“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
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 Cannabinoid Receptors as Target for Treatment of Osteoporosis: A Tale of Two Therapies Aymen I Idris
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