Cannabis regulatory science: risk-benefit considerations for mental disorders
Jacob T. Borodovskya,b, Alan J. Budneya
aDartmouth Geisel School of Medicine, Center for Technology and Behavioral Health, 46 Centerra
Parkway, Lebanon, NH 03766, United States; bThe Dartmouth Institute for Health Policy and
Clinical Practice, 74 College St. Hanover, NH 03755, United States
Corresponding Author: Jacob T. Borodovsky
Center for Technology and Behavioral Health
46 Centerra Parkway
Lebanon, NH 03766, United States
Cannabis regulatory science: risk-benefit considerations for mental disorders
The evolving legal cannabis landscape in the U.S. continues to present novel regulatory challenges
that necessitate the development of a Cannabis Regulatory Science. Two specific issues of concern
within Cannabis Regulatory Science are (1) the impact that cannabis use has on the incidence,
prevalence, and severity of mental disorders, and (2) how cannabis laws and regulations modify this
impact. In this paper, we first provide several conceptual points that are useful for evaluating the
relationship between cannabis use and mental disorders. Second, we selectively review and
comment on data relevant to the relationship between cannabis use and depression, several forms of
anxiety, posttraumatic stress disorder, schizophrenia, and bipolar disorder. Next, we discuss
regulatory and public health parallels between the nascent cannabis industry and the pharmaceutical,
tobacco, and alcohol industries. We focus on specific types of industry practices that may harm
those with or at risk for mental disorders. We then offer recommendations for legal cannabis
regulations that could mitigate this harm. Last, we discuss future research goals for building the
field of Cannabis Regulatory Science and addressing the potential negative impact of cannabis on
those with mental disorders.
Keywords: cannabis, marijuana, legalization, mental disorders, psychiatric, regulatory science
Cannabis legalization has gained unprecedented momentum around the world and continues to
evolve rapidly. In the U.S., states not only differ in whether they have legalized medical or
commercial (i.e., recreational) cannabis, or both, but importantly, each state has taken a unique
approach to designing its legal cannabis laws (LCL). States vary dramatically in the number and
types of qualifying medical conditions, requirements for becoming a medical cannabis patient, the
types and potency of products that can be used, the amount of personal cannabis one can possess,
and the regulation of production, distribution, marketing, and sale of cannabis (Barry & Glantz,
2016; Bestrashniy & Winters, 2015; Chapman, Spetz, Lin, Chan, & Schmidt, 2016; Pacula, Hunt,
& Boustead, 2014; Pacula, Powell, Heaton, & Sevigny, 2015; Williams, Olfson, Kim, Martins, &
Kleber, 2016). These specific components of laws warrant careful consideration and study as each
has the potential to mitigate or increase the negative or positive public health consequences related
to cannabis use. Unfortunately, few states have effectively utilized scientific evidence concerning
cannabis or the public health effects of various regulatory mechanisms, to construct their laws and
regulations (Barry & Glantz, 2016; Weiss, Howlett, & Baler, 2017).
This article concentrates on the potential impact of components (i.e., provisions) of legal
cannabis laws on one vulnerable subgroup - those with and those predisposed to developing mental
disorders. Historically in the United States, individuals with mental disorders have experienced
stigma, marginalization (Perese, 2016), and a disproportionate amount of burden engendered by
legal and illegal addictive substances (Centers for Disease & Prevention, 2013; Jane-Llopis &
Matytsina, 2006; Kessler, 2004). Those with mental disorders account for a substantial portion of
the total amount of tobacco and alcohol consumed in the U.S. (Grant, Hasin, Chou, Stinson, &
Dawson, 2004; Lasser et al., 2000; Meier, Purshouse, & Brennan, 2010). Cannabis consumption
patterns are no different. It is estimated that those with past-year mental disorders consume
approximately 80% of all cannabis consumed in the U.S. (Lev-Ran, Le Foll, McKenzie, George, &
Rehm, 2013). Thus, this population will clearly be affected by legal cannabis – perhaps more so
than other subgroups. The design of legal cannabis laws and corresponding regulations should
reflect an acute awareness of this disproportionate vulnerability.
Developing regulations that mitigate the impact of cannabis on those with mental disorders is
complicated by the interacting dynamics of commercial and medical cannabis legalization. From a
commercialization perspective, a multibillion-dollar for-profit cannabis industry (ArcView Market
Research, 2016) is emerging and behaving in ways reminiscent of the tobacco and alcohol
industries (Barry & Glantz, 2016; Carlini, Garrett, & Harwick, 2017; Pacula, Kilmer, Wagenaar,
Chaloupka, & Caulkins, 2014; Richter & Levy, 2014; Subritzky, Lenton, & Pettigrew, 2016;
Subritzky, Pettigrew, & Lenton, 2015). Our history with the tobacco and alcohol industries has
clearly demonstrated that loose regulation of these industries and their products is detrimental to
public health (Bero, 2003; Jahiel & Babor, 2007) – particularly for vulnerable populations such as
those with mental disorders (Apollonio & Malone, 2005; Hirshbein, 2012; Prochaska, Hall, &
In addition to concerns about commercial cannabis, the medical cannabis laws that are now
effective in 29 U.S. states and Washington D.C. permit therapeutic cannabis use for diverse and
often diagnostically ambiguous medical conditions. These medical cannabis laws convey to the
public that cannabis is an effective therapeutic agent for the multitude of conditions listed within
and across state laws. The combination of commercialization and medicalization of cannabis
appears to be contributing to individuals supplementing or replacing their use of FDA-approved
psychiatric medications with cannabis to treat depression, anxiety, and symptoms of psychosis
(Boehnke, Litinas, & Clauw, 2016; Bradford & Bradford, 2016; Corroon, Mischley, & Sexton,
2017; Nunberg, Kilmer, Pacula, & Burgdorf, 2011; Piper et al., 2017; Reiman, 2016; Reinarman,
Nunberg, Lanthier, & Heddleston, 2011). Similar trends are emerging in Canada (Lucas & Walsh,
2017; Lucas et al., 2016; Walsh et al., 2013). This is occurring despite little to no controlled clinical
evidence supporting the therapeutic efficacy of cannabis for mental disorders (Belendiuk, Baldini,
& Bonn-Miller, 2015), and despite data indicating that medical cannabis patients with a history of
psychiatric problems have more problematic cannabis use than medical cannabis patients without a
history of psychiatric problems (Ware, Martel, Jovey, Lynch, & Singer, 2018).
This chaotic regulatory landscape necessitates the expeditious development of a Cannabis
Regulatory Science to generate the data necessary for creating evidence-based cannabis regulations
that maximize public health benefits and minimize public health harms. The goal of the present
commentary is to contribute to this effort by focusing on the relationships among cannabis use,
cannabis legalization, and mental disorders. Specifically, this paper will (1) present conceptual
points regarding the relationship between cannabis and mental disorders that may be useful for
readers; (2) review the relevant relationships between cannabis and mental disorders at multiple
levels of analysis (e.g., epidemiological, clinical, behavioral pharmacological); (3) draw several
parallels from the pharmaceutical, tobacco, and alcohol industries to identify how legal cannabis
laws and a for-profit cannabis industry will likely influence cannabis use among those with mental
disorders; (4) present recommendations for regulations based on the current literature and historical
precedents with other substances; and (5) present considerations for future research that will help
create a robust Cannabis Regulatory Science body of research related to cannabis and mental
Of note, we will not address how cannabis use and legalization may affect non-cannabis
substance use disorders (SUD) (e.g., alcohol, cocaine, opioid, or tobacco use disorder) even though
such SUDs are a subgroup of “mental disorders” and disproportionately co-occur with mood,
anxiety, and psychotic disorders (Grant et al., 2016). A meaningful discussion of this topic requires
an analysis of several additional concepts (e.g., gateway hypothesis, substitution effects,
pharmacological synergy, etc.) that are beyond the scope of this commentary. Second, we discuss
cannabis use disorder (CUD) but do so within the context of its significant co-occurrence with
other mental disorders. We refer those interested in a discussion of the specific relationships among
cannabis legalization, cannabis use, and CUD (excluding other types of mental disorders) to our
previous commentary (Budney & Borodovsky, 2017).
The relationship between cannabis and mental disorders
Before addressing the known relationships between cannabis use and specific mental disorders,
several broad concepts warrant discussion. The concepts outlined below will help guide critical
evaluation of the relevant scientific literature.
First, the cannabis plant contains over 100 distinct cannabinoid compounds, and the amount
of each compound varies substantially across plants (ElSohly & Gul, 2014). The compounds most
relevant to this discussion (but certainly not the only relevant compounds) are delta-9-
tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the primary psychoactive constituent
of cannabis and exhibits reinforcing and rewarding properties (Cooper & Haney, 2009). Synthetic
pharmaceutical-grade THC is FDA approved to treat weight loss in AIDS patients and
chemotherapy-induced nausea (AbbVie Inc., 2018). A closely related compound – nabilone – is
also FDA approved for treating the latter condition (Throckmorton, 2016). In contrast, to date,
studies on CBD have not shown any clear signs of abuse liability (Babalonis et al., 2017), and
individuals who have consumed as much as 600 mg of CBD reportedly did not demonstrate signs
of intoxication in a laboratory study (Martin-Santos et al., 2012). Additionally, emerging data
suggest that CBD-based medications may be promising therapeutic agents for several neurological
disorders (Fasinu, Phillips, ElSohly, & Walker, 2016).
The effects and therapeutic value of consuming a pharmaceutical-grade formulation of a
single cannabinoid (e.g., THC or CBD) can be dramatically different from the effects of ingesting
the entire cannabis plant. Furthermore, ingesting the entire plant (or a formulation) that has
differing amounts of each compound, (e.g., a plant containing 20% THC and 0.3% CBD vs. a plant
containing 0.5% THC and 4.0% CBD), would have obvious differential pharmacological effects.
Thus, not only is it essential to identify the specific compounds being administered when
evaluating the effects of “cannabis” on behavior and specific health conditions, but the dose of each
compound and the commensurate interactions must be considered as well. Evaluation of dose is
further complicated by other potential pharmacodynamic characteristics of cannabinoid
compounds. For example, biphasic effect profiles have been posited for cannabinoids; that is, a low
dose may produce one effect (e.g., reduction in anxiety) and a high dose may cause the opposite
effect (e.g., increased anxiety) (Mechoulam & Parker, 2013).
Second, the chronicity of use of a particular cannabinoid or combination of cannabinoids
(such as those present in the cannabis plant) could impact the medical risk-benefit profile. For
example, a cannabinoid could have a clinically meaningful impact on a mental disorder when
administered acutely, but adversely affect the development or course of a mental disorder when
repeatedly administered over time. Paradoxical characteristics like these are not uncommon among
medications. Consider benzodiazepines for example. This class of medications is effective as a
short-term aid for reducing debilitating symptoms of anxiety disorders (Dell'osso & Lader, 2013).
And yet, long-term benzodiazepine use carries several risks such as development of a substance use
disorder, cognitive decline, and exacerbation of anxiety (Dell'osso & Lader, 2013). The point is that
evaluating the risk-benefit profile of a psychoactive compound used for medical purposes requires
consideration of both short- and long-term consequences.
Third, a drug’s reinforcing effect should not be mistaken as a therapeutic one. Psychoactive
substances like THC (or alcohol, stimulants, opioids) produce euphoric effects via interactions with
reward-related neurocircuitry. More relevantly, these substances can also temporarily reduce pre-
drug negative mood states without resolving the underlying cause of the mood disturbance. This
combination of effects likely renders the substance more reinforcing for persons with mental
disorders. That is, in addition to the typical positive reinforcing effects experienced by users,
individuals with mental disorders may also experience negative reinforcement when ingesting the
substance (i.e., relief from negative emotional states such as depressed mood). One might interpret
this latter effect as therapeutic, but it in fact likely contributes to the increased vulnerability to
substance use and development of substance use disorders (SUD) among those with mental
disorders. Whether or not this constitutes “self-medication” (Khantzian, 1997) in the traditional
sense of the term is of little importance. The relevant point is that using a substance to achieve
temporary symptomatic relief may not be therapeutic, particularly if continued use of the substance
exacerbates or helps maintain (rather than resolving) a mental disorder.
Last, when interpreting the results of research studies or case illustrations, it is essential to
consider the history of cannabis use of the individuals under study. Whether individuals have ever
used cannabis, how recently they have used, and how frequently they have been using all can
contribute to tolerance to cannabis effects, and to the probability and severity of cannabis
withdrawal when cannabis is discontinued. This, in turn, may have a dramatic impact on the
observed effects in any one study (Kirk & De Wit, 1999; Schlienz, Budney, Lee, & Vandrey,
In sum, any meaningful discussion and evaluation of the effects of cannabis on mental
disorders must explicitly specify what cannabinoid compounds are being evaluated, how much of
and for how long the compounds were administered and evaluated, the potential conflation of
reinforcing properties and therapeutic utility, and the cannabis use history of the persons included
in the evaluation.
The prevalence and co-occurrence of cannabis use and mental disorders.
The cross-sectional relationship between cannabis use and mental disorders can be understood in
two ways – the prevalence of cannabis use among those with mental disorders (Lev-Ran, Le Foll,
et al., 2013) or the prevalence of mental disorders among cannabis users (Stinson, Ruan, Pickering,
& Grant, 2006). In both cases, the scientific literature is clear that the co-occurrence of cannabis
use or CUD and major depressive, psychotic, anxiety, posttraumatic stress, and bipolar disorders is
disproportionally large when compared to either those who do not use cannabis or to those without
mental disorders (Agosti, Nunes, & Levin, 2002; Green, Young, & Kavanagh, 2005; Hasin et al.,
2016; Lev-Ran, Imtiaz, Rehm, & Le Foll, 2013; Lev-Ran, Le Foll, et al., 2013; Teesson et al.,
2012). Furthermore, the prevalence of mental disorders among cannabis users appears to rise in
parallel with the frequency and severity of self-reported cannabis use (Cheung et al., 2010;
Degenhardt, Hall, & Lynskey, 2001; Stinson et al., 2006; Zvolensky, Cougle, Johnson, Bonn-
Miller, & Bernstein, 2010). Of note, the elevated prevalence of CUD among those with mental
disorders does not appear to be simply a function of an elevated prevalence of lifetime cannabis
use. Several cross-sectional and longitudinal studies have demonstrated that cannabis users with
mental disorders are approximately twice as likely as cannabis users without mental disorders to
have or develop CUD (Florez-Salamanca et al., 2013; Lev-Ran, Le Foll, et al., 2013; Lopez-
Quintero et al., 2011; Martins & Gorelick, 2011).
Specific mental disorders and their relationships with cannabis use.
In this section, we present summaries of the known and potential therapeutic and adverse effects of
cannabis and cannabinoids on depression, anxiety, posttraumatic stress disorder, schizophrenia, and
bipolar disorder. Given space limitations, this summary is broad in scope, but lacking in detail.
More in-depth discussions of this literature can be ascertained from cited original articles and
Cannabis users commonly report that they use cannabis to help with their depression (Aggarwal et
al., 2013; Bonn-Miller, Boden, Bucossi, & Babson, 2014; Reinarman et al., 2011; Walsh et al.,
2013). However, there are no randomized controlled clinical trial data demonstrating the use of
medical cannabis (plant) or pharmaceutical-grade cannabinoids for the treatment of major
depressive disorder (Whiting et al., 2015). Several studies of various patient populations with
serious physical medical conditions (e.g., HIV, Multiple sclerosis) have measured depressive
symptoms as a secondary outcome, and have noted improvements in mood (Walsh et al., 2017).
However depressive symptoms were not the primary endpoints in these studies, and this effect was
not on Major Depressive Disorder. Relief from the symptoms associated with serious chronic
medical conditions like HIV or Multiple sclerosis would be expected to improve negative moods
commonly associated with enduring chronic illness. Interestingly, the medication rimonabant, a
CB1 receptor antagonist (i.e., blocks the effects of cannabinoids like THC), was removed from the
U.S. and European markets after determining that a small portion of those who used it experienced
side effects of depression and suicidality. This observation reflects an important relationship
between the endocannabinoid system and mood regulation, and hence, raises the possibility of
developing cannabinoid-based medications to treat mood disorders (Hill & Gorzalka, 2009; Le
Foll, Gorelick, & Goldberg, 2009; Micale, Di Marzo, Sulcova, Wotjak, & Drago, 2013). Moreover,
preclinical data indicate that CB1 receptor agonism may increase serotonergic-related neural
activity suggesting that cannabinoid compounds may be useful for improving negative mood
(Bambico, Katz, Debonnel, & Gobbi, 2007; Gobbi et al., 2005).
The extant data that address whether or not cannabis use can contribute to depression are
equivocal, but when a relationship has been observed, cannabis use is most often associated with an
increased, rather than decreased risk of depression. A systematic review of longitudinal studies
that controlled for baseline depression indicated that cannabis use (particularly heavy cannabis use)
was associated with increased risk for subsequently developing depression (Lev-Ran et al., 2014).
However, some nationally representative longitudinal data suggest that this relationship is mediated
by associations with other SUDs (Blanco et al., 2016), or suggest an opposite causal direction (i.e.,
that having major depressive disorder at baseline increases the risk of subsequent cannabis
initiation) (Feingold, Weiser, Rehm, & Lev-Ran, 2015). Studies that have not accounted for the
frequency of cannabis use or the age of cannabis use onset have found no relationship (Danielsson,
Lundin, Agardh, Allebeck, & Forsell, 2016). Clinically, individuals with depression who continue
to use cannabis throughout treatment make less improvement on their mental health symptoms than
individuals with depression who do not use cannabis during treatment (Bahorik et al., 2017). Last,
individuals from twin pairs who use cannabis frequently (≥100 times) are more likely to report
major depression than their less frequent or non-using monozygotic twin (Agrawal et al., 2017).
In sum, the endocannabinoid system is involved in mood regulation, and thus there may be
potential for development of cannabinoid-based medications for depression. However, use of
cannabis plant material ingested by the general population likely facilitates the onset or worsening
of symptoms of depression. Interpretation of positive findings from cannabis studies that observe
decreased depression secondary to relief from chronic medical conditions (e.g., Multiple sclerosis),
must consider and test alternative explanations such as that the improved mood is caused by the
reduction in the chronic condition. Last, self-reported temporary relief from depression (negative
reinforcement) likely contributes to the high prevalence of CUD among those with depressive
disorders. Caution is warranted in labeling such acute symptomatic relief as therapeutic.
The relationship between cannabis and anxiety that can be gleaned from the extant literature is
complex. Some CB1 receptor agonist compounds, e.g., THC, have demonstrated potential
anxiogenesis, while other compounds such as CBD have shown anxiolytic properties (Crippa et
al., 2009). The potential relations between cannabis and anxiety are further complicated by
evidence suggesting that a single cannabinoid - such as THC - can mitigate stress responses when
consumed at low doses (7.5 mg), but exacerbate stress at higher doses (12.5 mg) (Childs, Lutz, &
de Wit, 2017). Moreover, anxiety is a common symptom reported during cannabis withdrawal
(Budney, Moore, Vandrey, & Hughes, 2003), and thus some reports of anxiolytic effects of
cannabis may merely reflect mitigation of anxiety-related cannabis withdrawal symptoms.
That said, cannabis users commonly report that cannabis helps with their anxiety (Bonn-
Miller, Boden, et al., 2014; Reinarman et al., 2011; Walsh et al., 2013) and daily cannabis users
provided with 3% THC cannabis cigarettes report feeling more relaxed after use (Hart et al., 2002).
However, there are few controlled studies that clarify the effect of cannabinoid compounds on
clinical anxiety. Some data suggest that CBD reduces public speaking anxiety (Bergamaschi et al.,
2011) and self-reported anxiety symptoms among patients with social anxiety disorder (Crippa et
al., 2011). Studies of patients with chronic pain treated with pharmaceutical-grade cannabinoids
(e.g., dronabinol, nabilone, and nabiximols) demonstrate improvements in symptoms of anxiety
compared to placebo (Whiting et al., 2015). However, similar to the depression data reported, these
types of studies focused on treatment of non-psychiatric medical conditions and impact on anxiety
or anxiety disorders were secondary outcomes. Thus these reductions could readily be explained by
indirect effects that stem from a reduction in chronic pain.
Cannabis use can elicit acute episodes of intense anxiety as well as exacerbate symptoms of
anxiety among those with an anxiety disorder (Crippa et al., 2009). Several controlled laboratory
studies on the acute effects of cannabis or cannabinoids in humans support this notion. For
example, individuals with varied lifetime histories of cannabis use who were given up to 5 mg of
intravenous THC reported significant increases in anxiety (D'Souza et al., 2004). Similar results
were observed among subjects with varying patterns of cannabis use administered oral THC (15
mg) or a combination of 16.2 mg THC/15.0 mg CBD delivered via an oromucosal spray
(Karschner et al., 2011). In a study of cannabis edible products, 18 participants with no past 90-day
cannabis use, consumed a cannabis brownie containing either 10, 25, or 50 mg of THC. One
participant provided with a 25 mg brownie, experienced severe anxiety and had to temporarily
discontinue study participation (Vandrey et al., 2017). In another study, individuals who had used
cannabis less than 15 times in their life, had not used cannabis in the past month, and had never
experienced negative psychological effects from cannabis were given either 10 mg of oral THC,
600 mg of oral CBD, or placebo over three sessions (Martin-Santos et al., 2012). The dose of THC
significantly increased anxiety compared to placebo and CBD, but no differences were observed
between CBD and placebo. Finally, relatively infrequent cannabis users (<10 cannabis joints per
month) have reported greater anxiety after using increasingly more potent (29–69 mg THC)
cannabis joints (Hunault et al., 2014).
Some have suggested that the impact of cannabis on anxiety may also vary by sub-type of
anxiety disorder (Walsh et al., 2017). For example, two independent analyses of longitudinal data
from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) study
indicate that baseline cannabis use is associated with elevated incidence of social anxiety (Blanco
et al., 2016; Feingold, Weiser, Rehm, & Lev-Ran, 2016) but not other types of anxiety. Frequency
of use may also impact the relationship between cannabis and anxiety. Longitudinal analyses of
youth indicate that daily cannabis use is associated with having an anxiety disorder later in life
(Degenhardt et al., 2013). Studies that have not accounted for the frequency of cannabis use or age
of cannabis use onset have found no relationship in either direction, that is, early cannabis use did
not relate to later anxiety nor did early anxiety predict later cannabis use (Danielsson et al., 2016).
In sum, the relationship between cannabis and anxiety is complex, similar to observed
relationships between depression and cannabis use. Factors such as cannabis use history, cannabis
potency, predisposition to an anxiety disorder, and consumers’ ability to titrate dose, may all affect
the extent to which individuals experience the acute effects of cannabis as being anxiogenic or
anxiolytic. This last factor concerning titration warrants special attention. Cannabis products and
methods of administration that allow a person to closely titrate his or her level of intoxication (e.g.,
vaping low-THC plant material) reduce the risk of over-intoxication and thus the risk of an acute
episode of anxiety. Currently available high-THC cannabis products (e.g., concentrates) consumed
via rapid methods of administration such as “dabbing” (M. Loflin & Earleywine, 2014), offer little
ability to titrate and thus place individuals at a higher risk of ingesting anxiogenic doses of THC.
Finally, as with depressed mood, cannabis (with THC or THC and CBD) can provide temporary
relief from some anxiety symptoms in some individuals who are feeling stressed or anxious, but
there are no controlled data to suggest it helps resolve anxiety disorders. Available data suggest that
CBD-based (non-THC) compounds may warrant controlled testing for certain anxiety disorders,
but to date, their clinical utility as an anxiolytic has not been demonstrated.
Posttraumatic stress disorder (PTSD)
Most recently, cannabis has garnered a great deal of media, legislative, and scientific attention as a
potential treatment for PTSD. Such attention can likely be tied to two sources. Military veteran
groups have been publicly lobbying for legal access to cannabis for their PTSD (Ugwu, 2017).
Second, human studies have reported that both THC and CBD may help facilitate extinction of
conditioned fear memories (albeit under different administration procedures) (Das et al., 2013;
Rabinak et al., 2013). Moreover, two studies report that pure pharmaceutical-grade THC has
significantly reduced nightmares in those with PTSD (Jetly, Heber, Fraser, & Boisvert, 2015;
Roitman, Mechoulam, Cooper-Kazaz, & Shalev, 2014) and veterans with PTSD often endorse
using cannabis as a sleep-aid (Bonn-Miller, Babson, & Vandrey, 2014). However, other research
suggests potential adverse impact of cannabis and cannabinoids on PTSD symptoms and its course.
One study has demonstrated that compared to adults who do not use cannabis, chronic cannabis
users showed worse ability to extinguish previously conditioned fear responses (Papini et al.,
2017). Cannabis use and CUD have been associated with worse PTSD treatment outcomes, and
stopping cannabis use has been associated with better PTSD treatment outcomes (Bonn-Miller,
Boden, Vujanovic, & Drescher, 2013; Wilkinson, Stefanovics, & Rosenheck, 2015). Moreover,
veterans with PTSD and a history of heavy cannabis use who discontinue cannabis use at the start
of their PTSD treatment are less responsive to treatment than those with no history of cannabis use
or lighter cannabis use (Bonn-Miller et al., 2013).
As with depression and other anxiety disorders, the data on the relationship between PTSD
and cannabis are highly complex and equivocal (Haney & Evins, 2016; M. J. Loflin, Babson, &
Bonn-Miller, 2017). Generally, the clinical data suggest a negative impact of cannabis use on
PTSD outcomes. Nonetheless, additional research is warranted that addresses the aforementioned
issues: testing of specific cannabinoids and doses, acute vs. chronic administration, cannabis
tolerant vs. non-tolerant patients, and symptomatic relief versus impact on resolution of the
disorder. Clinical trials addressing some of these issues are underway (O'Neil et al., 2017).
An extensive literature has accumulated over the past 20 years on the effects of cannabis on the
development and course of schizophrenia and related psychotic disorders, and many reviews of this
issue are available (Hamilton, 2017; Rabin & George, 2017; Radhakrishnan, Wilkinson, &
D'Souza, 2014; Schoeler et al., 2016). THC and other synthetic CB1 receptor agonists have the
potential to elicit the onset of acute transient psychotic symptoms and produce cognitive
dysfunction. THC appears to exert a dose-dependent risk (albeit a relatively small risk) for
increasing the probability of developing a psychotic disorder, particularly among those with an
initial increased risk (e.g., genetic vulnerability, exhibiting prodromal signs or symptoms, earlier
onset cannabis use). Regular use of high potency cannabis (i.e., high THC content) appears to
confer markedly higher risk. Cannabis use has also been associated with worsening of symptoms of
schizophrenia, as well as adversely impacting the clinical course (i.e., trigger relapse, and outcomes
for those with psychotic disorders).
Some preclinical and clinical data, however, suggest that some cannabinoid compounds,
most notably CBD, might have potential for exerting positive effects on schizophrenia (Gururajan
& Malone, 2016; Leweke, Mueller, Lange, & Rohleder, 2016). A double-blind, randomized
controlled trial testing CBD against amisulpride reported that both compounds reduced symptom
severity, and CBD caused fewer extrapyramidal symptom side effects (Leweke et al., 2012).
Another recent double-blind placebo-controlled trial of CBD used in conjunction with treatment as
usual, demonstrated that CBD helped significantly reduce positive psychotic symptoms and
improved scores on the Clinical Global Impressions Scale (McGuire et al., 2017). There do not
appear to be any published clinical trials evaluating the cannabis plant as a treatment for psychosis
(Walsh et al., 2017). Interestingly, while individuals with schizophrenia who use cannabis have
worse symptoms of psychosis, there is some evidence to suggest that they have better cognitive
functioning (e.g., attentional control, visuospatial abilities) than individuals with schizophrenia who
do not use cannabis (Rabin, Zakzanis, & George, 2011). However, methodological differences
across studies, such as poorly defining cannabis use or inadequate control groups, warrant cautious
interpretation of this observation (Rabin et al., 2011; Segev & Lev-Ran, 2012). Moreover,
selection biases may explain these observations; that is, persons with schizophrenia who are able to
obtain and use cannabis may generally be higher functioning than those with schizophrenia who
cannot and don’t (Rabin et al., 2011; Segev & Lev-Ran, 2012).
In sum, there is convincing evidence from studies examining the use of cannabis plant
material that cannabis use is related to an increased likelihood of developing psychosis in
subgroups of the population and worsens existing symptoms of psychosis. Nonetheless, the
literature highlights the complexity of the problem and the need to consider the effects of various
compounds in the cannabis plant. Preclinical and clinical data on CBD suggest that additional
research is warranted to examine the potential for CBD to reduce the risk of developing
schizophrenia or for use as a medication for schizophrenia.
To date, we are not aware of any data from controlled studies which suggest that either the use of
the cannabis plant in its entirety or CBD has potential as an effective therapeutic agent for bipolar
disorder. One published case study of two adults with bipolar disorder who were given up to 1200
mg CBD over the course of 25 days reported no significant improvement in symptoms (Zuardi et
al., 2010). As with schizophrenia, there are data to suggest that cannabis either has no effect or
improves cognition among individuals with bipolar disorder (Braga, Burdick, Derosse, & Malhotra,
2012; Sagar et al., 2016). Again, however, such results could reasonably be ascribed to selection
biases stemming from higher functioning individuals’ greater likelihood of using cannabis.
Clinical survey data suggest an association between use of cannabis and both the
development of bipolar disorder as well as negative course and outcomes among those with bipolar
disorder, although some studies have found no directional relationship. For example, data from the
Netherlands Mental Health Survey and Incidence Study indicate that cannabis use at baseline
increased the risk for bipolar disorder at follow up (van Laar, van Dorsselaer, Monshouwer, & de
Graaf, 2007), and according to analyses of NESARC data, a diagnosis of Bipolar Disorder at
baseline is not associated with subsequent cannabis initiation (Feingold et al., 2015). As with other
mental disorders, the risk of experiencing the onset of bipolar disorder at a younger age may
increase in relation to lifetime severity and frequency of cannabis use (Lagerberg et al., 2014; van
Laar et al., 2007).
Additional data from several other large longitudinal studies have shown that individuals
with bipolar disorder who use cannabis do not fare well. Among individuals with bipolar disorder,
those who use cannabis experience worse clinical outcomes (disorders severity, mania, and
psychosis) (van Rossum, Boomsma, Tenback, Reed, & van Os, 2009), are less likely to have their
symptoms go into remission (Kim et al., 2015), and have a significantly shorter time to recurrence
of bipolar disorder symptoms (Zorrilla et al., 2015) than those who do not use cannabis. Meta-
analyses of experimental and prospective observational studies lend further support to the
relationship between cannabis use and subsequent onset of bipolar disorder or worsening of
existing symptoms of bipolar disorder (Gibbs et al., 2015).
Summary: cannabis and mental disorders.
A few points of emphasis on the relationships between cannabis and mental disorders are worthy of
(1) The scientific and clinical literature has yet to adequately differentiate the cannabis plant
from isolated compounds of the plant or from synthetic cannabinoid compounds.
Summaries of information that do not account for these differences provide a poor
representation of how “cannabis” interacts with mental disorders. Such unreliable
information has great potential for misleading policymakers and the public about the
therapeutic potential and efficacy of the cannabis plant or isolated cannabinoid compounds.
(2) Currently, there are little to no controlled data from clinical science that support the use of
the cannabis plant containing effective doses of THC for any of the psychiatric conditions
reviewed above (National Academies of Sciences Engineering Medicine, 2017). Indeed,
there are fairly strong clinical data to indicate that use of the cannabis plant containing
effective doses of THC may cause or worsen many of these conditions. However, there are
no clinical data to suggest that CBD has a negative effect on psychiatric conditions; and
there are some preliminary clinical data to suggest that CBD warrants more controlled study
as a potential therapeutic agent for some psychiatric conditions. Moreover, basic and
laboratory research suggest that compounds that target the endogenous cannabinoid system
should be explored as potential therapies for psychiatric conditions. That said, such
observations do not indicate that use of the cannabis plant has utility in treating such
(3) Those with mental disorders are most vulnerable to the negative effects of cannabis use and
the development of CUD. As legal cannabis laws are considered or enacted, regulatory
provisions and public health initiatives are sorely needed to prevent even greater health
disparities related to cannabis use and CUD among those at risk for or that have a mental
disorder. We discuss these concerns in more detail below.
The potential impact of cannabis laws and regulations on individuals with mental disorders:
lessons from pharmaceutical, tobacco, and alcohol regulation.
Legally deeming cannabis as both a commercial and medical product makes effective regulation
even more difficult than that of traditional commercial-only substances like tobacco and alcohol.
This difficulty is especially pronounced in regards to protecting those with mental disorders.
Medical cannabis laws that legitimize the use of cannabis for multiple, diagnostically ambiguous
health conditions including some psychiatric conditions, have the potential to further increase the
prevalence, frequency, and dose of cannabis use among those with or at risk for mental disorders.
Thus, when considering optimal regulatory strategies for cannabis, it would seem prudent to start
by examining not only the U.S.’s history of regulatory efforts to mitigate the harms of tobacco and
alcohol, but also the concepts and systems that guide pharmaceutical industry regulation. Below,
we provide examples of several parallels between the emerging cannabis industry and the
pharmaceutical, tobacco, and alcohol industries. We believe these parallels can inform preliminary
designs of public health-oriented regulatory approaches to cannabis that may help prevent
escalation of the risk of harm among those with mental disorders.
Making scientifically unsubstantiated medical claims and using them for promotional purposes.
For-profit companies benefit from selling as much of their products as possible, to as many people
as possible. However, when the product being sold is a medication, there is a unique tension to
consider. The revenue generated by a medication is bound to the incidence and prevalence of the
medical condition that the medication has been approved to treat. It is largely for this reason that
pharmaceutical companies have often sought to expand the use of a medication in the population
by attempting to promote “off-label” use of that medication. Briefly, off-label use denotes the use
of a medication for indications not approved by FDA (i.e., treatment of conditions for which there
are few if any data supporting the use of that medication). Psychiatry is particularly vulnerable to
the influence of off-label promotion (Moncrieff, 2011; Moncrieff, Hopker, & Thomas, 2018). It is
not difficult to find instances in which pharmaceutical companies have attempted to increase off-
label prescribing of psychiatric medications to treat non-approved mental disorders (Kesselheim,
Mello, & Studdert, 2011; Mack, 2003; McKean & Monasterio, 2012; Mello, Studdert, & Brennan,
2009; Vedula, Bero, Scherer, & Dickersin, 2009), and not surprisingly, off-label prescribing of
psychiatric medications is common (Alexander, Gallagher, Mascola, Moloney, & Stafford, 2011;
Eguale et al., 2012; Stafford, 2008). However, this tactic is not limited to pharmaceutical
companies. There is evidence that the tobacco industry promoted the idea that smoking and
nicotine helped reduce anxiety and regulate emotions (Hirshbein, 2012), and that nicotine provided
a means for individuals with schizophrenia to self-medicate (Prochaska et al., 2008).
Similarly, few U.S. legal cannabis laws have explicitly deemed anxiety or depressive
disorders as qualifying conditions for medical cannabis. Yet survey data clearly indicate that
anxiety and depression are consistently two of the most common reasons for using medical
cannabis (Aggarwal et al., 2013; Bonn-Miller, Boden, et al., 2014; Lankenau et al., 2018; Nunberg
et al., 2011; Reinarman et al., 2011; Sexton, Cuttler, Finnell, & Mischley, 2016; Troutt &
DiDonato, 2015). Understanding why this is happening is critical. As mentioned above, many
positively rewarding psychoactive substances also produce acute relief from current negative
emotional states. Such negative reinforcement is a likely contributor to the high prevalence of
cannabis (and other substance) use among those with mood disorders.
Because a substantial amount of the cannabis consumed in the United States is consumed
by individuals with mental disorders (Lev-Ran, Le Foll, et al., 2013), it is in the interest of the
cannabis industry to continue to promote the idea that cannabis is a useful “treatment” for mental
disorders. Indeed, cannabis product distributors are now making scientifically unsubstantiated
claims about using cannabis to treat depression and anxiety (Bierut, Krauss, Sowles, & Cavazos-
Rehg, 2017; Caulkins, 2018; U.S. Food and Drug Administration, 2016), and it is easy to find
examples of legally-registered dispensaries in states like Colorado (The Clinic Marijuana Center,
2017), New Jersey (Garden State Dispensary, 2017), Delaware (First State Compassion Center,
2018), Rhode Island (Summit Medical Compassion Center, 2017), Nevada (Deep Roots Medical,
2017), and New Hampshire (Sanctuary Alternative Treatment Center, 2017) tacitly or explicitly
promoting the use of cannabis or cannabinoids to treat mental disorders on their websites even
though such disorders are not on the list of state-approved conditions. Furthermore, many
dispensaries are staffed by budtenders who provide point-of-sale verbal recommendations or
written materials concerning which type of cannabis (%THC, %CBD) can be used to treat various
mental disorders and negative moods states (Haug et al., 2016).
What makes these observations concerning is that information that “legitimizes” or
provides messages of hope related to cannabis’ proclivity for relief from mental disorders has great
potential for increasing initiation and possibly maintenance of cannabis use among those with
mental disorders. Potential for this impetus to cause such harm can manifest in at least two ways:
(1) use of cannabis rather than or in addition to known effective medications, and (2) facilitating
rationalization of use of a substance (cannabis) with known potential for addiction and likely long-
term adverse effects on psychiatric conditions.
Despite such industry behavior, one is hard-pressed to find any provisions of legal cannabis
laws requiring that cannabis product labels, dispensary websites, or dispensary staff, detail the fact
that the scientific literature does not support cannabis as a treatment for mental disorders, and that
cannabis use has potential for adversely impacting such conditions.
Cannabis sales outlets (i.e., dispensary) location and density.
The disproportionately large prevalence of alcohol and tobacco use disorders among those with
mental disorders may be attributed, in part, to the fact that mental disorders and outlets for selling
alcohol and tobacco are both highly concentrated in the same geographic areas – primarily
socioeconomically disadvantaged neighborhoods (Pearson, Bowie, & Thornton, 2014; Pereira,
Wood, Foster, & Haggar, 2013; Young-Wolff, Henriksen, Delucchi, & Prochaska, 2014). It is well
known that systems-level contextual variables such as the location and density of tobacco and
alcohol outlets are strongly related to having a tobacco or alcohol use disorder and having a more
difficult time discontinuing use (Campbell et al., 2009; Chuang, Cubbin, Ahn, & Winkleby, 2005;
Reitzel et al., 2011).
Again, as might be expected, a growing body of literature examining the location and
density of cannabis dispensaries reveals patterns similar to those for alcohol and tobacco. Often,
states pass non-preemptive legal cannabis laws, letting municipal governments decide whether or
not to permit sale of cannabis in their particular jurisdiction. Consequently, dispensaries have
become more concentrated in socioeconomically disadvantaged areas (Morrison, Gruenewald,
Freisthler, Ponicki, & Remer, 2014; Nemeth & Ross, 2014) that also have high densities of alcohol
outlets (Morrison et al., 2014; Shi, Meseck, & Jankowska, 2016; Thomas & Freisthler, 2016). By
some estimates, for each additional dispensary per square mile, the annual number of cannabis use
disorder-related hospitalizations increases by 7% (Mair, Freisthler, Ponicki, & Gaidus, 2015).
Individuals living in states with a greater number of dispensaries per person are also more likely to
have used alternative methods of cannabis administration (e.g., edibles and vaping), illustrating the
influence that dispensary proliferation may have on use patterns (Borodovsky, Crosier, Lee,
Sargent, & Budney, 2016).
Some efforts have been made to prevent dispensaries from being located near mental health
treatment clinics (Freisthler, Kepple, Sims, & Martin, 2013). However utilization of mental health
treatment is extremely low (most notably among socioeconomically disadvantaged individuals) (P.
S. Wang et al., 2005). Thus this solution, although well-meaning, targets locations where only a
fraction of this vulnerable population is found.
Cannabis products: potency, content, and diversification.
At the turn of the 20th century, the mechanization of the tobacco industry brought about increased
product development and alterations (Richter & Levy, 2014). Given that those with mental
disorders are more likely than the general population to become and stay addicted to nicotine
(Prochaska, Das, & Young-Wolff, 2017) and have the highest prevalence of nicotine use disorder
(Grant et al., 2004; Hurt & Robertson, 1998), one could reasonably argue that tobacco company
efforts to develop products that increased the amount of nicotine delivered to the user affected
those with mental disorders more than any other subpopulation. A similar dynamic appears to be
taking place with regard to the nascent legal cannabis industry (ArcView Market Research, 2016;
Richter & Levy, 2014). Since the mid-1990’s, the average potency (i.e., %THC) of street cannabis
seized by the DEA has increased from 4% to 12% THC (ElSohly et al., 2016). Remarkably, the
cannabis products sold in dispensaries can exceed these levels by up to 7-fold (Carlini et al., 2017).
Moreover, these high potency THC concentrates are being consumed using new rapid and efficient
methods of administration (M. Loflin & Earleywine, 2014). Survey data have begun to link the use
of these high-potency products to increased risk of depression, anxiety, and psychosis (Chan et al.,
2017; Daniulaityte et al., 2017; Keller, Chen, Brodsky, & Yoon, 2016) - supporting prior findings
from the United Kingdom that indicate similar relationships (M. Di Forti et al., 2009; Marta Di
Forti et al., 2014). Despite this, few states have attempted to regulate the potency of cannabis
concentrate products, and additionally, to our knowledge, there are no regulatory requirements to
warn consumers about the concerns associated with use of high potency cannabis concentrate
Historically, tobacco companies also have profiled the product preferences of subgroups of
tobacco users, and in doing so learned about the potential reinforcing effects of product flavoring
(Ahijevych & Garrett, 2010; Cook, Wayne, Keithly, & Connolly, 2003). For example, those with
mental disorders are more likely than other groups of smokers to be using menthol-flavored
cigarettes (Cohn, Johnson, Hair, Rath, & Villanti, 2016; Prochaska et al., 2017). Menthol flavoring
enhances the reinforcing effects of nicotine (Ahijevych & Garrett, 2010), leads individuals to
believe that tobacco is less harmful (Anderson, 2011), and is associated with more difficulty
quitting (D. T. Levy et al., 2011). Similar tactics and associated concerns are apparent with
cannabis product design and flavoring. There has been an unprecedented diversification of
attractive cannabis edible products (e.g., baked goods, drinks, lollipops, gummies)(Barrus et al.,
2016). Such products may reduce risk perceptions of cannabis use and increase the reinforcing
potential of cannabis because they are highly palatable and allow users to avoid the unpleasant
sensations associated with smoking. Additionally, different strains of cannabis are known to smell
and taste different putatively in large part because they contain different profiles of a class of
compounds called terpenes. Terpenes found in the cannabis plant have also been touted for their
potential anti-anxiety properties (Russo, 2011). The cannabis industry has now begun filing patents
for methods to create cannabis plants with terpene profiles that they believe are useful for treating
anxiety and depression (Lewis, Backes, & Giese, 2015; Weed, 2017). In summary, effective
regulation of cannabis will need to focus on various aspects of cannabis product design. This
includes not only THC and CBD content, but other product constituents that may alter the
reinforcing effects of cannabis (e.g., edible flavors and terpenes).
Recommendations for legislative and regulatory actions
Based on extant literature and historical knowledge of the for-profit sale of psychoactive
substances, the following recommendations may help prevent or reduce legal cannabis-related
harms among those with mental disorders.
(1) States with medical cannabis laws should remove any psychiatric conditions from their list
of qualifying conditions.
(2) States with medical cannabis laws should remove any clauses in their legislation that
provide medical condition loopholes (i.e., allowing use for any conditions that a physician
(3) Medical and commercial cannabis dispensary personnel, product labels, publications, on-
site display materials, websites, and social media profiles should:
not be permitted to tacitly or explicitly make scientifically unsubstantiated claims
about the therapeutic utility of the cannabis plant for mental disorders (or any other
not be permitted to use psychiatric proxy terms such as “stress,” “happy,” or
“relaxed” to describe the effects of consuming cannabis products.
clearly inform consumers that cannabis may contribute to the onset of mental
clearly inform consumers that cannabis may worsen symptoms of a mental disorder
and adversely impact its course.
not be permitted to use terms referring to the cannabis plant (e.g., “marijuana” or
“cannabis”) when describing published scientific investigations of isolated
cannabinoid compounds (e.g., THC or CBD).
(4) States with medical and commercial cannabis laws should actively enforce licensed
dispensaries’ adherence to regulations via compliance checks and audits similar to those
used for tobacco (Jason, Ji, Anes, & Birkhead, 1991) and alcohol (Wagenaar, Toomey, &
Erickson, 2005). Failure to comply with regulations would result in heavy, financially-
related penalties. Compliance checks might involve active monitoring of dispensaries’
online behavior (e.g., dispensary website or social media page)(Peiper et al., 2017) or
having government personnel attempt to purchase cannabis explicitly for psychiatric
(5) Regulations should limit THC potency in all cannabis products. Data are not available to
inform a specific %THC limit, thus setting this limit would be partially, but not completely
arbitrary. A growing literature raises concern about the association between the use of high-
THC products and development of mental disorders, and in the last few years we have seen
an escalation in hospitalizations associated with excessive intoxication from consumption of
high-THC products (particularly edibles and concentrates)(Pierre, Gandal, & Son, 2016; G.
S. Wang et al., 2016). There is little justification for selling and consuming cannabis
products with THC levels over 15%, particularly for “medical” use. Such limits would help
curb industry attempts to devise cannabis formulations with greater reinforcing effects that
might be especially harmful to those with mental disorders.
(6) Legal cannabis laws (medical or commercial) or the regulations enacted by municipalities
in states with non-preemptive legal cannabis laws should restrict the total number of
dispensaries permitted within the state or specific municipalities, with special consideration
for the location of dispensaries. For example, states could limit the total number of
dispensaries located in neighborhoods with average household incomes at or below the
federal poverty level.
(7) Develop a research agenda that allows regulatory agencies to implement cannabis product
standards–analogous to FDA’s tobacco product standards–that protect public mental health.
The core mission of this research agenda should be to determine if potential new product
standards could (1) increase the likelihood that current cannabis users who have or are at
risk for developing a mental disorder discontinue cannabis use, and (2) decrease the
likelihood that individuals who are not using cannabis and either have or are at risk for
developing a mental disorder, start using cannabis (Villanti et al., 2011).
(8) States with both a commercial and medical cannabis law should tighten restrictions in their
commercial law and, although highly improbable, repeal their medical cannabis law to
allow time for clinical science to develop and test cannabinoid compounds that are safe and
effective for treating mental disorders.
(9) States with only a medical cannabis law should replace their law with either a restrictive
commercial cannabis law or decriminalization.
Future directions: research and data infrastructure
It is necessary to begin building a body of scientific knowledge that can be used to design cannabis
regulations that protect those with or predisposed to developing mental disorders. The question is:
where do we start? Perhaps the best place to look for the types of research questions that must be
addressed is in the tobacco, alcohol, and pharmaceutical regulation and control literature (Ashley &
Backinger, 2012; Ashley, Backinger, van Bemmel, & Neveleff, 2014; Barry & Glantz, 2016;
Pacula, Kilmer, et al., 2014). For example, in the same way that tobacco product content has been
evaluated for its impact on those with or at risk for mental disorders (Cohn et al., 2016), it will be
essential to evaluate the impact of cannabis product content (e.g., THC, CBD, other cannabinoids,
terpenes) on one's risk for developing a mental disorder or the course of an existing mental
disorder. Similar thinking should apply to various product labeling and marketing tactics that the
cannabis industry is likely to employ. More broadly speaking, perhaps one of the most fundamental
concepts for cannabis regulatory scientists to consider is the interaction between the medical and
commercial cannabis industries. Well-designed research that results in effective regulation of the
medical cannabis industry may have suboptimal impact if similar regulations cannot
simultaneously be applied to the commercial industry.
Permitting the for-profit sale of addictive substances creates a unique set of public health concerns
- particularly when the substance is sold both as a medicine and a commercial product. As cannabis
transitions from illicit to licit substance in the U.S., our ability to monitor and isolate potential
causes of acute and long-term benefits and adverse effects of cannabis use on a population-level
scale must keep pace. Although some states have created medical cannabis patient registration
systems, the resulting data fall short of what will be necessary for creating effective regulations.
Several researchers have noted that effective monitoring will be impossible unless there is a
concerted effort to create new local, state, and federal cannabis data collection systems (Freeman &
Swift, 2016; Hoffman, Terashima, McCarty, & Muench, 2017; Kilmer & Pacula, 2017a, 2017b;
Lenton & Subritzky, 2017; S. Levy & Weitzman, 2016; Pacula, Kilmer, et al., 2014; van Ours,
The Sentinel System currently utilized by FDA for pharmacovigilance provides an excellent
first step towards conceptualizing a cannabis data system. Launched in February 2016, the Sentinel
System allows FDA to query de-identified, individual-level data from a diverse but synchronized
network of relevant partners (i.e., hospitals, insurance companies, pharmacies) to answer questions
concerning medication safety (Behrman et al., 2011; U.S. Food and Drug Administration, 2018).
State-specific sentinel initiatives (or perhaps even collaborative inter-state systems) for cannabis
could require all registered dispensaries and relevant healthcare entities to comply with
standardized, individual-level, data collection and reporting procedures. Such data systems could
provide the vital information necessary for creating more nuanced cannabis exposure variables and
uncovering links to important health outcomes. For example, states could classify types of products
based on cannabinoid concentrations (e.g., CBD-oils, THC concentrates) and monitor the number
of units and total volume of each type of product sold in particular jurisdictions. These data could
then be linked with local-, county- and state-level mental disorder incidence and prevalence data.
The combined dataset could be used to detect correlative relationships worthy of further
investigation and possible intervention.
The extant data indicate that those with mental disorders are negatively and disproportionately
impacted by cannabis use, and are decidedly vulnerable to poorly regulated for-profit industries
that market addictive substances such as cannabis. Policy-makers must recognize and consider
these facts when developing or modifying cannabis laws and regulations. By building a robust
Cannabis Regulatory Science, scientists will generate knowledge that can be translated into novel
evidence-based regulations. As part of this effort, cannabis regulatory scientists should remain
sensitive to the clear vulnerability of those with mental disorders and aim to discover and
implement evidence-based policies that protect this and other vulnerable populations.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and
writing of the paper. Funding: NIH grants: 5T32DA037202, 5R01DA032243, P30DA029926. The
funding sources had no involvement in the study design; collection, analysis, and interpretation of
data; writing of the report; or in the decision to submit the article for publication.
This work was supported by NIH grant funding: 5T32DA037202, 5R01DA032243,
P30DA029926. The funding sources had no involvement in the study design; collection, analysis,
and interpretation of data; writing of the report; or in the decision to submit the article for
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