THC Worsened Absence Seizures in Epileptic Rats While CBD Cut Them in Half
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Evidence Grade:
- 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.
- Study Age:
- Published in 2022. This is an animal study; clinical trials testing these findings in human absence epilepsy patients may not yet exist.
- Original Title:
- Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.
- Published In:
- The European journal of neuroscience, 55(4), 1063-1078 (2022) — The European Journal of Neuroscience is a well-regarded journal focusing on neuroscience research.
- Authors:
- Roebuck, Andrew J(4), Greba, Quentin(6), Onofrychuk, Timothy J(4), McElroy, Dan L, Sandini, Thaísa M, Zagzoog, Ayat, Simone, Jonathan, Cain, Stuart M, Snutch, Terrance P, Laprairie, Robert B, Howland, John G
- Database ID:
- RTHC-04178
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Read More on RethinkTHC
- CBD-oil-quality-guide
- anxiety-medication-after-quitting-weed
- cannabis-chemotherapy-nausea
- cannabis-chronic-pain-research
- cannabis-epilepsy-CBD-Epidiolex
- cbd-anxiety-research-evidence
- cbd-for-weed-withdrawal
- cbd-vs-thc-difference
- medical-benefits-of-cannabis
- quitting-weed-before-surgery
- quitting-weed-medication-interactions
- quitting-weed-pregnancy
- quitting-weed-pregnant
- seniors-older-adults-cannabis-risks-medications
- weed-breastfeeding-THC-breast-milk
Cite This Study
https://rethinkthc.com/research/RTHC-04178APA
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
MLA
Roebuck, Andrew J, et al. "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, 2022. https://doi.org/10.1111/ejn.15096
RethinkTHC
RethinkTHC Research Database. "Dissociable changes in spike and wave discharges following e..." RTHC-04178. Retrieved from https://rethinkthc.com/research/roebuck-2022-dissociable-changes-in-spike
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.