The use of cannabis for management of a wide variety of symptoms dates back thousands of years.1 In the16th and 17th centuries, English herbalists used cannabis for flatulence, gout, joint, and hip pain. Dr. William O’Shaughnessy returned from India in 1842 to introduce British physicians to cannabis for disorders such as rheumatism, menstrual cramps, and epilepsy.2 U.S. Pharmacopeias in the 19th and early 20th centuries recommended cannabis for many conditions, including alcohol and opiate addiction, neuralgia, and others.3 This wide range of cannabis-associated symptom management has relevance for patients in the palliative care setting.
The rapidly growing use of cannabis in the majority of states is leading to increasing numbers of patients asking their medical providers about medical cannabis.4 Particularly for patients with terminal illnesses, there is a conglomerate of symptoms, including sleep, pain, anorexia/nausea, and depression/anxiety, which can severely impact quality of life.5Although these patients may have abandoned survival as an outcome, quality of life becomes central.6
A 2002 review encompassed clinical trial literature on cannabis in palliative care concluding that there is a lack of medical support for use of cannabis in the palliative care setting.7 This conclusion is logically based on the dearth of clinical trial data, confounded by a lack of standardization of cannabis used (from synthetic tetrahydrocannabinol [THC] to smoked cannabis); however, often quality of life is not considered as an outcome. In addition, the randomized controlled trial model is a useful tool, however not infallible, and will likely not represent the unique clinical picture of each patient (personalized medicine) seen by palliative care doctors.8Real-world data have better established the cannabis landscape for patients.9
The National Academy of Sciences 2017 report cited conclusive or substantial evidence that cannabis and/or cannabinoids are effective for the treatment for chronic pain in adults, as antiemetics in the treatment of chemotherapy-induced nausea and vomiting, and for improving patient-reported multiple sclerosis spasticity symptoms.10 Other studies of cancer patients have found that medical cannabis helps relieve their nausea, pain, anxiety, and poor appetite, as well as enhance their feelings of well-being.11 The potential for cannabis to address multiple symptoms can minimize the need for drug cocktails and reduce their side effect profiles for this vulnerable patient population. In addition, cannabis’s psychoactive effects, which include induced heightened mindfulness, while offering some degree of dissociation from physical symptoms, can be invaluable in last days of life.12
Access to a variety forms for cannabis administration allows patients to experience some control with regard to how and when they use it for symptom sets. Phamacokinetics and pharmacodynamics of cannabinoids compounds can be highly variable across individuals. For this reason, n-of-1 trials may be the best fit for cannabis in palliative care. In addition, not only does cannabis appear to be safe when combined with opioids, but also there is evidence for opioid-sparing effects that can enhance the quality of time spent with their loved ones.13
In a recent comprehensive review of the use of cannabis in palliative care, Cyr et al. summarized the best clinical evidence, outlined current challenges, and offered practical recommendations for prescribing providers.14 This review provides practical lessons. However, one major exception is the variability in state laws, which makes it difficult to provide universal high-quality educational programs for U.S. clinicians. As a result only few academic centers offer continuous medical education (CMEs) programs on use of medical cannabis in clinical practice. Although some states, for example, District of Columbia, offer online courses through approved education vendors, these are not required to recommend cannabis to patients, and not specific to field of palliative care.15 Clearly this needs to change to assure adequate training of palliative care providers. One solution could be adding state-specific didactics to palliative care fellowships and more general CME opportunities through American Academy of Hospice and Palliative Medicine. A general overview of the proposed utility of cannabis in palliative care is found in Table 1.
|Symptom||Associated condition||Route/dosage||Best evidence references||Notes|
|Neuropsychiatric symptoms: agitation, anxiety, insomnia, depression, and aggression||Dementia||THC:CBD mixes
Doses ranging from 5 to 10 mg of THC and 10–20 mg of CBD/day at twice daily frequency
|Maust et al.16, Peprah and McCormack17||– Safest pharmacologic treatment method. Standard prescription alternatives such as typical or atypical antipsychotics are all in Beers list criteria and increase mortality.
– In one study patients decreased use of narcotics by 2/3 in 2 months.
|Chronic pain||Cancer related and others||Inhaled, or oral, variable dosing can probably start with just 1–2 mg of THC (self-titration model works well)||National Academies of Science10||– As per NAS strong evidence, however, NAS expert panel did not provide practical dosing recommendation.
– Likely sublingual concentrates of THC will also work, but there are no trials supporting this approach.
|Nausea||Cancer related||Inhaled variable dosing can probably start with just 1–2 mg of THC||National Academies of Science10||– As per NAS strong evidence, however, NAS expert panel did not provide practical dosing recommendation.
– Likely sublingual concentrates of THC will also work, but there are no trials supporting this approach.
|Appetite stimulation and cachexia||Cancer and advanced dementia||Inhaled, sublingual, or oral variable dosing can probably start with just 1–2 mg of THC||National Academies of Science10||Data are weak at best, despite number of anecdotal cases.|
|Sleep disturbances||Chronic pain, cancer-related pain, peripheral neuropathy||Oral dosing of 2.5 up to 30 mg of THC (self-titration model works well)||Bestard and Toth,18Narang et al.,19 Blake et al.,20 Babson et al.21||Mixed evidence (dose related). The best evidence for THC as CBD has not been shown to affect sleep architecture.
THC may also reduce episodes of sleep apnea.
CBD, cannabidiol; NAS, National Academies of Science; THC, tetrahydrocannabinol.
Although it is very unlikely that high-quality randomized studies of medical cannabis in palliative care will be seen in a near future there is one approach that seems to be realistic. Because many palliative care patients already using medical cannabis and all states with legalized medical cannabis have some form of information tracking and able to assist researchers in data assessment, incentivizing such data gathering and analysis research should be encouraged. This type of epidemiologic research will not violate any federal or local laws and will provide pilot data for future controlled trials. Authors encourage collaborations between local hospices, academic institutions, and governments to not only engage in data assessment but also building in additional research assessment tools into existing infrastructures. For example, in both Washington, District of Columbia, and Maryland providers filling out medical cannabis recommendation forms must select medical conditions. Adding a check box that asks if the patient is enrolled in hospice will simplify further data gathering and will not add any additional time/effort for providers or the system. Since both District of Columbia and Maryland allow hospice patients to obtain expedited cards (24 h instead of 3–4 weeks for regular) this seems to be a very logical step that will simplify application process for patients, caregivers, providers, and medical cannabis programs alike. In addition, authors believe that collaborations between local hospices and local dispensaries may also be possible and allow interested hospice patients to have faster and easier access to medical cannabis to manage their symptoms.
Finally, the current schedule 1 Drug Enforcement Administration (DEA) status that is a major road block for federal funding can be avoided by looking for private funding. Many hospices are 501c3 nonprofit organizations and have part of their operational costs supported by philanthropy. Donors may like to have an opportunity to support groundbreaking studies on medical cannabis. In addition, larger hospices located in areas where medical cannabis use is legalized may see financial incentive to conduct such studies; medical cannabis cost is lower than cost of generic narcotics and other medications. Hospices are covering cost of all palliative medications and approaches out of per diem payments received from insurances. Thus, all hospices are looking for lower cost symptoms management approaches all the time. For example, typical cost of sublingual high % THC oil used for cancer-related pain at retail prices is between $40 and $60 for a 15 mL/300 mg bottle that would last for several weeks, whereas single bottle of liquid morphine 20 mg/mL (15 mL/300) is $30 and at typical use will last only for few days. This example gets more extreme with other narcotics or other medications such as Oxycodone 20 mg/mL (30 mL) at cost of $300 or Megestrol, often used by palliative care providers to try to stimulate appetite, with typical monthly cost of liquid form of over $400. If a hospice provider wants to prescribe the only available oral Food and Drug Administration-approved THC drug Dronabinol the monthly cost will be at least $1000 and can be as much as $10,000 making it cost prohibitive for all hospices. Moreover, in many locations, dispensaries are giving substantial discounts for palliative care patients, and hospices likely will be able to negotiate wholesale discounts for their patients. In one author’s (M.K.) experience one Maryland dispensary has specially trained palliative care provider on dispensary staff because leadership felt that it is their “duty” to provide high-quality advice and discounts for patients suffering from end-of-life conditions. However, these lay persons may be operating with conflicts of interest and are not oriented toward fundamentals of medical ethics, including informed consent regarding other treatment options. In most instances they are, effectively, practicing medicine without a license. They may be making recommendations that conflict with guidelines from national organizations, and/or have no evidence base. This highlights the need for educated medical professionals who can safely guide the palliative care patients in the use of medical cannabis at the end of life.
Regardless of what happens with DEA’s federal scheduling of cannabis in years to come, it is clear that medical cannabis is here to stay, and that more and more patients suffering from incurable illnesses will turn to it for relief of their symptoms. As clinical evidence grows, there is a good possibility that cannabis will one day become part of the standard palliative care toolbox.