“I am here to apologize…"
"...we have been terribly and systematically misled for nearly 70 years in the United States…the science is there...[cannabis] doesn’t have a high potential for abuse, and there are very legitimate medical applications…it could compete with A LOT of things…we are on the cusp of a marijuana revolution”
- Dr. Sanjay Gupta, M.D., Assistant Professor of Neurosurgery at Emory University, CNN Chief Medical Correspondent, nominated by President Obama for U.S. Surgeon General
"...therapeutic potential in almost all diseases affecting humans"
"modulating [endocannabinoid system] activity may have therapeutic potential in almost all diseases affecting humans, including obesity/metabolic syndrome, diabetes and diabetic complications, neurodegenerative, inflammatory, cardiovascular, liver, gastrointestinal, skin diseases, pain, psychiatric disorders, cachexia, cancer, chemotherapy-induced nausea and vomiting, among many others.”
-Dr. Pal Pacher, MD/PhD & Dr. George Kunos, MD/PhD, Senior Investigators at the National Institutes of Health, an agency of the U.S. Department of Health and Human Services
“Cannabinoids are a pharmacologic treasure trove!”
– Dr. Raphael Mechoulam, PhD, Professor of Medicinal Chemistry, Hebrew University. Known as the “Father of cannabinoid science" for discoveries of THC, CBD, and the endocannabinoid system.
"...[no] significant side effects across a wide range of dosages"
"pre-clinical research...has shown CBD to have a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties. A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages...there is extensive information available with regard to its metabolism, toxicology, and safety”
-Dr. Nora Volkow, M.D., Director, U.S. National Institute on Drug Abuse, testifying in front of congress in 2015.
"Cannabinoids are found to have particular application as neuroprotectants"
"Cannabinoid's [anti-oxidant properties] are useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. Cannabinoids are found to have particular application as neuroprotectants...such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidiol, are particularly advantageous..."
-Summary of the U.S. government-owned patent (#6,630,507): "Cannabinoids as anti-oxidants and neuroprotectants."
HISTORY OF MEDICAL CANNABIS
From the Egyptians to the Americans
Cannabis’ long and storied history begins in 2900 BCE, when the Chinese emperor Fu Hsi espoused its popularity as a medicine for a variety of ailments. Over the next 3000 years, cannabis appeared in an astonishing number of religious and medicinal texts from across the world: in 1500 BCE, it was lauded in the Chinese Rh-Ya pharmacopeia for treating dozens of ailments; cannabis residue was found on the body of King Ramses II of Ancient Egypt, where it was prescribed for pain and glaucoma; the plant and its extracts were extolled as the most important of 10,000 medicines in the Venidad and the Vedas, the two most important texts for Zoroastrianism and Hinduism; and Roman and Greek medical texts from circa 0 CE cite cannabis as treatment for various forms of inflammation like gout and joint pain.
This knowledge of cannabis’ medicinal power did not disappear after antiquity. The Oxford scholar and clergyman Robert Burton suggested cannabis as a treatment for depression in The Anatomy of Melacholy in 1621 while Napoleonic France widely prescribed it as treatment for pain and insomnia. By the middle of the 19th century, most countries around the world had accepted the varied uses of cannabis.
In 1850, cannabis was admitted into the United States Pharmacopeia, an official standards-setting authority for all prescription and over-the-counter medications. There, it listed cannabis as a treatment for pain, opiate and alcohol addiction, epilepsy, and a dozen other conditions. American pharmaceutical companies like Eli Lilly produced standardized cannabis extracts for patients across the nation.
By 1936, every US state had outlawed or heavily regulated cannabis consumption. New, synthetic, patentable, drugs like morphine were developed, replacing cannabis as the West’s preferred pain medication. Hysteria and misinformation about cannabis was spread by its opponents, pushing cannabis further and further from the medical canon. By 1970, marijuana was classified by the Controlled Substances Act as a Schedule I drug—one so dangerous as to not have any conceivable medical merit, lumping it together with drugs like heroin and LSD. This designation continues to this day, wherein the U.S. federal government prevents the medical use of marijuana and blocks research into the medical potential. Without adequate research, how can we have reliable information on the harms and benefits of cannabis use in humans?
Cannabinoids and the Endocannabinoid System
Cannabinoids are a family of molecules that are produced by both the cannabis plant and the human body. Cannabinoids from the cannabis plant interact with the human Endocannabinoid System--a complex system that scientists only recently discovered in the 1990's. The Endocannabinoid System is present is nearly all vertebrates on Earth, ranging from birds and reptiles, to fish and sea squirts, and is believed to have evolved nearly 300 million years ago. We know it is involved in a wide range of functions, including mood, memory, sleep, appetite, pain, stress response, immune function, metabolism, and homeostasis.
Over eighty-five unique cannabinoids have been identified in the cannabis plant, while only a handful have been pharmacologically studied. Most cannabinoids in cannabis are nonpsychoactive, with one notable exception. The chemical mainly responsible for cannabis’ psychoactivity—including the euphoric and analgesic effects that have caused its demonization for the last 70 years—is tetrahydrocannabinol or THC.
Because of its outright and visible effects, THC has been the most studied and characterized cannabinoid by far. THC has been shown to have mild to moderate analgesic ability, proving successful in treatment of cancer pain, as well as reducing the amount of opiods needed in acute, escape medication treatments. In animal studies, THC displays neuroprotective and anti-oxidant properties (which have been documented in Patent #6,630,507, owned by the U.S. federal government), making it a candidate for treatment of Alzheimer’s and other neurodegenerative disorders. We also see significant anti-depressant like effects of THC in animal trials. THC also exhibits anti-nausea and appetite stimulating properties, making it useful for patients undergoing chemotherapy or suffering from HIV/AIDs associated cachexia. However, THC's psychoactive properties are controversial and may limit its widespread, regular use as a medication. It is THC's lesser-known sister cannabinoid cannabidiol (CBD), that appears to have significantly more medical promise.
Cannabidiol, or CBD, is the other main active constituent in cannabis and is an isomer of THC. While this molecule is non-psychoactive, (producing none of the intoxication that is associated with THC), it is no less physiologically active. Cannabidiol’s therapeutic actions are incredibly wide: it has not only anti-anxiety and anti-psychotic properties, but also potent antioxidant action that is stronger than a- and b-tocopherol (vitamin E) and ascorbate (vitamin C). CBD has also been shown to exert neuroprotective effects--animal studies have demonstrated CBD benefitting degenerative neurological disorders like Alzheimer’s Disease. CBD also has anti-inflammatory effects, demonstrating benefit in animal models of inflammatory bowel disease and Type 1 Diabetes. CBD's analgesic effects have also been demonstrated and may eventually prove useful for the treatment of a wide variety of pain, from arthritis to nerve pain. Preliminary studies suggest that CBD has a very favorable safety and side effect profile, making it an attractive option from a patient compliance standpoint.
Thus far, we have briefly described the effects of the two most well characterized cannabinoids found in cannabis. Scientists have identified more than 80 other cannabinoids in cannabis, and for a vast majority of these we know very little about their pharmacologic effects. What discoveries lay in these other cannabinoids? What additional pharmacologic effects (both positive and negative) will we discover about cannabinoids like THC or CBD? What will our studies of cannabinoids tell us about our own Endocannabinoid System? From the evidence shown so far, this future is a promising one; and as our knowledge of cannabis and its cannabinoids grows, our world will surely grow NICER.