Cannabidiol is one of many compounds in the cannabis plant and accounts for up to 40% of the plant’s chemical makeup. Cannabis is now legal for medicinal use in 33 U.S. states and for recreational use in 11. Legal changes in recent years have opened the doors to dozens of new recreational products, including CBD-infused bath bombs, candles, chocolate, coffee, dog treats, and sex lube. The market will reach $41 billion by 2025, Nielsen predicts, and mainstream brands like Coca-Cola and Ben & Jerry’s are reportedly exploring new CBD brands.
The mode of action for most psychoactive plants is straightforward: Coca leaves contain benzoylmethylecgonine, which boosts levels of serotonin, dopamine, and norepinephrine, in turn elevating mood. Poppy plants ooze with morphine, which delivers the greatest dose of pain relief found on earth. But cannabis is far more complex: CBD is just one of 120 phytocannabinoids, and it alone interacts with several different receptors on the surface of human cells, which in turn influence the effects of other native neurotransmitters and foreign drugs. Untangling these different psychoactive compounds — and their interactions with each other and with neurotransmitters in the body — is crucial to developing drugs that harness the power of cannabis. It’s complicated, and getting it wrong could cause serious harm.
In 2006, French pharmaceutical giant Sanofi-Aventis released rimonabant, an appetite-reducing drug designed to block the CB1 receptor, one of the main targets for CBD. It was hoped that rimonabant could help curb obesity, but the drug had serious psychiatric side effects and led to a number of suicides. The experimental drug BIA 10–2474, developed by Portuguese pharmaceutical company Bial and also designed to interact with the receptors in the body that normally interact with CBD, came to a similar sad end in 2016 when one man fell into a coma and died during a clinical trial exploring the drug’s potential to alleviate neuropathic pain.
Like any natural compound, CBD can have a variety of beneficial and detrimental effects. For example, CBD slows the metabolism of enzymes in the liver, which can actually be a problem if somebody has been prescribed a life-saving drug, such as immunotherapy treatment for cancer. “There are good and bad things about the cannabinoid system — so with any molecule, there is always a benefit-risk ratio, and it’s always about the benefits compared to the risks,” says biochemist Roger Pertwee, professor emeritus at the Institute of Medical Sciences University of Aberdeen, who has studied cannabis since the 1960s. “Very few drugs have just benefits — all drugs have lots of different actions and lots of different effects.”
“Even the human clinical trials that have been done are limited. For example, a physician would absolutely not know what dose to prescribe for a CBD or CBD-THC mixture for most conditions we think it can treat.”
Raphael Mechoulam, a professor at the Hebrew University of Jerusalem in Israel, has spent his career studying cannabinoids. In 1963, he isolated CBD, and a year later THC. His own research has indicated that CBD would be helpful for arthritis, Type 1 diabetes, heart disease, graft-versus-host disease, and even psychosis. But many other possible treatments remain theoretical, because they rely on funding for expensive medical trials.
Mechoulam discovered the anticonvulsant properties of CBD, giving the molecule to a handful of epileptic and nonepileptic patients in a double-blind study published in 1980. “It took another 35 years until another clinical trial was conducted. We shouldn’t have waited so long,” he says. “Clinical trials cost millions, and the chances are that if there is no patent, drug companies will just not be interested.”
Lab tests on animals and cell cultures have so far found that CBD can protect cells from oxidative stress and ameliorate anxiety in rats. It even demonstrates anti-cancer properties in vitro. Yet promising lab studies based on nonhuman subjects are not sufficient to prove the same benefits in people.
Linda Parker, a professor at the University of Guelph in Canada, says trials need to be comprehensive, use human subjects, and explore all the complex interactions of each of the different cannabinoids. “Even the human clinical trials that have been done are limited — for example, a physician would absolutely not know what dose to prescribe for a CBD or CBD-THC mixture for most conditions we think it can treat,” Parker says.
Parker says one claim that particularly grates is the supposed power of the entourage effect, the concept that if taken together, all 120 phytocannabinoids act in a different way than they would independently. “That’s true of anything. If you consumed alcohol and nicotine and caffeine all together, you would have an entourage effect in that the effect of each when taken in combination would be different than if you consumed them individually,” Parker says. “It’s not some mystical, magical property.”