Prevalence and Characteristics of Medicinal Cannabis Use among Chronic Pain Patients; A Post- Legalization Study in a Tertiary Care Setting in Thailand

Raviwon Atisook, M.D.1, Chanya Mochadaporn, M.D.1, Pratamaporn Chanthong, M.D.2, Pinyo Sriveerachai, M.D.2, Nantthasorn Zinboonyahgoon, M.D.1

1Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 2Department of Palliative care, Faculty

of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

ABSTRACT

Objective: Cannabinoid products have been applied for numerous medical conditions, including chronic pain. Thailand was the first country in South East Asia to legalize medical cannabinoids. This study aims to explore prevalence, characters, attitude, side effects of medical cannabinoid use, and pain-related outcome among the chronic cancer and non-cancer pain population at Siriraj Hospital.

Materials and Methods: 200 chronic cancer pain and 670 chronic noncancer pain patients were collected by questionnaires and interviews. Data included demographic data, clinical diagnosis, pain treatment, knowledge, attitude, pattern of use, side effects and quality of life of cannabinoid extracts.

Results: Prevalence of active cannabis user was 15% in chronic cancer pain and 3.1% in noncancer pain. Oil extract sublingual was the most common form. Pain control was the most common initial reason for usage. No serious side effects were reported. Common side effects were dry oral mucosa, drowsiness, and headache. The most common source was obtained from friends. 36% of the patients believed they had enough understanding of medical cannabis, while 68.5% agreed that it is appropriate to use in Thailand. In cancer patients, the Edmonton Symptom Assessment System (ESAS) subscale for lack of appetite, anxiety, and subscale for a brief pain inventory (BPI) for enjoyment of life were higher among active users. In patients with noncancer pain, only the mood subscale BPI was lower among active users.

Conclusion: Medical cannabis usage is common compared with general population in Thai patients with chronic pain and may be associated with increased pain interference and cancer-related symptoms. Nonmedical license prescription and nonmedical license cannabis products were common in Thailand.

Keywords: Cannabis; prevalence; chronic pain; quality of life; side effect of cannabis; cancer pain; noncancer pain (Siriraj Med J 2024; 76: 21-30)

INTRODUCTION

Cannabinoids, cannabis, and cannabis-based products have been used for medical purposes for a variety of conditions such as Parkinson’s disease, Alzheimer’s disease, spasticity associated with multiple sclerosis,

and childhood seizure disorder.1,2 In a prospective study of pain and palliative medicine, several studies demonstrated cannabinoid products as adjunctive treatment in related conditions such as neuropathic pain, cancer pain, chemotherapy-induced nausea and

Corresponding author: Nantthasorn Zinboonyahgoon E-mail: nantthasorn@gmail.com

Received 7 October 2023 Revised 25 November 2023 Accepted 9 December 2023 ORCID ID:http://orcid.org/0000-0002-5946-7962 https://doi.org/10.33192/smj.v76i1.265605

All material is licensed under terms of the Creative Commons Attribution 4.0 International (CC-BY-NC-ND 4.0) license unless otherwise stated.

vomiting, and probably anticancer treatment.3-6 However, clinical application remains controversial due to the limited evidence of benefit, potential harm, and legal/ regulatory issues around the world.7-11

Public interest in cannabinoid products has increased globally and has been accelerated by legalization for medicinal and recreational purposes in many countries.11-16 In Thailand, cannabinoid products have been classified as controlled substances since the early 1930s. (Ref) However, in February 2019, Thailand was the first country in South East Asia to legalize the use of medicinal cannabis for therapeutic and research purposes.17,18

Although the Thai government established a multilevel system of safeguards that includes the implementation of standards on manufacture and prescribing, and monitoring and evaluation7,18, the first survey one year after legalization showed that off-labeled products were still common and illegal products were easily obtained.8,19 Some patients consume cannabinoid products without proper knowledge of indication, dose, route, and possible interaction with other medications, which can cause several unwanted effects, drug abuse, and life-threatening conditions.10,20-22 This is the subsequent research from our initial survey.8 The main objective of this study is to explore the prevalence of medical cannabinoid use among chronic pain patients in a tertiary care pain center in Thailand. Secondary research questions aim to explore the characteristic of medicinal cannabis use, including preparation, common route of administration, common side effects, symptoms, and pain-related interference among chronic cancer patients and noncancer pain

patients.

MATERIALS AND METHODS

This single-center cross-sectional study was conducted from June 2020 to July 2021. After approval of the institutional review board (IRB number Si 172/2020), 200 patients with chronic cancer pain and 670 patients with chronic noncancer pain who attended the pain or palliative clinic at Siriraj Hospital were interviewed. Data were collected using questionnaires, including Likert scales and open- ended questions focused on attitude, basic knowledge about medical cannabis, and descriptive data on cannabis use, such as formulation and side effects. The inclusion criteria required subjects to be 18 years or older with pain for more than 3 months. Patients who refused to participate and those with cognitive impairment were excluded. Demographic data, diagnosis, intensity of pain, current analgesic medications, and cannabis use patterns were also obtained by interview or review of medical records. Pain-related interference and symptoms were

evaluated using the Brief Pain Inventory and Edmonton Symptom Assessment System, Thai version.23,24

A brief pain inventory (BPI) was used to assess the severity of pain and the impact of this pain on the daily functioning of the patient ranging from 0 to 10. The higher the score means more interference from pain. Pain- related disability is the total sum of BPI in each modality. The Thai version (BPI-T) was also validated for use in patients with chronic pain.24

The Edmonton Symptom Assessment System (ESAS) was used to rate the intensity of common symptoms experienced by the cancer patient. Scoring from 0 to 10, the higher the score, the more intense the symptoms. The Thai version of the ESAS achieved good levels of validity and internal consistency.23

Statistical analysis

Demographic data were represented in descriptive analysis. Categorical variables were presented as counts and percent. Continuous and normal variables were presented as means with standard deviation or medians with an interquartile range (IQR). Comparison between group responses was made using the chi-square or Fisher’s exact test. The P-value < 0.05 was considered statistically significant. Data analyzes were performed using PASW Statistics version 18 (SPSS, Inc., Chicago, IL, USA).

RESULTS

The 870 participants has an average age of 58 years with a female predominance (57% in the cancer group and 65.7% in the noncancer group).62% in the cancer group and 68.7% in the noncancer group had a higher education level (>12 years of education, equal to or greater than high school). Demographic data are presented in Table 1.

Prevalence

The prevalence of current users was 5.86%; 15% for cancer patients, and 3.1% for noncancer patients. The average duration of treatment among current users was 75 days for cancer and 120 days for noncancer patients. 25.5% of cancer patients and 5.2%of noncancer patients used medicinal cannabis for an average of 30 and 75 days, respectively. 57%of cancer patients and 90% of noncancer patients had never used cannabis products.

Characteristic of the current users

Breast cancer was the most common primary cancer in current users (N=5) and noncurrent users (N=25) among cancer patients, while spinal stenosis was the most common diagnosis in current users

TABLE 1. Demographic data of cancer (N=200) and noncancer groups (N=670) (p value).

Values are presented by Mean±SD and number (percent), Lower education, ≤12 years of education or junior high school; Higher education,

>12 years of education

(N =3) and nonusers (N = 72) among noncancer patients. The average pain score and maximum pain score trend towards higher in current users in both cancer and non- cancer patients, but did not reach statistical significance. There were no statistically significant differences in age, sex, education level, duration of diagnosis, number of treatments (surgery, chemotherapy, radiation), PPS score (Palliative performance scale), opioid consumption, and current conventional pain medication between current and noncurrent cannabis users in cancer and noncancer patients. (Supplemental Table 1 and 2)

Compared to noncancer patients, cancer patients who received cannabis were more likely to receive opioids (step 3 analgesic ladder) (80% vs 0%) and more likely to receive strong opioids in greater opioid dose of opioid consumption (average morphine equivalent dose per day of 30 mg ). However, there were no significant differences in sex, age, education, duration of diagnosis, and pain score. (Supplemental Table 3)

Symptoms and pain-related interference among current users

Cancer patients

Compared to noncurrent users, current users in the cancer group reported a trend towards a higher pain score (average pain score 4.8 ± 2.28 VS 4.35 ± 2.48, P 0.361) and pain interference score (BPI) (36.5 VS 31, P 0.064) and statistically significant higher cancer-related symptoms (ESAS) (34 VS 27, P 0.017). All BPI and ESAS subscales tend to be higher or the same in current users. Additionally, the subscale of enjoyment of life from BPI, lack of appetite, and anxiety from ESAS was significantly higher in current users. (Figs 1&2)

Noncancer patients

Unlike cancer patients, current users in noncancer patients reported a trend toward a higher pain score (average pain score 5.29 ± 1.95 VS 4.56 ± 2.07, P 0.112), but a trend toward a lower pain interference score (BPI) (24 VS 29, P 0.503) and related symptoms (ESAS) (19 VS 24, P 0.445). There is no difference in BPI and ESAS subscale, expect mood subscale from BPI which were statistically significant lower in current users. (Figs 3&4)

Formulation and sources of cannabis products

Oil extract was the most common formulation in both cancer and non-cancer participants (79.1% N=68, 71.9% N=46). Cancer and noncancer cannabis users had statistically significant differences in tablet and tea formulation (P= 0.0.381, 0.105). Only 39.5% of cancer and 32.9% of noncancer patients obtained a medical cannabis license, either from the hospital or from registered practitioners. The main source of cannabis came from a neighbor or acquaintance (61.6% in cancer and 65.6% in non-cancer). No statistically significant differences were detected in the source of cannabis between the two groups. (Table 2)

Reasons to use and to continue

Pain control was the most common initial indication in both groups (45.3% and 53.1%, in cancer and noncancer patients, respectively) followed by the belief in adjuvants in insomnia treatment (37.2% and 25%). Palliative care and cure cancer purposes were statistically significantly higher in cancer compared to noncancer users (P=0.0001). However, users reported that sleeping aid was the most common benefit of medicinal cannabis in both groups

Fig 1. Comparison of noncurrent users and current users in the cancer group according to the Brief Pain Inventory score (BPI), Number above the bar represent average score (0-10) in each subscale, *=P<.05

Fig 2. Comparison of the noncurrent users and the current users in the cancer group according to the Edmonton symptom assessment system (ESAS), Number above the bar represent average score (0-10) in each subscale, *=P<.05

Fig 3. Comparison of the noncurrent users and the current users in the Noncancer group according to the Brief Pain Inventory score (BPI), Number above the bar represent average score (0-10) in each subscale,

*=P<.05

Fig 4. Comparison of the noncurrent users and the current users in the Noncancer group according to the Edmonton symptom assessment system (ESAS), Number above the bar represent average score (0-10) in each subscale, *=P<.05

TABLE 2. Formulation and sources of cannabis products in cancer (N=200) and noncancer groups (N=670).

Values are presented as number (percent)

(46.5% and 46.9%), while pain control was ranked as the second most common benefit in the cancer group (22.1%) and the third in the noncancer group (18.8%). The noncancer users continued to use cannabis believing in its advantage as a natural product and unspecified perspectives that was statistically significant compared to the other groups (P=0.0052, 0.0004). Finally, pain control was ranked as the second most common reason, after sleeping aid, to continue using medicinal cannabis among cancer patients (26.7%) and the most common reason to continue for noncancer patients. The only reason to continue using cannabis that was statistically significant between cancer and noncancer group was for an alternative purpose (P=0.0314).

Side effects

Most of the cannabis participants reported no side effects (48.8% and 40.6%). The most common side effects among cancer patients were drowsiness (27.9%), followed by dry mouth (23.3%) and intoxication (14%). The most common side effects among noncancer patients were headache (25%) that was statistically significant compared to cancer users (P=0.004), followed by dry mouth (21.9%), and drowsiness (17.2%). Serious side effects such as confusion / hallucination were reported in 4 persons (6.3%) in the noncancer group and 3 persons (3.5%) in the cancer group. (Table 3)

Attitude towards and knowledge about medicinal cannabis

Most of the participants (68.5% in cancer and 62.2% in noncancer patients) agreed that it was appropriate to use medical cannabis in the current context of Thailand closely monitored as narcotics (51% in cancer and 49.3% in noncancer patients). However, the majority of them also disagreed or were uncertain if they had enough understanding about medical cannabis. Number (30%) of patients with cancer pain and number (23.4%) noncancer believed that cannabis products can cure cancer. Most of the patients believed that cannabis can be used with other drugs without drug interaction and that a small amount should not cause serious side effects. Finally, most of the participants agreed that administration should be under medical supervision. (Table 4&5)

DISCUSSION

This observational cross-sectional study showed that the prevalence of active cannabis users in patients with chronic pain was much higher than in the general population.20 Surprisingly, the prevalence of current users among cancer patients was not only higher than that of noncancer patients, but was also associated with a higher cancer-related symptoms score and a trend toward higher pain intensity and pain interference, compared to noncurrent users. In contrast, symptoms

TABLE 3. Cannabis use in cancer (N=200) and noncancer groups (N=670).

I believe

Cancer group (N=200)

N (%)

Non-cancer group (N=670)

N (%)

TABLE 4. Attitude towards medical cannabinoid in cancer (N=200) and noncancer groups (N=670).

Values are presented as number (percent)

TABLE 5. Basic knowledge of cannabis in cancer (N=200) and noncancer groups (N=670).

can be used safely in patients with

heart disease, liver disease, kidney disease, and psychiatric conditions.

65 (32.5) 101 (50.5) 34 (17)

192 (28.7) 371 (55.4) 107 (16)

cause serious side effects.

Values are presented as number (percent)

and pain interference in current users trend toward the opposite direction in noncancer patients. Off-label use and illegal procurement were easy and common.8,14,19 However, adverse events have been reported, and terrible adverse events are not uncommon.19,21,22

Among the nearly 60 chemicals extracted from Cannabis Sativa L., the two main compounds are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ9-THC)25,26, which act on immune cells and the central nervous system, resulting in modulation of memory, emotion, pain, movement, and caused psychoactive effects.27 Although phytocannabinoids were theoretically beneficial for a variety of conditions, including seizures and spasticity; the clinical benefits, especially pain management, are controversial.28 Furthermore, the optimal route, dose range, composition of cannabinoids, and therapeutic efficacy in each disease have not been elucidated.4,7,9,18,29-32 Lastly, the potential harm and long-term side effect is concerning.33-35

In Thailand, phytocannabinoid was previously used for various types of condition as part of Thai traditional medicine until it was declared a controlled substance in the early 1930s. Subsequently, cannabis was found in the three most common uses of illicit substances together with Kratom and yaba (met-amphetamine tablet).36 After the Narcotic act of 2019, which legalized medicinal cannabis in Thailand, was introduced, there was an increasing prevalence of cannabis use from 2.6 to 10.6 per 100,000 patients in 2018 to 2019.10,17 Among the chronic pain population in our study, the overall prevalence of active cannabis use was 5.86%; 3.1% in chronic noncancer and 15% in cancer patients.

The analysis comparing the characteristics of current users and noncurrent users found that there is no difference in terms of sex, age, education or pain intensity, but the diagnosis of patients (cancer or noncancer) is the only significant factor associated with use. However, our data showed that the proportion of patients who used pain relievers was comparable between cancer and noncancer patients (45.3% vs 53.1%). The higher incidence of the current use in cancer patients is possibly due to non-pain indications such as for palliative care (30.2% vs. 1.6%) or believe that medical cannabis can cure cancer (30.2% vs 0%).

Our data showed that 30% of cancer patients believed that medical cannabis can cure cancer and 30.2% used medical cannabis (MC) for this reason, which is not recommended by Thai or international authorities.5-7,18,31,37 Furthermore, about a third of the patients in both cancer and noncancer pain group were uncertain of basic knowledge, including the prospective

of cannabis-cancer, drug interactions, and use in liver or kidney disease. Assanangkornchai found that the main source from which the respondents obtained information on MC was from friends and relatives (78.3%), followed by social networks (32.9%) and only 15.4% reported receiving information from healthcare providers or government organizations. Most of the patients obtained MC products from illegal sources and without supervision (about 2/3), in conjunction with a survey study in four regions of Thailand by Assanangkornchai et al.19 This information highlights the fact that public perception and education on medical cannabis is vital and must contribute to prevalence, nature of use, and outcome in the Thai population.

As this study was conducted in the pain center, it is not surprising that the most common reason for using medical cannabis was to control pain in both cancer and noncancer patients (45.3%,53.1%), which is consistent with the meta-analysis by Kosiba et al.30 and a systematic review by Pratt et al.33 However, pain control was ranked after sleep aid and mood control in terms of benefit from the user’s point of view in both cancer and noncancer patients. Pain was not the most common reason to continue using medical cannabis in cancer patients, but it remains the top reason among noncancer patients. Medical cannabis as an alternative treatment was significantly higher in non-cannabis users in our study, which could be explained by that noncancer group as chronic pain progression, some patients tried a variety of regimens on the market together with the standard medical treatment compared to cancer groups that at the time, if diagnosis needed to be strict with the standard medical regimen. This result showed that the analgesic benefit of medical cannabis between cancer patients and noncancer patients may be different. Oil extraction is the most common formulation, and the recommendation is to use only a few drops sublingually as to bypass first pass hepatic mechanism and direct to the systemic absorption because cannabis has poor oral bioavailability (only 10-20% with lower in combination with food consumption).38 Also from this reason and low amount of consumption, most cannabis users reported no side effects. Further research is needed to explain why headache was statistically significant in the noncancer group in our study.

Among cancer patients, the current medical cannabis user in the cancer group reported a trend toward a higher pain score, pain interference and a statistically significant higher subscale of interference of enjoyment of life from BPI, lack of appetite, and anxiety, and total cancer-related symptoms from ESAS. In contrast, the

current user in the noncancer group reported a trend toward a lower BPI and ESAS subscale, except the mood subscale from BPI which was statistically significantly lower. The associations of a worse outcome among medical cannabis users in cancer patients are possibly due to the different population, the different nature of the disease, or different types of pain (nociceptive and neuropathic). Even if this association can cause the use of MC or the result of the use of MC in cancer patients, these results raise questions about the overall effectiveness of MC, especially among cancer pain patients. Further research with a confounding factor-controlled prospective cohort study is needed to answer this question.

Legalization was not only associated with an increase in the prevalence of cannabis exposure20, adverse events from cannabis use also increased after legalization.8,19 Although most of the participants in our study reported no side effects or minor side effects (dry mouth, drowsiness), severe adverse events such as confusion or hallucination were common.33 The early report right after the legalization of the National Poison Center reported severe adverse events such as seizures, altered consciousness, and coma patients who underwent brain imaging or tracheal intubation for ventilator support.39 Furthermore, the long-term follow-up and monitoring of serious adverse outcomes such as psychosis, traffic accidents, abuse, and addiction have not been elucidated in this study and will be required in the future.

The Thai government subsequently initiated many strategies and regulations to mitigate the possible adverse outcomes of medical cannabis, including the implementation of standards around the manufacture and prescribing and a monitoring and evaluation system.17 However, despite the limited availability of standard preparations produced by the government Pharmaceutical Organization (GPO) and approved manufacturers, the illegal nonstandardized product was the main source of medical cannabis in our study. This problem may be the result of the limited availability and accessibility of legal products and law enforcement. Furthermore, the Thai FDA found variability in Δ9THC content in MC products, which could be one of the confounders of benefits and side effects in our research.17

There were several limitations in this study. First, as a single-center observation study in a tertiary care center, it could not represent prevalence in other settings or across the country. Furthermore, since there is still no standard dose and form recommendation for specific diseases in the use of medical cannabis, this observational study did not have control over the dose, route, and form of medical cannabis that can contribute to variability in individual

side effects and responses from cannabis.29,31,32,35 Lastly, since most of the medical cannabis in this study was an illegal product, the ingredient of medical cannabis was unknown, which can also contribute to the variable of the effect and side effects. More quantitative control research is needed to explore the effect of medicinal cannabis among chronic cancer and noncancer patients.

After legalization, the use of medical cannabis in chronic pain patients in Thailand is prevalent. Use among cancer patients is more common than among non cancer patients and may be associated with greater pain interference and cancer-related symptoms. Nonmedical license prescription and nonmedical cannabis license products were common. Although most of the patients in our study reported no side effects, minor adverse events were frequently reported. Improving public education, law enforcement, and monitoring long-term adverse outcomes is needed to ensure the safety of the use of medicinal cannabis.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the patients who generously agreed to participate in this study, Ms. Nattaya Bunwatsana for general research assistance and Ms. Julaporn Pooliam for her statistical analysis.

Conflict of interest

The authors have no conflicts of interest to declare.

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%E0%B8%AA%E0%B8%84%2065%2022Dec2022.pdf.