Medical Much is being made of the potential of cannabis to cure cancer, but the scientific community is far from reaching consensus on this. However, what is far more certain is cannabis’ ability to improve quality of life for cancer patients undergoing traditional treatments such as chemotherapy. Here, we look at how it can help.
Nausea and vomiting are extremely common side-effects of chemotherapy. Chemotherapy drugs (primarily cisplatin) cause nausea by producing excess serotonin in specialised enterochromaffin cells, which are found in high concentrations in the gastrointestinal (GI) tract.
The excess serotonin irritates the mucosa (inner lining) of the GI tract and stimulates the serotonin (HT-5) receptors of the vagus nerve— the main nerve controlling the parasympathetic nervous system of the GI tract. The vagus nerve then sends stimuli to the area postrema—a small area within the medulla oblongata (lower brainstem) that is known as the vomiting centre.
Cannabinoids (particularly CBD) are thought to reduce symptoms in chemotherapy patients by binding to the HT-5 receptors and blocking the action of serotonin. Cannabinoid receptor agonists such as THC also appear to directly suppress vomiting and nausea by agonising the CB1-receptor –while antagonists of the CB receptors such as CBD are neutral, and inverse agonists actually cause nausea. This suggests there is a role for both THC and CBD in managing nausea and vomiting—THC by agonising the CB1-receptor and CBD by antagonising the HT-5 receptors and blocking serotonin binding.
Chemotherapy drugs are well-known to cause anorexia (appetite loss), also partly due to their effects on the serotonin signalling system. Studies have demonstrated that presence of cisplatin leads to excess production of serotonin and overstimulation of the vagus nerve. This then leads to a reduction of ghrelin, the ‘hunger hormone’ that is secreted when the stomach is empty. Without ghrelin, the brain does not receive the stimuli needed to produce sensations of hunger.
Various studies have shown that presence of ghrelin or cannabinoid agonists such as THC cause increased production of an enzyme—AMP-activated protein kinase (AMPK)—in the hypothalamus. The enzyme is crucial to the metabolic processes that regulate energy homeostasis (energy balance) in the body, and is produced in response to stimulation of the GHS-R1a ghrelin receptors found in the GI tract. Thus, THC can effectively do the job of ghrelin by activating the receptors and directly stimulating the brain to produce sensations of hunger.
Diarrhoea can be a side-effect of chemotherapy and radiotherapy, and may also be a direct symptom of several cancers, including lymphoma, colon cancer, pancreatic cancer, and some carcinomas and neuroendocrine cancers. If episodes are prolonged, diarrhoea can cause dehydration, weight loss, fever and abdominal pain. Secretory diarrhoea, where the body release excess water or hormones into the GI tract, is the most common form associated with cancer.
Cannabinoids have been shown to reduce symptoms of secretory diarrhoea—particularly ??-THC, which agonises the CB1-receptors in the GI tract and thereby assists in the regulation of intestinal motility and secretions. Intestinal inflammation may also play a part in causing diarrhoea; use of cannabinoids is well-known to reduce inflammation.
Cancer sufferers undergoing chemotherapy often report pain including headaches, sore muscles, stomach ache and neuralgia (nerve pain). Much of the pain arising as a result of chemotherapy occurs due to inflammation, although it may also be caused by the formation of lesions or ulcers in the mucous membranes. As well as this, the disease itself can cause severe pain in its latter stages, often due to tumours exerting pressure on nerves, bones or organs as they grow.
Cannabis is widely used in the management of chronic pain arising from a range of conditions not limited to cancer. Cannabis’ ability to reduce inflammation is crucially important in the management of pain arising due to chemotherapy. Both antagonists such as CBD and agonists such as THC (and the endogenous agonist 2-AG) are thought to reduce inflammation by inhibiting macrophage function—macrophages are large, specialised white blood cells that are fundamental to various immune responses.
Furthermore, the hyperalgesia (increased sensitivity to pain) and neuropathic pain that occurs due to tumour-induced damage to the peripheral nerves may be directly controlled through use of cannabinoids. Studies have shown that cannabinoid receptor agonists such as THC and the synthetic cannabinoid WIN55,212-2 reduce hyperalgesia in deep tissues affected by tumour growth, by agonising the cannabinoid receptors on the nociceptors, or pain-sensing neurons.
Depression in cancer patients is one of the most overlooked symptoms, but can be severely detrimental to quality of life, and is experienced by the majority of sufferers. If untreated, depression can lead to a range of complications that can work together to effectively make the patient even more ill—for example, the appetite loss associated with chemotherapy can be significantly increased in depressed patients. It may also affect sleep quality and stress levels, both of which can lead to physiological health issues. Cancer patients treated with antidepressants also report feeling reduced fatigue, anxiety, and pain.
The ability of cannabis to treat depression is disputed, and there is substantial evidence on both sides. Several studies have indicated that ??-THC, CBD, and cannabichromene (CBC) can exert an antidepressant effect. The endocannabinoid system is known to play an important role in mood regulation and subjective levels of happiness, and endocannabinoids such as anandamide are fundamental to the process. It is believed that certain genetic variations in the expression of CB1-receptors render some individuals more susceptible to the mood-elevating effects of cannabis.
Cannabis may not benefit every individual suffering from cancer, and may even cause adverse effects in a small number of people—although any adverse effects experienced are usually far less severe than the side-effects of chemotherapy or radiotherapy. However, as our understanding of the properties of cannabis increases, we are beginning to comprehend just how important it could be in the management of cancer symptoms. Drugs with the ability to simultaneously treat a broad set of symptoms such as nausea, anorexia and diarrhoea are rare, and those can do so without causing severe side-effects of their own are rarer still.