The therapeutic potential of cannabis in oncological pathologies

According to the European Union (EU), cancer is the second leading cause of mortality in EU countries, after cardiovascular diseases. Every year, 2,6 million people are diagnosed with cancer and a further 1,2 million people die from the disease. The discovery of the endocannabinoid system boosted not only scientific research on the cannabis plant but also its use in alleviating symptoms arising from various pathologies, namely oncological ones.

Constant research, in an area of ​​intervention as important as cancer, is unquestionably necessary. Most treatments that currently exist are not effective and cause significant adverse effects, reducing the patient's quality of life and jeopardizing the patient's adherence to treatment.

The demand for solutions and, consequently, information about the therapeutic potential of cannabinoids in the field of oncology by patients has increased exponentially in recent years.

If, on the one hand, the beneficial impact of this demand is evident, namely through the legalization of cannabis for medicinal purposes in Portugal, on the other hand, the intervention by health professionals in the clarification and education of these patients is extremely important. Much of the information available is not based on scientific evidence, promoting the creation of false expectations and obtaining products through questionable ways, putting the health of patients at risk.

PAIN CONTROL

Cannabis and Pain – Source: 2. 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

A pain is a symptom associated with oncological disease and affects about 70 to 90% of patients with cancer in advanced stages. It can be characterized as neuropathic pain, when the tumor invades the nervous tissue, causing a lesion or primary dysfunction of the central or peripheral nervous system. When the tumor exerts pressure on an organ or radiates over adjacent tissues, it causes visceral pain with inflammatory characteristics.

There is no scientific evidence that proves the effectiveness of phytocannabinoids when used alone, as monotherapy, in the treatment of pain, however, when integrated into the therapeutic protocol associated with other analgesics they are effective in relieving pain, reducing adjuvant medication (opioids) and mitigating adverse effects from other medications.

1. Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain (https://pubmed.ncbi.nlm.nih.gov/28923526/)
2. 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 (https://www.jpsmjournal.com/article/S0885-3924(09)00787-8/fulltext)
3. The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis (https://www.japha.org/article/S1544-3191(19)30353-X/fulltext)
4. Efficacy, tolerability and safety of cannabis-based medicines for cancer pain: A systematic review with meta-analysis of randomized controlled trials (https://pubmed.ncbi.nlm.nih.gov/31073761/)

CONTROL OF NAUSEA AND VOMITING

Antineoplastic drugs used to treat oncological diseases have several adverse effects on patients, namely nausea and vomiting. These secondary manifestations are uncomfortable for the patient and influence not only their adherence to treatment but also their diet. According to human clinical trials, phytocannabinoids (THC) are effective in relieving nausea and vomiting associated with cancer treatments.

1. Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomized, placebo-controlled, phase II crossover trial. (https://pubmed.ncbi.nlm.nih.gov/32801017/)
2. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997305/)
3. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.(https://pubmed.ncbi.nlm.nih.gov/17355735/)
4. Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting(https://www.sciencedirect.com/science/article/pii/088539249190026Z)
5. Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial(https://pubmed.ncbi.nlm.nih.gov/3035479/)
6. Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis(https://pubmed.ncbi.nlm.nih.gov/3017596/)

APPETITE STIMULATION   

Cannabis and Pain: Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Anorexia and cachexia are multifactorial syndromes characterized by increasing wasting of skeletal muscle mass with or without loss of fat mass that cannot be completely reversed by conventional nutritional support and that lead to progressive functional disability. We know that the endocannabinoid system plays a crucial role in the regulation of several biological functions, namely in the appetite regulation and several scientific studies prove the therapeutic potential of phytocannabinoids, namely THC, in stimulating appetite. For this reason and taking into account the reduced toxicity, phytocannabinoids represent an important tool for cancer patients, in which lack of appetite and malnutrition are frequent symptoms.

1. Efficacy of medicinal cannabis for appetite-related symptoms in people with cancer: A systematic review (https://pubmed.ncbi.nlm.nih.gov/35360989/)
2. Medical marijuana for cancer (https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21260)
3. Pharmacokinetics of Cannabis in Cancer Cachexia-Anorexia Syndrome (https://pubmed.ncbi.nlm.nih.gov/26883879/)
4. New Prospect for Cancer Cachexia: Medical Cannabinoid (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360413/)

LIFE QUALITY

When cannabinoid-based treatment is properly implemented and monitored by health professionals, its impact is initially observable through the attenuation of certain symptoms such as pain, spasticity, etc. The modulation of these symptoms has a direct impact on improving sleep quality, which consequently promotes an improvement in mood, reduced anxiety levels and improved quality of life in general.

Sleep Quality:

1. Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo (https://pubmed.ncbi.nlm.nih.gov/34115851/)
2. Effect Of D-9-Tetrahydrocannabinol And Cannabidiol On Nocturnal Sleep And Early-Morning Behavior In Young Adults (https://pubmed.ncbi.nlm.nih.gov/15118485/)
3. Medical cannabis and cannabinoids for impaired sleep: a systematic review and meta-analysis of randomized clinical trials (https://pubmed.ncbi.nlm.nih.gov/34546363/)

Mood and Anxiety:

1. Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448997/)
2. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. 🇧🇷https://pubmed.ncbi.nlm.nih.gov/30328956/)
3. Neural Basis Of Anxiolytic Effects Of Cannabidiol (CBD) In ​​Generalized Social Anxiety Disorder: A Preliminary Report (https://pubmed.ncbi.nlm.nih.gov/20829306/)
4. Effects of Cannabidiol (CBD) on Regional Cerebral Blood Flow (https://www.nature.com/articles/1300340)

ANTI-TUMOR ACTIVITY

Mechanisms of antiproliferative, proapoptotic and proautophagic effects of cannabinoids on cancer cells. – Cannabinoids as anticancer drugs: current status of preclinical research

In preclinical models, it was possible to demonstrate the anti-tumor properties of phytocannabinoids (THC and CBD) in various types of tumors, namely gliomas, melanoma, among others. The anti-tumor mechanism of action is based on the ability to block several pathways involved in the progression of cancer cells. Thus, and according to the studies carried out, cannabinoids exert their anti-tumor activity by inhibiting the proliferation of cancer cells, interfering with angiogenesis and metastatic processes and inducing their death by autophagy and apoptosis.

The antitumor effect of cannabinoids demonstrated through cell lines and animal models is remarkable, however, it is not possible to guarantee to achieve the same results in humans.

1. The use of cannabinoids as anticancer agents (https://pubmed.ncbi.nlm.nih.gov/26071989/)
2. Towards the use of cannabinoids as antitumor agents (https://pubmed.ncbi.nlm.nih.gov/22555283/)
3. Anti-tumor action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation (https://pubmed.ncbi.nlm.nih.gov/10700234/)
4. Antineoplastic activity of cannabinoids (https://pubmed.ncbi.nlm.nih.gov/1159836/)
5. Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells (https://pubmed.ncbi.nlm.nih.gov/19425170/
6. Inhibition of tumor angiogenesis by cannabinoids (https://pubmed.ncbi.nlm.nih.gov/12514108/)
7. Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression (https://pubmed.ncbi.nlm.nih.gov/18339876/)
8. A combined preclinical therapy of cannabinoids and temozolomide against glioma (https://pubmed.ncbi.nlm.nih.gov/21220494/)
9. Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer (https://pubmed.ncbi.nlm.nih.gov/26863913/)

CONCLUSION

The therapeutic potential of cannabinoids in oncological pathologies is evident and undeniable, namely in terms of controlling various adverse symptoms resulting from treatments and from the pathology itself, and there are more and more studies that allow the acquisition and consolidation of knowledge in this area. The scarcity of studies that allow examining the anti-tumor potential of cannabinoids in humans is a reality and it is the responsibility of health professionals who accompany these patients to clarify the expected results of the implementation of a treatment based on cannabinoids.
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* Soraia Tomás is a Nurse, graduated from the Escola Superior de Enfermagem de Coimbra in 2015. She worked in the intensive care of Cardio-Thoracic surgery and lung transplantation in Lisbon. She currently works at the Spine Center, a spine surgery service and an intensive care unit for general surgery at Hospital da Luz in Coimbra, the city where she lives. Enthusiastic in the field of Medicinal Cannabis, he is a member of the scientific council of the Portuguese Observatory of Medicinal Cannabis, attended conferences in this area (Portugal Medical Cannabis, Cannabis Europa, CannX, among others) and obtained a postgraduate degree in GMP's for Medicinal Cannabis, course carried out by the Portuguese Observatory of Medicinal Cannabis in partnership with the Military Laboratory of Chemical and Pharmaceutical Products and the Faculty of Pharmacy of the University of Lisbon. President of the Board of APCNNA – Portuguese Association for Information on Cannabis, intends to develop projects dedicated to the dissemination, education and training in medical cannabis to health professionals and the general public, thus promoting excellence in professional practice and safe and effective access. to cannabinoid therapies.