l law or regulation

REVIEW ARTICLE

Cannabis use among U.S. adolescents in the era of marijuana legalization: a review of changing use patterns, comorbidity, and health correlates

Christopher J. Hammonda,b,c , Aldorian Chaneya,c, Brian Hendricksona,c and Pravesh Sharmad

aDivision of Child & Adolescent Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; bBehavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD, USA; cDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; dDepartment of Psychiatry, Mayo Clinic Health System and University of Wisconsin-Eau Claire, Eau Claire, WI, USA

ABSTRACT Decriminalization, medicalization, and legalization of cannabis use by a majority of U.S. states over the past 25 years have dramatically shifted societal perceptions and use patterns among Americans. How marijuana policy changes have affected population-wide health of U.S. youth and what the downstream public health implications of marijuana legalization are topics of sig- nificant debate. Cannabis remains the most commonly used federally illicit psychoactive drug by U.S. adolescents and is the main drug for which U.S. youth present for substance use treatment. Converging evidence indicates that adolescent-onset cannabis exposure is associated with short- and possibly long-term impairments in cognition, worse academic/vocational outcomes, and increased prevalence of psychotic, mood, and addictive disorders. Odds of negative develop- mental outcomes are increased in youth with early-onset, persistent, high frequency, and high- potency D-9-THC cannabis use, suggesting dose-dependent relationships. Cannabis use disor- ders are treatable conditions with clear childhood antecedents that respond to targeted preven- tion and early intervention strategies. This review indicates that marijuana policy changes have had mixed effects on U.S. adolescent health including potential benefits from decriminalization and negative health outcomes evidenced by increases in cannabis-related motor vehicle acci- dents, emergency department visits, and hospitalizations. Federal and state legislatures should apply a public health framework and consider the possible downstream effects of marijuana pol- icy change on paediatric health.

ARTICLE HISTORY Received 15 September 2019 Accepted 6 January 2020

KEYWORDS Adolescents; cannabis; marijuana; legalization; psychiatric comorbidity; health correlates

Introduction

Cannabis is a psychoactive drug derived from the plant species cannabis sativa and cannabis indica. It contains greater than 500 bioactive chemicals and more than 80 unique phytocannabinoids that have distinct and dose-dependent effects in humans, including D-9-tetra-hydrocannabidol (D-9-THC), the primary psychoactive constituent, and cannabidiol (CBD) another major constituent of the plant believed to have potential medical properties (NCCIH, 2018). Cannabinoids such as D-9-THC and CBD act cen- trally and peripherally at receptors that are part of an endogenous brain system involved in development and homeostasis called the endocannabinoid system. Cannabis is used by an estimated 183 million individ- uals worldwide (WHO, 2019). Use of cannabis is increasing among individuals living in North America, in part related to legalization, decriminaliza- tion, and expansion of availability in United States

(U.S.) and Canadian markets (Findlaw, 2019; WHO, 2019). Within the U.S. specifically, dramatic shifts in public policy have occurred over the past two deca- des. In 1996 California became the first U.S. state to approve legislation allowing for the medical use of marijuana. Since that time 32 other states and the District of Columbia have passed laws allowing for legal use of marijuana for medical purposes and 11 states have passed laws allowing for recreational use of marijuana (Findlaw, 2019). Accompanying these policy shifts in the U.S. have been changes in public opinion, perception regarding the harms of cannabis, cannabis use patterns, and the prevalence of cannabis use disorders (CUD) among U.S. adults (Cerda, Wall, Keyes, Galea, & Hasin, 2012; Hasin et al., 2017).

Over this period, there has also been a significant expansion in the number and type of cannabis prod- ucts available for consumption (e.g. plant, oil, edibles, concentrates) (Hopfer, 2014) and three-fold increase

CONTACT Christopher J. Hammond [email protected] Johns Hopkins Bayview, 5500 Lombard Street, Baltimore, MD 21224, USA � 2020 Institute of Psychiatry and Johns Hopkins University

INTERNATIONAL REVIEW OF PSYCHIATRY 2020, VOL. 32, NO. 3, 221–234 https://doi.org/10.1080/09540261.2020.1713056

in the average D-9-THC potency in cannabis products (ElSohly et al., 2016). While cannabis use is perceived by the average American to have few negative conse- quences, there is increasing evidence for poorer men- tal and physical health outcomes, including elevated risk for serious psychiatric illness with chronic recre- ational cannabis use, especially when high-potency cannabis is used (Davis et al., 2016; Dutra, Parish, Gourdet, Wylie, & Wiley, 2018). The risk for negative health outcomes related to cannabis use are amplified when use and progression to chronic use begin dur- ing adolescence.

Given the dramatic shifts in marijuana legislation that have occurred in the U.S. over the past 25 years, it is more important than ever for clinicians and pol- icy makers to be aware of the effects of adolescent cannabis use on mental and physical health and to understand potential down-stream consequences related to these policy shifts on perceptions, use pat- terns, and health outcomes of U.S. adolescents. Knowledge about the impact of marijuana policy on relevant health indicators in youth may inform cur- rent and future public health efforts. In this article, we provide a state of the science review on the effects of adolescent-onset cannabis use on health and behav- iour with a focus on cannabis use and CUDs among U.S. adolescents in the current era of state-based marijuana legalization. We discuss the epidemiology, recent trends in use, and examine relationships between adolescent cannabis use and developmental outcomes. Using a public health framework, we review marijuana-related legislation and public policy changes in the U.S. and examine the implications, positive and negative, for adolescent health outcomes.

Epidemiology and developmental trajectories

Prevalence and incidence of cannabis use among U.S. youth

Cannabis is the most commonly used federally illicit drug among U.S. adolescents and the most common drug problem reported by U.S. teens presenting for substance abuse treatment (SAMHSA, 2018, 2019). Over 1.6 million individuals between the ages of 12 and 17 equating to 6.5% of the U.S. adolescent popu- lation, and 7.6 million individuals between the ages of 18 and 25 equating to 22.5% of the U.S. young adult population reported current use of cannabis (SAMHSA, 2018). Among U.S. high school students, nearly half of all 12th graders (44%), one third of 10th graders (33%) and one in seven 8th graders (14%) reported lifetime cannabis use in 2018, with

22%, 17%, and 5.6% of U.S. 12th, 10th, and 8th graders reporting past month use respectively (Johnston et al., 2018). Daily cannabis use was reported by 5.8% of 12th graders, 3.4% of 10th graders and 0.7% of 8th

graders. Rates of current cannabis use amongst 12-to- 17 year-olds decreased between 2002 and 2009 and have remained stable since 2015 (SAMHSA, 2018). In contrast, rates of current cannabis use amongst young adults have risen significantly since 2002 (SAMHSA, 2018). At the time of this writing, prevalence rates of cannabis use in 19–22 year old ‘college age’ young adults have gradually increased since 2009 and are approaching their highest levels in the past three dec- ades (Michigan, 2018). Some subgroups have shown larger changes in cannabis use compared to others. For example, while daily cannabis use among college- enrolled U.S. youth peaked at 5.9% in 2014 and has plateaued since then, daily use has continued to rise for non-college enrolled U.S. youth and, at 13.2%, is currently at an all-time high in the past three decades (Schulenberg et al., 2018). This gap continues to widen and is worrisome given the negative health and functioning impact of recreational cannabis use.

Regarding incidence of cannabis initiation: In 2017, 1.2 million adolescents ages 12-to-17 and 1.3 million young adults ages 18-to-25 reported first time use of cannabis in the past year (SAMHSA, 2018). Since 2002, the incidence of cannabis use among U.S. ado- lescents has remained stable, but has increased among young adults (SAMHSA, 2018). Among youth, the prevalence of past year CUD reached a peak in the early 2000s, declined between 2002–2013, and has remained stable since 2014. In 2017, 2.2% of adoles- cents ages 12-to-17 equating to over 0.5 million U.S. adolescents and 5.2% of young adults ages 18-to-25 equating to 1.8 million U.S. young adults met DSM-5 criteria for CUD in the past year (SAMHSA, 2018).

The types of cannabis products and methods of administration among U.S. youth have also changed in the past 25 years. While combustible cannabis products (e.g. joints, blunts, bongs, water pipes) remain the most common method of use, youth have expanded to other types of cannabis products and ways of using (Hopfer, 2014; Johnston et al., 2018). In fact, data suggests that most current adolescent can- nabis users use multiple administration methods to consume cannabis (Peters, Bae, Barrington-Trimis, Jarvis, & Leventhal, 2018). A 2015 cross-sectional sur- vey study of 3177 adolescents found that 21.3% and 10.5% of 10th graders in California have tried edible and vaporized cannabis products respectively (Peters et al., 2018). The use of ‘concentrates’ (i.e. dabs, wax,

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budder, shatter), cannabinoid products with very high D-9-THC concentrations, are also increasing in popu- larity among U.S. youth (Sagar & Gruber, 2018; Zhang, Zheng, Zeng, & Leischow, 2016).

With the increasing availability of portable elec- tronic ‘vaporized’ nicotine and cannabis delivery sys- tems in the U.S., vaping cannabis is becoming more common among youth. National survey data suggest that 10% of high school students have vaped cannabis with 12% and 14% of U.S. 10th and 12th graders reporting vaping cannabis in the past year (Johnston et al., 2018; Kowitt et al., 2019). While vaping has been promoted as a safer alternative to combustible smoking of tobacco and cannabis products, there have been recent reports of vaping-related acute lung disease, seizures, and deaths in young people, includ- ing those who vape cannabis (Schier, Meiman, & Layden, 2019). In response to this, the CDC has recently issued health warnings related to vaping (CDC, 2019).

In summary, across national surveys, prevalence and incidence of cannabis use among U.S. teens have remained stable and among U.S. young adults have increased over the past decade. During this period, there have been changes in the type and method of cannabis product used by U.S. youth. Many questions remain. Why cannabis use and CUD have not increased in adolescents as they have in adults is unclear. Additionally, over the same time period that cannabis use rates have remained unchanged, alcohol, combustible tobacco products, and non-marijuana illicit drug use among U.S. adolescents ages 12–17 years have all decreased and are at or near all- time low use patterns since data were first collected in the 1970s (Johnston et al., 2018; SAMHSA, 2018). Whether this comparative stability is a result of changing U.S. perceptions and policies related to can- nabis is unclear.

Individual differences in vulnerability and different developmental trajectories

Significant individual differences exist in the response to cannabis during youth (Coffey, Carlin, Lynskey, Li, & Patton, 2003). Not all youth who try cannabis develop problems related to its use. Some young peo- ple experiment with cannabis, use it sporadically for a limited duration, and experience few negative conse- quences. Others become chronic cannabis users whose use persists throughout adolescence and young adult- hood and contributes to long-term health problems and impaired functioning. Several studies have

identified different trajectories of cannabis use from adolescence into young adulthood including a persist- ent/chronic high use trajectory (�5–10%), a chronic occasional use trajectory (�5–10%), a sporadic/transi- ent use trajectory (�35%), and a no/low use trajectory (�45%) (Lee, Brook, Finch, & Brook, 2018; Swift, Coffey, Carlin, Degenhardt, & Patton, 2008; Windle & Wiesner, 2004). Relative to no/low use and sporadic/ transient use trajectory groups, individuals in the per- sistent/chronic high cannabis use trajectory group have increased psychiatric problems, delinquency, and other drug use by young adulthood (Lee et al., 2018; Swift et al., 2008; Windle & Wiesner, 2004). Understanding the risk and protective factors related to cannabis engagement trajectories and developing risk calculators to identify youth who are at elevated risk for developing persistent/chronic cannabis use may improve the precision and cost-effectiveness of targeted prevention efforts.

A widening treatment gap for adolescent cannabis use

Most individuals who experience drug-related prob- lems or who meet criteria for a SUD, including can- nabis, never receive treatment. In 2017, while 1.1 million U.S. adolescents met criteria for a SUD, fewer than one in 10 received substance abuse treat- ment (SAMHSA, 2018). Emerging evidence suggests that for cannabis, this treatment gap may be widening during the era of marijuana legalization. National data on treatment episodes for substance-related dis- orders indicate that fewer individuals are seeking treatment for cannabis use/CUD in recent years (Sahlem, Tomko, Sherman, Gray, & McRae-Clark, 2018; SAMHSA, 2019). For example, data on national admissions to substance abuse treatment from the treatment episode dataset (TEDS) showed a decrease in admissions to adolescent substance abuse treatment among 12–17-year-olds in general, and a 48% decrease in the total number of cannabis-related admissions between 2005 and 2015 (SAMHSA, 2017). The reduction in treatment seeking rates may be a result of increased social acceptability of cannabis use, a reduction of the perceived risk of cannabis use, or a result of the limited effectiveness of current treat- ments (Sahlem et al., 2018). If expansion of marijuana legalization results in increased cannabis engagement among U.S. youth, this widening treatment gap could portend a future public health crisis. Educational campaigns aimed at increasing public awareness about the harms of cannabis use to adolescents, and

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continued research funding aimed at enhancing can- nabis cessation outcomes and implementing and dis- seminating effective cannabis treatments nationally are needed. As more states change their views on can- nabis use and revise their laws related to marijuana, public health educational initiatives will be increas- ingly important.

Health outcomes related to adolescent cannabis use

Association with cognitive outcomes

The cognition impairing effects of cannabinoids in humans are well documented in the scientific literature in both adults and adolescents (Gorey, Kuhns, Smaragdi, Kroon, & Cousijn, 2019; Lisdahl, Wright, Kirchner-Medina, Maple, & Shollenbarger, 2014). Cannabis-related cognitive deficits may be both global and domain specific and can be temporally framed as acute/intoxication-, short-, and long-term effects. Acute cannabis intoxication is associated with transient mood alterations that may include euphoria, anxiety, or para- noia, along with impairments in cognitive function and sensory processing (Bloomfield et al., 2019; Hunault et al., 2009). When not intoxicated, adolescent cannabis users exhibit signs of cognitive impairments when compared to matched controls in the domains of attention, memory, executive function (including work- ing memory and inhibition), visual processing, and processing speed, along with decreased full-scale IQ and verbal IQ (Dougherty et al., 2013; Gruber, Sagar, Dahlgren, Racine, & Lukas, 2012; Jacobus, Bava, Cohen-Zion, Mahmood, & Tapert, 2009). Many of the domain-specific cognitive deficits improve with abstin- ence, but some may persist beyond early abstinence and represent long-term deficits (Hanson et al., 2010; Medina et al., 2007; Meier et al., 2012; Volkow et al., 2016). For example, a study by Hanson and colleagues found that following 3 weeks of abstinence from canna- bis that adolescent regular cannabis users showed improvements in verbal memory and inhibition but continued to exhibit impaired attention compared to controls (Hanson et al., 2010). Studies of adolescents with earlier, heavier, and more persistent cannabis use patterns generally show larger effect sizes for cognitive outcomes (Gorey et al., 2019; Gruber et al., 2012; Meier et al., 2012; Pope et al., 2003). Some studies indicate that long-term cognitive impairments occur primarily in early adolescent-onset of cannabis users (� age of 15 or 16), and that adult- or late adolescent- onset of cannabis users do not exhibit the same risk for long-term cognitive impairments (Fontes et al.,

2011; Gruber et al., 2012; Pope et al., 2003). Studies have also largely shown that adolescent-onset cannabis exposure produces similar cognitive deficits for both sexes (Levine, Clemenza, Rynn, & Lieberman, 2017; Meier et al., 2012; Pope et al., 2003).

Whether the cognitive impairments related to ado- lescent-onset cannabis exposure are permanent or resolve with abstinence is unclear. Mixed findings have been reported in the literature. A longitudinal study by Meier et al. (2012) found that full-scale IQ decrements related to adolescent cannabis exposure persisted into adulthood for individuals who contin- ued to use cannabis and did not fully remit in early adolescent-onset users who abstained from cannabis during adulthood (Meier et al., 2012). Analyses from other longitudinal studies suggest that some cognitive deficits including global FSIQ decrements remit with cessation and that length of abstinence is associated with greater cognitive recovery (Mokrysz et al., 2016; Tait, Mackinnon, & Christensen, 2011). Twins studies discordant for cannabis engagement during adoles- cence have also reported mixed findings related to whether cannabis-associated cognitive deficits remit or persist with abstinence in adulthood after control- ling for genetic and early-childhood vulnerability (Jackson et al., 2016; Lyon, Bar, & Panizzon, 2004).

Association with psychiatric symptoms and mental health outcomes

The associations between adolescent-onset cannabis use, psychiatric symptoms, and mental health out- comes are complex (Levine et al., 2017). Cannabis use and CUD commonly co-occur with psychiatric disor- ders in youth. Concurrent cannabis use and psychi- atric symptoms may track together in adolescents with studies suggesting parallel improvement in both during successful treatment (Hser et al., 2017; Jacobus et al., 2017; Moitra, Anderson, & Stein, 2016). Aside from concurrent relationships, long-term associations have been described in the literature. Longitudinal studies generally show that adolescent-onset cannabis exposure is associated in a dose-dependent way with an increased prevalence of psychotic, mood and addictive disorders and worse courses of these disor- ders into adulthood (Levine et al., 2017).

Psychotic disorders

Among all cannabis-related mental health outcomes, the evidence is strongest for a relationship between adolescent-onset cannabis use and psychotic disorders

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(D’souza et al., 2016; Moore et al., 2007). Adolescent- onset cannabis use increases the likelihood of devel- oping attenuated psychotic symptoms, psychotic like experiences, and full psychotic disorders by young adulthood (Fridberg, Vollmer, O’Donnell, & Skosnik, 2011; Hall & Degenhardt, 2008; Moore et al., 2007). Furthermore, among youth with psychotic disorders, cannabis use is associated with worse course and prognosis including greater risk for relapse to psych- osis, increased hospitalizations, and poorer medication adherence (Miller et al., 2009; Schoeler et al., 2016). In parallel with other developmental outcomes, dose- response relationships exist between cannabis use and psychosis with early-onset, high frequency (�weekly), and high-potency (�10% D-9-THC) conveying greater risk (Di Forti et al., 2014; Hall & Degenhardt, 2015). Additively, early-onset daily use of high- potency cannabis starting before age 15 poses a five- to six-fold greater risk for the development of a psychotic disorder compared to non-use (Di Forti et al., 2014). Different cannabis-psychosis relation- ships exist along different time-scales (Wilkinson, Radhakrishnan, & D’Souza, 2014). Acute cannabis intoxication can produce transient psychotic symp- toms that resolve spontaneously without intervention in some youth. Cannabis use can also lead to a pro- tracted psychotic symptom course including a transi- ent persistent psychosis or cannabis-induced psychosis, which lasts beyond the period of acute intoxication (Wilkinson, Radhakrishnan, & D’Souza, 2014). Cannabis-induced psychotic disorders may be a harbinger for long-term risk for chronic psychosis. A recent longitudinal study from Scotland found that 50–75% of individuals who experienced a cannabis- induced psychotic disorder went on to develop schizophrenia or bipolar disorder within 15 years (Alderson et al., 2017). The link between cannabis and psychosis is greater in individuals with child mal- treatment or genetic vulnerabilities (Wilkinson et al., 2014). Some but not all of the risk for developing psychosis in adolescent cannabis users is related to pre-existing vulnerability to psychosis. For example, while adolescent cannabis users with a family history of psychosis in a first-degree relative have a higher risk of developing psychosis, cannabis use still con- veys increased risk in adolescent cannabis users with no familial risk (D’souza et al., 2016).

Mood and anxiety disorders

Complex relationships exist between cannabis use and mood and anxiety disorders. Many cannabis using

youth self-report using cannabis to ‘self-medicate’ depression and anxiety, and to reduce stress (Hyman & Sinha, 2009). When adults are administered canna- binoids in the laboratory, D-9-THC exerts a biphasic dose-dependent acute effect on anxiety, with low-dose D-9-THC preparations being anxiolytic and high-dose D-9-THC preparations being anxiogenic (Bloomfield et al., 2019). In direct contradiction to these short- term effects, the majority of longitudinal studies show the opposite association, whereby adolescent-onset cannabis use is associated with increased likelihood and poorer course of mood and anxiety disorders during adolescence and into adulthood (Degenhardt, Hall, & Lynskey, 2003; Levine et al., 2017; Moore et al., 2007).

Adolescent-onset cannabis use has been linked to adverse mood outcomes including increased depres- sion and suicidality in both population-wide cross- sectional studies and a number of large longitudinal cohort studies (Degenhardt et al., 2003; Gobbi et al., 2019; Horwood et al., 2012; Moore et al., 2007; Silins et al., 2014). It is important to note that while numer- ous studies have reported a positive association between adolescent cannabis use and depression, there are also studies that failed to find this associ- ation (Scholes-Balog, Hemphill, Evans-Whipp, Toumbourou, & Patton, 2016). Results from a recent meta-analysis found that adolescent-onset cannabis use is associated with a modest increase in the odds of depression, suicidal ideations, and suicide attempts in young adulthood (Gobbi et al., 2019). Earlier meta- analyses have found evidence for a dose-dependent increase in risk for depression from adolescent canna- bis use (Lev-Ran et al., 2014) and an age of onset effect whereby initiation of cannabis before age 17 years conveys greater risk (Moore et al., 2007). Results from a large retrospective study involving 13,986 twins found that the monozygotic twin who reported more frequent cannabis use had a two-fold greater odds of depression and suicidal ideations compared with their twin counterpart who used less frequently (Agrawal et al., 2017). This study indicates that the association between cannabis and depression cannot be explained by common vulnerabilities alone. Interestingly, in parallel with cognitive sequelae, most studies have shown that adolescent-onset cannabis exposure results in similar mood outcomes for both males and females (Coffey & Patton, 2016; Degenhardt et al., 2013; Horwood et al., 2012).

Cross-sectional and longitudinal studies show that compared to controls adolescent and young adult cannabis users have increased anxiety, anxiety

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sensitivity, and panic attacks, and increased rates of co-occurring anxiety disorders including social anx- iety disorder, panic disorder, and post-traumatic stress disorders (PTSD) (Buckner et al., 2017; Cornelius et al., 2010; Zvolensky et al., 2006). A recent meta- analysis in adults suggests a modest relationship between cannabis use and anxiety (Kedzior & Laeber, 2014). Findings regarding the directionality of these associations are mixed. Adverse childhood experiences and chronic stress generally precede the onset of can- nabis use and increase the risk for early-onset canna- bis use and progression to CUD by young adulthood (Buckner et al., 2012; Hyman & Sinha, 2009). Some longitudinal studies have shown a long-term relation- ship between adolescent-cannabis use and increased risk for anxiety disorders in adulthood (Degenhardt et al., 2013; Fergusson & Horwood, 1997), while others have shown no association (Buckner et al., 2012) or the inverse association (Buckner et al., 2008). Adolescent cannabis use and CUDs have been prospectively associated with increased odds for panic attacks and disorders, but some of the variances in this relationship may be related to co-occurring tobacco use (Zvolensky et al., 2008). More recently, a 2019 meta-analysis of longitudinal studies failed to find an association between adolescent cannabis use and later anxiety disorders (Gobbi et al., 2019). Future research is needed in this area, especially given that many states have added anxiety disorders and PTSD as ‘indicated conditions’ for medical marijuana (Mitchell, 2019).

Addictive disorders

As with cognitive, mood, and psychotic outcomes, adolescent cannabis use is also associated with increased risk for developing addictive disorders in adulthood to cannabis and other drugs. Both cross- sectional and longitudinal studies have shown a sig- nificant relationship between early-onset cannabis exposure and a greater likelihood of developing an addictive disorder (Coffey & Patton, 2016; Fergusson, Boden, & Horwood, 2015; Nocon, Wittchen, Pfister, Zimmermann, & Lieb, 2006; E. Silins et al., 2017; Swift et al., 2008; Swift et al., 2012). Drug engagement typically follow a general sequence from ‘lite’ drugs such as alcohol, tobacco, and cannabis to ‘heavier’ illicit drugs including opioids, stimulants. Much debate has been made about the ‘gateway’ hypothesis, and reverse gateways going from cannabis to tobacco use have also been described (Patton, Coffey, Carlin, Sawyer, & Lynskey, 2005). While part of the variance

in association between early-onset cannabis use and escalation to other drugs can be explained by the common liability hypothesis, there is also evidence suggesting that cannabis’s effects on the developing brain may also play a role (Hall & Degenhardt, 2015). In animal models, adolescent-onset cannabinoid exposure sensitizes striatal dopamine systems and increases self-administration of opioids and stimulants in adulthood (Pistis et al., 2004; Renard et al., 2016). Some studies also suggest unique cannabis-opioid associations whereby cannabis, more so than other drugs, increases the risk for progression to opioid misuse (Kaminer, 2017; Olfson, Wall, Liu, & Blanco, 2018).

Summary of health outcome findings

In summary, current evidence indicates that adoles- cent-cannabis exposure is associated with a number of negative life outcomes including impairments in cogni- tion and increased prevalence and worse course of psychotic, mood, and addictive disorders. These associ- ations are stronger in adolescents with earlier age of onset, frequent and heavy use, and high-potency can- nabis use, which is worrisome given the rising potency and availability of cannabis throughout the U.S. As findings are associative, causality cannot be deter- mined. Next-level studies should aim to characterize associations between adolescent-onset cannabis expos- ure and health outcomes across different time scales and at different levels of analysis (i.e. genomics, brain circuits, behaviour, self-report). Future research should incorporate cross-translational approaches; such as, combining animal models, which have hinted at a causal association, with longitudinal human studies that assess both genetic and environmental factors and include non-invasive brain imaging and deep behav- ioural phenotyping as is being done in the Adolescent Brain Cognitive Development (ABCD) study, a large longitudinal study following 10,000U.S. preadolescents over a 10-year period (Jernigan, Brown, & ABCD Consortium Coordinators, 2018).

Marijuana legalization and its impact on adolescent cannabis use

Changes in marijuana legislation in the U.S

Despite mass expansion of state-level marijuana legal- ization in the U.S., the federal government has not taken major legislative action related to marijuana in the past two decades. Under current federal laws in the U.S., cannabis possession and use are still considered

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illegal and can be subject to federal prosecution (Findlaw, 2019). Cannabis also remains classified as a Schedule I substance by the U.S. Drug Enforcement Agency (DEA), limiting its access for study by scientists (DEA, 2019). The incongruence between federal and state marijuana laws in the U.S. has resulted in confu- sion, limited or delayed implementation of state laws, and created complicated financing operations and state- to-state legal implications for commerce (Findlaw, 2019; Vandrey, 2018). While the federal government has been noncommittal regarding reclassifying canna- bis, a majority of states within the U.S. have now passed laws to legalize marijuana, in some form or other, for medical and recreational use, as well as to decriminalize possession of cannabis (Governing, 2019).

Medical and recreational marijuana in the U.S

Ongoing public advocacy related to marijuana use for medicinal purposes, termed medical marijuana, con- tinues to be a major reason for promotion of mari- juana legalization initiatives (Pacula & Smart, 2017; Vandrey, 2018). Cannabinoids have shown early promise as novel treatments for a number of medical conditions in early preclinical studies (Whiting et al., 2015). For most of these conditions though, follow up with controlled studies in humans have yet to confirm these benefits. The use of marijuana as treatment for medical conditions is complicated. Marijuana contains multiple bioactive molecules including D-9-THC and CBD, which have distinct and dose-dependent effects in humans (NCCIH, 2018). Medical marijuana laws vary widely by state and, in many states, marijuana products are not consistently standardized in dose, potency, or chemical constituency (Pacula & Smart, 2017; Vandrey et al., 2015). This is problematic if spe- cific cannabinoids need to be used at specific doses to be effective. While some states have set regulations requiring quality control and labelling of dispensary- sold medical marijuana preparations, it is unclear how reliable these labels are. A recent study by Vandrey and colleagues found that dispensary- sourced marijuana edibles from multiple states had poor accuracy of labelled doses (Vandrey et al., 2015). Further complicating the application of medical mari- juana are the issues of minimal physician documenta- tion and supervision, which varies widely from state- to-state (NCSL, 2019; Pacula & Smart, 2017). Despite the limitations described above, medical marijuana has been shown to be useful in adults for the treat- ment of certain medical conditions including nausea, vomiting, cachexia secondary to HIV/AIDs or cancer,

neuropathic pain, multiple sclerosis, and some forms of epilepsy (NIDA, 2019; Whiting et al., 2015). Beyond these conditions though, state legislatures have approved medical marijuana for the treatment of multiple other ‘indicated’ conditions (e.g. PTSD and more recently Autism) based upon limited scientific evidence in humans (Mitchell, 2019).

The use of medical marijuana for treatment of childhood-onset medical conditions is controversial. In states with medical marijuana legislation cannabis is being prescribed to youth as a treatment for ADHD, Autism, anxiety disorders, and bipolar dis- order without any scientific evidence to support this practice (Jaffe & Klein, 2010; Mitchell, 2019). Many adolescents have obtained medical marijuana with parents’ written permission (Ammerman, Ryan, Adelman, Committee on Substance Abuse, & the Committee on Adolescence, 2015). Young people who use medical marijuana are more likely to have used cannabis regularly between ages 13-19 years, and may experience poorer developmental outcomes than youth who use conventional medical treatments (Tucker et al., 2019). To date, the only childhood onset medical conditions that medical marijuana has demonstrated preliminary efficacy in human studies for are Lennox-Gastaut syndrome and Dravet syn- drome, two rare childhood-onset seizure disorders (� 0.006% of U.S. population) (Volkow et al., 2016).

More research is clearly needed to determine both potential benefits and harm or side effects from med- ical marijuana use, and if there is any role for the use of medical marijuana in childhood-onset medical con- ditions and psychiatric conditions. For conditions with a strong evidence base, comparative effectiveness studies are needed to determine how marijuana may be used in relation to FDA-approved medications. Additional research is also needed to clarify the role of medical marijuana in standard medical practice. Overall, marijuana legislation has many moving parts, which continually need to be examined as more states legalize cannabis in various capacities. With all the various forms of cannabis products, more studies are needed to clarify how individuals uniquely utilize and respond to different formulations (Hopfer, 2014).

Impact of marijuana legalization on youth

States that have legalized medical and recreational use of cannabis continue to spark many discussions, par- ticularly about the impact it may have on adolescent health. Concerns have been raised that marijuana laws have not taken into consideration the societal

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and long-term public health impact legalization of recreational and medical cannabis use will have on communities. Alterations in perception of the harmful effects of cannabis; unregulated commercialization of cannabis products geared towards adolescents; and decreased treatment utilization for excessive con- sumption of cannabis are societal and public health concerns that have been raised related to marijuana legalization (Davis et al., 2016; Hall & Lynskey, 2016; Wang, 2017).

An important caveat when considering the public health outcomes related to marijuana legislation is decriminalization and the potential for positive out- comes in youth because of reduced juvenile justice involvement. The illegality of marijuana has resulted in the incarceration of hundreds of thousands of ado- lescents, with overrepresentation of minority youth (Ammerman et al., 2015). A criminal record can have lifelong negative effects on an adolescent who other- wise had no criminal justice history. These effects can include ineligibility for college loans, housing, finan- cial aid and certain kinds of jobs (Firth, Maher, Dilley, Darnell, & Lovrich, 2019). Despite cannabis being considered illegal for any use under federal law, certain states have passed laws reducing penalties for cannabis offences. Rather than criminal prosecution or threat of arrest (Findlaw, 2019), civil penalties, with the lowest misdemeanour, including no possibil- ity for jail time have been created for individuals caught with small, personal amounts of cannabis (NCSL, 2019). Of note, while cannabis possession and use remains federally illegal, the Justice Department has not enforced federal law in states that have legal- ized cannabis, under the guidance of the Cole Memorandum that was adopted in August 2013 (DAG, 2013). However, this Memorandum has been rescinded in January 2018, granting U.S. Attorneys greater authority to enforce federal law (DAG, 2013, 2018). It is the hope that decriminalization of mari- juana will positively impact youth and minority com- munities, resulting in lower utilization of the criminal justice system, overall diminished incarceration rates, and potentially decreased rates of disproportionally incarcerated minority youth (ACLU, 2019).

Regarding the impact of changes in marijuana legislation on beliefs, behaviours, and health outcomes in U.S. youth, the results to date have been mixed and difficult to interpret. Adolescents living in states that have passed marijuana legislation report that can- nabis is more easily accessible (Harpin, Brooks- Russell, Ma, James, & Levinson, 2018). Over the past two decades during which time most marijuana

legislation has passed, the perception that cannabis is harmful has decreased dramatically and is near all-time low levels among U.S. adolescents and young adults nationally, regardless of state of residence (Keyes et al., 2016; Miech, Johnston, & O’Malley, 2017). This is wor- risome given the historic data showing that increased use typically follows a reduction in perception of harm for psychoactive drugs. The impact of marijuana legis- lation on cannabis engagement patterns in adolescents stratified by state of residence show minimal impact. For example, numerous studies have shown that legal- ization of medical marijuana has not led to an increase in recreational use by adolescents (Ammerman et al., 2015). However, states that have legalized marijuana already had relatively higher rates of adolescent canna- bis use before legalization occurred (Ammerman et al., 2015). Additionally, with the legalization of marijuana other deleterious effects from cannabis use have increased in states with marijuana legislation including: increased motor vehicle accidents and fatalities second- ary to cannabis use; accidental overdoses of cannabis by young children and pets; and increased emergency department visits and hospitalizations as a result of higher-potency cannabis use leading to psychosis, depression and anxiety (Committee on Substance Abuse, & the Committee on Adolescence, 2015; Hall et al., 2018; Hopfer, 2014; Sevigny, 2018; Tefft, Arnold, & Grabowski, 2016; Wang, 2017). Marijuana legaliza- tion has also led to increased intention to use, diver- sion from dispensaries, and recreational use of medical marijuana by U.S. adolescents, including those enrolled in substance abuse treatment (Boyd, Veliz, & McCabe, 2015; Harpin et al., 2018; Salomonsen-Sautel, Sakai, Thurstone, Corley, & Hopfer, 2012). Furthermore, legalization impacts the likelihood, and age at which, youth use non-combustible cannabis methods such as vaping and edible cannabis (Borodovsky et al., 2017). Most published studies in this area have come from ecological state-level analyses comparing population- wide rates of use, beliefs, and negative outcomes between adolescents residing in states that have and have not passed marijuana related legislation. These ecological studies are highly limited in their interpret- ability and causal associations cannot be drawn from them (McCarty, 2018). Future studies, examining dif- ferences at the individual person-level are greatly needed.

Conclusions

Over the past 25 years changing marijuana policies have contributed to reductions in public perception of

228 C. J. HAMMOND ET AL.

harm, increased accessibility, and shifts in types and modes of cannabis use among U.S. youth, but has not resulted in increased use to date as feared by many opponents of marijuana legalization. Still, given the increased rates of cannabis use and related disorders among U.S. adults (including parents) and growing evidence that adolescent-onset cannabis use is associ- ated with multiple negative health outcomes, children and adolescents clearly represent a high-risk group. Adolescent cannabis use, especially early-onset, chronic, high frequency, and high-potency cannabis use is associated with impairments in cognitive func- tion; increased prevalence of mood, psychotic, and addictive disorders; and poorer academic/vocational outcomes. While some of the variances in these out- comes can be attributed to socioeconomic status, IQ, and mental health conditions that predate cannabis initiation, many studies have identified significant effects of adolescent-onset cannabis use even after controlling for these variables suggesting that canna- bis use itself may play a central role. Future research is needed to determine whether this represents causal- ity and to clarify whether direct or indirect pathways exist. Identifying youth at elevated risk for initiating cannabis early and for developing chronic high fre- quency cannabis use and CUD is highly important. Risk and prognostic factors emerging during child- hood and adolescence can provide a roadmap for tar- geted prevention and early intervention strategies that are part of a larger continuum of treatment for CUD. In addition to clarifying potential medical benefits, future cannabis research efforts should also focus on prevention and early intervention for cannabis use and on clarifying individual differences in vulnerabil- ity to developing CUD.

With significant marijuana legalization lobbyist efforts and changing public perception regarding marijuana amongst Americans, marijuana legalization policies are poised to continue in the U.S. As U.S. marijuana legalization policy initiatives move forward, state legislatures should rely more on scientific evi- dence from high quality replicated studies in humans and less on preclinical studies, anecdotal reports, and public opinion in developing future legislation. Elected officials should be transparent about potential conflicts of interest, such as marijuana lobbyist contri- butions or their own personal investments in the marijuana industry, as the presence of these conflicts may influence or compromise professional judgment and objectivity.

Marijuana legislation in the U.S. has resulted in a number of downstream effects, some positive such as

decriminalization and reduced justice involvement, and some negative such as increasing rates of CUDs and emergency-related healthcare visits. Future mari- juana legislation should find a balance between poten- tial risks and benefits for individuals of all ages across the lifespan, and not discount the risk for negative consequences of policy change on youth.

Disclosure statement

Dr. Hammond receives grant support from the National Institute on Drug Abuse/American Academy of Child & Adolescent Psychiatry (NIDA/AACAP) career development award (K12DA000357) and serves as a scientific advisor for the National Courts and Science Institute. Dr. Sharma receives grant support from an AACAP Pilot Research Award for Junior Faculty. Drs. Chaney and Hendrickson report no conflicts or financial disclosures.

Funding

Support for this study came from a National Institute on Drug Abuse/American Academy of Child & Adolescent Psychiatry (NIDA/AACAP) Physician Scholar in Substance Abuse Research grant K12DA000357 (Hammond) and an AACAP Pilot Research Award for Junior Faculty (Sharma).

ORCID

Christopher J. Hammond http://orcid.org/0000-0003- 3540-8201

References

ACLU (2019). Marijuana Law Reform. American Civil Liberties Union. Retrieved from https://www.aclu.org/ issues/criminacl-law-reform/drug-law-reform/marijuana- law-reform?redirect=criminal-law-reform/marijuana-law- reform

Agrawal, A., Nelson, E. C., Bucholz, K. K., Tillman, R., Grucza, R. A., Statham, D. J., … Lynskey, M. T. (2017). Major depressive disorder, suicidal thoughts and behav- iours, and cannabis involvement in discordant twins: A retrospective cohort study. The Lancet Psychiatry, 4(9), 706–714. doi:10.1016/S2215-0366(17)30280-8

Alderson, H. L., Semple, D. M., Blayney, C., Queirazza, F., Chekuri, V., & Lawrie, S. M. (2017). Risk of transition to schizophrenia following first admission with substance- induced psychotic disorder: A population-based longitu- dinal cohort study. Psychological Medicine, 47(14), 2548–2555. doi:10.1017/S0033291717001118

Ammerman, S., Ryan, S., Adelman, W. P., Committee on Substance Abuse, & the Committee on Adolescence, (2015). The impact of marijuana policies on youth: Clinical, research, and legal update. PEDIATRICS, 135(3), e769–e785. doi:10.1542/peds.2014-4147

INTERNATIONAL REVIEW OF PSYCHIATRY 229

Bloomfield, M. A. P., Hindocha, C., Green, S. F., Wall, M. B., Lees, R., Petrilli, K., … Freeman, T. P. (2019). The neuropsychopharmacology of cannabis: A review of human imaging studies. Pharmacology & Therapeutics, 195, 132–161. doi:10.1016/j.pharmthera.2018.10.006

Borodovsky, J. T., Lee, D. C., Crosier, B. S., Gabrielli, J. L., Sargent, J. D., & Budney, A. J. (2017). U.S. cannabis legalization and use of vaping and edible products among youth. Drug and Alcohol Dependence, 177, 299–306. doi:10.1016/j.drugalcdep.2017.02.017

Boyd, C. J., Veliz, P. T., & McCabe, S. E. (2015). Adolescents’ Use of Medical Marijuana: A Secondary Analysis of Monitoring the Future Data. Journal of Adolescent Health, 57(2), 241–244. doi:10.1016/j.jado- health.2015.04.008

Buckner, J. D., Heimberg, R. G., Schneier, F. R., Liu, S. M., Wang, S., & Blanco, C. (2012). The relationship between cannabis use disorders and social anxiety disorder in the National Epidemiological Study of Alcohol and Related Conditions (NESARC). Drug and Alcohol Dependence, 124(1-2), 128–134. doi:10.1016/j.drugalcdep.2011.12.023

Buckner, J. D., Schmidt, N. B., Lang, A. R., Small, J. W., Schlauch, R. C., & Lewinsohn, P. M. (2008). Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. Journal of Psychiatric Research, 42(3), 230–239. doi:10.1016/j.jpsychires.2007.01.002

Buckner, J. D., Zvolensky, M. J., Ecker, A. H., Jeffries, E. R., Lemke, A. W., Dean, K. E., … Gallagher, M. W. (2017). Anxiety and cannabis-related problem severity among dually diagnosed outpatients: The impact of false safety behaviors. Addictive Behaviors, 70, 49–53. doi:10.1016/j. addbeh.2017.02.014

CDC (2019). Outbreak of Lung Illness Associated with Using E-cigarette Products. Investigation Notice. Retrieved from https://www.cdc.gov/tobacco/basic_infor- mation/e-cigarettes/severe-lung-disease.html

Cerda, M., Wall, M., Keyes, K. M., Galea, S., & Hasin, D. (2012). Medical marijuana laws in 50 states: Investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence. Drug and Alcohol Dependence, 120(1-3), 22–27. doi:10. 1016/j.drugalcdep.2011.06.011

Coffey, C., Carlin, J. B., Lynskey, M., Li, N., & Patton, G. C. (2003). Adolescent precursors of cannabis depend- ence: Findings from the Victorian Adolescent Health Cohort Study. British Journal of Psychiatry, 182(4), 330–336. doi:10.1192/bjp.182.4.330

Coffey, C., & Patton, G. C. (2016). Cannabis use in adoles- cence and young adulthood: A review of findings from the Victorian adolescent health cohort study. The Canadian Journal of Psychiatry, 61(6), 318–327. doi:10. 1177/0706743716645289

Committee on Substance Abuse, & Committee on Adolescence. (2015). The impact of marijuana policies on youth: Clinical, research, and legal update. Pediatrics, 135(3), 584–587. doi:10.1542/peds.2014-4146

Cornelius, J. R., Kirisci, L., Reynolds, M., Clark, D. B., Hayes, J., & Tarter, R. (2010). PTSD contributes to teen and young adult cannabis use disorders. Addictive Behaviors, 35(2), 91–94. doi:10.1016/j.addbeh.2009.09.007

D’souza, D. C., Radhakrishnan, R., Sherif, M., Cortes- Briones, J., Cahill, J., Gupta, S., … M, R. (2016).

Cannabinoids and Psychosis. Current Pharmaceutical Design, 22(42), 6380–6391. doi:10.2174/ 1381612822666160826105628

DAG (2013). Memorandum for All United States Attorneys: Guidance Regarding Marijuana Enforcement. Office of the Deputy Attorney General Retrieved from https://www.justice.gov/opa/press-release/file/1022196/ download

DAG (2018). Memorandum for All United States Attorneys: Marijuana Enforcement. Office of the Deputy Attorney General Retrieved from https://www.justice.gov/ opa/press-release/file/1022196/download

Davis, J. M., Mendelson, B., Berkes, J. J., Suleta, K., Corsi, K. F., & Booth, R. E. (2016). Public Health Effects of Medical Marijuana Legalization in Colorado. American Journal of Preventive Medicine, 50(3), 373–379. doi:10. 1016/j.amepre.2015.06.034

DEA (2019). U.S. Drug Enforcement Agency. Drug Scheduling. Retrieved from https://www.dea.gov/drug- scheduling

Degenhardt, L., Coffey, C., Romaniuk, H., Swift, W., Carlin, J. B., Hall, W. D., & Patton, G. C. (2013). The persist- ence of the association between adolescent cannabis use and common mental disorders into young adulthood. Addiction, 108(1), 124–133. doi:10.1111/j.1360-0443.2012. 04015.x

Degenhardt, L., Hall, W., & Lynskey, M. (2003). Exploring the association between cannabis use and depression. Addiction, 98(11), 1493–1504. doi:10.1046/j.1360-0443. 2003.00437.x

Di Forti, M., Sallis, H., Allegri, F., Trotta, A., Ferraro, L., Stilo, S. A., … Murray, R. M. (2014). Daily use, espe- cially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophrenia Bulletin, 40(6), 1509–1517. doi:10.1093/schbul/sbt181

Dougherty, D. M., Mathias, C. W., Dawes, M. A., Furr, R. M., Charles, N. E., Liguori, A., … Acheson, A. (2013). Impulsivity, attention, memory, and decision- making among adolescent marijuana users. Psychopharmacology, 226(2), 307–319. doi:10.1007/ s00213-012-2908-5

Dutra, L. M., Parish, W. J., Gourdet, C. K., Wylie, S. A., & Wiley, J. L. (2018). Medical cannabis legalization and state-level prevalence of serious mental illness in the National Survey on Drug Use and Health (NSDUH) 2008-2015. International Review of Psychiatry, 30(3), 203–215. doi:10.1080/09540261.2018.1467385

ElSohly, M. A., Mehmedic, Z., Foster, S., Gon, C., Chandra, S., & Church, J. C. (2016). Changes in Cannabis Potency Over the Last 2 Decades (1995-2014): Analysis of Current Data in the United States. Biological Psychiatry, 79(7), 613–619. doi:10.1016/j.biopsych.2016.01.004

Fergusson, D. M., Boden, J. M., & Horwood, L. J. (2015). Psychosocial sequelae of cannabis use and implications for policy: Findings from the Christchurch Health and Development Study. Social Psychiatry and Psychiatric Epidemiology, 50(9), 1317–1326. doi:10.1007/s00127-015- 1070-x

Fergusson, D. M., & Horwood, L. J. (1997). Early onset cannabis use and psychosocial adjustment in young adults. Addiction, 92(3), 279–296. doi:10.1111/j.1360- 0443.1997.tb03198.x

230 C. J. HAMMOND ET AL.

Findlaw (2019). Marijuana Legalization and Decriminalization Overview Retrieved from https://crim- inal.findlaw.com/criminal-charges/marijuana-legalization- and-decriminalization-overview.html

Firth, C. L., Maher, J. E., Dilley, J. A., Darnell, A., & Lovrich, N. P. (2019). Did marijuana legalization in Washington State reduce racial disparities in adult mari- juana arrests? Substance Use & Misuse, 54, 1582–1587. doi:10.1080/10826084.2019.1593007

Fontes, M. A., Bolla, K. I., Cunha, P. J., Almeida, P. P., Jungerman, F., Laranjeira, R. R., … Lacerda, A. L. T. (2011). Cannabis use before age 15 and subsequent executive functioning. British Journal of Psychiatry, 198(6), 442–447. doi:10.1192/bjp.bp.110.077479

Fridberg, D. J., Vollmer, J. M., O’Donnell, B. F., & Skosnik, P. D. (2011). Cannabis users differ from non-users on measures of personality and schizotypy. Psychiatry Research, 186(1), 46–52. doi:10.1016/j.psychres.2010.07. 035

Gobbi, G., Atkin, T., Zytynski, T., Wang, S., Askari, S., Boruff, J., … Mayo, N. (2019). Association of Cannabis Use in Adolescence and Risk of Depression, Anxiety, and Suicidality in Young Adulthood: A Systematic Review and Meta-analysis. JAMA Psychiatry, 76(4), 426–434. doi: 10.1001/jamapsychiatry.2018.4500

Gorey, C., Kuhns, L., Smaragdi, E., Kroon, E., & Cousijn, J. (2019). Age-related differences in the impact of cannabis use on the brain and cognition: A systematic review. European Archives of Psychiatry and Clinical Neuroscience, 269(1), 37–58. doi:10.1007/s00406-019- 00981-7

Governing (2019). State Marijuana Laws in 2019 Map. Governing. Retrieved from https://www.governing.com/ gov-data/safety-justice/state-marijuana-laws-map-med- ical-recreational.html

Gruber, S. A., Sagar, K. A., Dahlgren, M. K., Racine, M., & Lukas, S. E. (2012). Age of onset of marijuana use and executive function. Psychology of Addictive Behaviors, 26(3), 496–506. doi:10.1037/a0026269

Hall, K. E., Monte, A. A., Chang, T., Fox, J., Brevik, C., Vigil, D. I., … James, K. A. (2018). Mental health- related emergency department visits associated with Cannabis in Colorado. Academic Emergency Medicine, 25(5), 526–537. doi:10.1111/acem.13393

Hall, W., & Degenhardt, L. (2008). Cannabis use and the risk of developing a psychotic disorder. World Psychiatry, 7(2), 68–71. doi:10.1002/j.2051-5545.2008.tb00158.x

Hall, W., & Degenhardt, L. (2015). High potency cannabis. BMJ, 350(mar04 4), h1205–h1205. doi:10.1136/bmj.h1205

Hall, W., & Lynskey, M. (2016). Evaluating the public health impacts of legalizing recreational cannabis use in the United States. Addiction, 111(10), 1764–1773. doi:10. 1111/add.13428

Hanson, K. L., Winward, J. L., Schweinsburg, A. D., Medina, K. L., Brown, S. A., & Tapert, S. F. (2010). Longitudinal study of cognition among adolescent mari- juana users over three weeks of abstinence. Addictive Behaviors, 35(11), 970–976. doi:10.1016/j.addbeh.2010.06. 012

Harpin, S. B., Brooks-Russell, A., Ma, M., James, K. A., & Levinson, A. H. (2018). Adolescent marijuana use and perceived ease of access before and after recreational

marijuana implementation in Colorado. Substance Use & Misuse, 53(3), 451–456. doi:10.1080/10826084.2017. 1334069

Hasin, D. S., Sarvet, A. L., Cerda, M., Keyes, K. M., Stohl, M., Galea, S., & Wall, M. M. (2017). US adult illicit can- nabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013. JAMA Psychiatry, 74(6), 579–588. doi:10.1001/jamapsychiatry.2017.0724

Hopfer, C. (2014). Implications of marijuana legalization for adolescent substance use. Substance Abuse, 35(4), 331–335. doi:10.1080/08897077.2014.943386

Horwood, L. J., Fergusson, D. M., Coffey, C., Patton, G. C., Tait, R., Smart, D., … Hutchinson, D. M. (2012). Cannabis and depression: An integrative data analysis of four Australasian cohorts. Drug and Alcohol Dependence, 126(3), 369–378. doi:10.1016/j.drugalcdep.2012.06.002

Hser, Y.-I., Mooney, L. J., Huang, D., Zhu, Y., Tomko, R. L., McClure, E., … Gray, K. M. (2017). Reductions in cannabis use are associated with improvements in anx- iety, depression, and sleep quality, but not quality of life. Journal of Substance Abuse Treatment, 81, 53–58. doi:10. 1016/j.jsat.2017.07.012

Hunault, C. C., Mensinga, T. T., B€ocker, K. B. E., Schipper, C. M. A., Kruidenier, M., Leenders, M. E. C., … Meulenbelt, J. (2009). Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9-tetrahydro- cannabinol (THC). Psychopharmacology, 204(1), 85–94. doi:10.1007/s00213-008-1440-0

Hyman, S. M., & Sinha, R. (2009). Stress-related factors in cannabis use and misuse: Implications for prevention and treatment. Journal of Substance Abuse Treatment, 36(4), 400–413. doi:10.1016/j.jsat.2008.08.005

Jackson, N. J., Isen, J. D., Khoddam, R., Irons, D., Tuvblad, C., Iacono, W. G., … Baker, L. A. (2016). Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies. Proceedings of the National Academy of Sciences of the United States of America, 113(5), E500–E508. doi:10.1073/pnas.1516648113

Jacobus, J., Bava, S., Cohen-Zion, M., Mahmood, O., & Tapert, S. F. (2009). Functional consequences of mari- juana use in adolescents. Pharmacology Biochemistry and Behavior, 92(4), 559–565. doi:10.1016/j.pbb.2009.04.001

Jacobus, J., Squeglia, L. M., Escobar, S., McKenna, B. M., Hernandez, M. M., Bagot, K. S., … Huestis, M. A. (2017). Changes in marijuana use symptoms and emo- tional functioning over 28-days of monitored abstinence in adolescent marijuana users. Psychopharmacology, 234(23-24), 3431–3442. doi:10.1007/s00213-017-4725-3

Jaffe, S. L., & Klein, M. (2010). Medical marijuana and ado- lescent treatment. The American Journal on Addictions, 19(5), 460–461. doi:10.1111/j.1521-0391.2010.00063.x

Jernigan, T. L., & Brown, S. A, & ABCD Consortium Coordinators. (2018). Introduction. Developmental Cognitive Neuroscience, 32, 1–3. doi:10.1016/j.dcn.2018. 02.002

Johnston, L. D., Miech, R. A., O’Malley, P. M., Bachman, J. G., Schulenberg, J. E., & Patrick, M. E. (2018). Monitoring the Future national survey results on drug use, 1975-2017: Overview, key findings on adolescent drug use.

INTERNATIONAL REVIEW OF PSYCHIATRY 231

Kaminer, Y. (2017). The denial of the association between youth cannabis and opiate use: A “Split Brain Syndrome”? Substance Abuse, 38(4), 367–368. doi:10. 1080/08897077.2017.1380456

Kedzior, K. K., & Laeber, L. T. (2014). A positive associ- ation between anxiety disorders and cannabis use or can- nabis use disorders in the general population–a meta- analysis of 31 studies. BMC Psychiatry, 14(1), 136. doi:10. 1186/1471-244X-14-136

Keyes, K. M., Wall, M., Cerd�a, M., Schulenberg, J., O’Malley, P. M., Galea, S., … Hasin, D. S. (2016). How does state marijuana policy affect US youth? Medical marijuana laws, marijuana use and perceived harmful- ness: 1991-2014. Addiction, 111(12), 2187–2195. doi:10. 1111/add.13523

Kowitt, S. D., Osman, A., Meernik, C., Zarkin, G. A., Ranney, L. M., Martin, J., … Goldstein, A. O. (2019). Vaping cannabis among adolescents: Prevalence and associations with tobacco use from a cross-sectional study in the USA. BMJ Open, 9(6), e028535. doi:10.1136/ bmjopen-2018-028535

Lee, J. Y., Brook, J. S., Finch, S. J., & Brook, D. W. (2018). Trajectories of cannabis use beginning in adolescence associated with symptoms of posttraumatic stress dis- order in the mid-thirties. Substance Abuse, 39(1), 39–45. doi:10.1080/08897077.2017.1363121

Lev-Ran, S., Roerecke, M., Le Foll, B., George, T. P., McKenzie, K., & Rehm, J. (2014). The association between cannabis use and depression: A systematic review and meta-analysis of longitudinal studies. Psychological Medicine, 44(4), 797–810. doi:10.1017/ S0033291713001438

Levine, A., Clemenza, K., Rynn, M., & Lieberman, J. (2017). Evidence for the Risks and Consequences of Adolescent Cannabis Exposure. Journal of the American Academy of Child & Adolescent Psychiatry, 56(3), 214–225. doi:10. 1016/j.jaac.2016.12.014

Lisdahl, K. M., Wright, N. E., Kirchner-Medina, C., Maple, K. E., & Shollenbarger, S. (2014). The effects of regular cannabis use on neurocognition in adolescents and young adults. Current Addiction Reports, 1(2), 144–156. doi:10.1007/s40429-014-0019-6

Lyon, M. J., Bar, J. L., & Panizzon, M. S. (2004). Neuropsychological consequences of regular marijuana use: A twin study. Psychological Medicine, 34, 1239–1250. doi:10.1017/S0033291704002260

McCarty, D. (2018). Does medical cannabis reduce use of prescription opioids? American Journal of Psychiatry, 175(1), 6–7. doi:10.1176/appi.ajp.2017.17090958

Medina, K. L., Hanson, K. L., Schweinsburg, A. D., Cohen- Zion, M., Nagel, B. J., & Tapert, S. F. (2007). Neuropsychological functioning in adolescent marijuana users: Subtle deficits detectable after a month of abstin- ence. Journal of the International Neuropsychological Society , 13(5), 807–820. doi:10.1017/S1355617707071032

Meier, M. H., Caspi, A., Ambler, A., Harrington, H., Houts, R., Keefe, R. S. E., … Moffitt, T. E. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Sciences, 109(40), E2657–2664. doi:10.1073/ pnas.1206820109

Michigan, U. o. (2018). National study shows marijuana use among U.S. college students remains at highest level in three decades; Heavy marijuana use rising among youth not in college. [Press release]. Retrieved from https://isr.umich.edu/news-events/news-releases/national- study-shows-marijuana-use-among-u-s-college-students- remains-at-highest-level-in-three-decades-heavy-mari- juana-use-rising-among-youth-not-in-college/

Miech, R., Johnston, L., & O’Malley, P. M. (2017). Prevalence and attitudes regarding marijuana use among adolescents over the past decade. Pediatrics, 140(6), e20170982. doi:10.1542/peds.2017-0982

Miller, R., Ream, G., McCormack, J., Gunduz-Bruce, H., Sevy, S., & Robinson, D. (2009). A prospective study of cannabis use as a risk factor for non-adherence and treatment dropout in first-episode schizophrenia. Schizophrenia Research, 113(2-3), 138–144. doi:10.1016/j. schres.2009.04.018

Mitchell, T. (2019). July 18, 2019). State health officials in colorado preparing for more medical marijuana access. WestWorld. Retrieved from https://www.westword.com/ marijuana/colorado-health-officials-preparing-for-more- medical-marijuana-access-11414656

Moitra, E., Anderson, B. J., & Stein, M. D. (2016). Reductions in cannabis use are associated with mood improvement in female emerging adults. Depression and Anxiety, 33(4), 332–338. doi:10.1002/da.22460

Mokrysz, C., Landy, R., Gage, S. H., Munaf�o, M. R., Roiser, J. P., & Curran, H. V. (2016). Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study. Journal of Psychopharmacology, 30(2), 159–168. doi:10.1177/0269881115622241

Moore, T. H., Zammit, S., Lingford-Hughes, A., Barnes, T. R., Jones, P. B., Burke, M., & Lewis, G. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. The Lancet, 370(9584), 319–328. doi:10.1016/S0140-6736(07)61162-3

NCCIH (2018). Marijuana and Cannabinoids Retrieved from https://nccih.nih.gov/health/marijuana

NCSL (2019). Marijuana Overview. Retrieved from http:// www.ncsl.org/research/civil-and-criminal-justice/mari- juana-overview.aspx

NIDA (2019). Marijuana as Medicine. Retrieved from https://www.drugabuse.gov/publications/drugfacts/mari- juana-medicine

Nocon, A., Wittchen, H. U., Pfister, H., Zimmermann, P., & Lieb, R. (2006). Dependence symptoms in young can- nabis users? A prospective epidemiological study. Journal of Psychiatric Research, 40(5), 394–403. doi:10.1016/j. jpsychires.2005.07.011

Olfson, M., Wall, M. M., Liu, S. M., & Blanco, C. (2018). Cannabis use and risk of prescription opioid use disorder in the United States. American Journal of Psychiatry, 175(1), 47–53. doi:10.1176/appi.ajp.2017.17040413

Pacula, R. L., & Smart, R. (2017). Medical marijuana and marijuana legalization. Annual Review of Clinical Psychology, 13(1), 397–419. doi:10.1146/annurev-clinpsy- 032816-045128

Patton, G. C., Coffey, C., Carlin, J. B., Sawyer, S. M., & Lynskey, M. (2005). Reverse gateways? Frequent cannabis use as a predictor of tobacco initiation and nicotine

232 C. J. HAMMOND ET AL.

dependence. Addiction, 100(10), 1518–1525. doi:10.1111/ j.1360-0443.2005.01220.x

Peters, E. N., Bae, D., Barrington-Trimis, J. L., Jarvis, B. P., & Leventhal, A. M. (2018). Prevalence and Sociodemographic Correlates of Adolescent Use and Polyuse of Combustible, Vaporized, and Edible Cannabis Products. JAMA Network Open, 1(5), e182765. doi:10. 1001/jamanetworkopen.2018.2765

Pistis, M., Perra, S., Pillolla, G., Melis, M., Muntoni, A. L., & Gessa, G. L. (2004). Adolescent exposure to cannabi- noids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biological Psychiatry, 56(2), 86–94. doi:10.1016/j.biop- sych.2004.05.006

Pope, H. G., Gruber, A. J., Hudson, J. I., Cohane, G., Huestis, M. A., & Yurgelun-Todd, D. (2003). Early-onset cannabis use and cognitive deficits: What is the nature of the association? Drug and Alcohol Dependence, 69(3), 303–310. doi:10.1016/S0376-8716(02)00334-4

Renard, J., Rosen, L. G., Loureiro, M., De Oliveira, C., Schmid, S., Rushlow, W. J., & Laviolette, S. R. (2016). Adolescent cannabinoid exposure induces a persistent sub-cortical hyper-dopaminergic state and associated molecular adaptations in the prefrontal cortex. Cereb Cortex, 27, 1297–1310 doi:10.1093/cercor/bhv335

Sagar, K. A., & Gruber, S. A. (2018). Marijuana matters: Reviewing the impact of marijuana on cognition, brain structure and function, & exploring policy implications and barriers to research. International Review of Psychiatry, 30(3), 251–267. doi:10.1080/09540261.2018. 1460334

Sahlem, G. L., Tomko, R. L., Sherman, B. J., Gray, K. M., & McRae-Clark, A. L. (2018). Impact of cannabis legaliza- tion on treatment and research priorities for cannabis use disorder. International Review of Psychiatry, 30(3), 216–225. doi:10.1080/09540261.2018.1465398

Salomonsen-Sautel, S., Sakai, J. T., Thurstone, C., Corley, R., & Hopfer, C. (2012). Medical marijuana use among adolescents in substance abuse treatment. Journal of the American Academy of Child and Adolescent Psychiatry, 51(7), 694–702. doi:10.1016/j.jaac.2012.04.004

Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Behavioral Health Statistics and Quality. (2017). Treatment Episode Data Set (TEDS): 2005-2015. National Admissions to Substance Abuse Treatment Services. BHSIS Series S-91, HHS Publication No. (SMA) 17-5037. Rockville, MD: Substance Abuse and Mental Health Services Administration.

SAMHSA (2018). Key substance use and mental health indicators in the United States: Results from the 2016 National Survey on Drug Use and Health (HHS Publication No. SMA 17-5044, NSDUH Series H-52). Rockville, MD: Substance Abuse and Mental Health Services Administration.

SAMHSA (2019). Treatment Episode Data Set (TEDS): 2017. Admissions to and Discharges from Publicly- Funded Substance Use Treatment. Retrieved from Rockville, MD: Substance Abuse and Mental Health Services Administration.

Schier, J., Meiman, J., & Layden, J. (2019). Severe pulmon- ary disease associated with electronic-cigarette–product

use — interim guidance. MMWR Morb Mortal Wkly Rep 68, 787–790. doi:10.15585/mmwr.mm6836e2

Schoeler, T., Petros, N., Di Forti, M., Pingault, J.-B., Klamerus, E., Foglia, E., … Bhattacharyya, S. (2016). Association between continued cannabis use and risk of relapse in first-episode psychosis: A Quasi-experimental investigation within an observational study. JAMA Psychiatry, 73(11), 1173–1179. doi:10.1001/jamapsychia- try.2016.2427

Scholes-Balog, K. E., Hemphill, S. A., Evans-Whipp, T. J., Toumbourou, J. W., & Patton, G. C. (2016). Developmental trajectories of adolescent cannabis use and their relationship to young adult social and behav- ioural adjustment: A longitudinal study of Australian youth. Addictive Behaviors, 53, 11–18. doi:10.1016/j.add- beh.2015.09.008

Schulenberg, J., Johnston, L., O’Malley, P., Bachman, J., Miech, R., & Patrick, M. (2018). Monitoring the Future national survey results on drug use, 1975-2017: Volume 2, College students and adults ages 19-55. Ann Arbor, MI.

Sevigny, E. L. (2018). The effects of medical marijuana laws on cannabis-involved driving. Accident Analysis & Prevention, 118, 57–65. doi:10.1016/j.aap.2018.05.023

Silins, E., Horwood, L. J., Patton, G. C., Fergusson, D. M., Olsson, C. A., Hutchinson, D. M., … Mattick, R. P. (2014). Young adult sequelae of adolescent cannabis use: An integrative analysis. The Lancet Psychiatry, 1(4), 286–293. doi:10.1016/S2215-0366(14)70307-4

Silins, E., Swift, W., Slade, T., Toson, B., Rodgers, B., & Hutchinson, D. M. (2017). A prospective study of the substance use and mental health outcomes of young adult former and current cannabis users. Drug and Alcohol Review, 36(5), 618–625. doi:10.1111/dar.12512

Swift, W., Coffey, C., Carlin, J. B., Degenhardt, L., & Patton, G. C. (2008). Adolescent cannabis users at 24 years: Trajectories to regular weekly use and dependence in young adulthood. Addiction, 103(8), 1361–1370. doi: 10.1111/j.1360-0443.2008.02246.x

Swift, W., Coffey, C., Degenhardt, L., Carlin, J. B., Romaniuk, H., & Patton, G. C. (2012). Cannabis and progression to other substance use in young adults: Findings from a 13-year prospective population-based study. Journal of Epidemiology and Community Health, 66(7), e26–e26. doi:10.1136/jech.2010.129056

Tait, R. J., Mackinnon, A., & Christensen, H. (2011). Cannabis use and cognitive function: 8-year trajectory in a young adult cohort. Addiction, 106(12), 2195–2203. doi:10.1111/j.1360-0443.2011.03574.x

Tefft, B. C., Arnold, L. S., & Grabowski, J. G. (2016). Prevalence of marijuana involvement in fatal crashes: Washington, 2010 – 2014. Retrieved from Washington, DC: https://aaafoundation.org/wp-content/uploads/2017/ 12/PrevalenceOfMarijuanaInvolvement.pdf

Tucker, J. S., Rodriguez, A., Pedersen, E. R., Seelam, R., Shih, R. A., & D’Amico, E. J. (2019). Greater risk for fre- quent marijuana use and problems among young adult marijuana users with a medical marijuana card. Drug and Alcohol Dependence, 194, 178–183. doi:10.1016/j.dru- galcdep.2018.09.028

Vandrey, R. (2018). The cannabis conundrum: Steering pol- icy and medicine with insufficient data. International

INTERNATIONAL REVIEW OF PSYCHIATRY 233

Review of Psychiatry, 30(3), 181–182. doi:10.1080/ 09540261.2018.1491107

Vandrey, R., Raber, J. C., Raber, M. E., Douglass, B., Miller, C., & Bonn-Miller, M. O. (2015). Cannabinoid dose and label accuracy in edible medical cannabis products. JAMA, 313(24), 2491–2493. doi:10.1001/jama.2015.6613

Volkow, N. D., Swanson, J. M., Evins, A. E., DeLisi, L. E., Meier, M. H., Gonzalez, R., … Baler, R. (2016). Effects of cannabis use on human behavior, including cognition, motivation, and psychosis: a review. JAMA Psychiatry, 73(3), 292–297. doi:10.1001/jamapsychiatry.2015.3278

Wang, G. S. (2017). Pediatric concerns due to expanded cannabis use: Unintended consequences of legalization. Journal of Medical Toxicology, 13, 99–105. doi:10.1007/ s13181-016-0552-x

Whiting, P. F., Wolff, R. F., Deshpande, S., Di Nisio, M., Duffy, S., Hernandez, A. V., … Kleijnen, J. (2015). Cannabinoids for medical use: a systematic review and meta-analysis. JAMA, 313(24), 2456–2473. doi:10.1001/ jama.2015.6358

WHO (2019). The health and social effects of nonmedical cannabis use. Retrieved from https://www.who.int/sub- stance_abuse/publications/cannabis_report/en/

Wilkinson, S. T., Radhakrishnan, R., & D’Souza, D. C. (2014). Impact of cannabis use on the development of psychotic disorders. Current Addiction Reports, 1(2), 115–128. doi:10.1007/s40429-014-0018-7

Windle, M., & Wiesner, M. (2004). Trajectories of marijuana use from adolescence to young adulthood: Predictors and outcomes. Development and Psychopathology, 16(4), 1007–1027. doi:10.1017/s0954579404040118

Zhang, Z., Zheng, X., Zeng, D. D., & Leischow, S. J. (2016). Tracking dabbing using search query surveillance: a case study in the United States. Journal of Medical Internet Research, 18(9), e252. doi:10.2196/jmir.5802

Zvolensky, M. J., Bernstein, A., Sachs-Ericsson, N., Schmidt, N. B., Buckner, J. D., & Bonn-Miller, M. O. (2006). Lifetime associations between cannabis, use, abuse, and dependence and panic attacks in a representative sample. Journal of Psychiatric Research, 40(6), 477–486. doi:10. 1016/j.jpsychires.2005.09.005

Zvolensky, M. J., Lewinsohn, P., Bernstein, A., Schmidt, N. B., Buckner, J. D., Seeley, J., & Bonn-Miller, M. O. (2008). Prospective associations between cannabis use, abuse, and dependence and panic attacks and disorder. Journal of Psychiatric Research, 42(12), 1017–1023. doi: 10.1016/j.jpsychires.2007.10.012

234 C. J. HAMMOND ET AL.

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