Epilepsy refers to a group of conditions characterised by recurrent seizures, which may be convulsive or non-convulsive. Cannabis and cannabis-based therapies have been shown to have beneficial effects on several types of epilepsy, through a variety of biological mechanisms.
Around 60% of all epileptic seizures are convulsive, which means that they are characterised by rapid, involuntary contractions of the muscles that can cause the entire body to shake or jerk uncontrollably. The most common type is the tonic-clonic seizure, which involves a short period of immobility followed by uncontrollable shaking. Both convulsive and non-convulsive epileptic seizures are caused by excessive activity in the neurons of the brain; if severe and prolonged, seizures can result in damage to brain tissue—particularly in young children, when the brain is still developing. Dravet syndrome is just one type of childhood-onset epilepsy that can cause neurological impairment.
The anticonvulsant properties of cannabis have been known to humans for centuries, if not millennia. Cannabinoids were tested for their anticonvulsant properties by modern researchers as early as 1947. An early study conducted at the University of Sydney in 1974 demonstrated that Δ⁹-THC given in high doses had an anticonvulsant effect on mice that were induced to experience seizures via administration of chemical and electrical shocks. It was noted that CBD increased this effect of Δ⁹-THC, although the researchers did not find that CBD was effective in its own right.
Since then, various studies have found that CBD does in fact possess remarkable anticonvulsant properties in its own right, as well as potentiating the effects of Δ⁹-THC. A 2001 study demonstrated that Δ⁹-THC and the synthetic Δ⁹-THC analogue WIN 55,212-2 exerted their effect by agonising the CB₁-receptors; CBD exerts its effects via a different means, as it does not agonise the CB₁-receptor but instead acts as a weak antagonist. Due to its effect on the CB₁-receptors of the central nervous system, Δ⁹-THC can actually cause convulsions in rare cases, while CBD does not appear to have this side-effect due to its independent mechanism of action.
The precise mechanism utilised by CBD when working to control convulsions has still not been established, but it is proving highly effective in treating various types of epilepsy including Dravet syndrome in young children, and has gained ground rapidly as a potential treatment due to its lack of psychoactivity.
As research into the endocannabinoid system advances, it is becoming clear that it plays an important role in regulating the duration and frequency of seizures—in fact, some researchers believe that epilepsy could occur as a result of an inherent imbalance of the endocannabinoid system (a condition speculatively known as clinical endocannabinoid deficiency), which could arise due to brain injury, infection or genetic predisposition.
In 2008, a study published in Nature indicated that patients suffering from temporal lobe epilepsy appeared to have dysfunctional endocannabinoid systems. As the name suggests, temporal lobe epilepsy affects the temporal lobe of the brain, and typically produces non-convulsive seizures that involve some degree of sensory (visual, auditory, olfactory or even gustatory) disturbance—although it may also produce tonic-clonic seizures in severe cases.
The common cause of convulsive and non-convulsive seizures is excessive excitation of the neurons of the brain, with the affected region of the brain varying according to the type of epilepsy. In healthy patients, the endogenous cannabinoids anandamide and 2-AG are thought to play a fundamental role in regulating the level of neuronal excitation and thereby reducing the likelihood that a seizure is triggered. Thus, in patients who possess a dysfunctional endocannabinoid system, cannabis and cannabis-based therapies can actually target the cause of epilepsy and provide a neuroprotective effect that reduces the severity and frequency of symptoms.
In extremely severe cases of epilepsy, a condition known as status epilepticus may occur. Status epilepticus may involve convulsive or non-convulsive seizures, which either last for a duration of over five minutes each, or occur at a frequency of more than one seizure per five minutes with no return to full consciousness in between. If the patient is not provided immediate medical care during an episode of status epilepticus, the prolonged loss of normal brain function may result in brain damage or even death. If adequate medical care is provided, epileptic patients usually survive an episode of status epilepticus without major complications.
Status epilepticus is typically treated with benzodiazepines or barbiturates; both classes of drugs are well-known for their often debilitating side-effects, and are far from effective across the board. However, there is evidence that cannabinoids—specifically CB₁-receptor agonists like anandamide, Δ⁹-THC, and the synthetic analogue WIN 55,212-2—may provide stronger protection against status epilepticus. In a 2006 study published in the Journal of Pharmacology, WIN 55,212-2 demonstrated the ability to totally suppress all seizure activity, including the prolonged episodes associated with status epilepticus. The study also noted that WIN 55,212-2 significantly outperformed phenytoin and phenobarbital in suppressing status epilepticus.
From this and various related studies conducted over the last decade or so, it has been well-established that agonists of the CB₁-receptors are fundamentally important to terminating seizures and preventing the onset of status epilepticus, and that in epileptic patients, an imbalance in the endocannabinoid system increases the frequency and severity of seizures. A 2007 paper noted that if epileptic neurons were administered CB₁-receptor antagonists, it would cause continuous epileptic activity as seen in patients with status epilepticus. If then treated with CB₁-receptor agonists, the excessive activity would stop. Conversely, when non-epileptic neurons were treated with CB₁-receptor antagonists, the excessive activity resembling status epilepticus did not occur.
Thus, it is clear that both Δ⁹-THC and CBD have an important role to play in the management of seizures in epilepsy. However, the respective mechanisms of action are not fully understood, particularly in the case of CBD, which exerts its effect through means that are independent of the main cannabinoid receptors.