Introduction

Since the passing of the Controlled Substances Act, marijuana has been traditionally disregarded as an alternative to conventional analgesic treatment, but recent studies may support an alternative view. The US opioid epidemic is characterized by a steep increase in opioid prescription rates followed by a rise in opioid-related deaths in the early 1990s. Opioid prescriptions quadrupled from 1998 to 2008, and resulted in alarming overdose rates.1 Provisional data indicate 87 000 drug overdoses from October 2019 to September 2020, which is a 29% increase over the prior year.2 Nationwide opioid prescription rates steadily increased from 2006 to 2012, but started decreasing from 2013 to 2018,3 showing there has been an effort to alleviate the crisis.

Removing pain as the fifth vital sign, implementing drug disposal programs, and returning unused medications are several measures that have been enacted to reduce the calamitous effects of the opioid epidemic. However, these measures have had little to no effect on opioid distribution and control of opioid-related deaths. In fact, there were approximately 65 000 deaths in 2016, an increase of 21% from the year prior.1 California reported 6 opioid-related deaths per 100 000 people in 2018.4 Comparably, Texas reported 5 opioid-related deaths per 100 000 people in 2018.5 The opioid prescription rate was 35.1 prescriptions per 100 persons in California6 and 47.2 in Texas5 in 2018.

The effects of medical cannabis remain underresearched, particularly the products available at dispensaries. Therefore, the relationship between cannabis use and trends in opioid distribution and narcotic overdoses has not been fully elucidated. However, reports on cannabis sales show a significant upward trend as distribution and overdose rates decrease.7 California legalized medicinal cannabis in 1996 and recreational cannabis in 2016. Recreational dispensaries opened to individuals who were at least 21 years of age in January 2018. As data demonstrating cannabis’s success as an alternative or substitute for opioids has emerged,8–14 resulting opioid trends can be analyzed. This study compares opioid distribution rates in California, where medical cannabis and recreational cannabis use was legalized, by zip code and per capita, to those in Texas, which has not legalized recreational or medical cannabis. We hypothesized that there will be a greater decrease in opioid distribution in California following the change in cannabis legislation than in Texas.

Methods

Procedure

The US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) database is used to track controlled substances from manufacture through distribution channels to point of sale at the level of hospitals, pharmacies, practitioners, and teaching institutions. The data are organized in several reports summarizing drug distribution by first three digits of zip code per 100 000 population gathered and includes summaries of purchases. Report 1, which reports drug distribution by zip code, and Report 3, which reports quarterly drug distribution by state per 100 000 population by gram, were selected for analysis.15 Fentanyl, oxycodone, morphine, hydrocodone, and codeine were chosen based on their familiarity in the general population and inclusion in prior research.16–19 ARCOS data have been previously validated by comparing results to a state prescription drug monitoring program, which showed a satisfactory (r = 0.985) agreement.20

The Centers for Disease Control’s WONDER database was constructed to facilitate access to public health information for state and local health departments and the academic public health community.21,22 The mortality data was extracted from WONDER as “Drug-induced causes” set as the underlying cause of death with the Multiple Cause of Death ICD-10 codes T40.1 (“Heroin”) and T40.2 (“Other opioids”). ICD-10 code T40.1 is limited to heroin-induced deaths. ICD-10 code T40.2 excludes non-opioid narcotics, such as cocaine, opium, and LSD, and may include but is not limited to codeine, fentanyl, hydrocodone, hydromorphone, morphine, oxycodone, and tramadol. Total overdose rate includes deaths induced by heroin and other opioids.

Data analysis

The weights of five common opioids (codeine, fentanyl, hydrocodone, morphine, and oxycodone) were converted to oral morphine milligram equivalents (MME).22 Grubbs’ test was used to detect outliers on GraphPad Prism. Oxycodone distribution per zip code was unavailable in ARCOS for the year 2018. To account for this, oxycodone distribution in the last two quarters of 2017 was averaged with oxycodone distribution in the first two quarters of 2019 to represent oxycodone distribution in 2018. Heat maps and graphs were constructed using Microsoft Excel and GraphPad Prism 8. Two-tailed paired equal variance t-tests were performed using GraphPad Prism 8 software on zip code distribution data to determine statistical differences with P < 0.05 considered significant.

Results

Opioid distribution by zip code

In both 2014 and 2018, California showed much more widespread and substantial cumulative opioid distribution than Texas (Figure 1). In 2014, portions of California surrounding the Bay Area and portions of Southern California had cumulative opioid distributions as high as 1 388 000 MME and 900 000 MME, respectively. In contrast, the highest distribution in Texas was 790 000 MME in the surrounding Dallas area. Most of Texas had a distribution of 100 000 or less while most zip codes in California ranged from 150 000 to 650 000 (Figure 1A). However, in 2018, the largest distributions in California dropped to 720 000 MME in the Bay Area and 525 000 MME in Southern California, decreases of 50% and 40%, respectively (Figure 1B). The surrounding Dallas area saw a decrease of 25%, while most of Texas did not show a comparable decrease (Figure 1C). Both California (P < 0.0001) and Texas (P < 0.0001) showed statistically significant decreases in opioid distribution, but California had a more than two-fold difference per zip code (162 476 versus 62 808 MME) over this five-year span. This represents a − 43.7% decrease in California relative to only − 27.3% in Texas (Figure 2). There was an increase of 6000 MME in a 16 zip code area of Southern California near Glendale and Burbank. In this area, fentanyl, morphine, and oxycodone saw 1.5-, 2.4-, and 1.8-fold increases, respectively, while codeine and hydrocodone did not undergo appreciable changes (Figure 1C).

Figure 1.Total opioid distribution in California and Texas in MME by zip code.

Data reported to ARCOS15 in 2014 (1A) and 2018 (1B), and the percent change from 2014 to 2018 (1C).

Figure 2.Opioid distribution (±SEM) per zip code as reported to ARCOS15 in California and Texas 2014 and 2018.

*P < .05 vs 2014.

Opioid distribution per capita

Opioid distribution per capita decreased in both California and Texas from 2014 to 2018 (− 38.9% and − 26.4%, respectively). The change in California was more linear for all opioids, while Texas experienced more variable change (Figure 3). Distribution of all five opioids in California decreased to a greater extent than their Texas counterparts (hydrocodone, − 65.4%; fentanyl, − 50.3%; morphine, − 42.7%; oxycodone, − 32.4%; and codeine, − 19.1%) (Figure 3). Individual opioid distribution changes in Texas showed much more variability with hydrocodone, fentanyl, and morphine distribution decreasing (− 42.3%, − 36.7%, and − 27.8%, respectively); oxycodone remaining essentially unchanged (− 0.5%); and codeine distribution increasing 150.1% (Figure 3).

Figure 3.Per capita distribution of selected opioids from 2014 to 2018 as reported to ARCOS.15

The percent change from 2014 to 2018 in California and Texas is in the key for 3A and 3B, respectively.

Overdose rates

Opioid-related deaths increased in California (11.6%) and Texas (272.7%) between 1999 and 2019. California showed a decline in deaths from non-heroin opioids between 2014 and 2019 (Figure 4A), while Texas had an increase in deaths from 2014 to 2017, and then experienced a decline in 2018 (Figure 4B). Heroin-related deaths increased continuously in California (71.4%) and Texas (400%) between 1999 and 2019.

Figure 4.Opioid overdose rates as reported by the CDC’s WONDER database21 from 1999 to 2019.

The percent change from 1999 to 2019 in California and Texas is in the key for 4A and 4B, respectively.

Discussion

The observed trends in opioid distribution by zip code and per capita in California and Texas support recreational cannabis legalization as a practical measure to help reduce prescription opioid use. The five years analyzed (2014–2018) show a greater decrease in California than in Texas (Figure 2). Opioid distribution per 100 000 people in California decreased 38.9% from 2014 to 2018, while distribution in Texas decreased by only 26.4% (Figure 3). Similarly, heat-map analysis (Figure 1) illustrates a greater decrease in opioid distribution over large areas of California compared to Texas from 2014 to 2018. A similar study showed a significant correlation between increased cannabis use as a treatment for chronic pain and reduced opioid use,9 suggesting a potential public health benefit of replacing opioids with cannabis. Other studies have found less clear-cut benefits.23,24

The drop in hydrocodone and increase in codeine and oxycodone distribution per capita seen in Texas (Figure 3) is consistent with previous data showing that oxycodone and codeine increased by weight distribution from 2014 to 2017, specifically in Texas.7 The reclassification of hydrocodone in 2014 from a Schedule III to a Schedule II drug may be a factor behind this trend.7,18,23 Increased restrictions surrounding hydrocodone may have created an environment for the distribution of oxycodone and codeine to rise, as fewer powerful analgesic options, such as cannabis products, were available.

The decreasing trends observed in California (Figure 3) may be explained by current approaches to treating pain and the reduction in opioid use due to medicinal and recreational cannabis legalization. Three-fifths (62%) of women surveyed in California and Colorado with gynecological malignancies stated their interest in nonprescription cannabis, and 35.6% were interested in using cannabis under the guidance of physicians. One-quarter (26.7%) of these patients reported already using nonprescription cannabis products to manage various cancer-related symptoms.10 A California market report shows sales for medical and recreational cannabis projected to rise from 2018 to 2023, displaying an inverse relationship to opioid distribution, which continues to decrease in the state.8

Results from our data could be accounted for by the implementation of laws across the United States designed to mitigate overdoses by limiting opioid prescriptions and institutionalizing prescription drug monitoring programs introduced in 2017.25 Prior research has found that any association between medical cannabis and opioid overdoses is complicated,24,26,27 but further studies will help describe the relationship between changing cannabis legislation and opioid overdoses.

Although the availability of harm-reduction policies and medication-assisted treatments for opioid dependence (e.g., sterile syringe access programs and methadone) has increased,24,25 alternative pain-management strategies must be employed to decrease access and use of opioids to lower addiction and overdose rates. States that enacted medical cannabis laws had a 24.8% reduction in opioid overdose mortality, which further decreased in the years following their implementation.27 Evidence supports the promotion of safer and less addictive alternatives for analgesic relief and implementation of laws that could reduce the misuse and abuse of opioids.

There were a variety of limitations to our study. Limited research on recreational and nonprescription cannabis for analgesic effects makes it difficult to make accurate analysis and inferences. Most findings on cannabis and chronic pain refer to medical cannabis, but patients have reported using recreational and nonprescription cannabis for medical benefits.9 Surveys taken to assess the use of recreational and nonprescription cannabis from dispensaries would help differentiate between recreational and medicinal cannabis use. The data extracted from ARCOS presented a further limitation, as the census data used by the Drug Enforcement Administration was from 2010. Including more comparison states18,20,21 and utilizing 2020 census data, when available, might be beneficial in future studies.28 Also, differences exist in baseline (i.e., pre-legislation) levels of licit opioid and prescription opioid use. Additionally, drug overdoses are poly deterministic. Cannabis legislation is just one of many factors that could contribute to changes in the endpoints measured. Lastly, statistics gathered from CDC WONDER database do not provide specific details on overdoses (e.g., the involvement of alcohol) and includes overdoses from all opioids. Overdose data from WONDER may also be underestimated and consistency in death determinations varies considerably from state to state, as no standardized national reporting practices existed.6,7,25 However, both California and Texas were rated by the CDC as in the same “less than good” category for death determination quality.25

Conclusion

Prescription opioid distribution in California showed a greater decrease compared to Texas (43.7% and 27.3%, respectively). These findings suggest a relationship between California’s marijuana legislation, the decreased opioid distribution and prescription-related overdose deaths when compared to a state that has legislation prohibiting medicinal or recreational cannabis use. As more states increase access to cannabis, trends in opioid distribution and use, as well as opioid overdoses, must be further analyzed to promote legislation to help offset opioid overprescription and the overdose epidemic.


Contributor Roles

Michelle N Anyaehie conceived and designed the study, performed the literature search and review, authored drafts of the paper, analyzed the data and approved the final manuscript.

Christian Pardo conceived and designed the study, preformed literature search and review, analyzed the data, prepared figures, authored drafts of the paper, and approved the final manuscript.

Daniel E. Kaufman analyzed the data, prepared figures, authored drafts of the paper, and approved the final manuscript.

Dr. Brian Piper authored drafts of the paper, analyzed data, and approved the final manuscript.

Disclosure Statement

BJP was part of an osteoarthritis research team supported by Pfizer and Eli Lilly. BJP is a member of the Editorial Board of The Guthrie Journal, for which he receives no financial compensation. The other authors do not report any conflicts of interest.

Institutional Review Board Statement

This study was deemed exempt by the IRB of Geisinger 2020-0223.

Acknowledgment

We would like to thank Elizabeth Kuchinski, MPH, at Geisinger Commonwealth School of Medicine for their guidance and feedback throughout this study. We would like to thank Elijah Johnson, MBS, and Chucks Anachebe, MBS, for their contributions to an earlier version of this manuscript.

Publisher’s Note

A preliminary version of this article appeared in Scholarly Research in Progress (SCRIP), which is “aimed at promoting and disseminating student scholarly activity at Geisinger Commonwealth School of Medicine.” See Anyaehie M, Johnson, EJ, Pardo C. Analysis of opioid distribution before and after recreational marijuana legalization in California. Scholarly Research in Progress. 2020;4:107-111. This version underwent full peer review by The Guthrie Journal prior to acceptance. Published with permission.