Factors Affecting the Decision on Cannabis Use in Gynecologic Cancer Patients After the Legalization of Cannabis

Abstract

Introduction

Among cancer patients suffering from symptoms associated with cancer or anticancer therapy, cannabis has been proven to be useful in relieving pain, anorexia, chemotherapy-induced nausea and vomiting, insomnia, and depression.^1 –7 The reasons for cannabis use in most patients are relief from pain, stress, and anxiety,^2,6 while some use it for cancer cure.⁶Nevertheless, though animal studies support the anticancer effect of cannabis,^1,2,7 –9 there has been no clinical trial on cancer cure in humans. Anticancer mechanisms are possibly linked to antiproliferative, antimetastatic, antiangiogenic, and proapoptotic effects.^1,8,9

Cannabis contains 2 major active components: tetrahydrocannabinol (THC) and cannabidiol (CBD), which are effective in reducing cancer-associated pain.^{1,8,10 –12} The raw plant could not directly act on the receptors. It needs to be heated to decarboxylate the acid to activate THC and CBD.⁸Most users worldwide employ cannabis through inhalation, oral consumption, and both modalities.⁶In Thailand, people use cannabis in the following ways: smoking, vaporizing, oral intake, oral spray, oral drops, suppositories, or topical use.^8,12 With inhalation, the cannabinoids are more rapidly absorbed and their levels in the bloodstream more rapidly decline than with the oral route, achieving higher peak concentration and a shorter duration of effect with less formation of the psychoactive 11- OH-THC metabolites.^9,11,12

Among current users, 1 study reported the most common drug interactions with CNS depressants but no difference between nonusers and users in terms of tiredness or drowsiness, an expected adverse effect associated with cannabis use.⁷The common side effects are drowsiness, dry mouth, gastrointestinal irritation, constipation, lethargy, palpitations, sweating, paranoia, and increased appetite.^13,14 More than half of cannabis users received no counseling on potentially harmful or beneficial effects.⁷Most start taking it on their own or due to the advice of friends, without proper counseling by healthcare providers.^6,7 Moreover, most oncology healthcare providers lack sufficient knowledge about cannabis to make recommendations.¹⁵Their perceived barriers are monitoring the patient’s use of cannabis, accurate dose prescription, and insufficient research.¹⁵There is a lack of dosing guidelines for the use of cannabinoid-based therapies in clinical practice, though side effects could be controlled through dose titration and are not treatment-limiting.^8,10,12

Never-users reported a high level of interest in learning more about the role of cannabis in cancer care and most wanted the information from their oncology providers, but they were more likely to get information from sources outside the healthcare system.^6,15,16 The main barrier to cannabis use was the concern of addiction and worsening the cancer.²

In Thailand, since 2019, all parts of the cannabis and hemp plants have been legalized for medical therapy. The main purpose of this study is to understand patient perceptions of these treatments and the barriers to effective management of cancer-related symptoms. This study was conducted to explore the proportion of our gynecologic cancer patients with a history of cannabis use, their information sources, and the accessible sources of cannabis. Understanding the reasons for using and not using in addition to the patients’ concerns would aid in the holistic care of cancer patients in all processes of treatment and even during palliation, probably improving quality of life eventually.

Medical cannabis use is becoming increasingly popular all over the world. In Thailand, legalized use has just been approved as a national policy. It is expected to gain much more popularity shortly. Nevertheless, baseline understanding of cannabis, prevalence of illegal use, and medical use of cannabis among various medical conditions vary among different populations. For effective implementation of medical cannabis use in cancer patients, there is a need to first improve knowledge regarding its risks and benefits, as well as the expectations of patients from the medical use of cannabis. Each population should develop its own data. This information is essential for the development of a specific strategy to overcome the observed barriers with proper direction; such barriers may be different among various countries. Therefore, we conducted this study to characterize the patterns of cannabis use among gynecologic cancer patients, in terms of potential factors influencing their decision-making on cannabis use, the reasons for use or non-use, and sources of information on cannabis use. We conducted this study in the hope that the results could guide the direction of a strategy of cannabis use among patients with gynecologic cancers.

Patients and Methods

This prospective, descriptive study was conducted at a university hospital, a tertiary medical teaching center, with ethical approval by the Institutional Review Board, Faculty of Medicine, Chiang Mai University, Thailand (Research ID, OBG-2565-08825). The study population was gynecologic cancer patients attending the outpatient gynecologic oncology clinic of Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand from March to July 2022. We conducted a structured review using a Google form, with a research assistant recording the patient’s answers. The patients were screened for eligibility. The inclusion criteria were as follows: (1) age of 20 years or greater, (2) having been diagnosed with 1 gynecologic cancer and treated at Maharaj Nakorn Chiang Mai Hospital, and (3) ability to communicate fluently in Thai. They could be in any process of treatment: during treatment, during surveillance, and palliative care. Exclusion criteria included unstable conditions and refusal to participate. All participants were required to give informed consent and authorization to disclose protected health information from the hospital database by appending their signature on a consent document. Patients were assigned a code number to keep them anonymous. A total of 240 eligible individuals responded to the consent form and all completed the survey. The survey took approximately 10 minutes to complete. Each participant was given a hand alcohol spray as a gift.

Results

From March to July 2022, 240 eligible patients were approached for consent, and all agreed to participate in the research. The enrolled patients were categorized into 3 groups, current users: 28 patients (11.67%), ex-users: 68 patients (28.33%), and never-users: 144 patients (60%). The demographics and characteristics of the enrolled patients are summarized, as presented in Table 1. At initial diagnosis, approximately half the patients were assigned to early and half to advanced stages in each group. Around 39.3%-51.5% of the patients in each group were undergoing treatment at the time of recruitment. The 3 most common cancers among the total participants were cancer of the uterus, cervix, and ovary/fallopian tubes, accounting for approximately 30% each.

The characteristics and demographic data of the 3 groups categorized by cannabis use were not different in terms of mean age, underlying diseases, marital status, and income. In terms of symptoms associated with cancer, most of the patients, approximately three-fourths, had no symptoms (pain, nausea vomiting, sleeping problems, and appetite), as presented in Table 2. The most common symptoms among the current users and ex-users were decreased appetite, sleeping problems, pain, nausea vomiting. Of the participants with pain problems, the rates of patients not using pain medication during the symptom (79.2%-85.7%) were not significantly different among the 3 groups.

Discussion

Insights gained from this study are as follows: (1) Nearly 40% of our gynecologic cancer patients have experienced cannabis use. (2) The most influential factor regarding their decision-making on cannabis use was advanced stage of cancer. (3) Healthcare providers need more training or education to provide updated and proper knowledge to cancer patients, which is helpful in their decision-making. (4) Most patients used cannabis in the hope of a cancer cure, probably implying over-expectation since the ASCO 2023 guideline presents updated evidence indicating potential improvement of quality of life in some difficult conditions e.g. refractory chemotherapy-induced nausea and vomiting (CINV) rather than a cancer cure.^17,18 (5) Though based on subjective assessment, our study supports the notion that cannabis use seems to improve the quality of life of gynecologic cancer patients with minimal side effects.

The main reason for cannabis interest reported in previous studies was symptom management, such as sleep, appetite, pain, neuropathy, depression, and anxiety.^3,4,13,14,19 The most common symptom leading to cannabis use was pain.⁵Also, 29% of the patients were taking cannabis for treatment of their cancer.³These reasons are consistent with our results, but more of our patients reported the hope of anticancer effects from their cannabis use (57.4%-60.7%). Though some studies proposed cannabis anticancer mechanisms through antiproliferative, antimetastatic, antiangiogenic, and proapoptotic effects,^1,8,9 these anticancer effects have only been reported in animal studies. Data from clinical trials regarding cancer cure in humans are still lacking.^1,7 –9 Other reasons for cannabis use among our participants were advertisement and accessibility to cannabis through other people.

Side effects were reported by about 50% of participants in a previous study.³On the contrary, only 28.6% of our participants reported adverse events. The most common side effect was central nervous system disturbance. Other reported side effects were dry mouth, psychiatric problems, addiction, and cardiovascular problems. The Multinational Association of Supportive Care in Cancer (MASCC) guideline²⁰suggests avoiding cancer-related pain treatment with cannabis because it has potentially harmful side effects on the psychiatric and central nervous system. In the studies,^3,20 participants used THC extract with various methods, while our study found that the participants used the raw plant more than cannabis extract. Thus, the different forms of cannabis use might explain the fewer adverse events in our study. This may also reflect the absence of standard cannabis extract forms in our country. In addition, our study found that 40% of never-users were concerned about treatment interference. According to MASCC,²⁰cannabis can counteract checkpoint inhibitors and decrease overall survival. Healthcare providers must discuss this issue with patients, especially given the growing use of checkpoint inhibitors in cancer treatment.

Several studies^1,6,9,11,13 reported that the majority of medical cannabis users were greatly relieved of their cancer pain and reduced their opioid use. This result was not found in our study because three-fourths of our participants reported no pain symptoms before starting cannabis use. Nonetheless, the current users group reported a mean satisfaction score of 5 out of 5 (range 3-5). The reasons for their satisfaction were improvement in sleep, appetite, physical status, mood, and adverse events from cancer therapy. These results are consistent with a previous study,¹³which reported that 83% of patients with medical cannabis use had their other symptoms relieved. Cannabis might improve patients’ quality of life in any cancer treatment status. On the other hand, according to the MASCC^20,21 reports, there is currently insufficient high-quality evidence to support the positive effects of cannabis on gastrointestinal symptoms and cancer-related pain. If patients are considering using cannabis as an additional treatment, they should be closely monitored.

Notably, most patients received information on cannabis from non-healthcare providers. Also, the majority of patients made their decisions based on the information they got from other people’s suggestions, not from their healthcare providers. In addition, 42.9% of participants in the current users group, 36.8% in the ex-users group, and 47.2% in the never-users group stated that the information from their healthcare providers was insufficient to make the decision. They were still undecided on whether to use cannabis-based on such information or not. McLennan et al¹⁵showed that 84% of healthcare providers thought they lacked knowledge about cannabis to make recommendations to their patients. They worried about adverse event monitoring, dose prescription, and the shortage of research about cannabis use in cancer patients. More than half of the healthcare providers were willing to learn more information or undergo training about medical cannabis.

Furthermore, 23% of the participants reported that the reason why they stopped cannabis use was difficulty in accessing cannabis. Various international studies reported that most patients used cannabis in extracted form, but 1 study mentioned that there is still a lack of dosing guidelines for cannabis therapies in clinical practice.¹⁰This might be another reason why healthcare providers are reluctant to make recommendations to the patients.

Clinical implication: Our findings can guide the direction of clinical practice strategy for effective medical cannabis use among our patients, by focusing on improvement in the understanding of healthcare providers, making them good sources of information for their patients with regard to providing scientific evidence on the risks and benefits of cannabis use. Finally, this study might encourage healthcare providers in other geographical areas to develop their own data to guide the development of an appropriate strategy for their population.

The strengths of this study are as follows: (1) prospective direct interview by the same well-trained team with systematic questionnaires could assure the patients’ understandings on the questions. (2) High homogeneity of the patients, representing a specific group of cancer patients, could result in high reliability of the results.

The study limitation is that the sample size of current users was relatively small. Nevertheless, together with ex-users who could provide the same many items of questions, the total number of cases could increase power of our analysis. Additionally, this study consisted of only patients from a single country where nationwide legalization had occurred, and patients were only from 1 institution.

Conclusion

Among gynecologic cancer patients, 40% had a history of cannabis use, including current and ex-users. The essential factors affecting a patient’s decision on medical cannabis use are advanced FIGO stage of cancer at diagnosis and information about cannabis use. Most patients received advice from other experienced patients and family, instead of their healthcare providers. Most patients intended to use cannabis for cancer cure, not for symptom relief. The main reasons for quitting cannabis use were the unavailability of cannabis and the absence of persistent cancer symptoms. Among the never-users group, the main reason for never trying cannabis was the concern of interference with current cancer treatment. They reported a score of 5 out of 10 concerning their interest in cannabis use in case of adequate information and accessibility.

Acknowledgments

Footnotes

References