Medical Cannabis for Healthcare Professionals

What is Medical Cannabis?

Medical cannabis is a plant product of Cannabis sativa L., Cannabis indica or hybrid plant varieties, either obtained as raw or dried or as an extract for medical use. Cannabinoids are naturally occurring compounds of cannabis. The common compound of medical cannabis includes delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). All cannabinoids are reported to be psychoactive; however, THC is reported to be the only cannabinoid that causes intoxication​1​.

Mechanism of Action of Medical Cannabis

The exact mechanism of action of medical cannabis is not properly understood. Cannabis is composed of 3 bioactive molecules called terpenoids, flavonoids, and cannabinoids. Δ9-tetrahydrocannabinol (THC) is the most well-studied cannabinoid. In addition to THC, cannabis also has concentrations of Cannabidiol (CBD). Cancer treatment using medical cannabis uses the various ratio of both THC and CBD. Medical cannabis functions by binding to specific receptors known as cannabinoid receptors, which makes up the endogenous cannabinoid system. These receptors, called cannabinoid receptors 1 and 2 (CB1 and CB2), work as G-protein coupled receptors, where they inhibit both calcium channels and adenylate cyclase and activate the potassium channels. CB1 receptors are found to be located throughout the body, with the highest concentration of receptors observed in the central nervous system. CB2 receptors are highly expressed in the immune system, where the highest expression of the receptors is observed in B-lymphocytes, involved in cell migration induction and immune suppression. The mechanism of action of Cannabidiol is not clearly understood; however, it is reported to modify the effects and metabolism of THC while acting as an antagonist of CB1 and CB2 receptors due to its low binding affinity. Cannabidiol is also reported to be a potent anti-inflammatory agent​2​.

Uses of Medical cannabis in Cancer patients

  • Chemotherapy-Induced Nausea and Vomiting

Medical cannabis find great importance in medical treatment for its antiemetic properties, for which it finds great importance in the treatment of chemotherapy-induced nausea and vomiting. It has been reported that THC helps in the treatment of nausea via the emetic reflex pathways in which it acts at receptors located in the nucleus tractus solitarii at the level of the area postrema. THC is also reported to reverse the effects of 5-HT3 receptor agonists, which induces vomiting.

Medical cannabis has been found to be effective in suppressing anticipatory nausea. Studies have reported that medical cannabis helps in the suppression of anticipatory nausea better than 5-HT3 receptor antagonists. Various studies have reported that the combination of other antiemetics with THC derivatives works best for nausea​3​.

  • Cancer-Associated Pain

Cannabinoids were also reported to have analgesic properties in cancer-associated pain, particularly neuropathic pain. CB1 receptors in the central nervous system are observed to be in high concentrations in regions of the brain. Cannabinoids is also reported to act on mast cell receptors, inhibiting the release of inflammatory substances as well as boosting the release of analgesic opioids to prevent inflammation. Cannabinoids also found their uses in the treatment of neuropathic pain by preventing the acute pain response in C-fibers​4​.

  • Medical Cannabis as an Antitumor Agent

Evidence suggesting the use of cannabis as a potential chemotherapeutic treatment is reported. Endocannabinoid signalling is observed to increase in some human tissue malignant neoplasms compared to noncancerous tissue, specifically in highly invasive cancers, thus reporting the role of endocannabinoids in tumor growth. Cannabinoids are reported to induce apoptotic cancer cell death through cellular signalling pathways. A study reported that Cannabinoids might play an important role in preventing cancer metastasis​5​. In another study by Guzman et al., it was reported that cancer treatment with THC decreased tumor progression and growth, as assessed by biomarker expression and magnetic resonance imaging. Research on cannabis proposed that cannabinoids can prevent tumor growth through several mechanisms, including suppression of cell proliferation and increased cellular apoptosis​6​.

  • Medical Cannabis for reduced anxiety and increased sleep

Studies have suggested that medicinal cannabis may be useful for enhancing sleep and post-traumatic stress disorder; however, the number of such evidence is low. CBD is used by cancer patients often in low doses to manage self-perceived stress, anxiety, sleep, and other symptoms, and these patterns differ by demographic characteristics. Further research is needed for understanding the dose-dependent effect of CBD in reducing mental health symptoms such as anxiety, stress and sleeping problems.

Studies on the efficacy of medical cannabis on cancer treatment

Due to various legal issues surrounding medical cannabis, there are very limited studies of medical cannabis and its anticancer effects on humans, although animal studies have been reported by many.

A 2019 review of in vivo and in vitro studies focusing on pancreatic cancer reported that cannabinoids could help reduce tumor growth, slow tumor invasion, and stimulate tumor cell death. However, research focussing on the effectiveness of different dosing, formulations, and the exact mode of action is lacking​7​.

A 2019 study reported that CBD could induce cell death and make the glioblastoma cells more sensitive to radiation therapy, without any effect on healthy cells​8​.

Noyes et al. studied the effect of medical cannabis on advanced cancer patients and reported a significant correlation between higher doses of THC and increased pain relief.

Portenoy et al. reported that in comparison to the placebo, low and medium medical cannabis doses were significantly more effective in reducing average daily pain​9​.

In another study by Noyes et al., conducted in advanced cancer patients’ significant difference in pain reduction was observed between placebo and 20 mg THC.

Dosage of Medical cannabis and THC:CBD ratio

There are no legalized medical or recreational ratios of THC: CBD in drafted regulations. Healthcare providers are therefore required to understand the medical impacts of cannabis as well as the interactions among various ratios of THC and CBD before it is prescribed in a medical setting.

The Food and Drug Administration (FDA) has approved low-dose THC (initial oral dose 0.04 mg/kg b.i.d.) for the treatment of treating nausea/vomiting associated with cancer chemotherapy for non-responders.

Previous studies have reported various therapeutic dosages of medical cannabis for the treatment of cancer. Wide variations in the therapeutic doses were reported where the dosage of 0.5 mg/day THC: 10 mg/day CBD to 100 mg/day or 50 mg/day combined THC and CBD to 40 mg/day THC and 600 mg/day CBD was observed. Dosage forms were also found to vary greatly, with sublingual oil reported being the most common form of medical cannabis administration among children while vaporization being the most common dosage form among adults for the maximum conservation of cannabidiols and cannabinoids​10​.

In a study on brain cancer patients, a CBD: THC ratio of 1:1 was found to be effective in improving the functional and physical capabilities, as well as sleep qualities of cancer patients in comparison to the use of CBD: THC ratio of 1:4​11​.

Approval by Regulatory Bodies

The AYUSH Ministry in India permits the use of the Vijaya or cannabis extract for medical purposes. Both CBD and THC are permitted to be used for treatment. The mentioning of ingredients on the box of the medical cannabis-based medicines is at the discretion of the manufacturer or distributor. The Narcotic Drugs and Psychotropic Substances Act, 1985 (NDPS Act) prohibits the recreational use of cannabis; however, it does not apply to the seeds or leaves of the plant. Besides, the medicinal use of medical cannabis is encouraged once proper regulations and licenses are obtained​12​.

After Effects of Medical cannabis

Several after effects have been reported after the intake of medical cannabis and cannabinoids. Some may be beneficial for cancer patients, such as sedation and mood enhancement. Some of the common side effects include:

  • Alteration of mood (dysphoria as well as euphoria)
  • Dry mouth
  • Anxiety and paranoia
  • Depression
  • Hallucinations
  • Sensation of depersonalisation
  • Memory impairment
  • Dizziness
  • Blurred vision

Medical cannabis in cancer treatment may have potential in its use for managing refractory cancer pain, reducing chemotherapy-induced nausea and vomiting anticipatory and and as an antitumor agent. Currently, medical cannabis is not the primary means of treatment for any cancer type or treatment-related to adverse effect; however, it can be used as an alternative medicine in cancer treatment.

References

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    Bridgeman M, Abazia D. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188. https://www.ncbi.nlm.nih.gov/pubmed/28250701
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    Wilkie G, Sakr B, Rizack T. Medical Marijuana Use in Oncology. JAMA Oncol. Published online May 1, 2016:670. doi:10.1001/jamaoncol.2016.0155
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    Himmi T, Dallaporta M, Perrin J, Orsini JC. Neuronal responses to Δ9-tetrahydrocannabinol in the solitary tract nucleus. European Journal of Pharmacology. Published online October 1996:273-279. doi:10.1016/0014-2999(96)00490-6
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    Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006;4(3):239-257. doi:10.2174/157015906778019527
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    Qamri Z, Preet A, Nasser M, et al. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther. 2009;8(11):3117-3129. doi:10.1158/1535-7163.MCT-09-0448
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    Di M, Bifulco M, De P. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004;3(9):771-784. doi:10.1038/nrd1495
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    Sharafi G, He H, Nikfarjam M. Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer. J Pancreat Cancer. 2019;5(1):1-7. doi:10.1089/pancan.2018.0019
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    Ivanov V, Wu J, Wang T, Hei T. Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells. Oncotarget. 2019;10(8):825-846. doi:10.18632/oncotarget.26582
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    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. The Journal of Pain. Published online May 2012:438-449. doi:10.1016/j.jpain.2012.01.003
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    Zeyl V, Sawyer K, Wightman R. What Do You Know About Maryjane? A Systematic Review of the Current Data on the THC:CBD Ratio. Subst Use Misuse. 2020;55(8):1223-1227. doi:10.1080/10826084.2020.1731547
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    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. Published online May 21, 2021. doi:10.3389/fonc.2021.649555
  12. 12.
    General Guidelines for Drug Development of Ayurvedic Formulations . Central Council for Research in Ayurvedic Sciences Ministry of Ayush, Government of India. Published 2018. Accessed March 2022. https://www.ayush.gov.in/docs/guideline-drug-development.pdf