The report begins with an important summary of the history of Cannabis:
Cannabis use for medicinal purposes dates back at least 3,000 years.[1–5] It was introduced into Western medicine in the 1840s by W.B. O’Shaughnessy, a surgeonwho learned of its medicinal properties while working in India for the British East Indies Company. Its use was promoted for reported analgesic, sedative, anti-inflammatory, antispasmodic, and anticonvulsant effects.
In 1937, the U.S. Treasury Department introduced the Marihuana Tax Act. This Act imposed a levy of $1 per ounce for medicinal use of Cannabis and $100 per ounce for recreational use. Physicians in the United States were the principal opponents of the Act. The American Medical Association (AMA) opposed the Act because physicians were required to pay a special tax for prescribing Cannabis, use special order forms to procure it, and keep special records concerning its professional use. In addition, the AMA believed that objective evidence that Cannabis was harmful was lacking and that passage of the Act would impede further research into its medicinal worth.[6] In 1942, Cannabis was removed from the U.S. Pharmacopoeia because of persistent concerns about its potential to cause harm.[2,3]
In 1951, Congress passed the Boggs Act, which for the first time, included Cannabis with narcoticdrugs. In 1970, with the passage of the Controlled Substances Act,marijuana was classified as a Schedule I drug. Drugs in this category are distinguished as having no accepted medicinal use. Other Schedule I substances include heroin, LSD, mescaline, methaqualone, and gamma-hydroxybutyrate.
Despite its designation as having no medicinal use, Cannabis was distributed to patients by the U.S. government on a case-by-case basis under the Compassionate Use Investigational New Drug program established in 1978. Distribution of Cannabis through this program was discontinued in 1992.[1–4] Although federal law prohibits the use of Cannabis, the table below lists the localities that permit its use for certain medical conditions.
The main psychoactive constituent of Cannabis was identified as delta-9-tetrahydrocannabinol (THC). In 1986, synthetic delta-9-THC in sesame oil was licensed and approved for the treatment of chemotherapy-associated nausea andvomiting under the generic name dronabinol. Clinical trials determined that dronabinol was as effective as or better than other antiemetic agents available at the time.[7] Dronabinol was also studied for its ability to stimulate weight gain in patients withAIDS in the late 1980s. Thus, the indications were expanded to include treatment of anorexia associated with human immunodeficiency virus infection in 1992. Clinical trial results showed no statistically significant weight gain, although patients reported an improvement in appetite.[8,9]
Within the past 20 years, the neurobiology of cannabinoids has been analyzed.[10–13] The first cannabinoid receptor, CB1, was identified in the brain in 1988. A second cannabinoid receptor, CB2, was identified in 1993. The highest concentration of CB2 receptors is located on B lymphocytes and natural killer cells, suggesting a possible role in immunity. Endogenous cannabinoids (endocannabinoids) have been identified and appear to have a role in pain modulation, control of movement, feeding behavior, and memory.[11]
Cannabinoids are a group of 21-carbon–containing terpenophenolic compoundsproduced uniquely by Cannabis sativa and Cannabis indica species.[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biologic activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to havesignificant analgesic and anti-inflammatoryactivity without the psychoactive effect (high) of delta-9-THC.The report then goes on to outline several key potential benefits of cannabis that should be noted in the race for a cure for cancer, and also in the debate to further legalize cannabis in the United States.
Cannabis protects against cancer:
One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.” They continue; “Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis. One review summarizes the molecular mechanisms of action of cannabinoids as antitumor agents. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.
Cannabis targets and kills lung cancer and breast cancer cells:
An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor–positiveand estrogen receptor–negative breast cancer cell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic,mammary cells.
In addition, both plant-derived and endogenous cannabinoids have been studied for anti-inflammatory effects. A mouse study demonstrated that endogenous cannabinoid system signaling is likely to provide intrinsic protection against colonic inflammation.[23] As a result, a hypothesis that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer has been developed.[24–27]
CBD may also enhance uptake of cytotoxic drugs into malignant cells. Activation of the transient receptor potential vanilloid type 2 (TRPV2) has been shown to inhibit proliferation of human glioblastoma multiforme cells and overcome resistance to the chemotherapy agent carmustine.[28] In an in vitro model, CBD increased TRPV2 activation and increased uptake of cytotoxic drugs, leading to apoptosis of glioma cells without affecting normal human astrocytes. This suggests that coadministration of CBD with cytotoxic agents may increase drug uptake and potentiate cell death in human glioma cells.
Many animal studies have previously demonstrated that delta-9-THC and other cannabinoids have a stimulatory effect on appetite and increase food intake. It is believed that the endogenous cannabinoid system may serve as a regulator of feeding behavior. The endogenous cannabinoid anandamide potently enhances appetite in mice.[29] Moreover, CB1receptors in the hypothalamus may be involved in the motivational or reward aspects of eating.[30]
Cannabinoids may also contribute to pain modulation through an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cellreceptors to attenuate the release of inflammatory agents, such as histamine andserotonin, and on keratinocytes to enhance the release of analgesic opioids has been described.[34–36] One study reported that the efficacy of synthetic CB1- and CB2-receptor agonists were comparable with the efficacy of morphine in a murine model of tumor pain.[37]
As the report states, “cannabis has been used for medicinal purposes for thousands of years,” and only recently has it been targeted for prohibition. At a time when cancer is now the leading cause of death of children and cancer rates are climbing for everyone, those without safe access to medical cannabis absolutely deserve the right to add this to their medicine cabinet if they so choose.
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