Alarming CBD Research Results
Cannabidiol (CBD) has been heavily hyped. Unfortunately, peer-reviewed medical research into the true therapeutic and healing properties of CBD has been limited. Marijuana research has been repressed as a consequence of the drug being listed under the federal government’s Controlled Substances Act, where it remains under Schedule I status.
The DEA hasn’t budged in its anti-cannabis stance. Other agencies have been more open-minded. Both the National Institutes of Health (NIH) and the U.S. Food and Drug Administration have supported or approved more research into the medicinal benefits of CBD and other cannabinoids.
CBD AND LIVER TOXICITY
GW Pharmaceuticals got approval from the FDA in 2018 to begin selling its seizure drug Epidiolex, which is a form of CBD used to treat cases of severe childhood epilepsy. To get approval for Epidiolex, GW Pharmaceuticals had to sponsor clinical trials to demonstrate its efficacy. They succeeded in doing just that, but some alarming results were also obtained during these evaluation procedures.
“When they actually went and tested it in a clinical trial, they found a number of toxicities that were of significant concern,” explains Dr. Douglas Brenneman, a medical researcher employed by Kannalife Sciences, Inc., a biotech firm involved in the search for CBD-based medicines. “The number one concern is liver toxicity.”
Elevated levels of certain liver enzymes in distress alerted researchers off to the problem. One of these enzymes, called transaminases, was found in 15 percent of the patients involved in the trial.
More concerns were raised about the potential for CBD to cause harm to developing organisms, including human fetuses. It is also uncertain how CBD interacts with other medicines and the harmful physiological responses that might be provoked by such combinations.
The results of the testing on Epidiolex have caught some people by surprise. However, researchers at Kannalife already knew there were problems, based on their internal evaluations.
“We were early to identify possible developmental toxicity issues from long-term use,” says Kannalife founder and CEO Dean Petkanas. “We were also able to point out in our preclinical work that there were liver toxicity issues, potentially. When we saw the limitations, we said ‘well, maybe we can endeavor to make CBD better.’”
Kannalife has created CBD analogs to treat neurodegenerative disorders. The most promising synthetic candidate at the moment is KLS-13019, which is designed to treat neuropathic pain.
“Now we have a potent neuroprotective molecule,” says Dr. Brenneman, who is Kannalife’s lead biochemical researcher. “We’re getting some understanding of properties; it can elicit that CBD cannot.”
The potential liver toxicity of KLS-13019, and other such compounds, remains a concern. As of yet, Kannalife’s research on the drug has not been able to quantify the exact level of risk this medicine might create, and at what doses. It cannot say, for example, if the risk of liver damage is lesser or greater than that associated with prolonged use of the painkillers acetaminophen and ibuprofen, which carry FDA warning labels but are still available in over-the-counter formulations.
THE FDA CRACKS DOWN
Some companies marketing products containing CBD have been over-exuberant in their claims about its effectiveness. They have been guilty of some clever (and illegal) sleight-of-hand, exploiting public enthusiasm over cannabis by portraying all cannabis compounds as not only safe but capable of ameliorating the symptoms of many serious medical conditions.
“In the world of commerce, if you can get into the marketplace without federal regulation or oversight, you do it,” Petkanas explains. With the trade in cannabis-related “health” products growing by leaps and bounds, however, it was only a matter of time before government authorities took notice.
In November 2019, the U.S. Food and Drug Administration took action to crack down on some of the more egregious violators. It issued warning letters to 15 companies, telling some of them to cease and desist making unproven and extravagant claims about the capacity of CBD to cure or prevent disease. Other companies were tagged for selling CBD as a dietary supplement, while others were guilty of illegally adding CBD to human and animal foods.
To justify its actions, the FDA pointed to studies that have revealed potentially dangerous side effects that may be experienced by at least some users of CBD. The FDA issued a revised Consumer Update detailing some of these side effects, with the risk of liver injury mentioned prominently. The report emphasized that research on the impact of long-term cannabinoid use, and into the effects of CBD on developing fetuses, was too sparse to ease concerns.
“It’s a bit of a conundrum for the marketplace,” says Petkanas. “The tail got busy wagging the dog for the last couple of years. Now we’re starting to see the market cool off a little bit for these over-the-counter products, and the FDA is taking a more active role in how they’re going to treat CBD going forward.”
CBD IS WORTH THE WAIT
Under the current regulatory structure, before the FDA approves any CBD-based medicine, it must be verified as safe in preclinical research and clinical trials. Potential risks must be weighed against potential benefits, and the final decision must be made based on the results of these calculations. FDA approval doesn’t guarantee the complete absence of side effects in users, but it does signify the capacity of a drug to help most patients who take it as prescribed.
Unlike some other companies looking for the pot of gold at the end of the CBD rainbow, Kannalife has signaled its intentions to stay patient and proceed responsibly. It will follow all standard research protocols and only release and market its medicines when they have been approved, and the company itself is confident of their efficacy.
This is the most sustainable approach for cannabis producers and manufacturers in the long run. It is an approach that will allow CBD and its analogs to prove their worth as potent, versatile, and safe medicinal remedies for a variety of disorders and conditions.