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Few topics in workers compensation have created as much commentary and controversy over the last several years as the evolving status of marijuana and marijuana-derived products when used by employees. In this article, I review some of the recent scientific articles regarding the efficacy of marijuana and its derivatives (henceforth, “cannabis”) as treatments for occupational conditions, and go on to discuss how the use of medical cannabis for nonoccupational conditions may also have workplace implications.
I will focus on medical evidence and its implications alone, without any formal legal or legislative review regarding medical or recreational marijuana at the state level, though variability in state and federal law may be mentioned in the context of the medical discussion. Those who wish for a more complete discussion of some of the areas touched on should download the recent comprehensive review by the National Academies of Sciences, Engineering, and Medicine (NASEM), which is an excellent summary of the state of the science as of late 2016.1 NCCI has recently reviewed many of the legal and regulatory issues in its Marijuana Conversationseries.
Marijuana and Marijuana-Derived Products
A brief review of marijuana biology and chemistry is necessary to make sense of the many articles on its use as a treatment. Marijuana refers to two closely related plant species, Cannabis indica and Cannabis sativa; the term “cannabis” is applied to both. The two most important biologically active compounds in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD), but cannabis also contains a mixture of hundreds of other organic compounds. Many of these, including both THC and CBD, are known as cannabinoids, because they all have effects on human physiology via receptors referred to as the endocannabinoid system (ECS). Both recreational and medical cannabis may be smoked or eaten; some cannabis is refined into cannabis oil, which can also be vaporized, ingested, or used topically.
THC and CBD have substantially different effects on the human ECS, and many cannabis strains have been extensively cultivated over the last 20–30 years to produce different concentrations of THC and CBD.1 THC acts primarily on central nervous system (CNS) receptors known as CB1; to oversimplify, stimulation of CB1 receptors appears to account for most of the effects of THC, including euphoria and appetite stimulation, but there are CB1 receptors in other tissues as well, including the gastrointestinal tract and skeletal muscle.1,2 The effects of CBD are more complex.
While CBD has been considered “nonpsychoactive” because it does not activate CB1 receptors, it may modulate the effects of THC.1 CBD acts on several other receptors in the CNS, including those involved with the serotonergic system, and may have a variety of effects, including reduction of anxiety and inflammation.1,3,4
There are several pharmaceutical products based on THC and/or CBD that have been derived, some currently available and some in various stages of testing (see Table). There are also multiple synthetic cannabinoid derivatives that have been produced primarily for the illegal market that have a variety of psychoactive properties. (1) (click here for the graphic)
Several aspects of the above are particularly important in understanding the evidence for and against the use of cannabis and cannabis derivatives in the treatment of various conditions:
The human ECS system was not discovered until the 1990s. Much remains to be learned regarding how cannabinoids, including THC and CBD, interact with the ECS to produce therapeutic effects.1,5,6
Marijuana has been classified as a Schedule I drug by the FDA for more than 50 years. This has created several limitations on medical research, including:
Difficulty in obtaining necessary permits and grants to perform human trials.
Requirements that researchers must use a single strain of marijuana grown by the US Department of Agriculture. This strain is not representative of strains available in dispensaries in states where the use of marijuana is legal under various scenarios.
Medical vs. Recreational Marijuana
The terms “medical marijuana” and “recreational marijuana” are primarily legal and regulatory constructs. Some substances may be both medicinal and recreational, while other substances are one but not the other. This has added to the confusion concerning the medical efficacy of cannabis.
In legalizing marijuana for medical use, many states have specified a wide variety of conditions for which patients may obtain authorization from a medical professional to purchase marijuana from a dispensary or, in some instances, cultivate it themselves. As the NASEM review1 notes, there is limited or no evidence for the efficacy of cannabis for some of those conditions; but given the limited research, absence of evidence cannot be considered evidence of absence of benefit (see below). In some states, such as New York, a limit on the potency of the THC content is specified. An updated summary of state laws is available.7
Recreational marijuana is cannabis used for nonmedical purposes, primarily euphoria and other CNS effects. There are vast numbers of strains, bred for varying amounts of THC, but all contain some CBD. Medical marijuana (sometimes referred to as “medicinal”) was initially marijuana obtained legally for treatment of a specified medical condition, often with the same THC content as recreational marijuana. As marijuana legislation has evolved toward complete legalization in some states and an expansion of medical marijuana laws in others,7 strains that have much higher CBD and much lower THC content have been developed, producing little or no euphoric effect. Further complicating the picture are the promotions of the marijuana industry, where strains are characterized according to their effects on energy levels, stress, pain, depression, anxiety, etc., with multiple-user reviews (see endnotes 8 and 9 for examples, not intended as endorsements).
The term “medical marijuana” does not have any scientific meaning in terms of chemical composition or potency.
While many users of cannabis prefer low THC:high CBD strains to avoid the euphoric and psychomotor side effects of THC, some of the medically beneficial effects of cannabis are likely to be due to THC and/or the THC:CBD combination (see discussions on chronic pain below).
There is great variability in the potency of different cultivated strains of marijuana, along with variability in the ratio of THC to CBD. Added to this, the pharmacologic effects of cannabinoids depend on the method of consumption (i.e., smoking vs. ingestion vs. vaporization). Many of the research articles regarding the effectiveness or ineffectiveness of cannabis for various conditions have not adequately accounted for these factors.1
Many of the effects reported by users in studies of the use of cannabis for various conditions are likely due to a combination of THC, CBD, and possibly other cannabinoids.
Summary: Cannabis in the Treatment of Medical Conditions
The recent NASEM review discusses the evidence for the efficacy of cannabis and cannabis-derived products for a variety of conditions and concludes that there is at least limited evidence that cannabis or cannabinoids may be useful for:1
Treatment of chemotherapy-induced nausea and vomiting
Spasticity due to multiple sclerosis
Improving short-term sleep outcomes due to a variety of conditions
Increasing appetite and decreasing weight loss associated with HIV/AIDS
Improving symptoms of Tourette syndrome
Some symptoms of PTSD
In addition, there is increasing evidence for efficacy of CBD in the treatment of some forms of epilepsy,10–12 though data remains quite limited.
Cannabis has also been proposed as a treatment for many other medical conditions, and some states have been quite broad in their listing of approved uses.13 The NASEM review was unable to find sufficient evidence to support or refute treatment efficacy for most of these conditions, including:
Cancers and cancer-associated anorexia
Irritable bowel syndrome
Amyotrophic lateral sclerosis
Mental health outcomes in individuals with schizophrenia
There is limited evidence against efficacy for the treatment of dementia, glaucoma, or depression.1
Most of the conditions above are unlikely to be occupationally related; those that may be, under some circumstances, are discussed in more detail below.
Efficacy of Cannabis as Treatment for Occupationally Related Conditions
Five recent comprehensive reviews have all concluded that there is evidence for the efficacy of cannabis in the treatment of chronic pain, a conclusion consistent with centuries of anecdotal evidence.1,5,14–16 The most recent systematic review15 notes that the evidence is strongest for treatment of neuropathic pain, and the NASEM review notes that the THC component of cannabis seems most likely responsible for at least some of the analgesic effects.1,17 While this is clearly relevant to the many injured workers with neuropathic pain from spine injuries, many questions regarding dose, long-term efficacy, and relative safety remain to be answered. As others have noted, the potential effects on reaction time and cognition are a particular issue for safe return to work.18,19
With respect to the use of cannabis for chronic pain due to occupational injury, it is important to note the following:
No medical guidelines currently consider any cannabinoid to be a first-line treatment for chronic pain, including neuropathic pain
There are potential problems with the overuse of cannabis
Some data suggest that the use of cannabis as an analgesic in selected individuals with chronic pain may be medically appropriate
Psychotropic and other side effects must be considered in planning for return to work
Anxiety and Depression
While not traditionally considered workplace injuries, both anxiety and depression are common comorbidities that accompany many severe and/or chronic workplace conditions. Per the NASEM review, there is “limited” evidence to suggest a benefit from cannabis in the management of anxiety symptoms.1 There is no scientific evidence at present to suggest any benefit in the management of depressive symptoms, and some data that suggest a lack of effectiveness, though there are many favorable patient anecdotes.1,5,20 As all reviewers note, it is difficult to analyze placebo effects and psychosocial confounders in the studies that have been done to date.1,5,16,20
Post-Traumatic Stress Disorder (PTSD)
While cannabis is approved for use for PTSD in many jurisdictions where medical marijuana is legal, the most recent systematic review of available studies concludes that evidence of its benefit is insufficient. There is anecdotal evidence of benefit but also evidence of harms.21 The same review also notes that there are several studies in progress that may help to provide additional data on the use of cannabis for this indication.
Traumatic Brain Injury (TBI)
There is one observational study that links the use of marijuana to better outcomes after TBI.22 The mechanism by which this might occur is unknown, and any neuroprotective benefits are speculative at present. It is likewise unknown if there are any treatment benefits from cannabinoids during recovery from TBI.
Spasticity Following Spinal Cord Injury (SCI)
Two recent reviews1,5 found insufficient evidence of benefit for cannabinoids in the treatment of spasticity following SCI. Trials were very small. There is some evidence of benefit in the treatment of spasticity due to multiple sclerosis,10 suggesting that further research may be indicated.
Cannabis and Opioids
Several recent reports (discussed below) propose that cannabinoids may be helpful in reducing the use of opioids, which would clearly represent a benefit to injured workers with opioid dependence or abuse. There are two distinct hypotheses, both with some supporting evidence, regarding how this might occur: 1) an opioid-sparing effect where cannabis is used to treat chronic pain, thereby eliminating or reducing the need for an individual patient to use opioids; and 2) the use of cannabinoids to treat opioid addiction.
As discussed above, there is evidence for efficacy of cannabis in the treatment of neuropathic pain, most likely via the effects of THC on receptors in the ECS. No individual studies have specifically demonstrated a reduction in opioid dose used by individual patients when any cannabis preparations are added to their treatment.
However, there is highly suggestive evidence from several ecological studies. State death certificate data from 1999–2010 from the Centers for Disease Control and Prevention shows a significantly slower rise in opioid-related deaths in states with medical marijuana laws.23 Using data from two national databases, the National Bureau of Economic Research reported in 2015 that states with medical marijuana dispensaries had relatively fewer treatment admissions for opioid addiction and fewer opioid deaths than states without such laws.24
In two separate retrospective analyses, Bradford and colleagues evaluated the amount of opioids prescribed to Medicare25 and Medicaid26 patients in states where medical and/or recreational use of marijuana has been legalized. Both studies consistently showed lower prescribed quantities of opioids in states where cannabis could be legally used. There are many confounders, and it is impossible to say whether an opioid-sparing effect, if it truly exists, would carry over to WC claims. In a more limited study, Kim et al.,27 found that the probability of fatally injured drivers aged 21–40 testing positive for opioids was reduced in states with laws allowing the use of cannabis for medical conditions. As these are all population-level studies, the risks and benefits to individual patients cannot be evaluated, but taken together, they suggest a need for further investigation.
Data suggesting that cannabinoids might be useful in the treatment of opioid addiction in humans is quite limited, but there are a number of biologically plausible mechanisms and some animal studies.3 Cannabidiol has been shown to act on the central nervous system to reduce opioid craving and the probability of relapse after withdrawal.4,28,29 There are many interactions between the ECS and opioid receptors within the central nervous system;6 given the emergent nature of opioid abuse in the United States, this is an area where further research is urgently needed.
Marijuana in the Workplace
With medical marijuana now legal in 29 states, employers are increasingly likely to encounter situations where current and prospective employees are using some form of cannabis for medical conditions. Use for workplace injuries is less common, but also increasing. Colorado's Department of Labor and Employment has included a discussion on cannabis as a treatment for chronic pain in the latest update to its Medical Treatment Guidelines, and at least one payer has established review policies to evaluate the medical appropriateness of cannabis in the management of workplace injuries.30
Employers remain concerned about the potential adverse effects of cannabis on workplace safety given the multiple studies that have linked cannabis to impairment of reaction times, cognitive performance, and increased rates of motor vehicle accidents.31,32 To date, the right of employers to maintain drug-free workplaces has been supported by the courts, even in states where marijuana has been legalized (see NCCI's Marijuana Conversation series for a complete review). This is an area that is rapidly changing, and readers are advised to monitor their individual jurisdiction for updates.
Of particular concern for workplaces are data indicating prolonged effects on cognitive performance for days after acute intoxications symptoms have passed.1,18There are some data indicating a favorable effect of drug-free workplace policies on occupational injuries, but these studies include alcohol and other substance abuse.33 It is important to note, however, that the NASEM review found “insufficient evidence to support or refute a statistical association between cannabis use … and occupational accidents or injuries”.1 Research has been difficult in this area for a variety of reasons; one important challenge is that blood concentrations of THC (which are difficult to measure) can indicate acute intoxication, but do not correlate well with ongoing impairment.34,35 It is also worth noting that legalization of recreational marijuana in Washington and Colorado has not resulted in measurable increases in motor vehicle crash fatality rates.36
Summary and Conclusions
Perhaps the most important finding from the comprehensive review by NASEM is that the scientific evidence base for both benefits and harms from cannabis and cannabinoids is either nonexistent or inadequate to answer many important treatment and public policy questions.1 This will improve over the next several years. Employers (and workers compensation insurers) will need to keep abreast of changes in treatment recommendations and regulations, given:
The evidence to date of some benefits
The fact that medical marijuana is legal in 29 states
The public policy data indicating substantial popular support for permissive medical use as well as legalization of recreational use
With this in mind, employers may wish to consider the following with respect to the medical uses of cannabis as they may impact the workplace and the management of workplace injuries:
Many medications, including nonprescription cold remedies, can be sedating or otherwise impair physical or cognitive performance. Workplace policies to promote safety should include recognition of these issues as part of any discussion on impairment from the use of prescription or recreational drugs (including alcohol and cannabis).
There remains a scientific rationale for prohibiting the use of cannabis at any time by employees (or contractors) under drug-free workplace policies. This is discussed in detail by Goldsmith et al.,18 who also provide guidance for employers who wish to accommodate, under certain circumstances, the use of medical marijuana by employees. Again, NCCI's Marijuana Conversation series provides a recent synopsis of the legal and regulatory policies in this rapidly changing area.
Cannabis and cannabinoids may have a role in the treatment of some workplace conditions in states where their use is legal. However, for all situations in which cannabis has treatment benefits, it is not a recommended first-line option for any. Treatment regimens including cannabis for neuropathic pain, for example, should be subjected to the same evidence-based review as any other proposed treatments, and ongoing efficacy evaluated. Treatment regimens that rely on cannabis as an initial treatment for any workplace condition are a red flag.
The medical use of cannabis and cannabinoids presents both potential benefits as well as harms for injured workers. These need to be evaluated for each individual patient in the context of other medical and psychosocial issues, along with the possible impacts on safe return to work. Employer policies will need to evolve with changes in science, law, and regulation. With millions of Americans using cannabis daily and more studies in progress, we should not have to wait long for new data.
ABOUT THE ARTICLE
This piece, written by David Deitz (MD, PhD) of David Deitz & Associates, was featured in NCCI's Workers' Compensation Insights.
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