Cannabis and Cancer
Cannabis and Cancer
Cannabis and Cancer – In the last 15 years there has been a major shift in the laws governing medical use of cannabis in the United States. Corresponding with this change there has been escalating interest in the role that cannabis, commonly referred to as marijuana, and cannabinoids play in the care of patients with cancer. This review will examine cannabis’ and cannabinoids’ current and potential roles in cancer care. Specifically, we will examine five areas of cannabis medicine: (1) pharmacologic properties of cannabis; (2) its potential role in the development of human cancers, particularly smoking-related malignancies; (3) cannabinoids’ potential as anti-cancer therapies; (4) cannabis and cannabinoids in the palliation of common cancer-associated symptoms; (5) current legal status of cannabis for medical purposes in the United States.
Cannabis and Cancer –Cannabis, commonly known as marijuana, is a natural product derived from the Cannabis sativa plant. The psychoactive properties of its active ingredients, cannabinoids, have led to its use for religious and medicinal purposes for thousands of years. Increasingly, cancer care professionals are expected to answer questions from patients and other health care providers on the role of cannabis and cannabinoids in clinical practice, often with little more information than the National Cancer Institute’s PDQ® on cannabis and cannabinoids . This review will explore the intersection of cannabis, synthetic cannabinoids, and cancer in the United States (US). We will examine the pharmacologic properties of cannabis and cannabinoids, the role that cannabis may play in cancer development and symptom palliation, as well as its potential as an anti-cancer therapy. Finally we will review the current legal status of medical cannabis in the United States. The epidemiology and non-cancer related effects of cannabis use have recently been reviewed elsewhere and will not be addressed here .
Cannabis and Cancer – Pharmacology of cannabinoids
Cannabis and Cancer – Cannabinoids are divided into phytocannabinoids, endogenous endocannabinoids, and synthetic cannabinoids. More than 60 phytocannabinoids have been identified within the cannabis plant . The primary phytocannabinoid responsible for cannabis’ psychoactive and physiological effects is Δ9-tetrahydrocannabinol (THC) . Cannabinoids mediate their actions through cannabinoids receptor type 1 (CB1) and CB2, two G-coupled receptors in the endocannabinoid signaling system. Activation of either receptor leads to the inhibition of adenylate cyclase, decreased the production of cyclic adenosine monophosphate (cAMP), and activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways [, ]. CB1 receptors are found predominantly in the central and peripheral nervous systems and suppress neuronal excitability and transmitter release, leading to hypothermia, sedation, euphoria, and altered mental status . CB2 receptors are found in higher concentrations in immune tissues and may modulate the immune system via cytokine release. They are not related to psychoactive effects . CB1 and CB2 are reviewed extensively elsewhere [, ]. Cannabidiol (CBD), another phytocannabinoid, can also exert anti-inflammatory effects by activation of transient receptor potential vanillin (TRPV) channel proteins and inhibiting cyclooxygenase enzymes 1 and 2 (COX-1/2) [, ].
Cannabis and Cancer – Inhalation and oral ingestion are the most common routes of administration for natural and synthetic cannabis products but rectal, sublingual, transdermal, ophthalmic, intrathecal, and intravenous routes have also been developed. Concentrations of THC in natural cannabis preparations can vary significantly based on a number of factors including the plant variety, type of preparation (hash oil > hash > sinsemilla [seedless plant] > smoked or ingested leaves and flowers) and cultivation technique. There is evidence that cannabis’ potency has doubled in the US and abroad since the 1980s [, ]. Dronabinol (Marinol™), a synthetic THC, and nabilone (Cesamet™), a synthetic THC-mimetic, are FDA-approved cannabinoids. Nabiximols (Sativex™) is an oromucosal spray containing THC and cannabidiol extract approved in Canada and the United Kingdom that is currently undergoing clinical testing in the US and Europe.
Cannabis and Cancer – THC’s pharmacologic parameters vary based upon the delivery form. THC is highly protein-bound in the blood but the steady-state volume of distribution is large (approximately 10 L/kg) due to its lipophilicity . THC’s half-life (t1/2) is variable based on the route of administration and dose but can be generally characterized by an initial t1/2 of 3–4 h, followed by a terminal t1/2 of 25–36 h with low levels of drug being eliminated over a longer period of time due to its large volume of distribution . Vaporized cannabis has a similar pharmacokinetic profile to smoked cannabis but with less carbon monoxide exposure . THC is primarily metabolized in the liver by the CYP2C subfamily and is eliminated predominantly in the feces and less in the urine. 11-OH-THC is the principal metabolite formed when THC is ingested by mouth . Detectable levels of THC can be found in the urine for up to 12 days after use due to extensive enterohepatic recirculation of metabolites; however, this period could be longer for regular users .