Polypharmacy

Polypharmacy—the concurrent use of multiple medications—is a significant and growing health care issue. As the number of medications a person takes increases, there’s a corresponding increase in the risk of medication-related problems, including adverse drug reactions, drug interactions, medication adherence concerns, and higher costs. Because cannabis is a multimodal medication capable of treating a number of medical conditions, its use has tremendous potential to help address polypharmacy concerns for many patients.

Factors Influencing Polypharmacy
Increasing age, chronic medical conditions, and prescribing cascades—in which a new medicine is prescribed to treat or prevent an adverse drug reaction associated with another medicine—contribute to polypharmacy. The incidence of chronic medical conditions increases with age. And while polypharmacy can occur at any age, the risk for polypharmacy is greatest in older adults and other persons suffering from chronic medical conditions that are typically managed using multiple medications.

Consequences of Polypharmacy
Research has clearly established a strong relationship between polypharmacy and a number of negative clinical consequences such as falls, fractures, gait disturbances, urinary incontinence, cognitive impairment, delirium, weight loss and malnourishment, and declines in activities of daily living. The risk of adverse drug reactions and drug interactions increases significantly as the number of medications used increases.

Cannabis Synergy
Cannabis contains hundreds of different constituents including cannabinoids and terpenes that work together synergistically, commonly referred to as the entourage effect, accounting for the vast medicinal properties of cannabis. The most well-known and studied cannabinoids are THC and CBD. THC accounts for most of cannabis’ psychoactive and intoxicating properties, while CBD is believed to counteract many of the undesirable effects of THC, such as the intensity of its intoxicating effects or tachycardia (increased heart rate). In general, cannabis products with higher amounts of THC will contain less CBD to counteract THC’s intoxicating effects.

Cannabis as a Substitute Medication
Cannabis products (eg, CBD oil) increasingly are being used as substitutes for both prescription and over-the-counter medications. In a 2015 Canadian cross-sectional survey, 80.3% of 410 respondents substituted cannabis for at least one prescription drug.1 In another cross-sectional study from 2017, a total of 1,248 (46%) respondents reported using cannabis as a substitute for prescription drugs.2 The most common classes of drugs substituted were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%), and antidepressants (12.7%).

For the study, a total of 2,473 substitutions were reported—approximately two drug substitutions per affirmative respondent. The odds of reporting substitutions were 4.59 times (95% confidence interval [CI], 3.87–5.43) greater among medical cannabis users compared with nonmedical users and 1.66 (95% CI, 1.27–2.16) times greater among those reporting use for managing the comorbidities of pain, anxiety, and depression.

How Cannabis Can Reduce Polypharmacy
A reduction in overall medication use has been described both anecdotally and in smaller studies evaluating the use of medical cannabis. Because of its multimodal properties, cannabis potentially can be used to manage one or more chronic medical conditions simultaneously (eg, to treat both pain and anxiety). In doing so, one or more conventional medications may be discontinued.

Another way cannabis can help reduce polypharmacy is by decreasing the potential for prescribing cascades. In many cases, cannabis can be used to replace high-risk medications, which frequently require another medication to treat or prevent a side effect. A common prescribing cascade resulting from opioid use is the need to use one or more laxatives to address opioid-induced constipation.

Cannabis Substitution for Pain Management
The opioid crisis is well documented, with 128 people in the United States dying from opioid overdose each day.3 Consequently, there’s tremendous need for safe and effective alternatives to opioids. Its improved safety profile along with its analgesic effects and other properties including its ability to reduce spasticity and anxiety make cannabis a viable alternative to opioids for a number of patients suffering from chronic pain.

The analgesic potency of cannabis has been found to be comparable to the narcotic pain reliever codeine. A 1970 double-blind study on a single patient with spasticity and pain due to spinal cord injury demonstrated that 5 mg of THC was as effective as 50 mg of the narcotic pain reliever codeine, while also providing additional benefit in reducing muscle spasticity.4

In another study, the analgesic effect of 10 mg of THC was found to be slightly less effective than 60 mg codeine, while 20 mg of THC was found to be slightly more effective than 120 mg of codeine. THC appeared to be more sedating than codeine while providing patients a greater sense of well-being and less anxiety.5

In an open-label study conducted in Israel, patients given medical cannabis for treatment-resistant chronic pain experienced improved pain and functional outcomes, and a significant (44%) reduction in opioid use. At follow-up, patients’ pain symptom score and pain interference score, along with social most social and emotional disability scores, improved.6 Improvements in quality of life and reduced opioid use were also reported in a 2016 retrospective cross-sectional survey of 244 medicinal cannabis patients suffering from chronic pain. Medical cannabis use was associated with a 64% reduction in opioid use, while quality scores improved by 45%.7

The use of medical cannabis has shown benefits in helping combat the opioid crisis as well. One study found that states with medical marijuana laws experienced a 5.88% reduction in opioid prescribing, which represents 39.41 fewer opioid prescriptions per 1,000 Medicaid enrollees annually.8 Furthermore, there was an 8.36% reduction in prescriptions for nonopioid pain medications.

States with medical cannabis laws also have been reported lower rates of opioid deaths compared with those states without such laws. A 2014 study reviewed data from 13 states that enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate.9 A 2017 study found that while there have been fewer opioid-related deaths, new state policies loosening cannabis restrictions haven’t resulted in increased changes in cannabis dependence or abuse hospitalizations but have been associated with a 23% reduction in opioid dependence/abuse hospitalizations and a 13% reduction in opioid overdose hospitalizations.10

Patients with severe pain may have a continued need for opioids; however, cannabis use is also appropriate as an adjunct to existing opioid treatments. The combined use of cannabis and opioids has been shown to provide greater cumulative pain relief while reducing the dose of opioids needed along with decreased opioid-related side effects.11

Reducing the use of opioids can also influence polypharmacy by helping minimize prescribing cascades. Opioid-related side effects are common and include constipation, nausea, vomiting, impaired concentration, confusion, sleep, and memory problems. Opioid-induced constipation is seen in more than 40% to 60% in patients without cancer who are receiving opioids.12 Whereas tolerance to many opioid side effects develops over time, tolerance to constipation doesn’t generally occur. As a result, the need for one or more laxatives can contribute to polypharmacy concerns. Other prescribing cascades associated with opioids include the need for antiemetics to counteract nausea and vomiting and the need for an antihistamine to counteract opioid-related itching.

Cannabis use to help reduce nonopioid analgesic use is also of great importance. Nonsteroidal anti-inflammatory drugs, or NSAIDs (eg, ibuprofen and naproxen), are widely used in pain conditions due to their analgesic and anti-inflammatory properties. NSAID use is associated with gastrointestinal bleeding, renal impairment, and adverse cardiovascular events.

In one study, 19% of 2,508 community-dwelling older adults were using one or more medications inappropriately, with NSAIDs and benzodiazepine anxiety medications (eg, alprazolam) being the drug classes with the most potential problems.11 Furthermore, a 2017 systematic review and meta-analysis of 42 studies of hospitalizations among adults 60 years of age and older conducted in 21 countries (the majority in Europe), found a mean prevalence of adverse drug reaction–related hospitalizations of 8.7% (95% CI, 7.6–9.8), with NSAIDs being the most commonly implicated class of medications.13

Substituting cannabis for NSAIDs has great potential to reduce polypharmacy-related prescribing cascades. Because of concerns with peptic ulcer disease and increased gastrointestinal bleeding, patients taking NSAIDs routinely are advised to take a proton-pump inhibitor (eg, omeprazole) as well, which increases the potential for further prescribing cascades. For example, chronic proton-pump inhibitor use may lead to vitamin B12 and magnesium deficiencies, which may result in the addition of supplements. Another prescribing cascade associated with NSAIDs is related to their potential to cause cardiovascular side effects including hypertension, which then may result in the need for blood pressure medications, possibly causing further prescribing cascades.

Cannabis Substitution for Benzodiazepines
Benzodiazepines (eg, alprazolam, diazepam, lorazepam, and clonazepam) are widely used to treat a number of conditions such as anxiety, insomnia, seizures, and spasticity. Despite their widespread use, benzodiazepines are almost never recommended as first-line medications for any indication. Side effects include ataxia, dizziness, drowsiness, fatigue, slowed reaction, and muscle weakness. Tolerance to benzodiazepines develops rapidly; for example, tolerance to its hypnotic effects can develop in a matter of days or weeks with regular use, while tolerance to its anxiolytic effects develops over a few months.

Of great concern is physical dependence, which can occur in as little as a month with regular use. After a period of one to six months, severe withdrawal symptoms are common, and the abrupt cessation of benzodiazepines can cause life-threatening seizures, delirium, and death.14 Reducing the dose of benzodiazepines can be extremely difficult and often requires a slow tapering of the dose over an extended period of time. The need for other medications due to tolerance is common; anticonvulsants, antihistamines, and others are routinely required to assist with the successful tapering.

Cannabis is frequently reported as a substitute for benzodiazepines for use in treating symptoms of anxiety, insomnia, spasticity, and seizures. Several studies evaluating the use of cannabis have described benefits in reducing benzodiazepine use. One such study reported that after an average two-month course of medical cannabis, 30.1% of patients had discontinued benzodiazepines. At a follow-up after two prescriptions, 65 patients (44.5%) had discontinued benzodiazepines, and at the final follow-up period after three medical cannabis prescription courses, 66 total patients (45.2%) had discontinued benzodiazepines, showing a stable cessation rate over an average of six months.15

Autism
CBD has been observed to help alleviate psychosis, reduce anxiety, facilitate REM sleep, and suppress seizure activity.16 Based on these previously reported observations, researchers conducted a retrospective feasibility study of 60 children with autism who were given CBD-enriched cannabis. Behavioral outbreaks improved in 61% of patients, communication problems improved in 47%, anxiety was reduced in 39%, stress was reduced in 33%, and disruptive behaviors improved in 33%.17

A prospective case study of the THC-based drug dronabinol showed significant improvements in hyperactivity, lethargy, irritability, stereotypy, and inappropriate speech at six-month follow-up.18 In another study, dronabinol use in 10 adolescent patients with intellectual disability resulted in eight patients showing improved management of treatment-resistant self-injurious behavior.19

A study conducted in Israel found that cannabis oil (typically 30% CBD and 1.5% THC) is an effective treatment for a variety of autism-related symptoms including seizures, tics, depression, restlessness, and rage attacks for patients aged 18. Furthermore, the study demonstrated reductions in polypharmacy for this younger population of patients. At the beginning of the study, the most common concomitant chronic medications used were antipsychotics (56.9%), antiepileptics (26.0%), hypnotics and sedatives (14.9%), and antidepressants (10.6%).

Out of 93 patients responding to the follow-up questionnaire, 67 reported use of chronic medications at intake. Overall, six patients (8.9%) reported an increase in their drugs consumption. For 38 patients (56.7%), drug consumption remained the same, while 23 patients (34.3%) reported a decrease, mainly of the following drug families: antipsychotics, antiepileptics, antidepressants, and hypnotics and sedatives. Antipsychotics were the most prevalent class of medications taken at intake (55 patients, 33.9%). At six months, they were taken at the same dosage by 41 (75%); three patients (5.4%) decreased dosage, and 11 patients (20%) stopped taking this medication.20

Final Thoughts
As medical cannabis laws continue to be loosened and there’s increased availability and marketing of cannabis products such as CBD oil, the potential for substitution of these products for traditional prescription medications is likely to increase significantly. Health care providers should continue to increase their knowledge about both the potential medicinal benefits and risks associated with cannabis use. While substitution may provide a number of benefits to patients, including the possible reduction of polypharmacy, not all patients can or should use cannabis, and substitution without health care provider oversight could result in patient harm. Encouraging patients to discuss the use of cannabis and related products will allow health care providers to offer much needed guidance and assistance with respect to the appropriateness of substituting cannabis products, as well as allowing the opportunity to monitor the effectiveness of such substitutions.

— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

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