You’ve probably heard all about cannabinoids like cannabidiol (CBD) and tetrahydrocannabinol (THC), both of which have become the focus of intense scientific debate. Yet cannabis also contains an array of lesser-known cannabinoids, three of which have now been singled out for their ability to treat epileptic seizures in mice.
Recently, cannabis-based medications have become increasingly popular as treatments for epilepsy, with CBD often administered in conjunction with anti-seizure drugs such as clobazam. This approach has been found to enhance the efficacy of the drug, and the authors of a new study in the British Journal of Pharmacology wanted to see if other cannabinoids have a similar effect.
The researchers administered a range of different cannabinoids to mice that had been genetically altered to develop an animal model of Dravet syndrome, which is an intractable form of childhood epilepsy. Results indicated that numerous minor cannabinoids, known as cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA) all displayed anticonvulsant properties.
Of these, CBGA was the most effective, found to provide even greater protection than CBD against certain seizures. Specifically, CBGA was extremely potent against heat-induced seizures, capable of producing the same benefits as CBD at much lower doses.
Conversely, however, high doses of CBGA were actually found to provoke spontaneous seizures, highlighting the complexity of the interactions between cannabis and epilepsy.
“We found that CBGA was more potent than CBD in reducing seizures triggered by a febrile event in a mouse model of Dravet syndrome,” explained lead author Dr Lyndsey Anderson in a statement. “Although higher doses of CBGA also had proconvulsant effects on other seizure types highlighting a limitation of this cannabis constituent. We also found CBGA to affect many epilepsy-relevant drug targets.”
These findings are intriguing for a number of reasons beyond the fact that CBGA had never previously been identified as a treatment for epilepsy. The fact that it is a cannabinoid acid, for instance, is significant as these compounds are rarely present in cannabis-based medications.
In raw cannabis, most cannabinoids exist as acids, but become decarboxylated when the plant is heated. In this way, tetrahydrocannabinolic acid (THCA) is converted into THC, and cannabidiolic acid (CBDA) becomes CBD when cannabis is smoked, vaped, cooked, or otherwise processed. Rarely do people consume un-decarboxylated cannabinoid acids, and this study hints at the possibility that we may therefore be missing a trick.
Furthermore, CBGA is in fact the precursor to most other cannabinoid acids in cannabis, including THCA and CBDA. For this reason, study author Jonathan Arnold has described CBGA as “the mother of all cannabinoids”.
Overall, these results raise a number of intriguing questions about which cannabinoids should be targeted as treatments for epilepsy. The findings also give credence to the so-called “entourage effect” theory, which holds that the interactions between all of the components in cannabis potentiate its therapeutic effect, and that is therefore better to use the whole plant rather than its isolated constituents.
“We have assessed the cannabinoids one by one and now we are exploring what happens when you put them all back together,” said Anderson. “There remains a real possibility that all these individual anticonvulsant cannabinoids might work better when combined.”