This study, conducted by researchers at the University of Arkansas for Medical Sciences in Little Rock, was published in the journal Molecules at the end of April. It was in this journal that they explained their method of using a mouse model to look for the level of hepatoxicity, or drug-induced live disease, for CBD.
Dr Koturbash, who led the team of researchers on this study, said that calculations were a key part of this study.
This is because there is currently very little information about the dosage and safety of CBD. In fact, all of the information from this point has come from work completed by English company GW Pharma in the development of its drug Epidiolex.
This drug went on to be approved by the US Food and Drug Administration, as well other agencies around the world, for the treatment of seizures in two fairly rare forms of childhood epilepsy.
Even the calculations from the study into Epidiolex takes us no closer to truly understanding the safe dosages of CBD, due to unusual circumstances which meant it was rushed through on a compassionate basis to provide treatment for children with grave seizure disorders who had not responded to alternative medications.
In Dr Koturbash’s words, it was not a typical ground-up drug development process.
Things were taken a lot more serious in this study, however, with dosage calculations calculated using a standard model for toxicity dosages in a mouse model. The dosages used were based on what is already being used in humans today.
As with all toxicity investigations, to fully investigate CBD, Dr Koturbash and his Arkansas research team had two conduct the study in two phases; the acute and sub-acute phase.
In the acute phase, mice were administered with 0, 246, 738, or 2460 mg/kg of CBD and observed for 24 hours.
In the mice on the highest dosage, a significant increase in live-to-body weight (LBW) ratios, plasma, ALT, AST (enzyme markers for liver damage) and total bilirubin were noted.
The results were notably worse in the sub-acute phase, where 8 week old mice were gavaged for 10 days with dosages of 0, 61.5, 184.5, or 615 mg/kg of CBD for 10 days.
Dr Koturbash says these doses were, “the allometrically scaled mouse equivalent doses (MED) or the maximum recommend human maintenance dose of CBD in Epidiolex (20 mg/kg).”.
Essentially, the mice in this study were receiving the same dosage as the maximum maintenance dose for children with rare epilepsy disorders.
Worryingly, 75% of the mice on the 615mg dose of CBD during the sub-acute phase had died or were near death on days three or four. They also showed similar manifestations of liver damage as the mice on the highest dose in the acute phase possessed.
Regarding he results, Dr Koturbash said, “There is a potential for liver injury. If you look at the Epidiolex label, it clearly states a warning for liver injury; it states you have to monitor the liver enzyme levels of the patients. In the clinical trials [for Epidiolex], 5% to 20% of the patients developed elevated live enzymes and some patients were withdrawn from the trials”.
This information, alongside the results from Koturbash’s own trial, highlight a need for further investigation of the safety parameters of hemp extracts.
Considering the CBD market is currently experiencing exponential growth, and more states throughout the US are becoming lenient on the matter, it’s something that needs to be done sooner rather than later. Recently, TSA has even started allowing Americans to carry CBD oil while flying domestically.
Another danger, that Dr Koturbash aims to further explore in another study, is that CBD also alters the regulation of more than 50 genes, many of which are linked to oxidative stress responses, lipid metabolism pathways and drug metabolism enzymes.
Regarding this study, it is important to recognize that the outcome was not trying to decrease the popularity of the CBD in the long term.
Koturbash says, “I don’t want to say that CBD is bad and we should ban it. But in my opinion there is clearly not enough research.”.
To put it bluntly, research like this study are extremely important in allowing us to truly understand the impact of long-term CBD use.
It’s also crucial for dictating the rules of safe dosages, and tightening restrictions on what can and cannot be sold by those looking to get involved in the cannabis market in the near future.