Page 3 - Top Ten Tips Palliative Care Clinicians Should Know About Medical Cannabis

PALLIATIVE CARE CLINICIANS AND MEDICAL CANNABIS 3

Anecdotal reports in managing refractory CINV with can- be vigilant for increased side effects or diminished effec-
nabis have provided some impetus for more thorough in- tiveness as a result. It is important to explore whether patients
vestigation. have had experience using cannabis through a particular
Cannabinoids, including the prescribed agents dronabinol route of administration, why they chose that route, and if
and nabilone, have been used for many years and are effec- another route is more appropriate. There may be other unique
tive in treating CINV. 9,24 The type of chemotherapy used outcomes patients have experienced or else they should be
may impact the antiemetic effectiveness of cannabinoids, advised may occur. For example, vaporizing cannabis oil
as demonstrated by their positive effect on CINV from high- may result in a higher dose of cannabinoids and subsequent
dose methotrexate, but not doxorubicin or cyclophospha- adverse effects such as psychosis.
mide. 25,26 The emetogenicity of the regimen should be
considered, as oral cannabinoids are effective but likely only
Tip 6: The Evidence for the Use of Cannabis
as adjunctive agents in the setting of highly emetogenic
chemotherapy. 6,27 There is a dearth of high-quality evidence in Psychiatric Illness Is Limited and Varied
supporting the use of cannabinoids through other routes of Although some patients may claim that the use of cannabis
administration for CINV. It also remains unclear what the helps their sleep, anxiety, or mood, an assessment of their
appropriate ratio of THC to CBD might be in managing psychiatric and substance use history may actually bear out
CINV, and if CBD alone can provide antiemetic effects. At that cannabis is contributing to rather than helping the
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best, then, cannabinoids are likely to provide adjunctive problem. Therefore, differentiating substance-induced and
support to other agents in a patient’s antiemetic regimen. independent psychiatric disorders is critical. Psychiatric ill-
Importantly, overuse of cannabis can result in cannabinoid nesses are heterogeneous, and evidence in favor of one
hyperemesis syndrome (described as follows), but this has condition or symptom cannot be extrapolated to another
not been described with mild to moderate use in the medical condition or symptom. Furthermore, patients with psychiatric
setting. illness are themselves diverse, and often have histories
complicated by substance abuse, childhood trauma, home-
lessness, and medical illness. Due to this variation, it can be
Tip 5: Differences in Bioavailability Among Routes
difficult to design robust studies with results that are gener-
of Administration for Medical Cannabis Have Been
alizable. Furthermore, the route of administration may im-
Inadequately Studied for Medical Uses
pact efficacy. For instance, a short-acting effect from inhaled
Medical cannabis can be administered through smoking, medical cannabis may differ in the management of a sleep
vaporization (‘‘vaping’’), eating, tinctures, and salves. Each disorder when compared with the longer-acting effect from
route of administration impacts the onset of action as well as eaten medical cannabis. Nevertheless, preclinical studies are
the intensity and duration of effects. Smoking and vaporizing promising. 31,32
have similarly rapid onsets of action, reach peak blood levels Trials are underway examining the impact of medical
within 30 minutes and then drop within 1 to 3.5 hours. 6 cannabis in managing different aspects of post-traumatic
Enteral administration of medical cannabis, in contrast, will stress disorder, as there is some evidence to suggest that
result in a slower onset of action and a prolonged duration of cannabinoids may be helpful in decreasing the severity of
effect. Notably, cannabinoids undergo first pass metabolism nightmares. 32 Although no trials exist that directly examine
and their bioavailability is reduced when eaten. The first pass the use of medical cannabis in treating depression, some trials
effect does not appear to apply to buccal administration in the that used cannabinoids as an intervention for other problems
form of sprays or lozenges. A patient’s comorbidities may (e.g., multiple sclerosis and chronic pain) measured depres-
thus influence the preferred route of administration (e.g., sion as a secondary outcome and failed to demonstrate im-
preexisting lung disease may prefer edible route vs. smok- provement in that domain. 9,33,34 Medical cannabis is not
ing). Patients may also have preferred routes of administra- beneficial in the management of dementia. 6,35 One system-
tion they have discovered through experimentation. atic review identified one trial that supported the use of CBD
9
Cannabinoids can interact with other medications, both in reducing anxiety associated with public speaking. With
pharmacokinetically and with synergistic side effects. For the current evidence, we cannot recommend cannabinoids for
example, CBD increases levels of clobazam and clobazam- pharmacologic management of psychiatric illness. Some
associated side effects in pediatric patients with epilepsy. 28 patients may nevertheless claim benefit, in which case cli-
Because it is extensively protein-bound, THC (and other nicians should document their use, frequency, amount, and
cannabinoids) may displace other medications and increase monitor for side effects and medication interactions (e.g.,
their effect. CBD is metabolized by CYP2C9, CYP2C19, and increased somnolence with benzodiazepines or opioids).
CYP3A4, and may be impacted by concomitant use of in-
29
ducers and inhibitors of these enzymes. Studies are limited, Tip 7: Although Useful for the Treatment of Anorexia
but at least one trial demonstrated that cannabinoids (spe- Associated with AIDS, There Is Little Evidence
cifically CBD) can be used without diminishing the efficacy for the Use of Medical Cannabis in Cancer-Associated
of paclitaxel; this cannot be generalized to other chemo- Cachexia and Anorexia
therapy or immunotherapy. 3
Although these and other routes of administration are for Some patients report that recreational use of cannabis
recreational use of cannabis, they have not been individually improves their appetite, which provides an impetus for in-
or comparatively studied in medical applications. 30 There- vestigating whether medical cannabis can impact anorexia
fore, medical comorbidities may influence the effects of and weight loss. Dronabinol, a synthetic THC compound, is
medical cannabis in unexpected ways and clinicians should FDA approved for the treatment of HIV/AIDS-associated