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Marihuana: Effects on Neuronal Excitability and Seizure Threshold

  • Elisabeth Gordon
  • Orrin Devinsky

Abstract

In the late 19th century, British neurologists found that cannabis had a limited role in epilepsy therapy. Cannabinoid receptors are found in the brainstem, limbic and neocortical areas that modulate seizure activity. The recent studies of the effects of THC, CBD, and related cannabinoids in animal models of epilepsy reveal that (1) the effects vary significantly in different models, in different species, and for the different derivatives; (2) the mechanisms by which the cannabinoids exert their anti-or proconvulsant effects is not well-defined; and (3) the effects of acute administration (e.g., increasing seizure threshold) may be followed, in certain models, by a rebound effect (e.g., decreasing seizure threshold).

No well-controlled studies have evaluated cannabinoids in the treatment of epilepsy patients. However, clinical anecdotes and single case reports suggest that marijuana may reduce seizure frequency or, conversely may provoke seizure activity in select cases, while in most instances it has no significant effect on seizure activity. Several clinical studies have examined the efficacy of CBD on seizure frequency. These studies found either some reduction in seizure frequency or no statistically significant reduction compared to placebo. The few epidemiological studies that have been conducted suggest that marijuana use may protect against seizures induced by illicit drugs such as heroin and cocaine. The limited evidence therefore suggest that marijuana and the cannabinoids may have antiepileptic effects in man, but these effects may be specific to partial or tonic-clonic seizures.

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In the late 19th century, British neurologists found that cannabis had a limited role in epilepsy therapy. Cannabinoid receptors are found in the brainstem, limbic and neocortical areas that modulate…

Marijuana and ‘spice’ could trigger seizures, study says

While a number of studies have suggested that marijuana may be effective for reducing seizures, new research cautions that potent and synthetic forms of the drug have the opposite effect.

Share on Pinterest Researchers suggest that the use of potent cannabinoids have the potential to trigger seizures.

Researchers from the University of Tsukuba in Japan found that natural tetrahydrocannabinol (THC) – the psychoactive chemical in marijuana – and the synthetic cannabinoid JWH-018 caused seizures in mice.

Study leader Olga Malyshevskaya and colleagues say that their findings – which are published in the journal Scientific Reports – should serve as a “public alert” to the potential harms caused by high-potency and synthetic marijuana.

While marijuana remains that “most commonly used illicit drug” in the United States, it is becoming increasingly legalized in individual states for medicinal purposes, recreational purposes, or both.

There has been increasing research for the use of marijuana – particularly a cannabinoid in the drug called cannabidiol (CBD) – in the treatment of seizures in patients with epilepsy, though a debate surrounding its efficacy continues.

The new study from Malyshevskaya and team suggests that general use of high-potency marijuana – that is, marijuana that contains high amounts of THC – may actually trigger seizures.

The research also found that seizures could be prompted by JWH-018, which is a manmade cannabinoid that is the primary component of the synthetic marijuana known as “spice.”

The researchers came to their findings by analyzing the brain activity of male mice after they received THC or JWH-018.

THC was given to the rodents in doses of 10 milligrams per kilogram (the equivalent to around 0.8 milligrams per kilogram in humans) and JWH-018 was administered in doses of 2.5 milligrams per kilogram (the equivalent to around 0.2 milligrams per kilograms in humans).

The team implanted electroencephalography (EEG) and electromyogram electrodes into the brains of the mice, which allowed them to monitor any seizure-related electrical activity in response to the drug compounds.

The movement and behavior of the rodents was also monitored through video recording.

The study revealed that the mice experienced seizures shortly after administration with both THC and JWH-018, though seizure frequency was significantly higher with JWH-018.

Seizure-related brain activity persisted for 4 hours after the administration of each drug, the team reports, but brain activity had returned to normal by the next day.

Interestingly, the researchers found that pre-treating the mice with AM-251 – which is a compound that binds to the cannabinoid-1-receptor – prevented seizures in response to THC and JWH-018.

As such, the team suggests that cannabinoid receptor antagonists could be useful for preventing seizures in the case of marijuana overdose.

According to the researchers, their results “provide strong evidence” that both plant-derived and synthetic cannabinoids have the potential to trigger seizures.

“On the other hand,” the authors note, “a substantial body of literature on cannabinoids in animal models shows mostly anticonvulsive effects.”

“However,” they add, “few of these used EEG recordings to assess epileptic events and many of them induced seizures either electrically or pharmacologically, changing signaling pathways and brain states prior to cannabinoid application.”

The team cautions that the doses of THC and JWH-018 used in their study were high and may not represent the doses normally seen with medicinal or recreational use in humans.

“It would be interesting in the future to also test lower doses, typically used medicinally or recreationally to determine whether the effect is lost or diminished,” they add.

Still, they believe that their findings should be viewed as a warning of the potential dangers of cannabinoids, particularly synthetic marijuana.

“ Our study is quite important because unaware of the particularly severe effect by those cannabinoids, people see marijuana as a soft drug, without dangerous health effects.”

High-potency natural and synthetic cannabinoids were found to trigger seizures in mice, say researchers, with the latter posing the strongest effects.