Medical cannabis as an anticonvulsant 

Medical cannabis has gained significant attention in recent years for its potential use as an anticonvulsant medication. Anticonvulsants are a class of drugs used to treat seizures and epilepsy, which is a neurological disorder characterised by recurrent seizures. While traditional anticonvulsant medications can be effective in controlling seizures, they often have significant side effects and are not effective in all patients. This has led to interest in exploring the potential of cannabis-based treatments as an alternative or adjunct to traditional anticonvulsants.

Cannabis plants contain a number of active compounds, known as cannabinoids, which have been shown to have anticonvulsant properties. The two most well-known cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). While THC is known for its psychoactive effects, CBD is non-psychoactive and has been found to have a range of potential therapeutic benefits, including as an anticonvulsant.

CBD and Anticonvulsant Properties

A number of preclinical and clinical studies have investigated the potential of CBD as an anticonvulsant. These studies have found that CBD can be effective in reducing the frequency and severity of seizures in a range of animal models of epilepsy, including models of Dravet syndrome, Lennox-Gastaut syndrome, and temporal lobe epilepsy. Additionally, several clinical trials have shown that CBD can be effective in reducing seizures in patients with treatment-resistant epilepsy.

One of the most well-known examples of the use of CBD as an anticonvulsant is in the treatment of Dravet syndrome. Dravet syndrome is a rare form of epilepsy that typically begins in infancy and is characterized by frequent and prolonged seizures. Many patients with Dravet syndrome do not respond to traditional anticonvulsant medications, and the condition can be life-threatening. In a landmark clinical trial, researchers found that treatment with CBD resulted in a significant reduction in seizures in patients with Dravet syndrome. This led to the approval of the first cannabis-based medication, Epidiolex, for the treatment of Dravet syndrome and Lennox-Gastaut syndrome in the United States in 2018.

Mechanism of Action

The exact mechanism by which CBD exerts its anticonvulsant effects is not fully understood, but several potential mechanisms have been proposed. One proposed mechanism is through the modulation of ion channels in the brain that are involved in the generation and propagation of seizures. CBD has been found to interact with a number of different ion channels, including sodium and calcium channels, which can lead to a reduction in neuronal excitability and a decrease in the likelihood of seizures.

Another proposed mechanism is through the modulation of the endocannabinoid system, which is a complex signaling system in the body that plays a role in a range of physiological processes, including pain sensation, mood, and appetite. The endocannabinoid system is comprised of two main receptors, CB1 and CB2, which are activated by endocannabinoids, which are naturally occurring compounds in the body, as well as by phytocannabinoids, which are compounds found in the cannabis plant. CBD has been found to interact with both CB1 and CB2 receptors, which can lead to a reduction in seizure activity.

Side Effects

While CBD has been found to be generally well-tolerated, it can have side effects in some patients. The most commonly reported side effects of CBD include fatigue, decreased appetite, and diarrhea. Additionally, CBD can interact with some medications, including anticoagulants and antiepileptic medications, which can lead to changes in blood levels of these drugs and potential adverse effects. For this reason, it is important for patients to discuss the use of CBD with their healthcare provider.

Research on medical cannabis in literature

CBD ANTICONVULSANT 

1. The anticonvulsant activity of cannabidiol and cannabinol

Abstract

The anticonvulsant activity of delta-9-tetrahydrocannabinol was compared with that of two other naturally occurring cannabinoids, cannabidiol and cannabinol, in a maximal electroshock test in mice. The drugs were administered as an emulsion of sesame seed oil, Tween 80 and saline to mice i.p. The results indicate that all three cannabinoids are effective anticonvulsants. The time for peak effect is about 2 hr. In terms of relative potencies, cannabidiol and delta-9-THC are similar but both of them are more active than cannabinol.

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2. The anticonvulsant effects of cannabidiol in experimental models of epileptic seizures: From behavior and mechanisms to clinical insights

Abstract

Epilepsy is a neurological disorder characterized by the presence of seizures and neuropsychiatric comorbidities. Despite the number of antiepileptic drugs, one-third of patients did not have their seizures under control, leading to pharmacoresistance epilepsy. Cannabis sativa has been used since ancient times in Medicine for the treatment of many diseases, including convulsive seizures. In this context, Cannabidiol (CBD), a non-psychoactive phytocannabinoid present in Cannabis, has been a promising compound for treating epilepsies due to its anticonvulsant properties in animal models and humans, especially in pharmacoresistant patients. In this review, we summarize evidence of the CBD anticonvulsant activities present in a great diversity of animal models. Special attention was given to behavioral CBD effects and its translation to human epilepsies. CBD anticonvulsant effects are associated with a great variety of mechanisms of action such as endocannabinoid and calcium signaling. CBD has shown effectiveness in the clinical scenario for epilepsies, but its effects on epilepsy-related comorbidities are scarce even in basic research. More detailed and complex behavioral evaluation about CBD effects on seizures and epilepsy-related comorbidities are required.

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3. Anticonvulsant Effects of the (–) and (+)Isomers of Cannabidiol and Their Dimethylheptyl Homologs

Abstract

The anticonvulsant actions of the (–) and (+)isomers of cannabidiol and di-methylheptyl-cannabidiol were studied with the maximal electroconvulsive shock model in mice. The ratio of the times for hindlimb extension and fore limb flexion was recorded as an anticonvulsant index. All the cannabinoids were anticonvulsant. They also potentiated pen-tobarbitone sleeping time. The (+)isomer was more active than the (–)isomer. Possible mechanisms of actions on receptors or membranes are discussed.

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4. Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels

Abstract

Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60 mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.

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5. Anticonvulsant activity of four oxygenated cannabidiol derivatives.

Abstract

A pharmacological comparison between cannabidiol (CBD) and four CBD derivatives, namely CBD-aldehyde-diacetate (I), 6-oxo-CBD-diacetate (II), 6-hydroxy-CBD-tri-acetate (III), and 9-hydroxy-CBD-triacetate (IV) was carried out in mice. Protection against maximal electroshock convulsions, potentiation of pentobarbital sleeping-time and reduction of spontaneous motor activity were the effects measured. All 5 compounds were equally potent in potentiating barbiturate sleeping time at doses ranging from 6.25 to 100 mg/kg. At 12.5 and 25 mg/kg only CBD and IV were able to decrease significantly the spontaneous motor activity. CBD, II, III and IV were also active in protecting mice against electroconvulsive shock at doses of 100-200 mg/kg, although at the larger dose CBD and compound II were the most efficient. Compound I was toxic, killing about half of the animals within 24 h after injection.

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