The intersection between cannabis and cancer in the United States
Introduction
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 [1]. 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 [2].
Section snippets
Pharmacology of cannabinoids
Cannabinoids are divided into phytocannabinoids, endogenous endocannabinoids, and synthetic cannabinoids. More than 60 phytocannabinoids have been identified within the cannabis plant [3]. The primary phytocannabinoid responsible for cannabis’ psychoactive and physiological effects is Δ9-tetrahydrocannabinol (THC) [3]. Cannabinoids mediate their actions through cannabinoids receptor type 1 (CB1) and CB2, two G-coupled receptors in the endocannabinoid signaling system. Activation of either
Cannabinoids and cancer development
One of the principle concerns over the medical use of cannabinoids, particularly inhaled cannabis, is their carcinogenic potential. There is little direct evidence that THC or other cannabinoids are carcinogenic. THC is not carcinogenic in skin tests on rodents [14] and THC and other cannabinoids are not mutagenic according to the Ames test [15]. By contrast, cannabis smoke is carcinogenic in rodents [16] and mutagenic in the Ames test [17]. Cannabis smoke contains several of the same
Cannabinoids and cancer therapy
There is evidence that cannabinoids may have anti-cancer effects. This was noted in lung adenocarcinoma models in the 1970s [41] and subsequent studies have demonstrated tumor growth inhibition in vitro and in vivo in glioblastoma multiforme, breast, prostate, thyroid, colon, skin, pancreatic, leukemia and lymphoma models [42]. The exact mechanism by which this anti-tumor effect occurs may involve suppression of proliferative cell signaling pathways, inhibition of angiogenesis and cell
Cannabinoids and cancer symptom management
In the 1970s researchers began investigating purified and synthesized cannabinoids’ roles in the palliation of cancer symptoms [61]. Numerous trials of cannabinoids have subsequently been performed for several indications. The use of cannabinoids for cancer palliation has now extended to cannabis itself, as cancer is a qualifying condition for cannabis use in every state in the US where cannabis is approved for medical purposes. Acknowledging that symptom palliation may vary based upon the
The legal climate in the United States
The laws governing the use of “medical cannabis” in the United States are dynamic and varied. In 1970 the Controlled Substances Act (CSA) classified cannabis as a schedule I agent. Since then the Institute of Medicine, American College of Physicians, and American Medical Association have recommended that the federal government re-evaluate its current regulations to enable research into cannabis’ medicinal value [82], [83], [84]. In response to its federal schedule I status, states began
Conclusions
Interest in and use of medicinal cannabis and cannabinoids have risen dramatically in the last 30 years as synthetic and purified cannabinoids have entered the market and states have passed laws eliminating criminal penalties for cannabis possession, use, or physician recommendation for approved medical purposes. Medical cannabis remains a paradox in many ways. Cannabis smoke may be carcinogenic but it has been difficult to conclusively link cannabis use and cancer development epidemiologically,
Conflicts of interest statement
The authors state no conflicts of interest.
Funding
This review was not supported by any research funding.
Reviewers
Mark Ware, M.D., Assistant Professor in Family Medicine & Anesthesia, McGill University, Centre for Medical Education, Lady House, 1110 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada.
Donald I. Abrams, M.D., Professor, Clinical Medicine, UCSF, University of California, San Francisco, Divisions of Hematology & Oncology, Box 0874, UCSF, San Fransisco, CA 94143-0874, United States.
Acknowledgements
We thank Bonnie Bowles, Richard Fuquay, Stephen Keysar, and Wells Messersmith for reviewing the manuscript.
Dr. Bowles is a fellow in hematology and medical oncology at the University of Colorado. His clinical and research interests are in head and neck cancer, developmental therapeutics, and cannabinoids and malignancies. He serves as the oncology representative on the State of Colorado's Marijuana Advisory Committee.Dr. O’Bryant is an Associate Professor of Pharmacy at the University of Colorado Cancer Center (UCCC).Dr. Camidge is an Associate Professor of Medical Oncology at the UCCC specializing
References (106)
- et al.
Adverse health effects of non-medical cannabis use
Lancet
(2009) - et al.
Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside
Neurotherapeutics
(2009) - et al.
Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice
Fundam Appl Toxicol
(1996) - et al.
Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco
Chest
(1997) - et al.
An analysis of risk factors for oral cancer in young people: a case–control study
Oral Oncol
(2004) - et al.
Cannabis use and cancer of the head and neck: case–control study
Otolaryngol Head Neck Surg
(2008) - et al.
Cannabis smoking and risk of lung cancer in men: a pooled analysis of three studies in Maghreb
J Thorac Oncol
(2008) - et al.
Association between marijuana use and transitional cell carcinoma
Urology
(2006) - et al.
Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents
Best Pract Res Clin Endocrinol Metab
(2009) - et al.
The endocannabinoid system in cancer-potential therapeutic target?
Semin Cancer Biol
(2008)
Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma
Cancer Genet Cytogenet
Distinctive pattern of cannabinoid receptor type II (CB2) expression in adult and pediatric brain tumors
Brain Res
A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain
J Pain
Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain
J Pain Symptom Manage
Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference
Ann Oncol
Medicinal cannabis in oncology
Eur J Cancer
Examining the roles of cannabinoids in pain and other therapeutic indications: a review
Expert Opin Pharmacother
Pharmacokinetics and pharmacodynamics of cannabinoids
Clin Pharmacokinet
Signal transduction of the CB1 cannabinoid receptor
J Mol Endocrinol
CB2: a cannabinoid receptor with an identity crisis
Br J Pharmacol
Role of myeloid-derived suppressor cells in amelioration of experimental autoimmune hepatitis following activation of TRPV1 receptors by cannabidiol
PLoS One
Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa
Biol Pharm Bull
Cannabis potency and contamination: a review of the literature
Addiction
Strong increase in total delta-THC in cannabis preparations sold in Dutch coffee shops
Addict Biol
Vaporization as a smokeless cannabis delivery system: a pilot study
Clin Pharmacol Ther
Comparative pharmacology of Delta9-tetrahydrocannabinol and its metabolite, 11-OH-Delta9-tetrahydrocannabinol
J Clin Invest
Cannabis use and cancer
Addiction
Effects of marijuana on cell nuclei. A review of the literature relating to the genotoxicity of cannabis
Mutagenicity, developmental toxicity and carcinogenicity of cannabis
Addict Biol
A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke
Experientia
A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two machine smoking conditions
Chem Res Toxicol
Evaluation of the DNA damaging potential of cannabis cigarette smoke by the determination of acetaldehyde derived N2-ethyl-2′-deoxyguanosine adducts
Chem Res Toxicol
Pulmonary hazards of smoking marijuana as compared with tobacco
N Engl J Med
Histopathologic and molecular alterations in bronchial epithelium in habitual smokers of marijuana, cocaine, and/or tobacco
J Natl Cancer Inst
Marijuana use and increased risk of squamous cell carcinoma of the head and neck
Cancer Epidemiol Biomarkers Prev
Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa
Br J Cancer
Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers
JNCI J Natl Cancer Inst
Risk factors for oral cancer in newly diagnosed patients aged 45 years and younger: a case–control study in Southern England
J Oral Pathol Med
Marijuana use and risk of oral squamous cell carcinoma
Cancer Res
Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case–control study
Cancer Epidemiol Biomarkers Prev
Marijuana smoking and the risk of head and neck cancer: pooled analysis in the INHANCE Consortium
Cancer Epidemiol Biomarkers Prev
A population-based case–control study of marijuana use and head and neck squamous cell carcinoma
Cancer Prev Res
The association between marijuana smoking and lung cancer: a systematic review
Arch Intern Med
Cannabis use and risk of lung cancer: a case–control study
Eur Respir J
Marijuana use and mortality
Am J Public Health
The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: cigarette smoking and other lifestyle behaviors
J Neurooncol
Marijuana use and testicular germ cell tumors
Cancer
Antineoplastic activity of cannabinoids
J Natl Cancer Inst
Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells
J Clin Invest
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Dr. Bowles is a fellow in hematology and medical oncology at the University of Colorado. His clinical and research interests are in head and neck cancer, developmental therapeutics, and cannabinoids and malignancies. He serves as the oncology representative on the State of Colorado's Marijuana Advisory Committee.Dr. O’Bryant is an Associate Professor of Pharmacy at the University of Colorado Cancer Center (UCCC).Dr. Camidge is an Associate Professor of Medical Oncology at the UCCC specializing in lung cancer and drug development.Dr. Jimeno is an Associate Professor of Medical Oncology at the UCCC specializing in head and neck cancers and drug development.