Cannabis in Cancer

Written by Gemma Wilson

  Introduction

Each year in New Zealand there are over 60,000 outpatient sessions of chemotherapy clinics. This number is steadily growing due to an overall increase in population, an ageing population and an increase in the prevalence of cancer (Cancer Society, 2011). Many patients with a diagnosis of cancer will require chemotherapy treatment, the use of cytotoxic medication in attempt to eliminate cancer. According to Ware, Daeninck and Maida (2008) 70-80 percent of patients having chemotherapy will experience Chemothapy Induced Nausea and Vomiting (CINV). Chemotherapy stimulates the chemoreceptor trigger zone in the brain resulting in nausea and vomiting. Despite the progress of antiemetic therapies in recent years chemotherapy induced nausea and vomiting still remains a significant problem (Slatkin, 2007).

CINV is a distressing side effect that affects the individual as well as their families, caregivers and healthcare providers (Slatkin, 2007). A number of studies have shown that CINV is the number one side effect that is most stressful for cancer patients, with up to 30 percent of patients considering discontinuing treatment because of it (Ware, Daeninck & Maida, 2008). CIVN can lead to comorbidities such as anorexia, weight loss, malnutrition, metabolic imbalances and esophageal tears. CINV can negatively impact a patient’s quality of life limiting their ability to perform activities of daily living, rest, work and participate in social activities which could possibly lead to depression, anxiety and feelings of hopelessness (Ware, Daeninck & Maida, 2008).  During cancer treatment patients may spend time in a range of different health care settings, therefore it is important for all nurses to be aware of the impact of CINV has on patient’s health and wellbeing.

The challenges of lack of control of CINV have prompted new research and investigations into the possible effectiveness of both new and existing medications and how to better control CINV. One of these existing medications that is currently being researched and reviewed more and more are a class of compounds known as cannabinoids. Using cannabinoids as a therapeutic medicine is a controversial topic that spans over the last fifty years. Therapeutic properties of cannabinoids have been well established; however the clinical use of both synthetic and plant based cannabinoids remains limited in New Zealand and many other countries around the world (Cotter, 2009). Currently the use of cannabinoids in medical settings are only legal in some countries around the world, however many medical institutions, groups and communities around the world are encouraging it to be legalized. Cannabinoids compounds are synthesized by a plant called cannabis sativa (marijuana) and also by synthetically created molecules that activate the same endocannabinoid system in the brain. The active element in cannabinoids is known as 9-tetrahydrocannabinol (THC). Cannabinoids have been used to treat pain, inflammation, epilepsy, mood control, appetite, nausea, vomiting and motor function for many different diseases and illnesses (Behrend, 2013).  By using the PECOT model (below) to acquire a formal searchable question this literature review will aim to critically explore and understand the question "How effective are cannabinoids in controlling chemotherapy induced nausea and vomiting compared to standard antiemetics.”

PECOT   category

Information   relating to question

Explanation

Population

People   over the age of 16 with any type of cancer receiving chemotherapy.   Irrespective of gender, race or chemotherapy scheme.

An   age limit of 16 years was selected because participants need to consent and   understand the drug given and possible side effects. Gender, race and   chemotherapy scheme was kept open as this may have limited finding studies.

Exposure   (intervention)

Cancer   patients who used cannabinoids (synthetic or smoked) as pharmacological   intervention for the management of chemotherapy induced nausea and vomiting

I   will be looking for articles that used an experimental design in which   cannabinoids were compared to standard antiemetics in the treatment of CINV

Comparison   / Control

Cancer   patients who used standard antiemetics as a pharmacological intervention for   the management of chemotherapy induced nausea and vomiting

Same   as above.

Outcome

Complete   control or significant decrease in nausea and vomiting during any point of   chemotherapy scheme (e.g during chemotherapy cycle and between chemotherapy   cycles)

There   are many types of CINV (anticipatory, acute, delayed, breakthrough and   refractory) therefore it important to look for articles that focused on   control of CINV during any point of chemotherapy treatment.

Time

Time   frame of each participant’s chemotherapy scheme.

Different   Chemotherapy agents have different time frames. Therefore there is no   specific time frame identified.

 (Whitehead, 2013)

  Evidence and findings

According to the literature by Slatkin (2007) the development and advances in antiemetics including serotonin receptor antagonists and neurokinin-1 inhibitors has reduced rates of acute vomiting during chemotherapy treatment. Despite these advances in treatment these medications have decreased efficacy in preventing nausea, delayed CINV and breakthrough CINV which remain significant problems for patients going through chemotherapy. Delayed CINV develops within 24 hours after chemotherapy treatment whereas breakthrough CINV occurs despite the administration of prophylactic treatment. This literature by Slatkin (2007) indicates that cannabinoids act at multiple central control points for nausea and vomiting indicating that cannabinoids have an important role in the reduction of these symptoms. This research suggests that combining these antiemetics with cannabis based medications that act on the same neurotransmitter systems in the brain will be more effective in controlling delayed and breakthrough CINV which remain the two most stressful types of CINV for cancer patients (Slatkin, 2007). Furthermore, Slatkin (2007) emphasizes how nausea can often be overlooked and undertreated during chemotherapy. Nausea is a subjective experience compared to the objective experience of vomiting which means nausea is frequently suffered in silence and remains highly distressing for the patient. Both research by Slatkin (2007) and Cotter (2009) indicate that cannabinoid based mediations have been more effective at controlling nausea compared to certain antiemetics. In addition there is evidence that suggests that the combination of dopamine receptor antagonists and cannabinoid based medications are superior to either alone and are predominantly effective at preventing nausea (Slatkin, 2007).

Carroll, Campbell, McQuay, Moore, Reynolds and Tramèr (2001) reviewed patients preferences of three oral synthetic cannabinoids compared to antiemetics during chemotherapy treatment. Their research indicated that patients preferred and believed that cannabinoids were more effective at controlling CINV compared to conventional antiemetics. Carroll, et al. (2001) discuss the potential of positive and negative side effects of cannabinoids for patients having chemotherapy. Sedation, somnolence, a “high” sensation and euphoria were potentially beneficial side effects during chemotherapy. Negative side effects that patients described were dizziness, dysphoria, hallucinations and paranoia. These symptoms disappeared after three hours of administration.  Further research by Ware, Daeninck and Maida (2008) suggests that although the incidence of side effects of cannabinoids remains higher than conventional antiemetics these side effects are usually mild to moderate in intensity, decrease over time and do not generally impact patient preference towards them (Ware, Daeninck & Maida, 2008).

Pérez, et al. (2010) conducted a study of 50 cancer patients having chemotherapy. They investigated the tolerability, pharmacokinetics and efficacy of an acute dose of cannabis based medication compared to conventional antiemetics in the control of CINV. They explored the effectiveness of the oromucosal route in contrast to the common oral and inhaled routes. Their research suggests that rapid absorption of a cannabis based medication appears to be well tolerated by many patients and effective in the control of delayed chemotherapy induced nausea and vomiting. They believe that a short titration dose of a cannabis based medication was well tolerated with minimal adverse effects reported. They emphasize that delayed CINV still remains a significant problem for individuals and that an unknown proportion of patients self-medicate with cannabinoids to treat CINV. Their research indicates that it is important to optimize the use of cannabinoids alongside other mediations used to treat CINV by targeting various systems involved in the inhibition of nausea and vomiting including the endocannabinoid system. The endocannabinoid system is a neurotransmitter system within the brain that has specific cannabinoid one and two receptors. When these receptors are activated by the administration of cannabinoids it has been shown to inhibit nausea and vomiting (Perez, et al., 2010).

In studies undertaken by both Carroll, et al. (2001) and Rocha, Stefano, Haiek, Oliveira, and Da Silveira (2008) suggested that patients who have been previously exposed to cannabis may have superior antiemetic efficacy and may believe more highly of its efficacy to reduce CINV. In addition they experienced the adverse effects such as somnolence, sensations of a “high” and drowsiness more positively than patients who had no previous exposure to cannabis. Another study by Cotter (2009) compared cannabinoids and antiemetics for the treatment of CINV as well as oncologists views on cannabis during chemotherapy treatment. Out of 1035 oncologists who were interviewed 77 percent had observed or discussed use of cannabinoids for CINV.  However, 44 percent of this group recommended the use of cannabinoids to their patients for treatment of CINV and believed strongly in the efficacy of it when combined with conventional antiemetics (Musty & Rossi, 2011).

  Recommendations and implications for nursing practice

In future, if cannabinoids are available to patients with cancer having chemotherapy in New Zealand it is important for nurses be aware of the implications this can have on their practice. As cancer is becoming more prevalent in New Zealand it is important for nurses working with patients with cancer experiencing CINV to be aware how this may affect their health and wellbeing. As nurses have the most one on one contact with patients during their cancer treatment it is important to advocate for them and ensure they are getting the best treatment for their CINV. If oral synthetic cannabinoids became available nurses should be able to provide up to date, appropriate information and education to the patient. This may include information on the side effect profile of the medication. Assessment of patients before administration of cannabinoids is important. Cannabinoids should not be taken with alcohol, sedatives or hypnotics due to the potential of intensification of CNS effects. Patients may have limited knowledge on the effectiveness of the antiemetics they have been prescribed so it is important for nurses to advocate for them and provide them with this information. Like all medications cannabinoids have side effects. Just like any other medication, the medical team should discuss the side effect profile of cannabinoids and let the individual decide whether they would like to use it with their treatment. In addition if synthetic cannabinoids did become available for the treatment of CINV nurses should feel supported by up to date literature to recommend and administer them.

  Conclusion

In conclusion this literature review has critically reviewed and explored the question "how effective are cannabinoids in controlling chemotherapy induced nausea and vomiting compared to standard antiemetics ?”. Overall a number of studies suggest that the use of cannabinoids play an important role in the reduction of CINV (Ware, Daeninck & Maida, 2008). Cannabinoids may not be superior to antiemetics alone, but when they are combined with conventional antiemetics have been show to improve CINV especially if a patient does not have a great response to standard antiemetics (Cotter, 2009). The side effect profile of cannabinoids is unique, but patients with cancer have reported they can be potentially beneficial during treatment. Patients should be able to determine whether they want to use the drug or not and if they can tolerate the side effects. An important implementation for nurses is to educate and advocate for their patients so they get the best possible control for CINV.  CINV has a significant impact on a patient’s quality of life therefore it should treated quickly and effectively. Cannabinoids should not be overlooked for treatment of CINV.

  References

Behrend, S. (2013). Cannabinoids May Be Therapeutic in Breast Cancer. Oncology Nursing Forum, 40(2), 191-192.

Cancer Society. (2011). Cancer Statistics. Retrieved from: http://www.cancernz.org.nz/divisions/auckland/about/cancer-statistics

Carroll, D., Campbell, F., McQuay H., Moore, A., Reynolds, J., & Tramèr, M. (2001). Cannabinoids for control of chemotherapy induced nausea and vomiting: quantative systematic review. British Medical Journal, 323 (7303), 1-8.

Cotter, J. (2009). Efficacy of crude marijuana and synthetic Delta-9-Tetrahydrocannabinol as treatment for chemotherapy-induced nausea and vomiting: a systematic literature review. Oncology Nursing Forum, 36(3), 345-352.

Duran, M., Pérez, E., Abanades, S., Vidal, X., Saura, C., Majem, M., … Capellà, D. (2010). Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy- induced nausea and vomiting. British Journal of Clinical Pharmacology, 70(5), 656-663. 

Rocha, M., Stefano, S., Haiek, R., Oliveira, L., & Da Silveira, D. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. European Journal of Cancer Care, 17(5), 431-443.

Musty, R., & Rossi, R. (2001). Effects of smoked cannabis and oral delta9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. Journal of Cannabis Therapeutics, 1(1), 29-42.

Schneider, Z., Whitehead., D. (2013). Identifying research ideas, questions, statement & hypotheses. In Z. Schneider, D. Whitehead, G. LoBiondo-Wood, & J. Haber. Schneider, Z., Whitehead., D. Nursing and midwifery research methods and appraisal for evidence – based practice (4th ed.). (pp. 57-76).  Sydney, Australia: Mosby. 

Slatkin, N. (2007). Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis. Journal of Supportive Oncology, 5(5), 1-9

Ware, M., Daeninck, P.,& Maida, V. (2008). A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting. Journal of Therapeutics and Clinical Risk Management, 4(1), 99-107.