THC Worsened Absence Seizures in Epileptic Rats While CBD Cut Them in Half | Research

The takeaway

In rats genetically prone to absence epilepsy, THC more than doubled seizure activity while CBD reduced it by about 50% — and smoked high-THC cannabis increased seizures too.

Read this if you or someone you know has absence epilepsy and uses or is considering cannabis — the THC vs. CBD distinction here is directly relevant to product choices.

What the researchers found

Absence epilepsy causes brief seizure episodes (staring spells) characterized by distinctive spike-and-wave discharges (SWDs) on EEG. There's enormous interest in using cannabinoids for epilepsy — CBD-based Epidiolex is already FDA-approved for some forms — but the effects on absence epilepsy specifically have been unclear.

This study used GAERS (Genetic Absence Epilepsy Rats from Strasbourg), a well-validated animal model of absence epilepsy, to test how THC and CBD affect seizure activity. The results were striking and went in opposite directions.

Injected THC at doses from 1–10 mg/kg dose-dependently increased spike-and-wave discharges to over 200% of baseline. More THC meant substantially more seizure activity. In sharp contrast, CBD at doses of 30–100 mg/kg produced approximately a 50% reduction in SWDs.

The researchers then took the innovative step of exposing the rats to actual cannabis smoke from two different strains: a high-THC strain (Mohawk) and a high-CBD/low-THC strain (Treasure Island). The smoked high-THC cannabis increased seizures, consistent with the injected THC results. The high-CBD strain had no significant effect on seizures — it didn't increase them like THC but didn't reduce them as dramatically as pure injected CBD either.

Pre-treatment with a CB1 receptor antagonist blocked THC's seizure-increasing effect, confirming the mechanism works through the CB1 receptor system.

Why it matters

The divergence between THC and CBD is critical for the millions of people with absence epilepsy. While CBD-based treatments are gaining acceptance for certain epilepsy types, this study warns that THC could actually worsen absence seizures. For patients with absence epilepsy who use cannabis, the THC:CBD ratio of their product could be the difference between reducing and increasing their seizure activity.

The numbers in context

THC (1–10 mg/kg) increased spike-and-wave discharges to over 200% of baseline in a dose-dependent manner. CBD (30–100 mg/kg) reduced SWDs by approximately 50%. Smoked high-THC cannabis also increased SWDs. CB1 receptor antagonist pre-treatment blocked THC's pro-seizure effect.

How the study worked

Animal study using GAERS rats implanted with bipolar EEG electrodes in the somatosensory cortex. EEGs were recorded for 2 hours after administration of: injected THC (1–10 mg/kg), injected CBD (30–100 mg/kg), smoked high-THC cannabis (Mohawk strain), or smoked high-CBD/low-THC cannabis (Treasure Island strain). CB1 receptor antagonist pre-treatment was used to confirm the mechanism.

Who was studied

Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model for absence epilepsy.

What this study cannot tell us

Animal study — results in GAERS rats may not directly translate to human absence epilepsy. The smoked cannabis exposure method, while innovative, makes precise dose control difficult. The high-CBD smoked cannabis didn't reduce seizures the way injected CBD did, possibly because the CBD dose delivered via smoke was lower or because other compounds in the smoke interfered. The study examined acute effects only; chronic exposure effects may differ.

How to read the evidence

This is a well-designed animal study using a validated genetic model of absence epilepsy. The dose-response data and mechanistic confirmation (CB1 antagonist) are strong, but translation to human absence epilepsy requires clinical studies.

When this study was published

Published in 2022. This is an animal study; clinical trials testing these findings in human absence epilepsy patients may not yet exist.

The bigger picture

This adds an important nuance to the 'CBD for epilepsy' narrative. While CBD appears protective — consistent with its approved use in Epidiolex for Dravet and Lennox-Gastaut syndromes — THC appears actively harmful for absence seizures. This has direct implications for the product composition findings in RTHC-00086 (THC:CBD ratios in dispensary products), where most products are THC-dominant and would be expected to worsen rather than help absence epilepsy.

Replication

Not stated in abstract.

Funding

Not reported in abstract.

Conflicts of interest

Not reported in abstract.

Questions still open

Does THC worsen absence seizures in human patients? Would high-CBD, low-THC cannabis products be beneficial for people with absence epilepsy, or does the THC content (even if small) counteract the CBD benefit? What's the mechanism behind CBD's seizure reduction — is it working through different receptors than the CB1 pathway that mediates THC's effect?

Read the original research

Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

The European journal of neuroscience, 55(4), 1063-1078

The European Journal of Neuroscience is a well-regarded journal focusing on neuroscience research.

View on PubMed ↗Publisher’s paper ↗

Citation

Roebuck, Andrew J; Greba, Quentin; Onofrychuk, Timothy J; McElroy, Dan L; Sandini, Thaísa M; Zagzoog, Ayat; Simone, Jonathan; Cain, Stuart M; Snutch, Terrance P; Laprairie, Robert B; Howland, John G. (2022). Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.. The European journal of neuroscience, 55(4), 1063-1078. https://doi.org/10.1111/ejn.15096