New Australian research is systematically investigating the anticonvulsant effects of a number of rare compounds in cannabis. A new study is reporting cannabigerolic acid (CBGA), informally known as the “mother of all cannabinoids,” may be more effective at reducing seizures than cannabidiol (CBD).
“From the early nineteenth century cannabis extracts were used in Western medicine to treat seizures but cannabis prohibition got in the way of advancing the science,” explains Jonathon Arnold, corresponding author on the new study. “Now we are able to explore how the compounds in this plant can be adapted for modern therapeutic treatments.”
There are dozens of unique compounds in cannabis plants. Known as cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD) are perhaps the most well-known. Others compounds such as tetrahydrocannabiphorol (THCP) have only just been discovered.
In 2018 a CBD formulation called Epidiolex became the first cannabis-derived medicine to be approved for any medical use by the US Food and Drug Administration (FDA). Epidiolex was found to reduce seizure frequency in severe forms of childhood-onset epilepsy.
“However, many childhood epilepsy patients continue to be treated with unregulated artisanal products extracted from the cannabis plant, often due to high expense and limited availability of Epidiolex and, in some cases, a preference for extracts containing a ‘full spectrum’ of multiple phytocannabinoids and terpenoids rather than isolated CBD,” the researchers write in the newly published study.
For several years pharmacologists at the University of Sydney have been studying the individual anticonvulsant effects of a number of rare cannabinoids. This new study reports on the effects of seven cannabinoids, with a particular focus on cannabigerolic acid (CBGA).
CBGA is often referred to as the "mother of all cannabinoids" because it is the precursor to many more well-known cannabinoids, including CBD and THC. Every cannabis plant contains CBGA, but as the plant matures this compound is converted into other cannabinoids. This means CBGA levels are often very low in mature harvested cannabis, as it already has been transformed into other chemicals.
“The cannabinoid acids are abundant in cannabis but have received much less scientific attention,” notes Arnold. “We are just beginning to understand their therapeutic potential.”
The study tested the anticonvulsant effects of CBGA in a few different preclinical seizure models. In several, but not all, models CBGA was found more effective than CBD at reducing seizures. Lead author Lyndsey Anderson says CBGA didn’t reduce seizure activity in all animal models suggesting it probably isn’t as versatile as CBD, but it was a superior anticonvulsant in models such as hyperthermia-induced seizures.
“We found that CBGA was more potent than CBD in reducing seizures triggered by a febrile event in a mouse model of Dravet syndrome,” says Anderson. “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.”
Most interesting is perhaps the next stages of the research, which will begin investigating the anticonvulsant effects of different combinations of cannabinoids. This touches on a controversial idea known as the entourage effect.
The entourage effect argues the therapeutic benefits of cannabis are not solely the result of single cannabinoids such as CBD, but instead are influenced by the broader interactions between different compounds in the plant. Researchers have yet to clearly demonstrate the entourage effect in clinical studies, but Anderson believes it is possible novel combinations of cannabinoids could lead to more effective treatments than any one single compound.
“We have assessed the cannabinoids one by one and now we are exploring what happens when you put them all back together,” says Anderson. “There remains a real possibility that all these individual anticonvulsant cannabinoids might work better when combined.”
The new study was published in the British Journal of Pharmacology.
Source: University of Sydney
