Research
by Hazelden Betty Ford
Clearing Away the
Confusion
With more than 70,200
deaths occurring in 2017, the public health crisis of fatal drug overdoses is
headline news and shows no signs of abating (National Institute on Drug Abuse,
2019). Beneath this alarming statistic are also tens of millions of individuals
and their loved ones who live every day with addiction.
Expanding access to naloxone to help prevent opioid overdose deaths in the
short term is critical, but we cannot let short-term solutions overshadow or
replace the need to provide high-quality treatment services to individuals with
all forms of addiction to stem the tide of future overdose cases. Individuals
with opioid use disorder usually use other substances: cocaine and
benzodiazepines figure prominently in overdose deaths, for example. Another
fast-growing concern is methamphetamine use. Of course, alcohol remains
ever-present as well and is part of the picture for the vast majority of people
who suffer from addiction. As previously discussed in the Emerging Drug
Trends Report “Widening the Lens on the Opioid Crisis,” a continuum of
approaches to identify high-risk individuals and intervene appropriately is
needed to make progress.
Recently, some advocates
have claimed that marijuana might be part of the solution to the opioid crisis.
Within the past year, states such as New York and Illinois have passed
legislation making medical marijuana more accessible to individuals with opioid
prescriptions (Illinois General Assembly, 2018; New York State Department of
Health, 2018). However, clinical evidence produced from rigorous research
methodology that marijuana is an effective treatment for pain or opioid use
disorder does not exist; therefore, marijuana should not be promoted as a safe
alternative (Humphreys & Saitz, 2019). The notion that increased access to
marijuana will help the country shed its current addiction crisis does not have
scientific merit, and distracts from planning and implementing a longer-term
and broader set of evidence-based strategies. A recent study by Chen et al.
(2019) reaffirmed the urgency of implementing a multifaceted approach involving
prevention, treatment and harm reduction to address the opioid overdose crisis.
The annual number of overdose deaths is expected to increase by nearly 150%
between 2015 and 2025.
This report clarifies the
current state of scientific understanding on the relationship between marijuana
and opioid use. While more research is needed to fully comprehend the complex
issues discussed, and to develop new interventions and treatments for
addiction, decades of existing research findings should serve as the foundation
of policy decisions.
State-level correlations between marijuana
policies and opioid medication prescribing
A recent study examined
data for Medicare Part D recipients living in all 50 states. The authors
investigated whether prescribing patterns for opioids were different based on
the state’s marijuana policies. Bradford and colleagues (2018) specifically measured
the total number of daily doses for any opioid medication prescribed to a
person from 2010 through 2015. States with any type of medical marijuana law
had an estimated 2.1 million fewer daily doses of opioid prescriptions per year
than states without a medical marijuana law (the average among all states was
23.1 million daily doses). States with medical marijuana dispensaries and those
that allow home cultivation were estimated to have 14.4% and 6.9% fewer,
respectively, daily doses of opioids prescribed. Although it is tempting to
speculate that the lower prescribing was due to marijuana policies, the study
results cannot conclude that differences in marijuana policies were the reason
for the different opioid prescribing rates. There could have been several other
reasons for the state-level differences in opioid prescribing rates besides the
marijuana laws that were in place at the time the data were examined.
Wen and Hockenberry (2018)
examined opioid prescribing patterns among Medicaid recipients living in the
eight states that implemented medical marijuana laws between 2011 and 2016. In
four of the eight states, statistically significant reductions in opioid
prescribing rates were found during this period. Of the four states that
implemented recreational marijuana laws, three also experienced significant
reductions in opioid prescribing rates. Just as in the study described above,
however, this study cannot determine that the decrease in opioid prescribing
was due to differences in the marijuana laws. It must also be noted that the
results from these studies (Bradford et al., 2018; Wen & Hockenberry, 2018)
were observed among specific groups of individuals: Medicare and Medicaid
recipients. The researchers cannot say if state-level reductions in opioid prescribing
have been or will be observed among the general public in states with marijuana
laws. Caution is warranted when considering whether to use these findings when
making policy decisions about access to marijuana that will affect the general
public.
State-level correlations between marijuana
policies and opioid overdoses
Bachhuber and colleagues
(2014) compared opioid overdose death rates, rather than prescribing patterns,
in states with and without marijuana legalization. Between 1999 and 2010, the opioid-related
death rate rose in all states, but states with a medical marijuana law had
higher rates of opioid-related mortality than states without such a law.
However, when the influence of medical marijuana policies was isolated from the
influence of the state and year in which the data were collected, the
researchers found that states with a medical marijuana law had an estimated
24.8% fewer opioid overdoses per year on average compared with states that had
no medical marijuana law. A more recent study (Shover, Davis, Gordon, &
Humphreys, in press) refutes the findings of Bachhuber (2014). Using
essentially the same approach but extending the time of analysis through 2017,
the newer study found that the direction of the association reversed—states
enacting a medical marijuana law experienced a 22.7% increase in opioid
overdoses. When Shover and colleagues (in press) applied additional statistical
controls that were not part of the earlier study, they found no association
between the two variables. This more recent study seriously calls into question
the claim that medical marijuana laws have any beneficial impact on opioid
overdose death rates and suggests instead that such laws could potentially have
a negative impact.
Beware of the "ecological fallacy"
The most important
consideration when evaluating the studies cited earlier is that they were all
conducted at the state level. Ecological studies like these, which utilize
measurements of health that have been averaged across a population, are often
valuable first steps in identifying a possible relationship between an exposure
and some outcome—in this case, marijuana policies and opioid prescribing rates
or overdose deaths. However, studies conducted at the state level cannot and
should not be used to draw conclusions about individual behaviors; such
conclusions are known in public health science as “ecological fallacies.”
For example, if you
compared volunteering across multiple schools, you would discover that some
schools have a higher proportion than others of students who volunteer in their
community. Yet the reason for volunteering might not have anything to do with
school policies or school environments. Rather, the choice to volunteer might
stem from many other influences, such as home life, work schedules or personal
interests. Similarly, it would be an ecological fallacy to assume that because
opioid prescribing or overdose deaths decreased among states with legal
marijuana policies, individuals in those states reduced their opioid use
because of increased availability of marijuana.
Studies at the individual level: Marijuana
use increases risk for subsequent opioid use and dependence
The other side to the
story regarding marijuana and opioids is how the two substances are related to
each other at the individual level. The vast majority of individuals who misuse
prescription pain medication and/or heroin initiated their drug use early in
their teens, usually beginning with alcohol and marijuana. Biologically, early
initiation of drug use primes the brain for enhanced responses to other drugs
later in life. Most recently, Caputi and Humphreys (2018) show the heightened
risk of prescription opioid misuse among medical marijuana users. Using
nationally representative data, they found that medical marijuana users have
twice the risk for prescription opioid misuse compared with non-users of
medical marijuana. Although this study used data collected at one point in
time, the findings raise doubts that medical marijuana can be protective
against the development of opioid use disorder.
Similarly, Olfson and
colleagues (2018) analyzed a different nationally representative dataset from
two time periods—2001 to 2002 and 2004 to 2005. Individuals who used marijuana
from 2001 to 2002 had nearly three times the odds of starting to use opioids
nonmedically three years later compared with their counterparts who did not use
marijuana (after adjusting for demographic factors and other substance use
history). Increased risk for beginning to use opioids nonmedically was observed
among a subset of adults with moderate to severe pain as well.
Opioid use disorder is the
clinical diagnosis used to identify whether or not use of pain relief
medication or heroin causes an individual significant impairment, including
health problems, physical withdrawal, persistent or increasing use, and failure
to satisfy responsibilities at work, school or home (Substance Abuse and Mental
Health Services Administration, 2017). In Olfson et al. (2018), marijuana use
was associated with two times the odds of developing opioid use disorder within
three years, compared with those who did not use marijuana. Figure 1 shows that
the proportion of individuals who developed opioid use disorder by 2004 to 2005
increased as 2001 to 2002 frequency of marijuana use increased.
Another study utilizing
several years of data also observed that marijuana use increases risk for
subsequent nonmedical use of opioids. Fiellin et al. (2013) examined the
association between marijuana use and subsequent misuse of prescription opioids
among young adults 18 to 25 years old using nationally representative data from
2006 to 2008. More than one-third of young adults who misused opioids had
already initiated marijuana use in their lifetime prior to prescription opioid
misuse. Young adults who had previously used marijuana had 2.5 times the odds
of starting to misuse prescription opioids compared with those who had not used
marijuana. The risk posed by previous marijuana use was about twice the risk
from using other common substances, such as alcohol and cigarettes (1.2 and 1.3
times the odds, respectively). A recent study by Butelman et al. (2018)
underscored young adulthood as a critical developmental period for intervention
as individuals with opioid dependence started their heaviest use of marijuana
at 19 years old on average.
Substituting one drug for another has
implications
Some authors of ecological
studies examining the relationship between marijuana use and opioid prescribing
rates have argued that more liberalized marijuana laws might help combat the
current opioid epidemic by allowing individuals to manage their pain with marijuana
rather than prescription opioids. However, these studies do not determine if
successful pain treatment replacement is actually occurring. To our knowledge,
the majority of studies of this nature conducted so far have utilized online
questionnaires at one time point to ask individuals who already used
marijuana—medically and nonmedically—about their opioid use and substitution
practice (Boehnke, Litinas, & Clauw, 2016; Corroon, Mischley, & Sexton,
2017; Reiman, Welty, & Solomon, 2017; Sexton et al. 2016). These studies
have shown that marijuana is being used to manage pain regardless of
legalization laws; unfortunately, weak methodology prevents more substantive
conclusions about the efficacy of replacing prescription opioid use with
marijuana use. Longitudinal studies with longer-term data collection that could
provide a clearer picture of the benefits and harms of pain management
substitution have not yet been conducted.
Perhaps the
methodologically strongest study that attempts to determine whether or not
marijuana use for pain treatment improves patient outcomes is “The Pain and
Opioids in Treatment” study (Campbell et al., 2018). Campbell et al. recruited
1,514 participants from pharmacies across Australia with non-cancer pain who
were prescribed opioids between 2012 and 2014, and then followed up with them
four years later. By the end of the study, 24% of the participants had also
used marijuana for pain management and 60% had interest in using marijuana for
pain (compared with 33% who had interest at the beginning of the study).
Participants who used marijuana for pain had greater pain severity, reported
that pain interfered with life more and had greater generalized anxiety
disorder compared with their peers who did not use marijuana. Importantly, the
research team did not find any relationship between marijuana use for pain and
actual pain severity as time progressed. The study concluded that marijuana use
did not reduce an individual’s prescriptions for opioids or increase opioid
discontinuation. While this study was conducted in Australia, and therefore
cannot be directly generalized to the United States due to differences in
marijuana use policies, this study offers the strongest evidence to date that
at the individual level, marijuana use for pain does not decrease opioid use or
improve pain outcomes.
As described earlier,
several studies assessing risk for opioid use conducted at the individual level
have found that those who use marijuana are more likely to start misusing
prescription opioids and developing opioid use disorder compared with those who
do not use marijuana (Fiellin et al., 2013; Olfson et al., 2018). Individuals
with chronic pain who use marijuana are also not immune from the increased risk
for starting to misuse prescription opioids, a finding that further calls into
question the claim that increased medical marijuana use would reduce opioid
misuse and overdose (Olfson et al., 2018).
Conclusions
· The claim that increased
access to marijuana through legalization policies could help combat the opioid
crisis must be viewed with skepticism. These ideas were never directly tested
but were derived from ecological studies comparing prescribing rates and overdose
rates at a state level. From ecological studies, there is no way to attribute
prescribing patterns and overdoses to the laws and not to other factors. The
most recent replication of these earlier ecological studies utilizing data that
extended through 2017 did not find any evidence that medical marijuana laws
were associated with a decrease in opioid overdose mortality. Some analyses
from the replication study actually suggested that comprehensive medical
marijuana laws were associated with increases in overdose deaths.
· Studies using strong
scientific methods show that marijuana use increases the risk for starting to
misuse prescription opioids, rather than lowering the risk. Moreover,
individuals with addiction to prescription opioids often have a history of
using other drugs, including marijuana, and therefore need comprehensive
addiction intervention and treatment.
· Marijuana use to manage
pain does not appear to be related to decreases in pain, and evidence that
marijuana is an effective treatment for opioid use disorder is even weaker
(Humphreys & Saitz, 2019).
· Experts predict that the
opioid overdose crisis will worsen in the coming decade. As a result, there is
a need for novel, multipronged interventions in order to change the epidemic’s
trajectory.
· When dealing with the
addiction and overdose crisis facing the U.S., policymakers should make
decisions that have a strong scientific justification.
Making marijuana more
available might appear to be a solution to the current drug crisis in our
nation. However, a more critical look at the research evidence suggests just
the opposite. Decades of research findings have shown that marijuana use puts
an individual at heightened risk for misuse of prescription opioids, heroin and
other drugs.
Insights and Perspectives
Marvin D. Seppala, MD, Chief Medical
Officer, Hazelden Betty Ford Foundation
"We need to study
cannabis and its derivatives (i.e., CBD) to determine which health conditions
could benefit and how such products would work. As important, we need to
determine the limitations—what cannabis and its derivatives do not affect or
help. We’ve jumped the gun and allowed relatively indiscriminate use by a large
portion of the population without adequate scientific study."
George Dawson, MD, Psychiatrist, Hazelden
Betty Ford Foundation
"The commercially
driven political aspects of medical cannabis are undeniable. The legalization
of cannabis for recreational purposes had no traction with American politicians
or voters until it was promoted as a miracle drug. Due to that widespread
promotion, medical cannabis is now legal in 33 states, and recreational
cannabis is legal in 10. The legalization arguments have also suggested that
the U.S. was behind other countries of the world despite the fact only two
countries—Canada and Uruguay—have completely legalized cannabis for medical and
recreational sale and purchase. In fact, only 22 of 195 countries have
legalized medical cannabis, with widely varying restrictions on its use. The
Netherlands is often cited as an example of recreational cannabis legalization,
but most Americans don’t realize that cannabis is illegal for recreational use
in most places there, with use and sale allowed only in specially licensed
coffee shops. The promotion of cannabis as a solution to the opioid overuse and
chronic pain problems can be seen as an extension of the commercially driven
political arguments for legalization that outpace any science to back them up.
"At the scientific level, areas of research in the epigenetics of cannabis
smoke and how that may predispose people to substance use problems has been
left out of the debate. The neurobiological mechanisms of how cannabis can
modify the underlying brain substrate at various developmental stages is
currently an area of active research. Many such studies focus on the issue of
whether cannabis-induced epigenetic changes predispose to the development of
opioid use disorders."
Kate Gliske, PhD, Research Scientist, Butler
Center for Research, Hazelden Betty Ford Foundation
"These studies, and
others like them, highlight an increasing trend across the U.S. and worldwide
to minimize the harm associated with marijuana use. This is particularly
problematic given the substantial evidence of marijuana’s harmful effects on
mental health disorders, pregnancy outcomes and brain functioning (see
Memedovich et al., 2018 for review) among a significant minority of the
population. Very little research currently exists about the relationship
between marijuana legalization and its effects on the opioid crisis, and what
is available presents a conflicted picture of its effectiveness. We are still
years away from understanding the full effect of current marijuana legalization
policies on opioid use, and it would be rash to base further policy decisions
on so little data."
Stephen Delisi, MD, Medical Director,
Professional Education Solutions, Hazelden Betty Ford Foundation
"All aspects of the
debate around medical cannabis for chronic pain and opioid use disorder point
to the dire need for a deliberate, thoughtful and science-driven approach.
Medical providers, payers, patients, governmental agencies and the general
public should demand that science and research guide decision-making and
policies around this issue."
Nick Motu, Vice President and Chief External
Affairs Officer, Hazelden Betty Ford Foundation
"The dialogue around
cannabis legalization has been muddied by the federal government’s neglect of
this issue and the desperate desire for solutions to the nation’s opioid
crisis. It is time for Congress and the Administration to course-correct in a
responsible, necessary and politically viable way—by having the science drive
the policy to protect the health and well-being of Americans."
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