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. Author manuscript; available in PMC: 2019 Jun 29.
Published in final edited form as: Int Rev Psychiatry. 2018 Jun 29;30(3):216–225. doi: 10.1080/09540261.2018.1465398

Impact of cannabis legalization on treatment and research priorities for Cannabis Use Disorder

Gregory L Sahlem 1, Rachel L Tomko 1, Brian J Sherman 1, Kevin M Gray 1, Aimee L McRae-Clark 1,2
PMCID: PMC6322658  NIHMSID: NIHMS1507155  PMID: 29956576

Abstract

An increasing portion of the world has legalized cannabis for medicinal or recreational use. The legalization trend appears to be continuing. These changes in the legislative landscape may have important health, treatment, and research implications. This review discusses public health outcomes that may be impacted by increases in cannabis availability and use. It additionally considers potential research and treatment priorities in the face of widespread cannabis legalization.

Keywords: cannabis, legalization, marijuana, treatment, cannabis use disorder

Introduction

As of early 2018, many parts of the world, including twenty-nine of the United States (U.S.) have adopted laws broadly legalizing cannabis in some form, ranging from decriminalization, to outright legalization for recreational purposes. Changes in the legal landscape for cannabis have followed large scale shifts in public opinion towards cannabis. The perceived risks associated with regular cannabis use appear to have decreased for both adolescents (Johnston et al., 2016; Compton & Han, 2018) and adults (Compton & Han, 2018). In an initial 1969 Gallup poll, 12% of American citizens supported cannabis legalization in the U.S.; the most recent poll in October 2017 found 64% of respondents in favor of making cannabis legal (Gallup, 2017). In addition, approximately 17% of cannabis users identify themselves as medicinal users, further normalizing the use of cannabis (Lin et al., 2016).

As large-scale efforts to legalize cannabis will likely continue to be successful, it is important to consider the potential implications of increased cannabis acceptability, availability, and use. Given that there is a dearth of literature clearly delineating medicinal from recreational cannabis users in terms of health outcomes, for the purposes of this paper, we will consider these groups together. The overall goal of this review is to discuss public health outcomes that may be impacted by increases in cannabis availability. Further, we also consider potential future research and treatment priorities in the face of widespread cannabis legalization.

Known consequences of Cannabis Use Disorder

A portion of cannabis users will develop the psychiatric syndrome Cannabis Use Disorder (CUD). The current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines Cannabis Use Disorder as a “problematic pattern of cannabis use leading to clinically significant impairment or distress” in 11 distinct realms of functioning. Examples of dysfunction include: withdrawal; unsuccessful efforts to cut down or control use; failure to fulfill obligations at work, home, or school; and continued use despite negative psychological or physical consequences of use, among others (American Psychiatric Association, 2013). Coinciding with the DSM-5 criteria for CUD, there are several lines of research that link cannabis use to impairment, and several comprehensive review articles have been written reviewing this topic (see for example Hall, 2015 and Volkow et al., 2014). Budney and colleagues were the first to demonstrate that CUD is as impairing as other substance use disorders (Budney et al., 1998), and also to establish that there is a clear withdrawal syndrome associated with CUD (Budney et al., 2008). Those seeking treatment have a low abstinence rate (see treatment section below), demonstrating that those with CUD are often not able to control their use of cannabis.

Individuals with CUD often suffer from medical comorbidities associated with cannabis use including psychiatric and cardiorespiratory illnesses. For instance, there is an established connection between cannabis use, and several psychiatric illnesses (reviewed in Moore et al., 2007), including anxiety disorders, depression, and psychosis. The most worrisome such connection is data that links the use of cannabis with an increased rate of schizophrenia and an earlier onset of schizophrenia in those who are susceptible to its development (Di Fort et al., 2014; Large et al., 2011). Similarly, there are multiple reports of adverse effects of cannabis use on the cardiovascular system (reviewed in Franz and Frishman, 2016 and Thomas et al., 2014). The existent data suggests that cannabis use increases the rate of myocardial infarction (MI), increases the rate of mortality following MI, and increases the rate of overall cardiovascular mortality. Further, regular use of cannabis has been shown to result in an increased rate of respiratory symptoms such as wheeze and cough, though it remains unclear currently if cannabis use in the absence of concomitant tobacco use results in an increased rate of chronic obstructive pulmonary disease (COPD) or airway cancer (Owen et al., 2014).

Several studies have examined the cognitive effects of regular cannabis use, and have consistently demonstrated some level of impairment (reviewed in Crane et al., 2013). Regular cannabis use in adolescence is associated with neuropsychological decline in adulthood (Meier et al., 2012), and academic achievement (Lynskey et al., 2000); however, it is unclear if cannabis use alone drives this effect (Verweij et al., 2013). In this regard, adolescent-onset cannabis use appears to be particularly problematic. Use that begins in adolescence has been theorized to interfere with the normal brain development process, and several animal studies suggest there is a causative link (Levine et al., 2017).

A recent meta-analysis examining the risk of cannabis use while driving found that those responsible for serious or fatal motor vehicle collisions (MVC’s) had approximately twice the rate of driving under the influence of cannabis compared to those not responsible for the MVC’s (Asbridge et al., 2012). This apparent increased risk of serious MVC is especially salient given that the frequency of which cannabis has been found in fatal accidents has increased substantially following its legalization (Brady and Li 2014; Salomonsen-Sautel et al., 2014).

Known consequences of Cannabis Use Disorder: Potential implications of legalization

Further research is needed to more firmly establish the causal nature of cannabis use to the above described negative consequences of CUD. However, it deserves special note that several of the reported adverse effects of CUD are irreversible. Schizophrenia is a devastating psychiatric illness that is chronic in nature, and is a major cause of disability in the U.S. and abroad (Collaborators UBoD, 2013). There are many pharmacologic treatments for schizophrenia; however, they are only moderately effective (Kennedy et al., 2014). Subsequently, if there is in fact a doubling of the risk of schizophrenia with heavy cannabis use in adolescence, it is possible that the overall prevalence of this illness may increase with cannabis legalization. Similarly, if driving under the influence of cannabis increases the rate of MVC’s, it is possible that there will be an increased number of cannabis related deaths. It is currently unclear if cannabis legalization has led to an increased number of MVC’s and motor related fatalities; however, of note, a recent analysis by the Insurance Institute for Highway Safety (IIHS) found that there was a larger than expected increase in MVC’s in states that have legalized recreational cannabis (Safety IIHS, 2017). New cannabis users may be particularly susceptible to driving under the influence of cannabis due to the popular but false assertion that cannabis use does not impair driving. Of additional note, even the reversible adverse effects of CUD are not without consequence. For instance, CUD does appear to be treatable; however, as discussed below, the majority of patients with CUD are not able to achieve long term abstinence even after receiving currently available evidence-based treatments.

Conversion from cannabis use to Cannabis Use Disorder

Current data suggest that 1.5-2.5% of adults 18 and older (Hasin et al., 2016; Compton & Han, 2018) and 3.0% of 12-17 year olds (Han et al., 2017) in the U.S. meet DSM criteria for CUD (DSM-IV or DSM 5). Though estimates vary, several studies have suggested that approximately 8-10% of individuals who have experimented with cannabis at least once in their lifetime develop CUD (Anthony 2006; Lopez-Quintero et al. 2011; Wagner and Anthony 2002). Estimates from a more recent, nationally representative survey in the U.S. suggest that the conversion rate to CUD may not be as high for those with lifetime cannabis use (3.5%), but higher among past year users as an estimated 11.6% met criteria for CUD (Richter et al. 2017). The rate of conversion from initiation to CUD appears to be higher among adolescents relative to adults. For instance, in a study completed in New Zealand, approximately 22% of adolescents who initiated cannabis use by age 16 met criteria for CUD by 21 (Fergusson et al., 2003). In a similar study in the U.S., individuals who began using cannabis before age 15, developed CUD more than twice as often as those who began using cannabis at age 15 or older (Richter et al. 2017).

Conversion from cannabis use to Cannabis Use Disorder: Potential implications of legalization

The most salient public health question in reference to cannabis legalization is not whether there be more cannabis use, but if there will be more problematic cannabis use, and CUD. It is well known that individuals who use cannabis despite its illegality have higher levels of trait impulsivity and risk taking (Blanco et al., 2014) than non-cannabis users. This particular point is important given that trait impulsivity and risk taking are risk factors for both the development of CUD, and for involvement in illegal activities in general. It is subsequently not clear whether, or not, the individuals who will use cannabis when it becomes legal, but abstained when it was illegal, have the same rate of conversion to CUD as those who use cannabis regardless of its legal status. Further, looking at the U.S. as a whole, two recent studies conflict one another regarding the trajectory of CUD’s prevalence as cannabis has become more available and acceptable. Compton and Han (2018) found that rates of adult CUD in the U.S. remained stable from 2002 to 2014 despite a slight increase in the number of adults who considered themselves to be cannabis users over the same time frame, whereas Hasin et al. (2015) reported that the prevalence of CUD in the U.S. has increased from 2001-2002 to 2012-2013 in all adult age groups.

Data comparing the rates of conversion from non-problematic cannabis use to CUD in areas with varying restrictions on cannabis use may offer insight regarding whether or not the legalization of cannabis will increase the prevalence of CUD (Reviewed in Hall & Weier, 2015). For example, one study compared the prevalence of adults who used cannabis in the past year and the prevalence of CUD in U.S. states with and without legal medical cannabis. In that study, the odds of any use in the past year and CUD were almost double in states with legal medical cannabis relative to states without legal medical cannabis (Cerdá et al., 2012). However, despite the doubled prevalence of last year use and CUD, the findings by Cerdá and colleagues also show that the prevalence of CUD among past year cannabis users does not differ depending on the legality of medical cannabis. Taken together, the findings of this study imply that in the U.S. states where cannabis is legal, there are more users, and more individuals with CUD, but the conversion rate from non-problematic cannabis use to CUD is not different compared to states where it is illegal. Subsequently, this study suggests that if the conversion rate remains constant, and there are more overall users, there will likely be an increase in the prevalence of CUD. As noted by Hall and Weier (2015), a limitation of the study design used in the Cerdá study is that it does not account for the differences in the states that may have led to the varying legal status.

As described above, adolescents are a group that is of particular interest due to the possible increased risk of converting from non-problematic cannabis use to CUD and the possible impact cannabis poses to neural development. Some recent data suggests that paradoxically, while the perceived risk of using cannabis has decreased over the past decade, so has the prevalence of past year use (Johnston et al., 2016; Compton & Han, 2018). Despite reporting a decrease in the prevalence of any use in the past year among adolescents, Johnston and colleagues also reported that the number of adolescents who used nearly daily or more remained relatively stable. One final area worth considering when speculating on the impact of cannabis legalization on the prevalence of CUD among adolescents is the downstream effect that more adults using cannabis might have on the rate of use of their children. For example, parental cannabis use has been proximally associated with adolescent cannabis use (Miller et al., 2013). Subsequently, if there is in fact an increase in the prevalence of cannabis use among adults, there may also be an increase in the prevalence of cannabis use among adolescents (Hall & Weier, 2015).

In sum, it is currently unclear whether, or not, there will be an increase in the prevalence of CUD if the trend of legalization continues; however, the existent data suggests that it is likely.

Current treatments for Cannabis Use Disorder

A number of approaches have been explored in the hopes of finding a treatment that is effective for CUD (for recent reviews see Nordstrom & Levin, 2007; Sherman & McRae-Clark, 2016; Vandrey & Haney, 2009). Despite attempting several approaches over a multitude of trials, the observed efficacy and durability of interventions have been modest.

The approaches that have consistently showed the best results are psychosocial treatments. Motivational enhancement therapy (MET), cognitive-behavioral therapy (CBT), and contingency management (CM), have all shown efficacy in clinical trials. The end of treatment abstinence rates in psychosocial trials have ranged from 13% to 43% (Budney et al., 2006; Copeland et al., 2001; Dennis et al., 2004; Martin & Copeland, 2008) with some evidence that suggests that longer treatment duration is associated with improved outcomes (MTPRG, 2004). The available trials have shown that abstinence durability is generally poor, although one study that combined CBT with abstinence-based CM achieved an abstinence rate of 37% that persisted for a year (Budney et al., 2006). Overall, the trials utilizing CM have resulted in longer periods of continuous abstinence during treatment, while those trials utilizing MET/CBT have resulted in improved abstinence durability once treatment was discontinued (Budney et al., 2000; Kadden et al., 2007).

In contrast to the modest, but consistently positive results found when testing psychosocial approaches to treat CUD, to date no pharmacologic approach has proven to be effective in a large placebo-controlled trial (with the exception of N-acetylcysteine, which is described further below). Antidepressants and anxiolytics including sustained-release buproprion, nefazadone, escitalopram, and buspirone, were some of the first tested in clinical trials, yet none performed better than placebo in achieving abstinence (Carpenter et al., 2009; McRae-Clark et al., 2015; Weinstein et al., 2014). Cannabinoid agonists, including nabilone and dronabinol, evaluated in laboratory studies (Budney 2007; Haney et al., 2004; 2008; 2013; Vandrey 2013) and clinical trials (Levin 2011 & 2016) have consistently shown suppression of withdrawal, but have been ineffective in increasing cannabis abstinence among individuals seeking treatment for CUD. The anticonvulsant divalproex showed no treatment effect in a clinical trial (Levin et al., 2004); however, the anticonvulsant gabapentin did reduce cannabis use and improve cognitive function compared to placebo in a small pilot trial (Mason et al., 2012). A trial utilizing the glutamatergic agent N-acetylcysteine (NAC) reduced cannabis use in a cohort of adolescents (Gray et al., 2012), but a similar trial in adults failed to show an effect (Gray et al., 2017). Lastly, a small controlled trial utilizing the neuropeptide oxytocin had a positive effect in reducing cannabis use when combined with MET (Sherman et al., 2017).

Current treatments for Cannabis Use Disorder: Potential implications of legalization

As described above, it is likely that there will be an increase in the prevalence of CUD as the trend towards cannabis legalization continues. Even assuming a modest increase in the prevalence of CUD, there is a need for more effective and durable treatments. This is particularly the case in adolescents, given the data suggesting that cannabis use in this age group may be especially detrimental. The development of treatments that focus on utilizing technology including computerized CBT (Budney et al., 2015), cognitive bias modification (Sherman et al., 2018), and online interventions (Rooke et al., 2013; Tossman et al., 2011), may prove especially useful given that they are especially efficient in terms of accessibility and cost effectiveness.

Despite a likely increase in the prevalence of CUD, given the increase in perceived safety and acceptability of cannabis use treatment seeking may actually decline. For instance, between 2002 and 2014, the percentage of adults who perceived ‘no risk’ from smoking cannabis increased from 5.6% to 15.1% (Compton & Han, 2017), while during that same time, the number of admissions for Cannabis Use Disorder decreased from a high of 373,000 in 2009 to 250,000 in 2014 (SAMHSA, 2014; 2016). Such a decrease in treatment seeking may lead to an increase in the overall prevalence of CUD. To combat such a decrease in treatment seeking, it may be necessary to increase research funding, education, and awareness. Such an increase in funding would have the advantage of bolstering treatment development efforts, increasing public knowledge about Cannabis Use Disorder, and dispelling the notion that cannabis is not addictive. Relatedly, in a legal use landscape increased research on and implementation of harm reduction approaches may increase treatment utilization and reduce the public health burden of cannabis use (see Discussion section).

Prevention of Cannabis Use Disorder

Well designed and implemented prevention programs that target school-aged children and adolescents have the potential to substantially mitigate the negative impact of readily available cannabis. However, studies have demonstrated that a number of variables may affect the reach and effect of these programs. Notable among these variables, are setting, theoretical foundation, and the group that is targeted. Several recent reviews and meta-analyses have evaluated the characteristics associated with positive effects of these programs.

There have been a number of investigations that have evaluated the efficacy of school-based prevention programs. The majority of such investigations were randomized controlled trials focused on universal prevention among middle school students. Lize and colleagues (2017) reviewed trials of interactive programs which emphasized skill-building and peer interactions rather than relying on a traditional didactic, lecture-style model. These programs yielded a small pooled effect on reducing cannabis use, but did not reduce intention to use or improve refusal skills relative to control conditions. Flynn and colleagues (2015) conducted a systematic review of middle school-based programs, revealing few statistically significant positive effects of active interventions when compared to control conditions. Only one intervention, the Lions-Quest Skills for Adolescence, yielded a statistically significant positive effect at final follow-up. MacArthur and colleagues (2016) observed methodological limitations of studies investigating peer-led interventions, but did note evidence of reduced cannabis use among participants receiving active versus control interventions. Faggiano and colleagues (2014) emphasized that, given the overall small effects of school-based universal prevention programs, they should form part of a more comprehensive strategy to achieve a population-level impact.

While most school-based prevention strategies have been universal in orientation, some school-based programs have focused specifically on high-risk groups with tailored interventions. Mahu and colleagues (2015) tested brief personality-targeted interventions to students with one of four high-risk personality profiles: anxiety sensitivity, hopelessness, impulsivity, and sensation-seeking. The intervention targeting sensation seekers had the largest effect, with a significant delay in the onset of cannabis use in this group. In addition to the effect seen in sensation seekers, there were also reductions in how frequently the other groups used cannabis. Palmgreen and colleagues (2001) also observed an effect in sensation-seekers in a study of prevention messaging via a television campaign.

The majority of prevention based research has occurred in school-based settings; however, some research has also examined the potential efficacy of programs based outside of the school. For instance, Gates and colleagues (2006) reviewed the existent literature base of programs outside of school, and noted limited evidence of significant effects. Despite not observing significant effects, they did note that some family-based and motivation-targeted programs were promising areas for further study. Additionally, parent-child dyad-based family programs may serve as effective strategies, as reviewed by Vermeleuen-Smit and colleagues (2015). Another strategy that has been explored is the use of a computer-delivered brief intervention in primary care (Walton et. Al, 2014). That study indicated that the computer-delivered intervention was more effective than a control intervention in lowering rates of cannabis use for 12 months. A similar effect was not seen among participants who received a therapist-delivered brief intervention, which suggests that the use of technology to deliver prevention programming may hold particular promise.

Prevention of Cannabis Use Disorder: Potential implications of legalization

Cannabis will most certainly be more available as it becomes legal. Additionally, its use will be more societally acceptable as its perceived risk continues to fall. Subsequently, the further development and implementation of prevention programs is critical. As described above, the programs that are currently available have only had a small beneficial effect, making research in this area of particular importance. Programs targeting adolescents utilizing comprehensive educational programs would likely have the largest overall impact given that the rate of conversion to CUD appears to be highest in this group. Further, given the increased vulnerability of this group to cannabis’ negative effects, programs that delay the onset of use beyond this critical time period may be of particular benefit in reducing the adverse impacts of cannabis use.

Discussion

Widespread legalization of cannabis is quickly occurring. Although it will be difficult to predict the ramifications, we have outlined key areas to monitor. We further highlight areas of research that will be of particular interest with legalization.

As stated above, approximately 17% of cannabis users self-identify as medicinal users (Lin et al., 2016). Lin and colleagues found that medicinal users were more likely to use cannabis daily, considered themselves generally to be less healthy, and tended to be older, compared to recreational users. Interestingly, in another study of users that self-identify as medicinal users, only the minority found cannabis to be helpful for their medicinal indication (Bonn-Miller et al., 2014). Currently there are few, well controlled studies, demonstrating cannabis is effective for any well-defined medical purpose (Whiting et al., 2015). There is a particular dearth of evidence when it comes to combusted cannabis for medicinal use (Bowen et al., 2018). It remains unknown whether or not there will be evidence based medicinal indications for cannabis. Notably, however, it is possible that there will be more cannabis-related research when cannabis can be legally purchased and used, and subsequently there will be more well controlled trials.

Fewer people have sought treatment for CUD in recent years. It is unclear why there are fewer treatment seekers; however, possible reasons include: 1) cannabis’s increased social acceptability; 2) a reduction of the perceived risk of cannabis use; and 3) the lack of effective treatments. Subsequently, educational campaigns aimed at increasing public awareness about the harm caused by cannabis, research further clarifying the harms caused by cannabis, and research developing more effective treatments may increase the number of Cannabis Use Disordered patients who seek treatment. We highlighted the need for more research on how to educate the public. The recent media campaigns related to smoking cessation may serve as a roadmap in this area. The likely most impactful area to explore in terms of ill effects of cannabis relates to the cognitive effects of cannabis use during adolescence. As stated earlier, the data linking cannabis use in adolescence to dysfunctional brain development is predominantly in the realm of animal research. Definitively linking this effect in humans may have a large impact on public opinion. Fortunately, the link is currently being explored in humans in an ongoing, longitudinal neuroimaging study in a large cohort of pre-adolescent children prior to the initiation of cannabis use (Volkow et al., 2017). It is hoped that this large trial will definitively parse out the complex association. Also as stated earlier, the lack of effective treatments for CUD may be de-motivating treatment seeking. If there were more effective treatment options available, there may be more individuals with CUD who seek treatment. Unfortunately, to date the majority of psychosocial treatments have shown limited efficacy and durability, and no pharmacologic treatment has been FDA-approved for the reduction of cannabis use. Potential future areas of investigation include strategies to reduce cannabis withdrawal, medications targeting the endocannabinoid system, and neurostimulation based treatments (Sahlem et al., 2018). Further, treatments that target adolescents and alternative treatments utilizing technology that can be widely implemented may have a greater reach.

With increasing legalization of cannabis, treatment researchers may also consider identifying clinical endpoints in addition to abstinence, consistent with a “harm reduction” approach for those who develop CUD. Though recent guidelines clearly state that the best way to avoid the adverse effects of cannabis use is abstinence (Fischer et al., 2017), a harm reduction treatment approach may be more acceptable for treatment seeking patients. A harm reduction approach provides individual patients the freedom to set their own treatment goals, and emphasizes a reduction in negative consequences related to cannabis use (Collins et al., 2011). Reduction-based programs may subsequently increase the number of treatment-seeking individuals with CUD who recognize that their use of cannabis is associated with harm, but do not want to abstain entirely. Harm reduction approaches may modify both how and what clinicians communicate with patients in treatment settings. For example, treatment protocols may include specific education regarding strategies that reduce adverse effects of cannabis use, such as delaying use until later adulthood, avoiding daily or near daily use, avoiding certain cannabis products (i.e., high potency tetrahydrocannabinol (THC) products, products with a high THC to cannabidiol ratio, combustible cannabis, synthetic cannabinoids) and inhalation practices, and refraining from using cannabis when driving (Fischer et al., 2017). In order to establish that treatments are potentially efficacious for patients with non-abstinence goals, researchers will need to develop objective, valid, and reliable measures for cannabis reduction and associated reductions in negative cannabis-related consequences. Clinical trials examining reduction-related outcomes to date generally rely on the patient’s self-reported number of days used (i.e., de Dios et al., 2012; MTPRG, 2004). However, biomarkers that indicate harmful levels of cannabis use, similar to carbohydrate deficient transferrin (CDT) to indicate heavy alcohol consumption, may become more critical with legalization and an increase in harm reduction treatment programs.

In sum, we suggest that legalization will increase the need for effective prevention and intervention programs, particularly targeting adolescents. It will be critical to monitor adolescent outcomes longitudinally in nations in which cannabis is legal. Education regarding “safer” means of using cannabis will become critical, and monitoring reduction in cannabis-related impairment and reduction in use will be imperative. Future research is necessary to understand modifiers of risk, such as medicinal versus recreational use and the risk associated with varying cannabis products sold in legalized markets.

Footnotes

Declaration of interest:

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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