Article critique

Cannabis Use and Risk of Prescription Opioid Use Disorder in the United States Mark Olfson, M.D., M.P.H., Melanie M. Wall, Ph.D., Shang-Min Liu, M.S., Carlos Blanco, M.D., Ph.D.

Objective: The authors sought to determine whether can- nabis use is associated with a change in the risk of incident nonmedical prescription opioid use and opioid use disorder at 3-year follow-up.

Method: The authors used logistic regression models to assess prospective associations between cannabis use at wave 1 (2001–2002) and nonmedical prescription opioid use and prescription opioid use disorder at wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Corresponding analyses were performed among adults with moderate or more severe pain and with non- medical opioid use at wave 1. Cannabis and prescription opioid use were measured with a structured interview (the Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV version). Other covariates included age, sex, race/ethnicity, anxiety or mood disorders, family history of drug, alcohol, and behavioral problems, and, in opioid use disorder analyses, nonmedical opioid use.

Results: In logistic regression models, cannabis use at wave 1 was associated with increased incident nonmedical prescription

opioid use (odds ratio=5.78, 95% CI=4.23–7.90) and opioid use disorder (odds ratio=7.76, 95% CI=4.95–12.16) at wave 2. These associations remained significant after adjustment for background characteristics (nonmedical opioid use: ad- justed odds ratio=2.62, 95% CI=1.86–3.69; opioid use dis- order: adjusted odds ratio=2.18, 95% CI=1.14–4.14). Among adults with pain at wave 1, cannabis use was also associated with increased incident nonmedical opioid use (adjusted odds ratio=2.99, 95% CI=1.63–5.47) at wave 2; it was also associated with increased incident prescription opioid use disorder, although the association fell short of significance (adjusted odds ratio=2.14, 95% CI=0.95–4.83). Among adults with nonmedical opioid use at wave 1, cannabis use was also associated with an increase in nonmedical opioid use (ad- justed odds ratio=3.13, 95% CI=1.19–8.23).

Conclusions: Cannabis use appears to increase rather than decrease the risk of developing nonmedical prescription opioid use and opioid use disorder.

Am J Psychiatry 2018; 175:47–53; doi: 10.1176/appi.ajp.2017.17040413

After more than two decades of increasing prevalence of prescriptionopioidusedisorderintheUnitedStates(1,2),the number of people in the U.S. population with prescription opioidusedisordersreached2millionin2015(3).Risingrates of prescription opioid use disorder have coincided with the largestepidemicofopioidoverdosedeathsinU.S.history.In2015, unintentional drug overdose deaths, most of which involved opioids, claimed over 47,000 lives (4). The crisis in nonmedical use of prescription opioids, which has exacted a heavy burden not only on individuals but also on their families and communi- ties, has prompted federal policy makers to consider prescrip- tion opioid use disorder a threat to public health (5).

In the wake of rising rates of nonmedical prescription opioid use, there has been increased public (6) and pro- fessional (7) interest in the possibility that cannabis might help to curb or prevent opioid use disorder. Support comes from two widely publicized ecological analyses indicating

that compared with states that do not permit medical mari- juana, annual death rates due to opioid overdoses were nearly one-quarter lower in states that do permit medical marijuana (8, 9). Significant reductions in opioid prescribing have also been reported following passage of medical marijuana laws (10). Such ecologic analyses, however, provide no information on whether individual patients who use cannabis have a lower or higher risk of developing opioid use disorders (11).

The possibility that cannabis lowers the risk of opioid- related morbidity has fueled speculation concerning potential mechanisms. A leading hypothesis is that cannabis use tends to lower opioid use and risk of opioid use disorder through increased control of pain (8, 12). A recent meta-analysis of randomized controlled trials provides a moderate level of ev- idence that cannabinoids improve some forms of chronic pain (13). AlargeDutch study reportedthat just overhalf ofadults in registered cannabis programs also received prescriptions for

See related features: Editorial by Dr. McCarty (p. 6), Clinical Guidance (Table of Contents), and AJP Audio (online)

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ARTICLES

pain medications, suggesting that medical marijuana is frequently used for pain control (14). In a small, uncontrolled cross-sectional survey of medical marijuana users with chronic pain recruited from a cannabis dispensary, cannabis use was associated with a 64%declineinopioiduse(N=118)(12).Cannabisexposurehasalso been associated with increased analgesia among opioid-treated patients with chronic pain (15), suggesting that cannabis may potentiate antinociceptive effects of opioids, permitting lower and presumably safer opioid dosing to achieve comparable analgesia.

Much remains to be learned about the association be- tween cannabis use and nonmedical prescription opioid use or opioid use disorders. No prospective epidemiological or clinical studies have demonstrated that cannabis use reduces use of opioids. Moreover, epidemiologic research suggests that cannabis may actually increase the risk of other drug use disorders, including opioids. A retrospective Australian twin study reported that early initiation of cannabis use was associated with increased risks of other drug use and abuse/dependence, including opioid use and opioid abuse/ dependence (16). Prospective epidemiological research fur- thersuggeststhatcannabisuseisariskfactorforotherdruguse disorders (17). However, prospectiveepidemiological research has not previously examined the specific association between cannabisuseandnonmedicalprescriptionopioiduse oropioid use disorder to inform clinical practice and policy.

We sought to address this critical gap in knowledge with prospective data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a large, na- tionally representative sample. We examined the association between cannabis use and incident nonmedical prescription opioid use and disorder 3 years later, after adjusting for several relevant demographic and clinical covariates. We also evalu- ated whether cannabis use among adults with nonmedical prescription opioid use was associated with a subsequent decrease in nonmedical opioid use.

METHOD

Sample The 2001–2002 NESARC (wave 1), and the 2004–2005 follow- up (wave 2) is a nationally representative sample of the non- institutionalized adult U.S. population conducted by the U.S. Census Bureau under the direction of the National Institute on Alcoholism and Alcohol Abuse (18, 19). The response rate for wave 1 was 81.0%. Excluding ineligible respondents (e.g., those who were deceased), the wave 2 response rate was 86.7%, re- sulting in a cumulative response rate of 70.2% (N=34,653). Wave 2 NESARC weights include adjustments for nonresponse, de- mographic factors, and psychiatric diagnoses to ensure that the wave 2 sample approximated the target population, which was the original sample minus attrition between the two waves (18).

Assessment All diagnoses were made according to DSM-IV criteria, using the Alcohol Use Disorder and Associated Disabilities Interview Schedule–DSM-IV version (AUDADIS-IV) for

waves 1 and 2 (20). Consistent with previous reports, nonmedical use of a prescription opioid was defined as using a prescription analgesic “without a prescription, in greater amounts,more often,orlongerthanprescribed, orfor a reason other than a doctor said you should use them” during the 12 months preceding the interview. More than 30 symptom items were used by the AUDADIS-IV to define 12-month prescription opioiduse disorder according to DSM-IVcriteria.TheNESARC also collected information for other substance use disorders (nicotine dependence, alcohol use disorder, and drug use dis- orders, including other prescription drug use disorders). The reliability of the AUDADIS-IV prescription opioiduse questions (kappa=0.66) and associated substance use disorder diagnoses (kappa=0.53–0.84) are well documented in several psycho- metricstudies,includinginclinical(20)andgeneralpopulation (21) samples. Further concurrent and predictive validity of the prescription opioid use disorder diagnosis has been documented by increased risk of related psychopathology, impairment, and probability of seeking treatment (22).

Thefrequencyofpast-yearcannabisusewasassessedwith an 11-level item ranging from no use in the past 12 months to use every day in the past 12 months. Cannabis use was col- lapsed into a four-level variable including no use in the past last 12 months, occasional use (at least once a year but less than once a month), frequent use (from once a month or more to twice a week), and very frequent use (from three times a week to every day) (23). A similar four-level scale was de- veloped for past-year prescription opioid use.

Mood disorders included DSM-IV major depressive dis- order, dysthymia, bipolar I disorder, and bipolar II disorder. Anxiety disorders included DSM-IV panic disorder, social anxiety disorder, specific phobia, and generalized anxiety disorder. Test-retest reliabilities for AUDADIS-IV mood, anx- iety, and personality disorders in the noninstitutionalized population and clinical settings have been found to be fair to good. The criterion validity of mood and substance use dis- orders with psychiatrist reappraisal has also been found to be good to excellent (kappa values, 0.64–0.83) (24). Family his- tories of alcohol use disorder, drug use disorders, depression, and antisocial personality disorder referred to first-degree relatives. The test-retest reliability of AUDADIS family history variables has been shown to be very good to excellent (25).

Pain was assessed using the pain item of the Medical Outcomes Study 12-Item Short Form Health Survey, Version 2 (SF-12) (26), a valid measure that is commonly used in population surveys (27). The pain item uses a 5-point scale (not at all,a little bit, moderately,quitea bit,and extremely) to measure the degree to which pain interferes with daily ac- tivities during the past 4 weeks (28). The pain measure was collapsed into two levels depending on whether pain was associated with no or little interference (“no pain”), or with moderate to extreme interference (“pain”) (29).

Statistical Analysis Wave 1 descriptive demographic and clinical characteristics were compared between individuals with and without any

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cannabis use in the year before the wave 1 interview. Group differenceswereevaluatedwithchi-squareorttests.Unadjusted percentages of respondents with wave 2 incident opioid use disorders were determined by frequency of wave 1 cannabis use.

Separate logistic regression models were fitted with non- medical opioid use and disorder outcomes at wave 2 predicted by past-year cannabis use at wave 1. To differentiate between prevalent and incident opioid outcomes at wave 2, we de- fined four outcomes: 1) prevalent nonmedical opioid use, defined as any nonmedical opioid use since the wave 1 in- terview; 2) incident nonmedical opioid use, defined as any nonmedical opioid use since wave 1, restricted to respon- dents with no lifetime nonmedical opioid use at wave 1; 3) prevalent prescription opioid use disorder, defined as meeting opioid use disorder criteria since wave 1; and 4) incident prescriptionopioidusedisorder, defined as meetingopioiduse disorder criteria since wave 1, restricted to respondents with no lifetimeopioiduse disorder at wave 1. Results arepresented as unadjusted odds ratios and adjusted odds ratios controlling for age, sex, race/ethnicity, family history variables, antisocial personality disorder, and other substance use disorders and mood or anxiety disorders at wave 1 (29). Adjusted models of wave 2 opioid use disorder also controlled for wave 1 past-year nonmedical opioid use. Regressions were fitted among the overall population of NESARC wave 1 and 2 respondents and then repeated, as a sensitivity analysis, among respondents without wave 1 past-year cannabis use disorders and among respondents with moderate or more severe pain impairment.

We further examined whether, among respondents with wave 1 past-year nonmedical opioid use, cannabis use was associated with an increase or decrease in the level of opioid use at wave 2. A separate logistic regression was fitted for respondents with wave 1 opioid use and moderate or more severe pain. All analyses were performed using SUDAAN to take into account the complex design features of the NESARC.

RESULTS

Background CharacteristicsofAdultsWho UseCannabis At wave 1, individuals with any past-year cannabis use were youngeronaveragethanthosewithoutcannabisuse,morelikely tobemale,andmorelikelytohavepast-yearopioidusedisorder, cannabis use disorder, other substance use disorders, or any past-yearmoodoranxietydisorder.Theywerealsosignificantly morelikelytohaveafamilyhistoryofalcoholusedisorders,drug use disorders, depression, and antisocial personality disorder. The two groups did not differ significantly with respect to the proportion who reported moderate or more severe pain during the month before the wave 1 interview (Table 1).

Prospective Associations Between Cannabis Use and Nonmedical Prescription Opioid Use Withintheoverallsurveypopulation,cannabisuseatwave1was associated with a significant increase in the odds of prevalent nonmedicalprescriptionopioiduseduringthefollow-upperiod (Table 2). After adjustment for the background demographic

and clinical characteristics, a strong association persisted be- tween wave 1 cannabis use and wave 2 prevalent nonmedical opioid use. These associations were also observed among adults without past-year cannabis use disorder and among adults with moderate or more severe pain at wave 1. Among individuals without nonmedical opioid use during the 12 months before the wave 1 interview, there was a significant association between cannabis use at wave 1 and incident nonmedical opioid use during the follow-up period. This association was also observed among adults without cannabis use disorder at wave 1 and among adults with moderate or more severe pain at wave 1.

In analyses restricted to individuals with past-year non- medical opioid use, in unadjusted and adjusted regressions, wave 1 cannabis use was significantly associated with an in- creaseinthelevelofopioiduseduringtheyearbeforethewave 2 interview. Cannabis use was also associated with lower odds of decreasing the level of opioid use. When the sample was further restricted to adults with wave 1 nonmedical opioid use and moderate or more severe pain, wave 1 cannabis use was associated with lower unadjusted odds of decreasing opioid use, although the other regressions did not yield significant associations. Among individuals with nonmedical opioid use at wave 1 who either used or did not use cannabis, however, decreasesinopioiduseatwave2weremarkedlymorecommon than increases in opioid use (Table 3).

Prospective Associations Between Cannabis Use and Prescription Opioid Use Disorder In unadjusted analyses, the percentage of adults who de- velopedanew-onsetopioidusedisorderduringthefollow-up period was lowest for individuals who did not use cannabis in the year before the wave 1 interview (0.51%), followed by occasional cannabis users (2.86%), frequent cannabis users (4.30%), and very frequent cannabis users (4.43%) (Figure 1).

In the overall survey population, cannabis use at wave 1 was associated with a significant increase in the odds of prevalent and incident prescription opioid use disorder during the follow-up period (Table 4). After adjustment for the background demographic and clinical covariates, in- cluding wave 1 nonmedical opioid use, significant associa- tions persisted between wave 1 cannabis use and prevalent as well as incident nonmedical opioid use disorder at wave 2. A similar association was observed among adults without past-year cannabis use disorders and prevalent opioid use disorder, although the association with incident opioid use disorder fell below the level of statistical significance. Among adults with moderate or more severe pain at wave 1, cannabis use was associated with prevalent and incident opioid use disorders in unadjusted analyses and with prevalent opioid use disorder in adjusted analyses (Table 4).

DISCUSSION

In a nationally representative sample of adults evaluated at waves 3 years apart, cannabis use was strongly associated with subsequent onset of nonmedical prescription opioid use

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and opioid use disorder. These results remained robust after controlling for the potentially confounding effects of several demographic and clinical covariates that were strongly as- sociated with cannabis use. The association of cannabis use with the development of nonmedical opioid use was evident among adults without cannabis use disorders and among

adultswithmoderate ormoreseverepain.Among adultswith nonmedical prescription opioid use, cannabis use was asso- ciated with an increase in the level of nonmedical prescription opioid use at follow-up.

An independent prospective association between canna- bis use and onset of prescription opioid use disorder extends

TABLE 2. Prospective Associations of Wave 1 Cannabis Use and Wave 2 Prevalent and Incident Nonmedical Prescription Opioid Use in the NESARCa

Wave 1 Past-Year Cannabis Use Predicting: N in

Analysis Odds Ratio 95% CI Adjusted

Odds Ratiob 95% CI

Overall population Wave 2 prevalent nonmedical opioid use 34,534 8.74 6.98–10.93 3.54 2.74–4.57 Wave 2 incident nonmedical opioid use 32,888 5.78 4.23–7.90 2.62 1.86–3.69

Population without wave 1 cannabis use disorders Wave 2 prevalent nonmedical opioid use 34,091 7.43 5.59–9.87 3.35 2.48–4.52 Wave 2 incident nonmedical opioid use 32,616 5.67 3.97–8.09 2.78 1.91–4.04

Population with painc

Wave 2 prevalent nonmedical opioid use 6,920 10.30 6.89–15.39 3.97 2.44–6.46 Wave 2 incident nonmedical opioid use 6,518 6.74 4.09–11.10 2.99 1.63–5.47

a NESARC=National Epidemiologic Survey on Alcohol and Related Conditions; wave 1 was conducted in 2001 and 2002, and wave 2 in 2004 and 2005. b Adjusted for age, sex, race/ethnicity, other substance use disorders, any mood or anxiety disorder, and family history of drug use disorder, alcohol use disorder, depression, and antisocial personality disorder at wave 1. The “overall population” and “population without wave 1 cannabis use disorders” analyses were also adjusted for pain at wave 1.

c Pain is defined as presence of pain causing moderate to extreme interference with daily activities in the past 4 weeks.

TABLE 1. Background Characteristics of NESARC Respondents, by Any Past-Year Cannabis Use at Wave 1a

Characteristic Cannabis Use (N=1,267) No Cannabis Use (N=33,352) p

Mean SD Mean SD

Age (years) 29.91 10.66 45.72 17.27 ,0.001

N % N %

Sex Male 766 66.49 13,780 47.14 ,0.001 Female 501 33.51 19,572 52.86 ,0.001

Race/ethnicity 0.96 White, non-Hispanic 789 70.82 19,360 70.91 Other 478 29.18 13,992 29.09

Family history Alcohol use disorders 598 46.51 11,636 33.96 ,0.001 Drug use disorders 427 33.08 5,537 15.97 ,0.001 Depression 614 48.39 10,503 31.98 ,0.001 Antisocial personality disorder 248 21.42 902 2.89 ,0.001

Painb 254 20.06 6,680 18.60 0.29 Nonmedical prescription opioid use, past 12 months

,0.001

None 1,064 81.92 33,020 98.94 Occasional use 108 10.11 150 0.54 Frequent use 56 4.37 99 0.32 Very frequent use 39 3.61 83 0.21

Mental disorders, past 12 months Opioid use disorder 45 4.05 58 0.18 ,0.001 Cannabis use disorder 443 36.21 0 0.00 ,0.001 Other substance use disorder 591 48.89 2,160 6.78 ,0.001 Mood or anxiety disorder 440 33.00 5,478 15.53 ,0.001

a NESARC=National Epidemiologic Survey on Alcohol and Related Conditions; wave 1 was conducted in 2001 and 2002. Percentages are based on weighted sampling.

b Pain is defined as presence of pain causing moderate to extreme interference with daily activities in the past 4 weeks.

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results from previous epidemiological research concerning a link between cannabis use and other forms of problematic drug use (15–17). Previous work in this area has either been retrospectiveindesign(15)orfocusedongeneralassociations between cannabis use and substance use disorders (17) or problems (16) rather than specifically nonmedical opioid use or opioid use disorder. Because in the present study the as- sociation was observed among adults with less than disorder- level of cannabis use and followed a dose-response pattern, it suggests that some increased risk extends to a relatively large population of adult cannabis users. If cannabis use tends to increase opioid use, it is possible that the recent increase in cannabis use (30) may have worsened the opioid crisis.

Several factors may contribute to a tendency for indi- viduals with cannabis use to develop opioid use disorder or increase the frequency of opioid use among opioid users. Heroin and D9-tetrahydrocannabinol (D9-THC) have similar effects on dopamine transmission through the m1 opioid receptor (31). As compared with controls, adolescent rats exposed to D9-THC have been shown to develop enhanced heroin self-administration as adults (32). Also in relation to controls, rats exposed to D9-THC have been found to have a greater behavioralresponsetomorphinechallenge(33).These results are consistent with cross-sensitization between can- nabis and opioids. In clinical research, cannabis use can lead to behavioral disinhibition, which can increase the risk of using other substances, including opioids (34). Access to cannabis may also provide increased availability and social exposure to other drugs of abuse through peer affiliations (35), although such environmental influences may be less powerfulinrecentyearswithincreasedprevalenceofcannabis use and changing public attitudes.

Ecological studies reporting fewer opioid-related deaths (8, 9) and decreased opioid prescribing following passage of medical marijuana laws (10) have been interpreted in the

TABLE 3. Prospective Associations Between Wave 1 Cannabis Use and Increase or Decrease in Nonmedical Prescription Opioid Use at Wave 2 Among Adults With Wave 1 Nonmedical Prescription Opioid Use in the NESARCa

Wave 1 Past-Year Cannabis Use Predicting:

Respondents With Change in Opioid Use Between Wave 1 and Wave 2

Cannabis Use No Cannabis Use

N % N % Odds Ratio 95% CI Adjusted

Odds Ratiob 95% CI

Adults with wave 1 nonmedical opioid use

203 332

Increase in opioid use at wave 2

9 5.15 4 0.97 5.57 1.47–21.11 3.13 1.19–8.23

Decrease in opioid use at wave 2

169 81.27 307 93.70 0.29 0.14–0.61 0.42 0.19–0.91

Adults with wave 1 nonmedical opioid use and painc

60 105

Increase in opioid use at wave 2

2 7.78 3 1.97 4.20 0.64–27.50 2.60 0.42–16.05

Decrease in opioid use at wave 2

53 79.97 96 93.04 0.30 0.10–0.86 0.60 0.18–2.03

a NESARC=National Epidemiologic Survey on Alcohol and Related Conditions; wave 1 was conducted in 2001 and 2002, and wave 2 in 2004 and 2005. Per- centages are based on weighted sampling.

b Adjusted for age, sex, race/ethnicity, other substance use disorders, any mood or anxiety disorder, and family history of drug use disorder, alcohol use disorder, depression, and antisocial personality disorder at wave 1.

c Pain is defined as presence of pain causing moderate to extreme interference with daily activities in the past 4 weeks.

FIGURE 1. Level of Wave 1 Cannabis Use and Incident Wave 2 Prescription Opioid Use Disorder in the NESARCa

4.5

4.0

5.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0

Level of Wave 1 Cannabis Use

W a

v e

2 O

p io

id U

se D

is o

rd e

r (%

)

No use Occasional use

Frequent use

Very frequent use

a NESARC=National Epidemiological Survey on Alcohol and Related Condi- tions; wave 1 was conducted in 2001 and 2002, and wave 2 in 2004 and 2005.

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OLFSON ET AL.

media (6) and scientific literature (7) as supporting can- nabis as a means of reducing opioid use disorder. Yet drawing inferences about the behavior of individuals from aggregated data can be misleading. It is possible, for ex- ample, that passage of medical marijuana laws increased local clinical awareness of opioid misuse, leading to earlier detection of high-risk patients or more cautious opioid prescribing practices. At the individual level, cannabis use appears to substantially increase the risk of nonmedical opioid use. Moreover, the general association between cannabis use and subsequent use of illicit drugs is not explained by the legal status of cannabis. An association of early cannabis use with increased subsequent risk of other drug abuse has been reported in prospective co-twin studies in Australia (15), which has restrictive cannabis laws, and in the Netherlands, where cannabis is readily available (36).

In accord with previous studies, several demographic and clinical covariates were associated with cannabis use (17). These findings converge to highlight the wide range of fac- tors that may influence initiation of cannabis. However, because cannabis use was not associated with significant pain at baseline, relief from pain does not appear to be a strong determinant of cannabis use in the general U.S. adult pop- ulation, although we have no means of evaluating the anal- gesic effects of cannabis with NESARC data.

This study has several limitations. First, the NESARC sampled individuals age 18 and older. The relationship be- tween cannabis and opioid use may differ in younger indi- viduals (16). Second, information on cannabis and opioid use was based on self-report and was not confirmed with urine toxicology, which may have led to underestimates. Third, the analysis was limited to two time points 3 years apart, which may have been too short an interval to observe delayed consequences of cannabis use on later risk of opioid use. Fourth, the data were collected over a decade ago, and the social context of cannabis use may have changed during this period (30). Nevertheless, the NESARC remains the

most recent nationally representative prospective cohort of U.S. adults with detailed information on substance use. Fifth, we were unable to distinguish recreational from medical marijuana use. However, typical medical mari- juana participants have been reported to be young males with a history of recreational cannabis use (37), and adults often combine medical and nonmedical cannabis use (38). Sixth, some of the associations are based on a small number of individuals and should therefore be interpreted with appro- priate caution. Seventh, the NESARC did not assess inmate populations, which may have a high prevalence of substance use disorders (39). Finally, the assessment of nonmedical use of prescription opioids, although extensive, was not exhaus- tive and included two nonopioid medications (celecoxib and rofecoxib).

A long-standing controversy in drug research and policy concerns the extent to which use of cannabis predisposes to subsequent use of opioids and other drugs of abuse. We report that cannabis use, even among adults with moderate to severe pain, was associated with a substantially increased risk of nonmedical prescription opioid use at 3-year follow-up. Although the great majority of adults who used cannabis did not go on to initiate or increase their nonmedical opioid use, a strong prospective association between cannabis and opioid use disorder should nevertheless sound a note of caution in ongoing policy discussions concerning cannabis andinclinicaldebateoverauthorizationofmedicalmarijuana to reduce nonmedical use of prescription opioids and fatal opioid overdoses.

AUTHOR AND ARTICLE INFORMATION

From the Department of Psychiatry, New York State Psychiatric Institute and Columbia University Medical Center, New York; and the Division of Epidemiology, Services and Prevention Research, NIDA, Bethesda, Md.

Address correspondence to Dr. Olfson ([email protected]).

Supported by NIH grant DA019606 (to Dr. Olfson). The National Epide- miologic Survey on Alcohol and Related Conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and funded in part by the NIAAA Intramural Research Program.

TABLE 4. Prospective Associations of Wave 1 Cannabis Use and Wave 2 Prevalent and Incident Nonmedical Prescription Opioid Disorder in the NESARCa

Wave 1 Past-Year Cannabis Use Predicting:

N in Analysis Odds Ratio 95% CI

Adjusted Odds Ratiob 95% CI

Overall population Wave 2 prevalent opioid use disorder 34,619 10.63 7.09–15.93 2.49 1.35–4.59 Wave 2 incident opioid use disorder 34,190 7.76 4.95–12.16 2.18 1.14–4.14

Population without wave 1 cannabis use disorders Wave 2 prevalent opioid use disorder 34,176 9.03 5.21–15.64 2.15 1.16–3.99 Wave 2 incident opioid use disorder 33,798 5.42 2.99–9.82 1.72 0.81–3.63

Population with painc

Wave 2 prevalent opioid use disorder 6,934 13.21 7.03–24.83 3.70 1.70–8.08 Wave 2 incident opioid use disorder 6,772 6.70 3.08–14.55 2.14 0.95–4.83

a NESARC=National Epidemiologic Survey on Alcohol and Related Conditions; wave 1 was conducted in 2001 and 2002, and wave 2 in 2004 and 2005. b Adjusted for age, sex, race/ethnicity, other substance use disorders, any mood or anxiety disorder, nonmedical opioid use, and family history of drug use disorder, alcohol use disorder, depression, and antisocial personality disorder at wave 1. The “overall population” and “population without wave 1 cannabis use disorders” were also adjusted for pain at wave 1.

c Pain is defined as presence of pain causing moderate to extreme interference with daily activities in the past 4 weeks.

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The views and opinions expressed here are those of the authors and should not be construed to represent the views of any of the sponsoring organizations or agencies or the U.S. government.

Dr. Blanco owns stock in Eli Lilly, General Electric, and Sanofi. The other authors report no financial relationships with commercial interests.

Received April 12, 2017; revision received May 26, 2017; accepted July 10, 2017; published online September 26, 2017.

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