As oncologists, we treat patients who have devastating diagnoses with potent therapies. Hence, we demand solid evidence before recommending any intervention. Unfortunately, when it comes to supporting the use of cannabis in clinical situations, we are frustrated by a dearth of convincing evidence. Data from gold-standard prospective randomized controlled clinical trials are virtually nonexistent. One reason for this is that the only legal source of cannabis for research in the United States is the National Institute on Drug Abuse (NIDA). NIDA has a congressional mandate to study substances of abuse only as substances of abuse and not as therapeutic interventions. Although NIDA can supply cannabis for clinical trials to assess its effectiveness, funding must come from elsewhere. However, in this era of gene therapy and nanotechnology, few investigators are interested in studying this ancient botanical medicine. In addition, just as cancer is many diseases, cannabis is many different strains, so standardization of cannabis medicine is a challenge.
How Has Medical Cannabis Been Utilized in Clinical Practice?
International Association for Cannabinoid Medicines (IACM)
NCI PDQ CAM Cannabis and Cannabinoids (www.cancer.gov/about- cancer/treatment/cam/hp/ cannabis-pdq)
Patients Out of Time
Society of Cannabis Clinicians (http://cannabisclinicians. org/)
The Canadian Consortium for the Investigation of Cannabinoids (www.ccic.net)
University of California Center for Medicinal Cannabis Research (www.cmcr.ucsd.edu)
Cannabis Pharmacy: The Practical Guide to Medical Marijuana
Stoned: A Doctor’s Case for Medical Marijuana
The Pot Book: A Complete Guide to Cannabis - Its Role in Medicine, Politics, Science, and Culture
Handbook of Cannabis
Marijuana Gateway to Health: How Cannabis Protects Us from Cancer and Alzheimer’s Disease
Delta-9-tetrahydrocannabinol (THC) is the most psychoactive of the 100 or so of the plant’s 21-carbon–containing terpenophenolic compounds known as cannabinoids. A number of other cannabinoids are thought to have medicinal benefit as well. Cannabidiol (CBD), for example, is believed to be analgesic and anti-inflammatory but is not psychoactive. THC has been available as a licensed medicine in the United States since 1986, when dronabinol was approved for the treatment of chemotherapy-induced nausea and vomiting (CINV). The indication was expanded in 1992 to include treatment of anorexia associated with the AIDS wasting syndrome. Nabilone is another synthetic THC that became available in the United States in 2006 for the treatment of nausea and vomiting. Nabiximols is a whole plant extract delivered as an oromucosal spray that contains THC and CBD in a 1:1 ratio.[3-5] Nabiximols is approved in most of the European Union and Canada and continues to undergo clinical trials in the United States. Most of the available published research on the use of cannabis-based medicines involves these pharmaceutical agents, as studying the whole plant has been difficult, based on the reasons stated previously.
Dronabinol was approved 30 years ago for the treatment of CINV, and as such, it would stand to reason that the parent compound might also have activity for this indication. Again, most of the trial-generated data come from evaluation of the licensed pharmaceuticals and not the botanical itself. Only three trials have investigated cannabis, and in two of those trials the cannabis was only made available after dronabinol had failed.[6-8] Data from systematic reviews are generally more supportive of a benefit from cannabinoids.[9-12] My clinical experience as an oncologist practicing in San Francisco for 35 years is that cannabis is an effective antiemetic, even in situations where other pharmaceuticals have failed. Many patients choose cannabis over serotonin antagonists in hopes of avoiding the troublesome constipation often associated with those medications. Cannabis is also the only antiemetic that is an appetite stimulant. However, no clinical trials have been conducted to date evaluating the effect of the botanical therapy on cancer-related anorexia/cachexia syndrome. A trial of dronabinol found enhanced chemosensory perception of food in the treatment group compared with placebo, but larger studies with appetite and weight change endpoints were not impressive. Nonetheless, patients employing cannabis in clinical practice often benefit from its orexigenic effect.
Our bodies have an intricate system of cannabinoid receptors and endogenous cannabinoids, known as endocannabinoids. It has been postulated that the function of this system is to help us to process pain. Cannabis-based medicines have been tested in a number of pain models, and recent meta-analyses and systematic reviews suggest that they are beneficial in patients with chronic pain syndromes.[12,15,16] Patients with cancer pain as well as neuropathic pain from a number of causes have been included in these reviews. There is a convincing body of evidence showing cannabis itself is effective in a number of neuropathic pain syndromes, and cannabinoids seem to be able to treat, as well as prevent, chemotherapy-induced peripheral neuropathy caused by vinca alkaloids, platinums, and taxanes in rodent models; however, only one small study of nabiximols has been published investigating this indication. In the 16-patient placebo-controlled crossover trial, 5 responders reported a greater than 2-point decrease in their pain on a 0 to 10 numeric rating scale. Hence, further clinical trials of cannabis-based therapies in chemotherapy-induced peripheral neuropathy are warranted.
In animal models, cannabinoids appear to be synergistic with opioids in producing analgesia. Based on these preclinical observations, we conducted a small pharmacokinetic interaction study. Although we saw no effect on plasma concentration of morphine or oxycodone when adding vaporized cannabis to steady-state dosages of sustained-release preparations, we did appreciate synergistic pain relief, although the study was too small to make a definitive statement about a pain endpoint. That said, in my clinical practice I have seen many patients decrease their dose of narcotics or wean off them altogether with the addition of cannabis to their regimen. Pain relief, with or without opiates, is another area where cannabis may be quite useful. In a number of the published pain studies, medicinal cannabis has also been reported to be effective in improving sleep quality. Patients report that CBD-rich products may be particularly effective for insomnia.
Investigators at the National Cancer Institute first published results of in vitro and animal studies demonstrating the inhibitory effects of cannabinoids—delta-9-THC, delta-8-THC, and CBD—on cancer cell growth and proliferation. This line of research subsequently moved to Spain and Italy, where an increasing body of preclinical evidence has been accumulating that confirms the early observations.[1,2,22-27] Internet testimonials abound from patients claiming to have cured their cancer by using highly concentrated oil extractions of cannabis, enriched for THC, CBD, or both. These reports have generated an interest in some patients to forego conventional cancer therapies and to treat their cancer with cannabis oil alone. This is a distressing situation, especially when faced with a patient with a potentially curable malignancy who chooses to go down this alternative pathway. As yet, there have been no clinical trials investigating highly concentrated cannabis products as anticancer agents, so patients must be reminded that what is observed in the test tube or animal models does not necessarily translate into benefit in humans.
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