Medical cannabis has a long history dating back thousands of years, and it was not until the 19th century that cannabis entered the realm of western medicine. Some of the earliest evidence of cannabis as medicine is found in the Pen-ts’ao ching, the oldest pharmacopoeia compiled in China around AD 100 based on oral traditions passed down from as early as 2700 BC. Cannabis is thought to have disseminated in India, where it became widely used for medical purposes—including as an analgesic, anti-convulsant, anti-inflammatory, diuretic, and many others—around 1000 BC. There is also evidence of cannabis use in Persian medicine for the treatment of infectious wounds and gout, and in Arabic medicine as a treatment for epilepsy. By the 15th century, it was used throughout Africa to facilitate childbirth, as well as for diseases including malaria and dysentery. Cannabis is thought to have reached the Americas by the 16th century.
Introduction to western medicine
During his travels through North Africa in the 1830s, French psychiatrist Jacques-Joseph Moreau observed the use of hashish (cannabis resin). He proposed that drug intoxication and hallucinations involved similar mechanisms, and upon his return to Paris, began to experiment on the subject. In 1845, his book, Du hachisch et de l'aliénation mentale: études psychologiques was published (and translated into English, Hashish and Mental Illness, in 1973). Moreau was also a point of connection between cannabis and the art world, as “Club des Haschichins” (Hashish Club) included Dumas, Baudelaire, and others who participated in his experiments.
William O’Shaughnessy, an Irish physician, is credited with introducing cannabis into western medicine with his publication, “On the Preparations of the Indian Hemp, or Gunjah- Cannabis Indica their Effects on the Animal System in Health, and their Utility in the Treatment of Tetanus and other Convulsive Diseases” in 1843. O’Shaughnessy joined the British East India Company, and became a professor of chemistry at Calcutta Medical College. His experiments examined the effects of cannabis in animals, and eventually included human subjects. He returned to England with a large amount of cannabis and shared his findings with other physicians, leading to the widespread adoption of medical cannabis across Europe and North America.
Despite early interest in the therapeutic effects of cannabis, the passing of several key acts imposed significant limitations to cannabis research. The Marihuana Tax Act of 1937 imposed extremely high taxes on the substance, and led to the exclusion of cannabis from the United States Pharmacopoeia in 1941. This was followed by the enactment of the Boggs Act in 1951, and the Narcotic Control Act in 1956. By 1970, cannabis was prohibited under federal law with the Controlled Substances Act.
A surge in recreational cannabis use from the late 1960s to early 1970s and the concomitant discovery of Δ 1 3,4-trans-tetrahydrocannabinol (Δ9 THC), the main active compound in cannabis, spurred renewed interest in cannabis research. Cannabis receptors and drug approvals It was not until 1988 that studies in rat brains revealed the presence of a cannabinoid receptor, CB1 , which was later confirmed in human brain sections, dispersed in outflow nuclei of the basal ganglia, the hippocampus, and cerebellum. A second cannabinoid receptor, CB2 , was later discovered in the periphery. Around the same time, the search for endogenous substances capable of interaction with cannabinoid receptors led to the discovery of the endocannabinoid system (ECS). The ECS maintains homeostasis, and regulates multiple processes including learning, sleep, and metabolism, among others. To this day, its full complexity has yet to be elucidated.
Preclinical and clinical research led to the approval of THC for one of its most well-known uses to date: the treatment of nausea and vomiting associated with cancer chemotherapy. A synthetic form of Δ9 -THC, dronabinol (trade name Marinol) received FDA approval for this indication in 1985. Later, in 1992, it was approved for the treatment of anorexia and weight loss in patients with AIDS.
Still, there was no consensus on the value of medical cannabis, and the White House Office of National Drug Control Policy requested a review of the scientific evidence, to be carried out by the Institute of Medicine. The 1999 IOM report concluded: “Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation…” The report also included support for further research and clinical trials to examine the physiological and psychological effects of cannabinoids.
In 2003, the large placebo-controlled study, “Cannabinoids for the treatment of spasticity and other symptoms related to multiple sclerosis (CAMS),” was published. Six-hundred-and-thirty participants with multiple sclerosis-related spasticity were randomized into groups and received an oral natural cannabis extract (a 2:1 ratio of THC and cannabidiol), synthetic THC, or a placebo for 15 weeks. Findings revealed no association between cannabinoids and improved spasticity as assessed by physicians using the Ashworth scale. However, patients reported improved spasticity and pain, leading researchers to conclude that cannabinoids may be clinically useful. In 2005, SATIVEX® (delta-9-tetrahydrocannibinol and cannabidiol in the EU, nabiximols in the US) received approval from Health Canada as an adjunctive treatment for neuropathic pain in adults with multiple sclerosis, and it was later approved for pain management in patients with advanced cancer in 2007. Nabiximols remains an investigational product in the US.
Access to medical cannabis
Cannabis laws are complex, and while cannabis use and distribution remains prohibited under federal law in the US, several different liberalization policies have passed.
California was the first state to pass a medical marijuana law (Proposition 215, passed in 1996) that removed state penalties for patients using marijuana for specified medical conditions. Numerous other states have since passed similar legislation.
In 2017, the National Academies of Sciences, Engineering, and Medicine published a report on the health effects of marijuana and derived products. Following a review of the scientific research pertaining to therapeutic effect, the committee concluded there was evidence to support the use of cannabis and cannabinoids for pain reduction, and oral cannabinoids for multiple-sclerosis related muscle spasm and chemotherapy-induced nausea and vomiting.
Since then, cannabis science has continued to advance and evolve, and so have the laws pertaining to its use. Legalization removes all prohibitions against cannabis possession and use for recreational purposes, and as of 2020, cannabis has been legalized in 11 states—Colorado, Washington, Alaska, Oregon, California, Maine, Massachusetts, Nevada, Michigan, Vermont, Illinois—and the District of Columbia. Alternatively, several states have decriminalized cannabis, meaning it remains illegal, but individuals possessing less than a specified amount are not prosecuted by the legal system. To date, 26 states have decriminalized small amounts for personal consumption.
Medical cannabis has a long, complex history, and the science has just begun to catch up to centuries of anecdotal evidence supporting its use as medicine. Results from ongoing clinical trials will surely shape the future of cannabis cultivation, pharmaceutical development, legalization, and patient care.