By Gregory L. Smith, MD, MPH
Cannabis Sativa evolved as a separate species of plant on the steppe terrain of what is now Mongolia at the end of the last Ice Age over 12,000 years ago. It is believed that human civilization discovered this fragrant, oily plant not long after discovering grain-bearing plants approximately 10,000 years ago. The seeds of the plants would have thrived in the nutrient-rich dump sites of prehistoric hunters and gatherers. The first recorded medicinal use goes back to 4,000 BCE, where it was reported to have been used as an anesthetic for surgery. In 2,737 BCE, an important Chinese pharmacopeia of the time recommended cannabis for the treatment of “gout, constipation, rheumatism, and forgetfulness.” Throughout most of its history, the cannabis flower was used to make an oily, sticky balm that was applied topically, strained in hot water to make a tea, or infused in various milks. In 440 BCE, the Scythians, a nomadic Indo-European people, brought cannabis to Europe. The Greek historian Herodotus discusses in detail how they used cannabis as incense in heated braziers. In 79 AD, the famous Roman scientist and historian, Pliny the Elder, used cannabis topically to “ease cramped joints, gout, and similar violent pain.”
Cannabis’s recreational and medicinal benefits in humans would mostly occur in the East. This is because, due to environmental and ecological pressures, Cannabis Sativa genetically developed into two different strains. One strain was a short, bushy, fat-leafed plant with high levels of THC and very low levels of CBD. This strain is officially known as Cannabis Sativa Indica. It was this high-THC flower that was first recognized for its psychedelic effects associated with religious rituals. But it was also THC that had profound effects of pain, spasticity, and cramping (muscular and intestinal). The other strain developed into a tall, thin plant with thin leaves. This strain, officially known as Cannabis Sativa, was low in THC and high in CBD. This strain, now commonly known as hemp, was used for rope, clothes, as a food source, and for heating oil. Any potential effects from this high-CBD strain were not easily identified in ancient times.
It was not until the 16th century and the discovery of the Americas that fascination with inhaling smoke began. The indigenous peoples had been smoking tobacco since 1,000 BCE. Cannabis was not native to the Americas, but as this new smoking habit reached Western society, it wasn’t long before the ubiquitous Cannabis Sativa plant was smoked. The rapid and significant impact of inhaling intoxicating tetrahydrocannabinol (THC) totally changed the perception of the plant, which was originally smoked for purposes of intoxication. Smoking cannabis was never considered a means of using cannabis medically until very recent times.
The real cannabis as medicine arrived in Western society by way of an Irish physician named William O’Shaughnessy. In 1833, he was sent by the East India Company to Calcutta. There, he observed and validated the locals’ use of cannabis for seizures, tetanus, and rheumatism. He also published one of the first medical scientific papers on cannabis in 1839. He focused on the application of cannabis tinctures and edibles, and his findings were rapidly recognized and adopted by the medical community in Europe and subsequently in the US. By the year 1900, cannabis tinctures and extracts were the second-most commonly sold medication in the US, with over 200 manufacturers and 2,700 products available. In fact, cannabis extracts were so popular that the federal government had to invent a new name to prohibit cannabis use in 1937. By the 1930s, alcohol prohibition had been in place for a decade, and average US citizens, not just migrant Mexican farmworkers, were starting to smoke cannabis for the first time for its intoxicating effects. The crossover of smoked cannabis from migrant farm workers to negro jazz musicians (and eventually to the young white community) resulted in a huge societal backlash against smoked cannabis. The federal government used the term, ‘Marihuna’ (marijuana) to prohibit cannabis. This term was “Mary Jane” in Spanish and was used to infer racist associations with cannabis. The 1937 Marijuana Tax Act passed the same time as “Reefer Madness” made it to movie theaters. Cannabis, including hemp, was soon federally illegal. The Controlled Substances Act (CSA) of 1970 under President Nixon completed the intense prohibition against cannabis and related medical research for decades to come.
Although cannabidiol (CBD) was discovered in the 1940s, and tetrahydrocannabinol (THC) in 1964, it was not until the early 1990s and the discovery of the endocannabinoids system that cannabis and cannabinoids took off as ‘real’ medicine. Dr. Raphael Mechoulam, while continuing the research he had done with THC in the 1960s at Hebrew University in Israel, discovered the largest receptor system in the human body. His work and the extensive research of those who have followed him helped reveal the many therapeutic benefits of cannabinoids.
The next step in the life of this amazing plant came with the advent of the HIV epidemic in the early 1980s. AIDS hit California especially hard. Many small, illegal co-ops developed that allowed patients to get locally-grown cannabis to treat symptoms. This mostly high-THC cannabis was used to treat neuropathic pain, wasting syndrome, nausea, and vomiting that comes with AIDS and the use of potent retroviral medications. At that time, inhaled THC was by far the best medication to treat these conditions. The use of smoked medical cannabis for rapid onset and potency spread to cancer patients with pain and wasting syndromes by the 1990s. Through a grassroots ballot initiative, the first medical cannabis law was passed in California in 1996.
The next piece in the ‘cannabis as medicine’ story comes from a little girl named Charlotte Figi, who had severe intractable seizures from Dravet’s syndrome. Both of her parents were physicians and were devastated by her frequent seizures despite using several potent seizure medications. At age 5, they tried medical cannabis that was potent in CBD. They quickly saw the therapeutic effects of CBD and subsequently started the second wave of cannabis as medicine starting in 2011. State legislators slowly but consistently passed laws legalizing “low-THC“ cannabis. These laws allowed parents to obtain CBD for their children. As the many benefits of CBD became obvious, CBD is now reported to be used regularly by 14% of the US population.
Formal, high-quality research by GW Pharma in the UK resulted in the FDA approval of a 99.7% CBD extract called Epidiolex in 2018. The positive Phase III trials of THC/CBD extract Sativex may result in the first FDA-approved THC extract.
The increasing amounts of basic science and clinical research on the other minor cannabinoids, such as THCV, CBN, and CBC, may make cannabis the most important medicine since the discovery of antibiotics.
Time will tell.