Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Franco, Valentina; Perucca, Emilio

doi:10.1007/s40265-019-01171-4

Cited by 113 publications

(111 citation statements)

References 127 publications

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“…Indeed, Kathmann and colleagues, using rat cerebral cortex membrane homogenates, performed kinetic binding studies in order to evaluate the allosteric interactions on this class of G protein-coupled receptors. This study demonstrated, for the first time, the capability of these compounds to strongly modulate the µ and δ opioid receptors adding more evidence to explain pCBs anti-nociceptive effects [36].…”

Section: Opioid Receptorsmentioning

confidence: 61%

“…TRPV proteins contribute to heat perception and inflammatory reactions and mediate pain sensation. CBD acts on TRPV channels as an agonist, especially on TRPV1 channel sub-type, inducing activation, dephosphorylation, and strong desensitization, which in turn decreases intracellular calcium levels and neuronal excitability [36], thus accounting for both the CBD anti-nociceptive and anti-convulsant effects.…”

Section: Transient Receptor Potential Vanilloid Sub-familymentioning

confidence: 99%

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Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

Cifelli

Ruffolo

Felice

et al. 2020

IJMS

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γ-Aminobutyric acid type A receptors (GABAARs) are the main inhibitory mediators in the central nervous system (CNS). GABAARs are pentameric ligand gated ion channels, and the main subunit composition is usually 2α2βγ, with various isotypes assembled within a set of 19 different subunits. The inhibitory function is mediated by chloride ion movement across the GABAARs, activated by synaptic GABA release, reducing neuronal excitability in the adult CNS. Several studies highlighted the importance of GABA-mediated transmission during neuro-development, and its involvement in different neurological and neurodevelopmental diseases, from anxiety to epilepsy. However, while it is well known how different classes of drugs are able to modulate the GABAARs function (benzodiazepines, barbiturates, neurosteroids, alcohol), up to now little is known about GABAARs and cannabinoids interaction in the CNS. Endocannabinoids and phytocannabinoids are lately emerging as a new class of promising drugs for a wide range of neurological conditions, but their safety as medication, and their mechanisms of action are still to be fully elucidated. In this review, we will focus our attention on two of the most promising molecules (Δ9-tetrahydrocannabinol; Δ9-THC and cannabidiol; CBD) of this new class of drugs and their possible mechanism of action on GABAARs.

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Section: Opioid Receptorsmentioning

confidence: 61%

Section: Transient Receptor Potential Vanilloid Sub-familymentioning

confidence: 99%

Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

Cifelli

Ruffolo

Felice

et al. 2020

IJMS

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“…CBD binds to cannabinoid CB 1 and CB 2 receptors with much lower affinity than ∆ 9 -tetrahydrocannabinol (THC) [3] and interacts with GPR18, GPR55 and TRPV1 receptors [4]; it possesses a very marked antioxidant effect [5][6][7]. CBD is licensed for the treatment of some types of childhood epilepsy (Dravet and Lennox-Gastaut syndrome) in the United States [4,8] and, in combination with THC, for the treatment of multiple sclerosis-associated spasticity in Canada and in the European Union [4]. In addition, a potential therapeutic action of CBD is being considered in anxiety disorders, schizophrenia, depression, Alzheimer's disease, Parkinson's disease, pain, cancer, inflammatory and autoimmune diseases and diabetic complications [2,4,9].…”

Section: Introductionmentioning

confidence: 99%

Chronic Cannabidiol Administration Fails to Diminish Blood Pressure in Rats with Primary and Secondary Hypertension Despite Its Effects on Cardiac and Plasma Endocannabinoid System, Oxidative Stress and Lipid Metabolism

Remiszewski

Jarocka-Karpowicz

Biernacki

et al. 2020

IJMS

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We investigated the influence of cannabidiol (CBD) on blood pressure (BP) and heart rate (HR) in spontaneously (SHR) and deoxycorticosterone (DOCA-salt) hypertensive rats. Hypertension was connected with increases in cardiac and plasma markers of lipid peroxidation in both models, whereas cardiac endocannabinoid levels decreased in SHR and increased in DOCA-salt. CBD (10 mg/kg once a day for 2 weeks) did not modify BP and HR in hypertension but counteracted pro-oxidant effects. Moreover, it decreased cardiac or plasma levels of anandamide, 2-arachidonoylglycerol and oleoyl ethanolamide in DOCA-salt and inhibited the activity of fatty acid amide hydrolase (FAAH) in both models. In the respective normotensive control rats, CBD increased lipid peroxidation, free fatty acid levels and FAAH activity. In conclusion, chronic CBD administration does not possess antihypertensive activity in a model of primary and secondary (DOCA-salt) hypertension, despite its antioxidant effect. The latter may be direct rather than based on the endocannabinoid system. The unexpected CBD-related increase in lipid peroxidation in normotensive controls may lead to untoward effects; thus, caution should be kept if CBD is used therapeutically.

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“…Furthermore, serum levels of topiramate, rufinamide, and desmethylclobazam increased moderately in children and adults, and zonisamide and eslicarbazepine levels were found to increase in adults with increasing dose of CBD (Gaston et al, 2017) (figure 3). This has to be studied more closely (Franco and Perucca, 2019). The concentration/dose ratio of topiramate increased by 25% in one of our patients in combination with CBD at 20 mg/kg.…”

Section: What Do We Know So Far?mentioning

confidence: 87%

“…Pharmacokinetic interactions with CBD. The pharmacokinetic interactions that have been documented so far are related to metabolism; enzyme inhibition of various CYP and UGT enzymes (Geffrey et al, 2015;Gaston et al, 2017;Bialer et al, 2018;Franco and Perucca, 2019). No interactions regarding protein binding have been identified, however, such interactions are possible based on the high degree of protein binding of CBD as well as other AEDs (valproate, stiripentol).…”

Section: What We Do Not Know?mentioning

confidence: 99%

Pharmacology and drug interactions of cannabinoids

Landmark

Brandl

2020

Epileptic Disorders

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Cannabinoids include a variety of substances, of which cannabidiol (CBD) is the main substance investigated for the treatment of epilepsy, and this will be the focus in the present review. CBD preparations exist in various forms. There are significant differences in quality control regarding content and reproducibility for an approved drug versus herbal preparations. Cannabidiol has challenging pharmacological properties, and pharmaceutical and pharmacokinetic aspects will depend on the formulation or preparation of a certain product. This article will focus on the characteristics, pharmacokinetic challenges, and interactions of standardised CBD‐containing drugs based on evidence from clinical and pharmacokinetic studies.

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Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy

Cited by 113 publications

References 127 publications

Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

Chronic Cannabidiol Administration Fails to Diminish Blood Pressure in Rats with Primary and Secondary Hypertension Despite Its Effects on Cardiac and Plasma Endocannabinoid System, Oxidative Stress and Lipid Metabolism

Pharmacology and drug interactions of cannabinoids

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