With 29 states and the District of Columbia having laws permitting the use of medical cannabis and 9 states plus D.C. allowing legal recreational use of cannabis, it seems that marijuana has gone mainstream. As the prohibition of pot begins to fade, the facts begin to emerge. Cannabis, along with its derivatives, is classified as a Schedule I drug which places tough restrictions on obtaining licenses to study the plant and its applications; this puts the United States decades behind Israel, Italy, and numerous other countries in regards to cannabis research. Because pot is taboo in America, the National Institute of Health has been paying Raphael Mechoulam, an Israeli scientist, $100,000 per year for over 45 years to research marijuana. In the cannabis world, Mechoulam is known as the “Grandfather of Marijuana” because he and his staff were the first to isolate the most controversial molecular compound known to man: delta-9 tetrahydrocannabinol, or more commonly known as THC. Mechoulam is also responsible for the isolation and identification of cannabidiol (CBD) and of the first known endogenous cannabinoids: anandamide and 2-arachidonoyl glycerol. Thanks to his research and that of cannabis pioneers such as Dr. Ethan Russo, Dr. Prakash Nagarkatti, and Dr. Christina Sanchez, we are beginning to learn the truth about the complex history surrounding this simple plant.
The first historical mention of cannabis was around 2900 BC by the Chinese Emperor, Fu Hsi and later in written Ayurvedic Medicine study around 1100 BC. Cannabis has been used for agricultural, religious, and medicinal purposes for centuries. In the United States, a variety of cannabis known as hemp has been grown and used for fiber, rope, soap, and food. In fact, rom the Colonial years until the early 1900’s, hemp was one of the leading crops in America. Cannabis sativa l was included in the United States’ pharmacopeia from 1854 until 1941, and by 1937, there were around 28 over-the-counter medications that contained cannabis. However, it was also around this time that the ‘Reefer Madness’ phenomenon emerged and the Marijuana Tax Act was passed; the combination of which put a strain on the farming of hemp and ended legal access to medical cannabis. ‘Reefer Madness’ was fueled by Henry Anslinger, the first commissioner of the Federal Bureau of Narcotics (which laid the groundwork for the DEA as we know it today.) Anslinger spread his demonization of the cannabis plant by issuing racist and sensationalist articles in newspapers and magazines owned by his co-conspirator, William Randolph Hearst. Anslinger once stated in an article that “there are 100,000 total marijuana smokers in the U.S., and most are Negroes, Hispanics, Filipinos and entertainers. Their Satanic music, jazz and swing result from marijuana use. This marijuana causes white women to seek sexual relations with Negroes, entertainers and many others." As a result of their campaign, Anslinger and Hearst received support from Lammot du Pont of the DuPont Chemical Company and from several pharmaceutical corporations. It comes as no surprise that cannabis was a major competitor of DuPont’s companies as well as Hearst’s timber business.
In 1970, the Controlled Substances Act categorized cannabis as a Schedule 1 drug which means that it had a high potential for abuse with no medical benefit. It is important to note, however, that the American Medical Association testified against the Marijuana Tax Act and opposed the Schedule 1 delegation. In 2009, The AMA voted to request Congress and the DEA to re-categorize cannabis as a Schedule 2, but the effort failed. To this day, cannabis remains a Schedule 1 drug even though the United States government recognizes the medicinal value of the plant as is made obvious by the fact that they own a patent on cannabinoids used as an antioxidant and neuroprotectant.
Even though cannabis and its derivatives are Federally illegal, the FDA has approved several synthetic cannabinoids for medical use. Marinol (Dronabinol) was approved by the FDA in 1985 as treatment for wasting syndrome in AIDS patients and chemotherapy induced nausea and vomiting in cancer patients. The FDA has also approved a similar medicine consisting of synthetic THC called Nabilone. Because these medications are synthetic and only comprised of the single man-made molecule THC, they fail to tap into the “entourage effect” which is what makes full spectrum (utilizing all components of the plant) cannabinoid therapy so successful. In 2016, the FDA approved the synthetic cannabis medication Syndros which is a liquid formulation of Marinol. Syndros is manufactured by Insys Therapeutics, and it is important to note that this pharmaceutical company is the same one that makes a fentanyl-based medication that is 50 times stronger than heroin, and spent nearly half a million dollars to successfully lobby against cannabis legislation in their home state of Arizona.
While the federal government maintains its criminalization of marijuana, states have taken matters into their own hands. Oregon was the first state to decriminalize cannabis as early as 1973. California was the first state to legalize medical cannabis in 1996. Many other states began to follow suit over the next two decades. In 2012, Colorado and Washington became the first two states to legalize cannabis for recreational use. Now, two-thirds of the United States have implemented some sort of cannabis legalization, and 64% of Americans support the legalization cannabis. In recent years, Congress has passed legislation that protects state’s right in regards to their cannabis laws. The Farm Bill, the Cole Amendment, and the Rohrabacher-Farr Amendment have all provided states with cannabis legislation a safety net under which to operate within their state laws without fear of Federal intervention. In January of 2018, just days after California dispensaries began selling cannabis for recreational use, Attorney General Jeff Sessions issued a memo to all states’ Attorneys General on Federal marijuana enforcement policies encouraging them to pursue prosecutions related to marijuana activities. While many Americans and cannabis patients feel threatened by this statement by Sessions, most Attorneys General in states with legal access vow to continue to support the will of the people.
Cannabis is still a controversial plant, as there will always be arguments on each side of the cannabis debate. It appears obvious, however, that political favoritism, perhaps driven and funded by pharmaceutical, petroleum, and other industries, has kept this plant out of the hands of American citizens for almost a century, but the tide is turning. States are beginning to see the financial benefit to legalization and patients are gaining access to an alternate source of medicine; it isbe only a matter of time before the Federal prohibition of pot becomes the regulation of cannabis.
“Decoding the Dose: Dose One”
by Emily McSherry
Originally published in the March 2017 issue of Fete Magazine
Cannabis has been used for its medicinal properties for thousands of years, but it is only in the past two decades that scientists have researched the plant enough to quantify its healing properties. The advancement of science has rewarded us with a society that expects precision. But, sometimes, estimation breeds success. It is the hypothesis that reaps results.
Last month I informed you of the numerous cannabis related bills floating around our state capitol. One of these bills, The Compassionate Care Act, is progressing through both the House and Senate subcommittees. Objections and concerns have been expressed by stakeholders and legislators. One concern repeated by several legislators is the fact that medical cannabis does not have a prescribed dose.
Welcome to Dosing 101.
Physicians who prescribe pharmaceutical medications are required to comply with regulations and requirements set forth by the Food and Drug Act, Controlled Drugs and Substances Act, Narcotics Safety and Awareness Act, and the Drug and Pharmacies Regulation Act. All of this is set forth to protect American citizens because, while drugs can be lifesaving, they can be very harmful. Yes, indeed, drugs are bad. Drugs are the leading cause of accidental death in this country. Over 100,000 people die each year in American due to improper drug use or drug overdose.
No one has ever died due to a cannabis overdose. Never. Not ever. Not once.
This powerfully simple fact makes the quodlibet for cannabis dosing irrelevant. We have become accustomed to being given exact dosages based on weight, genetic factors, and lifestyle habits. In many cases, dosing, while never perfect on a case by case basis, does provide panoptic success. This success is seen mostly in common ailments that are easily treated and cured. Where dosing requirements flounder is in rare, chronic, and debilitating conditions and diseases. These are often the ailments for which there is no cure.
I have epilepsy. There is no cure for epilepsy. Thankfully it is one of the conditions listed in the Compassionate Care Act (as well as in the Put Patients First Act). If this legislation were to be passed, a person with epilepsy would be able to receive a recommendation from their physician that would allow them to treat their condition with medical cannabis. As anyone with epilepsy will tell you, there is a trial and error sequence for finding the correct drug at the correct dose to control seizure activity. When you finally find the correct dose, your epilepsy changes and you are back to square one. This is known amongst epileptic patients as “The Medicine Game”. I have had four neurologists. Every time that my medicine would need to be adjusted, they would each say, “you know how it goes…play around with the dose in combination with your other medicines to see what works best for you. Be safe.”
You see, with debilitating conditions the idea of dosing is relative to the individual because you are looking for the dose that will afford you the highest-level quality of life with the lowest amount of side effects. You are not dosing for a cure. (Well, sometimes you are as with the case with cancer, but we will talk about that another time.)
It is impossible to predict which dose, strain, and delivery of cannabis will prove successful for each patient. The assessment of the efficacy of cannabinoid based medicine must be customized to the individual.
I hope you will enjoy me for next month’s article “Decoding the Dose: Dose Two” in which we will delve deeper into the dosing of cannabis.
Originally published in the February 2017 issue of Fete Magazine.
I never considered myself political. I usually shied away from such talk and kept my opinions to myself. Admittedly, I knew little about the political process other than the basics of voting and, thanks to ‘Schoolhouse Rock’ a little about how a bill becomes a law.
All that changed in 2014 when I discovered that cannabis controlled my seizures. And, as the phrase goes, “It was on like Donkey Kong.” I literally threw myself into the world of politics and very quickly discovered it to be rife with pubescent drama. There were over one dozen cannabis-related bills introduced during this past two-year session. One of the bills, S672, gained heavy momentum and was receiving favorable reports. And then the Gas Bill exploded. With sentimental behavior rivaling a sitcom drama written by Aaron Spelling, the legislature debated the gas bill with vicious intensity. We watched as the aggrieved Senators allowed the aftermath to spill into the debate of the medical cannabis bill. It failed to pass out of the Medical Affairs Committee.
With high hopes, patients across South Carolina waited for the 2017-18 session to begin. We were delivered a bombshell in late November: Nikki Haley had been nominated for a UN position. What does this have to do with cannabis legislation in South Carolina, you ask? Everything. If you want to have power in the state, you become a senator. If you want to have power in the senate, you become President Pro Tempore. The state constitution establishes that the President Pro-Tem is to fill the vacancy of lieutenant governor. Haley resigns and up bumps McMaster. Constitutionally, that would mean the next play would be Hugh Leatherman sliding into position as our Lt. Governor. But why would Leatherman want such a powerless position? And how would he continue to write contracts from the state benefitting his company, Florence Concrete, if he was ‘just’ the Lt. Governor? The well-coffered senate quickly started giving free rides on the carousel. Leatherman resigned his position. Kevin Bryant was elected to take his place, and 20 minutes later, was sworn in as Lt. Governor. To end the most recent episode of “As the World Turns”, Leatherman was then re-elected as President Pro Tempore of the Senate. Whew. I’m dizzy.
Obviously, this was not done without emotional impact. Alliances were broken and new ones were formed. Those that survived were strained. So, now we enter the new legislative session with as much drama as when we left.
Since the first day of session on the 10th of January, five bills regarding cannabis have been introduced: one senate bill and four house bills. Senate bill 212 (also known as the Compassionate Care Act) would establish a medical cannabis program in South Carolina. It has a companion bill that has been introduced in the house, HB 3521. The other bills that have been introduced to the House are The Put Patients First Act (H3128 which would also establish a medical cannabis program but would allow for home grow) sponsored by Todd Rutherford who is also sponsoring H3162 which would allow honorably discharged veterans the ability to possess up to 28 grams of cannabis with a VA doctor recommendation. Closing out the list of cannabis related legislation is House bill 3559 which would establish an industrial hemp industry in South Carolina.
That is a whole heck of a lot of cannabis related legislation in just a few weeks. I certainly hope the “good ol’ boys” can do what the law allows.
Homeostasis. That word is synesthetic for me. The sound of a system functioning in complete balance rings sweetly in my ears. Our bodies strive to achieve this equilibrium and, in fact, have numerous systems that function together in perfect harmony to maintain this constancy. One of those systems is the endocannabinoid system. And, yes, it pretty much means what you think it means, “the inside cannabis” system.
The endocannabinoid system was discovered in the mid-1990s by Israeli researcher Dr. Ralph Mechoulam who also identified THC as the main active ingredient in cannabis in the early 1960s  . This discovery followed earlier research in the late 80’s that identified receptor sites in the mammalian brain that respond pharmacologically to compounds in cannabis resin. So basically, your brain and your body is designed to work cohesively with the compounds found in cannabis. Lucky us.
The endocannabinoid system (ECS) effects all aspects of homeostasis including the endocrine system, the immune system, and the nervous system. Our bodies make endogenous cannabinoids that interact with the cannabinoid receptors. Three of the most heavily researched endocannabinoids are anandamide (AEA), 2-arachidonoylglycerol (2AG), and arachidonyl glyceryl ether (noladin ether). The two most heavily researched receptors are the CB1 receptors (which are primarily located on nerve cells in the brain, spinal cord, but they are also found in some peripheral organs and tissues such as the spleen, white blood cells, endocrine gland and parts of the reproductive, gastrointestinal and urinary tracts.) and the CB2 receptors (which are mainly found on white blood cells, in the tonsils and in the spleen.) These cannabinoids are produced on the cell membrane of the post synaptic cell and travel in retrograde across the synapse to interact with the receptor on the presynaptic nerve terminal. It helps to think of this as a “lock and key” mechanism. New research is also showing that non-CB receptor targets may exist for these receptor molecules such as transient receptor potential channels (TRPV1 and TRPM8), the peroxisome proliferator activated receptors (PPAR alpha and gamma), G protein-coupled orphan receptors (GRP55), certain ion channels (e.g. calcium channels), transmitter-gated ion channels (e.g. glycine receptors) and finally established non-cannabinoid G protein-coupled receptors (e.g. acetylcholine muscarinic receptors). These non-CB receptor targets implicate the endocannabinoids system’s role in the regulation of metabolism, cell differentiation, and inflammation.
The endocannabinoid system is so important to the proper functioning of the human body, that it is believed that many disorders and functional conditions could be due to an endocannabinoid deficiency.  These deficits are associated with a reduced ability to adapt to chronic stress resulting in autoimmune disease or an inflammatory disorder. An efficient ECS is vital to the very basics of life, beginning with reproduction. Blastocyst implantation into the endometrium requires suitable levels of anandamide. In other words, you need anandamide to begin life. Endocannabinoids are found in breast milk and it is believed that the transference of these cannabinoids from mother to baby is the reason why breastfeeding boosts the infant’s immune system and prevents colic. The ECS also regulates the activity of the immune system by suppressing the production of TH1 cytokines and increasing the production of TH2 cytokines. It also induces apoptosis in malignant cells of immune origin leading new approaches to treatment of certain cancers. Dr. Prakash Nagarkatti, the Vice President of Research at the University of South Carolina, believes that the endocannabinoid system’s regulation of the immune system is the reason why administration of Tetrahydrocannabinol is successful in the treatment of graft-versus-host disease (GVHD) in organ transplant recipients. The endocannabinoid system also plays a role in the regulation of connective tissues. Stimulation of the CB2 receptors leads to decreased osteoclast activity and increased osteoblast activity thus increasing bone formation. Cannabinoids prevent cartilage destruction and decrease connective tissue inflammation. The sympathetic and parasympathetic nervous systems are also effected by the endocannabinoid system. It dampens sympathetically mediated pain and, when activated by exogenous cannabinoids, it causes antinociceptive effects in acute pain, inflammatory pain, and neuropathic pain. In almost every system in the body, there is a direct impact by the functioning of the endocannabinoid system.
Exogenous cannabinoids effect the ECS in different ways unique to the individual compound found in the cannabis plant. Two of the most commonly researched phytocannabinoids are THC (Tetrahydrocannabinol) and CBD (Cannabidiol). THC mimics the activity of anadamide and 2-AG by acting as a partial agonist at the CB1 and CB2 receptor sites. While CBD shows a low affinity for these receptors, it does activiate 5-HT1A and TRPV-2 vanilloid receptors which is why it is effective at treating pain. CBD also inhibits uptake of dopamine, GABBA and AEA. Synthetic cannabinoids can also activate the endocannabinoid system; however, only THC is currently being synthesized resulting in the absence of the entourage effect when using whole plant therapies. In most cases, it is best to go real or go home.
Cannabis is still a Schedule One drug and is illegal on a federal level, however 26 states plus the District of Columbia have enacted legislation that provides for medical cannabis programs. Cannabis has been studied over the last few decades more so than most leading FDA-approved pharmaceutical drugs. More and more scientists, researchers, and physicians are calling for the rescheduling or descheduling of cannabis. The scientific revelations of the endocannabinoid system are the driving catalyst behind much of the reduction of stigma associated with cannabis use. Way to go, ENDO!
 The Discovery of the Endocannabinoid System, By Martin A. Lee
 The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance - See more at: http://press.endocrine.org/doi/full/10.1210/er.2005-0009#sthash.OwFGw0L0.dpuf
 Endocannabinoids and immune regulation, Rupal Pandey, Khalida Mousawy, Mitzi Nagarkatti, and Prakash Nagarkatti
 The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans, Komorowski J, Stepień H. https://www.ncbi.nlm.nih.gov/pubmed/17369778
 Cannabinoid Receptors By Dr Ananya Mandal, MD
 Cannabinoid Receptors By Dr. Ananya Mandal, MD
 Clinical Endocannabinoid Deficiency (CECD): Can this Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and other Treatment-Resistant Conditions? By Ethan B. Russo
 The endocannabinoid system during development: emphasis on perinatal events and delayed effects.
Fride E1, Gobshtis N, Dahan H, Weller A, Giuffrida A, Ben-Shabat S.
 The endocannabinoid system and cancer: therapeutic implication Josée Guindon and Andrea G Hohmann
 Targeting Cannabinoid Receptors as a Novel Approach in the Treatment of Graft-versus-Host Disease: Evidence from an Experimental Murine Model
Rupal Pandey, Venkatesh L. Hegde, Mitzi Nagarkatti, and Prakash S. Nagarkatti
 Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies Aymen I Idris
 Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes J Manzanares, MD Julian, and A Carrascosa
 Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes Luciano De Petrocellis, Alessia Ligresti, Aniello Schiano Moriello, Marco Allarà, Tiziana Bisogno, Stefania Petrosino, Colin G Stott, and Vincenzo Di Marzo