ArticleLiterature Review

What does the ecological and epidemiological evidence indicate about the potential for cannabinoids to reduce opioid use and harms? A comprehensive review

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Abstract

Pre-clinical research supports that cannabinoids reduce opioid dose requirements, but few studies have tested this in humans. This review evaluates ecological and epidemiological studies that have been cited as evidence that medical cannabis use may reduce opioid use and opioid-related harms. Medline and Embase were searched for relevant articles. Data were extracted on study setting, analyses approach, covariates, and outcomes. Eleven ecological and 14 epidemiological studies were found. In ecological studies, states that allow medical cannabis laws have reported a slower rate of increase in opioid overdose deaths compared with states without such laws. These differences have increased over time and persisted after controlling for state sociodemographic characteristics and use of prescription monitoring programmes. Few studies have controlled for other potential confounders such as opioid dependence treatment and imprisonment rates. Some epidemiological studies provide evidence that cannabis availability may reduce opioid use, but are limited by selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects of cannabis. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and harms, although important methodological weaknesses were identified. Well-designed clinical studies may provide more conclusive evidence on whether cannabinoids can reduce opioid use and related harm.

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... Marijuana's association may be context dependent, as it has a mixed relationship with opioid use, misuse, and use disorder. [36] Polysubstance abuse must be critically assessed in context of opioid use as multiple associations may exist due to the varied effects of synergizing the opioid high. A better understanding of how polysubstance abuse occurs in context of multiple social and environmental factors is critical. ...
... [34] A more recent review found that medical marijuana use may decrease the probability of opioid use. [36] Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
... [34] A more recent review found that medical marijuana use may decrease the probability of opioid use. [36] Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
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Background: Few studies have comprehensively and contextually examined the relationship of variables associated with opioid use. Our purpose was to fill a critical gap in comprehensive risk models of opioid misuse and use disorder in the United States by identifying the most salient predictors. Methods: A multivariate logistic regression was used on the 2017 and 2018 National Survey on Drug Use and Health, which included all 50 states and the District of Columbia of the United States. The sample included all noninstitutionalized civilian adults aged 18 and older (N=85,580; weighted N=248,008,986). The outcome of opioid misuse and/or use disorder was based on reported prescription pain reliever and/or heroin use dependence, abuse, or misuse. Biopsychosocial predictors of opioid misuse and use disorder in addition to sociodemographic characteristics and other substance dependence or abuse were examined in our comprehensive model. Biopsychosocial characteristics included socioecological and health indicators. Criminality was the socioecological indicator. Health indicators included self-reported health, private health insurance, psychological distress, and suicidality. Sociodemographic variables included age, sex/gender, race/ethnicity, sexual identity, education, residence, income, and employment status. Substance dependence or abuse included both licit and illicit substances (i.e., nicotine, alcohol, marijuana, cocaine, inhalants, methamphetamine, tranquilizers, stimulants, sedatives). Results. The comprehensive model found that criminality (adjusted odds ratio [AOR]=2.58, 95% confidence interval [CI]=1.98-3.37, p<0.001), self-reported health (i.e., excellent compared to fair/poor [AOR=3.71, 95%CI=2.19-6.29, p<0.001], good [AOR=3.43, 95%CI=2.20-5.34, p<0.001], and very good [AOR=2.75, 95%CI=1.90-3.98, p<0.001]), no private health insurance (AOR=2.12, 95%CI=1.55-2.89, p<0.001), serious psychological distress (AOR=2.12, 95%CI=1.55-2.89, p<0.001), suicidality (AOR=1.58, 95%CI=1.17-2.14, p=0.004), and other substance dependence or abuse were significant predictors of opioid misuse and/or use disorder. Substances associated were nicotine (AOR=3.01, 95%CI=2.30-3.93, p<0.001), alcohol (AOR=1.40, 95%CI=1.02-1.92, p=0.038), marijuana (AOR=2.24, 95%CI=1.40-3.58, p=0.001), cocaine (AOR=3.92, 95%CI=2.14-7.17, p<0.001), methamphetamine (AOR=3.32, 95%CI=1.96-5.64, p<0.001), tranquilizers (AOR=16.72, 95%CI=9.75-28.65, p<0.001), and stimulants (AOR=2.45, 95%CI=1.03-5.87, p=0.044). Conclusions. Biopsychosocial characteristics such as socioecological and health indicators, as well as other substance dependence or abuse were stronger predictors of opioid misuse and use disorder than sociodemographic characteristics.
... Concurrent substance use such as nicotine and tobacco dependence [25,26], alcohol [27], sedatives [28], methamphetamines [29], tranquilizers [30][31][32], other analgesics [33], and marijuana [34] have been positively associated with opioid misuse and use disorder [34,35]. Marijuana's association may be context dependent, as it has a mixed relationship with opioid use, misuse, and use disorder [36]. Polysubstance abuse must be critically assessed in context of opioid use as multiple associations may exist due to the varied effects of synergizing the opioid high. ...
... In the cases of marijuana dependence or abuse there is a positive relationship with opioid misuse [34]. A more recent review found that medical marijuana use may decrease the probability of opioid use [36]. Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. ...
... A more recent review found that medical marijuana use may decrease the probability of opioid use [36]. Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
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Article
Background Few studies have comprehensively and contextually examined the relationship of variables associated with opioid use. Our purpose was to fill a critical gap in comprehensive risk models of opioid misuse and use disorder in the United States by identifying the most salient predictors. Methods A multivariate logistic regression was used on the 2017 and 2018 National Survey on Drug Use and Health, which included all 50 states and the District of Columbia of the United States. The sample included all noninstitutionalized civilian adults aged 18 and older (N = 85,580; weighted N = 248,008,986). The outcome of opioid misuse and/or use disorder was based on reported prescription pain reliever and/or heroin use dependence, abuse, or misuse. Biopsychosocial predictors of opioid misuse and use disorder in addition to sociodemographic characteristics and other substance dependence or abuse were examined in our comprehensive model. Biopsychosocial characteristics included socioecological and health indicators. Criminality was the socioecological indicator. Health indicators included self-reported health, private health insurance, psychological distress, and suicidality. Sociodemographic variables included age, sex/gender, race/ethnicity, sexual identity, education, residence, income, and employment status. Substance dependence or abuse included both licit and illicit substances (i.e., nicotine, alcohol, marijuana, cocaine, inhalants, methamphetamine, tranquilizers, stimulants, sedatives). Results The comprehensive model found that criminality (adjusted odds ratio [AOR] = 2.58, 95% confidence interval [CI] = 1.98–3.37, p < 0.001), self-reported health (i.e., excellent compared to fair/poor [AOR = 3.71, 95% CI = 2.19–6.29, p < 0.001], good [AOR = 3.43, 95% CI = 2.20–5.34, p < 0.001], and very good [AOR = 2.75, 95% CI = 1.90–3.98, p < 0.001]), no private health insurance (AOR = 2.12, 95% CI = 1.55–2.89, p < 0.001), serious psychological distress (AOR = 2.12, 95% CI = 1.55–2.89, p < 0.001), suicidality (AOR = 1.58, 95% CI = 1.17–2.14, p = 0.004), and other substance dependence or abuse were significant predictors of opioid misuse and/or use disorder. Substances associated were nicotine (AOR = 3.01, 95% CI = 2.30–3.93, p < 0.001), alcohol (AOR = 1.40, 95% CI = 1.02–1.92, p = 0.038), marijuana (AOR = 2.24, 95% CI = 1.40–3.58, p = 0.001), cocaine (AOR = 3.92, 95% CI = 2.14–7.17, p < 0.001), methamphetamine (AOR = 3.32, 95% CI = 1.96–5.64, p < 0.001), tranquilizers (AOR = 16.72, 95% CI = 9.75–28.65, p < 0.001), and stimulants (AOR = 2.45, 95% CI = 1.03–5.87, p = 0.044). Conclusions Biopsychosocial characteristics such as socioecological and health indicators, as well as other substance dependence or abuse were stronger predictors of opioid misuse and use disorder than sociodemographic characteristics.
... Marijuana may be context dependent as it has a mixed relationship with opioid use, misuse, and use disorder. [39] Medical cannabis use, speci cally, has been suggested to reduce opioid use in general, and may also reduce opioid overdose deaths in states with medical cannabis laws. [39] While epidemiologic studies have examined the relationship of various risk factors on opioid misuse and use disorder among noninstitutionalized populations, comprehensive models are relatively absent. ...
... [39] Medical cannabis use, speci cally, has been suggested to reduce opioid use in general, and may also reduce opioid overdose deaths in states with medical cannabis laws. [39] While epidemiologic studies have examined the relationship of various risk factors on opioid misuse and use disorder among noninstitutionalized populations, comprehensive models are relatively absent. To ameliorate the effect of the opioid epidemic, we must identify the risk factors associated with the etiology of misuse to intervene and prevent the distal events of use disorder like overdose. ...
... [37] A more recent review, however, found that medical marijuana use may decrease the probability of opioid use. [39] Campbell et al. [39] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
Full-text available
Preprint
Background: Few studies have comprehensively and contextually examined the relationship of variables associated with opioid use. Our purpose was to fill a critical gap in comprehensive risk models of opioid misuse and use disorder in the United States by identifying the most salient predictors. Methods: A multivariate logistic regression was used on the 2017 and 2018 National Survey on Drug Use and Health, which included all 50 states and the District of Columbia of the United States. The sample included all noninstitutionalized civilian adults aged 18 and older (N=85,580; weighted N=248,008,986). The outcome of opioid misuse and/or use disorder was based on reported prescription pain reliever and/or heroin use dependence, abuse, or misuse. Biopsychosocial predictors of opioid misuse and use disorder in addition to sociodemographic characteristics and other substance dependence or abuse were examined in our comprehensive model. Biopsychosocial characteristics included socioecological and health indicators. Criminality was the socioecological indicator. Health indicators included self-reported health, private health insurance, psychological distress, and suicidality. Sociodemographic variables included age, sex/gender, race/ethnicity, sexual identity, education, residence, income, and employment status. Substance dependence or abuse included both licit and illicit substances (i.e., nicotine, alcohol, marijuana, cocaine, inhalants, methamphetamine, tranquilizers, stimulants, sedatives). Results. The comprehensive model found that criminality (adjusted odds ratio [AOR]=2.58, 95% confidence interval [CI]=1.98-3.37, p<0.001), self-reported health (i.e., excellent compared to fair/poor [AOR=3.71, 95%CI=2.19-6.29, p<0.001], good [AOR=3.43, 95%CI=2.20-5.34, p<0.001], and very good [AOR=2.75, 95%CI=1.90-3.98, p<0.001]), no private health insurance (AOR=2.12, 95%CI=1.55-2.89, p<0.001), serious psychological distress (AOR=2.12, 95%CI=1.55-2.89, p<0.001), suicidality (AOR=1.58, 95%CI=1.17-2.14, p=0.004), and other substance dependence or abuse were significant predictors of opioid misuse and/or use disorder. Substances associated were nicotine (AOR=3.01, 95%CI=2.30-3.93, p<0.001), alcohol (AOR=1.40, 95%CI=1.02-1.92, p=0.038), marijuana (AOR=2.24, 95%CI=1.40-3.58, p=0.001), cocaine (AOR=3.92, 95%CI=2.14-7.17, p<0.001), methamphetamine (AOR=3.32, 95%CI=1.96-5.64, p<0.001), tranquilizers (AOR=16.72, 95%CI=9.75-28.65, p<0.001), and stimulants (AOR=2.45, 95%CI=1.03-5.87, p=0.044). Conclusions. Biopsychosocial characteristics such as socioecological and health indicators, as well as other substance dependence or abuse were stronger predictors of opioid misuse and use disorder than sociodemographic characteristics.
... When considering potential population level benefits of cannabinoids, the potential for cannabinoids to reduce reliance on high dose opioids, and consequently reduce opioidrelated overdose and mortality, is an area of both clinical and public health interest. Pre-clinical evidence certainly supports this possibility [53], and ecological [54][55][56][57] and epidemiological [58][59][60][61] studies also suggest that this is possible [62], though not all studies find cannabis use is associated with reduced opioid use [40]. The evidence base suggesting that cannabinoids may reduce opioid consumption and related mortality is not without its limitations [62]. ...
... Pre-clinical evidence certainly supports this possibility [53], and ecological [54][55][56][57] and epidemiological [58][59][60][61] studies also suggest that this is possible [62], though not all studies find cannabis use is associated with reduced opioid use [40]. The evidence base suggesting that cannabinoids may reduce opioid consumption and related mortality is not without its limitations [62]. Few studies have controlled for other interventions that reduce opioid-related mortality (e.g. ...
... opioid dependence treatment availability). Epidemiological studies have been limited by their design and recruitment strategies [62]. To date, despite promising pre-clinical and ecological evidence, no well-conducted clinical trials that address these limitations and can demonstrate clear causality have confirmed the potential for cannabinoids to reduce opioid use or harms [53]. ...
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Article
The use of medical cannabis and cannabis-based medicines has received increasing interest in recent years; with a corresponding surge in the number of studies and reviews conducted in the field. Despite this growth in evidence, the findings and conclusions of these studies have been inconsistent. In this paper, we outline the current evidence for medical cannabis and cannabis-based medicines in the treatment and management of chronic non-cancer pain. We discuss limitations of the current evidence, including limitations of randomised control trials in the field, limits on generalisability of previous findings and common issues such as problems with measurements of dose and type of cannabinoids. We discuss future directions for medicinal cannabinoid research, including addressing limitations in trial design; developing frameworks to monitor for use disorder and other unintended outcomes; and considering endpoints other than 30% or 50% reductions in pain severity.
... [34] A more recent review, however, found that medical marijuana use may decrease the probability of opioid use. [36] Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
... [34] A more recent review, however, found that medical marijuana use may decrease the probability of opioid use. [36] Campbell et al. [36] further revealed that medical cannabis laws may slow the increase of opioid overdose deaths in states with medical cannabis laws compared to states with none. Alcohol has been another substance with mixed associations for opioid misuse and use disorder. ...
Full-text available
Preprint
Background: Few studies have comprehensively and contextually examined the relationship of variables associated with opioid use. Our purpose was to fill a critical gap in comprehensive risk models of opioid misuse and use disorder in the United States by identifying the most salient predictors. Methods: A multivariate logistic regression was used on the 2017 and 2018 National Survey on Drug Use and Health, which included all 50 states and the District of Columbia of the United States. The sample included all noninstitutionalized civilian adults aged 18 and older (N=85,580; weighted N=248,008,986). The outcome of opioid misuse and/or use disorder was based on reported prescription pain reliever and/or heroin use dependence, abuse, or misuse. Biopsychosocial predictors of opioid misuse and use disorder in addition to sociodemographic characteristics and other substance dependence or abuse were examined in our comprehensive model. Biopsychosocial characteristics included socioecological and health indicators. Criminality was the socioecological indicator. Health indicators included self-reported health, private health insurance, psychological distress, and suicidality. Sociodemographic variables included age, sex/gender, race/ethnicity, sexual identity, education, residence, income, and employment status. Substance dependence or abuse included both licit and illicit substances (i.e., nicotine, alcohol, marijuana, cocaine, inhalants, methamphetamine, tranquilizers, stimulants, sedatives). Results. The comprehensive model found that criminality (adjusted odds ratio [AOR]=2.58, 95% confidence interval [CI]=1.98-3.37, p<0.001), self-reported health (i.e., excellent compared to fair/poor [AOR=3.71, 95%CI=2.19-6.29, p<0.001], good [AOR=3.43, 95%CI=2.20-5.34, p<0.001], and very good [AOR=2.75, 95%CI=1.90-3.98, p<0.001]), no private health insurance (AOR=2.12, 95%CI=1.55-2.89, p<0.001), serious psychological distress (AOR=2.12, 95%CI=1.55-2.89, p<0.001), suicidality (AOR=1.58, 95%CI=1.17-2.14, p=0.004), and other substance dependence or abuse were significant predictors of opioid misuse and/or use disorder. Substances associated were nicotine (AOR=3.01, 95%CI=2.30-3.93, p<0.001), alcohol (AOR=1.40, 95%CI=1.02-1.92, p=0.038), marijuana (AOR=2.24, 95%CI=1.40-3.58, p=0.001), cocaine (AOR=3.92, 95%CI=2.14-7.17, p<0.001), methamphetamine (AOR=3.32, 95%CI=1.96-5.64, p<0.001), tranquilizers (AOR=16.72, 95%CI=9.75-28.65, p<0.001), and stimulants (AOR=2.45, 95%CI=1.03-5.87, p=0.044). Conclusions. Biopsychosocial characteristics such as socioecological and health indicators, as well as other substance dependence or abuse were stronger predictors of opioid misuse and use disorder than sociodemographic characteristics.
... It is important to note two previous systematic reviews of the research on cannabis-based reductions of opioid-related harms [30][31]. These provided an important scholarly service as they systematically replicated a probable association. ...
... This meta-analysis found much support for the marijuana protection hypothesis [30][31] Consistent with previous systematic reviews, this meta-analytic review observed consistent inverse associations between cannabis legalization and opioid-related harms. Ten of the 11 primary studies analyzed, in fact 14 of 15 of their outcomes, supported the hypothesis. ...
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Background. Rhetoric abounds about harms associated with easier access to cannabis. Yet, surveys of medical marijuana patients and recreational users in Canada and the USA observed that they prevalently substitute cannabis for alcohol, opioids and other drugs. This synthetic study focused on arguably the most harmful substance, opioids, and hypothesized reduced harms with medical and recreational cannabis legalization. Methods. Broad keyword searches of interdisciplinary research databases, peer-reviewed and gray, between 2010 and 2020 retrieved 11 studies. Their outcomes were synthesized with a sample-weighted meta-analysis that compared opioid-related outcomes before and after marijuana legalization in states that legalized marijuana versus those that had not. Results. All but one of the primary studies supported the marijuana protection or harm reduction hypothesis. In aggregate and controlling for typically eight state-level covariates, risks associated with opioid use diminished by 7% (RR = 0.93, 95% CI 0.92, 0.94) after legalization; 7% after medical marijuana and 35% after recreational marijuana legalization (p < .05). Opioid prescriptions decreased by 8% and opioid overdose mortality diminished by 25% after medical marijuana legalization. Both were further diminished after recreational marijuana was legalized. Conclusions. Their potential public health significances is clear, suggesting that such legislation profoundly affects the behaviors of physicians, patients and addicts in protective ways. However, all the studies, thus far, have been state-level, ecological analyses. Further multilevel and clinic-based analyses in ought to be accomplished to systematically replicate (or refute) this study’s harm reduction estimates and to put them into clinical practice where indicated.
... Some studies have shown the replacement of other prescription pharmaceuticals by MC as well [23][24][25] . However, it is important to emphasize that many of those studies were limited in terms of statistical indexes, database volume, and the perspective of time, calling for further exploration [26] . Regardless, the reported positive results may play a significant role in the "opioid crisis", as through promotion of treatment with MC, overdoses of prescription opioid medications will decrease, thereby reducing the staggering statistics of deaths from overdose [26,27] . ...
... However, it is important to emphasize that many of those studies were limited in terms of statistical indexes, database volume, and the perspective of time, calling for further exploration [26] . Regardless, the reported positive results may play a significant role in the "opioid crisis", as through promotion of treatment with MC, overdoses of prescription opioid medications will decrease, thereby reducing the staggering statistics of deaths from overdose [26,27] . Simultaneously, it curbs the amount of hazardous pharmaceutical residues spilling into and threatening water sources and the environment. ...
... A more recent review found that marijuana use may decrease the probability of opioid misuse. 35 Campbell et al. 35 further revealed that medical cannabis laws/use decreases opioid overdose deaths in states that allow marijuana use compared to states that do not have medical marijuana laws. ...
... A more recent review found that marijuana use may decrease the probability of opioid misuse. 35 Campbell et al. 35 further revealed that medical cannabis laws/use decreases opioid overdose deaths in states that allow marijuana use compared to states that do not have medical marijuana laws. ...
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Background Few studies have comprehensively and contextually examined the relationship of variables associated with opioid misuse. Our purpose was to fill a critical gap in comprehensive risk models of opioid misuse in the United States by identifying the most salient predictors. Methods A multivariate logistic regression was used on the 2017 and 2018 National Survey on Drug Use and Health, which included all 50 states and the District of Columbia of the United States. The sample included all noninstitutionalized civilian adults aged 18 and older (N=85,580; weighted N=248,008,986). The outcome of opioid misuse was based on reported prescription pain reliever and/or heroin dependence or abuse. Biopsychosocial predictors of opioid misuse in addition to sociodemographic characteristics and other substance dependence or abuse were examined in our comprehensive model. Biopsychosocial characteristics included socioecological and health indicators. Criminality was the socioecological indicator. Health indicators included self-reported health, private health insurance, psychological distress, and suicidality. Sociodemographic variables included age, sex/gender, race/ethnicity, sexual identity, education, residence, income, and employment status. Substance dependence or abuse included both licit and illicit substances (i.e., nicotine, alcohol, marijuana, cocaine, inhalants, methamphetamine, tranquilizers, stimulants, sedatives). Results The comprehensive model found that criminality (adjusted odds ratio [AOR]=2.58, 95% confidence interval [CI]=1.98-3.37, p<0.001), self-reported health (i.e., excellent compared to fair/poor [AOR=3.71, 95%CI=2.19-6.29, p<0.001], good [AOR=3.43, 95%CI=2.20-5.34, p<0.001], and very good [AOR=2.75, 95%CI=1.90-3.98, p<0.001]), no private health insurance (AOR=2.12, 95%CI=1.55-2.89, p<0.001), serious psychological distress (AOR=2.12, 95%CI=1.55-2.89, p<0.001), suicidality (AOR=1.58, 95%CI=1.17-2.14, p=0.004), and other substance dependence or abuse were significant predictors of opioid misuse. Substances associated were nicotine (AOR=3.01, 95%CI=2.30-3.93, p<0.001), alcohol (AOR=1.40, 95%CI=1.02-1.92, p=0.038), marijuana (AOR=2.24, 95%CI=1.40-3.58, p=0.001), cocaine (AOR=3.92, 95%CI=2.14-7.17, p<0.001), methamphetamine (AOR=3.32, 95%CI=1.96-5.64, p<0.001), tranquilizers (AOR=16.72, 95%CI=9.75-28.65, p<0.001), and stimulants (AOR=2.45, 95%CI=1.03-5.87, p=0.044). Conclusions Biopsychosocial characteristics such as socioecological and health indicators, as well as other substance dependence or abuse were stronger predictors of opioid misuse than sociodemographic characteristics.
... Preclinical data have consistently demonstrated opioid-sparing effects [3]. Interest from policy makers has been further driven by ecological and epidemiological research [4]; however, highly publicized findings have recently been questioned [5]. ...
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Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.
... As Canada and most U.S. states enact decriminalization and legalization of cannabis for medical and recreational adult use, there is considerable interest in determining whether cannabis and cannabinoid products are viable alternatives to opioids for pain management or a potential adjunctive therapy for OUD. Recent interest is spurred in part by several studies that found relationships between cannabis legalization at the state level and reductions in opioid-related deaths [3][4][5][6][7][8], though the ecological association between state-level medical cannabis legislation and reduced opioid overdose mortality reported previously [3] was not replicated in a study examining additional years [9]. Additionally, several studies have found that medical cannabis patients report pain management as one of the most common reasons for cannabis use [10][11][12] and that cannabis use was associated with lower opioid use among people who use illicit drugs [13,14]. ...
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Article
A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform ("subreddits") to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., "weed", "cannabis", "marijuana") from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a "treatment." The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress "comfort meds," and to enhance the "high" when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.
... Furthermore, some epidemiological studies provide evidence that cannabis availability may reduce opioid administration. However, interpretation is limited by the lack of characterisation of the cannabinergic products, selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects (Campbell et al. 2018a). According to a retrospective cross-sectional survey of patients with chronic pain, medical cannabis use was associated with a 64% decrease in opioid use (Boehnke et al. 2016); according to another survey, about 80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management (Boehnke et al. 2019). ...
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Article
Currently, there is a renewed interest in treatments with medical cannabis and cannabinoids. Based on an increasing number of publications over the last decades that permitted new insights into mechanisms, efficacy and safety of cannabinoids, the use of cannabinergic medications is authorised in an increasing number of European and non-European countries. The alleviation of chronic, painful conditions is, since thousands of years, one of the primary reasons for the use of cannabis. Depending on the country, a wide range of medicinal cannabis preparations are available:ranging from defined cultivars of medical cannabis, mainly varying in their THC:CBD ratio, that are inhaled or taken as whole plant extracts,to highly purified single cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD),or mixtures of two enriched extracts, standardised to a 1:1 ratio of THC:CBD (nabiximols). Although conflicting opinions continue to exist, the majority of reviews in the past concluded that medical cannabis and cannabinoids play a significant role in the management of pain. Surprisingly, systematic studies to date do not support an “entourage effect” of the other plant constituents of cannabis (mainly terpenoids) in treatment of chronic pain. An emerging cannabinoid is CBD which is the only cannabinergic medication available at present that does not cause the typical “cannabis high”; it is not a “controlled substance”. However, despite years of research, there is either no study or no well-conducted, head-to-head, comparison available between different cannabis cultivars, between pure cannabinoids, and between pure cannabinoids and extracts. It remains unanswered which is the optimal treatment approach. Graphical abstract
... The opioid-sparing properties of cannabinoids were first acknowledged in 1889 [10], and are evident within preclinical studies that report high potency cannabinoids produce robust and meaningful shifts in opioid-induced analgesia [11,12]. Patient surveys [13][14][15][16] and epidemiological evidence reports that reductions in opioid-reliance and consequences following medicinal cannabis exposure [17,18] suggested these preclinical outcomes might generalize into human clinical samples, and this collective information was the basis upon which several states added OUD as a qualifying condition for medicinal cannabis prescribing [19]. ...
Article
This Phase II study evaluated analgesia, abuse liability, and cognitive performance of hydromorphone and oral delta-9-tetrahydrocannabinol (THC; dronabinol) using a within-subject, double-blind, randomized, placebo-controlled, human laboratory trial. Healthy adults (N = 29) with no history of drug use disorder received combinations of placebo, hydromorphone (4 mg; oral), and dronabinol (2.5 mg, 5.0 mg, 10 mg; oral). Primary outcomes were quantitative sensory testing (QST) measures of acute (thermal, pressure pain; thermal, punctate probe temporal summation; cold pressor; conditioned pain modulation) and chronic pain (capsaicin 10% topical cream with thermal rekindling), measures of drug abuse liability, cognitive functioning, and adverse events. Subgroup analyses were conducted within opioid-responders (endorsed >20 on a Drug Effect visual analog scale during the hydromorphone-only condition) and nonresponders. A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Hydromorphone + dronabinol 2.5 mg showed the lowest and hydromorphone+dronabinol 5 mg showed the highest risk for abuse. Hydromorphone+dronabinol 10 mg produced a high rate of dysphoric effects, and hydromorphone+dronabinol 5 mg and hydromorphone + dronabinol 10 mg produced AEs. Subgroup analyses showed subjective effects and abuse risk was increased among opioid responders and largely absent among nonresponders. Overall, only hydromorphone+dronabinol 2.5 mg modestly enhanced hydromorphone-based analgesia and hydromorphone + dronabinol 5 mg and 10 mg increased risk for abuse and AEs. These data can help inform opioid-sparing efforts in clinical pain populations. Demonstration that potential opioid effects varied as a function of participant opioid sensitivity (e.g., responder status) is a novel finding that warrants additional research.
... In particular, cannabinoid use should be monitored given the recent increase in cannabinoid use for pain and suggestions that cannabis and other cannabinoids can reduce opioid dosages for pain. 11,48,52,62 Data from prescription monitoring systems could also be used to evaluate whether participants are getting undisclosed prescriptions from prescribers not associated with the study. Sensitivity analyses should investigate whether the use of prohibited drugs potentially affected the trial results. ...
Article
Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (e.g., opioid use disorder) and adverse outcomes (e.g., respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents IMMPACT consensus recommendations for the design of opioid sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.
... Furthermore, the movement away from opiates as an analgesic has fuelled an increased interest in applications for cannabinoids in the treatment of chronic noncancer-related pain. It is well documented that cannabis therapy is associated with a significant reduction in opioid requirements [32][33][34] and, consequently, a reduction in opioid-related adverse effects. Nonsteroidal anti-inflammatory drugs are also commonly used in the treatment of chronic pain [35,36] but are associated with higher a risk of gastrointestinal events (risk ratio compared to placebo: 1.38, 95% CI 1.21, 1.57) [36,37] and account for nearly 30% of adverse drug reactions causing hospital admission [38]. ...
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Article
Purpose: Medical cannabis for patients with chronic noncancer pain (CNCP) has been the focus of numerous health care recommendations. We conducted a systematic review to identify and summarize the currently available evidence-based recommendations. Methods: We searched MEDLINE, EMBASE, PsycINFO, the Cochrane database of systematic reviews, and websites for clinical guidelines and recommendations. We summarized the type of the publications, developers, approach of health care recommendation development, year and country of publication, and conditions that were addressed. We categorized the direction and strength of each recommendation. Results: We identified 12 eligible publications. Publication years ranged from 2007 to 2019; four (33.3%) of them were published in 2018. Canada ranked first for the number of publications (n = 4, 33.3%). Most (n = 11, 92%) of the included recommendations were based on both a systematic review of the best evidence and expert consensus. All the included publications provided a recommendation supporting medical cannabis for CNCP in general and for the specific conditions of neuropathic pain, chronic pain in people living with Human Immunodeficiency Virus (HIV), and chronic abdominal pain, with detailed information sharing and comprehensive consideration of a patient's own values and preferences. Conclusion: Clinicians can attend to the guidance currently offered, being aware that only weak recommendations are available for medical cannabis in patients with CNCP, as a third- or fourth-line therapy. Detailed discussions with patients regarding the benefits in reducing pain and potential adverse effects are required before its prescription.
... Some population-level studies observed that state marijuana therapeutic-use laws correlate with lower rates of opioid prescribing (McMichael et al., 2020;Wen and Hockenberry, 2018), use (Flexon et al., 2019;Shah et al., 2019), and overdose mortality (Bachhuber et al., 2014;Chihuri and Li, 2019). However, confounds between marijuana laws and opioid use have not been controlled (Campbell et al., 2018;Shover et al., 2019;Smart and Pacula, 2019), and epidemiological and ecological data cannot predict individual-level use patterns (Caputi and Sabet, 2018;Hall et al., 2018). Thus, prospective longitudinal research is needed to examine whether the effect of opioid use on demand for marijuana and/or certification is independent of pain severity and illicit/sanctioned use; and whether enabling use of marijuana through legalization/medicalization might mediate reductions in opioid analgesic use. ...
Article
Background Despite medicalization and legalization of marijuana use, factors influencing demand for marijuana among persons living with HIV (PLWH) are incompletely understood. This knowledge gap undermines effective clinical management and policies. This study used demand curve simulation methods to address these issues. Methods Marijuana-using PLWH (N = 119) completed experimental tasks to simulate amount of marijuana purchasing/use across different costs (money or time), and likelihood of reselling marijuana or marijuana therapeutic-use registration card in relation to profits. Additional simulations assessed purchasing of marijuana relative to other drug and non-drug goods. Results Simulated marijuana use decreased as money and time costs increased. Consumption was greater for participants with more severe Cannabis Use Disorder (CUD) and anxiety, intermediate pain levels, and past 90-day opioid use. Whereas few participants chose to sell their registration card, marijuana resale (diversion) steeply increased with profit. Likelihood of seeking marijuana therapeutic-use certification decreased in relation to registration card money cost, having to visit more physicians to get a signature, and delay to receiving the card, and increased with duration of certification. Participants who reported recent opioid use were more likely to seek certification. Consumption of several commodities assessed was independent of marijuana. Conclusions Simulated marijuana use was related to participants’ clinical profile (CUD, anxiety and pain symptoms, recent opioid use), and unrelated to purchasing other goods. Likelihood of seeking marijuana therapeutic-use registration was affected by several types of costs and recent opioid use. Participants were unlikely to divert registration cards. We discuss clinical and policy implications of these findings.
... 11 An important limitation of this research, however, is that this state-level data presents 'the weakest type of evidence for causal inferences,' given that population level analyses cannot establish a causal connection between MC and RC laws themselves and the rates of opioid prescribing and harms because they are unable to chart individual patterns of substance use and substitution. 12 However, there are studies that have been conducted with patients enrolled in dispensaries and medical cannabis programs in Canada and the US that track individual use and substitution patterns. Importantly, they confirm that patients with chronic pain (whether physical, psychological, or both) value cannabis as a useful medication for pain relief and see cannabis as an important adjunct therapy. ...
... The younger polyopioid misuse group was found to be at decreased odds of marijuana dependence and abuse when compared to the female prescription misuse profile. Marijuana has a mixed relationship with opioid misuse, and has been associated with increased and decreased use [38]. ...
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Article
Opioid misuse can lead to use disorder and other adverse outcomes. Identifying sociodemographic risk profiles and understanding misuse patterns in combination with health indicators can inform prevention science and clinical practice. A latent class analysis of opioid misuse was conducted on noninstitutionalized United States civilians aged 18 and older that reported opioid dependence or abuse in the 2017 National Survey of Drug Use and Health (n = 476; weighted n = 2,018,922). Opioid misuse was based on heroin and/or prescription pain reliever use, and associated determinants of health and mental health indicators. Five misuse profiles were identified: (1) single heroin or prescription misuse with high-income; (2) female prescription pain reliever misuse with psychological distress and suicidality; (3) younger polyopioid misuse with the highest proportion of Hispanics and heroin use; (4) older polyopioid misuse with the highest proportion of non-Hispanic blacks and disability; and (5) older non-Hispanic white male exclusive dual heroin and/or prescription misuse (27%, 20%, 38%, 10%, and 5% of sample, respectively). The identified risk profiles can inform public health practice to develop interventions for acute and immediate response by providing etiological evidence and to inform prevention and intervention efforts along the continuum from opioid initiation to use disorder.
... For example, we observed that males were much more likely than females to currently be using opioids, and male MM patients reported having used cannabis products previously for five years or longer at a significantly higher rate than female MM patients. Currently, there is tremendous interest in elucidating the potential for MM use to potentially decrease the use of opioids in some medical conditions and, conversely, the potential for MM to potentially exacerbate opioid abuse and the negative effects of opioid use in some patients [17][18][19][20]. The majority of opioid-related studies to date have focused on the interplay between opioid use and recreational marijuana use and have not specifically examined marijuana use as part of MM programs. ...
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Article
Relatively little is known in terms of patient demographics, indications, previous cannabis use, or the forms and dosages of medical marijuana (MM) dispensed for patients at MM dispensaries. Even less is known in terms of how male and female patients may differ in each of these aspects. The goal of the current study was to examine each of these variables using a retrospective analysis of deidentified patient data from MM dispensaries in Louisiana. Deidentified data were analyzed from web-based pharmacist–patient consultations at MM dispensaries throughout Louisiana. Data were collected during the first 6 months following the initiation of the MM dispensing program in Louisiana. A total of 1195 MM patients (598 male/597 female) were included in the analyses. The average age of the sample was 51.9 years (±14.8) and it was composed primarily of white patients (86.7%). Males and females were nearly identical in terms of average age, race, previous cannabis use, indication profile, and MM recommendations. Differences between males and females were observed in terms of opioid use, history of psychosis, presence of more than one indication, and the duration of previous cannabis use. Our data indicate that, in MM dispensaries of the Deep South state, there are numerous similarities—and some potentially important differences—between male and female MM patients. The importance of these differences, and the importance of continued data collection/analysis, for improving MM dispensing are discussed.
... One notable time-series analysis reported states that legalized medical cannabis experienced lower annual rates of opioid analgesic overdose deaths compared to states that maintained barriers to cannabis (Bachhuber et al., 2014). However, although these data provide a valuable signal, this effect is not reliably replicated and evidence suggests it may be more related to differences in state-level healthcare policies than inherent relationships between opioids and cannabinoids (for a review see Campbell et al., 2018). In other survey-based studies, 30-72% of cannabis users qualitatively reported 'substituting' cannabis for opioids (Corroon et al., 2017;Lucas, 2017). ...
Article
Background Cannabinoids may potentiate opioid analgesia and therefore could be used to reduce reliance on opioids for analgesia. Aims The current study evaluated whether the concurrent availability of cannabis influences opioid consumption using a behavioral economic demand framework. Methods An online survey assessed cannabis and opioid use frequency and dependence measures, pain severity, and demand for both cannabis and opioids alone and when concurrently available using hypothetical purchase tasks. Adults reporting current use of opioids for pain management and past 30-day cannabis exposure ( N=155) completed two hypothetical purchase tasks in which only grams of cannabis or units of participants’ index opioids were available for purchase, and two hypothetical tasks in which both were concurrently available and the price of one drug increased whereas the other was kept constant. Paired-sample t-tests compared the demand of each drug alone with when it was available concurrently with an alternative. Results Demand intensity was significantly reduced and demand elasticity was significantly increased for both cannabis and opioids when the alternate commodity was available, although the reductions in cannabis consumption were more pronounced than they were for opioid consumption in the presence of the alternate commodity. Conclusions These data provide behavioral economic evidence that cannabis access may modestly reduce demand for opioids in persons who have pain. Additional clinical studies that evaluate the analgesic effects of cannabis and cannabis-opioid effects on pain are warranted.
... Considering that buprenorphine as part of OMT decreased the risk for both non-fatal and fatal overdoses shows that there is clearly a need for further education on use of alternative therapies to full agonist opioids and benzodiazepines (Griggs et al., 2019). At present, there is an increased focus on cannabis' potential as an analgesic alternative that may help to alleviate opioid withdrawal symptoms, decrease the likelihood of relapse, and ultimately prevent opioid misuse (Campbell et al., 2018;Wiese and Wilson-Poe, 2018). ...
Article
Background: Drug overdoses remain a significant public health burden throughout the world. This study assessed the incidence and predictors of non-fatal and fatal drug overdoses among patients with an opioid use, treated for drug use disorders (DUD) at public treatment centers in Denmark. Methods: A consecutive cohort of patients (n = 11,199) were tracked from date of first registered enrollment between the year 2000 and 2010 to first registered drug overdose, death or December 31st 2010, whichever occurred first. Competing-risks regression models were fitted to estimate the sub hazard ratios (SHRs) of non-fatal and fatal drug overdoses and confounding risk factors. Results: A total of 3186 (28%) patients experienced a non-fatal drug overdose during follow-up, and 572 (6%) died from an overdose. Use of benzodiazepines (SHR: 1.15 95% CI 1.03, 1.28) was significantly associated with non-fatal overdose. Intravenous drug use and previous hospitalization for a non-fatal overdose increased the risk of later non-fatal (SHR: 1.57 95% CI 1.42, 1.73) and fatal overdoses (SHR: 1.43 95% CI 1.12, 1.82). Conclusions: Patients who use opioids remain at risk of overdoses for a long time after discharge from drug treatment. Besides relevant monitoring and psychosocial support in opioid maintenance treatment, there is a need for informing and educating opioid users in risk factors and preventive measures in settings where they are often difficult to access for traditional treatment services.
... Addiction's editors (including the two authors of this editorial) pointed out that correlations between state-level overdose death data and whether or not states had a medical cannabis program should be not interpreted as evidence that individuals could reduce their opioid overdose risk by using cannabis [5]. We also highlighted other peer-reviewed studies that provided stronger evidence that was inconsistent with this claim (see [6][7][8][9]). ...
... The papers in this edition cover different elements of the opioid epidemic, spanning potential substitutions for pain management, opioid treatment innovations, characteristics that may impact opioid response, and consequences of extended opioid exposure. The edition begins with a review by Campbell, Hall, and Nielsen (2018) that summarizes ecological and epidemiological signals regarding the use of cannabinoid products to effectively mitigate opioidrelated harms. This paper is premised upon strong preclinical evidence that cannabinoids interact with the endogenous opioid system in a meaningful way (Nielsen et al., 2017), and will contribute to ongoing national and international discussions regarding the potential to leverage cannabinoids for opioid use disorder treatment as well as pain management. ...
Article
Despite a rapid expansion of cannabis use for pain management, how cannabis and prescription opioids are co-used and whether co-use improves analgesia and promotes reduction of opioid use in the daily lives of individuals with chronic pain is poorly understood. Based upon ecological momentary assessment (EMA), the present study examined 1) how pain and use of opioids and/or cannabis in the previous moment is associated with individuals’ choice of opioids and/or cannabis in the next moment, 2) the effects of co-use on pain severity and pain relief, and 3) whether daily total opioid consumption differs on days when people only used opioids versus co-used. Adults with chronic pain (N = 46) using both opioids and cannabis who were recruited online completed a 30-day EMA. Elevated pain did not increase the likelihood of co-use in subsequent momentary assessments. Switching from sole use of either opioids and cannabis to co-use was common. Neither co-use nor sole use of either cannabis or opioids were associated with reductions in pain in the next moment. However, participants reported the highest daily perceived pain relief from co-use compared to cannabis and opioid use only. Post hoc analysis suggested recall bias as a potential source of this discrepant findings between momentary versus retrospective assessment. Lastly, there was no evidence of an opioid-sparing effect of cannabis in this sample. The present study shows preliminary evidence on cannabis and opioid co-use patterns, as well as the effects of co-use on pain and opoid dose in the real-world setting. Perspective This article presents the overall patterns and effects of co-using cannabis and prescription opioids among individuals with chronic pain employing ecological momentary assessment. There were conflicting findings on the association between co-use and analgesia. Co-use was not associated with a reduction in daily opioid consumption in this sample.
Article
Background The ongoing opioid overdose crisis is driven largely by exposure to illicitly-manufactured fentanyl. Preliminary observational and experimental research suggests that cannabis could potentially play a role in reducing use of prescription opioids among individuals with chronic pain. However, there is limited data on the effects of cannabis on illicit opioid consumption, particularly fentanyl, especially among individuals on opioid agonist therapy (OAT). We sought to assess the longitudinal association between cannabis use and exposure to fentanyl among people on OAT. Methods Data were drawn from two community-recruited prospective cohorts of people who use drugs in Vancouver, Canada. We used generalized linear mixed-effects modeling, adjusted by relevant confounders, to investigate the relationship between cannabis use and recent fentanyl exposure (both assessed by urine drug testing) among participants on OAT between 2016 and 2018. Results Among the 819 participants on OAT who contributed 1989 observations over the study period, fentanyl exposure was common. At the baseline interview, fentanyl was detected in a majority of participants (431, 53 %), with lower prevalence among individuals with urine drug tests positive for tetrahydrocannabinol (47 vs. 56 %, p = 0.028). Over all study interviews, cannabis use was independently associated with reduced likelihood of being recently exposed to fentanyl (Adjusted Prevalence Ratio = 0.91, 95 % Confidence Interval: 0.83 – 0.99). Conclusions Participants on OAT using cannabis had significantly lower risk of being exposed to fentanyl. Our findings reinforce the need for experimental trials to investigate the potential benefits and risks of controlled cannabinoid administration for people on OAT.
Article
A converging line of evidence is indicating that cannabinoids may have an opioid-sparing effect. This property, well validated in preclinical studies, allow when both drugs are co-administered to reduce the dose of opioids without loss of analgesic effects. A meta-analysis of pre-clinical studies indicated in 2017 that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower than the ED50 of morphine alone (Nielsen et al., 2017). However, very few studies have been conducted in humans to validate this effect. This narrative review provides an update on whether or not cannabinoid drugs can be used to produce an opioid sparing effect. For this, various line of evidence ranging from preclinical, epidemiological and human studies will be summarized. Overall, this review indicates that the preclinical results are strongly and consistently supportive of the presence of an opioid sparing effect of cannabinoid drugs. However, to date the clinical studies have been mostly negative. However, the evidence collected in humans so far is so limited that it is premature to conclude. However, prospective high quality controlled clinical trials are still required to validate this. Priorities for future research are also discussed.
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Background: No prior studies have characterized long-term patterns of opioid use regardless of source or reason for use among patients with HIV (PWH). We sought to identify trajectories of self-reported opioid use and their correlates among a national sample of PWH engaged in care. Setting: Veterans Aging Cohort Study, a prospective cohort including PWH receiving care at 8 US Veterans Health Administration (VA) sites. Methods: Between 2002 and 2018, we assessed past year opioid use frequency based on self-reported "prescription painkillers" and/or heroin use at baseline and follow-up. We used group-based trajectory models to identify opioid use trajectories and multinomial logistic regression to determine baseline factors independently associated with escalating opioid use compared to stable, infrequent use. Results: Among 3702 PWH, we identified 4 opioid use trajectories: (1) no lifetime use (25%); (2) stable, infrequent use (58%); (3) escalating use (7%); and (4) de-escalating use (11%). In bivariate analysis, anxiety; pain interference; prescribed opioids, benzodiazepines and gabapentinoids; and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. In multivariable analysis, illness severity, pain interference, receipt of prescribed benzodiazepine medications, and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. Conclusion: Among PWH engaged in VA care, 1 in 15 reported escalating opioid use. Future research is needed to understand the impact of psychoactive medications and marijuana use on opioid use and whether enhanced uptake of evidence-based treatment of pain and psychiatric symptoms can prevent escalating use among PWH.
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Opioid misuse and abuse is a major international public health issue. Opioid use disorder (OUD) is largely maintained by a desire to suppress aversive opioid withdrawal symptoms. Opioid withdrawal in patients seeking abstinence from illicit or prescribed opioids is often managed by provision of a μ-opioid agonist/partial agonist in combination with concomitant medications. Concomitant medications are administered based on their ability to treat specific symptoms rather than a mechanistic understanding of the opioid withdrawal syndrome; however, their use has not been statistically associated with improved treatment outcomes. Understanding the central and/or peripheral mechanisms that underlie individual withdrawal symptom expression in humans will help promote medication development for opioid withdrawal management. To support focused examination of mechanistically supported concomitant medications, this review summarizes evidence from preclinical (N = 68) and human (N = 30) studies that administered drugs acting on the dopamine, serotonin, cannabinoid, orexin/hypocretin, and glutamate systems and reported outcomes related to opioid withdrawal. These studies provide evidence that each of these systems contribute to opioid withdrawal severity. The Food and Drug Administration has approved medications acting on these respective systems for other indications and research in this area could support the repurposing of these medications to enhance opioid withdrawal treatment. These data support a focused examination of mechanistically informed concomitant medications to help reduce opioid withdrawal severity and enhance the continuum of care available for persons with OUD.
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Background The use of medical cannabis is increasing, most commonly for pain, anxiety and depression. Emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal. The aim of this study was to survey cannabis users to determine whether they had intentionally substituted cannabis for prescription drugs. Methods A total of 2,774 individuals were a self-selected convenience sample who reported having used cannabis at least once in the previous 90 days. Subjects were surveyed via an online anonymous questionnaire on cannabis substitution effects. Participants were recruited through social media and cannabis dispensaries in Washington State. Results A total of 1,248 (46%) respondents reported using cannabis as a substitute for prescription drugs. The most common classes of drugs substituted were narcotics/opioids (35.8%), anxiolytics/benzodiazepines (13.6%) and antidepressants (12.7%). A total of 2,473 substitutions were reported or approximately two drug substitutions per affirmative respondent. The odds of reporting substituting were 4.59 (95% confidence interval [CI], 3.87–5.43) greater among medical cannabis users compared with non-medical users and 1.66 (95% CI, 1.27–2.16) greater among those reporting use for managing the comorbidities of pain, anxiety and depression. A slightly higher percentage of those who reported substituting resided in states where medical cannabis was legal at the time of the survey (47% vs. 45%, p=0.58), but this difference was not statistically significant. Discussion These patient-reported outcomes support prior research that individuals are using cannabis as a substitute for prescription drugs, particularly, narcotics/opioids, and independent of whether they identify themselves as medical or non-medical users. This is especially true if they suffer from pain, anxiety and depression. Additionally, this study suggests that state laws allowing access to, and use of, medical cannabis may not be influencing individual decision-making in this area.
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Background: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. Funding: National Health and Medical Research Council and the Australian Government.
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This review examines evidence cannabinoids in chronic non-cancer pain (CNCP), and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 RCTs and 57 observational studies. Forty-eight studies examined neuropathic pain, seven studies examined fibromyalgia, one rheumatoid arthritis, and 48 other CNCP (13 MS-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, PERs for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo), significant effect for cannabinoids, number needed to treat to benefit (NNTB): 24 (95%CI 15-61); for 50% reduction in pain, PERs were 18.2% vs. 14.4%; no significant difference. Pooled change in pain intensity (standardised mean difference: -0.14, 95%CI -0.20, -0.08) was equivalent to 3mm on a 100mm visual analogue scale greater than placebo. In RCTs, PERs for all-cause AEs were 81.2% vs. 66.2%; number needed to treat to harm (NNTH): 6 (95%CI 5-8). There were no significant impacts upon physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest NNTB are high, and NNTH low, with limited impact on other domains. It appears unlikely that cannabinoids are highly effective medicines for CNCP.
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During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3),†CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids),§cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid.¶From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.
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BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. OBJECTIVES: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. SEARCH METHODS: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. SELECTION CRITERIA: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). AUTHORS' CONCLUSIONS: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.
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Background: Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives. Purpose: A preliminary, historical, cohort study was used to examine the association between enrollment in the New Mexico Medical Cannabis Program (MCP) and opioid prescription use. Methods: Thirty-seven habitual opioid using, chronic pain patients (mean age = 54 years; 54% male; 86% chronic back pain) enrolled in the MCP between 4/1/2010 and 10/3/2015 were compared to 29 non-enrolled patients (mean age = 60 years; 69% male; 100% chronic back pain). We used Prescription Monitoring Program opioid records over a 21 month period (first three months prior to enrollment for the MCP patients) to measure cessation (defined as the absence of opioid prescriptions activity during the last three months of observation) and reduction (calculated in average daily intravenous [IV] morphine dosages). MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected. Results: By the end of the 21 month observation period, MCP enrollment was associated with 17.27 higher age- and gender-adjusted odds of ceasing opioid prescriptions (CI 1.89 to 157.36, p = 0.012), 5.12 higher odds of reducing daily prescription opioid dosages (CI 1.56 to 16.88, p = 0.007), and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10.4 percentage points in the comparison group (CI -90.68 to -3.59, p = 0.034). The monthly trend in opioid prescriptions over time was negative among MCP patients (-0.64mg IV morphine, CI -1.10 to -0.18, p = 0.008), but not statistically different from zero in the comparison group (0.18mg IV morphine, CI -0.02 to 0.39, p = 0.081). Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP (ps<0.001). Conclusions: The clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.
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Background With the Canadian government legalizing cannabis in the year 2018, the potential harms to certain populations—including those with opioid use disorder—must be investigated. Cannabis is one of the most commonly used substances by patients who are engaged in medication-assisted treatment for opioid use disorder, the effects of which are largely unknown. In this study, we examine the impact of baseline and ongoing cannabis use, and whether these are impacted differentially by gender. Methods We conducted a retrospective cohort study using anonymized electronic medical records from 58 clinics offering opioid agonist therapy in Ontario, Canada. One-year treatment retention was the primary outcome of interest and was measured for patients who did and did not have a cannabis positive urine sample in their first month of treatment, and as a function of the proportion of cannabis-positive urine samples throughout treatment. Results Our cohort consisted of 644 patients, 328 of which were considered baseline cannabis users and 256 considered heavy users. Patients with baseline cannabis use and heavy cannabis use were at increased risk of dropout (38.9% and 48.1%, respectively). When evaluating these trends by gender, only female baseline users and male heavy users are at increased risk of premature dropout. Interpretation Both baseline and heavy cannabis use are predictive of decreased treatment retention, and differences do exist between genders. With cannabis being legalized in the near future, physicians should closely monitor cannabis-using patients and provide education surrounding the potential harms of using cannabis while receiving treatment for opioid use disorder.
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p> OBJECTIVE: To investigate the prevalence of therapeutic cannabis use within a general population sample of adults and to describe various characteristics associated with use. METHODS: Data were derived from the 2013 and 2014 CAMH Monitor Survey of adults in Ontario, Canada. This repeated cross-sectional survey employed a regionally stratified design and utilized computer-assisted telephone interviewing. Analyses were based on 401 respondents who reported using cannabis. RESULTS: The data indicated that 28.8% of those who used cannabis in the past year self-reported using cannabis for therapeutic purposes. Of therapeutic users, 15.2% reported having medical approval to use cannabis for therapeutic purposes. Cannabis use for therapeutic purposes was associated with more frequent use of cannabis, a moderate to high risk of problematic cannabis use, and a greater likelihood of using prescription opioids for medical purposes. There was little difference in cannabis use for therapeutic purposes according to sex, age, and marital status after adjusting for opioid use and problematic cannabis use. CONCLUSION: Findings suggest some potential negative consequences of cannabis use for therapeutic purposes; however, further research is needed to better understand the range and patterns of use and their corresponding vulnerabilities.</p
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Background: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. Purpose: To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. Data sources: MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017. Study selection: Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes. Data extraction: Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria. Data synthesis: From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient. Limitation: Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily. Conclusion: Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects. Primary funding source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016033623).
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Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion: Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample “strongly agreed/agreed” that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% “strongly agreed/agreed” that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence.
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Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.
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Unlabelled: Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use. Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%). This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding. Perspective: This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management.
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Objectives: The objective this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in subjects with treatment-resistant chronic pain. Methods: The primary outcome was change in pain symptom score on the S-TOPS (Treatment Outcomes in Pain Survey - Short Form) questionnaire at 6 months follow-up in intent-to-treat (ITT) population. The secondary outcomes included change in S-TOPS physical, social and emotional disability scales, pain severity and pain interference on brief pain inventory (BPI), sleep problems, and change in opioid consumption. Results: 274 subjects were approved for treatment; complete baseline data were available for 206 (ITT), and complete follow-up data for 176 subjects. At follow-up, pain symptom score improved from median 83.3 (95% CI 79.2-87.5) to 75.0 (95% CI 70.8-79.2), P<0.001. Pain severity score (7.50 [95% CI 6.75-7.75] to 6.25 [95% CI 5.75-6.75] and pain interference score (8.14 [95% CI 7.28-8.43] to 6.71 [95% CI 6.14-7.14]) improved (both P<0.001), together with most social and emotional disability scores. Opioid consumption at follow-up decreased by 44% (P<0.001). Serious adverse effects led to treatment discontinuation in two subjects. Discussion: The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and significant reduction in opioid use. The results suggest long-term benefit of cannabis treatment in this group of patients, but the study's non-controlled nature should be considered when extrapolating the results.
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Background Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines. Methods We calculated defined daily doses for statistical purposes (S-DDD) per million inhabitants per day of opioid analgesics worldwide and for regions and countries from 2001 to 2013, and we used generalised estimating equation analysis to assess longitudinal change in use. We compared use data against the prevalence of some health disorders needing opioid use. We surveyed 214 countries or territories about impediments to availability of these medicines, and used regression analyses to establish the strength of associations between impediments and use. Findings The S-DDD of opioid analgesic use more than doubled worldwide between 2001–03 and 2011–13, from 1417 S-DDD (95% CI −732 to 3565; totalling about 3·01 billion defined daily doses per annum) to 3027 S-DDD (−1162 to 7215; totalling about 7·35 billion defined daily doses per annum). Substantial increases occurred in North America (16 046 S-DDD [95% CI 4032–28 061] to 31 453 S-DDD [8121–54 785]), western and central Europe (3079 S-DDD [1274–4883] to 9320 S-DDD [3969–14 672]), and Oceania (2275 S-DDD [763–3787] to 9136 S-DDD [2508–15 765]). Countries in other regions have shown no substantial increase in use. Impediments to use included an absence of training and awareness in medical professionals, fear of dependence, restricted financial resources, issues in sourcing, cultural attitudes, fear of diversion, international trade controls, and onerous regulation. Higher number of impediments reported was significantly associated with lower use (unadjusted incidence rate ratio 0·39 [95% CI 0·29–0·52]; p<0·0001), but not when adjusted for gross domestic product and human development index (0·91 [0·73–1·14]; p=0·4271). Interpretation Use of opioid analgesics has increased, but remains low in Africa, Asia, Central America, the Caribbean, South America, and eastern and southeastern Europe. Identified impediments to use urgently need to be addressed by governments and international agencies. Funding International Narcotics Control Board, UN.
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A large fraction of heroin users now report that they formerly used prescription opioids nonmedically, a finding that has led to restrictions on opioid prescribing. Nevertheless, only a small fraction of prescription-opioid users move on to heroin use.
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Aim: To analyze interrelationships in the consumption of opiates and cannabinoids in a legal regime and, specifically, whether consumers of opiates and cannabinoids treat them as substitutes for each other. Method: Econometric dynamic panel data models for opium consumption are estimated using the generalized method of moments (GMM). A unique dataset containing information about opiate (opium) consumption from the Punjab province of British India for the years 1907-1918 is analyzed (n=252) as a function of its own price, the prices of two forms of cannabis (the leaf (bhang), and the resin (charas, or hashish)), and wage income. Cross-price elasticities are examined to reveal substitution or complementarity between opium and cannabis. Results: Opium is a substitute for charas (or hashish), with a cross price elasticity (βˆ3) of 0.14 (p<0.05), but not for bhang (cannabis leaves; cross price elasticity=0.00, p>0.10). Opium consumption (βˆ1=0.47 to 0.49, p<0.01) shows properties of habit persistence consistent with addiction. The consumption of opium is slightly responsive (inelastic) to changes in its own price (βˆ2=-0.34 to -0.35, p<0.05 to 0.01) and consumer wages (βˆ1=0.15, p<0.05). Conclusion: Opium and hashish, a form of cannabis, are substitutes. In addition, opium consumption displays properties of habit persistence and slight price and wage income responsiveness (inelasticity) consistent with an addictive substance.
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Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Twenty-eight databases from inception to April 2015. Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], -0.46 [95% CI, -0.80 to -0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 [95% CI, -0.69 to -0.05]; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
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Prescription opioid abuse and addiction, along with consequences such as overdose death and increasing transition to heroin use, constitute a devastating public health problem in the United States. Increasingly it is clear that overprescription of these medications over the past two decades has been a major upstream driver of the opioid abuse epidemic. This commentary considers the factors that have led to overprescription of opioids by clinicians, discusses recent evidence casting doubt on the efficacy of opioids for treating chronic pain, and describes the ongoing efforts by federal and community stakeholders to address this epidemic. For example, supporting prescription drug monitoring programs and improved clinician training in pain management to help reduce the supply of opioids, increasing dissemination of evidence-based primary prevention programs to reduce demand for opioids, and expanding access to effective opioid agonist therapies and antagonist medications for both treatment and overdose prevention. Copyright © 2015. Published by Elsevier Inc.
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Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction. Expected final online publication date for the Annual Review of Public Health Volume 36 is March 18, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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There is increasing debate about cannabis use for medical purposes, including for symptomatic treatment of chronic pain. We investigated patterns and correlates of cannabis use in a large community sample of people who had been prescribed opioids for chronic non-cancer pain. The POINT study included 1514 people in Australia who had been prescribed pharmaceutical opioids for chronic non-cancer pain. Data on cannabis use, ICD-10 cannabis use disorder and cannabis use for pain were collected. We explored associations between demographic, pain and other patient characteristics and cannabis use for pain. One in six (16%) had used cannabis for pain relief, 6% in the previous month. A quarter reported that they would use it for pain relief if they had access. Those using cannabis for pain on average were younger, reported greater pain severity, greater interference from and poorer coping with pain, and more days out of role in the past year. They had been prescribed opioids for longer, were on higher opioid doses, and were more likely to be non-adherent with their opioid use. Those using cannabis for pain had higher pain interference after controlling for reported pain severity. Almost half (43%) of the sample had ever used cannabis for recreational purposes, and 12% of the entire cohort met criteria for an ICD-10 cannabis use disorder. Cannabis use for pain relief purposes appears common among people living with chronic non-cancer pain, and users report greater pain relief in combination with opioids than when opioids are used alone. Copyright © 2014. Published by Elsevier Ireland Ltd.
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The rapid acceleration of prescription opioid–related overdose deaths in the United States is correlated with the availability of stronger opioid medications, as well as a change in medical practice from withholding opioid medication because of dependence risk¹ to treating patients with chronic pain with opioids. Subsequently, the pendulum of concern has swung again, driven by the public health crisis of rising opioid analgesic addiction, overdose, and death. Opioid medications are problematic as a treatment for chronic pain. Opioid pharmaceuticals cause other adverse effects when used for long periods, such as tolerance, hyperalgesia, and gastrointestinal complications, making this class of drugs a poor choice for long-term use. As is well known, prescription opioids also have great abuse potential due to their influence on stress and reward circuits in the brain, promoting nonmedical use and abuse and diversion of prescription medications.
Article
Importance Overprescribing of opioids is considered a major driving force behind the opioid epidemic in the United States. Marijuana is one of the potential nonopioid alternatives that can relieve pain at a relatively lower risk of addiction and virtually no risk of overdose. Marijuana liberalization, including medical and adult-use marijuana laws, has made marijuana available to more Americans. Objective To examine the association of state implementation of medical and adult-use marijuana laws with opioid prescribing rates and spending among Medicaid enrollees. Design, Setting, and Participants This cross-sectional study used a quasi-experimental difference-in-differences design comparing opioid prescribing trends between states that started to implement medical and adult-use marijuana laws between 2011 and 2016 and the remaining states. This population-based study across the United States included all Medicaid fee-for-service and managed care enrollees, a high-risk population for chronic pain, opioid use disorder, and opioid overdose. Exposures State implementation of medical and adult-use marijuana laws from 2011 to 2016. Main Outcomes and Measures Opioid prescribing rate, measured as the number of opioid prescriptions covered by Medicaid on a quarterly, per-1000-Medicaid-enrollee basis. Results State implementation of medical marijuana laws was associated with a 5.88% lower rate of opioid prescribing (95% CI, −11.55% to approximately −0.21%). Moreover, the implementation of adult-use marijuana laws, which all occurred in states with existing medical marijuana laws, was associated with a 6.38% lower rate of opioid prescribing (95% CI, −12.20% to approximately −0.56%). Conclusions and Relevance The potential of marijuana liberalization to reduce the use and consequences of prescription opioids among Medicaid enrollees deserves consideration during the policy discussions about marijuana reform and the opioid epidemic.
Article
Importance Opioid-related mortality increased by 15.6% from 2014 to 2015 and increased almost 320% between 2000 and 2015. Recent research finds that the use of all pain medications (opioid and nonopioid collectively) decreases in Medicare Part D and Medicaid populations when states approve medical cannabis laws (MCLs). The association between MCLs and opioid prescriptions is not well understood. Objective To examine the association between prescribing patterns for opioids in Medicare Part D and the implementation of state MCLs. Design, Setting, and Participants Longitudinal analysis of the daily doses of opioids filled in Medicare Part D for all opioids as a group and for categories of opioids by state and state-level MCLs from 2010 through 2015. Separate models were estimated first for whether the state had implemented any MCL and second for whether a state had implemented either a dispensary-based or a home cultivation only–based MCL. Main Outcomes and Measures The primary outcome measure was the total number of daily opioid doses prescribed (in millions) in each US state for all opioids. The secondary analysis examined the association between MCLs separately by opioid class. Results From 2010 to 2015 there were 23.08 million daily doses of any opioid dispensed per year in the average state under Medicare Part D. Multiple regression analysis results found that patients filled fewer daily doses of any opioid in states with an MCL. The associations between MCLs and any opioid prescribing were statistically significant when we took the type of MCL into account: states with active dispensaries saw 3.742 million fewer daily doses filled (95% CI, −6.289 to −1.194); states with home cultivation only MCLs saw 1.792 million fewer filled daily doses (95% CI, −3.532 to −0.052). Results varied by type of opioid, with statistically significant estimated negative associations observed for hydrocodone and morphine. Hydrocodone use decreased by 2.320 million daily doses (or 17.4%) filled with dispensary-based MCLs (95% CI, −3.782 to −0.859; P = .002) and decreased by 1.256 million daily doses (or 9.4%) filled with home-cultivation–only-based MCLs (95% CI, −2.319 to −0.193; P = .02). Morphine use decreased by 0.361 million daily doses (or 20.7%) filled with dispensary-based MCLs (95% CI, −0.718 to −0.005; P = .047). Conclusions and Relevance Medical cannabis laws are associated with significant reductions in opioid prescribing in the Medicare Part D population. This finding was particularly strong in states that permit dispensaries, and for reductions in hydrocodone and morphine prescriptions.
Article
The United States remains gripped by the opioid crisis. Each day, 90 Americans die from opioid overdoses.¹ Owing to the incredible reach of the opioid crisis—it has affected people of every race, sex, and age across our country—many stakeholders are trying to combat the crisis using multipronged approaches emphasizing prevention, treatment, and law enforcement.
Article
Objectives: Use of various psychoactive substances can influence outcomes of patients on opioid agonist treatment (OAT). While use of alcohol and cocaine has shown to adversely affect OAT results, associated cannabis use shows mixed results. This study aimed to assess the pattern of cannabis use among opioid-dependent patients maintained on buprenorphine. Additionally, the study compared the dose of buprenorphine, opioid-related craving and withdrawals, productivity, and also quality of life between those with and without recent (past 90-day) cannabis use. Methods: We collected data on demographic and drug use details in 100 randomly selected adult male patients attending a community drug treatment clinic, who were stabilized on buprenorphine for more than 3 months. Other measures included scores on World Health Organization (WHO)-Alcohol, Smoking and Substance Involvement Screening Tool and WHO-Quality of Life-Brief (WHOQOL-Bref) version. Results: The average duration of maintenance treatment with buprenorphine was 96 months, with excellent compliance for buprenorphine (86.92 ± 9.58 days in 90 days). Thirty-five per cent had used cannabis in past 90 days, with lifetime use of cannabis in 77%. Participants using cannabis currently were on lower doses of buprenorphine (mean dose per day: 7.9 mg vs 8.9 mg; P = 0.04). Yet, there was no significant difference in the rates of opioid use or opioid withdrawals and craving between the 2 groups. Compliance to OAT, number of days of employment, daily earning, and WHOQOL-Bref scores in all domains were comparable between those with and without cannabis use. Duration of cannabis use, current use of alcohol, and dose of buprenorphine predicted current cannabis use in multivariable logistic regression analysis. Conclusions: Cannabis use does not negatively influence opioid outcomes among patients receiving buprenorphine maintenance treatment. There is no difference in productivity and quality of life between individuals maintained on buprenorphine with and without current cannabis use.
Article
Recent work finds that medical marijuana laws reduce the daily doses filled for opioid analgesics among Medicare Part-D and Medicaid enrollees, as well as population-wide opioid overdose deaths. We replicate the result for opioid overdose deaths and explore the potential mechanism. The key feature of a medical marijuana law that facilitates a reduction in overdose death rates is a relatively liberal allowance for dispensaries. As states have become more stringent in their regulation of dispensaries, the protective value generally has fallen. These findings suggest that broader access to medical marijuana facilitates substitution of marijuana for powerful and addictive opioids.
Article
Introduction: There is a substantial growth in the use of medical cannabis in recent years and with the aging of the population, medical cannabis is increasingly used by the elderly. We aimed to assess the characteristics of elderly people using medical cannabis and to evaluate the safety and efficacy of the treatment. Methods: A prospective study that included all patients above 65 years of age who received medical cannabis from January 2015 to October 2017 in a specialized medical cannabis clinic and were willing to answer the initial questionnaire. Outcomes were pain intensity, quality of life and adverse events at six months. Results: During the study period, 2736 patients above 65 years of age began cannabis treatment and answered the initial questionnaire. The mean age was 74.5 ± 7.5 years. The most common indications for cannabis treatment were pain (66.6%) and cancer (60.8%). After six months of treatment, 93.7% of the respondents reported improvement in their condition and the reported pain level was reduced from a median of 8 on a scale of 0-10 to a median of 4. Most common adverse events were: dizziness (9.7%) and dry mouth (7.1%). After six months, 18.1% stopped using opioid analgesics or reduced their dose. Conclusion: Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids. Gathering more evidence-based data, including data from double-blind randomized-controlled trials, in this special population is imperative.
Article
Background: Chronic pain is common in the United States and prescribed opioid analgesics use for noncancer pain has increased dramatically in the past two decades, possibly accounting for the current opioid addiction epidemic. Co-morbid drug use in those prescribed opioid analgesics is common, but there are few data on polysubstance use patterns. Objective: We explored patterns of use of cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain who were prescribed opioid analgesics. Methods: We conducted a secondary data analysis of screening interviews conducted as part of a parent randomized trial of financial incentives to improve HIV outcomes among drug users. In a convenience sample of people with HIV and chronic pain, we collected self-report data on demographic characteristics; pain; patterns of opioid analgesic use (both prescribed and illicit); cigarette, alcohol, and illicit drug use (including cannabis, heroin, and cocaine) within the past 30 days; and current treatment for drug use and HIV. Results: Almost half of the sample of people with HIV and chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%). Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis use was significantly associated with lower odds of prescribed opioid analgesic use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87). Conclusions/Importance: Our data suggest that new medical cannabis legislation might reduce the need for opioid analgesics for pain management, which could help to address adverse events associated with opioid analgesic use.
Article
Background: Historical shifts have taken place in the last twenty years in marijuana policy. The impact of medical marijuana laws (MML) on use of substances other than marijuana is not well understood. We examined the relationship between state MML and use of marijuana, cigarettes, illicit drugs, nonmedical use of prescription opioids, amphetamines, and tranquilizers, as well as binge drinking. Methods: Pre-post MML difference-in-difference analyses were performed on a nationally representative sample of adolescents in 48 contiguous U.S. states. Participants were 1,179,372U.S. 8th, 10th, and 12th graders in the national Monitoring the Future annual surveys conducted in 1991-2015. Measurements were any self-reported past-30-day use of marijuana, cigarettes, non-medical use of opioids, amphetamines and tranquilizers, other illicit substances, and any past-two-week binge drinking (5+ drinks per occasion). Results: Among 8th graders, the prevalence of marijuana, binge drinking, cigarette use, non-medical use of opioids, amphetamines and tranquilizers, and any non-marijuana illicit drug use decreased after MML enactment (0.2-2.4% decrease; p-values:<0.0001-0.0293). Among 10th graders, the prevalence of substance use did not change after MML enactment (p-values: 0.177-0.938). Among 12th graders, non-medical prescription opioid and cigarette use increased after MML enactment (0.9-2.7% increase; p-values: <0.0001-0.0026). Conclusions: MML enactment is associated with decreases in marijuana and other drugs in early adolescence in those states. Mechanisms that explain the increase in non-medical prescription opioid and cigarette use among 12th graders following MML enactment deserve further study.
Article
Objectives: To examine the association between Colorado's legalization of recreational cannabis use and opioid-related deaths. Methods: We used an interrupted time-series design (2000-2015) to compare changes in level and slope of monthly opioid-related deaths before and after Colorado stores began selling recreational cannabis. We also describe the percent change in opioid-related deaths by comparing the unadjusted model-smoothed number of deaths at the end of follow-up with the number of deaths just prior to legalization. Results: Colorado's legalization of recreational cannabis sales and use resulted in a 0.7 deaths per month (b = -0.68; 95% confidence interval = -1.34, -0.03) reduction in opioid-related deaths. This reduction represents a reversal of the upward trend in opioid-related deaths in Colorado. Conclusions: Legalization of cannabis in Colorado was associated with short-term reductions in opioid-related deaths. As additional data become available, research should replicate these analyses in other states with legal recreational cannabis.
Article
Introduction: Adults in Medication-Assisted Treatment (MAT) for opioid addiction are at risk for substance use relapse and opioid overdose. They often have high rates of cannabis use and comorbid symptoms of pain, depression, and anxiety. Low levels of self-efficacy (confidence that one can self-manage symptoms) are linked to higher symptom burdens and increased substance use. The effects of cannabis use on symptom management among adults with MAT are currently unclear. Therefore, the primary purpose of this study is to examine whether cannabis use moderates the relationships between pain and negative affect (i.e., depression and anxiety) and whether self-efficacy influences these interactions. Methods: A total of 150 adults receiving MAT and attending one of two opioid treatment program clinics were administered a survey containing measures of pain, depression, anxiety, self-efficacy, and cannabis use. Results: Cannabis use frequency moderated the relationships between pain and depression as well as pain and anxiety. Specifically, as cannabis use frequency increased, the positive relationships between pain and depression and pain and anxiety grew stronger. However, cannabis use was no longer a significant moderator after controlling for self-efficacy. Conclusions: Results suggest that cannabis use strengthens, rather than weakens, the relationships between pain and depression and pain and anxiety. These effects appear to be driven by decreased self-efficacy in cannabis users. It is important to understand how self-efficacy can be improved through symptom self-management interventions and whether self-efficacy can improve distressing symptoms for people in MAT.
Article
Objectives: To determine whether specific state legislation has an effect on opioid overdose mortality rates compared to states without those types of legislation. Design: Ecological study estimating opioid-related mortality in states with and without a prescription drug monitoring program (PDMP) and/or medical cannabis legislation. Setting and participants: Opioid-related mortality rates for 50 states and Washington DC from 2011 to 2014 were obtained from CDC WONDER. PDMP data were obtained from the National Alliance for Model State Drug Laws, and data on medical cannabis legislation from the National Organization for the Reform of Marijuana Laws. Main outcomes and measures: The relationship between PDMPs with mandatory access provisions, medical cannabis legislation, and opioid-related mortality rates. Methods: Multivariate repeated measures analysis performed with software and services. Results: Medical cannabis laws were associated with an increase of 21.7 percent in mean age-adjusted opioid-related mortality (p < 0.0001). PDMPs were associated with an increase of 11.4 percent in mean age-adjusted opioid-related mortality (p = 0.005). For every additional year since enactment, mean age-adjusted opioid-related mortality rate increased by 1.7 percent in states with medical cannabis (p = 0.049) and 5.8 percent for states with a PDMP (p = 0.005). Interaction between both types of legislation produced a borderline significant decrease of 10.1 percent (p = 0.055). For every year states had both types of legislation, interaction resulted in a 0.6 percent decrease in rate (p = 0.013). Conclusion: When combined with the availability of medical cannabis as an alternative analgesic therapy, PDMPs may be more effective at decreasing opioid-related mortality.
Article
Background: High rates of depression and anxiety have been consistently reported among patients suffering from chronic pain. Prescription opioids are one of the most common modalities for pharmacological treatment of pain, however in recent years medical marijuana(MM) has been increasingly used for pain control in the US and in several countries worldwide. The aim of this study was to compare levels of depression and anxiety among pain patients receiving prescription opioids and MM. Methods: Participants were patients suffering from chronic pain treated with prescription opioids (OP,N=474), MM (N=329) or both (OPMM,N=77). Depression and anxiety were assessed using the depression module of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7). Results: Prevalence of depression among patients in the OP, MM and OPMM groups was 57.1%, 22.3% and 51.4%, respectively and rates of anxiety were 48.4%, 21.5% and 38.7%, respectively. After controlling for confounders, patients in the OP group were significantly more likely to screen positive for depression (Adjusted Odds Ratio(AOR)=6.18;95%CI=4.12-9.338) and anxiety(AOR=4.12;CI=3.84-5.71)) compared to those in the MM group. Individuals in the OPMM group were more prone for depression (AOR for depression=3.34;CI=1.52-7.34)) compared to those in the MM group. Limitations: Cross-sectional study, restricting inference of causality. Conclusions: Levels of depression and anxiety are higher among chronic pain patients receiving prescription opioids compared to those receiving MM. Findings should be taken into consideration when deciding on the most appropriate treatment modality for chronic pain, particularly among those at risk for depression and anxiety.
Article
Introduction Cannabis is increasingly being used in the treatment of chronic pain. However, there is a lack of available research in the population of patients with chronic pain who are using cannabis. The current study examines clinical and treatment characteristics for patients who are admitted to a 3-week outpatient interdisciplinary chronic pain rehabilitation program. Method Participants (N = 48) included patients with a positive urine drug screen for 9-carboxy-tetrahydrocannabinol (THC(+); n = 24) and a matched comparison sample of patients with a negative screen (THC(−); n = 24). Participants were matched for age, gender, race, education, and current prescription opioid use. Measures of pain, functioning, and quality of life were completed at admission and discharge. Medical chart review was conducted to assess medication and substance use history. Results Participants with a positive screen for THC were more likely to report a past history of illicit substance use, alcohol abuse, and current tobacco use. Cannabis use was not associated with a significantly lower morphine equivalence level for participants using prescription opioids (n = 14). Both groups of participants reported significant improvement in pain severity, pain interference, depressive symptoms, and pain catastrophizing. There were no group- or treatment-related differences in these outcome variables. Discussion Results provide preliminary evidence that patients with chronic pain using cannabis may benefit from an interdisciplinary chronic pain program. Patients with chronic pain using cannabis may be at higher risk for substance-related negative outcomes, although more research is needed to understand this relationship.
Article
Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% CI 1.95, 6.76; n=6) than the ED50 of morphine alone. In addition, the ED50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED50 of codeine alone. One case series (n=3) provided very low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, while one of the nine clinical studies identified provided very low-quality evidence of such an effect. Prospective high-quality controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.
Article
Objectives: Twenty-eight states in the U.S have legalized medical marijuana, yet its impacts on severe health consequences such as hospitalizations remain unknown. Meanwhile, the prevalence of opioid pain reliever (OPR) use and outcomes has increased dramatically. Recent studies suggested unintended impacts of legalizing medical marijuana on OPR, but the evidence is still limited. This study examined the associations between state medical marijuana policies and hospitalizations related to marijuana and OPR. Methods: State-level annual administrative records of hospital discharges during 1997-2014 were obtained from the State Inpatient Databases (SID). The outcome variables were rates of hospitalizations involving marijuana dependence or abuse, opioid dependence or abuse, and OPR overdose in 1000 discharges. Linear time-series regressions were used to assess the associations of implementing medical marijuana policies to hospitalizations, controlling for other marijuana- and OPR-related policies, socioeconomic factors, and state and year fixed effects. Results: Hospitalizations related to marijuana and OPR increased sharply by 300% on average in all states. Medical marijuana legalization was associated with 23% (p=0.008) and 13% (p=0.025) reductions in hospitalizations related to opioid dependence or abuse and OPR overdose, respectively; lagged effects were observed after policy implementation. The operation of medical marijuana dispensaries had no independent impacts on OPR-related hospitalizations. Medical marijuana polices had no associations with marijuana-related hospitalizations. Conclusion: Medical marijuana policies were significantly associated with reduced OPR-related hospitalizations but had no associations with marijuana-related hospitalizations. Given the epidemic of problematic use of OPR, future investigation is needed to explore the causal pathways of these findings.
Article
Background: In 2014 Health Canada replaced the Marihuana for Medical Access Regulations (MMAR) with the Marihuana for Medical Purposes Regulations (MMPR). One of the primary changes in the new program has been to move from a single Licensed Producer (LP) of cannabis to multiple Licensed Producers. This is the first comprehensive survey of patients enrolled in the MMPR. Methods: Patients registered to purchase cannabis from Tilray, a federally authorized Licenced Producer (LP) within the MMPR, were invited to complete an online survey consisting of 107 questions on demographics, patterns of use, and cannabis substitution effect. The survey was completed by 271 respondents. Results: Cannabis is perceived to be an effective treatment for diverse conditions, with pain and mental health the most prominent. Findings include high self-reported use of cannabis as a substitute for prescription drugs (63%), particularly pharmaceutical opioids (30%), benzodiazepines (16%), and antidepressants (12%). Patients also reported substituting cannabis for alcohol (25%), cigarettes/tobacco (12%), and illicit drugs (3%). A significant percentage of patients (42%) reported accessing cannabis from illegal/unregulated sources in addition to access via LPs, and over half (55%) were charged to receive a medical recommendation to use cannabis, with nearly 25% paying $300 or more. Conclusion: The finding that patients report its use as a substitute for prescription drugs supports prior research on medical cannabis users; however, this study is the first to specify the classes of prescription drugs for which cannabis it is used as a substitute, and to match this substitution to specific diagnostic categories. The findings that some authorized patients purchase cannabis from unregulated sources and that a significant percentage of patients were charged for medical cannabis recommendations highlight ongoing policy challenges for this federal program.
Article
Background and aims: In the United States, overdose deaths attributed to opioid pain relievers (OPR) have quadrupled since 1999, prompting many states to adopt Prescription Drug Monitoring Programs (PMP). This study aimed to 1) estimate the relationship of PMP strength with OPR overdose deaths across states and over time; 2) measure what threshold in PMP strength is associated with the greatest reduction in OPR overdose; and 3) assess the relationship of medical marijuana dispensaries with OPR overdose deaths. Design: Panel data from the Centres for Disease Control and Prevention's (CDC's) Wide-ranging Online Data for Epidemiologic Research database (WONDER) were analyzed using fixed effects to regress state-year death rates on an index variable compiled from the Prescription Drug Abuse Policy System (PDAPS) while controlling for PMP administration, demographic factors and laws that might affect OPR overdose. Setting and participants: Age-adjusted opioid overdose death rates for all fifty states and the District of Columbia between 1999 and 2014 for a total of 816 observations. Measurements: PMP strength was calculated using legal data compiled by the Prescription Drug Abuse Policy System (PDAPS). In addition to demographic controls, other covariates included laws that regulate pain clinics, access to naloxone, use of emergency services (Good Samaritan Laws), and medical marijuana. Findings: PMP strength was negatively associated with OPR overdose deaths. For every one point increase in PMP strength was associated with a 1% (95%CI = 0.2-2%) reduction in overdose deaths. When collapsed into quartiles, PMPs in the third quartile were associated with an approximately 18% (95%CI = 1.6-29%) reduction in OPR overdose death rates compared with states absent a PMP. States with medical marijuana dispensaries reported a 16% (95%CI = 1-30%) reduction in OPR overdoses. Conclusions: US states that have more robust prescription drug monitoring programs (PMPs) have fewer prescription opioid overdose deaths than states with weaker PMPs. States with medical marijuana dispensaries also report fewer opioid overdose deaths than states without these.
Article
Objectives: To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use. Methods: We analyzed 1999-2013 Fatality Analysis Reporting System (FARS) data from 18 states that tested for alcohol and other drugs in at least 80% of drivers who died within 1 hour of crashing (n = 68 394). Within-state and between-state comparisons assessed opioid positivity among drivers crashing in states with an operational MML (i.e., allowances for home cultivation or active dispensaries) versus drivers crashing in states before a future MML was operational. Results: State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML, although none of these estimates were significant. When we combined states, we observed no significant overall association (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.61, 1.03). However, age-stratified analyses indicated a significant reduction in opioid positivity for drivers aged 21 to 40 years (OR = 0.50; 95% CI = 0.37, 0.67; interaction P < .001). Conclusions: Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose. (Am J Public Health. Published online ahead of print September 15, 2016: e1-e6. doi:10.2105/AJPH.2016.303426).
Article
Background: This study examined poly-drug use involving the use of cannabis with nonmedical prescription pain reliever use (NMPR) and alcohol use. Methods: Computer-assisted survey data from the National Survey on Drug Use and Health were examined. The NSDUH is an annual, cross-sectional survey of non-institutionalized citizens in the United States (ages 12+). Replicate analyses were conducted using the 2013 and 2003 survey waves. Results: Higher levels of cannabis use were consistently associated with more frequent consumption of prescription pain relievers, with findings replicating in both 2013 and 2003. While the prevalence of dual users declined from 2003 (2.5%) to 2013 (2.3%), the average number of days used among dual users increased by an average of 20 days over that period. These changes largely occurred among those aged 35 or older, males, whites, and non-illicit drug users. Past-year marijuana use increased by 16% (10.8-12.6%, p-value<.001) whereas NMPR decreased by 15% (4.9-4.2%, p-value<.001). The largest changes occurred after 2011. Persons using the most cannabis generally had higher levels of alcohol use relative to those using the least amount of cannabis. There was a significant increase in the prevalence of dual use between 2003 (10.2%) and 2013 (11.6%), while the prevalence of past-year alcohol use remained relatively stable. Conclusions: Clinical efforts and public health interventions should consider the possible co-ingestion of cannabis with NMPR and alcohol, as concomitant use may portend negative health effects in the short and long-term.
Article
Significance Midlife increases in suicides and drug poisonings have been previously noted. However, that these upward trends were persistent and large enough to drive up all-cause midlife mortality has, to our knowledge, been overlooked. If the white mortality rate for ages 45−54 had held at their 1998 value, 96,000 deaths would have been avoided from 1999–2013, 7,000 in 2013 alone. If it had continued to decline at its previous (1979‒1998) rate, half a million deaths would have been avoided in the period 1999‒2013, comparable to lives lost in the US AIDS epidemic through mid-2015. Concurrent declines in self-reported health, mental health, and ability to work, increased reports of pain, and deteriorating measures of liver function all point to increasing midlife distress.
Article
Background: Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. Methods: Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30mgqid. Double-blind placebo substitutions occurred for 21h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. Results: Dronabinol 40mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). Conclusion: Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal.
Article
Clinical, experimental, and ethnographic research suggests that cannabis may be used to help manage pain. Ethnographic research has revealed that some people are using cannabis to temper their illicit opioid use. We seek to learn if there is an association between cannabis use and the frequency of nonmedical opioid use among people who inject drugs (PWID). PWID were recruited using targeted sampling methods in Los Angeles and San Francisco, California, 2011-2013. We limited analysis to people who used opioids in past 30 days (N=653). number of times used any opioids non-medically in past 30 days. Explanatory variable: any cannabis use past 30 days. multivariable linear regression with a log-transformed outcome variable. About half reported cannabis use in the past 30 days. The mean and median number of times using opioids in past 30 days were significantly lower for people who used cannabis than those who did not use cannabis (mean: 58.3 vs. 76.4 times; median: 30 vs 60 times, respectively; p<0.003). In multivariable analysis, people who used cannabis used opioids less often than those who did not use cannabis (Beta: -0.346; 95% confidence interval: -0.575, -0.116; p<0.003). There is a statistical association between recent cannabis use and lower frequency of nonmedical opioid use among PWID. This may suggest that PWID use cannabis to reduce their pain and/or nonmedical use of opioids. However, more research, including prospective longitudinal studies, is needed to determine the validity of these findings. Copyright © 2015. Published by Elsevier Ireland Ltd.
Article
To support medication development with cannabinoids, smoked cannabis has been said to alleviate symptoms of opioid withdrawal. We evaluated that hypothesis. We analyzed data from the methadone-taper phase of a clinical trial we had conducted. Participants were 116 outpatient heroin and cocaine users (of whom 46 were also cannabis users) who stayed for the 10-week taper. Main outcome measures were weekly urine screens for cannabinoids, plus every-two-week assessments of opioid-withdrawal symptoms. Opioid-withdrawal scores did not differ overall between users and nonusers of cannabis. In a lagged analysis in the 46 users, there was a slight (not statistically significant) indication that weeks of higher opiate-withdrawal symptoms preceded weeks of cannabis use (effect-size r = .20, 95% CI -.10 to .46, p = .52). Even if this finding is taken to suggest self-medication with cannabis, a lagged analysis in the other temporal direction showed no indication that cannabis use predicted lower opiate-withdrawal symptoms the next week (effect-size r = .01, 95% CI -.28 to .30, p = .69). These findings persisted in sensitivity analyses controlling for each of 17 potential confounds. With our findings, the clinical evidence for smoked cannabis as a reducer of opioid-withdrawal symptoms moves slightly further from "inconclusive" or "mixed" and closer to negative, at least in the context of a methadone dose taper like the one used here. This finding may remove one rationale for medication development using cannabinoids to treat opioid withdrawal, but leaves other rationales intact. (Am J Addict 2015;XX: XX-XX). Copyright © American Academy of Addiction Psychiatry.
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To the Editor Bachhuber et al¹ found that states with legalized medical marijuana and those that had longer periods of legalized medical marijuana had lower adjusted opioid analgesic mortality rates than those that did not. Although they acknowledged that mechanisms underlying these relationships are speculative, the one receiving the most attention was that medical marijuana may reduce patients’ reliance on opioid pain medications, thereby reducing their mortality risk. The authors noted that one limitation of their analyses was that they were “ecologic” (ie, linking state-level variables), so they “cannot adjust for characteristics of individuals within the states….”¹(p1671) We would suggest that the primary drawback of the ecologic analyses is that they provide no information whether individual pain patients who use marijuana have a lower or higher opioid analgesic mortality risk.
Article
Importance Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.Objective To determine the association between the presence of state medical cannabis laws and opioid analgesic overdose mortality.Design, Setting, and Participants A time-series analysis was conducted of medical cannabis laws and state-level death certificate data in the United States from 1999 to 2010; all 50 states were included.Exposures Presence of a law establishing a medical cannabis program in the state.Main Outcomes and Measures Age-adjusted opioid analgesic overdose death rate per 100 000 population in each state. Regression models were developed including state and year fixed effects, the presence of 3 different policies regarding opioid analgesics, and the state-specific unemployment rate.Results Three states (California, Oregon, and Washington) had medical cannabis laws effective prior to 1999. Ten states (Alaska, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Rhode Island, and Vermont) enacted medical cannabis laws between 1999 and 2010. States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate (95% CI, −37.5% to −9.5%; P = .003) compared with states without medical cannabis laws. Examination of the association between medical cannabis laws and opioid analgesic overdose mortality in each year after implementation of the law showed that such laws were associated with a lower rate of overdose mortality that generally strengthened over time: year 1 (−19.9%; 95% CI, −30.6% to −7.7%; P = .002), year 2 (−25.2%; 95% CI, −40.6% to −5.9%; P = .01), year 3 (−23.6%; 95% CI, −41.1% to −1.0%; P = .04), year 4 (−20.2%; 95% CI, −33.6% to −4.0%; P = .02), year 5 (−33.7%; 95% CI, −50.9% to −10.4%; P = .008), and year 6 (−33.3%; 95% CI, −44.7% to −19.6%; P < .001). In secondary analyses, the findings remained similar.Conclusions and Relevance Medical cannabis laws are associated with significantly lower state-level opioid overdose mortality rates. Further investigation is required to determine how medical cannabis laws may interact with policies aimed at preventing opioid analgesic overdose.