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Introduction
Over the past several years, the politics and science of marijuana have been making headline news. Marijuana is categorized as a Schedule I drug by the Drug Enforcement Agency (DEA) under the Controlled Substances Act. As such, marijuana is described by the DEA as follows:
Schedule I drugs are classified as having a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use of the drug or other substance under medical supervision.1
Despite the federal government's views on marijuana, many states have pushed through legislation making marijuana available for medicinal purposes.2 These states have established laws that work to provide patients access to medical marijuana and to protect the doctors who recommend it. It should be noted that physicians do not write prescriptions for marijuana but make professional recommendations based on the patient's diagnosis and the scientific literature supporting marijuana's medicinal benefits.3
Recent changes in laws, such as the legalization of marijuana in Colorado and Washington, now allow for recreational use by decriminalizing possession of small amounts of marijuana.4 This further normalizes use and reduces the stigma and difficulty in filling medicinal cannabis prescriptions. The CNN-produced documentaries Weed and Weed2 feature Dr. Sanjay Gupta and the reversal of his position against marijuana.5 Gupta now recognizes the medical benefits of cannabis. The position of this well-known, mainstream physician and neurosurgeon echoes the shift in attitude throughout much of the US medical population and highlights the politics of pot. Physicians and patients are asking politicians and lawmakers to stand down and allow the safe prescription of medicinal cannabis and productive, impartial research to continue. Pharmaceutical companies, such as GW Pharmaceuticals in England, are advancing production, testing, and standardization. Marijuana collectives are compiling comprehensive patient outcomes from quality-of-life surveys.6,7
Understanding Cannabinoids:
Going beyond THC
The general public is for the most part familiar with tetrahydrocannabinol (THC) and its psychoactive qualities (euphoria, sedation, and appetite stimulation). Research is now blossoming around a lesser-known cannabinoid, cannabidiol, which is related to THC but does not share its psychoactive aspects.8 Cannabidiol, known by its chemical compound identifier, CBD, is present in the cannabis plant and has a wide spectrum of therapeutic abilities. Cannabidiol contains anti-inflammatory properties; has antiproliferative/anticancer effects; and can act as an antispasmodic, antimicrobial, and antipsychotic agent. Other properties include the capacity to function as a bone stimulant, a neuroprotective agent, and a vascular relaxant. Cannabidiol has also demonstrated effectiveness as a stabilizer for blood sugars, providing a potential therapy in the treatment of diabetes.9
Cannabidiol (CBD) is one of at least 60 active cannabinoids identified in the cannabis plant. It is a major constituent of the plant, accounting for up to 40% of the plant's extract, as a nonpsychotropic phytocannabinoid.10 CBD is considered to have a wider scope of medical applications than THC. An orally administered liquid containing CBD has received orphan drug status in the US, for use as a treatment for Dravet syndrome, which causes a seizure disorder in children, under the brand name, Epidiolex.11
Both THC and CBD have antinausea, neuroprotective, antianxiety, anti-inflammatory, and antiproliferative effects. These properties have been of great benefit to patients suffering from cancer and HIV.12
This once-maligned weed's medicinal effects may prove to be paradigm shifting over the next 5 to 10 years as more data are gathered and research completed. With more medical uses, an emphasis on cultivating high CBD cannabis is increasing.
Studies, Science, and Testimonials
Studies
Researchersare testing cannabinoids as a new family of antitumoral agents. Research by Arkaitz Carracedo, Meritxell Gironella, Mar Lorente, et al. is focused on pancreatic adenocarcinomas. Pancreatic adenocarcinomas are among the most malignantforms of cancer. It is of special interest to researchers to set new strategies aimed at improving the prognosis of this deadly disease. This study indicates that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue.13 Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) upregulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Findings indicate that cannabinoids induce apoptosis of pancreatic tumor cell lines in vitro and exert a remarkable growth-inhibiting effect in models of pancreatic cancer in vivo. The stress-regulated protein p8 is involved in THC-induced apoptosis of pancreatic tumor cells. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes.
Science
Laboratory analysis, along with ongoing research taking place around the world, is helping us to better understand medical cannabis and the therapeutic effects of the various chemical compounds in cannabis. Understanding medicinal cannabis begins with the examination of the chemical compounds, in particular cannabinoids and terpenoids. The available chemical compounds change with how the plant is processed and administered. Potential therapeutic benefits will vary if the cannabis is processed/administered in raw (unheated), heated, or aged (degraded) form. Results also alter with the presence or absence of cannabinoid combinations. The diverse compounds in cannabis appear to modulate each other in synergistic or antagonistic ways. The California-based cannabis collective Elemental Wellness cites that the cannabinoid CBD lessens to some degree the psychotropic effects of the cannabinoid THC; however, the terpinoid a-pinene synergizes the bronchodilator effects of THC. The complexity of these chemical interactions means that medical cannabis would be best viewed as an herbal medicine, with sensitive interactions modifying the therapeutic effects as well as potential side effects. Beyond preparation and compounding considerations are the many varieties of cannabis, which includes a broad scope of variance in chemical composition. The situation is indeed challenging from the perspective of standardizing treatment.
In response to the mounting evidence and constant flow of scientific and antidotal reports, Steep Hill Halent Labs are systematically testing and publishing current information with Elemental Wellness. The collective offers educational material to its members, staff, and community physicians with the goal of educating those seeking objective input with latest scientific concepts and understanding of medical cannabis so that we may better benefit from its diverse medicinal properties. Their findings are published at www.steephillhalent.com/resources.
Testimonial Accounts
The highly publicized video Run from the Cure documents a cancer sufferer in Canada, Rick Simpson, who used an extract of cannabis to successfully treat his mesothelioma and who created Phoenix Tears, a high-potency cannabis oil treatment that many patients are taking into their own hands to manufacture and administer as a last resort for terminal cancer and other life-threatening diseases.14,15
Patients have been known to use raw cannabis as an ingredient in juices and smoothies. Unlike cooked cannabis products, raw cannabis does not appear to activate the THC compound, allowing for medicinal properties to be isolated without any psychoactive effects. There is an emerging groundswell of patient self-care filling the gap between doctors' ability to prescribe, lagging legal formulas, politics, and patients' needs.
Cannabidiol can be used along with traditional cancer care in the treatment of side effects brought on by chemotherapy and radiation. Both THC and CBD have antinausea, neuroprotective, antianxiety, anti-inflammatory, and antiproliferative effects.16 These characteristics may play an important role in helping patients endure some of the hardships faced during treatment.
Cannabis is now being referred to as a "pharmaceutical treasure trove." Active practitioners are using science to inform and instruct for the optimal utilization. Efficient and effective treatment is the underlying motivation in bringing this ancient herbal medicine into treatment modalities that reduce suffering, indicate curative properties, and can be safely combined with other therapies.
Partial List of Commonly Recognized Cannabinoids and Their Chemical Element
Abbreviations17
CBGA Cannabigerolic acid
CBGVA Cannabigerivarinic acid
CBG Cannabigerol
CBGV Cannabigerivarin
THCA Tetrahydrocannabinolic acid
THCVA Tetrahydrocannabivarinic acid
THC Tetrahydrocannabivarin
THCV Cannabinolic acid
CBN Cannabinol
CBDA Cannabidiolic acid
CBDVA Cannabidivaric acid
CBD Cannabidiol
CBDV Cannabidivarin
CBCA Cannabichromic acid
CBCA Cannabichromivaric acid
CBC Cannabichromene
CBCV Cannabichromivarin
CBLA Cannabicyclol acid
CBL Cannabicyclol
Cannabinoids in the Cancer Patient
The specific applications for the cannabinoids in the cancer patient may include18:
1. antiproliferation
2. antiemetic
3. neuroprotection (i.e., for patients on platin-containing drugs)
4. anti-inflammation
5. analgesic
6. bone stimulation
Six cannabis compounds have been documented to act as antiproliferative agents, reducing cancer cell growth: THCA, CBDA, CBD, CBC, CBG, and THC.19
Medical marijuana testing and use as a nausea suppressant and appetite stimulant has been around since the 1970s. As early as 2003, GW Pharmaceuticals and Bayer AG were looking toward a safer alternative to smoking cannabis and with a mechanism that allowed for the quantifiable administration of cannabinoids.20 They developed a medicinal cannabis extract known as Sativex, which contains THC and CBD; it is administered by spraying it into the mouth. This drug is now legal in Canada under the name Nabiximols (USAN, trade name Sativex). This aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC. In 2005 Nabiximols was approved by Canadian authorities to alleviate pain associated with multiple sclerosis.21
Major laboratories are deeply involved in the pharmacokinetics of cannabis, yet in the US the results and formulas are often not readily available to practitioners today.22 As the medical market develops, and more growers demonstrate their capacities to produce and reproduce cannabis strains with consistent cannabinoid profiles, a registry and further quantification of cannabinoids may become more accessible for treatment.23
Here are some of the pharmaceutical cancer treatment applications that contain cannabinoids or their extracts approved or in the approval process today.
Drugs That Contain Chemicals Taken Directly from the Marijuana Plant24
Sativex
Manufacturer: GW Pharmaceuticals (GWPH on NASDAQ)
Sativex oral spray
Source: "Medical Marijuana aka Sativex Now Available in UK." examiner.com. June 19, 2010.
Cannabis-related properties:Mouth spray whose chemical compound is derived from natural extracts of the cannabis plant. Sativex contains two cannabinoids: THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol).
Suggested medical use: Treatment of neuropathic pain and spasticity in patients with multiple sclerosis (MS); analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain.
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