First and foremost, we are not legal scholars or attorneys and the following should not be considered advice or recommendations. We strongly suggest you seek the advice from legal professionals or your local medical professional. The responsibility for any use of the following information, or for proper medical treatment, rests with you.
PART ONE of THREE PARTS on Cannabis, CBD and Low THC Oil.
Historical references to marijuana date back to the Chinese in 1500 BC. Ancient references indicate that the substance was also widely used by the Egyptians and Greeks during antiquity. Documents dating to the early 1600's provide evidence that marijuana was brought to North America by the Jamestown settlers. The continued use of cannabis led to the addition of marijuana to the US pharmacopeia in 1850 and the passage of a marijuana tax act in 1937. However, increasing concerns about its usage such as shown in the 1936 classic film “Reefer Madness”, led to the removal of marijuana from US pharmacopeia in 1942. Subsequent legislation including both the Boggs Act of 1952 and Narcotics Control Act of 1956 lead to the criminalization of marijuana possession.
Although the psychoactive effects of marijuana have long been known, the active agent in cannabis, Delta-9 tetrahydrocannabinoid, or THC, was not isolated until the mid-1960s. Twenty to twenty five years later, cannabinoid receptors in the body, CB1 and CB2, were identified along with the endogenous (naturally occurring substances) cannabinoids. In 1996, California became the first state to legalize medicinal marijuana and in 2012, Colorado became the first state to legalize its recreational use. On April 16, 2015, Haleigh's Hope act was signed into law by Governor Nathan Deal in the state of Georgia making it the first state in the union to allow the use of medicinal marijuana in 8 specific diseases, one of which is mitochondrial disease patients.
Because of its classification as a schedule one substance, defined as a substance "with no currently accepted medical use and a high potential for abuse... with potentially severe psychological or physical dependence" very little research regarding cannabis has been completed in the United States. As such, most of the information available comes from the Israeli and European medical communities.
So, what do we know? Cannabinoid receptors are embedded within cell membranes throughout the body. When these receptors are stimulated, a variety of physiologic processes ensue. CB1 receptors are predominantly found in the central nervous system, connective tissue, gonads, glands and organs. CB2 receptors are primarily located in the immune system and its associated structures.
Endocannabinoids are the substances our bodies make naturally to stimulate these receptors. The two most well understood of these molecules are called anandamide and 2-arachidonoylglycerol.
Although we now recognize that our bodies have specific receptors for cannabinoids and produce naturally occurring substances such as anandamide, it is a variety of derivatives found in cannabis plants that are of primary focus for both recreational and medicinal purposes. Phytocannabinoids are the plant substances found in the three main species of cannabis plants, (Sativa, Indica, and Hybrid) that are known to stimulate cannabinoid receptors. There are over 80 known cannabinoids including Delta-9-tetrahydrocannabinoid, or THC, the most psychoactive and best known of these substances. Despite its psychoactive properties, THC has also been used medicinally as a:
A derivative of THC, Tetrahydrocannabinolic Acid, or THCa, is a non psychoactive form of THC utilized for its anti-inflammatory, antiproliferative and antispasmodic effects. In addition to THC and THCa, many of the other cannabinoids found in the cannabis plant are also deemed therapeutic. Among those most effective and utilized for medicinal purposes specifically are cannabidiol or CBD, cannabidiolic acid or CBDa, Cannabigerol or CBG, a precursor to CBD and THC and Cannibinol or CBN. Although these other cannabinoids have little or no psycho active properties, they all provide a number of other effects.
Currently, THC, THCa and CBD are the most widely used cannabinoids for medicinal purposes. Utilized in the past for pain control specifically, THC was previously the most popular cannabinoid. However, since CBD has been linked to improved seizure control without associated psychoactive effects it has been the focus of increased efforts by the medical and patient communities to improve epilepsy management, particularly those poorly controlled by typical anticonvulsant therapy.
At the annual American Academy of Neurology, or AAN, meeting held in Washington DC this week, the results of a study investigating the efficacy of cannabis therapy in 213 children and adults with 12 different forms of severe epilepsy including Dravet syndrome and Lennox-Gastaut (both associated with intellectual disability and lifelong seizures) treated with a liquid form of CBD daily for 12 weeks were presented.
Among the 137 patients who completed the study, the number of seizures fell by an average of 54% according to the principal investigator. Convulsive seizures fell by 53% in the 23 participating patients with Dravet syndrome and 11 patients with Lennox-Gastaut syndrome had a 55% decline in "atonic “seizures which cause a sudden loss of muscle tone.
Due to intolerance issues, 12 patients discontinued the cannabis citing drowsiness (21 percent), diarrhea (17 percent), fatigue (17 percent) and decreased appetite (16 percent) as the leading side effects.
While additional studies are needed, many experts are calling the findings reported at the AAN, "very exciting". Prior to this study, most reports have been anecdotal although the state of Colorado has earmarked about $8,000,000 for several studies investigating the medical efficacy of cannabis. Although ongoing studies are clearly needed to legalize and standardize cannabis use, personal correspondence with families receiving medical cannabis in Colorado note that 85%-90% of patients/families report improvement in (primarily) seizure control over previous baseline.
In our personal experience of one patient with Leigh disease and a progressive encephalopathy, using a cannabis oil including CBD, THC and THCa for intractable seizures and pain, the child showed a marked improvement in seizure control from 12 seizures per day to 1-4 daily, most often 3-4. His muscle pain also decreased by 60%-70% resulting in a complete elimination of morphine use from 2-3 times per month for severe episodic pain. Of note, though, his parents do use a THC topical cream in addition to the oil for any signs of breakthrough episodic pain. This patient also experienced increased awareness, improved demeanor and eye tracking, and increased vocalizations.
Although current data on the use of cannabis in mitochondrial patients is primarily anecdotal it appears that it provides symptomatic relief with improved seizure control and pain relief in treated individuals as seen with our one patient. Some patients also report that it provides relief of gastrointestinal symptoms as well. However, in a recent German study, researchers showed that exposure to cannabis can improve mitochondrial function in rodent models. This study is suggesting that marijuana (or the activation of the brain's cannabinoid system) triggers the release of antioxidants, which act as a cleansing mechanism. This process is known to remove damaged cells and improve the efficiency of mitochondria.
These discoveries shed new insight on how natural marijuana cannabinoids hold the capacity to literally kill the brain inflammation responsible for causing cognitive decline, neural failure, and brain degeneration. The authors postulate that by supplying these receptor sites with cannabinoids, patients may be able to overcome brain conditions like Alzheimer's disease, Parkinson's disease, Huntington's disease, and more, not to mention premature brain aging. Certainly, mitochondrial disease, particularly the subset associated with neurodegenerative symptoms, would also fall into this basket and may benefit more broadly with the use of cannabis compounds.
Dosing of cannabis is based on a given patient's weight and the type of cannabinoid to be used and is typically administered at least several times a day. Although some individuals experience mild side effects to include drowsiness and fatigue, agitation and diarrhea, similar findings reported recently in the study presented at the AAN, 10% of patients on high dose THC can experience seizures. Despite this rare but serious complication, cannabis is considered safe and annual death statistics reported by the CDC in 2013 notes no deaths associated with the use of cannabinoids. The safety of cannabis was emphasized in a statement by the National Cancer Institute "Because cannabinoid receptors, unlike opioid receptors, are not located in the brainstem areas controlling respiration, lethal overdoses from Cannabis and cannabinoids do not occur".
Cannabinoids can be administered in a number of delivery systems depending on the product and purpose of the medication. These mechanisms of administration include smoking, dabbing, edibles, oils (olive, MCT/coconut, safflower), tinctures (alcohol and vegetable glycerin), and topicals in the form of a patch, gel, salve/cream.
In summary, cannabis and various cannabinoids have medicinal effects for a broad range of clinical symptoms and disorders as supported by both anecdotal reports and a recent study presented at the AAN meeting in Washington DC this past week. While additional studies are needed, the results are promising and increased availability will likely lead to improved quality of life for many patients, including those with mitochondrial disease. Stay tuned for ongoing discussion and reports in our patient population.
Coming next week.... legalities of cannabis.
Fran Kendall, M.D.
This post is not meant to be a recommendation or a substitute for professional advice and services rendered by qualified doctors, allied medical personnel, and other professional services. The responsibility for any use of this information, or for proper medical treatment, rests with you.