By Owen Smith

Criminal Trials or Clinical Trials

In the previous edition, I pursued the historical records of medical cannabis use around the world. For much of its documented medical history cannabis preparations and applications have taken advantage of simple processes that separate the active chemicals (cannabinoids and terpenes) from the plant bulk.

However, during the last 75 years of cannabis prohibition, this has changed dramatically. Underground markets reap enormous profits as cannabis use is now more widespread than ever. Doctors no longer educate about its proper uses, and the frivolous methods of recreational misuse proliferate in the media. The threat of criminal prosecution has created an environment that often forces cannabis producers to work in haste, secrecy, and isolation. These factors are anathema to the production of medicines that require quality control and standardization to ensure the safety of chronically ill people. This has effectively reduced the general knowledge of cannabis medicine to simple baked goods and high potency flower buds.

While operating in an unstable legal grey zone, clubs like the CBC of C have helped to deepen the understanding of medical cannabis products, while widening the possibilities for prospective patients. For four weeks in Feb., I sat in the front row of the Supreme Court of British Columbia to attend the Voir Dire (trial within a trial) of the charge “Possession for the purpose of trafficking THC.” I was caught in the act of making these products for the members of the CBC of C late in 2009. The arrest involved the seizure of cookies, lozenges, gel caps, and massage oils made with cannabis infused vegetable oils (see the CBC of C Recipe Book).1

These four weeks were our opportunity to challenge the constitutionality of the Marihuana Medical Access Regulations (MMAR) and make available, to those with access, medically suitable methods of ingestion alternative to inhalation, specifically oral and topical. In order to qualify the refinement process necessary for making these products, we attempted to explain in detail exactly where in the plant, the medicine that should be available to those in need, is.

Few people know that while “dried marihuana” can be authorized under the MMAR in Canada, any process that separates the medical compounds from the plant material is illegal: including sieve, colander, or cheesecloth. When an authorized MMAR patient, with their doctor, check a box on the B1 or B2 application form marked “Oral,” nowhere is this micron thin definition of illegal production made clear. To help clarify matters for the court, we invited Dr. David Pate from California to share his expert knowledge in Botany and Pharmaceutical Chemistry.

Dr. Pate explained that while the chemical precursors for the creation of cannabinoids are absorbed through the roots from the soil and are found throughout the plant, cannabinoids and terpenes are manufactured within the trichomes by a rosette of cells at the base of each trichome head. “The glandular trichomes […] are characterized by a secretory disc of one to 13 cells supported by a layer of stipe cells above a layer of base cells embedded in the epidermis. The secretory cells of mature glandular trichomes produce a resinous fluid which accumulates beneath a membranous sheath.” 2

The casing of the trichome is composed of a waxy cellulose that has no therapeutic value, other than acting as a container for the resin prior to and during the act of extraction into fat, alcohol, solvents, or fatty bodily fluids. Trichomes occur at various sizes and stages of maturity, in greater amounts nearer the top of the plant on the flowering buds. The Journal of Industrial Hemp of which Dr. Pate is a co-founder, provides a detailed passage on the chemical transformations that occur inside the trichome:

“These compounds appear to be produced beginning in specialized plastids called lipoplasts. These produce spheres of oily secretions, including terpenes, which pass through the cell membrane and wall to accumulate as vesicles in the secretory cavity. Final reaction to cannabinoids appears to occur outside the disk cell cytoplasm. The glands gradually darken as they mature, with loss of cannabinoids over time (perhaps to evaporation) and eventually undergo abscission from the plant.”3

For ease of reference Dr. Pate compared the trichome to a golf ball on a tee. At the base of the tee components required for the production of Cannabinoids are transported from the plant up the tee and are transformed as they enter the golf ball on top. The structure of the trichome with its thin neck makes it easy for the heads containing the resin compounds to fall off. Shaking the plant with ice or water over a screen will easily separate the trichomes from the plant, producing a form of dry hash.4

Dr. Pate explained that the dried plant matter may contain heavy metals, fertilizer residue, pesticides, moulds, and insect remnants. Plant matter is composed of non-digestible cellulose which, while not harmful, may be contra-indicated for persons with gastro-intestinal conditions. He explained that there are micro-abrasive silicified trichomes that act as the plant’s self defence against hungry animals. He concluded that the dried plant matter has no medical utility apart from being a vehicle to carry the medical compounds prior to and during smoke inhalation—the cellulose providing the fuel for the superheated ember at the end of a doobie.

Dr. Pate highlighted an important principle of therapeutic application: apply the medication as close to the source of the problem as possible. One example is if somebody has a skin lesion, an anti-biotic skin cream is preferable to an oral dose. Oral doses are appropriate for gastro-intestinal conditions as they coat the G.I. tract like an internal topical. Dose by inhalation is preferred for immediate relief from acute conditions. Appropriate application methods attempt to maximize desired effects and minimize undesired side effects, however many people have to tolerate the undesired side effects of a drug in exchange for the desired effects.

The undesired effects of cannabis range from mild to serious, but are transient, not permanent or fatal. The undesired effects for medical cannabis users are often the desired effects of recreational users. The reason for this safe profile is the absence cannabinoid receptors in the part of the brain that controls breathing. Often fatalities related to opiate based drugs like Morphine and Oxycodone are caused by respiratory depression during sleep. Isolated drug compounds are highly concentrated making overdose more likely. Natural plant based health products are diluted by a variety of other compounds, some of which induce effects counterproductive to overdose like vomiting, numbness, or in the case of cannabis, sleep.
Much testimony was given by members of the club as to the efficacy of edible and topical cannabis medicines in contrast to the inadequacy of the medications they had used before finding cannabis.

Dr. Pate’s extensive experience with laboratory research involves the “upstream” development of products with medical potential. Upstream development takes feedback from the patient and attempts to find evidence to support or refute the claims being made. For example, when a number of patients tell there doctor that topical cannabis is working for them, that substance could become the basis for laboratory research. Dr. Pate has conducted many laboratory studies that support the claims for medical cannabis and helped G.W. Pharmaceuticals develop the recently introduced oromucosal cannabis spray Sativex which succeeded laboratory testing and passed clinical trials.

Prohibition supporters are loathe to accept that cannabis has any medical uses because of the inherent illogic in something being harmful to society at large, but essential for those who are very ill. Health Canada’s expert scientist, Dr. Abramovici, stuck closely to this script, dodging with “I don’t know” or “I guess” when pressed for answers. He denied that anecdotal and laboratory research qualifies as scientific evidence wherever it supports cannabis’ safe profile, yet suggested the same kinds of research where a risk or harm was found. This fruitless and lopsided analysis from Health Canada’s senior scientific information officer appeared especially dubious when we discovered that the doctor’s superior at Health Canada had actually written his conclusions.

Dr. Abramovici continually expressed the need for “downstream” clinical trials for cannabis safety in the general population. Downstream development moves from producer to patient, involving human trials in clinical settings of substances that have shown success in “upstream” laboratory testing. Abramovici confirmed that the government has stopped all research into medical cannabis, and drug companies are the only groups with the resources to perform them. To complete the catch-22, Abramovici accused GW pharmaceuticals of having a bias and deemed the clinical studies they completed, with Dr. Pate’s assistance, scientifically invalid.

His only experience working with cannabis is in preparing the paper called Health Canada’s MMAR information for health care professionals,5 which is a literary review composed entirely of anecdotal and laboratory studies.

Dr. Abramovici’s testimony was marked by stark contradictions in opinion. Where at first he suggested that topically administered cannabis can cause “detectable levels” of THC in the blood stream (thus causing psycho-activity), he later claimed that there is no evidence that it is an effective method of delivering those same cannabinoids into the bloodstream. Ironically, a study from Abramovici and Health Canada’s MMAR information for health care professionals provided some clarity on the matter.

Studies measuring the nanogram per millilitre of THC in the bloodstream have shown that anywhere in the range of 7-29ng/mL is enough to produce the subjective “high” effect.6 A study on trans-dermal cannabinoid delivery found that after an hour and a half exposure blood plasma levels reached only 4.4ng/mL. This evidence supports the testimony of our members who find benefit from topical cannabis but experience no high effect. The consumption of a chocolate cookie containing 20 mg THC resulted in peak plasma THC concentrations ranging from 4.4 to 11 ng/mL,7 barely passing into the psychoactive range. Studies on very weak cannabis (1.6% THC) when smoked resulted in mean peak THC blood plasma levels of 77 ng/mL,8 approximately 10 times that of eating a cookie, and 20 times the topical administration.

Dr. Pate, through his expertise in pharmacodynamiks, the study of the action or effect of drugs on living organisms, explained that because topical cannabis only minimally passes through the skin into the bloodstream doesn’t mean it’s ineffective. Cannabinoid ligands, like THC, bind to specific receptor sites in our bodies. CB1 and CB2 receptors have been located in nerve fibres of the skin, skin cells (keratinocytes), cells of the hair follicles, sweat glands, and other cells present in the skin. “Abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists.”9

Dr. Abromovici shared his expertise in pharmacokinetics, the study of how drugs are absorbed, distributed, metabolized, and eliminated by the body. He emphasized that oral doses are absorbed slowly, creating a longer period before one feels the effects and opined that this would make it harder for individuals to self-moderate their doses. In his literary review, Abramovici states that smoking is preferred over oral because the psychotropic effect or “high” occurs more quickly. Abromiovici disregards that many patients use cannabis to help them to sleep, during which slow release is more logical than waking up once an hour to re-dose by inhalation.

Abramovici held that without placebo controlled clinical trials there is no evidence that cannabis taken orally is safe or even works at all. He suggested that oral cannabis undergoing first pass metabolism on its way to the colon breaks down so significantly that it is ineffective. The crown suggested that to avoid this loss of medicinal content patients should grind their cannabis, wrap it, and insert it in their rectum. While this is technically accurate, it’s insensitive to the point of absurdity.

During final arguments the Crown held the position that there would be no problem with making edible products so long as the leaf used remains with the liquid, so that an inspector could guarantee that the amounts being stored were within the personal use limits of an authorized person under the Marihuana Medical Access Regulations. This has the ridiculous implications of making what’s in the teapot legal, but not what’s poured into the teacup. The current system of limits and measurements used by Health Canada is not up to this task. I believe that licensing laboratories to test the contents and requiring licensed distributors to provide detailed labels are necessary steps toward resolving these concerns and improving the condition of medical cannabis in Canada.

Working for the CBC of C has been a heart opening experience. For the three and a half years I have been employed by the CBC of C, I have seen the product selection change and expand in response to the needs of the club’s members. I am overcome by the gratitude expressed by many of the 3000 club members for creating something so simple that nobody is legally allowed to make. The dedication of the staff, despite the constant threat of criminal prosecution, serves as an ongoing example of compassion and fellowship.
All people in need of medical cannabis are in the most unfortunate situations. Not only do they suffer from a permanent disability or disease, but they haven’t responded well to any of the currently available allopathic treatments. Hearing a patient’s experience going through a gauntlet of unwanted side-effects that accompanied their pharmaceutical medications—ranging from loss of contact with their families to loss of control over their bodily functions—one would need an iron heart to deny them this safe and reasonable option.

Fortunately on Fri. Apr. the 13, 2012, Justice Johnson agreed with us and found the law unconstitutional. Subsequent to his decision, patients in the MMAR program will lawfully be able to produce derivative cannabis products from their quantities of dried marijuana.

The decision was met by a statement from the B.C. Chief Medical Officer, Dr. Perry Kendall “By consuming cannabis in these ways, patients are able to avoid the negative health effects of smoking, which we know to be harmful to the lungs.” However, because “society’s interests in having the charges against Mr. Smith tried on their merits outweighs the violation of Mr. Smith’s liberty.”10

The judge did not throw out the charges against me, opening up the potential for another trial—this time with a jury. I anticipate most Canadians share Dr. Kendall’s common sense perspective.
I am very thankful for all of the support shown to me by individuals who see the value in our work at the CBC of C. Today, it feels like I have helped to unfetter the limb of an ancient healing God, perhaps Shiva with mortar, pestle, cloth, and cup preparing a draught of bhang,11 or that of Jesus and his apostles using the holy anointing oil on the skin of the sick, and I think there are good days ahead.

 

References

1 CBCoC Official Medical Cannabis Recipe Book <http://www.cbc-canada.ca/recipes/cbcoc-official-recipe-book>
2 R. Clarke 1981 Marijuana Botany: Propagation and Breeding of Distintive Cannabis. P.167

3 Paul G. Mahlberg and Eun Soo Kim (2004-06). “THC (tetrahydrocannibinol) accumulation in glands of Cannabis (Cannabaceae)”. Journal of Industrial Hemp 9 (1).

4 Dry Ice Hash from ACCTECH Seattle <http://www.cannacare.org/bulletin/showthread.php?p=46673>

5 MMAR information for healthcare professionals <http://www.hc-sc.gc.ca/dhp-mps/marihuana/how-comment/medpract/infoprof/index-eng.php>

6 Cone, E. J. and Huestis, M. A. (1993). Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage. Ther.Drug Monit. 15: 527-532. <http://www.ncbi.nlm.nih.gov/pubmed/8122288>

7 Ohlsson, A., Lindgren, J. E., Wahlen, A., Agurell, S. and others. (1980). Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin.Pharmacol.Ther. 28: 409-416. <http://www.ncbi.nlm.nih.gov/pubmed/6250760>

8 MMAR information for healthcare professionals, 2.2.1.1 Smoked cannabis <http://www.hc-sc.gc.ca/dhp-mps/marihuana/how-comment/medpract/infoprof/index-eng.php#a2_2_1>

9 Stander S, et al. J Dermatol Sci 2005;38(3):177-88.

10 Legal Ordeal not over in pot case, Times Colonist, April 14, 2012 <http://www.timescolonist.com/news/Legal+ordeal+over+case/6459567/story.html#ixzz1s4rLeV2t>

11 Chris Bennett, Cannabis and the Soma Solution, 2011. Back Cover <www.Forbiddenfruitpublishing.com>