG activate the M2 microglia, anti-inflammatory effect, improve ischemic neuron damage 30 Multiple sclerosis Sativex® (△ 9 -THC + CBD) activate M2 microglia, inhibit CD4 + T cells in EAE mice, treat multiple sclerosis 13 , 64 …”

Section: Discussionmentioning

confidence: 99%

“…Studies have pointed out that when CBC is used in combination with other cannabinoids such as CBD (0.2 ng/nL, intracranial infusions) and THC (0.2 ng/nL, intracranial infusions), it has an effect on improving insomnia and antidepressants. 49 , 50 However, some research pointed out that cannabis has two opposite effects on depression. On the one hand, the heavy use of cannabis is associated with a higher incidence of depression.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

See 1 more Smart Citation

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

Zhang

Zhang²,

Guo³

et al. 2023

Journal of Traditional and Complementary Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Pharmacological Activitiesmentioning

confidence: 99%

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

Zhang

Zhang²,

Guo³

et al. 2023

Journal of Traditional and Complementary Medicine

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“…56 In addition, it has been shown that THC induces phosphorylation of extracellular signal-regulated kinases one-half pathway in rat brain structures like the hippocampus and that the prefrontal cortex and CBD coadministration was able to prevent this effect. 57,58 In humans, a single oral CBD (600 mg) administration has shown reduction in psychotic symptoms related to changes in these same brain areas. 59 There is also evidence of the underlying antipsychotic mechanisms of CBD, and some neuronal receptors have been proposed as the targets for this effect.…”

Section: Discussionmentioning

confidence: 99%

Opposite Roles for Cannabidiol and δ-9-Tetrahydrocannabinol in Psychotomimetic Effects of Cannabis Extracts

Sainz-Cort

Jiménez-Garrido²,

Muñoz-Marrón

et al. 2021

J Clin Psychopharmacol

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Background: Although δ-9-tetrahydrocannabinol (THC), the main cannabinoid from the cannabis plant, is responsible for the psychotomimetic effects of cannabis, cannabidiol (CBD), the second most abundant cannabinoid in the cannabis plant, does not show any psychotomimetic effect. Cannabidiol has even been proposed to be antipsychotic and to counteract some of the psychotomimetic effects of THC. The aim of this study was to test the potential antipsychotomimetic effects of CBD.Method: Eighteen members from a cannabis social club were tested for subjective and psychotomimetic effects under the effects of different full-spectrum cannabis extracts containing either THC, CBD, THC + CBD, or placebo in a naturalistic, randomized, double-blind, crossover, placebo-controlled study.Results: Results showed that participants under the effects of THC + CBD showed lower psychotomimetic scores in subjective scales when compared with THC alone. Subjective scores were lower under the effects of CBD and placebo when compared with THC + CBD. Cannabidiol and placebo did not show any psychotomimetic effect. Conclusions:This study provides evidence for both the psychotomimetic effects of THC and the antipsychotomimetic effects of CBD when it is coadministered with THC in real-world situations, which can be very relevant for the clinical practice of medical cannabis. Ultimately, this study substantiates the link between the endocannabinoid system and psychotic-like symptoms and has important implications for the understanding of schizophrenia and the therapeutic potential of CBD as an antipsychotic. Lastly, we demonstrate how reliable methodologies can be implemented in real situations to collect valid ecological evidence outside classic laboratory settings.

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“…CBC is one of the most abundant cannabinoids in cannabis but has not been well studied with respect to epilepsy, but is known to exhibit neuroprotective effects in cultured mouse neural cells 23 . There is also evidence that CBC when used in combination with CBD or Δ 9 -THC can help alleviate symptoms of insomnia and depression in humans and rats 24,25 . CBG was determined to be non-psychotropic and is of interest commercially as it is abundant in some commonly used hemp plants, but little is known as to its potential anticonvulsant properties 26 .…”

Section: Introductionmentioning

confidence: 99%

CBD can be combined with additional cannabinoids for optimal seizure reduction and requires GPR55 for its anticonvulsant effects

Kollipara

Langille

Tobin

et al. 2023

Preprint

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Background: Cannabis has demonstrated anticonvulsant properties, and cannabis-based medicines are approved to treat pediatric patients with severe pediatric epilepsies that are particularly refractive to approved anti-epileptic drugs (AEDs). About thirty percent of epileptic patients do not have satisfactory seizure management with AEDs and could potentially benefit from cannabis-based intervention. Here we report the use of single and combined cannabinoids to treat Pentylenetetrazol (PTZ) induced convulsions in a zebrafish model, their effect on gene expression, and a simple assay for assessing their uptake in zebrafish tissues. These data provide novel insights as to the potential of treating epilepsy with cannabinoids. Methods: Zebrafish larvae were treated with cannabinoids and their seizures measured through an optimized behaviour tracking method. Cannabinoid uptake was measured with a novel HPLC-UV method. Gene expression changes were assessed using quantitative PCR (qPCR), and chemical inhibitors of potential cannabinoid receptors were used to block activity. Results: Treatment with cannabinol (CBN), cannabichromene (CBC) and cannabigerol (CBG) decreased seizure intensity at lower doses than CBD when accounting for the amount of cannabinoid recovered from exposed larvae. Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC) were effective at higher doses. Synergistic effects were observed between CBD and other cannabinoids such as Δ9-THC, Δ8-THC, and CBG. The reduction of PTZ induced seizures via CBD is partially mediated by the G-protein coupled receptor GPR55, as pharmacological inhibition of the receptor reduced the therapeutic action of CBD. Changes in expression of endocannabinoid system (napepld, gde1, faah, ptgs2a) and neural (fosab, pyya) genes in response to phytocannabinoid treatment were observed and highlight novel mechanisms of phytocannabinoid action. Conclusions: CBD can be combined with additional cannabinoids for optimal reduction of seizure activity and requires the activity of GPR55. Changes in fosab regulation of gene expression and endocannabinoid signalling may influence the anticonvulsant effects of cannabis, however further investigation is required.

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THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways

Cited by 16 publications

References 77 publications

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review

Opposite Roles for Cannabidiol and δ-9-Tetrahydrocannabinol in Psychotomimetic Effects of Cannabis Extracts

CBD can be combined with additional cannabinoids for optimal seizure reduction and requires GPR55 for its anticonvulsant effects

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