Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety. A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050. Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0–384.0 mg) and 1.3 mg (Range: 1.0–16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity. This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments. End-of-Life Care: Dying With Dignity and Comfort — The Role of Medical Cannabis The principal goal of palliative care is to reduce suffering experienced by patients who are at or near end of
UK Medical Cannabis Registry palliative care patients cohort: initial experience and outcomes
Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety.
A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value< 0.050.
Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0–384.0 mg) and 1.3 mg (Range: 1.0–16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity.
This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments.
Achieving optimal pain and symptom control is a crucial component of palliative and end-of-life care. There is a pertinent need for the provision of effective treatment with up to 40 million people requiring palliative care globally each year (World Health Organization, 2020). Furthermore, evidence suggests that the pain incurred by life-limiting illnesses, particularly cancer, remains largely under-treated (Breivik et al., 2009).
A growing body of literature suggests that cannabinoids, terpenes, and flavonoids exert widespread effects on neurotransmission, neuroendocrine signalling, and inflammatory processes (Huang et al., 2016). This potentially makes cannabis-based medicinal products (CBMPs) an emerging multi-faceted therapeutic option in managing primary chronic pain, cancer pain and neuropathic pain (Romero-Sandoval et al., 2018). CBMPs, generally refer to pharmaceuticals and non-approved compounds which interact with the endocannabinoid system. However, they can also refer to cannabinoid-based medicines, endocannabinoid system modulators or cannabinoid receptor modulators, in light of lack of consensus of nomenclature. Possible benefits have also been shown for some neurological and psychiatric conditions, such as anxiety-predominant disorders. Combined, these effects make the use of CBMPs as part of end-of-life care for patients a promising yet relatively unexplored avenue.
There is a paucity of evidence to guide best prescribing practices and optimal therapeutic regimes. Whilst randomised control trials (RCTs) constitute the highest quality evidence, current research remains limited in providing CBMP patient data. Formalised patient registries can be the source of high-quality, naturalistic observational data to answer these questions until RCTs are conducted. We therefore describe a preliminary exploratory analysis of outcomes of patients from the UK Medical Cannabis Registry who were treated with CBMPs for diagnoses related to palliative care. We aimed to investigate therapeutic formulations, adverse events incidence and character, and patient-reported outcome measures pertaining to the quality of life.
A case series of the initial participants of the UK Medical Cannabis Registry treated with CBMPs for indications of palliative care, cancer pain and chemotherapy-induced nausea and vomiting was undertaken. Palliative care was defined as treatments for physical and psychological symptoms caused by life-threatening or life-limiting conditions. Participants who had recorded PROMs at baseline with at least 1 follow-up date (1 and/or 3 months) were included in the study (n = 16).
The UK Medical Cannabis Registry is the first registry in the UK that collates prospective longitudinal clinical data from patients treated with CBMPs. It was set up in 2019, and captures patients treated within the United Kingdom and outside of the National Health Service (NHS). The UK Medical Cannabis Registry is privately owned and managed by Sapphire Medical Clinics. Clinicopathological information, comorbidities, drug and alcohol history and medication details are inputted into the registry prospectively by clinical staff. Data on cannabis use status was also collected, and for those who had previously or were presently taking non-prescription cannabis, a novel metric of “gram years” was calculated as previously described by our group (Erridge et al., 2021). Pseudonymised clinical data on patient-reported outcome measures (PROMs) and adverse events were collected.
All participants completed five validated quality of life PROMs, including the EQ-5D-5L (Herdman et al., 2011), a health status measure assessing quality of life amongst 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and extreme problems), General Anxiety Disorder-7 (GAD-7) (Löwe et al., 2008), Single-Item Sleep Quality Scale (SQS) (Snyder et al., 2018), the Australia-Modified Karnofsky Performance Scale (AKPS) (Abernethy et al., 2005) and the Pain Visual Analog Scale (VAS), a unidimensional measure of pain intensity anchored by “0 – no pain at all” and “10 – pain as bad as it could be” (Hawker et al., 2011). Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
PROMs data were compared from baseline to 1- and 3-month follow-ups. Paired matched Wilcoxon rank sum tests were utilised for non-parametric data sets and paired t-test were used for parametric data sets, as determined by Shapiro-Wilks normality tests. Statistical significance was defined as p-value 0.050. All statistical analyses were conducted using Statistical Package for Social Sciences (SPSS) version 27.0.
Sixteen patients were included in the analysis. The mean age of participants was 63.25 ± 12.27 years, with equal sex distribution. Half of the participants (n = 8, 50%) had never used cannabis previously, 4 (25%) were current cannabis users, and 4 (25%) were ex-users. Amongst the current users, gram-years ranged from 1 to 10, with the mean of 2.4; amongst ex-users gram-years ranged from 0.1 to 1, with an average of 0.35. Amongst current users, the average daily THC consumption (estimated based on 18–20% THC content in cannabis) was 20–400 mg, with an average of 120 mg per day. 6 (37.5%) participants died during the study period.
The most common primary diagnosis was palliative care (n = 12, 75%), followed by cancer pain (n = 3, 18.75%) and chemotherapy-induced nausea and vomiting (n = 1, 6.25%).
Most participants (n = 14, 87.5%) were prescribed two different CBMPs, all of which were oil preparations. The median initial CBD dose was 32.0 mg (Range: 20.0–384.0 mg). The median initial THC dose was 1.3 mg (Range: 1.0–16.0 mg). The most commonly used preparations were 50 mg/ml CBD oil (Adven 50, Curaleaf International) and 20 mg/ml THC oil (Adven 20, Curaleaf International).
In total, there were three adverse events (n = 3, 8.75%). Adverse events experienced by participants included lethargy (n = 1, 6.25%), ataxia (n = 1, 6.25%) and dysgeusia (n = 1, 6.25%). Of these, 2 (12.5%) were reported as mild and 1 (6.25%) was reported as moderate. When analysed based on the cannabis use status, ex-users, current users and those who never used cannabis had equal adverse event rates, with one event in each subgroup.
Pain VAS was initially reported as ‘severe’ (6.5 ± 2.07) however reduced to ‘mild to moderate’ (4.24 ± 2.91) at 1 month, and to ‘mild’ (1.00 ± 1.41) at 3 months. Mean SQS scores improved from 4.89 (± 2.32) at baseline to 6.89 (± 2.03) at 1 month, and 5.25 (± 3.02) at baseline to 7.75 (± 1.71) at 3 months. Mean SQS scores improved by 40.9% from baseline to 1 month, and 46.7% from baseline to 3 months. Overall, there were no significant improvements in mean SQS, median EQ-5D-5L Mobility, EQ-5D-5L Pain and Discomfort, EQ-5D-5L Anxiety and Depression, EQ-5D-5L Index, EQ-VAS and Pain VAS at 1-month and 3-month, when compared to the baseline (p > 0.05).
CBMPs were well tolerated with few adverse events, all of which were mild to moderate in severity and resolved spontaneously. No significant improvements were found in any of the outcome measures due to the small sample size of the study (n = 16). A post-hoc power calculation using data from this case series determined a sample size of 56 would be required to determine a significant difference at 3 months in reported EQ-5D-5L index values. An updated analysis shall be performed when this is available.
This preliminary exploratory study provides an initial analysis of the role of CBMPs in palliative care in the first reported cohort of patients since the legalisation of CBMPs in the United Kingdom. CBMP treatment was well-tolerated with few adverse events, which were all mild to moderate in severity and resolved spontaneously. This data provides an insight into the safety and outcomes of CBMP treatment amongst palliative care patients and may help guide future clinical studies and prescribing practice. Further long-term safety and efficacy studies involving larger cohorts are needed to evaluate long-term prescribing outcomes, with comparisons with placebo and standard treatments for palliative symptom control.
Availability of data and materials
Data that support the findings of this study are available from the UK Medical Cannabis Registry. Restrictions apply to the availability of these data. Data specifications and applications are available from the corresponding author.
Cannabis-based medicinal products
General Anxiety Disorder-7
Visual Analog Scale
Australia-Modified Karnofsky Performance Scale
Patient-Reported Outcome Measures
Common Terminology Criteria for Adverse Events
Statistical Package for Social Sciences
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Breivik H, Cherny N, Collett B, de Conno F, Filbet M, Foubert AJ, et al. Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol. 2009;20(8):1420–33. https://doi.org/10.1093/annonc/mdp001.
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End-of-Life Care: Dying With Dignity and Comfort — The Role of Medical Cannabis
The principal goal of palliative care is to reduce suffering experienced by patients who are at or near end of life. Palliative care is multidimensional, attending to the physical, emotional, psychological, and spiritual needs of patients with life-limiting disease. Hospice and palliative care services may be provided in a patient’s home, a nursing home, or an inpatient hospice unit.1 Historically, end of-life palliation utilizes a combination of opioids, benzodiazepines, serotonin 5-HT3 receptor antagonists, and antipsychotic medications to help ease patients’ suffering. While often necessary, these medications come with many unwanted—and sometimes dangerous—side effects, particularly at the increased doses typically needed to achieve relief of symptoms. Integrating cannabis has been shown to reduce harm and unwanted side effects when used in combination with medications.
The benefits of using medical cannabis for improving quality of life among palliative care and hospice patients are numerous. Several benefits are explored here.
The Synergistic Relationship Between Cannabinoids and Opioids
The overlap of the endocannabinoid and endogenous opioid systems offers an understanding of why cannabis and opioids work well synergistically. Both provide analgesic effects, with evidence of cannabis producing analgesia at both the central and peripheral levels.1 Both systems consist of G-coupled protein receptors found throughout the brain,2 and both cannabinoids and opioids are produced endogenously and are part of the homeostatic processes necessary for life.3
Cannabis is an ancient medicine with millennia of safe usage. With a toxicity profile that’s less harmful to the body than water, cannabis is particularly effective when dosed consistently and appropriately. Opioids are also an ancient medicine, regarded as most effective for treating pain but with a much more harmful toxicity profile that includes respiratory depression from overdose. With morphine, the most common opioid used in end-of-life care, difficulty breathing is a common side effect. Constipation, nausea, vomiting, and drowsiness are also commonly reported at the doses often required for comfort.
Many of these side effects can be mitigated with the use of medical cannabis. Research has demonstrated that subanalgesic doses of morphine and THC are equally unsuccessful at mitigating pain. However, the combination of morphine and THC shows a significant reduction in affective pain, and preclinical trials suggest coadministration attenuates tolerance.4 This translates to the patient requiring lower doses of opioid medication for symptom control, thereby reducing respiratory depressive effects that are commonly experienced at higher doses.
Medical cannabis also has been shown to reduce the doses of antidepressant or antianxiety drugs in patients at the end of life.5
These examples support the concept of combining cannabis with conventional medications to reduce the doses of prescribed opioids, anxiolytic, and antidepressant medications, all of which are often titrated up significantly at end of life.
Cannabis Promotes Presence of Mind for Dying Patients
Cannabis has been associated with euphoria, aversive memory extinction, and sensorium enhancement, and can serve as a spiritual insight catalysis. This experience may mitigate any number of anxious thoughts and behaviors that accompany the end of life. Cannabis has also been used as an enhancer to heighten sensory perceptions and awareness.6 People with terminal illnesses may be looking to evaluate the meaning of their lives and deepen their connections with loved ones during the limited time they have left. If used properly, euphoria and enhanced sensorium may help overcome the barriers to achieving mindfulness at the end of life. This may help patients achieve a moment-to-moment presence and abstain from focusing only on the future.
Cannabis also holds potential to ease the psychological trauma that a terminal diagnosis often brings. This spiritual growth and development may offer a more dignified experience for patients. Families may also benefit as they witness their loved ones experience a more peaceful state of being. The resultant lucidity makes possible a more conscious, connected, and dignified passing.
Barriers to More Widespread Use
In a national survey examining the knowledge, experience, and views of hospice professionals toward medical cannabis, 91% of individuals support cannabis use in hospice. Three-fourths of these clinicians care for patients for whom cannabis was most successful in managing their nausea, vomiting, pain, and anxiety; however, less than 50% certify their patients. The most common reason for providers not utilizing cannabis is a general confusion and discomfort over their insufficient knowledge and training.7 This inadequate preparation begins at the core of providers’ careers, with traditional education at medical, nursing, and pharmacy schools neglecting to include appropriate cannabis education.
Additionally, hospices and other health care settings that receive federal funding preclude the use of cannabis, as it remains a federally illegal substance. Many hospice settings are left to either look the other way or maintain a hands-off policy, leaving someone close to the patient to procure and administer the medicine.7 The result is typically a “don’t ask, don’t tell” approach that can lead to an unsafe and ineffective combination of cannabis with other medications. With patients and families continually asking hospice clinicians about cannabis, we’ve clearly reached a time in which hospice clinicians must either receive appropriate cannabis education or refer their patients to a provider who specializes in medical cannabis.
Overcoming the Roadblocks
While rescheduling or descheduling cannabis would certainly be helpful, patients are suffering now. We cannot wait for hospice clinicians to educate themselves, as cannabis therapeutics is a specialty in and of itself that requires time and experience. Being in such high demand, most cannabis providers don’t provide in-home or nursing home visits. One silver lining in the dark COVID-19 cloud is telehealth. With telehealth, cannabis therapeutics specialists, such as recommending providers and cannabis nurses, are able to consult with suffering patients and their families from the safety of their residences. To meet patients’ needs, many medical dispensaries are implementing or expanding their delivery services so patients have access to cannabis during this unprecedented time.
Death With Dignity
In summary, medical cannabis holds the potential to help terminal patients remain comfortable mentally, emotionally, and physically at the end of their lives. The synergistic effect of combining cannabis with opioids, anxiolytics, or mood stabilizers reduces the necessary dose of both cannabis and these medications. This offers patients an approach that can better manage many symptoms associated with the end of life, while reducing the unwanted side effects of interventions. With appropriate guidance and support, hospice patients have an opportunity to die peacefully, comfortably, and with the dignity we all deserve.
— Ryan D. Zaklin, MD, MA, PC, is trained in internal, geriatric, integrative, mind-body, and cannabinoid medicine. He earned his MD from the University of Virginia and completed his training in internal medicine at Massachusetts General Hospital and served on the faculty at Harvard Medical School. He works with Partners Network in skilled nursing facilities and maintains a private practice in integrative medicine.
— Meghan Clements, FNP-BC, graduated with her bachelor’s degree in biochemistry from Merrimack Collage (2009) and her master’s in nursing from Simmons University (2013). Starting her career as a nurse practitioner, she cared for geriatric patients during their short term rehabilitation or long term care stay, helping to manage their acute illnesses, chronic conditions, and end-of-life care. She also works as an orthopedic nurse practitioner.
— Marissa Fratoni, BSN-RN, LMT, RYT, INHC, is a holistic nurse and multidisciplined health practitioner specializing in women’s health and behavioral health and further specializing in cannabinoid therapeutics. She’s well versed in complementary healing modalities including massage therapy modalities, yoga, and integrative nutrition. Her published work and adventures in the cannabis space can be found at holisticnursemama.blog.
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