The relationship between cannabis use and seizures is highly nuanced, depending on the specific chemical compounds and the individual. The cannabis plant contains compounds whose effects on the brain’s electrical stability can be opposing. For some individuals, cannabis may be a seizure trigger, while for others, it may offer potential therapeutic benefit. Understanding this complex relationship requires distinguishing between the acute effects of high-potency products, the distinct actions of the plant’s main components, and the clinical risks for people already diagnosed with a seizure disorder.
Acute Effects of Cannabis Use on Seizure Threshold
Cannabis’s potential to trigger a seizure is primarily linked to the acute effects of products containing high levels of Delta-9-tetrahydrocannabinol (THC). The seizure threshold is the level of electrical activity required to provoke a seizure, and high doses of THC appear to lower this threshold in some users, making the brain more susceptible to an electrical storm. This phenomenon is often observed following the use of high-potency cannabis, or in cases of heavy and chronic use.
Studies have noted a higher incidence of seizures in populations exposed to cannabis than would be expected in the general population. This risk is particularly relevant with modern products that have been selectively bred to contain far greater concentrations of THC than in past decades. The risk of acute intoxication is especially pronounced in children who accidentally ingest high-THC edibles, which can lead to new-onset seizures.
Clinical data reports a connection between recreational cannabis use and an increased risk of seizure-related hospitalization. While the precise mechanism for THC lowering the seizure threshold remains under investigation, the pattern suggests that the psychoactive compound can disrupt the normal balance of neuronal signaling necessary for maintaining brain stability. This acute effect contrasts sharply with the established use of certain cannabis components as anti-seizure treatments.
How THC and CBD Affect Brain Excitability
Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) have distinct, often opposing, effects on neuronal excitability. THC acts as a partial agonist at the cannabinoid receptor 1 (\(\text{CB}_1\text{R}\)), which is highly concentrated on presynaptic nerve terminals in the central nervous system. Activation of these receptors by THC modulates the release of neurotransmitters, including the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate.
While THC’s primary action is to reduce neurotransmitter release, which can sometimes be protective, its complex activity can also lead to pro-convulsant effects in certain contexts, potentially by activating nonselective calcium channels that cause neuronal depolarization. In contrast, CBD is non-intoxicating and acts as a multi-target drug. CBD is thought to exert its anti-convulsant effects through several mechanisms, including the antagonism of the GPR55 receptor and the desensitization of the TRPV1 receptor, both of which are involved in regulating neuronal hyperexcitability.
Unlike THC, CBD does not directly activate the \(\text{CB}_1\) and \(\text{CB}_2\) receptors, which explains its lack of psychoactive effect. The overall effect of CBD is to calm the excessive electrical activity associated with seizures. This is why a pharmaceutical-grade CBD oral solution has been approved for treating specific, severe forms of pediatric epilepsy. The therapeutic or triggering outcome of cannabis use is therefore largely dependent on the ratio of CBD to THC in the consumed product.
Clinical Risks for Individuals with Epilepsy
Individuals diagnosed with epilepsy face specific clinical risks when using cannabis, particularly concerning interactions with prescribed anti-epileptic medications (AEDs). One of the most significant concerns is the potential for drug-drug interactions, known as pharmacokinetic interactions, where cannabis compounds interfere with the metabolism of AEDs. This interference occurs because both CBD and THC inhibit or induce certain liver enzymes, particularly the cytochrome P450 (CYP450) enzymes, which are responsible for breaking down many AEDs.
When CBD is consumed alongside certain medications, such as clobazam or valproate, it can inhibit the enzymes that metabolize these drugs, leading to elevated concentrations of the AEDs in the bloodstream. For instance, CBD can significantly increase the serum levels of clobazam and its active metabolite, N-desmethylclobazam, sometimes resulting in side effects like somnolence and sedation. Co-administration of CBD and valproate also carries a risk of elevated liver enzymes, which indicates abnormal liver function and requires careful monitoring.
Substituting prescribed AEDs with cannabis or high-CBD products without physician oversight is a major clinical risk. While CBD has demonstrated efficacy for some seizure disorders, abruptly stopping established medication can lead to a dangerous increase in seizure frequency or severity. Because unregulated cannabis products have inconsistent potency and chemical ratios, any patient with epilepsy must consult with their neurologist to ensure proper monitoring and dose adjustments.