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Prescription Opioid Distribution After the Legalization of Recreational Marijuana in Colorado, 2007-2017

Importance Opioid related overdoses and overprescribing continue to be an ongoing issue within the United States. Further consideration of nonopioid alternatives as a substitute to treat chronic noncancer pain and in the treatment of opioid use disorders (OUD) is warranted. Objective To examine the association between the legalization of Colorado’s recreational marijuana and prescription opioid distribution trends. Two states that have not legalized recreational marijuana were selected for comparison. Methods The United States Drug Enforcement Administration’s Automation of Report and Consolidated Orders System (ARCOS) was used to examine nine pain medications: oxycodone, fentanyl, morphine, hydrocodone, hydromorphone, oxymorphone, tapentadol, codeine, meperidine and two OUD medications: methadone and buprenorphine from 2007-2017 in Colorado, Utah, and Maryland. The drug weights were extracted, examined, and graphed. Medications were converted to their oral morphine milligram equivalents (MME) using standard conversion factors. Results Colorado reached a peak of pain MME weight in 2012 and had an −11.66% reduction from 2007 to 2017. During the same interval, Utah had a +9.64% increase in pain medication distribution and Maryland, a −6.02% reduction. As for medications used for OUD, Colorado, Utah, and Maryland had +19.42% increase, −31.45% reduction, and +66.56% increase, respectively. Analysis of the interval pre (2007-2009) versus post (2013-2017) marijuana legalization was completed. Statistically significant changes were observed for Colorado (P=0.033) and Maryland (P=0.007), but not Utah (P=0.659) for pain medications. Analysis of the OUD medications identified significant changes for Colorado (P=0.0003) and Maryland (P=0.0001), but not Utah (P=0.0935). Over the decade, Colorado’s opioid distribution was predominantly (72.49%) for pain with one-quarter (27.51%) for an OUD. Utah distributed 61.00% for pain and 39.00% for OUD. However, Maryland was one-third (37.89%) for pain but over-three-fifths (62.11%) for an OUD. Conclusion There has been a significant decrease in the prescription opioid distribution after the legalization of marijuana in Colorado. This finding was particularly notable for opioids indicated predominantly for analgesia such as hydrocodone, morphine and fentanyl. Colorado had a larger decrease in opioid distribution after 2012 than Utah or Maryland. Therefore, marijuana could be considered as an alternative treatment for chronic pain and reducing use of opioids. Also, when combined with other novel research, it may also reduce the overdose death rate. Additional research with more comparison states is ongoing.


Introduction
An epidemic is plaguing the United States regarding the misuse of prescription opioids over the last fifteen years. The opioid epidemic stems from the early 1990s when the medical community started to recognize pain as a fifth vital sign. 1 3 Although the intent of these guidelines was to improve pain care, there was no significant increase in the quality of pain management. 1 This has had long-lasting and devasting effects that have rippled throughout the entire country as more people became dependent and overdosed on opioids. While there have been downward trends in prescribing of opioids after 2012, patients are still dying. Ninety Americans die each day due to overdoses 4 . There has been an increase of 320% between 2000 and 2015 in opioid-related mortality and it is still three-times higher than in 1999. 5 Physicians and other healthcare providers have the responsibility to treat their patient's non-cancer pain, while also considering nonopioid alternatives.
Since California first legalized medical marijuana in 1996, 33 states and the District of Columbia have passed laws broadly legalizing marijuana, either medically or recreationally, as of June 2019. Washington D.C. and ten other states have expanded to recreational marijuana use. 6 With the endorsement of the states, more objective, clinical evidence is surfacing that marijuana can be used to manage chronic pain 7 , reduce overdose mortality rates 8,9 , treat opioid withdrawal 10 , and decrease opioid prescribing rates. 5,11,12 Marijuana has a much lower risk of addiction and virtually no overdose danger, which is in stark contrast to opioids. 13,14,15,16 In Jan. 2017, the National Academies of Sciences, Engineering and Medicine released a peer-reviewed, comprehensive review showing, "conclusive evidence" that marijuana can be used safely and effectively to treat chronic pain. 17 According to a Pew research center poll conducted in 2018, 62% of Americans are supportive of legalized marijuana for medical purposes, which has doubled in over a decade from 31% in 2000. 18 The popularity of marijuana is quickly rising in the 50 and older age group. 19 This age group may be most likely to experience chronic pain related conditions and are open to the analgesic effects of marijuana. 7 Overall, marijuana is gaining strong support politically. This rising acceptance also helps dispels myth of marijuana being a gateway drug, decreasing the stigma of this alternative treatment. All eleven medications were converted to their oral morphine milligram equivalents (MME). This enabled the agents to be compared despite their differences in relative potency. Oral MME conversions were completed using the following multipliers:  Utah had a +9.64% increase and Maryland, a -6.02% reduction in pain medication distribution. The two OUD medications were also looked at. Colorado, Utah, and

Discussion
There are several important findings of this novel pharmacoepidemiology and public policy research that supports recreational marijuana as a substitute for prescribing opioids. In research on overprescribing of opioids in states with medical and recreational marijuana laws, showed a 5.88% reduction in states with medical marijuana laws and a 6.38% decrease in states with adult use laws; including a decrease in Schedule II drugs of 7.79% and Schedule III to V by 10.40%. 12 Their study found that Maryland did not have significant statistically discernable changes in opioid prescribing and Colorado had significantly lower prescribing rates. 12 While in our research, P a g e | 8 Maryland did have a statistically different in the pre/post marijuana years, and Colorado still experienced a larger decrease in opioid distribution than Maryland or Utah.
Maryland actually had larger weights in every year, in every drug, when compared to Colorado and Utah. While Maryland did legalize medical marijuana, the law went into effect in June of 2014 with no real operations until late 2016. This rollout could have been less impactful due to bureaucratic and legal issues within the state leading to no significant changes in opioid prescribing. 12 Maryland also had extremely high amounts of drugs used for OUD compared to both Utah and Colorado. There seems to be a higher rate of distribution of these medications, over the medications being used to treat pain.
Utah, while demographically similar to Colorado, had lower rates in every year and every drug than Colorado. Utah follows Colorado's similar treads in Figure 1, 2, and 5.
Utah's drug distribution significantly differs from Colorado as represented in Marijuana has also not been found to help in every respect in regard to opioid use.
Olfson and colleagues found an association between illicit marijuana use with an increased incidence of nonmedical prescription opioid use (odds ratio = 5.8; 95% CI P a g e | 9 4.23-7.90) using the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). 23 However, the NESARC findings may not apply to our study which evaluated an association between legalized marijuana and prescription opioids rather than between illicit marijuana use and nonmedical opioid use. Regardless, further research is needed to establish the relationship between marijuana and opioid use.
Marijuana may also be considered helpful in lowering the opioid overdose rate. In 2014, a study found a 24.8% reduction in deaths among states that had medical cannabis laws (MCLs) 8 and fewer daily doses filled by patients (Medicare Part D population). 5 Another report found a 6.5% reduction in overdose deaths after the legalization of recreational marijuana in Colorado. 9 This represents an important reversal in the upward trend that Colorado was experiencing in opioid-related deaths. In combination of less opioid being distribution to the state, and concrete evidence that there has been a decrease in opioid-related deaths, Colorado's legalized recreational marijuana shows an encouraging tread to treat people's pain and keep them safe. Although, a more recent publication may have found a reversal in Bachhuber's data over time. This study cites an association between state medical cannabis laws and opioid overdose reversed from -21% to +23% during the full timeframe of 1999-2017. 24 Opioid prescribing practices were already beginning to decrease before any additional guidelines were released. When the CDC released the Guideline for Prescribing Opioids for Chronic Pain in March 2016, there was a substantial decrease in opioid prescribing practices. 25 Research from this study confirms this finding. Colorado and Maryland experienced an overall decrease in opioid distribution, but Colorado's decrease was larger. While the nation as a whole, was experiencing a decrease in