Both CBD and THC reduced seizures in a mouse model of generalized epilepsy, and adding a low, non-therapeutic dose of THC to CBD modestly improved CBD's effectiveness.
Read this if you have epilepsy and are interested in whether THC-containing cannabis products might add benefit to CBD treatment.
15:1 ratioCBD:THC ratio that improved seizure protection over CBD alone in mouse model
What the researchers found
In the mouse maximal electroshock seizure (MES) model, THC alone had an ED50 of 52 mg/kg (therapeutic index 1.7), while CBD alone had an ED50 of 190 mg/kg (therapeutic index 2.4). When combined at a 15:1 CBD:THC ratio, the ED50 dropped to 130 mg/kg CBD + 8.6 mg/kg THC, indicating a modest improvement. The benefit of adding THC to CBD was less dramatic than what the same research group previously observed in the amygdala-kindling model of focal seizures.
Why it matters
Most cannabis-based seizure medications focus on CBD alone. This study provides preclinical evidence that small amounts of THC could enhance CBD's anti-seizure effects, though the benefit may depend on seizure type.
The numbers in context
- THC alone ED50: 52 mg/kg, therapeutic index 1.7
- CBD alone ED50: 190 mg/kg, therapeutic index 2.4
- CBD+THC (15:1) ED50: 130 mg/kg + 8.6 mg/kg
- Combination benefit less dramatic than in focal seizure model
How the study worked
Male CF-1 mice received intraperitoneal injections of CBD, THC, or combinations. MES test conducted 2 hours post-CBD and 1 hour post-THC injection. Wide dose ranges tested for dose-response curves. Toxicity assessed via behavioral rating scale.
Who was studied
Male CF-1 mice
What this study cannot tell us
Mouse MES model may not fully predict human seizure responses. Intraperitoneal injection route differs from oral administration used clinically. Only one CBD:THC ratio (15:1) was tested in combination. Single sex (male mice only).
How to read the evidence
Preclinical animal study with well-established seizure model. Provides mechanistic evidence but requires human studies before clinical application.
When this study was published
Published in 2023. Builds on the research team's prior work with the amygdala-kindling model.
The bigger picture
The FDA-approved CBD medication Epidiolex has transformed epilepsy treatment, but response rates are not universal. Exploring whether THC can enhance CBD's effects at sub-psychoactive doses could improve outcomes for patients with treatment-resistant epilepsy.
Questions still open
- Would other CBD:THC ratios produce better results for generalized seizures?
- Does the seizure type (focal vs generalized) determine whether THC enhances CBD's effects?
- Could sub-psychoactive THC doses improve outcomes for patients already taking Epidiolex?
Read the original research
The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model.
Epilepsy research, 190, 107087
Citation
Dlugosz, Lukasz; Zhou, Han Zhong; Scott, Brian Wayne; Burnham, McIntyre. (2023). The effects of cannabidiol and Δ9-tetrahydrocannabinol, alone and in combination, in the maximal electroshock seizure model.. Epilepsy research, 190, 107087. https://doi.org/10.1016/j.eplepsyres.2023.107087