Canabinoids can have benefits in the treatment of cancer-related side effects
This summary contains the following important information:
Cannabis has been used for medicinal purposes for thousands of years. Chemical components of cannabis, called cannabinoids, activate specific receptors throughout the body to produce pharmacological effects, especially in the central nervous system and immune system. N Reference Nouns in some PDQ cancer information summaries may contain links to external websites managed by individuals or organizations with the aim of promoting the use of specific treatments or products..
Commercial cannabinoids, such as dronabinol and nabilone, are approved drugs for the treatment of cancer-related side effects. These reference quotations are only included for information. According to federal law, the possession of cannabis is illegal in the United States, except within recognized research institutions; however, a growing number of states, territories and the District of Columbia have passed laws to legalize their medical use. When a linked term is clicked, a definition appears in a separate window. , which is focused on situations without position.
The US Food and Drug Administration has not approved Cannabis as a treatment for cancer or any other medical condition.
Its inclusion should not be considered as approval of the content of the websites or of a treatment or product by the PDQ Integrative, Alternative and Complementary Therapies Editorial Board or the National Cancer Institute.
This information for cancer information 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. Many of the medical and scientific terms used in this summary are hypertext-linked (in the first use in each section) of the NCI Dictionary of Cancer Terms
Also See CBD For PTSD
The potential benefits of medicinal cannabis for people living with cancer include anti-emetic effects, appetite, pain relief and improved sleep. The highest concentration of cannabinoids can be found in the female flowers of the plant. 2 Although there are few relevant studies in clinical practice, it appears that doctors in the United States for cancer patients who recommend medicinal cannabis do so mainly for symptom control. To conduct clinical drug trials with cannabis in the United States, researchers must submit an Investigational New Drug (IND) request to the FDA, obtain a Schedule I license from the US Drug Enforcement Administration and obtain approval from the National Institute on Drug Abuse.).
The cannabis plant produces a resin with psychoactive substances called cannabinoids, in addition to other substances found in plants, such as terpenes and flavonoids. 4 The American Academy of Pediatrics did not approve cannabis and cannabinoids because of concerns about the development of the brain. 3 A growing number of pediatric patients seek symptom relief with cannabis or cannabinoids, although studies are limited. In the United States it is a controlled substance and is classified as a Schedule I agent (a high-risk medication and currently no accepted medical use). 1 Clinical trials with medicinal cannabis are limited. The US Food and Drug Administration (FDA) has not approved the use of cannabis as a treatment for a medical condition.
Cannabinoids are a group of terpenophenol compounds that occur in cannabis species (eg Cannabis sativa L. This summary discusses the role of cannabis and cannabinoids in the treatment of people with cancer and disease-related or treatment-related side effects.Cannabis, also known as marijuana, originates from Central Asia, but is now being grown worldwide.
- Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
- Abrams DI: Integrating cannabis into clinical cancer care. Curr Oncol 23 (2): S8-S14, 2016. [PUBMED Abstract]
- 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]
- Sallan SE, Cronin C, Zelen M, et al.: Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 302 (3): 135-8, 1980. [PUBMED Abstract]
1-5 It was introduced in Western medicine in 1839 by W. has been founded. Although federal law prohibits the use of cannabis, Figure 1 below shows the states and territories that legalized cannabis for medical purposes. In 1951 Congress passed the Boggs law, including Cannabis for the first time with narcotics. Pharmacopoeia because of the ongoing concerns about the potential to cause damage.
The indication that it has no medical use, cannabis was distributed case by case by the US government among patients under the Compassionate Use Investigational New Drug program. Other substances in list I include heroin, LSD, mescaline and methaqualone. Its use was promoted for reported analgesic, sedative, anti-inflammatory, antispasmodic and anticonvulsant effects.S. Medicines in Schedule I are distinguished because they currently have no accepted medical use in the United States.
In 1937, the US Treasury Department introduced the Marijuana Tax Code. 7. Some medical marijuana laws are broader than others and there is status-to-state variation in the types of medical conditions for which treatment is permitted.Cannabis use for medicinal purposes dates back at least 3000 years.B. This law imposed a charge of $ 1 per ounce for medical use of cannabis and $ 100 per ounce for non-medical use.
The American Medical Association (AMA) opposed the law because doctors had to pay a special tax for the prescription of cannabis, used special order forms to buy the cannabis and to keep special reports about their professional use. In 1970, with the passage of the Controlled Substances Act, marijuana was classified by Congress as a Schedule I drug. Doctors in the United States were the main opponents of the law. O’Shaughnessy, a surgeon who learned about his medicinal properties during his work in India for the British East India Company. Distribution of cannabis through this program was closed in 1992 for new patients. Moreover, the AMA believed that objective evidence that cannabis was harmful was missing and that the adoption of the law would prevent further investigation into its medicinal value. Additional states have legalized only one ingredient in cannabis, such as cannabidiol (CBD), and are not included in the card. 6 In 1942, Cannabis was removed from the United States.
The highest expression of CB2 receptors is on B lymphocytes and natural killer cells, indicating a possible role in immunity.
Another important cannabinoid found in Cannabis is CBD.
This is a non-psychoactive cannabinoid, an analogue of THC. 12-15 The first cannabinoid receptor, CB1, was identified in the brain in 1988. Clinical studies have determined that dronabinol was as effective or better than other antiemetic agents available at that time.
In recent decades, the neurobiology of cannabinoids has been analyzed. 17 Canada, New Zealand and some countries in Europe, nabiximoles also promote spasticity of multiple sclerosis, a common symptom that can include muscle stiffness, reduced mobility and pain and for which the existing therapy is unsatisfactory.
Nabiximols (Sativex), a Cannabis extract with a 1: 1 ratio of THC: CBD, has been approved in Canada (under the Notice of Compliance with Conditions) for symptomatic relief of pain in advanced cancer and multiple sclerosis. For example, the indications were extended with treatment of anorexia associated with infection with the human immunodeficiency virus in 1992. Clinical trial results did not show statistically significant weight gain, although patients reported an improvement in appetite. 9. 8 Dronabinol was also studied for the ability to stimulate weight gain in patients with AIDS in the late 1980s. Endogenous cannabinoids (endocannabinoids) have been identified and appear to play a role in pain modulation, movement control, feeding behavior, mood, bone growth, inflammation, neuroprotection and memory. A second cannabinoid receptor, CB2, was identified in 1993. In 1986, an isomer of synthetic delta-9-THC in sesame oil was approved and approved for the treatment of chemotherapy associated with nausea and vomiting under the generic name dronabinol.
The main psychoactive ingredient of cannabis was identified as delta-9-tetrahydrocannabinol (THC)
- Abel EL: Marihuana, The First Twelve Thousand Years. New York: Plenum Press, 1980. Also available online. Last accessed October 18, 2017.
- Joy JE, Watson SJ, Benson JA, eds.: Marijuana and Medicine: Assessing the Science Base. Washington, DC: National Academy Press, 1999. Also available online. Last accessed October 18, 2017.
- Mack A, Joy J: Marijuana As Medicine? The Science Beyond the Controversy. Washington, DC: National Academy Press, 2001. Also available online. Last accessed October 18, 2017.
- Booth M: Cannabis: A History. New York, NY: St Martin’s Press, 2003.
- 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]
- 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 October 18, 2017.
- National Academies of Sciences, Engineering, and Medicine: The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington, DC: The National Academies Press, 2017.
- Sallan SE, Zinberg NE, Frei E 3rd: Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 293 (16): 795-7, 1975. [PUBMED Abstract]
- Gorter R, Seefried M, Volberding P: Dronabinol effects on weight in patients with HIV infection. AIDS 6 (1): 127, 1992. [PUBMED Abstract]
- 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]
- 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 October 18, 2017.
- Devane WA, Dysarz FA 3rd, Johnson MR, et al.: Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34 (5): 605-13, 1988. [PUBMED Abstract]
- 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]
- 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]
- Felder CC, Glass M: Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 38: 179-200, 1998. [PUBMED Abstract]
- Pacher P, Bátkai S, Kunos G: The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (3): 389-462, 2006. [PUBMED Abstract]
- Howard P, Twycross R, Shuster J, et al.: Cannabinoids. J Pain Symptom Manage 46 (1): 142-9, 2013. [PUBMED Abstract]
Anti Tumor Effects
A study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors.)
Laboratory / animal / pre-clinical studies Cannabinoids are a group of 21-carbon-containing terpenophenolic compounds that are uniquely produced by Cannabis species (eg Cannabis sativa L. Tumor growth was inhibited by 60% in THC-treated mice compared with vehicle-treated control mice.
A meta-analysis of 34 in vitro and in vivo studies of cannabinoids in glioma reported that all but one study confirmed that cannabinoids selectively kill tumor cells CB1 receptor antagonists have been shown to induce vomiting in the least joint muscle that is reversed by cannabinoid agonists.38. The endogenous cannabinoid anandamide increases appetite in mice.
Another research into the role of CBD antitumor effects of intercellular adhesion molecule-1 (ICAM-1). 3 During this 2-year study, groups of mice and rats were given different doses of THC per sonde. CB1 receptors and 5-HT3 receptors are located together on gamma-aminobutyric acid (GABA) -ergic neurons, where they have opposite effects on the release of GABA. In rats, it was shown that these anxiolytic properties are mediated by unknown mechanisms 52. 55. 48 Cannabinoids have been shown to prevent chemotherapy-induced neuropathy in animal models exposed to paclitaxel, vincristine or cisplatin. In addition, CB1 receptors in the hypothalamus can be involved in the motivating or rewarding aspects of eating. Activation of the transient receptor potential vanilloid type 2 (TRPV2) has been shown to inhibit the proliferation of human multiform glioblastoma cells and to overcome the resistance to the chemotherapeutic drug carmustine.
Nutrition and sleep
The endocannabinoid system is believed to be centrally involved in the regulation of mood and the extinction of aversive memories., CBD and THC) in preclinical models of breast cancer. The involvement of CB1 receptor in vomiting prevention has been demonstrated by the ability of CB1 antagonists to translate the effects of THC and other synthetic cannabinoid CB1 agonists in suppressing vomiting caused by cisplatin in the musk pen and lithium chloride in the smallest shrews. Reduced incidences of benign tumors (polyps and adenomas) in other organs (mammary gland, uterus, pituitary, testis and pancreas) were also noted in the rats. CBD has also been shown to exert a chemopreventive effect in a mouse model of colon cancer. 26 As a result, a hypothesis has been developed that phytocannabinoids and endocannabinoids may be useful in the risk reduction and treatment of colorectal cancer 27-30. In the latter model, CBD also proved active. A in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines showed that CBD induced programmed cell death, independent of the CB1, CB2 or vanilloid receptors. A dose-dependent decrease in the incidence of hepatic adenoma cancer and hepatocellular carcinoma (HCC) was observed in the mice. 13, 14 Cannabinoids seem to kill tumor cells, but do not affect their non-transformed counterparts and can even protect against cell death. Animals treated with azoxymethane and CBD were simultaneously protected against the development of premalignant and malignant lesions. The studies documented that the anti-HCC effects are mediated via the CB2 receptor. Entry stimulation
Many animal studies
have previously shown that delta-9-THC and other cannabinoids have a stimulating effect on appetite and increase food intake. 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. 4 In addition, other tumors have been found to be sensitive to cannabinoids induced growth inhibition. As with findings in glioma cells, cannabinoids were found to cause cell death by stimulating an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. In particular, CBD is believed to have a significant analgesic, anti-inflammatory and anxiolytic activity without the psychoactive effect (high) of delta-9-THC. Anti-emetic effects
Principal research suggests that emetic circuits are tonically regulated by endocannabinoids. As with opioid receptors, elevated levels of the CB1 receptor are found in brain regions that regulate nociceptive processing. In an in vitro model, CBD increased the activation of TRPV2 and the increased uptake of cytotoxic drugs, leading to apoptosis of glioma cells without affecting normal human astrocytes. However, studies with immunocompetent murine tumor models have demonstrated immunosuppression and enhanced tumor growth in mice treated with THC. Both agents reduced the viability of HCC cells in vitro and showed antitumor effects in HCC subcutaneous xenografts in nude mice.
The understanding of the mechanism of cannabinoid-induced analgesia is enhanced by the study of cannabinoid receptors, endocannabinoids and synthetic agonists and antagonists. Other studies have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma 16 and breast cancer.
Cannabinoids can cause anti tumor effects by various mechanisms, including induction of cell death, inhibition of cell growth and inhibition of tumor angiogenesis invasion and metastasis. 21 In this experimental system, azoxymethane increased premalignant and malignant lesions in the large intestine of the mouse. 12 It has been reported that ICAM-1 expression is negatively correlated to cancer metastasis. 1,2 These plant-derived compounds can be called phytocannabinoids. The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in HCC.
CBD ICAM-1 increased in lung cancer cell lines, leading to reduced invasiveness of the cancer cell. CBD can also, together with THC, potentiate the antitumor activity of classical chemotherapies such as temozolomide in some mouse models of cancer. 41 The CB1 receptor is found in both the central nervous system (CNS) and peripheral nerve endings. It is thought that the anti-emetic action of cannabinoids is mediated via interaction with the 5-hydroxytryptamine 3 (5-HT3) receptor.54 The endocannabinoid system has also been shown to play a key role in the modulation of the sleep-wake cycle in rats. 13.
nCBD may also promote the uptake of cyto toxic drugs into malignant cells. Anxiolytic effects of CBD have been demonstrated in different animal models 53. In an in vivo model using severe combined immunodeficient mice, subcutaneous tumors were generated by inoculating the animals with human small cell lung carcinoma cell lines. In in vitro experiments with colorectal cancer cell lines, the researchers found that CBD protected DNA against oxidative damage, increased endocannabinoid levels and reduced cell proliferation. A mouse study showed that endogenous signals from the cannabinoid system probably provide intrinsic protection against intestinal inflammation. 42 CB2 receptors, located mainly in peripheral tissue, exist at very low levels in the CNS. For example, it has been shown that these compounds induce apoptosis in glioma cells in culture and induce regression of glioma tumors in mice and rats, while normal glioma cells of astroglial and oligodendroglial descendants are protected against apoptosis mediated by the CB1 receptor. 18 Other studies have also demonstrated the anti-tumor effect of cannabinoids (i.e. With the development of receptor-specific antagonists additional information on the roles of the receptors and endogenous cannabinoids in the modulation of pain has been obtained.
Cannabinoids can also contribute to pain modulation by an anti-inflammatory mechanism; a CB2 effect with cannabinoids acting on mast cell receptors to reduce the release of inflammatory agents, such as histamine and serotonin, and keratinocytes to improve the release of analgesic opioids has been described. It is believed that the endogenous cannabinoid system can serve as a regulator of nutritional behavior. This suggests that co-administration of CBD with cytotoxic agents may increase drug uptake and increase cell death in human glioma cells. 9-12 Two reviews summarize the molecular mechanisms of action of cannabinoids as anti-tumor agents.
Moreover, both plant and endogenous cannabinoids have been tested for anti-inflammatory effects. In another study, delta-9-THC, delta-8-THC and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo. In a subsequent study, the researchers discovered that the antiproliferative effect of CBD was counteracted by selective CB1 but not by CB2 receptor antagonists, indicating CB1 receptors.
Tumor specimens revealed that THC had antiangiogenic and antiproliferative effects.56. Cannabinoids produce analgesia through supraspinal, spinal and peripheral mechanisms of action, which act on both ascending and descending pain pathways. Animal studies have shown that CBD has anxiolytic properties. One study showed that concomitant administration of THC and CBD with the use of a single agent had greater antiproliferative activity in an in vitro study with multiple human multiform glioblastoma cell lines. CBD inhibited the survival of both estrogen receptor-positive and estrogen-receptor-negative breast cancer cell lines, induced apoptosis in a concentration-dependent manner and had little effect on non-tumorous breast cells. 45-47 One study reported that the efficacy of synthetic CB1 and CB2 receptor agonists was comparable to the efficacy of morphine in a mouse tumor model. There can also be a direct inhibitionition of 5-HT3 gated ion flows via non-CB1 receptor pathways
- Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 91 (11): 1585-614, 1996. [PUBMED Abstract]
- Grotenhermen F, Russo E, eds.: Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Binghamton, NY: The Haworth Press, 2002.
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Guzmán M: Cannabinoids: potential anticancer agents. Nat Rev Cancer 3 (10): 745-55, 2003. [PUBMED Abstract]
- Blázquez C, Casanova ML, Planas A, et al.: Inhibition of tumor angiogenesis by cannabinoids. FASEB J 17 (3): 529-31, 2003. [PUBMED Abstract]
- 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]
- 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]
- Velasco G, Sánchez C, Guzmán M: Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer 12 (6): 436-44, 2012. [PUBMED Abstract]
- Cridge BJ, Rosengren RJ: Critical appraisal of the potential use of cannabinoids in cancer management. Cancer Manag Res 5: 301-13, 2013. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Sarfaraz S, Adhami VM, Syed DN, et al.: Cannabinoids for cancer treatment: progress and promise. Cancer Res 68 (2): 339-42, 2008. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- Pacher P, Bátkai S, Kunos G: The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (3): 389-462, 2006. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- Baker D, Pryce G, Giovannoni G, et al.: The therapeutic potential of cannabis. Lancet Neurol 2 (5): 291-8, 2003. [PUBMED Abstract]
- Walker JM, Hohmann AG, Martin WJ, et al.: The neurobiology of cannabinoid analgesia. Life Sci 65 (6-7): 665-73, 1999. [PUBMED Abstract]
- Meng ID, Manning BH, Martin WJ, et al.: An analgesia circuit activated by cannabinoids. Nature 395 (6700): 381-3, 1998. [PUBMED Abstract]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Crippa JA, Zuardi AW, Hallak JE: [Therapeutical use of the cannabinoids in psychiatry]. Rev Bras Psiquiatr 32 (Suppl 1): S56-66, 2010. [PUBMED Abstract]
- 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]
- 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]
- 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]
Clinical Studies Conducted In Humans
When taken orally, delta-9-THC is first converted into 11-OH-THC in the liver, a potent psychoactive metabolite. 1,2 Peak plasma concentrations of delta-9-tetrahydrocannabinol (THC) occur after 1 to 6 hours and are increased with a terminal half-life of 20 to 30 hours.
When oral cannabis is taken, there is a low (6% -20%) and variable oral bioavailability. Inhaled cannabinoids are rapidly absorbed into the blood stream with a peak concentration in 2 to 10 minutes, rapidly decreasing over a period of 30 minutes and with less generation of the psychoactive 11-OH metabolite.
In one study, 24 cancer patients were treated with intravenous irinotecan (600 mg, n = 12) or docetaxel (180 mg, n = 12), followed 3 weeks later by the same drugs associated with medicinal cannabis taken for 15 consecutive days ..Cannabinoids are known to interact with the hepatic cytochrome P450 enzyme system. taken in the form of herbal tea, starting 12 days before the second treatment. 4 The administration of cannabis did not significantly affect the exposure and clearance of irinotecan or docetaxel, although the herbal tea route of administration may not replicate the effects of inhalation or oral intake of fat-soluble cannabinoids.
These early reports of cannabis use and TGCTs have shown that there is a need for larger, powerful prospective studies, pain particular, studies evaluating the role of endocannabinoid signaling and cannabinoid formulation in TGCTs.
Epidemiological studies of one link between cannabis use and head and neck squamous cell carcinomas were also inconsistent in their findings. large retrospective cohort study of 64,855 males aged 15-49 from the United States showed that cannabis use was not associated with tobacco-related cancers and a number of other common malignancies. These study results both reflect the inconsistent effects of cannabinoids on the incidence of cancer observed in previous studies and suggest that more work needs to be done to understand the potential role of a human papillomavirus infection.
Compared with those who had never smoked cannabis, smokers of cannabis had an increased risk of oropharyngeal cancers and a reduced risk of tongue cancer. A pooled analysis of nine case-control studies from the American / Latin American International Head and Neck Cancer Epidemiology (INHANCE) Consortium contained information from 1,921 oropharyngeal cases, 356 tongue cases and 7,639 controls.33-1.
A pooled analysis of three case cohort studies of men in Northwest Africa (430 cases and 778 controls) showed a significantly increased risk of lung cancer in tobacco smokers who also inhaled cannabis.
With the hypothesis that chronic marijuana use has negative effects on endocrine and reproductive systems in humans, the relationship between cannabis use and the incidence of testicular germ cell tumors (TGCTs) has been investigated.55, 95% confidence interval, 0. During 16 years of follow-up, 89 cannabis users.
Population-based case-control study of 611 lung cancer patients revealed that chronic low cannabis exposure was not associated with an increased risk of lung cancer or other upper aerodigestation cancers and showed no positiv associations with any form of cancer ( oral, pharynx, larynx, lung or esophagus) when adjusting different co founders, including cigarette smoking. 16.00).
A systematic assessment of 19 studies in which premalignant or malignant lung lesions were observed in subjects 18 years of age or older who inhaled cannabis, concluded that observational studies could not demonstrate statistically significant links between cannabis inhalation and lung cancer after adjustment for tobacco use.3%) developed bladder cancer compared to 190 (0. However, the study showed that, among non-smokers of tobacco, cannabis was once used in connection with an increased risk of prostate cancer.A number of studies have yielded conflicting evidence regarding the risks of various cancers associated with Cannabis smoking. After adjustment for age, race, ethnicity and body mass index, cannabis use was associated with a 45% reduction in the incidence of bladder cancer (hazard ratio, 0. 10 A systematic review and meta-analysis of nine case-control studies with 13,931 participants also concluded that there was insufficient evidence to support or refute a positive or negative association between smoking cannabis and the incidence of head and neck cancer.
However, the sample size in these studies was insufficient to address the cannabis dose by building associations with regard to recency, frequency and duration of use.
A comprehensive Health Canada monograph on marijuana concluded that although there are many cellular and molecular studies that provide strong evidence that inhaled marijuana is carcinogenic, the epidemiological evidence of a link between marijuana use and cancer is still not decisive. 12-14 Three population-based case-control studies reported a link between cannabis use and an increased risk of TGCTs, in particular non-menopausal or mixed histological tumors. 8 In the assessment of the published meta-analyzes, the report of the National Academies of Sciences, Engineering and Medicine (NASEM) concluded that there was moderate evidence that there was no statistical correlation between smoking cannabis and the incidence of lung cancer.
An analysis of 84,170 participants in the California Men’s Health Study was conducted to investigate the association between cannabis use and the incidence of bladder cancer.4%) men who did not report cannabis use of cannabis. .
A systematic review studied 30 randomized comparisons of delta-9-THC preparations with placebo or other anti-emetics, data of efficacy and injury were available. 29. Side effects were a feeling of being high, euphoria, sedation or drowsiness, dizziness, dysphoria or depression, hallucinations, paranoia and hypotension.
Despite advances in pharmacological and non-pharmacological management, nausea and vomiting remain worrying side effects for cancer patients and their families. Oral nabilone, oral dronabinol and intramuscular levonantradole (a synthetic analogue of dronabinol) were tested. Inhaled Cannabis trials were not included. 27 The anti-emetic guidelines of the American Society for Clinical Oncology (ASCO), updated in 2017, recommends that the FDA approve cannabinoids , dronabinol or nabilone, are used for N / V treatment that is resistant to standard anti-emetic therapies. Numerous clinical studies and meta-analyzes have shown that dronabinol and nabilone are effective in the treatment of N / V induced by chemotherapy. Nabilone, a synthetic derivative of delta-9-THC, was first approved in Canada in 1982 and is now also available in the United States. However, cannabinoids were not more effective for patients receiving very low or very high emetogenic chemotherapy.
A different analysis of 15 controlled studies compared nabilone with placebo or anti-emetics available. In 600 cancer patients nabilone was superior to prochlorperazine, domperidone and alizapride, with nabilone being preferred for continuous use. Dronabinol, a synthetically produced delta-9-THC, was approved in the United States in 1986 as an anti-emetic for use in cancer chemotherapy. 23-26 The National Comprehensive Cancer Network Guidelines recommend cannabinoids as a breakthrough for chemotherapy-related N / V. Of all 1,366 patients included in the review, cannabinoids were found to be more effective than the conventional anti-emetics prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone and alizapride. 22 Both dronabinol and nabilone have been approved by the US Food and Drug Administration (FDA) for the treatment of N / V associated with cancer chemotherapy in patients who have not responded to conventional anti-emetic therapy/
Individuals reported a higher preference for cannabinoids than placebo or prochlorperazine. Although selective neurokinin-1 antagonists that inhibit substance P have been approved for delayed N / V, a study has been conducted on their availability to determine whether dronabinol, ondansetron or its combination prevents chemotherapy-induced delayed
The overall response –
a composite endpoint – including nausea intensity, vomiting / retching and use of rescue medication was comparable to that of dronabinol (54%), ondansetron (58%) and combination therapy (47%) compared with placebo (20%) .
assessed the quality of the evidence as low for most outcomes. The chemotherapy treatments medicines with low, medium or high emetic potential. Ondansetron, a serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, is one of the pillars in current antiemetic instruments. There was no difference in the anti-emetic effect of cannabinoids compared to prochlorperazine.
Sixty-one patients were analyzed for efficacy.. The conclusion of the review was that people previously reported the complete absence of N / V when they received cannabinoids compared to placebo, although they were more likely to withdraw from the study due to an adverse reaction. The authors concluded that cannabis-based drugs may be useful for the treatment of refractory chemotherapy-induced N / V; however, they warned that their assessment could change with the availability of newer anti-emetic regimes.05 vs placebo for all).A Cochrane meta-analysis of 23 randomized, randomized RCT studies conducted between 1975 and 1991 in which dronabinol or nabilone was studied as monotherapy or as a supplement to the conventional dopamine antagonists that were the standard anti-emetics at that time 31. Prevalence rates for nausea intensity and vomit / retching were lowest in patients treated with dronabinol, suggesting that dronabinol is beneficial compared with ondansetron in this situation where a substance P inhibitor is currently the preferred drug.
At least 50% of patients receiving moderate emetogenic chemotherapy may experience delayed chemotherapy-induced N / V. In this study, the primary goal was to assess the response 2 to 5 days after moderate to severe emetogenic chemotherapy. Nausea absence was greater in the active treatment groups (dronabinol 71%, ondansetron 64%, combination therapy 53%) compared with placebo (15%;