Cannabis has been used by ancient cultures (documented back as far as 2900 BC) for a wide variety of therapeutic remedies and was one of the most prescribed drugs in the United States in the late 1920s and early 1930s, prior to prohibition. Among other available products, both Parke-Davis and Eli Lilly manufactured a tincture using an alcohol-based cannabis extract of Indian grown cannabis (Cannabis Indica). It was prescribed for gout, menstrual cramps, migraines, insomnia and many other indications where treatment included an analgesic, anti-spasmodic or a sedative. Cannabis has been used historically as medication in many different cultures, including the United States.
After prohibition occurred in the United States in the late 1930’s, most medical use of marijuana (outside of self-medication) had ceased. It wasn’t again until the mid-1970’s when Marijuana was decriminalized in the Netherlands (1976) and a couple years later in 1978 that a court case allowed for a single patient to have very limited, federally controlled use of the substance in the United States. Over the next 10 years, Marinol, a synthetic version of tetrahydrocannabinol (THC) was approved by the FDA, which led the way to further but limited research.
Big Breakthrough – 1990-1992, Endocannabinoid System Discovered
After more than 4000 years of varied therapeutic use of Cannabis with some but limited understanding of the chemistry of Cannabinoids and related compounds, scientists made a major breakthrough in the early 1990’s in understanding how some key compounds in Cannabis work on the human body. A system within the human body was discovered and named the Endocannabinoid System (create anchor).
There are differing articles that give credit to various researchers for these findings but it appears that different parts of the Endocannabinoid system (receptors, transmitters and chemical processes) were studied and documented between 1990 and 1992 stemming partially from work done in the early 1970’s at John’s Hopkins University. It was found that there were receptors in the brain that were capable of binding with Opioids. This work continued in the 1990’s at St. Louis University by government funded studies. This was in addition to further studies at the National Institute for Mental Health (NIMH) which published more encompassing information related to the Cannabinoid receptors inherent within all humans as well as base models for how these receptors work. Furthermore, there was now documented evidence that the human body has cannabinoid receptors internally as part of the endocannabinoid system. These receptors were found to be involved in a variety of physiological processes including appetite, pain-sensation, mood, memory and more.
For more information on the Endocannabinoid System (create anchor) and how it is currently known to work, please see our reference on the Endocannabinoid System which is a collection of summarized information and links to external research.
US Medical Marijuana Today
In 1996, California was the first state to legalize medical marijuana at the state level even though it was still federally illegal and considered a Schedule 1 drug by the DEA and FDA.
While California was the first to implement a medical marijuana program, it was not state regulated until 2017 where regulation was left to individual counties and municipalities within California to oversee/enforce. Since California first implemented their program in 1996, thirty (30) states and the District of Columbia have implemented medical marijuana programs as of April 2018. With the exception of Maine & Washington DC, program development has generally been led by a set of early adopting western US states including Washington, Colorado, Oregon, and California with a progression to the east. Arizona, Nevada, Illinois, Michigan, New York and Pennsylvania as well as many less populated states concurrently have implemented medical marijuana programs.
By in large, as the progression has moved east, states have implemented medically accepted use and/or compassionate use laws that have been increasingly restrictive in nature with varying levels of state government support and commitment. Some states restrict the use of flower material (and allow only concentrates). Some states restrict edibles. Other states limit the list of approved conditions for use, and some have prescriber registries that make it harder for doctors to recommend/prescribe cannabis.
This has led to regulations that vary greatly across states and has also led to varying program success rates in the different states based on physician participation, patient access and approved indications for use. Therefore, there is a large variation of product quality, availability and pricing. Many states have differing regulations from county to county (even city to city) which can negatively impact patient access and care.
As the public acceptance of cannabis expands, many manufacturers from west coast markets are moving east to follow demand and associated revenue. The legal cannabis industry grew from just over $1 billion USD in revenue in 2006 to in excess of $5 billion USD in revenue in 2014. The growing competition in both mature and new markets have caused many firms to step back to try to get ahead of the bubble and focus on ancillary services as well as medical research.
Most recently, a UK-based pharmaceutical manufacturer, GW Pharmaceuticals was awarded FDA approval for a cannabis-based medication indicated for two rare forms of childhood epilepsy.
Cannabinoids are chemicals compounds that are found in Cannabis (both marijuana and hemp plants). There are over 80 reported cannabinoids produced by the cannabis plant. These compounds act on various parts of the body that have cannabinoid receptors. Cannabinoids work on two main receptors in the human body called CB1 and CB2 receptors. There are other known cannabinoid receptors throughout the body. The CB1 receptor is found in the nervous system- typically the brain. CB2 receptors are found throughout the body. The most commonly known cannabinoid is tetrahydrocannabinol (THC). This is found in cannabis plants and is noted to have the psychoactive effect (feeling of being high). Among the other notable cannabinoids are Cannabidiol (CBD), Cannabigerol (CBG), Cannabichromene (CBC), Cannabinol (CBN) and Cannabivarin (CBV) to name a few. Each of these chemical compounds have different effects on the human body. CBD for example has been reported to have a calming effect for most people. Claims have been made that CBD has anti-psychotic, anti-depression and anti-tremor effects. In addition, there have been reports of other conditions being improved by its actions on receptors. CBG has been reported to have an anti-inflammatory effect. CBV can act as an appetite suppressant. CBN is a sleep aid. Naturally occurring cannabinoids in plants are not biologically active in the human body. These chemical compounds need to be converted from their naturally occurring acid form (e.g. THC-A, CBD-A) in plants to a biologically active form (“decarboxylated”: THC, CBD) to have their effect in the human body. This is achieved by a variety of methods. Some combination of heating, pressure, other chemical reactions and the time the compounds are exposed to these methods renders the cannabinoid “biologically active”. Most cannabis plants have trace amounts of many of these compounds. Breeding and hybridizing focus on concentrating 1 or perhaps 2 of these compounds in a single strain of cannabis plant for a desired physical effect. For example, there are some strains of bred cannabis marijuana plants that have over 30% THC. Yet another strain of cannabis plant has a very high level of CBD and very little THC known to treat children with seizure disorders. Much more research is needed to elucidate and confirm the effects of the various cannabinoids on the human body to potentially treat a wide variety of conditions and diseases.
Our bodies make natural cannabinoids and these compounds act on receptors which form the endocannabinoid system (ECS). Most creatures on earth have been found to have an endocannabinoid system - even small sea creatures. Like any chemical and receptor system the ECS can be compared to a simple lock and key relationship. The cannabinoid receptors CB1 and CB2 act as the locks and our own “natural” THC called anandamide acts like a key. When the key opens the lock, some physical effect occurs. It is widely believed that the endocannabinoid system is responsible for our overall health and well-being also known as homeostasis. Disease states and a multitude of medical conditions can be the result of a deficiency of the endocannabinoid system. Anandamide or THC has psycho-active effects on CB1 receptors which results in the overall well-being of the nervous system and even our mental state. The CB2 receptors can be found throughout our bodies including organs, immune system and digestive tract to name a few. The proper functioning of these receptors within the system can be responsible for preventing infection, inflammation, tumor growth, digestive issues etc. Interestingly, non- psychoactive cannabinoids such as CBD have no action on these receptors rather they help these receptors function by maintaining the levels of anandamide in our bodies. CBD has been identified in a process that prevents anandamide from being broken down. If the level of this compound can be maintained, then the function of all body systems can achieve overall wellness. Just as many people take vitamins, supplementing our bodies with THC and CBD can potentially lead to healthier individuals in the presence of deficiency. Studies have shown that even small doses of plant cannabinoids cause our bodies to actually produce more receptors and endocannabinoids. The endocannabinoid system relies on proper nutrition to function optimally. One of the most important compounds responsible for the proper regulation and formation of endocannabinoids are Omega-3 fatty acids. An excellent source of omega-3 fatty acids is hemp seed. Certain strains of Hemp are an excellent source of the omega-3 containing seeds and CBD. Continued research, as the cannabis plant becomes more widely accepted by various governmental agencies, can only help us develop a deeper understanding of how this system works and develop medicines to enhance it and prevent illnesses and alleviate symptoms.
Terpenes are a diverse group of compounds found in plants and their essential oils. It is these compounds that are responsible for giving a plant its particular scent and taste. In addition, terpenes can act either alone or in conjunction with cannabinoids to produce physical effects on the body. These compounds can be found in various preparations including but not limited to topical oils, creams, ointments, vape oils, and oral lozenges.
Terpenes are an essential component of cannabis plants. Often, strains of cannabis can be identified by the aroma produced by the terpenes alone. They are produced by the same part of the plant that produces THC and CBD. Terpenes can act on receptors as do the cannabinoids and give rise to various effects. Some terpenes have been shown to have similar effects to anti-depressants on the brain. These compounds produce a synergy with THC and CBD on the body for various different effects. In fact, the presence of all three types of compounds are responsible for the “entourage” or whole plant effect. This combined effect has been shown to be far more beneficial than any one compound alone.
Flavonoids are an extremely large group of compounds found within plants including cannabis which are responsible for anti-oxidant and anti-inflammatory effects. Extensive research has been and is currently being conducted surrounding flavonoids and their natural health benefits. Recent trends in medicine and research show that oxidative stress and inflammation may be the root cause of many conditions and disease states. These phytonutrients have taken a strong-hold in the world of over the counter antioxidant remedies.
Flavonoids, like THC, CBD and terpenes can produce a variety of effects on the body. These too are involved in the whole plant “entourage” effect. They also contribute to the color and taste of cannabis as they do in all other plants. The more specific “Cannaflavins” have been identified to have same effects as NSAIDS in reducing inflammation. The antioxidant effects of cannaflavins are just beginning to be understood and the role they might play in preventing certain types of cancers. More research is needed to further elucidate the ever-growing list of benefits of cannaflavins and the cannabis plant.
Medical Marijuana Future
The future of the medical marijuana industry is an exciting one. More and more states, countries and health organizations are beginning to see the benefits and need for medical marijuana. The stigma continues to be broken down as we begin to resume a treatment option that was prohibited for no other good reason than bias and politics over 80 years ago. Mature markets such as that in Colorado have established the learning curve for cultivation, extraction, distribution and prescription. The industry has reached a position on its own that now calls for the proper research and clinical trial of medical marijuana medications to treat ever worsening medical conditions currently being treated with toxic pharmaceuticals. One of the largest areas of impact that this research and medical marijuana’s accessibility can have a paradigm shift effect is on that of the opioid epidemic. Not only is medical marijuana showing promise in the treatment of actual pain conditions themselves, but new discoveries are being made that it can also treat withdraw symptoms, those deficiencies that predispose an individual to chronic pain and the physiology involved with addiction to opiates.
Medical marijuana’s acceptance is leading to more politicians realizing the need to explore and research the cannabis plant. As scientists, we understand that there is no single panacea. Cannabis is certainly not the curative treatment to all known and unknown medical diagnoses. We do acknowledge the natural relationship between the plant and our endogenous cannabis system cannot be ignored. Research of the effects of cannabinoids on our receptors and body systems must gain parity with that which is occurring at the large pharmaceutical companies in this country and abroad. As we elucidate the effects of these compounds at the cellular and sub-cellular level we will then be able to integrate medical marijuana with mainstream allopathic medicine. Fundamental questions arise as medical marijuana becomes more widely available. What is the interaction of the prescription drug a patient is taking with medical marijuana? What is the proper dosing of medical marijuana? What is the optimal route of administration? What is the absorption rate with oral medications? Agronomed’s mission is to be at the forefront of this research initiative. Our team of physicians, pharmacists, academics, technologists and leaders are unparalleled and are poised to set the standard for the industry.