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4 Articles in this Series
Introduction
AIPM 2017 Video Highlights
Cannabinoids versus Opioids for Chronic Pain Care
Congress Seeks Consensus on Policy Coverage for Integrative Medicine
Could Systemic Lidocaine be the New Standard of Care for Pain due to Inflammation?

Cannabinoids versus Opioids for Chronic Pain Care

Is the use of cannabis in place of opioids simply trading one problem for another, asked Mark Wallace, MD, at AIPM’s 28th Annual Meeting in San Diego. A professor of clinical anesthesiology and chair of the Pain Medicine Department at the University of California San Diego, Dr. Wallace set out to answer this question as part of his October 21 keynote presentation on “Science, Politics, and Medicine of the Medical Cannabis for Chronic Pain.” In short, he believes the answer is “no.”

Following is a recap of his packed-audience talk.

Historical & Regulatory Background

The use of medical marijuana dates back more than 5,000 years, specifically to relieve headache pain. Despite its long-term historical use and preclinical evidence confirming analgesic effects on a number of pain conditions, cannabis was removed from the pharmacopeia in 1942. Controversy over its recreational and, more pertinently, medical use, remains.

To date, 34 states and the District of Columbia (DC) have legalized the use of medical marijuana, while seven states and DC have legalized its recreational use. Legal possession limits range from 2 ounces to 24 ounces, and 15 plants. There are no federal laws legalizing the drug in either capacity, and there is no known lethal dose of cannabis, according to Dr. Wallace. “Cannabis ‘abuse’ is only considered ‘abuse’ because it’s currently illegal,” noted Dr. Wallace in reference to federal guidelines.

States do not require prescriptions for cannabinoids—instead, clinicians may provide patients with recommendations or referrals for the drug, but some states, such as California (medical marijuana’s first state adopter), do have guidelines for physicians. California also has a list of conditions that medical cannabis may be used for, including “any chronic medical condition that limits ability life activities”  – and this is precisely where pain care comes in, noted Dr. Wallace.

He added that new state policies have not to led to any reported changes in marijuana dependence or abuse discharges in hospitals, but have resulted in 23% reduction in opioid dependence/abuse discharges per a 2017 study (Shi Y, Drug and Alcohol Dependence, 2017). Another retrospective cross-sectional survey of patients with chronic pain using medical cannabis was associated with a 64% reduction in opioid use, as well as decreased side effects and improved quality of life, he shared (Boehnke et al, Journal of Pain, 17:739, 2016).

With regard to long-term safety and the use of medical cannabis to treat chronic pain, Dr. Wallace referenced a Canadian study by Ware et al published in the Journal of Pain in 2015, which found no significant difference in risks between groups using controlled cannabis and not using it. Furthermore, he noted that cannabis’s abuse potential is significantly less robust than that of heroin, cocaine, or nicotine, based on animal study findings (Cooper ZV, Haney M, Int Rev Psychiatry, 2009:104-112)

Pain Care Approach

Dr. Wallace shared that his approach for treating patients with chronic pain who are currently using opioids has been to wean them off of opioids first, and then to introduce medical cannabis. His aim in moving to the medical cannabis is to continue to provide pain relief for the patient, but with fewer side effects and more functionality. In some cases, he advises patients to begin cannabis as they wean off their opioid doses to help manage any withdrawal effects.

View a brief video clip with Dr. Wallace below.

He noted a few important factors that influence how practitioners may determine dosing and delivery method, pointing out that more research is needed in both areas. The cannabis leaf’s active ingredients, for example, make it more efficacious than its single component extract, he said. Because there is no current federal regulatory oversight on the production of medical marijuana, the final product is in the hands of the states, which vary in policies. Some states, such as California, are even leaving oversight up to their counties’ discretion. As a result, overall purity levels and contaminants of medical cannabis may be unknown. “I suggest using organically grown and vaporized leaves,” for this reason, Dr. Wallace explained, noting that extracts can be more questionable/unknown.

In terms of dosing, Dr. Wallace has found that habitual users report low-dose preference, which has been further documented in animal studies looking at conditioned placed preference versus aversion (Braida D, Pozzi M, Cavallini R, Sala M, Neuroscience. 2001: 104(4):923-926, among others). As little as 5 mg, he noted, may have a calming effect on a patient as an anxiolytic/analgesic, but higher doses of cannabis may lead to paranoia and sedative effects in some patients. There are also considerations to be made with regard to bi-phasic effects (ie, low and high doses can have opposite effects depending on the user profile) and the two compounds within cannabis.

THC, or tetrahydrocannabinol, is the principal psychoactive compound and acts as a CB1 and CB2 partial agonist. THC users may experience a delayed euphoric effect, including pain relief and reduced inflammation, as they metabolize the compound. Cannabidiol (CBD) may provide distinct medicinal applications from THC, including antidepressant effects and reported minimal psychoactive effects. CBD has a very low affinity for the two receptors and should be used with caution when considering drug-to-drug interactions due to an effect on metabolism and blood levels. Some seizure drugs, for example, might have a negative interaction with CBD, noted Dr. Wallace.

Overall tolerance to cannabis may be developed on the psychological side (eg, increased heart rate, drop in blood pressure) and the subjective side (ie, a feeling of euphoria), but there has not been a demonstrated tolerance with analgesic effects, according to Dr. Wallace. That said, a patient may experience withdrawal symptoms from cannabinoids depending on the dose of tetrahydrocannabinol (THC) and/or abrupt termination by habitual users. These withdrawals may exhibit similar symptoms to opioid withdrawal, but effects are less likely with lower dose cannabinoid consumption.

Another potential benefit of medical cannabis that still requires more research is its effect on sleep in patients with chronic pain. “There are no good studies on sleep,” said Dr. Wallace, but some research has shown improvement in patients using cannabis with regard to sleep and sleep apnea, in particular.

Pharmacology Factors & Patient Education

There are multiple drug delivery methods for cannabinoids: leaf combustion (ie, smoking), vaporization, oral ingestion, transmucosal, and sublingual (via spray).

Smoking releases everything in the leaf, including tar, which may produce negative health effects, but the vaporized leaf releases selective cannabinoids, as well as some terpenes (ie, the fragrant oils that give marijuana its distinct smell). 

Medical cannabis as a pain relieverMedical cannabis as a pain reliever

“This is why vapor is preferred for medicinal use,” explained Dr. Wallace. A disadvantage of the vaporization, however, is that the effect peaks (ie, THC and other cannabinoid blood levels reach their maximum) at approximately 5 minutes and may last about 2 hours. Effects via oral ingestion, on the other hand, may last 6 to 8 hours, but there is less control over the peak (some patients prefer to take this form of cannabis at night). Sublingual spray effects have a shorter duration, at approximately 4 hours, with a peak effect at 1 hour.

Based on the route-dependent pharmacology of medical cannabis and its biphasic effects Dr. Wallace advised practitioners to educate their patients about dosing and preparation form. For example, some patients may go to a dispensary and receive a high dose without proper guidance and, ultimately, worsen their pain. “Controlled dosing from a practitioner will provide for a better outcome,” he explained.

Safety Concerns: Alcohol & Driving

More research is needed on the effect of medical cannabis and a user’s ability to drive, said Dr. Wallace, who admitted that the issue is very controversial. Cannabis “appears to have much less effect on motor skills than alcohol,” but a combination of the two can result in severe impairment, he stated.

In his approach, Dr. Wallace has devised the following general rules for patients using medical cannabis: if ingested, no driving for 8 hours; if transmucosal, no driving for 4 hours; if inhaled, no driving for 2 hours. These are not official or legal guidelines. Dr. Wallace added that practitioners must warn their patients that if they have an accident after using cannabis, and test positive for THC, the patients may face a legal problem. He, therefore, advised practitioners to regularly document a lack of intoxication/sedation effect through regular urine drug testing in their cannabis-using patients.

Looking Ahead

At this time, healthcare companies are not prepared to handle dosing or delivery method coverage surrounding medical cannabis, according to Dr. Wallace. Many state laws allow only 4 ounces of marijuana to be dispensed at a time, he said, and dispensaries do not necessarily understand how to dose a patient with chronic pain versus an individual seeking other uses. Dr. Wallace said he is, therefore, working to develop a national education program to help practitioners gain a more in-depth understanding of all the factors at stake.

In the meantime, he concluded that the growth of cannabis as a pain reliever is likely to affect the prescribing of opioids for pain management going forward.  

 

Dr. Wallace noted the following disclosures: Research funding from the Center for Medical Cannabis Research and a consulting role for Zynerba, among other pharmaceutical companies, with Zynerba being the most relevant to the presented topic.

The information presented herein is based on Dr. Wallace’s presentation at AIPM’s 28th Annual Meeting and does not represent the official state or federal guidelines on medical cannabis use.

 

Next summary: Congress Seeks Consensus on Policy Coverage for Integrative Medicine
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