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

Zhang, Shan-Shan; Zhang, Niu-Niu; Guo, Tiantian; Sheen, Lee‐Yan; Ho, Chi‐Tang; Bai, Naisheng

doi:10.1016/j.jtcme.2022.10.004

Cited by 10 publications

(10 citation statements)

References 71 publications

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Section: Discussionsupporting

confidence: 88%

“…There was however a significant reduction of napepld and gde1 expression after Δ9-THC exposure in PTZ treated embryos. AEA and Δ 9 -THC have been reported to act on the same receptors 27,34,58 and this further supports literature on the putative mechanism of action of Δ 9 -THC. Expression of faah , required or the breakdown of AEA to AA, was significantly increased in PTZ exposed embryos pretreated with Δ 9 -THC when compared to PTZ treatment only.…”

Section: Discussionsupporting

confidence: 87%

“…CBN and CBC also showed a potent reduction of seizures at 1 µM dosage and interestingly, accumulated in tissue with similar values of 1.6 ± 0.1 ng/larva for CBN and 1.7 ± 0.3 ng/larva for CBC, the lowest abundance quantified that was associated with a reduction in seizures. Though previously reported to possess anti-epileptic properties, Δ 9 -THC [27][28][29] , and its structural isomer Δ 8 -THC, only provided seizure rescue at the highest concentrations used in this study (4 µM) and required higher accumulation within larvae for such effects. Interestingly, a 2 µM dose of CBG repeatedly increased seizure index significantly to a level higher than the vehicle control, yet higher doses reduce seizure index.…”

Section: Discussionmentioning

confidence: 55%

“…Treatment with Δ 9 -THC in combination with CBD has been the main focus of recent studies, and has been associated with improved symptoms of neurodegenerative diseases, pain perception, and depression as reviewed by Zhang and colleagues in 2022 27 . A combination of Δ 9 -THC and CBD has also been shown to be anti-epileptic in a mouse model of Dravet Syndrome and a zebrafish model of neuro-hyperactivity 28,29 .…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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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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show abstract

“…To further demonstrate the practical value of this method, we commenced to achieve the total synthesis of natural or pharmaceutically active molecules (Scheme ). Cannabinoids and cannabinoid prodrugs can be used for neuroprotection, treating pain, or treating disease associated with α-1 or α-3 glycine receptor deficiency . As shown in Scheme a, cannabinoid derivative 9f was invented by Beetlebung Pharma and contains a 1-aryl-2-alkyl-disubstituted cyclobutane unit; to date, only racemic synthesis was reported .…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Transfer Hydrogenation of Cyclobutenediones

Lan,

Huang,

Liu

et al. 2024

J. Am. Chem. Soc.

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Four-membered carbocycles are fundamental substructures in bioactive molecules and approved drugs and serve as irreplaceable building blocks in organic synthesis. However, developing efficient protocols furnishing diversified four-membered ring compounds in a highly regio-, diastereo-, and enantioselective fashion remains challenging but very desirable. Here, we report the unprecedented asymmetric transfer hydrogenation of cyclobutenediones. The reaction can selectively afford three types of four-membered products in high yields with high stereoselectivities, and the highly functionalized products enable a series of further transformations to form more diversified four-membered compounds. Asymmetric synthesis of di-, tri-, and tetrasubstituted bioactive molecules has also been achieved. Systematic mechanistic studies and theoretical calculations have revealed the origin of the regioselectivity, the key hydrogenation transition state models, and the sequence of the double and triple hydrogenation processes. The work provides a new choice for the catalytic asymmetric synthesis of cyclobutanes and related structures and demonstrates the robustness of asymmetric transfer hydrogenation in the accurate selectivity control of highly functionalized substrates.

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Affordable method for batch supercritical extraction using solid carbon dioxide–Extraction of cannabis threshing residues

Buitrago,

Ardila,

Orjuela

et al. 2024

Chemical Engineering and Processing - Process Intensification

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

Cited by 10 publications

References 71 publications

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

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

Asymmetric Transfer Hydrogenation of Cyclobutenediones

Affordable method for batch supercritical extraction using solid carbon dioxide–Extraction of cannabis threshing residues

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