The intersection between cannabis and cancer in the United States

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Abstract

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.

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

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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.

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