Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy

  title={Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy},
  author={Lyndsey L. Anderson and Marika Heblinski and Nathan L. Absalom and Nicole A. Hawkins and Matthew L. Bowen and Melissa J. Benson and F Zhang and Dilara Bahceci and Peter T. Doohan and Mary Chebib and Iain S. McGregor and Jennifer A. Kearney and Jonathon C Arnold},
  journal={British Journal of Pharmacology},
  pages={4826 - 4841}
Cannabis has been used to treat epilepsy for millennia, with such use validated by regulatory approval of cannabidiol (CBD) for Dravet syndrome. Unregulated artisanal cannabis‐based products used to treat children with intractable epilepsies often contain relatively low doses of CBD but are enriched in other phytocannabinoids. This raises the possibility that other cannabis constituents might have anticonvulsant properties. 

Implications of the effects of cannabigerolic acid on our understanding of the potential of phytocannabinoids in anti‐seizure treatment

  • A. McNeish
  • Biology
    British journal of pharmacology
  • 2021
Cannabigerolic acid (CBGA) was the most potent of the cannabinoids studied in preventing hyperthermia-induced seizures in this model and raises the possibility that cannabinoids such as CBGA may have synergistic effects with current ‘gold standard’ treatments for this form of epilepsy; however, due to the nonsigmoidal concentration response curve of CBGA, this was not possible.

Advances and Challenges of Cannabidiol as an Anti-Seizure Strategy: Preclinical Evidence

An overview of recent literature pointing out CBD’s pharmacological profile, its interactions with multiple molecular targets as well as advances in preclinical research concerning its anti-seizure effect on both acute seizure models and chronic models of epilepsy is presented.

Olivetolic acid, a cannabinoid precursor in Cannabis sativa, but not CBGA methyl ester exhibits a modest anticonvulsant effect in a mouse model of Dravet syndrome

Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a +/- mouse model of Dravet syndrome despite poor brain penetration, comparable to the known anticonVulsant cannabinoid cannabidiol in this model.

Acidic Cannabinoids Suppress Proinflammatory Cytokine Release by Blocking Store-operated Calcium Entry

Results indicate that cannabinoid-mediated inhibition of a proinflammatory target such as SOCE may at least partially explain the anti-inflammatory and analgesic effects of Cannabis.

The anticonvulsant phytocannabinoids CBGVA and CBDVA inhibit recombinant T-type channels

Findings show that CBGVA and CBDVA inhibit T-type calcium channels and GPR55, which may be relevant to the anti-seizure effects of this class of compounds.

Interacting binding insights and conformational consequences of the differential activity of cannabidiol with two endocannabinoid-activated G-protein-coupled receptors

This work investigates the interacting determinants of CBD in two closely related endocannabinoid-activated GPCRs, the G-protein-coupled receptor 55 (GPR55) and the cannabinoid type 1 receptor (CB1), and suggests a previously unknown sodium-binding site located in the extracellular domain of the CB1 receptor.

Single dose and chronic oral administration of cannabigerol and cannabigerolic acid-rich hemp extract in fed and fasted dogs: Physiological effect and pharmacokinetic evaluation.

Investigation of similar dosing of CBG and CBGA from hemp plants that have been used for cannabidiol pharmacokinetic studies suggests that when providing a hemp-derived CBG/CBGA formulation in equal quantities, CBGA is absorbed approximately 40-fold better than CBG regardless of being given to fed or fasted dogs.

Effects of cannabinoids on ligand-gated ion channels

The direct actions of endo-, phyto-, and synthetic cannabinoids on the functional properties of ligand-gated ion channels and the plausible mechanisms mediating these effects were reviewed and discussed.



Cannabidivarin is anticonvulsant in mouse and rat

For the first time, the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) is investigated in vitro and in in vivo seizure models.

Interactions between cannabidiol and Δ9‐tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome

The Scn1a+/− mouse model of Dravet syndrome is utilized to examine whether the presence of Δ9‐THC modulates the anticonvulsant efficacy of CBD.

Cannabidiolic acid methyl ester, a stable synthetic analogue of cannabidiolic acid, can produce 5‐HT1A receptor‐mediated suppression of nausea and anxiety in rats

The aim of this study was to compare the abilities of cannabidiolic acid methyl ester (HU‐580) and cannabidiolic acid (CBDA) to enhance 5‐HT1A receptor activation in vitro and produce 5‐HT1A‐mediated

Cannabidiol: State of the art and new challenges for therapeutic applications.

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions

The present study aimed to address the nature of the interaction between CBD and clobazam to address speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobzam exposure.

Phytocannabinoids and epilepsy

Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs.

Pharmacology of Medical Cannabis.

There is a lack of well-controlled, double blind, randomized clinical trials to provide clarity on the efficacy of either Δ9-THC or CBD as therapeutics, so attention is paid to the mechanisms by which medical cannabis may act to relieve pain and seizures.

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis

The objective of this paper is to describe the analysis of several observational clinical studies available on the literature regarding the treatment of child refractory epilepsy with cannabinoid based products, to establish the safety and efficacy of such products.

The proposed mechanisms of action of CBD in epilepsy.

The pharmacological data supporting the role of three such targets, namely Transient receptor potential vanilloid-1 (TRPV1), the orphan G protein-coupled receptor-55 (GPR55) and the equilibrative nucleoside transporter 1 (ENT-1) are presented.

The anticonvulsant activity of cannabidiol and cannabinol.