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5 Articles in this Series
Introduction
An AIPM 2018 Preview with Clay Jackson, MD
Can Nutritional Management Make a Dent in Pain Relief?
Challenges Faced When Implementing an Integrative Care Model
The Role of Cannabis in Pain Care Today
When Pain, Opioid Use, and Mental Health Intersect

The Role of Cannabis in Pain Care Today

An AIPM 2018 Meeting Highlight with Michael Schatman, PhD

Clinical psychologist Michael Schatman, PhD, director of research and network development for Boston PainCare, provided the AIPM 2018 Global Pain Clinician Summit audience with an update on cannabinoid use in pain management.

Today’s Legal Framework

Thirty-two states plus the District of Columbia currently have medical marijuana laws in place, but each state’s regulations continue to vary incredibly in terms of how the product is obtained, possession limits, dispensary rules, allowable medical conditions, and other parameters. The real questions come back to what constitutes “medical” marijuana, which in the eyes of pro-marijuana zealots may be everything, while in the eyes of FDA, is nothing. “The truth likely falls in between,” said Dr. Schatman.

Source: 123RFThe forms of medical marijuana differ in their TCH:CBD ratio.

What’s important to be aware of is that some states are now pulling back on their allowances for medical marijuana based on emerging safety data, the growth of questions being asked about its long-term impact, and, of course, politics. Years ago, federal policy was to go after those who violated both federal and state laws surrounding marijuana. For a while, the Department of Justice (DOJ) was raiding dispensaries in selected states. Then, enforcement swung back to support states’ rights, including those in which recreational usage was legal. Eventually, Congress defunded the DOJ from enforcing federal law in medical marijuana states. This defunding amendment has been renewed annually since 2014, however, noted Dr. Schatman, the stipulation is attached to the federal budget, so every time that is threatened, so are the states’ rights.

The Makeup of Available Cannabinoids

Marijuana contains over 100 cannabinoids. The recreational the goal has always been to maximize delta -9-tetrahydrocannabinol (THC) levels, but that seems to be the goal for “medical” products, too. Higher THC levels generally result in higher prices in marijuana sold in dispensaries, even though cannabidiol (CBD) is the most medically relevant constituent in marijuana.

In 2001, common THC:CBD ratios were 14:1 but in 2014, they were 80:1, cited Dr. Schatman.

A 1996-2008 study looked at 5,000 samples in which THC levels increased from 4.5% to 11.75%,  while CBD levels decreased in turn. Currently, CBD measurable levels are rarely found in herbal cannabis and the ratio is rarely examined in American studies. But understanding this ratio and its impact is essential to understanding health risks.

THC Safety Issues

Most safety concerns tied to marijuana are thought to be due to THC, not CBD (see Rehm J, et al, Int J Health Policy Manag, 2016). Smoking remains the most common route of administration and yet, pulmonary effects (now termed “marijuana lung") are worse than had been thought (see Leb JS, et al, Chronic Obstr Pum Dis, 2018) as the tars from smoked marijuana contain more carcinogens than do those from tobacco. Preliminary data shows vaporization is likely an improvement over smoking (see Laflin M, et al, Can J Respir Ther, 2015).

Common side effects of synthetic, pharmaceutical THC products (eg, dronabinol, nabilone) may include drowsiness, unsteady gait, confusion, mood changes, delusions, etc. “Its tolerability is dubious and therefore so is its clinical utility for pain,” said Dr. Schatman. Other safety issues associated with THC that have been empirically established include: increased risk of acute myocardial infarction and cardiovascular mortality, higher rates of acute ischemic stroke, increased risk of death from hypertension, impaired sexual functioning, and immunosuppression. Additional THC-related cases on the rise include: cannabinoid hyperemesis syndrome (2.75 million cases were reported in the US in 2018); higher rates of occupational injuries and traffic accidents / fatalities (96% of drugged driving involved cannabis per one 2018 study); higher risk of drinking behavior; greater physical injury among older adults using cannabis; increased use during pregnancy (22% are using, according to Olga EA, Matern Child Health J, 2018); and addiction with abrupt withdrawal symptoms that may include irritability, insomnia and anorexia (Haney M, et al, Neuropsychopharmaco, 2013).

Information on how marijuana affects cognition is still being researched, said Dr. Schatman. “We know it has an impact on diminution of grey matter,” especially as it affects the developing brain, executive functioning, and broad cognitive deficits in the long term. Mental health risks may be involved although there is no consensus as most research has focused on early onset psychosis. Bipolar disorder has been associated with marijuana use, as has anxiety, despite early studies that showed THC helped with anxiety. “This may have to do with Indica (relaxation) vs Sativa  (energizing) strains,” pointed out Dr. Schatman, and how the risks of cannabis use decades ago is different from those of today due to bizarrely high levels of THC currently found in cannabis. New studies are showing that marijuana use after initiating treatment may even make PTSD symptoms worse compared to previous schools of thought.

Available Products and Strains

THC products approved for research all come from the University of Mississippi, with NIDA approving strains at low (1.29%), medium (3.53%), and high (7%) potency doses.

Some oil/wax products found at dispensaries, however, may have THC contents of 90%, he emphasized. Just over 35% of all marijuana users are now using these products. In fact, dispensary medical marijuana is often sold at higher THC levels than street marijuana, said Dr. Schatman.

The popular edibles are infused with almost pure THC. A big problem with edibles is that they may last 4 to 12 hours, and do not peak until after 2 to 3 hours after ingestion, so it’s easy for a person to take too much as they wait for the high to take effect. Plus, labeling is often inaccurate, leading to more ER visits and intoxication.

CBD Safety Issues

Often described as the “nonpsychotropic” constituent of marijuana, Dr. Schatman said that a label may not necessarily be accurate. CBD has been shown to produce anxiolysis through increasing serotenergic transmission and has a mild antidepressant effect in those with low levels of serotonin. “It may be more appropriately called a ‘noneuphoriant,’” said Dr. Schatman, referring to a paper by Russo EB, Ther Clin Risk Manag, 2008.

However, the safety profile of CBD has been well established across the literature. It attenuates the “high” caused by THC at an 8:1 CBD:THC ratio. This ratio will not provide a “high” to most individuals. However, CBD is still considered a Schedule I drug when it comes from whole plant marijuana. FDA did recently approve the plant-derived Epidiolex for seizures and other indications, and 13 states had legalized CBD even before legalizing medical marijuana. New legal changes allow for CBD to come from the hemp plant as well, which is the same genus of the marijuana plant but contains no more than 0.3 % THC.

Use in Pain Management

CBD is most commonly used for pain, anxiety, depression, and sleep disorders today. It has also shown to serve as an anti-inflammatory analgesic for arthritis (cannabinoid injections could be offered in the future, suggested Dr. Schatman) and has shown to reduce chemotherapy-related peripheral neuropathy without affecting nervous system function or chemo efficacy. But beware, he advised, online products are often mislabeled. If patients report a high from a CBD product, that may be a warning sign that they are obtaining wrongly labeled and potentially dangerous substances.

Is CBD effective for chronic pain? The answer depends on its properties and one’s definition of “effective” (less pain versus functional) and depends on the patient’s goals (reduced symptoms versus quality of life). We know opioids are effective for many types of pain, but not neuropathic pain, said Dr. Schatman, pointing to several related studies. So clinicians need to look at the indication and consider overall that:

  • Cannabinoid cognitive side effects are dose-related
  • Cannabis has not been studied head to head against gabapentinoids, which have dose-related cognitive effects
  • More research is needed on CBD-specific content and on the types carried in dispensaries (25% or more THC)
  • For musculoskeletal pain and arthritis, more evidence is needed
  • For rheumatic conditions, there is no evidence for efficacy
  • For fibromyalgia, there is no empirical evidence for efficacy
  • For headache, there is very limited evidence for efficacy
  • For cancer pain, there is potential use but human studies are of poor quality and limited size, and outdated.

The most compelling evidence basis for medical marijuana use in treating chronic pain, he concluded, was for its opioid-sparing effects. However, a number of recent studies have indicated that “addiction is addiction is addiction,” Dr. Schatman suggested. The best and most recent studies strongly suggested that high-THC marijuana may actually be a “gateway drug” of sorts, and his group’s published research indicates that it increases the likelihood of opioid aberrancy in chronic pain patients two-and-a-half fold (see DiBenedetto, et al, Pain Med, 2018).

Before ending his talk, Dr. Schatman made a point of urging clinicians to use a written agreement with cannabis patients much like opioid agreements are put into place before prescribing. These agreements may cover diversion and inappropriate use, educate the patient about risks and withdrawal possibilities, and cover the clinician in terms of certain legal aspects.

 

Dr. Schatman disclosed that he is a consultant to Kaleo.

Of note, in a Fall 2018 PPM online patient poll, about half of respondents said they had tried medical marijuana to help alleviate their pain or pain-related symptoms but fewer numbers seem to have asked their healthcare providers about its use. 

Next summary: When Pain, Opioid Use, and Mental Health Intersect
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