Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

Farrelly, Aaron Mark; Vlachou, Styliani; Grintzalis, Konstantinos

doi:10.3390/ijerph18083993

Cited by 23 publications

(11 citation statements)

References 145 publications

(93 reference statements)

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“…This effect was observed in the presence of preserved theta activity in the ECoG and restrained FosB/∆FosB expression in the subiculum. These findings confirm the validity of hemp oils to address seizures, and further suggest a CBD-independent role of terpenes as an ASM [28][29][30].…”

Section: Fosb/∆fosb Immunoreactivitysupporting

confidence: 79%

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

et al. 2021

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Compounds present in Cannabis sativa L. preparations have recently attracted much attention in the treatment of drug-resistant epilepsy. Here, we screened two olive oil extracts from a non-psychoactive C. sativa variety, fully characterized by high-performance liquid chromatography and gas chromatography. Particularly, hemp oils with different concentrations of terpenes were administered at the same dose of cannabidiol (25 mg/kg/day orally), 1 h before the 6-Hz corneal stimulation test (44 mA). Mice were stimulated once a day for 5 days and evaluated by video-electrocorticographic recordings and behavioral analysis. Neuronal activation was assessed by FosB/ΔFosB immunoreactivity. Both oils significantly reduced the percentage of mice experiencing convulsive seizures in comparison to olive oil-treated mice (p < 0.050; Fisher’s exact test), but only the oil enriched with terpenes (K2) significantly accelerated full recovery from the seizure. These effects occurred in the presence of reduced power of delta rhythm, and, instead, increased power of theta rhythm, along with a lower FosB/ΔFosB expression in the subiculum (p < 0.050; Duncan’s method). The overall findings suggest that both cannabinoids and terpenes in oil extracts should be considered as potential therapeutic agents against epileptic seizures and epilepsy.

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Section: Fosb/∆fosb Immunoreactivitysupporting

confidence: 79%

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

et al. 2021

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“…In recent years, there has been scientific interest in cannabinoid-based drugs for the treatment of epilepsy, particularly treatment-resistant epilepsy (TRE) and paediatric-onset drug-resistant epilepsy. Phytocannabinoids such as CBD, cannabigerol (CBG), cannabidavarin (CBDV), and ∆ 9 -THCV have demonstrated anti-convulsant properties and may be promising opportunities to develop safer alternatives (and even adjuncts) to traditional antiepileptic drugs (AEDs) [146][147][148]. Of these cannabinoids, ∆ 9 -THC and CBD have been given the most attention for their anti-convulsant properties [149].…”

Section: Epilepsymentioning

confidence: 99%

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Lowe

Toyang²,

Steele

et al. 2021

IJMS

162

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The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

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“…All records identified consisted of animal studies, while no research conducted in humans was available. Previous reviews had mainly focused on the role of major phytocannabinoids, indicating that they may represent a complementary tool for the symptomatic management of refractory epilepsy [ 23 ]. Specifically, research findings converged on the efficacy of pure cannabidiol (CBD), the isolated chemical product, and CBD-enriched cannabis extracts, where the therapeutic effect is supposedly driven by the complex interactions between all the components of the cannabis plant and remains poorly understood [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence

et al. 2022

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Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA’s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.

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Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

Cited by 23 publications

References 145 publications

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

Antiseizure Effects of Fully Characterized Non-Psychoactive Cannabis sativa L. Extracts in the Repeated 6-Hz Corneal Stimulation Test

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence

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