Overview

• Cannabis, also known as marijuana, is a plant grown in many parts of the world (seeQuestion 1).
• The use of Cannabis for medicinal purposes dates back to ancient times (see Question 3).
• By federal law, possessing Cannabis is illegal in the United States (see Question 1).
• In the United States, Cannabis is a controlled substance that requires special licensing for its use (see Question 1 and Question 3).
• Cannabinoids are active chemicals in Cannabis that cause drug-like effects throughout the body, including the central nervous system and the immune system (see Question 2).
• Cannabinoids can be taken by mouth, inhaled, or sprayed under the tongue (seeQuestion 5).
• Cannabis and cannabinoids have been studied in the laboratory and the clinic for relief of pain, nausea and vomiting, anxiety, and loss of appetite (see Question 6 and Question 7).
• Cannabis and cannabinoids may have benefits in treating the symptoms of cancer or theside effects of cancer therapies (see Question 7).
• Two cannabinoids (dronabinol and nabilone) are drugs approved by the U.S. Food and Drug Administration (FDA) for the prevention or treatment of chemotherapy-related nausea and vomiting (see Question 7 and Question 10).
• Cannabis has been shown to kill cancer cells in the laboratory and to affect the immune system. However, there is no evidence that Cannabis’ effects on the immune system help the body fight cancer (see Question 6).
• At this time, there is not enough evidence to recommend that patients inhale or ingestCannabis as a treatment for cancer-related symptoms or side effects of cancer therapy (see Question 7).
• Cannabis is not approved by the FDA for use as a cancer treatment (see Question 9).

Questions and Answers About Cannabis

1. What is Cannabis?
   Cannabis, also known as marijuana, is a plant from Central Asia that is grown in many parts of the world today. In the United States, it is a controlled substance and has been classified as a Schedule I agent (a drug with increased potential for abuse and no known medical use).
   By federal law, possessing Cannabis (marijuana), is illegal in the United States.
2. What are cannabinoids?
   Cannabinoids are active chemicals in Cannabis that cause drug-like effects throughout the body, including the central nervous system and the immune system. They are also known as phytocannabinoids. The main active cannabinoid in Cannabis is delta-9-THC. Another active cannabinoid is cannabidiol, which may relieve pain and lowerinflammation without causing the “high” of delta-9-THC.
   Cannabinoids may be useful in treating the side effects of cancer and cancer treatment.
   Other possible effects of cannabinoids include:

   • Anti-inflammatory activity.
   • Blocking cell growth.
   • Preventing the growth of blood vessels that supply tumors.
   • Antiviral activity.
3. What is the history of the medical use of Cannabis?
   The use of Cannabis for medicinal purposes dates back at least 3,000 years. It came into use in Western medicine in the 19th century and was said to relieve pain, inflammation, spasms, and convulsions.
   In 1937, the U.S. Treasury began taxing Cannabis under the Marijuana Tax Act at one dollar per ounce for medicinal use and one hundred dollars per ounce for recreational use. The American Medical Association (AMA) opposed this regulation of Cannabis and did not want studies of its potential medicinal benefits to be limited. In 1942, Cannabiswas removed from the U.S. Pharmacopoeia because of continuing concerns about its safety. In 1951, Congress passed the Boggs Act, which included Cannabis with narcoticdrugs for the first time.
   Under the Controlled Substances Act of 1970, marijuana was classified as a Schedule I drug. Other Schedule I drugs include heroin, LSD, mescaline, methaqualone, and gamma-hydroxybutyrate (GHB).
   Although Cannabis was not believed to have any medicinal use, the U.S. government distributed it to patients on a case-by-case basis under the Compassionate UseInvestigational New Drug (IND) program between 1978 and 1992.
   In the past 20 years, researchers have studied how cannabinoids act on the brain and other parts of the body. Cannabinoid receptors (molecules that bind cannabinoids) have been discovered in brain cells and nerve cells in other parts of the body. The presence of cannabinoid receptors on immune system cells suggests that cannabinoids may have a role in immunity.
4. If Cannabis is illegal, how do some cancer patients in the United States use it?
   Though federal law prohibits the use of Cannabis, the table below lists the localities that allow its use for certain medical conditions.

   List of Localities That Permit Use of Cannabis for Certain Medical Conditions

   Alaska (AK)

   Arizona (AZ)

   California (CA)

   Colorado (CO)

   Connecticut (CT)

   Delaware (DE)

   District of Columbia (DC)

   Hawaii (HI)

   Maine (ME)

   Michigan (MI)

   Montana (MT)

   Nevada (NV)

   New Hampshire (NH)

   New Jersey (NJ)

   New Mexico (NM)

   Oregon (OR)

   Rhode Island (RI)

   Vermont (VT)

   Washington (WA)

5. How is Cannabis administered?
   Cannabis may be taken by mouth or may be inhaled. When taken by mouth (in baked products or as an herbal tea), the main psychoactive ingredient in Cannabis (delta-9-THC) is processed by the liver, making an additional psychoactive chemical (a substance that acts on the brain and changes mood or consciousness).
   When Cannabis is smoked and inhaled, cannabinoids quickly enter the bloodstream. The additional psychoactive chemical is produced in smaller amounts than when taken by mouth.
   A growing number of clinical trials are studying a medicine made from a whole-plantextract of Cannabis that contains specific amounts of cannabinoids. This medicine is sprayed under the tongue.
6. Have any preclinical (laboratory or animal) studies been conducted using Cannabisor cannabinoids?
   Preclinical studies of cannabinoids have investigated the following activities:
   Antitumor activity

   • Studies in mice and rats have shown that cannabinoids may inhibit tumor growth by causing cell death, blocking cell growth, and blocking the development of blood vessels needed by tumors to grow. Laboratory and animal studies have shown that cannabinoids may be able to kill cancer cells while protecting normal cells.
   • A study in mice showed that cannabinoids may protect against inflammation of the colon and may have potential in reducing the risk of colon cancer, and possibly in its treatment.
   • A laboratory study of delta-9-THC in hepatocellular carcinoma (liver cancer) cells showed that it damaged or killed the cancer cells. The same study of delta-9-THC in mouse models of liver cancer showed that it had antitumoreffects. Delta-9-THC has been shown to cause these effects by acting on molecules that may also be found in non-small cell lung cancer cells and breast cancer cells.
   • A laboratory study of cannabidiol in estrogen receptor positive and estrogen receptor negative breast cancer cells showed that it caused cancer cell death while having little effect on normal breast cells.
   • A laboratory study of cannabidiol in human glioma cells showed that when given along with chemotherapy, cannabidiol may make chemotherapy more effective and increase cancer cell death without harming normal cells.
   Stimulating appetite

   • Many animal studies have shown that delta-9-THC and other cannabinoids stimulate appetite and can increase food intake.
   Pain relief

   • Cannabinoid receptors (molecules that bind cannabinoids) have been studied in the brain, spinal cord, and nerve endings throughout the body to understand their roles in pain relief.
   • Cannabinoids have been studied for anti-inflammatory effects that may play a role in pain relief.
7. Have any clinical trials (research studies with people) of Cannabis or cannabinoid use by cancer patients been conducted?
   No clinical trials of Cannabis as a treatment for cancer in humans have been found in theCAM on PubMed database maintained by the National Institutes of Health.
   Cannabis and cannabinoids have been studied in clinical trials for ways to manage side effects of cancer and cancer therapies, including the following:
   Nausea and vomiting

   • Delta-9-THC taken by mouth: Two cannabinoid drugs approved in the United States are available under the names dronabinol and nabilone. Both dronabinoland nabilone are approved by the Food and Drug Administration (FDA) for the treatment of chemotherapy-related nausea and vomiting in patients who have not responded to standard therapy. Many clinical trials have shown that both dronabinol and nabilone worked as well as or better than some of the weaker FDA-approved drugs to relieve nausea and vomiting. Newer drugs given for chemotherapy-related nausea have not been directly compared with Cannabisor cannabinoids in cancer patients.
   • Inhaled Cannabis: Three small trials have studied inhaled Cannabis for the treatment of chemotherapy-related nausea and vomiting. Various study methods and chemotherapy agents were used with mixed results. There is not enough information to interpret these findings.
   Stimulating appetite

   • Delta-9-THC taken by mouth: A clinical trial compared delta-9-THC (dronabinol) and a standard drug (megestrol) in patients with advanced cancer and loss of appetite. Results showed that delta-9-THC was not as effective in increasing appetite or weight gain in advanced cancer patients compared with standard therapy. However, a clinical trial of patients with HIV/AIDS and weight loss found that those who took delta-9-THC had increased appetite and stopped losing weight compared with patients who took a placebo.
   • Inhaled Cannabis: There are no published studies of the effect of inhaledCannabis on cancer patients with loss of appetite. Studies of healthy people who inhaled Cannabis showed that they consumed more calories, especially high-fat and sweet snacks.
   Pain relief

   • Combining cannabinoids with opioids: In a small study of 21 patients withchronic pain, vaporized Cannabis was added to slow-release oxycodone ormorphine and given for five days. Results showed that combining vaporizedCannabis with morphine relieved pain better than morphine alone, while combining vaporized Cannabis with oxycodone did not produce significantly greater pain relief. These findings should be tested in further studies.
   • Delta-9-THC taken by mouth: Two small clinical trials of oral delta-9-THC showed that it relieved cancer pain. In the first study, patients had good pain relief as well as relief of nausea and vomiting and better appetite. A second study showed that delta-9-THC could be given in doses that gave pain relief comparable to codeine. Higher doses of delta-9-THC were found to be moresedating than codeine. An observational study of nabilone also showed that it relieved cancer pain along with nausea, anxiety, and distress when compared with no treatment. Neither dronabinol nor nabilone is approved by the FDA for pain management.
   • Whole Cannabis plant extract medicine: A study of a whole-plant extract ofCannabis that contained specific amounts of cannabinoids, which was sprayed under the tongue, found it was effective in patients with advanced cancer whose pain was not relieved by strong opioids alone. This treatment was studied using different doses in a randomized, placebo-controlled clinical trial of cancer patients with chronic pain not controlled by opioids. Patients who received the lower doses of cannabinoid spray showed markedly better pain control and less sleep loss compared with patients who received a placebo. Adverse side effects depended on the dose received. Only patients in the high-dose group had adverse side effects that made the treatment less beneficial than the placebo. Some patients using the cannabinoid spray were followed in a long-term study. Results showed that, for some patients, control of their cancer-related pain continued without needing higher doses of spray or higher doses of their other pain medicines.
   • Inhaled Cannabis: Various clinical trials have shown benefits of inhaledCannabis compared with placebo in relieving neuropathic pain. These include a study of inhaled Cannabis in patients with HIV-related peripheral neuropathy. Results found better pain control in the Cannabis group than in the placebo group. Another study involved patients with various kinds of chronic pain that was not relieved by other pain medicines. Results showed that those treated with either low-dose or medium-dose inhaled Cannabis had improved pain relief at both doses compared to patients treated with a placebo. Side effects of the inhaled Cannabis were minor. To date, no clinical trials have studied cannabinoids in the treatment of chemotherapy-related neuropathy in patients with cancer.
   Anxiety and sleep

   • Inhaled Cannabis: A small case series found that patients who inhaled marijuana had improved mood, improved sense of well-being, and less anxiety.
   • Whole Cannabis plant extract spray: A trial of a whole-plant extract of Cannabisthat contained specific amounts of cannabinoids, which was sprayed under the tongue, found that patients had improved sleep quality.
8. Have any side effects or risks been reported from Cannabis and cannabinoids?
   Adverse side effects of cannabinoids may include:

   • Rapid beating of the heart.
   • Low blood pressure.
   • Muscle relaxation.
   • Bloodshot eyes.
   • Slowed digestion and movement of food by the stomach and intestines.
   • Dizziness.
   • Depression.
   • Hallucinations.
   • Paranoia.
   Because Cannabis smoke contains many of the same substances as tobacco smoke, there are concerns about how smoked cannabis affects the lungs. A study of over 5,000 men and women without cancer over a period of 20 years found that smoking tobacco was linked with some loss of lung function but that occasional and low use of cannabis was not linked with loss of lung function.
   Because use of Cannabis over a long time may have harmful effects on the endocrineand reproductive systems, rates of testicular germ cell tumors (TGCTs) in Cannabisusers have been studied. Larger studies that follow patients over time and laboratory studies of cannabinoid receptors in TGCTs are needed to find if there is a link betweenCannabis use and a higher risk of TGCTs.
   Both Cannabis and cannabinoids may be addictive.
   Symptoms of withdrawal from cannabinoids may include:

   • Irritability.
   • Trouble sleeping.
   • Restlessness.
   • Hot flashes.
   • Nausea and cramping (rarely occur).
   These symptoms are mild compared to withdrawal from opiates and usually lessen after a few days.
9. Are Cannabis or cannabinoids approved by the U.S. Food and Drug Administration for use as a cancer treatment in the United States?
   The U.S. Food and Drug Administration has not approved Cannabis or cannabinoids for use as a cancer treatment.
10. Are Cannabis or cannabinoids approved by the U.S. Food and Drug Administration for use as a treatment for cancer-related symptoms or side effects of cancer therapy?
    Cannabis is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of any cancer-related symptom or side effect of cancer therapy.
    Two cannabinoids (dronabinol and nabilone) are approved by the FDA for the treatment of chemotherapy-related nausea and vomiting in patients who have not responded to standard therapy.

Current Clinical Trials

Check NCI’s list of cancer clinical trials for cancer CAM clinical trials on marijuana, nabilone,dronabinol and nabiximols that are actively enrolling patients.

General information about clinical trials is available from the NCI Web site.

Changes to This Summary (08/01/2013)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

In writing Cancer Information Summaries, PDQ Editorial Boards review current evidence. They do not make recommendations or develop guidelines. Their work is editorially independent of theNational Cancer Institute (NCI). This summary on Cannabis and cannabinoids does not represent a policy statement of NCI or NIH. The summary statement represents an independent review of the literature; that review is not influenced by NCI or any other federal agency.

About This PDQ Summary

General CAM Information

Complementary and alternative medicine (CAM)—also referred to as integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.

Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.

Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any therapeutic approach, because some complementary and alternative therapies may interfere with their standard treatment or may be harmful when used with conventional treatment.

Evaluation of CAM Approaches

It is important that the same rigorous scientific evaluation used to assess conventional approaches be used to evaluate CAM therapies. The National Cancer Institute (NCI) and the National Center for Complementary and Alternative Medicine (NCCAM) are sponsoring a number of clinical trials (research studies) at medical centers to evaluate CAM therapies for cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a rigorous scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have undergone rigorous evaluation. A small number of CAM therapies originally considered to be purely alternative approaches are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) Consensus Conference in November 1997, acupuncture has been found to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery. In contrast, some approaches, such as the use of laetrile, have been studied and found ineffective or potentially harmful.

The NCI Best Case Series Program, which was started in 1991, is one way CAM approaches that are being used in practice are being investigated. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM conducts a critical review of the materials and develops follow-up research strategies for approaches deemed to warrant NCI-initiated research.

Questions to Ask Your Health Care Provider About CAM

When considering complementary and alternative therapies, patients should ask their health care provider the following questions:

• What side effects can be expected?
• What are the risks associated with this therapy?
• Do the known benefits outweigh the risks?
• What benefits can be expected from this therapy?
• Will the therapy interfere with conventional treatment?
• Is this therapy part of a clinical trial?
• If so, who is sponsoring the trial?
• Will the therapy be covered by health insurance?

To Learn More About CAM

National Center for Complementary and Alternative Medicine (NCCAM)

The National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.

• NCCAM Clearinghouse
• Post Office Box 7923 Gaithersburg, MD 20898–7923
• Telephone: 1–888–644–6226 (toll free) 301–519–3153 (for International callers)
• TTY (for deaf and hard of hearing callers): 1–866–464–3615
• Fax: 1–866–464–3616
• E-mail: info@nccam.nih.gov
• Web site: http://nccam.nih.gov

CAM on PubMed

NCCAM and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM’s PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the Web sites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.) CAM on PubMed is available through the NCCAM Web site. It can also be accessed through NLM PubMed bibliographic database by selecting the “Limits” tab and choosing “Complementary Medicine” as a subset.

Office of Cancer Complementary and Alternative Medicine

The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI Web site.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the NCI Cancer Information Service toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 am to 8:00 pm. A trained Cancer Information Specialist is available to answer your questions.

Food and Drug Administration

The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.

• Food and Drug Administration
• 5600 Fishers Lane
• Rockville, MD 20857
• Telephone: 1–888–463–6332 (toll free)
• Web site: http://www.fda.gov/

Federal Trade Commission

The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:

• Who Cares: Sources of Information About Health Care Products and Services
• Fraudulent Health Claims: Don’t Be Fooled

• Consumer Response Center
• Federal Trade Commission
• CRC-240
• Washington, DC 20580
• Telephone: 1-877-FTC-HELP (1-877-382-4357) (toll free)
• TTY (for deaf and hearing impaired callers): 202-326-2502
• Web site: http://www.ftc.gov/

PDQ Cancer Information Summaries updated on September 4, 2013.