Over a third of adults with cancer in the United States use some form of complementary and alternative medicine (CAM) product. CAM products may include dietary supplements, herbal products, and special teas. Taking anticancer drugs and CAM products together may cause a person to have an undesired (adverse) reaction. Talk to your doctor about the CAM products you use before you begin treatment.

When dietary supplements, herbs, or other CAM products are taken with an anticancer drug, they could change the way the cancer drug works in a person’s body. They may change how the cancer drug is absorbed and distributed (metabolized) in the body tissues, or how it is removed (excreted) from the body.

Special enzymes and other proteins help drugs work against cancer in the body. The cytochrome P450 superfamily of enzymes are important for how the body metabolizes many cancer drugs. P-glycoprotein, a special protein that helps remove substances from cells, is also involved in how cancer drugs work in a person’s body. If a CAM product disturbs these systems, the cancer drug will not work like it should, and the person will not receive the full benefits of the drug.

Some studies have been done on taking CAM products with cancer drugs. This summary covers some of the possible adverse reactions from taking CAM products and cancer drugs together.

Complementary and alternative medicine (CAM)—also called 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 type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a 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 been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used 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) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. 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 carefully reviews these materials to see if any seem worth further research.

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

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) 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.

CAM on PubMed

NCCIH 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 websites 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.)

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 website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 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.

Federal Trade Commission

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

This cancer information summary provides an overview of the use of black cohosh as a treatment in breast cancer patients and survivors, generally for the relief of symptoms or side effects. The summary provides a brief history of black cohosh research, the results of laboratory and clinical trials, and possible side effects of black cohosh use.

This summary contains the following key information:

Native to eastern and midwestern North America, black cohosh (Actaea racemosa, also known as Cimicifuga racemosa) [1] is a member of the buttercup family (Ranunculaceae).[2,3] Black cohosh has many synonyms, including black snakeroot, bugbane, rattleroot, squawroot, and macrotrys or macrotys.[2–4] The roots and rhizomes of the black cohosh plant are used for medicinal preparations.

Various types of extracts of black cohosh roots and rhizomes have been studied for their chemical composition and biological activity. Lipophilic extracts have predominantly been used in laboratory studies and only infrequently in clinical trials.[3] The most commonly used clinical preparations of black cohosh (e.g., Remifemin® and BNO 1055) are made from hydrophilic (typically hydroalcoholic) extracts.[4] Lipophilic extracts have in vitro effects on estrogen-regulated genes, whereas hydrophilic extracts generally do not.[3]

Several of the chemical constituents of black cohosh extracts have biological activities that have been demonstrated through in vitro studies and are candidate markers for the observed in vivo and clinical effects. Triterpene glycosides have structures similar to steroids,[4] but no apparent direct binding to the estrogen receptor.[3] One of the most abundant of such glycosides, 23-epi-26-deoxyactein, is specific for black cohosh and is the constituent usually chosen for standardization of commercial products.[2,3] At least 40 different triterpene glycoside analogues have been identified in black cohosh (A. racemosa), including actein and cimicifugoside congeners.[2,3]

Other chemical constituents of black cohosh extracts include aromatic acid phenolpropanoids related to caffeic and ferulic acid, along with the black cohosh-specific fukinolic acid.[5] The plant also contains a large variety of guanidine alkaloids, which have been explored chemically but not studied biologically.

Various plants that resemble black cohosh have been mistakenly or intentionally included in some commercial black cohosh products or plants. Such adulteration can be detected by methods such as microscopy, high-performance thin-layer chromatography, high-performance liquid chromatography ultraviolet, and DNA barcoding.[2]

Black cohosh root, rhizome, and associated preparations have gained considerable international market and consumer interest for more than 60 years, particularly gaining U.S. interest within the last 15 years.[6] A market report released by the American Botanical Council stated that black cohosh extract was among the 15 top-selling herbal dietary supplements by the food, drug, and mass-market channel in the United States in 2019, with total sales nearing $30 million.[7] Growth in market demand for black cohosh has led to an increased need for scientific evidence of quality, safety, and efficacy.[4,5,8]

Companies distribute black cohosh as a dietary supplement. In the United States, dietary supplements are regulated by the U.S. Food and Drug Administration (FDA) as a separate category from foods, cosmetics, and drugs. Unlike drugs, dietary supplements do not require premarket evaluation and approval by the FDA unless specific disease prevention or treatment claims are made. The quality and amount of ingredients in dietary supplements are also regulated by the FDA through Good Manufacturing Practices (GMPs). The FDA GMPs requires that every finished batch of dietary supplement meets each product specification for identity, purity, strength, composition, and limits on contamination that may adulterate dietary supplements. The FDA can remove dietary supplements from the market that are deemed unsafe. Because dietary supplements are not formally reviewed for manufacturing consistency every year, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved the use of black cohosh as a treatment for cancer or any other medical condition.

References

1. European Union Herbal Monograph on Cimicifuga racemosa (L.) Nutt., rhizoma. London, United Kingdom: Committee on Herbal Medicinal Products, 2018. Available online. Last accessed September 18, 2024.
2. Predny ML, De Angelis P, Chamberlain JL: Black cohosh (Actaea racemosa): an annotated bibliography. U.S. Department of Agriculture Forest Service, Southern Research Station, 2006. General Technical Report SRS 97.
3. Fabricant DS, Krause EC, Farnsworth NR: Black cohosh. In: Coates PM, Blackman MR, Cragg GM: Encyclopedia of Dietary Supplements. 2nd ed. CRC Press, 2015, pp 60-74.
4. Qiu F, McAlpine JB, Krause EC, et al.: Pharmacognosy of black cohosh: the phytochemical and biological profile of a major botanical dietary supplement. Prog Chem Org Nat Prod 99: 1-68, 2014. [PUBMED Abstract]
5. Gafner S: Black Cohosh Laboratory Guidance Document. ABC-AHP-NCNPR Botanical Adulterants Program, 2015.
6. Foster S: Exploring the peripatetic maze of black cohosh adulteration: a review of the nomenclature, distribution, chemistry, market status, analytical methods, and safety. HerbalGram (98): 32-51, 2013. Available online. Last accessed September 18, 2024.
7. Smith T, May G, Eckl V, et al.: US sales of herbal supplements increase by 8.6% in 2019. HerbalGram (127): 54-69, 2020. Available online. Last accessed September 18, 2024.
8. Gafner S: Botanical adulterants bulletin on adulteration of actaea racemosa. Black Cohosh – Botanical Adulterants Bulletin 1-5, 2016.

Black cohosh was in use by American Indian or Alaska Native people when Europeans arrived in the New World.[1] Among the reported indications for black cohosh in traditional American Indian or Alaska Native medicine were various female conditions, rheumatism, fever (possibly due to malaria), general malaise, sore throat, childbirth, and snakebite.[1,2] Early European settlers, and subsequently American eclectic physicians, assimilated the use of black cohosh and began exporting the herb to Europe as early as the 18th century.[1]

Europeans have used black cohosh to treat menopausal symptoms for over 50 years. In Germany, the Commission E approved black cohosh as a treatment for dysmenorrhea, menopausal symptoms, heart palpitations, nervousness, irritability, sleep disturbances, tinnitus, vertigo, perspiration, and depression.[1]

Various sources suggested that the recommended dose of crude drug is 40 mg per day.[1,3] At least one trial compared two different doses (39 mg and 127.3 mg) [4] in women with menopausal symptoms and found equivalent beneficial effects at both doses. The lack of long-term safety studies has led some groups to recommend limiting the use of black cohosh to a maximum of 6 months.[1,5]

References

1. Predny ML, De Angelis P, Chamberlain JL: Black cohosh (Actaea racemosa): an annotated bibliography. U.S. Department of Agriculture Forest Service, Southern Research Station, 2006. General Technical Report SRS 97.
2. Qiu F, McAlpine JB, Krause EC, et al.: Pharmacognosy of black cohosh: the phytochemical and biological profile of a major botanical dietary supplement. Prog Chem Org Nat Prod 99: 1-68, 2014. [PUBMED Abstract]
3. Fabricant DS, Krause EC, Farnsworth NR: Black cohosh. In: Coates PM, Blackman MR, Cragg GM: Encyclopedia of Dietary Supplements. 2nd ed. CRC Press, 2015, pp 60-74.
4. Liske E, Hänggi W, Henneicke-von Zepelin HH, et al.: Physiological investigation of a unique extract of black cohosh (Cimicifugae racemosae rhizoma): a 6-month clinical study demonstrates no systemic estrogenic effect. J Womens Health Gend Based Med 11 (2): 163-74, 2002. [PUBMED Abstract]
5. Cimicifugae Rhizoma. Amsterdam, The Netherlands: European Medicines Agency, 2018. Available online. Last accessed September 18, 2024.

References

1. Fabricant DS, Krause EC, Farnsworth NR: Black cohosh. In: Coates PM, Blackman MR, Cragg GM: Encyclopedia of Dietary Supplements. 2nd ed. CRC Press, 2015, pp 60-74.
2. Qiu F, McAlpine JB, Krause EC, et al.: Pharmacognosy of black cohosh: the phytochemical and biological profile of a major botanical dietary supplement. Prog Chem Org Nat Prod 99: 1-68, 2014. [PUBMED Abstract]
3. Fritz H, Seely D, McGowan J, et al.: Black cohosh and breast cancer: a systematic review. Integr Cancer Ther 13 (1): 12-29, 2014. [PUBMED Abstract]
4. Reame NE, Lukacs JL, Padmanabhan V, et al.: Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause 15 (5): 832-40, 2008 Sep-Oct. [PUBMED Abstract]

References

1. van Breemen RB, Liang W, Banuvar S, et al.: Pharmacokinetics of 23-epi-26-deoxyactein in women after oral administration of a standardized extract of black cohosh. Clin Pharmacol Ther 87 (2): 219-25, 2010. [PUBMED Abstract]
2. Fritz H, Seely D, McGowan J, et al.: Black cohosh and breast cancer: a systematic review. Integr Cancer Ther 13 (1): 12-29, 2014. [PUBMED Abstract]
3. Wang C, Huang Q, Liang CL, et al.: Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer. J Ethnopharmacol 238: 111840, 2019. [PUBMED Abstract]
4. Wuttke W, Gorkow C, Seidlová-Wuttke D: Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Menopause 13 (2): 185-96, 2006 Mar-Apr. [PUBMED Abstract]
5. Gafner S: Black Cohosh Laboratory Guidance Document. ABC-AHP-NCNPR Botanical Adulterants Program, 2015.
6. Cohen SM, O’Connor AM, Hart J, et al.: Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 11 (5): 575-7, 2004 Sep-Oct. [PUBMED Abstract]
7. Naser B, Schnitker J, Minkin MJ, et al.: Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause 18 (4): 366-75, 2011. [PUBMED Abstract]
8. Foster S: Exploring the peripatetic maze of black cohosh adulteration: a review of the nomenclature, distribution, chemistry, market status, analytical methods, and safety. HerbalGram (98): 32-51, 2013. Available online. Last accessed September 18, 2024.
9. Gafner S: Botanical adulterants bulletin on adulteration of actaea racemosa. Black Cohosh – Botanical Adulterants Bulletin 1-5, 2016.
10. Gurley B, Hubbard MA, Williams DK, et al.: Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol 46 (2): 201-13, 2006. [PUBMED Abstract]
11. Rebbeck TR, Troxel AB, Norman S, et al.: A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer 120 (7): 1523-8, 2007. [PUBMED Abstract]
12. Qiu F, McAlpine JB, Krause EC, et al.: Pharmacognosy of black cohosh: the phytochemical and biological profile of a major botanical dietary supplement. Prog Chem Org Nat Prod 99: 1-68, 2014. [PUBMED Abstract]
13. Henneicke-von Zepelin HH, Meden H, Kostev K, et al.: Isopropanolic black cohosh extract and recurrence-free survival after breast cancer. Int J Clin Pharmacol Ther 45 (3): 143-54, 2007. [PUBMED Abstract]
14. Pockaj BA, Gallagher JG, Loprinzi CL, et al.: Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1. J Clin Oncol 24 (18): 2836-41, 2006. [PUBMED Abstract]
15. Jacobson JS, Troxel AB, Evans J, et al.: Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 19 (10): 2739-45, 2001. [PUBMED Abstract]
16. Leach MJ, Moore V: Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev (9): CD007244, 2012. [PUBMED Abstract]
17. Castelo-Branco C, Gambacciani M, Cano A, et al.: Review & meta-analysis: isopropanolic black cohosh extract iCR for menopausal symptoms – an update on the evidence. Climacteric 24 (2): 109-119, 2021. [PUBMED Abstract]
18. Geller SE, Shulman LP, van Breemen RB, et al.: Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 16 (6): 1156-66, 2009 Nov-Dec. [PUBMED Abstract]
19. Newton KM, Reed SD, Grothaus L, et al.: The Herbal Alternatives for Menopause (HALT) Study: background and study design. Maturitas 52 (2): 134-46, 2005. [PUBMED Abstract]
20. Reed SD, Newton KM, LaCroix AZ, et al.: Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause 15 (1): 51-8, 2008 Jan-Feb. [PUBMED Abstract]
21. Wuttke W, Seidlová-Wuttke D, Gorkow C: The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas 44 (Suppl 1): S67-77, 2003. [PUBMED Abstract]
22. Raus K, Brucker C, Gorkow C, et al.: First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause 13 (4): 678-91, 2006 Jul-Aug. [PUBMED Abstract]

In general, the hydroalcoholic black cohosh extracts that are widely used as components in commercially available products—and those used in clinical trials—have been very well tolerated, producing rare serious adverse effects, which are likely due to product quality issues (adulteration) rather than black cohosh itself. An overview of the adverse events from a systematic review of the results of several clinical trials, postmarketing surveillance studies, case series, and case reports found only rare serious adverse events that may not have been induced by black cohosh.[1] The most common minor adverse effects noted in these trials were gastrointestinal symptoms (e.g., nausea) and musculoskeletal and connective tissue disorders (e.g., joint pain, rashes).[1]

References

1. Borrelli F, Ernst E: Black cohosh (Cimicifuga racemosa): a systematic review of adverse events. Am J Obstet Gynecol 199 (5): 455-66, 2008. [PUBMED Abstract]
2. Gurley BJ, Gardner SF, Hubbard MA, et al.: In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 77 (5): 415-26, 2005. [PUBMED Abstract]
3. Gurley BJ, Swain A, Hubbard MA, et al.: Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John’s wort, and Echinacea. Mol Nutr Food Res 52 (7): 755-63, 2008. [PUBMED Abstract]
4. Asher GN, Corbett AH, Hawke RL: Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician 96 (2): 101-107, 2017. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

The Committee on Herbal Medicinal Products of the European Medicines Agency describes black cohosh products as a medicine that may be used for the treatment of menopausal symptoms, based on their assessment of the results of around 20 clinical trials involving over 6,000 patients who received black cohosh.[1] However, the lack of demonstration of a clinical benefit significantly greater than that of placebo and the fact that much less research has been performed with cancer patients should lead to extra caution when its use in such patients is being considered .

References

1. Cimicifugae Rhizoma. Amsterdam, The Netherlands: European Medicines Agency, 2018. Available online. Last accessed September 18, 2024.

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.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What is black cohosh?

   Black cohosh is a plant in the buttercup family that grows in eastern and midwestern North America. Its scientific name is Actaea racemosa (also called Cimicifuga racemosa). Black cohosh is also called black snakeroot, bugbane, rattleroot, squawroot, and macrotrys or macrotys. The underground stems and roots of the black cohosh plant are used in herbal supplements.

   Black cohosh was first used by American Indian or Alaska Native people. Extracts from black cohosh have been used as medicine to treat menopausal symptoms in Europe for over 50 years. In Germany, black cohosh has been approved to treat menstrual period pain, menopausal symptoms, fast heartbeat, nervousness, irritability, sleep problems, noise or ringing in the ears, dizziness, sweating, and depression.

2. How is black cohosh taken or given?

   Black cohosh is taken or given by mouth as a dietary supplement. It is sold as a powdered herb, whole herb, liquid, or dried extract in pill form.

3. What laboratory or animal studies have been done using black cohosh?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of black cohosh. For information on laboratory and animal studies done using black cohosh, see the Laboratory/Animal/Preclinical Studies section of the health professional version of Black Cohosh.

4. Have any studies of black cohosh been done in people?

   Observational studies of postmenopausal women without a history of breast cancer have not shown a link between black cohosh and breast cancer prevention. However, one case-control trial found that postmenopausal women who took black cohosh had a 53% decrease in risk of breast cancer compared to postmenopausal women who did not take black cohosh. A retrospective cohort study of patients with breast cancer and survivors of breast cancer who took black cohosh extract also showed lower risk of recurrence.

   Observational and open-label studies have shown some benefits of black cohosh on menopausal symptoms in cancer and noncancer populations. However, clinical trials have not confirmed these effects.

   A review of observational studies of patients with breast cancer and survivors of breast cancer looked at the effects of taking an herbal supplement with black cohosh extract with or without hormone therapy on menopausal symptoms. Patients who took black cohosh reported fewer and less severe hot flashes and other menopausal symptoms. An open label study in Germany showed similar results in breast cancer survivors who took black cohosh and a hormone therapy.

5. Have any side effects or risks been reported from black cohosh?

   Few side effects have been reported from the use of black cohosh. The most common side effects were nausea, joint pain, and rashes. Side effects are likely related to problems with product quality rather than black cohosh itself.

   A few studies have reported that the risk of interactions between black cohosh and other medicines is small. One study found that black cohosh may lower the effect of medicines that reduce cholesterol levels, such as statins.

6. Is black cohosh approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

   The FDA has not approved the use of black cohosh as a treatment for cancer or any other medical condition.

   The FDA regulates dietary supplements separately from foods, cosmetics, and drugs. The FDA’s Good Manufacturing Practices require that every finished batch of supplements is safe and that the claims on the label are true and do not mislead the consumer. However, the FDA does not regularly review the way that supplements are made, so all batches and brands of black cohosh supplements may not be the same.

Complementary and alternative medicine (CAM)—also called 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 type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a 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 been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used 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) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. 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 carefully reviews these materials to see if any seem worth further research.

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

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) 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.

CAM on PubMed

NCCIH 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 websites 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.)

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 website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 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.

Federal Trade Commission

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

This cancer information summary provides an overview of the use of aromatherapy with essential oils primarily to improve the quality of life of cancer patients. This summary includes a brief history of aromatherapy, a review of laboratory studies and clinical trials, and possible adverse effects associated with aromatherapy use.

This summary contains the following key information:

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.

Aromatherapy is a derivative of herbal medicine, which is itself a subset of the biological or nature-based complementary and alternative medicine (CAM) therapies. Aromatherapy has been defined as the therapeutic use of essential oils from plants for the improvement of physical, emotional, and spiritual well-being.

Essential oils are volatile liquid substances extracted from aromatic plant material by steam distillation or mechanical expression. Essential oils produced with the aid of chemical solvents are not considered true essential oils because the solvent residues can alter the quality of the essential oils and lead to adulteration of the fragrance or to skin irritation.

Essential oils are made up of a large array of chemical components that consist of the metabolites found in various plant materials. The major chemical components of essential oils include monoterpenes, esters, aldehydes, ketones, alcohols, phenols, and oxides, which are volatile and may produce characteristic odors. Different types of essential oils contain varying amounts of each of these compounds, which are said to give each essential oil its particular fragrance and therapeutic characteristics. Plant species may have different chemovarieties (variations of subspecies that produce essential oils with different chemical compositions, as a result of genetic variation and growth conditions).[1] Thus, their essential oils can occur as several chemotypes that differ in chemical composition and may produce different clinical effects. It should be noted that essential oils are distinctly different chemically from (fatty) oils, such as those used as food. As essential oils age, the chemical composition changes. Many essential oils do not have an expiration date.

Synthetic odors are often made up of many of the same compounds that are components of the essential oils. These compounds are synthesized and typically combined with other odor-producing chemicals. However, synthetic fragrances frequently contain irritants, such as solvents and propellants, that can trigger sensitivities in some people.[2–4] Most aromatherapists believe that synthetic fragrances are inferior to essential oils because they lack natural or vital energy; however, this has been contested by odor psychologists and biochemists.[5]

Aromatherapy is used or claimed to be useful for a vast array of symptoms and conditions. Published studies regarding the uses of aromatherapy have generally focused on its psychological effects as a stress reliever or anxiolytic agent or its use as a topical treatment for skin-related conditions.

A large body of literature has been published on the effects of odors on the human brain and emotions. Some studies have tested the effects of essential oils on mood, alertness, and mental stress in healthy participants. Other studies investigated the effects of various (usually synthetic) odors on task performance, reaction time, and autonomic parameters or evaluated the direct effects of odors on the brain via electroencephalogram patterns and functional imaging studies.[6] Such studies have consistently shown that odors can produce specific effects on human neuropsychological and autonomic function and that odors can influence mood, perceived health, and arousal. These studies suggest that odors may have therapeutic applications in the context of stressful and adverse psychological conditions.

Practitioners of aromatherapy apply essential oils using several different methods, including the following:

Other direct and indirect applications include mixing essential oils in bath salts and lotions or applying them to dressings.

Different aromatherapy practitioners may have different recipes for treating specific conditions, involving various combinations of essential oils and methods of application. Differences seem to be practitioner dependent, with some common uses more accepted throughout the aromatherapy community. Training and certification in aromatherapy for lay practitioners is available at several schools throughout the United States and United Kingdom; however, there is no professional standardization in the United States and no license is required to practice in either country. Thus, there is little consistency among practitioners in the specific treatments used for specific illnesses. This lack of standardization has led to variability in therapeutic protocols used in research on the effects of aromatherapy. Anecdotal evidence alone or previous experience has driven the choice of essential oils and different researchers choose different essential oils when studying the same applications. However, now there are specific courses for licensed health professionals that give nursing or continuing medical education credit hours, including a small research component and information about evaluating and measuring outcomes.

The National Association for Holistic Aromatherapy (NAHA) (www.naha.org/) and the Alliance of International Aromatherapists (www.alliance-aromatherapists.org) are the two governing bodies for national educational standards for aromatherapists. NAHA is taking steps toward standardizing aromatherapy certification in the United States. Many schools offer certificate programs approved by NAHA. A list of these schools can be found on the NAHA website (https://naha.org/index.php/education/approved-schools/). National examinations in aromatherapy are held twice per year.

The Canadian Federation of Aromatherapists has established standards for aromatherapy certification in Canada (www.cfacanada.com/). They also have standards for safety and professional conduct and a public directory of certified aromatherapists. Other countries may have similar organizations.

Although essential oils are given orally or internally by aromatherapists in France and Germany, their use is generally limited to inhalation or topical application in the United Kingdom and United States. Nonmedical use of essential oils is common in the flavoring and fragrance industries. Most essential oils have been classified as GRAS (generally recognized as safe), at specified concentration limits, by the U.S. Food and Drug Administration (FDA). For a list of international aromatherapy programs, see the International Federation of Aromatherapists website (www.ifaroma.org/).

Aromatherapy products do not need approval by the FDA.

References

1. Wildwood C: The Encyclopedia of Aromatherapy. Healing Arts Press, 1996.
2. Silva-Néto RP, Peres MF, Valença MM: Odorant substances that trigger headaches in migraine patients. Cephalalgia 34 (1): 14-21, 2014. [PUBMED Abstract]
3. Vethanayagam D, Vliagoftis H, Mah D, et al.: Fragrance materials in asthma: a pilot study using a surrogate aerosol product. J Asthma 50 (9): 975-82, 2013. [PUBMED Abstract]
4. Celeiro M, Guerra E, Lamas JP, et al.: Development of a multianalyte method based on micro-matrix-solid-phase dispersion for the analysis of fragrance allergens and preservatives in personal care products. J Chromatogr A 1344: 1-14, 2014. [PUBMED Abstract]
5. Dodd GH: The molecular dimension in perfumery. In: Van Toller S, Dodd GH, eds.: Perfumery: The Psychology and Biology of Fragrance. Chapman and Hall, 1988, pp 19-46.
6. Buchbauer G, Jirovetz L, Jäger W, et al.: Fragrance compounds and essential oils with sedative effects upon inhalation. J Pharm Sci 82 (6): 660-4, 1993. [PUBMED Abstract]

Proponents of aromatherapy report that aromatic or essential oils have been used for thousands of years as stimulants or sedatives of the nervous system and as treatments for a wide range of other disorders.[1] They link it historically to the use of infused oils and unguents in the Bible and ancient Egypt,[1] remedies used throughout the Middle Ages and the Renaissance,[2] and the burning of aromatic plants in various religious rites. The current applications of aromatherapy did not come about until the early 20th century when the French chemist and perfumer Rene Gattefosse coined the term aromatherapy and published a book of that name in 1937.[2] Gattefosse proposed the use of aromatherapy to treat diseases in virtually every organ system, citing mostly anecdotal and case-based evidence.[2]

Although Gattefosse and his colleagues in France, Italy, and Germany studied the effects of aromatherapy for some 30 years, its use went out of fashion midcentury and was rediscovered by another Frenchman, a physician, Jean Valnet, in the latter part of the century. Valnet published his book The Practice of Aromatherapy in 1982,[3] at which time the practice became more well-known in Britain and the United States. Through the 1980s and 1990s, as patients in Western countries became increasingly interested in complementary and alternative medicine (CAM) treatments, aromatherapy developed a following that continues to grow to this day. In addition to the use of essential oils by nurses and aromatherapy practitioners for specific medical issues, the popularity of aromatherapy has also been exploited by cosmetics companies that have created lines of essential oil-based (although often with a synthetic component) cosmetics and toiletries, claiming to improve mood and well-being in their users.

Despite the growing popularity of aromatherapy in the latter part of the 20th century (especially in the United Kingdom), little research on aromatherapy was available in the English-language medical literature until the early or mid-1990s. The research that began to appear in the 1990s was most often conducted by nurses, who tended to be the primary practitioners of aromatherapy in the United States and United Kingdom (although it is dispensed by medical doctors in France and Germany). Aromatherapists now publish their own journal, the International Journal of Essential Oil Therapeutics. Also, many studies regarding the effects of odor on the brain and other systems in animals and healthy humans have been published in the context of odor psychology and neurobiology (and in the absence of the specific term aromatherapy).

In addition to topical antimicrobial uses,[4] aromatherapy has also been proposed for use in wound care [5,6] and to treat a variety of localized symptoms and illnesses such as alopecia, eczema, and pruritus.[7–9] Aromatherapy has also been studied via inhalation for airway reactivity.[10]

Studies on aromatherapy have examined a variety of other conditions, including the following:

Published articles have described the use of aromatherapy in specific hospital settings such as cancer wards, hospices, and other areas where patients are critically ill and require palliative care for the following symptoms:

In addition, observational studies provide examples of the clinical uses of aromatherapy (and other CAM modalities), although they are generally not evidence based. Participants have included homebound patients with terminal disease,[50] and hospitalized patients with leukemia.[51] Aromatherapy has also been used to reduce malodor of necrotic ulcers in cancer patients.[52]

Studies of aromatherapy use with mental health patients have also been conducted.[53] Most of the resulting articles describe successful incorporation of aromatherapy into the treatment of these patients, although outcomes are clearly subjective.

Theories about the mechanism of action of aromatherapy with essential oils differ, depending on the community studying them. Proponents of aromatherapy often cite the connection between olfaction and the limbic system in the brain as the basis for the effects of aromatherapy on mood and emotions; less is said about proposed mechanisms for its effects on other parts of the body. Most of the aromatherapy literature, however, lacks in-depth neurophysiological studies on the nature of olfaction and its link to the limbic system, and it generally does not cite research that shows these links. Proponents of aromatherapy also believe that the effects of the treatments are based on the special nature of the essential oils used and that essential oils produce effects on the body that are greater than the sum of the individual chemical components of the scents.

These assertions have been contested by the biochemistry and psychology communities, which take a different view of the possible mechanism of action of odors on the human brain (most do not differentiate the odors produced by essential oils from those of synthetic fragrances).[30] This neurobiological view, which focuses mostly on the emotional and psychological effects of fragrances (as opposed to the other symptomatic effects claimed by aromatherapists), takes into account what is known about olfactory transduction and the connection of the olfactory system to other central nervous system functions, including memory; however, it is primarily theoretical because of the lack of significant research addressing this topic.

References

1. Tisserand R: Essential oils as psychotherapeutic agents. In: Van Toller S, Dodd GH, eds.: Perfumery: The Psychology and Biology of Fragrance. Chapman and Hall, 1988, pp 167-80.
2. Gattefosse RM: Gattefosse’s Aromatherapy. CW Daniel, 1993.
3. Valnet J: The Practice of Aromatherapy: A Classic Compendium of Plant Medicines & Their Healing Properties. Healing Arts Press, 1990.
4. Hartman D, Coetzee JC: Two US practitioners’ experience of using essential oils for wound care. J Wound Care 11 (8): 317-20, 2002. [PUBMED Abstract]
5. Asquith S: The use of aromatherapy in wound care. J Wound Care 8 (6): 318-20, 1999. [PUBMED Abstract]
6. Edwards-Jones V, Buck R, Shawcross SG, et al.: The effect of essential oils on methicillin-resistant Staphylococcus aureus using a dressing model. Burns 30 (8): 772-7, 2004. [PUBMED Abstract]
7. Hay IC, Jamieson M, Ormerod AD: Randomized trial of aromatherapy. Successful treatment for alopecia areata. Arch Dermatol 134 (11): 1349-52, 1998. [PUBMED Abstract]
8. Anderson C, Lis-Balchin M, Kirk-Smith M: Evaluation of massage with essential oils on childhood atopic eczema. Phytother Res 14 (6): 452-6, 2000. [PUBMED Abstract]
9. Ro YJ, Ha HC, Kim CG, et al.: The effects of aromatherapy on pruritus in patients undergoing hemodialysis. Dermatol Nurs 14 (4): 231-4, 237-8, 256; quiz 239, 2002. [PUBMED Abstract]
10. Cohen BM, Dressler WE: Acute aromatics inhalation modifies the airways. Effects of the common cold. Respiration 43 (4): 285-93, 1982. [PUBMED Abstract]
11. Diego MA, Jones NA, Field T, et al.: Aromatherapy positively affects mood, EEG patterns of alertness and math computations. Int J Neurosci 96 (3-4): 217-24, 1998. [PUBMED Abstract]
12. Motomura N, Sakurai A, Yotsuya Y: Reduction of mental stress with lavender odorant. Percept Mot Skills 93 (3): 713-8, 2001. [PUBMED Abstract]
13. Miltner W, Matjak M, Braun C, et al.: Emotional qualities of odors and their influence on the startle reflex in humans. Psychophysiology 31 (1): 107-10, 1994. [PUBMED Abstract]
14. Millot JL, Brand G, Morand N: Effects of ambient odors on reaction time in humans. Neurosci Lett 322 (2): 79-82, 2002. [PUBMED Abstract]
15. Stevenson C: Measuring the effects of aromatherapy. Nurs Times 88 (41): 62-3, 1992 Oct 7-13. [PUBMED Abstract]
16. Dunn C, Sleep J, Collett D: Sensing an improvement: an experimental study to evaluate the use of aromatherapy, massage and periods of rest in an intensive care unit. J Adv Nurs 21 (1): 34-40, 1995. [PUBMED Abstract]
17. Buckle J: Aromatherapy. Nurs Times 89 (20): 32-5, 1993 May 19-25. [PUBMED Abstract]
18. Hadfield N: The role of aromatherapy massage in reducing anxiety in patients with malignant brain tumours. Int J Palliat Nurs 7 (6): 279-85, 2001. [PUBMED Abstract]
19. Wilkinson S: Aromatherapy and massage in palliative care. Int J Palliat Nurs 1 (1): 21-30, 1995.
20. Wilkinson S, Aldridge J, Salmon I, et al.: An evaluation of aromatherapy massage in palliative care. Palliat Med 13 (5): 409-17, 1999. [PUBMED Abstract]
21. Corner J, Cawler N, Hildebrand S: An evaluation of the use of massage and essential oils on the wellbeing of cancer patients. Int J Palliat Nurs 1 (2): 67-73, 1995.
22. Louis M, Kowalski SD: Use of aromatherapy with hospice patients to decrease pain, anxiety, and depression and to promote an increased sense of well-being. Am J Hosp Palliat Care 19 (6): 381-6, 2002 Nov-Dec. [PUBMED Abstract]
23. Walsh E, Wilson C: Complementary therapies in long-stay neurology in-patient settings. Nurs Stand 13 (32): 32-5, 1999 Apr 28-May 4. [PUBMED Abstract]
24. Itai T, Amayasu H, Kuribayashi M, et al.: Psychological effects of aromatherapy on chronic hemodialysis patients. Psychiatry Clin Neurosci 54 (4): 393-7, 2000. [PUBMED Abstract]
25. Burns E, Blamey C: Complementary medicine. Using aromatherapy in childbirth. Nurs Times 90 (9): 54-60, 1994 Mar 2-8. [PUBMED Abstract]
26. Burns EE, Blamey C, Ersser SJ, et al.: An investigation into the use of aromatherapy in intrapartum midwifery practice. J Altern Complement Med 6 (2): 141-7, 2000. [PUBMED Abstract]
27. Kite SM, Maher EJ, Anderson K, et al.: Development of an aromatherapy service at a Cancer Centre. Palliat Med 12 (3): 171-80, 1998. [PUBMED Abstract]
28. Komori T, Fujiwara R, Tanida M, et al.: Effects of citrus fragrance on immune function and depressive states. Neuroimmunomodulation 2 (3): 174-80, 1995 May-Jun. [PUBMED Abstract]
29. Wiebe E: A randomized trial of aromatherapy to reduce anxiety before abortion. Eff Clin Pract 3 (4): 166-9, 2000 Jul-Aug. [PUBMED Abstract]
30. Perry N, Perry E: Aromatherapy in the management of psychiatric disorders: clinical and neuropharmacological perspectives. CNS Drugs 20 (4): 257-80, 2006. [PUBMED Abstract]
31. Ballard CG, O’Brien JT, Reichelt K, et al.: Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry 63 (7): 553-8, 2002. [PUBMED Abstract]
32. Smallwood J, Brown R, Coulter F, et al.: Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial. Int J Geriatr Psychiatry 16 (10): 1010-3, 2001. [PUBMED Abstract]
33. Holmes C, Hopkins V, Hensford C, et al.: Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry 17 (4): 305-8, 2002. [PUBMED Abstract]
34. Gray SG, Clair AA: Influence of aromatherapy on medication administration to residential-care residents with dementia and behavioral challenges. Am J Alzheimers Dis Other Demen 17 (3): 169-74, 2002 May-Jun. [PUBMED Abstract]
35. Snow LA, Hovanec L, Brandt J: A controlled trial of aromatherapy for agitation in nursing home patients with dementia. J Altern Complement Med 10 (3): 431-7, 2004. [PUBMED Abstract]
36. Rose JE, Behm FM: Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms. Drug Alcohol Depend 34 (3): 225-9, 1994. [PUBMED Abstract]
37. Sayette MA, Parrott DJ: Effects of olfactory stimuli on urge reduction in smokers. Exp Clin Psychopharmacol 7 (2): 151-9, 1999. [PUBMED Abstract]
38. Post-White N, Nichols W: Randomized trial testing of QueaseEase™ essential oil for motion sickness. International Journal of Essential Oil Therapeutics 1 (4): 158-66, 2007.
39. Tate S: Peppermint oil: a treatment for postoperative nausea. J Adv Nurs 26 (3): 543-9, 1997. [PUBMED Abstract]
40. Hines S, Steels E, Chang A, et al.: Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev 4: CD007598, 2012. [PUBMED Abstract]
41. Oyama H, Kaneda M, Katsumata N, et al.: Using the bedside wellness system during chemotherapy decreases fatigue and emesis in cancer patients. J Med Syst 24 (3): 173-82, 2000. [PUBMED Abstract]
42. Dale A, Cornwell S: The role of lavender oil in relieving perineal discomfort following childbirth: a blind randomized clinical trial. J Adv Nurs 19 (1): 89-96, 1994. [PUBMED Abstract]
43. Göbel H, Schmidt G, Soyka D: Effect of peppermint and eucalyptus oil preparations on neurophysiological and experimental algesimetric headache parameters. Cephalalgia 14 (3): 228-34; discussion 182, 1994. [PUBMED Abstract]
44. Marchand S, Arsenault P: Odors modulate pain perception: a gender-specific effect. Physiol Behav 76 (2): 251-6, 2002. [PUBMED Abstract]
45. Kim JT, Wajda M, Cuff G, et al.: Evaluation of aromatherapy in treating postoperative pain: pilot study. Pain Pract 6 (4): 273-7, 2006. [PUBMED Abstract]
46. Barclay J, Vestey J, Lambert A, et al.: Reducing the symptoms of lymphoedema: is there a role for aromatherapy? Eur J Oncol Nurs 10 (2): 140-9, 2006. [PUBMED Abstract]
47. Kohara H, Miyauchi T, Suehiro Y, et al.: Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer. J Palliat Med 7 (6): 791-6, 2004. [PUBMED Abstract]
48. Buckle J: Clinical Aromatherapy: Essential Oils in Practice. 2nd ed. Churchill Livingston, 2003.
49. Wilkinson SM, Love SB, Westcombe AM, et al.: Effectiveness of aromatherapy massage in the management of anxiety and depression in patients with cancer: a multicenter randomized controlled trial. J Clin Oncol 25 (5): 532-9, 2007. [PUBMED Abstract]
50. Rimmer L: The clinical use of aromatherapy in the reduction of stress. Home Healthc Nurse 16 (2): 123-6, 1998. [PUBMED Abstract]
51. Stringer J: Massage and aromatherapy on a leukaemia unit. Complement Ther Nurs Midwifery 6 (2): 72-6, 2000. [PUBMED Abstract]
52. Warnke PH, Sherry E, Russo PA, et al.: Antibacterial essential oils in malodorous cancer patients: clinical observations in 30 patients. Phytomedicine 13 (7): 463-7, 2006. [PUBMED Abstract]
53. Hicks G: Aromatherapy as an adjunct to care in a mental health day hospital. J Psychiatr Ment Health Nurs 5 (4): 317, 1998. [PUBMED Abstract]

Numerous studies on the topical antibacterial effects of essential oils have been published; most have found the essential oils to have significant antimicrobial activity.[1] Some essential oils are antiviral and inhibit replication of the herpes simplex virus.[2] Other essential oils are fungistatic and fungicidal against both vaginal and oropharyngeal Candida albicans.[3]

Studies on rats in Europe and Japan have shown that exposure to various odors can result in stimulation or sedation, as well as changes in behavioral responses to stress and pain. A study [4] on the sedative effects of essential oils and other fragrance compounds (mostly individual chemical components of the essential oils) on rat motility showed that lavender oil (Lavandula angustifolia Miller [synonyms: Lavandula spicata L.; Lavandula vera DC.]) in particular had a significant sedative effect, and several single-oil constituents (as opposed to whole essential oils) had similarly strong effects. The authors do not comment on the presumed mechanism for this effect. The differences in bioavailability are ascribed to different levels of lipophilicity, with the more lipophilic oils producing the most sedative effects. The researchers also found significant plasma levels of the fragrance compounds after inhalation, suggesting that the effects of aromatherapy result from a direct pharmacological interaction rather than an indirect central nervous system relay.

Other studies have investigated the effects of aromatherapy on rats’ behavioral and immunological responses to painful, stressful, or startling stimuli. In two European studies, rats exposed to pleasant odors during painful stimuli exhibited decreased pain-related behaviors, with some variation in response between the sexes.[5,6] Two studies from Japan showed an improvement in immunological and behavioral markers in rats exposed to fragrances while under stressful conditions.[7,8]

References

1. Aridoğan BC, Baydar H, Kaya S, et al.: Antimicrobial activity and chemical composition of some essential oils. Arch Pharm Res 25 (6): 860-4, 2002. [PUBMED Abstract]
2. Minami M, Kita M, Nakaya T, et al.: The inhibitory effect of essential oils on herpes simplex virus type-1 replication in vitro. Microbiol Immunol 47 (9): 681-4, 2003. [PUBMED Abstract]
3. D’Auria FD, Tecca M, Strippoli V, et al.: Antifungal activity of Lavandula angustifolia essential oil against Candida albicans yeast and mycelial form. Med Mycol 43 (5): 391-6, 2005. [PUBMED Abstract]
4. Buchbauer G, Jirovetz L, Jäger W, et al.: Fragrance compounds and essential oils with sedative effects upon inhalation. J Pharm Sci 82 (6): 660-4, 1993. [PUBMED Abstract]
5. Aloisi AM, Ceccarelli I, Masi F, et al.: Effects of the essential oil from citrus lemon in male and female rats exposed to a persistent painful stimulation. Behav Brain Res 136 (1): 127-35, 2002. [PUBMED Abstract]
6. Jahangeer AC, Mellier D, Caston J: Influence of olfactory stimulation on nociceptive behavior in mice. Physiol Behav 62 (2): 359-66, 1997. [PUBMED Abstract]
7. Shibata H, Fujiwara R, Iwamoto M, et al.: Immunological and behavioral effects of fragrance in mice. Int J Neurosci 57 (1-2): 151-9, 1991. [PUBMED Abstract]
8. Fujiwara R, Komori T, Noda Y, et al.: Effects of a long-term inhalation of fragrances on the stress-induced immunosuppression in mice. Neuroimmunomodulation 5 (6): 318-22, 1998 Nov-Dec. [PUBMED Abstract]

No studies in the published peer-reviewed literature discuss aromatherapy as a treatment for cancer specifically. The studies discussed below, most of which were conducted in patients with cancer, primarily focus on the following:

These studies purport to test the efficacy of aromatherapy, implying that the products used contain essential oils; however, only an occasional reference article includes significant descriptive information about the product(s) used (e.g., composition, source) thereby greatly limiting the ability of interested clinicians and researchers to compare or duplicate studies or produce meaningful meta-analyses of the research results.

References

1. Cooke B, Ernst E: Aromatherapy: a systematic review. Br J Gen Pract 50 (455): 493-6, 2000. [PUBMED Abstract]
2. Wilkinson S, Aldridge J, Salmon I, et al.: An evaluation of aromatherapy massage in palliative care. Palliat Med 13 (5): 409-17, 1999. [PUBMED Abstract]
3. Kite SM, Maher EJ, Anderson K, et al.: Development of an aromatherapy service at a Cancer Centre. Palliat Med 12 (3): 171-80, 1998. [PUBMED Abstract]
4. Graham PH, Browne L, Cox H, et al.: Inhalation aromatherapy during radiotherapy: results of a placebo-controlled double-blind randomized trial. J Clin Oncol 21 (12): 2372-6, 2003. [PUBMED Abstract]
5. Wilcock A, Manderson C, Weller R, et al.: Does aromatherapy massage benefit patients with cancer attending a specialist palliative care day centre? Palliat Med 18 (4): 287-90, 2004. [PUBMED Abstract]
6. Blackburn L, Achor S, Allen B, et al.: The Effect of Aromatherapy on Insomnia and Other Common Symptoms Among Patients With Acute Leukemia. Oncol Nurs Forum 44 (4): E185-E193, 2017. [PUBMED Abstract]
7. Soden K, Vincent K, Craske S, et al.: A randomized controlled trial of aromatherapy massage in a hospice setting. Palliat Med 18 (2): 87-92, 2004. [PUBMED Abstract]
8. Ozkaraman A, Dügüm Ö, Özen Yılmaz H, et al.: Aromatherapy: The Effect of Lavender on Anxiety and Sleep Quality in Patients Treated With Chemotherapy Clin J Oncol Nurs 22 (2): 203-210, 2018. [PUBMED Abstract]
9. Nakayama M, Okizaki A, Takahashi K: A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer. Biomed Res Int 2016: 9509810, 2016. [PUBMED Abstract]
10. Lua PL, Salihah N, Mazlan N: Effects of inhaled ginger aromatherapy on chemotherapy-induced nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med 23 (3): 396-404, 2015. [PUBMED Abstract]
11. Potter P, Eisenberg S, Cain KC, et al.: Orange interventions for symptoms associated with dimethyl sulfoxide during stem cell reinfusions: a feasibility study. Cancer Nurs 34 (5): 361-8, 2011 Sep-Oct. [PUBMED Abstract]
12. Trambert R, Kowalski MO, Wu B, et al.: A Randomized Controlled Trial Provides Evidence to Support Aromatherapy to Minimize Anxiety in Women Undergoing Breast Biopsy. Worldviews Evid Based Nurs 14 (5): 394-402, 2017. [PUBMED Abstract]
13. Yayla EM, Ozdemir L: Effect of Inhalation Aromatherapy on Procedural Pain and Anxiety After Needle Insertion Into an Implantable Central Venous Port Catheter: A Quasi-Randomized Controlled Pilot Study. Cancer Nurs 42 (1): 35-41, 2019 Jan/Feb. [PUBMED Abstract]
14. Deng C, Xie Y, Liu Y, et al.: Aromatherapy Plus Music Therapy Improve Pain Intensity and Anxiety Scores in Patients With Breast Cancer During Perioperative Periods: A Randomized Controlled Trial. Clin Breast Cancer 22 (2): 115-120, 2022. [PUBMED Abstract]
15. Hadfield N: The role of aromatherapy massage in reducing anxiety in patients with malignant brain tumours. Int J Palliat Nurs 7 (6): 279-85, 2001. [PUBMED Abstract]
16. Wilkinson S: Aromatherapy and massage in palliative care. Int J Palliat Nurs 1 (1): 21-30, 1995.
17. Corner J, Cawler N, Hildebrand S: An evaluation of the use of massage and essential oils on the wellbeing of cancer patients. Int J Palliat Nurs 1 (2): 67-73, 1995.
18. Zorba P, Ozdemir L: The Preliminary Effects of Massage and Inhalation Aromatherapy on Chemotherapy-Induced Acute Nausea and Vomiting: A Quasi-Randomized Controlled Pilot Trial. Cancer Nurs 41 (5): 359-366, 2018 Sep/Oct. [PUBMED Abstract]
19. Serfaty M, Wilkinson S, Freeman C, et al.: The ToT study: helping with Touch or Talk (ToT): a pilot randomised controlled trial to examine the clinical effectiveness of aromatherapy massage versus cognitive behaviour therapy for emotional distress in patients in cancer/palliative care. Psychooncology 21 (5): 563-9, 2012. [PUBMED Abstract]
20. Lai TK, Cheung MC, Lo CK, et al.: Effectiveness of aroma massage on advanced cancer patients with constipation: a pilot study. Complement Ther Clin Pract 17 (1): 37-43, 2011. [PUBMED Abstract]
21. Gravett P: Treatment of gastrointestinal upset following high-dose chemotherapy. International Journal of Aromatherapy 11 (2): 84-6, 2001.
22. Evans B: An audit into the effects of aromatherapy massage and the cancer patient in palliative and terminal care. Complement Ther Med 3 (4): 239-41, 1995.
23. Worwood VA: Aromatherapy for the Healthy Child: More Than 300 Natural, Non-Toxic, and Fragrant Essential Oil Blends. New World Library, 2000.
24. Ndao DH, Ladas EJ, Cheng B, et al.: Inhalation aromatherapy in children and adolescents undergoing stem cell infusion: results of a placebo-controlled double-blind trial. Psychooncology 21 (3): 247-54, 2012. [PUBMED Abstract]

Safety testing on essential oils has shown minimal adverse effects. Several essential oils have been approved for use as food additives and are classified as GRAS (generally recognized as safe) by the U.S. Food and Drug Administration; however, ingestion of large amounts of essential oils is not recommended. In addition, a few cases of contact dermatitis have been reported, mostly in aromatherapists who have had prolonged skin contact with essential oils in the context of aromatherapy massage.[1] Some essential oils (e.g., camphor oil) can cause local irritation; therefore, care should be taken when applying them. Phototoxicity has occurred when essential oils (particularly citrus oils) are applied directly to the skin before sun exposure. One case report also showed airborne contact dermatitis in the context of inhaled aromatherapy without massage.[2] Often, aromatherapy uses undefined mixtures of essential oils without specifying the plant sources. Allergic reactions are sometimes reported, especially after topical administration. Individual psychological associations with odors may result in adverse responses. Repeated exposure to lavender and tea tree oils by topical administration was shown in one study to be associated with reversible prepubertal gynecomastia.[3] The effects appear to have been caused by the purported weak estrogenic and antiandrogenic activities of lavender and tea tree oils. Therefore, avoiding these two essential oils is recommended in patients with estrogen-dependant tumors. However, this is the first published report of this type of adverse effect when using products containing tea tree or lavender oils.

References

1. Bilsland D, Strong A: Allergic contact dermatitis from the essential oil of French marigold (Tagetes patula) in an aromatherapist. Contact Dermatitis 23 (1): 55-6, 1990. [PUBMED Abstract]
2. Schaller M, Korting HC: Allergic airborne contact dermatitis from essential oils used in aromatherapy. Clin Exp Dermatol 20 (2): 143-5, 1995. [PUBMED Abstract]
3. Henley DV, Lipson N, Korach KS, et al.: Prepubertal gynecomastia linked to lavender and tea tree oils. N Engl J Med 356 (5): 479-85, 2007. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for people with cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score, with a score of 1 being the strongest evidence and a score of 4 being the weakest design (or sometime similar). For an explanation of the scores and additional information about levels of evidence analysis for people with cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What is aromatherapy?

   Aromatherapy is the use of essential oils from plants to improve the mind, body, and spirit. It is used by patients with cancer to improve quality of life and reduce stress, anxiety, pain, nausea, and vomiting caused by cancer and its treatment. Aromatherapy is often used with other complementary treatments like massage therapy and acupuncture, as well as with standard medical treatments, for symptom management.

   Essential oils are the fragrant (aromatic) part found in many plants, often under the surface of leaves, bark, or peel. The fragrance is released if the plant is crushed or a special steam process is used.

   There are many essential oils used in aromatherapy, including those from Roman chamomile, geranium, lavender, tea tree, lemon, ginger, cedarwood, and bergamot. Each plant’s essential oil has a different chemical make-up that affects how it smells, how it is absorbed, and how it affects the body.

   Essential oils are very concentrated. For example, it takes about 220 pounds of lavender flowers to make about 1 pound of essential oil. The aroma of essential oils fades away quickly when left open to air.

   The chemical compounds in essential oils can change as they get older. Many essential oils do not have an expiration date.

2. How is aromatherapy given or taken?

   Aromatherapy is used in several ways.

   • Indirect inhalation: The patient breathes in an essential oil by using a room diffuser, which spreads the essential oil through the air, or by placing drops on a tissue or piece of cotton nearby.
   • Direct inhalation: The patient breathes in an essential oil by using an individual inhaler made by floating essential oil drops on top of hot water.
   • Massage: In aromatherapy massage, one or more essential oils is diluted into a carrier oil and massaged into the skin.

   Essential oils may also be mixed with bath salts and lotions or applied to bandages.

   There are some essential oils used to treat specific conditions. However, the types of essential oils used and the ways they are combined vary, depending on the experience and training of the aromatherapist.

3. Have any preclinical (laboratory or animal) studies been done using aromatherapy?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   Laboratory and animal studies have tested the effects of essential oils. For information on laboratory and animal studies done using essential oils, see the Laboratory/Animal/Preclinical Studies section of the health professional version of Aromatherapy With Essential Oils.

4. Have any clinical trials (research studies with people) of aromatherapy been done?

   Clinical trials of aromatherapy have studied its use in the treatment of anxiety, nausea, vomiting, and other health-related conditions in cancer patients. No studies of aromatherapy used to treat cancer have been published in a peer-reviewed scientific journal.

   Studies of aromatherapy have shown mixed results. There have been some reports of improved mood, anxiety, sleep, nausea, and pain. Other studies reported that aromatherapy showed no change in symptoms.

   Studies on anxiety and depression

   • A trial of 103 cancer patients studied the effects of massage compared to massage with Roman chamomile essential oil. Two weeks later, a decrease in anxiety and improved symptoms were noted in the group that had massage with essential oil. The group that had massage only did not have the same benefit.
   • Another study of 58 patients with various cancers who completed six aromatherapy sessions showed a decrease in anxiety and depression compared with before the sessions began.
   • A randomized controlled trial studied the effects of inhalation aromatherapy on anxiety during radiation therapy. There were 313 patients randomly assigned to either lavender, bergamot, or cedarwood essential oils. There were no differences reported in depression or anxiety between the groups.

   Study on sleep

   • Newly diagnosed patients with acute myeloid leukemia who were hospitalized to receive intensive chemotherapy inhaled an essential oil through a diffuser overnight for 3 weeks. Patients were given the choice of lavender, peppermint, or chamomile. Improvement was reported in sleep, tiredness, drowsiness, lack of appetite, depression, anxiety, and well-being.

   Study on dry mouth

   • Radioactive iodine may cause damage to salivary glands. Increased saliva production during treatment may decrease damage to salivary glands. In a randomized controlled trial, patients who inhaled a mixture of lemon and ginger essential oils had increased saliva production compared with the placebo group.

   Studies on nausea and vomiting

   • A study of inhaled ginger essential oil in women receiving chemotherapy for breast cancer somewhat decreased acute nausea, but did not lessen vomiting or chronic nausea.
   • In a study of adult patients at the time of stem cell infusion, tasting or sniffing sliced oranges was more effective at reducing nausea, retching, and coughing than inhaling an orange essential oil.

   Study on aromatherapy in children

   Aromatherapy is used or claimed to be useful for a variety of childhood symptoms and conditions. When used safely, aromatherapy can help children feel calmer and sleep better.

   • A study of aromatherapy inhaled by children and adolescents undergoing stem cell transplant infusions compared essential oil from the peel of bergamot (a type of orange from trees grown in Italy) with a pleasant-smelling shampoo that did not contain essential oils. Bergamot oil is used in aromatherapy to relieve depression, anxiety, and poor digestion. The placebo-controlled, double-blind, randomized trial in 37 children and adolescents found that aromatherapy was not effective in reducing nausea, anxiety, or pain.

   Studies on procedure-related symptoms

   • Women having breast biopsies were randomly assigned to receive lavender-sandalwood or orange-peppermint essential oil drops placed on a felt tab and attached to their hospital gown or to no scent on the felt tab. Women who received the lavender-sandalwood aromatherapy tab had less anxiety than women who received the orange-peppermint aromatherapy tab or no scent tab.
   • In a study of inhaled lavender essential oil, eucalyptus essential oil, or no essential oil in cancer patients having needles inserted into a central venous port catheter, patients who inhaled lavender essential oil reported less pain.
   • A randomized controlled trial compared aromatherapy, music therapy, a combination of both, or a placebo in women with breast cancer before and after they had a mastectomy. The aromatherapy group received a mixture of lavender, bergamot, and geranium essential oils, while the music group was given a choice of music styles. The combination of treatments was found to be more effective in lessening pain and anxiety than either treatment alone.
5. Have any side effects or risks been reported from aromatherapy?

   Safety testing on essential oils shows very few side effects or risks when they are used as directed. Most essential oils have been approved as ingredients in food and fragrances and are labeled as GRAS (generally recognized as safe) by the U.S. Food and Drug Administration (FDA). Swallowing large amounts of essential oils is not recommended.

   Allergic reactions and skin irritation may occur when essential oils are in contact with the skin for long periods of time. Sun sensitivity may occur when citrus or other essential oils are applied to the skin before going out in the sun.

   Lavender and tea tree essential oils have been found to have effects similar to estrogen (female sex hormone) and also block or decrease the effect of androgens (male sex hormones). Applying lavender and tea tree essential oils to the skin over a long period of time was linked in one study to breast growth in boys who had not yet reached puberty.

6. Is aromatherapy approved by the FDA for use as a cancer treatment in the United States?

   Aromatherapy products do not need FDA approval.

   Aromatherapy is not regulated by state law, and there is no licensing required to practice aromatherapy in the United States. Practitioners often combine aromatherapy training with another field in which they are licensed, for example, massage therapy, nursing, acupuncture, or naturopathy.

   The National Association for Holistic Aromatherapy (www.naha.org) and the Alliance of International Aromatherapists (www.alliance-aromatherapists.org) are two organizations that have national educational standards for aromatherapists. A list of schools that offer certificate programs approved by NAHA can be found at https://naha.org/index.php/education/approved-schools/.

   The Canadian Federation of Aromatherapists (www.cfacanada.com) certifies aromatherapists in Canada. For a list of international aromatherapy programs, see the International Federation of Aromatherapists website (www.ifaroma.org/).

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Complementary and alternative medicine (CAM)—also called 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 type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a 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 been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used 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) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. 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 carefully reviews these materials to see if any seem worth further research.

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

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) 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.

CAM on PubMed

NCCIH 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 websites 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.)

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 website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 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.

Federal Trade Commission

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

This cancer information summary provides an overview of the use of Cannabis and its components as a treatment for people with cancer-related symptoms caused by the disease itself or its treatment.

This summary contains the following key information:

Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.

Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.

Cannabis, also known as marijuana, originated in Central Asia but is grown worldwide today. In the United States, it is a controlled substance and is classified as a Schedule I agent (a drug with a high potential for abuse, and no currently accepted medical use). The Cannabis plant produces a resin containing 21-carbon terpenophenolic compounds called cannabinoids, in addition to other compounds found in plants, such as terpenes and flavonoids. The highest concentration of cannabinoids is found in the female flowers of the plant.[1] Delta-9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid, but over 100 other cannabinoids have been reported to be present in the plant. Cannabidiol (CBD) does not produce the characteristic altered consciousness associated with Cannabis. CBD is thought to have potential therapeutic effectiveness and has recently been approved in the form of the pharmaceutical Epidiolex for the treatment of refractory seizure disorders in children. Other cannabinoids that are being investigated for potential medical benefits include cannabinol (CBN), cannabigerol (CBG), and tetrahydrocannabivarin (THCV).

Clinical trials conducted on medicinal Cannabis are limited. The U.S. Food and Drug Administration (FDA) has not approved the use of Cannabis as a treatment for any medical condition, although both isolated THC and CBD pharmaceuticals are licensed and approved. To conduct clinical drug research with botanical Cannabis in the United States, researchers must file an Investigational New Drug (IND) application with the FDA, obtain a Schedule I license from the U.S. Drug Enforcement Administration, and obtain approval from the National Institute on Drug Abuse.

In the 2018 United States Farm Bill, the term hemp is used to describe cultivars of the Cannabis species that contain less than 0.3% THC. Hemp oil or CBD oil are products manufactured from extracts of industrial hemp (i.e., low-THC cannabis cultivars), whereas hemp seed oil is an edible fatty oil that is essentially cannabinoid-free (see Table 1). Some products contain other botanical extracts and/or over-the-counter analgesics. These products are readily available as oral and topical tinctures or other formulations often advertised for pain management and other purposes. Hemp products containing less than 0.3% of delta-9-THC are not scheduled drugs and could be considered as Farm Bill compliant. While CBD is a controlled substance, hemp is not.

The potential benefits of medicinal Cannabis for people living with cancer include the following:[2]

A study of 13,180 patients with various cancers treated at 12 NCI-designated cancer centers revealed important insights into the prevalence, patterns, and perceptions of Cannabis use among people with cancer.[3] Estimates of frequency of use were obtained in a subset of 12,614 respondents from the 10 sites that drew probability samples, with 33% of the respondents reporting Cannabis use since their cancer diagnoses. Reported use showed little variation based on state legal status of Cannabis, with 26% usage reported in the one survey site in a state where Cannabis was fully illegal. Nearly 90% of Cannabis-using respondents reported various benefits: pain management (75%), better sleep (67%), nausea relief (65%), and improved appetite (56%). Sixty-five percent of patients with cancer reported some adverse effects such as inability to drive, difficulty concentrating, lung damage, and impaired memory. Reported risks of addiction and legal problems were more common in states where Cannabis was fully illegal. While 70% of patients expressed interest in learning more about medical Cannabis, only 21.5% discussed it with their cancer providers, and 15% reported receiving guidance from their healthcare team. The study highlights a significant gap between patient interest and provider engagement, emphasizing the need for better education and communication about Cannabis use in oncology care.

Although few relevant surveys of practice patterns exist, it appears that physicians caring for patients with cancer in the United States recommend medicinal Cannabis primarily for symptom management.[4]

This summary will review the role of Cannabis and the cannabinoids in the treatment of people with cancer and disease-related or treatment-related side effects. The NCI hosted a virtual meeting, the NCI Cannabis, Cannabinoids, and Cancer Research Symposium, on December 15–18, 2020. The seven sessions are summarized in the Journal of the National Cancer Institute Monographs and contain basic science and clinical information as well as a summary of the barriers to conducting Cannabis research.[5–11]

References

1. Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
2. Abrams DI: Integrating cannabis into clinical cancer care. Curr Oncol 23 (2): S8-S14, 2016. [PUBMED Abstract]
3. Ellison GL, Helzlsouer KJ, Rosenfield SM, et al.: Perceptions, prevalence, and patterns of cannabis use among cancer patients treated at 12 NCI-Designated Cancer Centers. J Natl Cancer Inst Monogr 2024 (66): 202-217, 2024. [PUBMED Abstract]
4. Doblin RE, Kleiman MA: Marijuana as antiemetic medicine: a survey of oncologists’ experiences and attitudes. J Clin Oncol 9 (7): 1314-9, 1991. [PUBMED Abstract]
5. Ellison GL, Alejandro Salicrup L, Freedman AN, et al.: The National Cancer Institute and Cannabis and Cannabinoids Research. J Natl Cancer Inst Monogr 2021 (58): 35-38, 2021. [PUBMED Abstract]
6. Sexton M, Garcia JM, Jatoi A, et al.: The Management of Cancer Symptoms and Treatment-Induced Side Effects With Cannabis or Cannabinoids. J Natl Cancer Inst Monogr 2021 (58): 86-98, 2021. [PUBMED Abstract]
7. Cooper ZD, Abrams DI, Gust S, et al.: Challenges for Clinical Cannabis and Cannabinoid Research in the United States. J Natl Cancer Inst Monogr 2021 (58): 114-122, 2021. [PUBMED Abstract]
8. Braun IM, Abrams DI, Blansky SE, et al.: Cannabis and the Cancer Patient. J Natl Cancer Inst Monogr 2021 (58): 68-77, 2021. [PUBMED Abstract]
9. Ward SJ, Lichtman AH, Piomelli D, et al.: Cannabinoids and Cancer Chemotherapy-Associated Adverse Effects. J Natl Cancer Inst Monogr 2021 (58): 78-85, 2021. [PUBMED Abstract]
10. McAllister SD, Abood ME, Califano J, et al.: Cannabinoid Cancer Biology and Prevention. J Natl Cancer Inst Monogr 2021 (58): 99-106, 2021. [PUBMED Abstract]
11. Abrams DI, Velasco G, Twelves C, et al.: Cancer Treatment: Preclinical & Clinical. J Natl Cancer Inst Monogr 2021 (58): 107-113, 2021. [PUBMED Abstract]

Cannabis use for medicinal purposes dates back at least 3,000 years.[1–5] It was introduced into Western medicine in 1839 by W.B. O’Shaughnessy, a surgeon who learned of its medicinal properties while working in India for the British East India Company. Its use was promoted for reported analgesic, sedative, anti-inflammatory, antispasmodic, and anticonvulsant effects.

In 1937, the U.S. Treasury Department introduced the Marihuana Tax Act. This Act imposed a levy of $1 per ounce for medicinal use of Cannabis and $100 per ounce for nonmedical use. Physicians in the United States were the principal opponents of the Act. The American Medical Association (AMA) opposed the Act because physicians were required to pay a special tax for prescribing Cannabis, use special order forms to procure it, and keep special records concerning its professional use. In addition, the AMA believed that objective evidence that Cannabis was harmful was lacking and that passage of the Act would impede further research into its medicinal worth.[6] In 1942, Cannabis was removed from the U.S. Pharmacopoeia because of persistent concerns about its potential to cause harm.[2,3] Recently, there has been renewed interest in Cannabis by the U.S. Pharmacopeia.[7]

In 1951, Congress passed the Boggs Act, which for the first time included Cannabis with narcotic drugs. In 1970, with the passage of the Controlled Substances Act, marijuana was classified by Congress as a Schedule I drug. Drugs in Schedule I are distinguished as having no currently accepted medicinal use in the United States. Other Schedule I substances include heroin, LSD, mescaline, and methaqualone.

Despite its designation as having no medicinal use, Cannabis was distributed by the U.S. government to patients on a case-by-case basis under the Compassionate Use Investigational New Drug program established in 1978. Distribution of Cannabis through this program was closed to new patients in 1992.[1–4] Although federal law prohibits the use of Cannabis, Figure 1 below shows the states and territories that have legalized Cannabis use for medical purposes. Additional states have legalized only one ingredient in Cannabis, such as cannabidiol (CBD), and are not included in the map. Some medical marijuana laws are broader than others, and there is state-to-state variation in the types of medical conditions for which treatment is allowed.[8]

Enlarge

The main psychoactive constituent of Cannabis was identified as delta-9-tetrahydrocannabinol (THC). In 1986, an isomer of synthetic delta-9-THC in sesame oil was licensed and approved for the treatment of chemotherapy-associated nausea and vomiting under the generic name dronabinol. Clinical trials determined that dronabinol was as effective as or better than other antiemetic agents available at the time.[9] Dronabinol was also studied for its ability to stimulate weight gain in patients with AIDS in the late 1980s. Thus, the indications were expanded to include treatment of anorexia associated with human immunodeficiency virus infection in 1992. Clinical trial results showed no statistically significant weight gain, although patients reported an improvement in appetite.[10,11] Another important cannabinoid found in Cannabis is CBD.[12] This is a nonpsychoactive cannabinoid, which is an analogue of THC.

In recent decades, the neurobiology of cannabinoids has been analyzed.[13–16] The first cannabinoid receptor, CB1, was identified in the brain in 1988. A second cannabinoid receptor, CB2, was identified in 1993. The highest expression of CB2 receptors is located on B lymphocytes and natural killer cells, suggesting a possible role in immunity. Endogenous cannabinoids (endocannabinoids) have been identified and appear to have a role in pain modulation, control of movement, feeding behavior, mood, bone growth, inflammation, neuroprotection, and memory.[17]

Nabiximols (Sativex), a Cannabis extract with a 1:1 ratio of THC:CBD, is approved in Canada (under the Notice of Compliance with Conditions) for symptomatic relief of pain in advanced cancer and multiple sclerosis.[18] Nabiximols is an herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains extracts from two Cannabis plant varieties. The extracts mixture is standardized to the concentrations of the psychoactive delta-9-THC and the nonpsychoactive CBD. The preparation also contains other, more minor cannabinoids, flavonoids, and terpenoids.[19] Canada, New Zealand, and most countries in western Europe also have approved nabiximols for spasticity of multiple sclerosis, a common symptom that may include muscle stiffness, reduced mobility, and pain, and for which existing therapy is unsatisfactory.

References

1. Abel EL: Marihuana, The First Twelve Thousand Years. Plenum Press, 1980. Also available online. Last accessed June 2, 2021.
2. Joy JE, Watson SJ, Benson JA, eds.: Marijuana and Medicine: Assessing the Science Base. National Academy Press, 1999. Also available online. Last accessed June 2, 2021.
3. Mack A, Joy J: Marijuana As Medicine? The Science Beyond the Controversy. National Academy Press, 2001. Also available online. Last accessed June 2, 2021.
4. Booth M: Cannabis: A History. St Martin’s Press, 2003.
5. Russo EB, Jiang HE, Li X, et al.: Phytochemical and genetic analyses of ancient cannabis from Central Asia. J Exp Bot 59 (15): 4171-82, 2008. [PUBMED Abstract]
6. Schaffer Library of Drug Policy: The Marihuana Tax Act of 1937: Taxation of Marihuana. Washington, DC: House of Representatives, Committee on Ways and Means, 1937. Available online. Last accessed June 2, 2021.
7. Sarma ND, Waye A, ElSohly MA, et al.: Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes. J Nat Prod 83 (4): 1334-1351, 2020. [PUBMED Abstract]
8. National Academies of Sciences, Engineering, and Medicine: The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. The National Academies Press, 2017.
9. Sallan SE, Zinberg NE, Frei E: Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 293 (16): 795-7, 1975. [PUBMED Abstract]
10. Gorter R, Seefried M, Volberding P: Dronabinol effects on weight in patients with HIV infection. AIDS 6 (1): 127, 1992. [PUBMED Abstract]
11. Beal JE, Olson R, Laubenstein L, et al.: Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10 (2): 89-97, 1995. [PUBMED Abstract]
12. Adams R, Hunt M, Clark JH: Structure of cannabidiol: a product isolated from the marihuana extract of Minnesota wild hemp. J Am Chem Soc 62 (1): 196-200, 1940. Also available online. Last accessed June 2, 2021.
13. Devane WA, Dysarz FA, Johnson MR, et al.: Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34 (5): 605-13, 1988. [PUBMED Abstract]
14. Devane WA, Hanus L, Breuer A, et al.: Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 (5090): 1946-9, 1992. [PUBMED Abstract]
15. Pertwee RG, Howlett AC, Abood ME, et al.: International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev 62 (4): 588-631, 2010. [PUBMED Abstract]
16. Felder CC, Glass M: Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 38: 179-200, 1998. [PUBMED Abstract]
17. Pacher P, Bátkai S, Kunos G: The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (3): 389-462, 2006. [PUBMED Abstract]
18. Howard P, Twycross R, Shuster J, et al.: Cannabinoids. J Pain Symptom Manage 46 (1): 142-9, 2013. [PUBMED Abstract]
19. Nabiximols. Bethesda, MD: National Center for Biotechnology Information, 2009. Available online. Last accessed June 2, 2021.

Cannabinoids are a group of 21-carbon–containing terpenophenolic compounds produced uniquely by Cannabis species (e.g., Cannabis sativa L.).[1,2] These plant-derived compounds may be referred to as phytocannabinoids. Although delta-9-tetrahydrocannabinol (THC) is the primary psychoactive ingredient, other known compounds with biological activity are cannabinol, cannabidiol (CBD), cannabichromene, cannabigerol, tetrahydrocannabivarin, and delta-8-THC. CBD, in particular, is thought to have significant analgesic, anti-inflammatory, and anxiolytic activity without the psychoactive effect (high) of delta-9-THC.

References

1. Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
2. Grotenhermen F, Russo E, eds.: Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. The Haworth Press, 2002.
3. National Toxicology Program: NTP toxicology and carcinogenesis studies of 1-trans-delta(9)-tetrahydrocannabinol (CAS No. 1972-08-3) in F344 rats and B6C3F1 mice (gavage studies). Natl Toxicol Program Tech Rep Ser 446: 1-317, 1996. [PUBMED Abstract]
4. Bifulco M, Laezza C, Pisanti S, et al.: Cannabinoids and cancer: pros and cons of an antitumour strategy. Br J Pharmacol 148 (2): 123-35, 2006. [PUBMED Abstract]
5. Sánchez C, de Ceballos ML, Gomez del Pulgar T, et al.: Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res 61 (15): 5784-9, 2001. [PUBMED Abstract]
6. McKallip RJ, Lombard C, Fisher M, et al.: Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100 (2): 627-34, 2002. [PUBMED Abstract]
7. Casanova ML, Blázquez C, Martínez-Palacio J, et al.: Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest 111 (1): 43-50, 2003. [PUBMED Abstract]
8. Blázquez C, González-Feria L, Alvarez L, et al.: Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas. Cancer Res 64 (16): 5617-23, 2004. [PUBMED Abstract]
9. Guzmán M: Cannabinoids: potential anticancer agents. Nat Rev Cancer 3 (10): 745-55, 2003. [PUBMED Abstract]
10. Blázquez C, Casanova ML, Planas A, et al.: Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17 (3): 529-31, 2003. [PUBMED Abstract]
11. Vaccani A, Massi P, Colombo A, et al.: Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism. Br J Pharmacol 144 (8): 1032-6, 2005. [PUBMED Abstract]
12. Ramer R, Bublitz K, Freimuth N, et al.: Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. FASEB J 26 (4): 1535-48, 2012. [PUBMED Abstract]
13. Velasco G, Sánchez C, Guzmán M: Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer 12 (6): 436-44, 2012. [PUBMED Abstract]
14. Cridge BJ, Rosengren RJ: Critical appraisal of the potential use of cannabinoids in cancer management. Cancer Manag Res 5: 301-13, 2013. [PUBMED Abstract]
15. Vara D, Salazar M, Olea-Herrero N, et al.: Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death Differ 18 (7): 1099-111, 2011. [PUBMED Abstract]
16. Preet A, Qamri Z, Nasser MW, et al.: Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. Cancer Prev Res (Phila) 4 (1): 65-75, 2011. [PUBMED Abstract]
17. Nasser MW, Qamri Z, Deol YS, et al.: Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. PLoS One 6 (9): e23901, 2011. [PUBMED Abstract]
18. Shrivastava A, Kuzontkoski PM, Groopman JE, et al.: Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Mol Cancer Ther 10 (7): 1161-72, 2011. [PUBMED Abstract]
19. Caffarel MM, Andradas C, Mira E, et al.: Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol Cancer 9: 196, 2010. [PUBMED Abstract]
20. McAllister SD, Murase R, Christian RT, et al.: Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res Treat 129 (1): 37-47, 2011. [PUBMED Abstract]
21. Aviello G, Romano B, Borrelli F, et al.: Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. J Mol Med (Berl) 90 (8): 925-34, 2012. [PUBMED Abstract]
22. Romano B, Borrelli F, Pagano E, et al.: Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine 21 (5): 631-9, 2014. [PUBMED Abstract]
23. Preet A, Ganju RK, Groopman JE: Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 27 (3): 339-46, 2008. [PUBMED Abstract]
24. Zhu LX, Sharma S, Stolina M, et al.: Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J Immunol 165 (1): 373-80, 2000. [PUBMED Abstract]
25. McKallip RJ, Nagarkatti M, Nagarkatti PS: Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 174 (6): 3281-9, 2005. [PUBMED Abstract]
26. Massa F, Marsicano G, Hermann H, et al.: The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 113 (8): 1202-9, 2004. [PUBMED Abstract]
27. Patsos HA, Hicks DJ, Greenhough A, et al.: Cannabinoids and cancer: potential for colorectal cancer therapy. Biochem Soc Trans 33 (Pt 4): 712-4, 2005. [PUBMED Abstract]
28. Liu WM, Fowler DW, Dalgleish AG: Cannabis-derived substances in cancer therapy–an emerging anti-inflammatory role for the cannabinoids. Curr Clin Pharmacol 5 (4): 281-7, 2010. [PUBMED Abstract]
29. Malfitano AM, Ciaglia E, Gangemi G, et al.: Update on the endocannabinoid system as an anticancer target. Expert Opin Ther Targets 15 (3): 297-308, 2011. [PUBMED Abstract]
30. Sarfaraz S, Adhami VM, Syed DN, et al.: Cannabinoids for cancer treatment: progress and promise. Cancer Res 68 (2): 339-42, 2008. [PUBMED Abstract]
31. Nabissi M, Morelli MB, Santoni M, et al.: Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis 34 (1): 48-57, 2013. [PUBMED Abstract]
32. Marcu JP, Christian RT, Lau D, et al.: Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol Cancer Ther 9 (1): 180-9, 2010. [PUBMED Abstract]
33. Torres S, Lorente M, Rodríguez-Fornés F, et al.: A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10 (1): 90-103, 2011. [PUBMED Abstract]
34. Rocha FC, Dos Santos Júnior JG, Stefano SC, et al.: Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas. J Neurooncol 116 (1): 11-24, 2014. [PUBMED Abstract]
35. Pacher P, Bátkai S, Kunos G: The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (3): 389-462, 2006. [PUBMED Abstract]
36. Darmani NA: Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB(1) receptor antagonist/inverse agonist SR 141716A. Neuropsychopharmacology 24 (2): 198-203, 2001. [PUBMED Abstract]
37. Darmani NA: Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew. Pharmacol Biochem Behav 69 (1-2): 239-49, 2001 May-Jun. [PUBMED Abstract]
38. Parker LA, Kwiatkowska M, Burton P, et al.: Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew). Psychopharmacology (Berl) 171 (2): 156-61, 2004. [PUBMED Abstract]
39. Mechoulam R, Berry EM, Avraham Y, et al.: Endocannabinoids, feeding and suckling–from our perspective. Int J Obes (Lond) 30 (Suppl 1): S24-8, 2006. [PUBMED Abstract]
40. Fride E, Bregman T, Kirkham TC: Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp Biol Med (Maywood) 230 (4): 225-34, 2005. [PUBMED Abstract]
41. Baker D, Pryce G, Giovannoni G, et al.: The therapeutic potential of cannabis. Lancet Neurol 2 (5): 291-8, 2003. [PUBMED Abstract]
42. Walker JM, Hohmann AG, Martin WJ, et al.: The neurobiology of cannabinoid analgesia. Life Sci 65 (6-7): 665-73, 1999. [PUBMED Abstract]
43. Meng ID, Manning BH, Martin WJ, et al.: An analgesia circuit activated by cannabinoids. Nature 395 (6700): 381-3, 1998. [PUBMED Abstract]
44. Walker JM, Huang SM, Strangman NM, et al.: Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci U S A 96 (21): 12198-203, 1999. [PUBMED Abstract]
45. Facci L, Dal Toso R, Romanello S, et al.: Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A 92 (8): 3376-80, 1995. [PUBMED Abstract]
46. Ibrahim MM, Porreca F, Lai J, et al.: CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci U S A 102 (8): 3093-8, 2005. [PUBMED Abstract]
47. Richardson JD, Kilo S, Hargreaves KM: Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors. Pain 75 (1): 111-9, 1998. [PUBMED Abstract]
48. Khasabova IA, Gielissen J, Chandiramani A, et al.: CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain. Behav Pharmacol 22 (5-6): 607-16, 2011. [PUBMED Abstract]
49. Ward SJ, McAllister SD, Kawamura R, et al.: Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT(1A) receptors without diminishing nervous system function or chemotherapy efficacy. Br J Pharmacol 171 (3): 636-45, 2014. [PUBMED Abstract]
50. Rahn EJ, Makriyannis A, Hohmann AG: Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. Br J Pharmacol 152 (5): 765-77, 2007. [PUBMED Abstract]
51. Khasabova IA, Khasabov S, Paz J, et al.: Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy. J Neurosci 32 (20): 7091-101, 2012. [PUBMED Abstract]
52. Campos AC, Guimarães FS: Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl) 199 (2): 223-30, 2008. [PUBMED Abstract]
53. Crippa JA, Zuardi AW, Hallak JE: [Therapeutical use of the cannabinoids in psychiatry]. Rev Bras Psiquiatr 32 (Suppl 1): S56-66, 2010. [PUBMED Abstract]
54. Guimarães FS, Chiaretti TM, Graeff FG, et al.: Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl) 100 (4): 558-9, 1990. [PUBMED Abstract]
55. Méndez-Díaz M, Caynas-Rojas S, Arteaga Santacruz V, et al.: Entopeduncular nucleus endocannabinoid system modulates sleep-waking cycle and mood in rats. Pharmacol Biochem Behav 107: 29-35, 2013. [PUBMED Abstract]
56. Pava MJ, den Hartog CR, Blanco-Centurion C, et al.: Endocannabinoid modulation of cortical up-states and NREM sleep. PLoS One 9 (2): e88672, 2014. [PUBMED Abstract]

References

1. Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
2. Agurell S, Halldin M, Lindgren JE, et al.: Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev 38 (1): 21-43, 1986. [PUBMED Abstract]
3. Yamamoto I, Watanabe K, Narimatsu S, et al.: Recent advances in the metabolism of cannabinoids. Int J Biochem Cell Biol 27 (8): 741-6, 1995. [PUBMED Abstract]
4. Engels FK, de Jong FA, Sparreboom A, et al.: Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. Oncologist 12 (3): 291-300, 2007. [PUBMED Abstract]
5. FDA Warns Companies Marketing Unproven Products, Derived From Marijuana, That Claim to Treat or Cure Cancer [News Release]. Silver Spring, Md: Food and Drug Administration, 2017. Available online. Last accessed January 4, 2019.
6. Yamaori S, Okamoto Y, Yamamoto I, et al.: Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 39 (11): 2049-56, 2011. [PUBMED Abstract]
7. Jiang R, Yamaori S, Okamoto Y, et al.: Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet 28 (4): 332-8, 2013. [PUBMED Abstract]
8. Azwell T, Ciotti C, Adams A: Variation among hemp (Cannabis sativus L.) analytical testing laboratories evinces regulatory and quality control issues for the industry. J Appl Res Med Aromat Plants 31: 100434, 2022. Available online. Last accessed October 17, 2024.
9. Berthiller J, Straif K, Boniol M, et al.: Cannabis smoking and risk of lung cancer in men: a pooled analysis of three studies in Maghreb. J Thorac Oncol 3 (12): 1398-403, 2008. [PUBMED Abstract]
10. Sidney S, Quesenberry CP, Friedman GD, et al.: Marijuana use and cancer incidence (California, United States). Cancer Causes Control 8 (5): 722-8, 1997. [PUBMED Abstract]
11. Hashibe M, Morgenstern H, Cui Y, et al.: Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol Biomarkers Prev 15 (10): 1829-34, 2006. [PUBMED Abstract]
12. Mehra R, Moore BA, Crothers K, et al.: The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med 166 (13): 1359-67, 2006. [PUBMED Abstract]
13. National Academies of Sciences, Engineering, and Medicine: The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. The National Academies Press, 2017.
14. Marks MA, Chaturvedi AK, Kelsey K, et al.: Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium. Cancer Epidemiol Biomarkers Prev 23 (1): 160-71, 2014. [PUBMED Abstract]
15. de Carvalho MF, Dourado MR, Fernandes IB, et al.: Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies. Arch Oral Biol 60 (12): 1750-5, 2015. [PUBMED Abstract]
16. Daling JR, Doody DR, Sun X, et al.: Association of marijuana use and the incidence of testicular germ cell tumors. Cancer 115 (6): 1215-23, 2009. [PUBMED Abstract]
17. Trabert B, Sigurdson AJ, Sweeney AM, et al.: Marijuana use and testicular germ cell tumors. Cancer 117 (4): 848-53, 2011. [PUBMED Abstract]
18. Lacson JC, Carroll JD, Tuazon E, et al.: Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer 118 (21): 5374-83, 2012. [PUBMED Abstract]
19. Callaghan RC, Allebeck P, Akre O, et al.: Cannabis Use and Incidence of Testicular Cancer: A 42-Year Follow-up of Swedish Men between 1970 and 2011. Cancer Epidemiol Biomarkers Prev 26 (11): 1644-1652, 2017. [PUBMED Abstract]
20. Thomas AA, Wallner LP, Quinn VP, et al.: Association between cannabis use and the risk of bladder cancer: results from the California Men’s Health Study. Urology 85 (2): 388-92, 2015. [PUBMED Abstract]
21. Health Canada: Marihuana (Marijuana, Cannabis): Dried Plant for Administration by Ingestion or Other Means. Ottawa, Canada: Health Canada, 2010. Available online. Last accessed October 18, 2017.
22. Pergam SA, Woodfield MC, Lee CM, et al.: Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer 123 (22): 4488-4497, 2017. [PUBMED Abstract]
23. Bar-Lev Schleider L, Mechoulam R, Lederman V, et al.: Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer. Eur J Intern Med 49: 37-43, 2018. [PUBMED Abstract]
24. Anderson SP, Zylla DM, McGriff DM, et al.: Impact of Medical Cannabis on Patient-Reported Symptoms for Patients With Cancer Enrolled in Minnesota’s Medical Cannabis Program. J Oncol Pract 15 (4): e338-e345, 2019. [PUBMED Abstract]
25. Weiss MC, Hibbs JE, Buckley ME, et al.: A Coala-T-Cannabis Survey Study of breast cancer patients’ use of cannabis before, during, and after treatment. Cancer 128 (1): 160-168, 2022. [PUBMED Abstract]
26. McClure EA, Walters KJ, Tomko RL, et al.: Cannabis use prevalence, patterns, and reasons for use among patients with cancer and survivors in a state without legal cannabis access. Support Care Cancer 31 (7): 429, 2023. [PUBMED Abstract]
27. Guzmán M, Duarte MJ, Blázquez C, et al.: A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer 95 (2): 197-203, 2006. [PUBMED Abstract]
28. Velasco G, Sánchez C, Guzmán M: Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer 12 (6): 436-44, 2012. [PUBMED Abstract]
29. Twelves C, Sabel M, Checketts D, et al.: A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma. Br J Cancer 124 (8): 1379-1387, 2021. [PUBMED Abstract]
30. Likar R, Koestenberger M, Stultschnig M, et al.: Concomitant Treatment of Malignant Brain Tumours With CBD – A Case Series and Review of the Literature. Anticancer Res 39 (10): 5797-5801, 2019. [PUBMED Abstract]
31. Yeshurun M, Shpilberg O, Herscovici C, et al.: Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study. Biol Blood Marrow Transplant 21 (10): 1770-5, 2015. [PUBMED Abstract]
32. Singh Y, Bali C: Cannabis extract treatment for terminal acute lymphoblastic leukemia with a Philadelphia chromosome mutation. Case Rep Oncol 6 (3): 585-92, 2013. [PUBMED Abstract]
33. Foroughi M, Hendson G, Sargent MA, et al.: Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas–possible role of Cannabis inhalation. Childs Nerv Syst 27 (4): 671-9, 2011. [PUBMED Abstract]
34. Goyal S, Kubendran S, Kogan M, et al.: High expectations: The landscape of clinical trials of medical marijuana in oncology. Complement Ther Med 49: 102336, 2020. [PUBMED Abstract]
35. Sutton IR, Daeninck P: Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J Support Oncol 4 (10): 531-5, 2006 Nov-Dec. [PUBMED Abstract]
36. Ahmedzai S, Carlyle DL, Calder IT, et al.: Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. Br J Cancer 48 (5): 657-63, 1983. [PUBMED Abstract]
37. Chan HS, Correia JA, MacLeod SM: Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. Pediatrics 79 (6): 946-52, 1987. [PUBMED Abstract]
38. Johansson R, Kilkku P, Groenroos M: A double-blind, controlled trial of nabilone vs. prochlorperazine for refractory emesis induced by cancer chemotherapy. Cancer Treat Rev 9 (Suppl B): 25-33, 1982. [PUBMED Abstract]
39. Niiranen A, Mattson K: A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 8 (4): 336-40, 1985. [PUBMED Abstract]
40. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2021. Plymouth Meeting, Pa: National Comprehensive Cancer Network, 2021. Available online with free registration. Last accessed August 26, 2021..
41. Hesketh PJ, Kris MG, Basch E, et al.: Antiemetics: ASCO Guideline Update. J Clin Oncol 38 (24): 2782-2797, 2020. [PUBMED Abstract]
42. Tramèr MR, Carroll D, Campbell FA, et al.: Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 323 (7303): 16-21, 2001. [PUBMED Abstract]
43. Ben Amar M: Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol 105 (1-2): 1-25, 2006. [PUBMED Abstract]
44. Smith LA, Azariah F, Lavender VT, et al.: Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database Syst Rev (11): CD009464, 2015. [PUBMED Abstract]
45. Meiri E, Jhangiani H, Vredenburgh JJ, et al.: Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 23 (3): 533-43, 2007. [PUBMED Abstract]
46. Chang AE, Shiling DJ, Stillman RC, et al.: A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer 47 (7): 1746-51, 1981. [PUBMED Abstract]
47. Chang AE, Shiling DJ, Stillman RC, et al.: Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Ann Intern Med 91 (6): 819-24, 1979. [PUBMED Abstract]
48. Levitt M, Faiman C, Hawks R, et al.: Randomized double blind comparison of delta-9-tetrahydrocannabinol and marijuana as chemotherapy antiemetics. [Abstract] Proceedings of the American Society of Clinical Oncology 3: A-C354, 91, 1984.
49. Musty RE, Rossi R: Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. Journal of Cannabis Therapeutics 1 (1): 29-56, 2001. Also available online. Last accessed October 18, 2017.
50. Duran M, Pérez E, Abanades S, et al.: Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70 (5): 656-63, 2010. [PUBMED Abstract]
51. Grimison P, Mersiades A, Kirby A, et al.: Oral Cannabis Extract for Secondary Prevention of Chemotherapy-Induced Nausea and Vomiting: Final Results of a Randomized, Placebo-Controlled, Phase II/III Trial. J Clin Oncol 42 (34): 4040-4050, 2024. [PUBMED Abstract]
52. Regelson W, Butler JR, Schulz J, et al.: Delta-9-tetrahydrocannabinol as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: Braude MC, Szara S: The Pharmacology of Marihuana. Raven Press, 1976, pp 763-76.
53. Brisbois TD, de Kock IH, Watanabe SM, et al.: Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 22 (9): 2086-93, 2011. [PUBMED Abstract]
54. Turcott JG, Del Rocío Guillen Núñez M, Flores-Estrada D, et al.: The effect of nabilone on appetite, nutritional status, and quality of life in lung cancer patients: a randomized, double-blind clinical trial. Support Care Cancer 26 (9): 3029-3038, 2018. [PUBMED Abstract]
55. Jatoi A, Windschitl HE, Loprinzi CL, et al.: Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 20 (2): 567-73, 2002. [PUBMED Abstract]
56. Foltin RW, Brady JV, Fischman MW: Behavioral analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 25 (3): 577-82, 1986. [PUBMED Abstract]
57. Foltin RW, Fischman MW, Byrne MF: Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 11 (1): 1-14, 1988. [PUBMED Abstract]
58. Strasser F, Luftner D, Possinger K, et al.: Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 24 (21): 3394-400, 2006. [PUBMED Abstract]
59. Aggarwal SK: Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain 29 (2): 162-71, 2013. [PUBMED Abstract]
60. Walker JM, Hohmann AG, Martin WJ, et al.: The neurobiology of cannabinoid analgesia. Life Sci 65 (6-7): 665-73, 1999. [PUBMED Abstract]
61. Calignano A, La Rana G, Giuffrida A, et al.: Control of pain initiation by endogenous cannabinoids. Nature 394 (6690): 277-81, 1998. [PUBMED Abstract]
62. Fields HL, Meng ID: Watching the pot boil. Nat Med 4 (9): 1008-9, 1998. [PUBMED Abstract]
63. Noyes R, Brunk SF, Baram DA, et al.: Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol 15 (2-3): 139-43, 1975 Feb-Mar. [PUBMED Abstract]
64. Noyes R, Brunk SF, Avery DA, et al.: The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther 18 (1): 84-9, 1975. [PUBMED Abstract]
65. Johnson JR, Burnell-Nugent M, Lossignol D, et al.: 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 39 (2): 167-79, 2010. [PUBMED Abstract]
66. Portenoy RK, Ganae-Motan ED, Allende S, et al.: Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain 13 (5): 438-49, 2012. [PUBMED Abstract]
67. Johnson JR, Lossignol D, Burnell-Nugent M, et al.: An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage 46 (2): 207-18, 2013. [PUBMED Abstract]
68. Maida V, Ennis M, Irani S, et al.: Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. J Support Oncol 6 (3): 119-24, 2008. [PUBMED Abstract]
69. Abrams DI, Couey P, Shade SB, et al.: Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther 90 (6): 844-51, 2011. [PUBMED Abstract]
70. Wilsey B, Marcotte T, Deutsch R, et al.: Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain 14 (2): 136-48, 2013. [PUBMED Abstract]
71. Wilsey B, Marcotte T, Tsodikov A, et al.: A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 9 (6): 506-21, 2008. [PUBMED Abstract]
72. Waissengrin B, Mirelman D, Pelles S, et al.: Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis. Ther Adv Med Oncol 13: 1758835921990203, 2021. [PUBMED Abstract]
73. Lynch ME, Cesar-Rittenberg P, Hohmann AG: A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 47 (1): 166-73, 2014. [PUBMED Abstract]
74. Zylla DM, Eklund J, Gilmore G, et al.: A randomized trial of medical cannabis in patients with stage IV cancers to assess feasibility, dose requirements, impact on pain and opioid use, safety, and overall patient satisfaction. Support Care Cancer 29 (12): 7471-7478, 2021. [PUBMED Abstract]
75. Noyes R, Baram DA: Cannabis analgesia. Compr Psychiatry 15 (6): 531-5, 1974 Nov-Dec. [PUBMED Abstract]
76. Zhang H, Xie M, Archibald SD, et al.: Association of Marijuana Use With Psychosocial and Quality of Life Outcomes Among Patients With Head and Neck Cancer. JAMA Otolaryngol Head Neck Surg 144 (11): 1017-1022, 2018. [PUBMED Abstract]
77. Schloss J, Lacey J, Sinclair J, et al.: A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas. Front Oncol 11: 649555, 2021. [PUBMED Abstract]
78. Hardy J, Greer R, Huggett G, et al.: Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD). J Clin Oncol 41 (7): 1444-1452, 2023. [PUBMED Abstract]
79. Chhabra M, Ben-Eltriki M, Paul A, et al.: Cannabinoids for symptom management in children with cancer: A systematic review and meta-analysis. Cancer 129 (22): 3656-3670, 2023. [PUBMED Abstract]
80. Ofir R, Bar-Sela G, Weyl Ben-Arush M, et al.: Medical marijuana use for pediatric oncology patients: single institution experience. Pediatr Hematol Oncol 36 (5): 255-266, 2019. [PUBMED Abstract]
81. Oberoi S, Protudjer JLP, Rapoport A, et al.: Perspectives of pediatric oncologists and palliative care physicians on the therapeutic use of cannabis in children with cancer. Cancer Rep (Hoboken) 5 (9): e1551, 2022. [PUBMED Abstract]
82. Ananth P, Ma C, Al-Sayegh H, et al.: Provider Perspectives on Use of Medical Marijuana in Children With Cancer. Pediatrics 141 (1): , 2018. [PUBMED Abstract]
83. Beal JE, Olson R, Laubenstein L, et al.: Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10 (2): 89-97, 1995. [PUBMED Abstract]

References

1. Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
2. Grotenhermen F, Russo E, eds.: Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. The Haworth Press, 2002.
3. Sutton IR, Daeninck P: Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J Support Oncol 4 (10): 531-5, 2006 Nov-Dec. [PUBMED Abstract]
4. Guzmán M: Cannabinoids: potential anticancer agents. Nat Rev Cancer 3 (10): 745-55, 2003. [PUBMED Abstract]
5. Yamaori S, Okamoto Y, Yamamoto I, et al.: Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 39 (11): 2049-56, 2011. [PUBMED Abstract]
6. Jiang R, Yamaori S, Okamoto Y, et al.: Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet 28 (4): 332-8, 2013. [PUBMED Abstract]
7. Guedon M, Le Bozec A, Brugel M, et al.: Cannabidiol-drug interaction in cancer patients: A retrospective study in a real-life setting. Br J Clin Pharmacol 89 (7): 2322-2328, 2023. [PUBMED Abstract]
8. Pletcher MJ, Vittinghoff E, Kalhan R, et al.: Association between marijuana exposure and pulmonary function over 20 years. JAMA 307 (2): 173-81, 2012. [PUBMED Abstract]
9. Kocis PT, Vrana KE: Delta-9-tetrahydrocannabinol and cannabidiol drug-drug interactions. Med Cannabis Cannabinoids 3 (1): 61-73, 2020.
10. Taha T, Meiri D, Talhamy S, et al.: Cannabis Impacts Tumor Response Rate to Nivolumab in Patients with Advanced Malignancies. Oncologist 24 (4): 549-554, 2019. [PUBMED Abstract]
11. Bar-Sela G, Cohen I, Campisi-Pinto S, et al.: Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome. Cancers (Basel) 12 (9): , 2020. [PUBMED Abstract]

To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for people with cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., end points) measured. The resulting two scores are then combined to produce an overall score. For an explanation of possible scores and additional information about levels of evidence analysis of Complementary and Alternative Medicine (CAM) treatments for people with cancer, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.

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.

General Information

Added text about the findings from a multicenter survey on perceptions, prevalence, and patterns of Cannabis use among 13,180 patients with various cancers treated at 12 National Cancer Institute-designated cancer centers (cited Ellison et al. as reference 4).

This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

1. What is Cannabis?

   Cannabis, also known as marijuana, is a plant first grown in Central Asia that is now grown in many parts of the world. The Cannabis plant makes a resin (thick substance) that contains compounds called cannabinoids. Some cannabinoids are psychoactive (affects your mind or mood). In the United States, Cannabis is a controlled substance and has been classified as a Schedule I agent (a drug with a high potential for abuse and no accepted medical use).

   Hemp is a mixture of the Cannabis plant with very low levels of psychoactive compounds. Hemp oil or cannabidiol (CBD) are made from extracts of industrial hemp, while hemp seed oil is an edible fatty oil that contains few or no cannabinoids. Hemp is not a controlled substance.

   For information on medicinal Cannabis products, see the General Information section in the health professional version of Cannabis and Cannabinoids.

   Clinical trials that study Cannabis for cancer treatment are limited. To start a clinical trial with Cannabis in the United States, researchers must file an Investigational New Drug (IND) application with the FDA, have a Schedule I license from the U.S. Drug Enforcement Administration, and have approval from the National Institute on Drug Abuse.

   By federal law, possessing Cannabis (marijuana) is illegal in the United States unless it is used in approved research settings. However, a growing number of states, territories, and the District of Columbia have passed laws to legalize medical and/or recreational marijuana. (See Question 3).

2. What are cannabinoids?

   Cannabinoids, also known as phytocannabinoids, are chemicals in Cannabis that cause drug-like effects in the body, including the central nervous system and the immune system. Over 100 cannabinoids have been found in Cannabis. The main psychoactive cannabinoid in Cannabis is delta-9-THC. Another active cannabinoid is cannabidiol (CBD).

   Cannabinoids may help treat the side effects of cancer and cancer treatment.

3. If Cannabis is illegal, how do some patients with cancer in the United States use it?

   Although federal law prohibits the use of Cannabis, the map below shows the states and territories that have legalized Cannabis for medical use. Some other states have legalized only one ingredient in Cannabis, such as cannabidiol (CBD), and these states are not included in the map. Medical marijuana laws vary from state to state.

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4. How is Cannabis given or taken?

   Cannabis may be taken by mouth (in baked goods or as an herbal tea) or may be inhaled. When taken by mouth, the main psychoactive part of Cannabis (delta-9-THC) goes through the liver and is changed into a different psychoactive chemical (11-OH-THC).

   When Cannabis is smoked and inhaled, cannabinoids quickly enter the bloodstream. The psychoactive chemical (11-OH-THC) is made in smaller amounts than when taken by mouth.

   Clinical trials are studying a medicine made from an extract of Cannabis that contains specific amounts of cannabinoids. This medicine is sprayed under the tongue.

5. Have any laboratory or animal studies been done using Cannabis or cannabinoids?

   In laboratory studies, tumor cells are used to test a substance to find out if it is likely to have any anticancer effects. In animal studies, tests are done to see if a drug, procedure, or treatment is safe and effective in animals. Laboratory and animal studies are done before a substance is tested in people.

   For information on laboratory and animal studies done using cannabinoids, see the Laboratory/Animal/Preclinical Studies section in the health professional version of Cannabis and Cannabinoids.

6. Have any studies of Cannabis or cannabinoids been done in people with cancer?

   No ongoing studies of Cannabis as a treatment for cancer in people have been found in the CAM on PubMed database maintained by the National Institutes of Health.

   Small studies have been done, but the results have not been reported or suggest a need for larger studies.

   • An oral spray of Cannabis extract given with temozolomide to treat recurrent glioblastoma multiforme.
   • CBD taken by mouth to treat acute graft-versus-host disease in patients who have undergone allogeneic hematopoietic stem cell transplantation.

   Cannabis and cannabinoids have been studied as ways to manage side effects of cancer and cancer therapies.

   Nausea and vomiting

   Cannabis and cannabinoids have been studied in the treatment of nausea and vomiting caused by cancer or cancer treatment:

   • Delta-9-THC taken by mouth: Two cannabinoid drugs, dronabinol and nabilone, approved by the U.S. Food and Drug Administration (FDA), are given to treat nausea and vomiting caused by chemotherapy in patients who have not responded to standard antiemetic therapy. Clinical trials have shown that both dronabinol and nabilone work as well as or better than other drugs to relieve nausea and vomiting.
   • Oral spray with delta-9-THC and CBD: Nabiximols, a Cannabis extract given as a mouth spray, was shown in a small randomized, placebo-controlled, double-blinded clinical trial in Spain to treat nausea and vomiting caused by chemotherapy.
   • Inhaled Cannabis: Small trials have studied inhaled Cannabis for the treatment of nausea and vomiting caused by chemotherapy.

   Newer drugs given for nausea caused by chemotherapy have not been compared with Cannabis or cannabinoids in patients with cancer.

   There is growing interest in treating children for symptoms such as nausea with Cannabis and cannabinoids, but studies are limited. The American Academy of Pediatrics has not endorsed Cannabis and cannabinoid use because of concerns about its effect on brain development.

   Appetite

   The ability of cannabinoids to increase appetite has been studied:

   • Delta-9-THC taken by mouth: A clinical trial compared delta-9-THC (dronabinol) and a standard drug (megestrol, an appetite stimulant) in patients with advanced cancer and loss of appetite. Results showed that delta-9-THC did not help increase appetite or weight gain in patients with advanced cancer compared with megestrol.
   • Inhaled Cannabis: There are no published studies of the effect of inhaled Cannabis on patients with cancer who have loss of appetite.

   Pain relief

   Cannabis and cannabinoids have been studied in the treatment of pain:

   • Vaporized Cannabis with opioids: In a study of 21 patients with chronic pain, vaporized Cannabis given with morphine relieved pain better than morphine alone, while vaporized Cannabis given with oxycodone did not give greater pain relief. Further studies are needed.
   • Inhaled Cannabis: Randomized controlled trials of inhaled Cannabis in patients with peripheral neuropathy or other nerve pain found that inhaled Cannabis relieved pain better than inhaled placebo. A retrospective study of patients who received an anticancer drug for gastrointestinal cancers found that those who also inhaled Cannabis had less nerve pain, including those who took Cannabis before they began the anticancer drug.
   • Cannabis plant extract: A study of Cannabis extract that was sprayed under the tongue found it helped patients with advanced cancer whose pain was not relieved by strong opioids alone. In another study, patients who were given lower doses of cannabinoid spray showed better pain control and less sleep loss than patients who received a placebo. Control of cancer-related pain in some patients was better without the need for higher doses of Cannabis extract spray or higher doses of their other pain medicines. Adverse events were related to high doses of cannabinoid spray.
   • 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, less nausea and vomiting, and better appetite. A second study showed that delta-9-THC could relieve pain as well as codeine. An observational study of nabilone also reported less cancer pain along with less nausea, anxiety, and distress when compared with no treatment. Neither dronabinol nor nabilone is approved by the FDA for pain relief.
   • Non-specific Cannabis products: A randomized controlled trial studied patients with advanced cancer who used Cannabis in addition to opioids early in treatment compared to patients who added Cannabis later in treatment. Patients who were given Cannabis later showed an increase in opioid use during the 3-month study. Opioid use was stable in patients who began Cannabis use earlier. There were no changes in symptoms or adverse effects between the two groups. Over 100 different Cannabis products were given during the study.

   Anxiety and sleep

   Cannabis and cannabinoids have been studied in the treatment of anxiety.

   • Inhaled Cannabis: A small case series found that patients who inhaled Cannabis had improved mood, improved sense of well-being, and less anxiety. In another study, 74 patients newly diagnosed with head and neck cancer who were Cannabis users were matched to 74 nonusers. The Cannabis users had lower anxiety or depression and less pain or discomfort than the nonusers. The Cannabis users were also less tired, had more appetite, and reported greater feelings of well-being.
   • Oral Cannabis oil: A randomized controlled trial studied two different doses of oral Cannabis oil in patients with brain cancer that could not be removed by surgery or had come back. Physical side effects such as sleep were noted to be better in the 1:1 ratio dose group. Both doses were well tolerated without any adverse effects.

   Relief of cancer symptoms with cannabidiol oil

   Cannabidiol (CBD) is a Cannabis compound that does not produce a “high” linked to Cannabis, but is felt to have possible health benefits.

   CBD oil has been studied for relief of cancer symptoms. A randomized, placebo-controlled, double-blinded trial of 144 patients studied the effect of oral CBD oil on cancer symptoms. All patients were treated by palliative care specialists. No difference was found in relief of cancer symptoms between the oral CBD group and the placebo group after 14 and 28 days. This trial has several limiting factors involving patients who participated, low levels of symptoms, and high levels of patients who did not complete the study.

7. Have any side effects or risks been reported from Cannabis and cannabinoids?

   Side effects of Cannabis and cannabinoids can include:

   • Fast heartbeat.
   • Low blood pressure.
   • Muscle relaxation.
   • Bloodshot eyes.
   • Slow digestion.
   • Dizziness.
   • Drowsiness.
   • Depression.
   • Hallucinations.
   • Paranoia.

   Both Cannabis and cannabinoids may be addictive. Symptoms of withdrawal from cannabinoids include:

   • Being easily annoyed or angered.
   • Trouble sleeping.
   • Unable to stay still.
   • Hot flashes.
   • Nausea and cramping (rare).

   These symptoms are mild compared with symptoms of withdrawal from opiates and usually go away after a few days.

   Studies on cancer risk from Cannabis use

   Studies on the risk of various cancers linked to Cannabis smoking have shown the following:

   • Lung cancer: Because Cannabis smoke contains many of the same substances as tobacco smoke, there are concerns about how inhaled Cannabis affects the lungs. A cohort study of men in Africa found that there was an increased risk of lung cancer in tobacco smokers who also inhaled Cannabis. A population study of patients with lung cancer found that low Cannabis use was not linked to an increased risk of lung cancer or other aerodigestive tract cancers.
   • Testicular cancer: A 1970 study interviewed over 49,000 Swedish men aged 19 to 21 years about their personal history of using Cannabis at the time they enlisted in the military and then followed them for up to 42 years. The study did not find a link between those who had “ever” used Cannabis and testicular cancer, but did find that “heavy” use of Cannabis (more than 50 times in a lifetime) was linked to more than twice the risk of testicular cancer. The study was limited by the way data was gathered and did not note whether the testicular cancers were seminoma or nonseminoma types or whether Cannabis use also occurred after enlistment.
   • Bladder cancer: A review of bladder cancer rates in Cannabis users and non-users was done in over 84,000 men who took part in the California Men’s Health Study. After more than 16 years of follow-up and adjusting for age, race, ethnic group, and body mass index, rates of bladder cancer were found to be 45% lower in Cannabis users than in men who did not report Cannabis use.

   Larger studies that follow patients over time are needed to find if there is a link between Cannabis use and a higher risk of testicular germ cell tumors.

   Studies on Cannabis use and impact on cancer treatment

   Few studies have been done to find out how Cannabis interacts with conventional treatment. A retrospective observational study in Israel showed that Cannabis reduced the effect of immunotherapy. A prospective observational study of immunotherapy and Cannabis in patients with metastatic cancer reported that the Cannabis users did not benefit from immunotherapy as much as those who did not use Cannabis.

8. Are Cannabis or cannabinoids approved by the U.S. Food and Drug Administration for use as a cancer treatment or treatment for cancer-related symptoms or side effects of cancer therapy?

   The U.S. Food and Drug Administration (FDA) has not approved Cannabis or cannabinoids for use as a cancer treatment.

   Cannabis is not approved by the 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 nausea and vomiting caused by chemotherapy in patients who have not responded to antiemetic therapy.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

Complementary and alternative medicine (CAM)—also called 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 type of treatment. Some complementary and alternative therapies may affect their standard treatment or may be harmful when used with conventional treatment.

It is important that the same scientific methods used to test conventional therapies are used to test CAM therapies. The National Cancer Institute and the National Center for Complementary and Integrative Health (NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer.

Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a 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 been tested using demanding scientific methods. A small number of CAM therapies that were thought to be purely alternative approaches are now being used 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) meeting in November 1997, acupuncture has been found to help control nausea and vomiting caused by chemotherapy and pain related to surgery. However, some approaches, such as the use of laetrile, have been studied and found not to work and to possibly cause harm.

The NCI Best Case Series Program which was started in 1991, is one way CAM approaches that are being used in practice are being studied. 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 carefully reviews these materials to see if any seem worth further research.

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

National Center for Complementary and Integrative Health (NCCIH)

The National Center for Complementary and Integrative Health (NCCIH) 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.

CAM on PubMed

NCCIH 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 websites 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.)

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 website.

National Cancer Institute (NCI) Cancer Information Service

U.S. residents may call the Cancer Information Service (CIS), NCI’s contact center, toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 9:00 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.

Federal Trade Commission

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