Cannabinoid interactions with ion channels and receptors

Watkins, Abeline R.

doi:10.1080/19336950.2019.1615824

Cited by 68 publications

(64 citation statements)

References 36 publications

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“…Specifically, this antagonism on CB2 receptors inhibits immune cell migration and might explain the anti-inflammatory effects of CBD, as well as the attenuation of THC psychoactive side-effects [13]. Recent studies have also shown that CBD can interact with a wide range of other targets, such as sodium, potassium, and calcium channels, and serotonin and glycine receptors, independently from the CB1 and CB2 receptors [14].…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Hegazy¹,

Platnick²

2019

Cureus

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Neurofibromatosis type 1 (NF1) is a common genetic disorder. Pain is a major symptom of this disease which can be secondary to the development of plexiform and subcutaneous neurofibromas, musculoskeletal symptoms (such as scoliosis and pseudoarthrosis), and headaches. Visible neurofibromas add significant psychosocial distress for NF1 patients. Along with the chronic pain, psychosocial distress contributes to associated mood disorders, such as depression and anxiety. Cannabis has been the focus of many studies for treating multiple conditions, including epilepsy, multiple sclerosis, Parkinsonism disease, and many chronic pain conditions. Cannabidiol (CBD) is the major non-psychotropic component of cannabis. CBD has shown anti-inflammatory and analgesic properties, as well as having mood stabilizer and anxiolytic effects. In this report, we present the use of cannabidiol (CBD) for the management of chronic pain and concomitant mood disorder in an NF1 patient.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Hegazy¹,

Platnick²

2019

Cureus

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“…Both of these diseases are rare early-onset epilepsies associated with Navs, with Dravet patients often having mutations in the hNav1.1 gene SCN1A ( Marini et al, 2011 ). Despite a significant amount of evidence reporting on the effectiveness of CBD for treating epileptic conditions ( Cross et al, 2017 ; Devinsky et al, 2018 ), the molecular basis of its target interactions with ion channels and receptors still remains unclear ( Watkins, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol interactions with voltage-gated sodium channels

Sait

Sula

Ghovanloo

et al. 2020

eLife

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Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels.

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“…Furthermore, CBD has been shown to attenuate seizures and social deficits in a mouse model of Dravet syndrome (Kaplan et al, 2017). Despite a significant amount of evidence reporting on the effectiveness of CBD for treating epileptic conditions (Cross et al, 2017;Devinsky et al, 2018), the molecular basis of its target interactions remain unclear (Watkins, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Interactions with Voltage-Gated Sodium Channels

Sait

Sula

Hollingworth

et al. 2020

Preprint

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Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, showing CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies illuminate why the closely-related psychoactive compound THC may not bind to these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD with sodium channels.Introduction:

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Cannabinoid interactions with ion channels and receptors

Cited by 68 publications

References 36 publications

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Cannabidiol (CBD) for Treatment of Neurofibromatosis-related Pain and Concomitant Mood Disorder: A Case Report

Cannabidiol interactions with voltage-gated sodium channels

Cannabidiol Interactions with Voltage-Gated Sodium Channels

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