Low-dose THC plus CBD helped seizures in Dravet mice, but chronic combination increased mortality | Research

The takeaway

In a Dravet syndrome mouse model, low-dose THC was anticonvulsant and enhanced by sub-threshold CBD for heat-induced seizures, but chronic combined CBD and THC unexpectedly increased seizure severity and mortality.

Epilepsy researchers, parents using cannabis products for seizure disorders, and neurologists.

Chronic CBD+THC combination increased mortality in Dravet mice

What the researchers found

CBD (100 mg/kg) alone was anticonvulsant against heat-induced seizures. Low-dose THC (0.1 and 0.3 mg/kg) was also anticonvulsant, but higher doses were not. A sub-threshold dose of CBD (12 mg/kg) enhanced THC's anticonvulsant effect. However, when CBD and THC were given together chronically, spontaneous seizure severity and mortality increased, a surprising and concerning finding.

Why it matters

Many cannabis products marketed for epilepsy contain both THC and CBD. This study suggests that while acute low-dose combinations may help, chronic use of the combination could be harmful.

The numbers in context

CBD anticonvulsant at 100 mg/kg. THC anticonvulsant at 0.1 and 0.3 mg/kg. Sub-threshold CBD (12 mg/kg) enhanced THC effect. Chronic co-administration increased seizure severity and mortality.

How the study worked

Preclinical study using Scn1a+/- mice (Dravet syndrome model). Tested CBD and THC alone and combined on heat-induced seizures, spontaneous seizures, and premature mortality.

What this study cannot tell us

Mouse model; results may not translate to humans. Doses used are relative to mouse physiology. Mechanisms of chronic harm were not fully elucidated.

How to read the evidence

Well-designed preclinical study in a validated disease model, but animal data that need human confirmation.

When this study was published

2020 preclinical study.

The bigger picture

The divergence between acute benefit and chronic harm from CBD+THC combinations is a critical finding for the medical cannabis community, where combined products are common.

Questions still open

Does chronic CBD+THC combination cause problems in human epilepsy patients? Are there safe ratios or dosing schedules that avoid the chronic mortality increase?

Common questions

Should epilepsy patients use cannabis products with both THC and CBD?

This mouse study found that while acute low-dose combinations helped seizures, chronic combined use increased seizure severity and mortality, raising concerns about long-term use of combined products.

Does THC help or hurt seizures?

In this Dravet model, very low doses of THC were anticonvulsant, but higher doses were not. The effect was enhanced by sub-threshold CBD, suggesting dose is critical.

Read the original research

Interactions between cannabidiol and Δ9 -tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome.

British journal of pharmacology, 177(18), 4261-4274

View on PubMed ↗Publisher’s paper ↗

Citation

Anderson, Lyndsey L; Low, Ivan K; McGregor, Iain S; Arnold, Jonathon C. (2020). Interactions between cannabidiol and Δ9 -tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome.. British journal of pharmacology, 177(18), 4261-4274. https://doi.org/10.1111/bph.15181