Perhaps the most intriguing property of THC is its ability to kill cancer cells without damaging normal cells.
Cannabis can be medically beneficial, but rogue synthetic chemists have caused harm
A zombie apocalypse. Stuff of movies, right? Maybe not.
On July 12, 2016, emergency teams answering a call from a Brooklyn nightclub were confronted by what appeared to be … zombies! They found some 33 people staggering about sluggishly with blank stares, making odd sounds.
As it turned out, they had all taken a street drug called “AK-47 24 Karat Gold.” Chemical analysis revealed it to be a synthetic cannabinoid known as “AMB-Fubinaca,” originally developed by Pfizer as a potential pain killer, modelled on the molecular structure of tetrahydrocannabinol (THC), the main active ingredient in marijuana. The compound never panned out as a drug, but its synthesis was published in the scientific literature. That’s all that clandestine chemists needed to start producing the substance and selling it on the street to anyone who was looking for a high.
An extract of the cannabis plant was widely available as a pharmaceutical product in North America until the 1930s, recommended for the treatment of pain as well as an appetite stimulant. Criminalization of marijuana in the 1930s put an end to its medical use, but certainly not to its use as a psychoactive substance.
The plant’s main active ingredient, tetrahydrocannabinol, or THC, was first isolated in 1964 by Raphael Meloucham at the Weizmann Institute in Israel. Its biological activity is due to a chemical resemblance to anandamide, a naturally occurring compound in the body that plays a role in regulating mood.
But THC is not the only component with activity. Cannabidiol, or CBD, has anti-inflammatory properties, and based on laboratory cell culture studies shows promise in the treatment of Crohn’s disease, probably because of its antioxidant property, meaning that it can neutralize those troublesome free radicals that are implicated in inflammation. Interestingly, cannabidiol tones down the psychoactive effect of THC, which is welcome in the case of medical use because patients do not want to feel stoned.
A common goal in pharmaceutical chemistry is to develop synthetic derivatives that maintain a drug’s desired activity but eliminate or reduce side effects. When it comes to THC, the pioneer in the field is John Huffman, an organic chemist, now retired from Clemson University in South Carolina. Starting in the early 1990s, Huffmann synthesized numerous analogues of THC and of cannabidiol with the goal of elucidating marijuana’s mechanism of action. The 18th compound he made, “JWH-018,” turned out to be four times more a psychoactive than THC.
Not surprisingly, this appealed to criminal chemists looking for a financial windfall, and soon Huffmann’s compound appeared on the street as “Spice” or “K2.” It has since been joined by other troublesome cannabinoids that may go by the same name. Unfortunately, in addition to zombielike states, sudden deaths related to irregular heartbeats have been linked with these clandestine drugs. There is also the issue that the underground chemists may not be especially interested in purity and some of the byproducts formed during synthesis may be harmful.
Another problem is that “fake marijuana,” as these substances have been dubbed by the media, casts a shadow on the legitimate medical use of cannabis. That is unfortunate because Canada, as well as a number of states in the U.S., now have provisions to make marijuana available to certain patients on the advice of a physician.
The most common uses are for the control of nausea after chemotherapy, for the alleviation of pain, for increasing the appetite of AIDS and cancer patients, for improving sleep and for treating anxiety and stress. But multiple sclerosis patients can also experience relief from such symptoms as burning sensations and spasticity.
Perhaps the most intriguing property of THC is its ability, at least in the lab, to kill cancer cells without damaging normal cells. THC binds to a receptor on the surface of cancer cells and triggers the formation of ceramide, a compound that prompts cell death. Healthy cells do not produce ceramide on contact with THC, a promising discovery.
Cannabis does not necessarily have to be smoked. Purified oils that can be used sublingually or added to food are available, but many patients claim that smoking the leaves is more effective. Of course, there is the problem of inhaling combustion products, which is not great for the lungs. A device that heats the plant without igniting it is now available and avoids the smoke inhalation problem.
Researchers are also high on the possible use of cannabis to treat post-traumatic stress disorder, diabetes, Tourette’s syndrome, epilepsy, depression, bipolar disorder and schizophrenia.
Obviously, marijuana can be a useful drug, but its use recreationally raises some questions. It can alter reaction times and cause driving accidents. And then there’s the open question of whether it may have longterm effects on the brain or lead to experimenting with more dangerous substances. But there is always the hope that some synthetic chemist will find a way to dull one edge of this doubleedged sword.