Blunted: The Effects of Cannabis on Cognition and Motivation
The recent political momentum to decriminalize, legalize, and commercialize cannabis has put a premium on the need for high-quality objective research on its neurobehavioral effects. Not only are scientists and healthcare professionals interested in cannabis research of late but also advocates, the media, venture capitalists, cannabis consumers, and government officials. Due to the different goals various groups have, messaging about cannabis use often leaves the public and many medical professionals increasingly confused as they hear what appears to be dueling science on the potential risks and benefits of cannabis use. Scanning the Internet today, it is not difficult to encounter the view that concerns over the negative effects of cannabis on cognitive skills are completely unfounded with cannabis even being cognitive enhancing. It is also easy to find sources claiming that even infrequent use of cannabis in adults can irrevocably rot the brain. Thus, the primary goal of this chapter is to provide a brief summary and synthesis on what is actually known scientifically about the associations between cannabis use and cognition: a domain that has been a concern to many for decades. Beyond the fundamental question of whether or not there is a causal link between cannabis and cognitive deficits, this chapter will also examine clinically relevant questions such as the magnitude of the link and impact of moderating factors. Secondarily, however, this chapter will attempt to describe how some of this scientific knowledge has been applied to the ongoing debate regarding cannabis legalization and commercialization with the hopes that readers will be better equipped to think through the current controversy for their own benefit and when speaking to interested patients, clients, and students.
Memory
Memory function encompasses a number of related but somewhat distinct domains and has been one of most heavily studied areas when it comes to its association with cannabis use. Verbal memory is often assessed through tasks that require the recalling of word lists at different time intervals. A number of studies have shown that cannabis can acutely impair verbal memory [1, 2] with intrusion errors (i.e., believing that a word that was not on a recall list actually was) being particularly prominent. Further, there is evidence that these effects cannot be solely accounted for by the effect of cannabis on attentional systems, which will be covered next [3]. Verbal learning and memory has also been consistently [4, 5], although not uniformly [6], associated with chronic cannabis use in the absence of acute intoxication. Poorer performance has been associated with higher frequency, duration, and quantity of use as well as an earlier age of onset [2]. Higher delta-9-tetra-hydrocannabinol (THC) content of consumed cannabis has also been associated with stronger impairment [7]. A period of abstinence, perhaps as short as a few weeks, may help improve or even eliminate these differences between cannabis users and non-users [8–10], although other studies have shown evidence of continued impairment even after cannabis use has stopped [11, 12]. One methodological complication from some of these studies which has limited conclusions regarding the causal impact of cannabis has been a lack of cognitive testing prior to the cannabis use, although efforts have been made to match users and non-users on early cognitive ability in some studies [11].
Working memory refers to processes that involve the ability to store and use information for short period of time. It is assessed through a number of procedures including digit recall or n-back tests. Working memory has also been shown to be vulnerable to the effects of cannabis in studies of both humans [13] and animals [14, 15] although the evidence has been judged as not as strong as it is in more verbally oriented skills [2].
Like many other areas of cannabis research, being able to demonstrate that cannabis actually causes cognitive deficits has been challenging from naturalistic studies of human beings, even those using statistical methods to try to account for non-causal associations. “Correlation does not prove causation” has been a frequent mantra of cannabis advocates eager to minimize the evidence that has demonstrated a link between cannabis use and decreased cognitive functioning. Consequently, some individual studies deserve mention due to their ability to offer stronger conclusions regarding causality. Some of this work is also quite recent and has yet to be fully incorporated into consensus opinions and documents.
One of those studies by Morin and colleagues involved the testing of 3826 students in the Montreal area who, beginning in the seventh grade, had multiple assessments of both substance use (alcohol and cannabis) and cognition across 4 years [16]. This provision allowed the researchers to look at different models of association including the possibility of reverse causation (i.e., that cognitive deficits lead to substance use rather than the other way around), common factors (that a shared factor leads to both cognitive deficits and substance use) and a more causal route. The study found that cannabis use was more strongly related to cognitive deficits such in areas such as working memory than alcohol. Further, some of these differences were not minor with cannabis using tenth graders showing levels of inhibitory control on par with non-cannabis using seventh graders. When it came to testing models of association, the authors found that there was evidence both that there may be common factors that lead to substance use and cognitive problems but also, for cannabis only, there was evidence of more direct “neurotoxic” effects of cannabis on cognitive domains of working memory and inhibitory control. This study is important not only scientifically but also with regard to public policy, as it suggests that the frequent debate that cognitive problems associated with cannabis represent either the presence of an unrelated third factor or a more direct effect may be a false dichotomy and that both mechanisms could be operating simultaneously.
From a large study published in JAMA Internal Medicine from the Coronary Artery Risk Development in Young Adults (CARDIA) study that followed a large cohort of young adults for 25 years, a dose-dependent association was found between lifetime cannabis use and worsening verbal memory in middle age, even after controlling for potential confounds [17]. For every additional 5 years of cannabis exposure, there was a reduction in 0.13 standardized units of verbal memory score compared to individuals who never used cannabis. Poorer processing speed and executive functioning was also found to be associated with cannabis use, but this link was no longer statistically significant when adjusting for other variables.
Experimental studies with animals can also be very valuable in lending confidence about causation when it comes to cannabis and cognitive problems. While this research tends not to be as well publicized as human studies, there indeed is a fairly sizable literature on the subject. Overall, many studies have demonstrated that cannabis exposure, especially to adolescent mice, rats, and monkeys, does result in deficits in memory and other cognitive functions [18–21]. Some of this dysfunction can be long-lasting [22]. At the same time, however, there have also been animal studies suggesting that THC may have positive cognitive effects and may be neuroprotective in studies involving animal models of Alzheimer’s disease [23]. While much more research is needed, it has been hypothesized that age and dose may be crucial factors with THC having generally negative effects on cognition for younger individuals (regardless of the dose) while perhaps showing more positive effects for people who are older when used at very low doses [24]. A small open trial of 10 people with dementia has been touted as evidence that cannabis should be considered as a treatment alternative, although it is important to point out that this study used an oral preparation that contained more cannabidiol than THC [25].
In summary, the research suggests that both acute and chronic cannabis use is related to non-trivial reductions in memory skills, particularly with regard to verbal memory. Some of these deficits, but perhaps not all, are recoverable with extended period of abstinence. Regarding the component parts of memory, it has been hypothesized that cannabis causes result in alterations in both the encoding and recall of information and may disrupt the process through which information is transferred into long-term memory [1]. Further discussion of the potential brain areas and neurobiological mechanisms affected are reviewed at the end of this chapter.
Attention
The domain of attention also encompasses a rather broad set of skills that allows someone to maintain a goal-directed focus on an individual stimulus while also being able to shift that focus in response to environmental demands. As with other cognitive abilities, the various aspects of attention are supported by interrelated but somewhat distinct neural pathways and substrates and can be assessed through a variety of tasks such as the continuous performance task (CPT), reaction time tests, and other attentional control tests.
A 2017 review from the National Academies of Sciences, Engineering, and Medicine concluded on the basis of four systematic reviews that there was good evidence that cannabis can acutely impair the ability to focus and sustain attention and can weaken performance in situations that require divided attention [2, 26–28]. These effects appear to progress in a dose-dependent manner. The case for more chronic deficits, however, particularly for cannabis users who have abstained for at least a month, is less compelling with the majority of studies indicating that attentional skills return to baseline within a matter of weeks [29, 30]. Interestingly, however, there is evidence from neuroimaging studies that chronic cannabis users, while having similar scores on attentional tasks as non-cannabis using individuals, recruit different neural networks and pathways as a possible compensatory strategy [26].
Executive Function
The term executive functioning is often applied to higher-order cognitive processes that involve skills such as organization, planning, inhibiting behaviors, overcoming interference, and problem-solving. As a group, these skills have been shown to be significantly related to improved mental health, well-being, and socioeconomic status.
Studies related to executive functioning and cannabis use have been fairly inconsistent relative to both acute affects and chronic use [31]. This inconsistency for acute effects may reflect some important moderating variables that have been identified such as earlier onset of use [32] and extent of cannabis use prior to testing [33]. While the critical role of various other factors with regard to the link between cannabis use and cognitive problems will be explored in more detail later in this chapter, the variable findings regarding chronic use have been hypothesized to be due to the fact that executive functioning skills are relatively slow to mature with deficits being harder to document until later in adulthood [2]. The review of cannabis effects on cognition by Broyd and colleagues points out that this theory is supported by some of the data on the recovery of executive functioning abilities with abstinence in which persistent alternations have been better documented for older [9, 34] compared to younger [12, 30] samples.
Intelligence and IQ
Given the fact that many of the previously mentioned cognitive domains such as working memory are a component of the broader area of intelligence, it would be surprising that overall intelligence would be spared by cannabis, and many studies have used overall intelligence and IQ as their primary variable of interest. Given the public familiarity and concern with the concept of intelligence and IQ along with its significance in other domains of functioning, these studies are also frequently cited and discussed in deliberations about the effects of cannabis decriminalization, legalization, and commercialization.
A study comparing adult twins who were discordant for regular marijuana use did show differences in intelligence [9], although only on the block design subtest of the Wechsler Adult Intelligence Scale. While no assessment of intelligence was done prior to the cannabis use, the cannabis-using twins in this study had been abstinent from use for at least 1 year with the average length of abstinence being approximately 20 years.
One of the most dramatic and often cited studies regarding cannabis and IQ comes from the well-known Dunedin study which has followed a cohort of over 1000 individuals from age 3 well into adulthood [35]. Subjects completed neuropsychological testing around the age of 13 and 38, while cannabis and other substance use was assessed at multiple waves between the ages of 18 and 38. The researchers found that those who were regular cannabis users during at least 3 waves of the study lost about 6 IQ points while those who never used experienced a slight increase in IQ. This decline was found across IQ domains, although was most apparent with regard to processing speed and executive functioning skills. Furthermore, cognition did not fully recover among participants who began using cannabis in adolescence but later stopped. This study was in contrast to a smaller and earlier study which also examined changes in IQ among youth before (between age 9 and 12) and after cannabis exposure (between age 17 and 20) [36]. While this report also showed that heavy cannabis users had declines in IQ (here 4.1 points) relative to light and non-users who gained IQ during this interval, the authors failed to find evidence of long-lasting deficits among previously heavy users who had become abstinent.
In 2016, another study by Jackson and colleagues reported contrasting findings from two samples of twins who were adolescents around the years 2003–2010 [37]. Like the Dunedin study, the researchers did find that cannabis users tested lower than their non-cannabis-using peers (around 4 IQ points difference) and, further, their scores declined between preadolescence and late adolescence. However, increased frequency of use was not related to greater cognitive declines. In addition, comparisons within twin pairs in which one twin used cannabis and another didn’t (an analysis that controls for other genetic predispositions and shared environmental variables) did not consistently show differences between the twins.
As might be expected, advocates for and against the promotion of cannabis tend to favor one study over another, but is it possible to reconcile these investigations? One clear difference among the Dunedin and Jackson studies relates to the threshold of what was defined as heavier cannabis use. In the Dunedin study, the amount of use among individuals with the IQ loss was quite extensive with many individuals using for long periods of time and at levels that would qualify them for a diagnosis of dependence. In the Jackson study, by contrast, heavy use only required using more than 30 times in one’s life. As will be discussed in more detail, differences in these important variables may help explain what otherwise appear as inconsistent findings and can offer clues about important factors that are highly relevant in understanding an individual’s risk.
Motivation
While the stereotype of the person who regularly uses cannabis often includes the idea of someone who has lost the drive and interest to do much of anything other than use more cannabis, the scientific literature has been more mixed in supporting such a caricature [38]. The topic of motivation is not usually considered a core dimension of cognition, but its discussion here is important not only because of its critical role for overall well-being and success [39] but also because it has been hypothesized that perhaps some of the cognitive differences found among cannabis users may be attributed to reduced motivation during these tasks rather than a cognitive deficit per se [40].
The term “amotivational syndrome” has often been used to describe many habitual cannabis users for decades [41]. What is controversial is not the frequent correlation that has been found between cannabis use and reduced levels of persistence, self-efficacy, and goal-directed behavior but the direction of causality, with some arguing that the association is primarily driven by less motivated individuals seeking out cannabis rather than any direct effect of the drug on motivational systems in the brain [42]. More recent work with designs better equipped to assess the direction of causality, however, continue to suggest that cannabis use can indeed lead to reduced motivation and self-efficacy. Using cross-lagged panel modeling, Lac and Luk demonstrated that cannabis use, but not alcohol or tobacco use, prospectively predicted lower initiative and persistence in the future while finding no evidence for causality going in the opposite direction [39]. An experimental study also demonstrated that acute cannabis use was associated with reduced effort in a money earning task with cannabidiol (CBD) partially moderating this effect [43]. Findings related to chronic cannabis users who had abstained for at least 12 hours, however, were more complicated with no differences found in comparison to controls when it came to effort-related decision-making but with cannabis-dependent subjects showing weaker overall reward learning. Further, randomized studies in animals, including one with rhesus monkeys, have also documented that cannabis can produce an amotivational-type syndrome among exposed animals, providing further support for this theory [44]. Overall, there continues to be evidence of motivation impairment associated particularly with acute cannabis use, but the data regarding more chronic and persistent effects is inconsistent and not as extensive as some of the stereotypes of cannabis users suggest.
Mechanisms of Action
Many researchers have moved beyond the question of if cannabis causes cognitive deficits to examine the topic of how cannabis exerts these effects. THC is known to inhibit cholinergic activity in many parts of the brain including the limbic system and cortex [25]. Mechanisms related to memory impairment have understandably focused on brain regions such as the hippocampus and its interactions with other areas of interest. Once again, studies with animals have proven very useful in this line of inquiry and a number of studies have indeed demonstrated changes in the structure and function of important cognitive processing brain regions such as the hippocampus and prefrontal cortex [45–47]. In an older study, chronic exposure to THC in young rats resulted in nerve cell loss in the hippocampus in patterns that resembled accelerated changes associated with aging [48].
One previously mentioned study that showed memory deficits in adolescent rats exposed to THC found that the induced deficits appeared to be mediated through increased expression of 56 genes involved in inflammation of hippocampal astrocyte cells [18]. Of additional interest in this study was the fact these mice also had an allele of the DISC1 gene that has been implicated with severe mental illness in a Scottish family study [49]. Adding confidence to the researchers’ conclusions was also the finding that the cognitive deficits could be counteracted when THC was given at the same time as some anti-inflammatory medications.
Studies that expose animals in earlier stages of development to THC have demonstrated alternations in the expression of genes related to glutaminergic and noradrenergic systems in the brain [22]. In one previously cited study demonstrating memory impairment with acute cannabis use, some of the effects were found to be reversible with rivastigmine but not vardenafil, suggesting a stronger role for acetylcholine over glutamate in these deficits [13]. At the cellular level, a relatively recent study published in Nature demonstrated that the cognitive effects of acute THC exposure operates, at least in part, through the depletion of energy production in the mitochondria of hippocampal neurons that also express the cannabinoid 1 (CB1) receptor [50]. Such changes in mitochondrial energy metabolism are also present in some neurodegenerative disorders and strokes.
With regard to motivation, much of the attention has predictably focused on the interaction between the brain’s endocannabinoid system and striatal dopaminergic pathways involved in reward processing and motivated behavior [51]. THC is known acutely to boost dopamine release which makes the effect of reduced motivation somewhat counterintuitive and illustrates the need for more research [43]. Chronic cannabis use, however, has been found to be related to reduced dopamine synthesis [52]. Using crossed-lagged models from multiple assessments of both cannabis use and functional brain activity, increased cannabis use was found to be associated with blunted activation of the nucleus accumbens, a region well-known for its role in addiction and behavioral response to reward [53].
Moderating Factors
As has been documented in many of the aforementioned studies, several factors have been shown to have a major impact on the link between cannabis use and cognitive/motivational deficits. Indeed, the variable presence and presentation of these factors from study to study may help explain much of what otherwise appears as inconsistency in the cannabis literature. The risk of 40-year-old who occasionally uses low potency cannabis appears to be quite different from the risk of a 16-year-old adolescent who is a regular consumer of cannabis with high levels of THC. Moreover, the direction in which some of these moderating factors alter the relations between cannabis use and cognition may vary between acute and more chronic settings. More experienced cannabis users, for example, may show less of a reduction in cognitive capacity with acute cannabis exposure compared to cannabis-naïve individuals, possibly through tolerance of the drug [40]. Over the long term, however, more cognitive impairment has generally been associated with earlier age of onset, more frequent use, and shorter periods of abstinence. Two characteristics of cannabis itself, namely, the concentrations of THC and CBD, also may play a significant role with regard to cognitive effects. While there is accumulating evidence suggesting that the potency of cannabis being used may be a critical factor when it comes to psychiatric risk for disorders like schizophrenia [54], this potentially important dimension has not been as well studied with regard to cognition.
Summary and Future Directions
Looking broadly over the scientific evidence that currently exists on the relations between cannabis use and cognition, several conclusions can reasonably be reached. First, there is robust evidence that cannabis use can impair cognition and motivation both in the short- and long-term. The supporting data span multiple areas of cognition but are arguably strongest when it comes to memory and attention. Lending credence to the likelihood that the noted associations represent a true causal effect of cannabis are the accumulating number of positive studies that are more experimental in nature (using both humans and animals as subjects) as well as the employment of more sophisticated analyses such as cross-lagged models that are able to examine various mechanisms of association. Interestingly, these studies have often shown evidence for both a direct neurotoxic effect of cannabis on cognition in addition to the presence of other mechanisms, such as third factors leading to both cannabis use and cognitive deficits. Public debates about the risks of cannabis use often assume that direct causal mechanisms and shared third factors are mutually exclusive in explaining the association between cannabis and negative outcomes, but the emerging research suggests that both pathways can be at play simultaneously.
In appreciation of the strength and diversity of studies that have looked at the link between cannabis use and decreased cognitive ability, the popular retort by some cannabis advocates that the scientific literature on this important topic is purely “correlational” and thus dismissible appears to be a gross underestimation of the current state of evidence. At the same time, claims of severe brain damage associated even with episodic use among adults also exaggerate the state of research findings. Like most complex topics in neuroscience, the literature on cannabis and cognition is not wholly consistent, leaving plenty of room for people to cherry pick studies that fit their personal, political, or financial objectives.
Related to this point, a second conclusion that can be made is that moderating factors such as the timing and amount of cannabis use may be extremely important when it comes to a person’s risk. These factors, combined with others such as underlying genetic vulnerabilities, can lead to very different outcomes following use. It is likely that a significant portion of the variability in findings that have been reported on this subject is due to the failure to completely sample and account for these important variables, and future research would benefit from a more comprehensive and uniform approach to these factors that interject a real “it depends” when it comes to answering questions about the cognitive risks of cannabis use. Varied and somewhat arbitrary definitions of what constitutes “heavy use” or “high potency,” for example, increase the likelihood of studies reaching different answers for the same question. Being able to account for CBD and THC concentrations may also prove to be important as well. As many of the long range prospective studies currently available are derived from cohorts who consumed cannabis with much smaller THC concentrations than is used today, it is possible that the risks associated with cannabis use from these studies have been understated, should THC concentration prove to be as important when it comes to cognition as it appears to be in other areas such as risk of psychosis. One promising development in the effort to resolve some of the many remaining questions about the effects of cannabis on cognition is the launch in 2015 of the Adolescent Brain Cognitive Development (ABCD) study which will be following a group of approximately 10,000 children for at least a decade, starting at the age of 9 [55]. This study will represent the largest and most comprehensive effort to date to examine cognitive development through adolescence and the impact of many factors, including cannabis.
Finally, a third conclusion that can be made is that there is reason to be hopeful that any cognitive deficits that occur can be mitigated and even reversed with a sustained period of abstinence. With a few exceptions, the literature does not support the notion that the typical cannabis user will suffer a substantial and irrevocable loss of cognitive skills once a period of abstinence has been achieved. Such a perspective could be useful in motivating those who need it to seek appropriate treatment for cannabis abuse and dependence once, of course, the public and the medical community are fully appraised about the many risks associated with this drug.
Cannabis and Psychiatric Conditions
Psychosis
The mechanisms by which psychoactive cannabinoids produce transient psychotic symptoms are unclear but may involve dopamine, GABA, and glutamate neurotransmission. Dose, length of exposure, and the age of first exposure to cannabinoids may be important factors as well. Genetic factors that interact with cannabinoid exposure to moderate or amplify the risk of psychosis are being examined. Neurobiological changes seen with cannabis use show similarities with those seen in patients with schizophrenia. However, the similarities do not establish a cause-effect relationship because not all cannabis users go on to develop schizophrenia. It is likely that multiple, non-neurobiological factors also play a role [56].
Many studies confirm that cannabis is definitively linked to the development of psychoses, including the thought disorder schizophrenia, especially in the context of pre-existing genetic vulnerability [57–60]. Cannabis use causes cognitive changes (discussed in another chapter) and dysfunction in dopamine transmission in genetically vulnerable subjects, which may be responsible for the psychotic-like experience.
Approximately 14% of psychotic outcomes in young people would not have occurred if cannabis had not been consumed. Heavy use of potent cannabis at a younger age in individuals at risk for developing schizophrenia exacerbates the course of the illness by advancing the time of a first psychotic break by 2–6 years. This has prognostic significance in that most individuals who develop schizophrenia do so at a later age, late teens to early twenties. With an earlier onset of illness, academic and social performance will be compromised, leading to a poorer prognosis compared with later onset of illness [61].
Among those who have used cannabis, the risk of developing psychosis increases by 40% and there appears to be a dose-response effect leading to an increased risk of psychosis up to 200% in the most frequent users [62, 63].
Cannabis use among adults with schizophrenia appears to be a double-edged sword. Low doses of cannabis consumption may improve frontal lobe function by acutely increasing blood flow to cortices concerned with cognition, mood, and perception, increasing the availability and utilization of dopamine. However continued use actually depresses cerebral flow and high consumption augments mesolimbic dopamine release, opposing the therapeutic effects of antipsychotic medications, thereby exacerbating psychosis. Finally, cannabis use in patients with schizophrenia suppresses prefrontal cortex dopamine utilization resulting in cognitive dysfunction [64].
In Australia, a sibling pair analysis within a prospective birth cohort was conducted. Of the 3801 studied, early cannabis use was associated with psychosis-related outcomes including non-affective psychosis, hallucinations, and delusions [65]. In London, a study of 780 people between the ages of 18 and 65 years with 410 experiencing a first episode of psychosis and 370 healthy controls demonstrated that high potency cannabis use was associated with a triple risk for psychosis [66]. Finally, 25 percent of patients diagnosed with schizophrenia meet the criteria for cannabis use disorder, making it one of the most commonly used drug among this patient population. Patients using cannabis experience more psychotic symptoms, respond poorly to antipsychotic medications, demonstrate poorer treatment compliance and worse clinical outcomes, and more relapses as well as more hospital admissions [62].
Depression and Anxiety
Several studies have demonstrated that cannabis use is associated with increased levels of anxiety and mood disorders [67–70], and it has been reported that heavier cannabis use in adolescents was associated with a heightened risk for developing an anxiety disorder [69].
Early-onset cannabis smoking is associated with an increased risk of depression [67]. One study conducted in Australia tracked 1600 girls over a 7-year period. Those who used cannabis daily were five times more likely to suffer from depression and anxiety than non-users. Additionally, teenage girls who used the drug at least weekly were twice as likely to develop depression compared to those who did not use [61]. At the UCSF Department of Psychiatry, 307 patients with depression were assessed at baseline and again at 3- and 6- month intervals for symptoms, functioning and cannabis use. Over 40 percent of the participants used cannabis within the 30 days of the start of the study. Cannabis use was associated with poor recovery. Those 50 years of age and older actually increased their cannabis use (P < .001) compared to the younger study participants. Cannabis use worsened depression (P < .001) as well as anxiety (P < .025) and led to poorer mental health functioning (P < .010) [71]. In addition to research showing that smoking cannabis exacerbates anxiety and depression, it has also been shown to worsen disorders of attention [72].
In Australia, 3239 young adults were followed from birth to the age of 21 years. Potential confounding factors were prospectively measured when the child was born and again at 14 years. After controlling for confounding variables, those who started using cannabis before the age of 15 years and used it frequently at 21 years were more likely to report symptoms of anxiety and depression in early adulthood than those who did not use cannabis (odds ratio 3.4; 95% CI 1.9–6.1) [73].
Cannabis -related visits to emergency and urgent care facilities by adolescents in Colorado increased dramatically between 2005 and 2015. In 2005, 161 visits were made, whereas in 2015, 777 visits were made. Behavioral health evaluations accounted for 67 percent of the contacts. Additionally, nearly three-fourths of the adolescents seen with diagnostic codes related to cannabis use were also diagnosed with depression, mood disorders, and anxiety. A large number of the patients also tested positive for alcohol, amphetamines, and opiate [74].
Many states legalizing cannabis for medicinal purposes have included post-traumatic stress disorder (PTSD) as a qualifying condition for treatment, despite the fact that little evidence exists evaluating the effect of whole plant cannabis use in PTSD. Whereas CBD may hold promise in helping REM sleep/behavioral disorders, mitigate hippocampal volume loss, and reduce symptoms of anxiety, THC does not appear to be therapeutic and, in fact, may aggravate the underlying disorder [75, 76].
Wilkinson et al. examined the association between cannabis use and PTSD symptom severity in a longitudinal, observational study of 2276 veterans over 4 months. The researchers concluded that cannabis use was significantly associated with worsened outcomes with regard to PTSD symptoms severity (P < .01). Specifically, more violent behavior was associated with cannabis use (P < .01) and, more alcohol and drug use was associated with cannabis use in PTSD patients (P < .01). The veterans participating in the study who had never used cannabis or had abstained from using cannabis during the study had the lowest PTSD symptoms at discharge (P < .0001). Finally, those who started using cannabis during the study exhibited the highest levels of violent behavior (P < .0001) [75]. The Veterans Affairs official site states clearly that any substance that is illegal on the federal level is not permitted to be used, recommended, prescribed, or endorsed by the Department of Veterans Affairs, up to and including the recommendation that veterans use cannabis to alleviate symptoms or pain. Any substance listed by the US Food and Drug Administration as a Schedule I controlled substance are subject to this prohibition at the VA level [77].
Addiction
Although historically cannabis has been thought to be less addictive than substances such as nicotine, cocaine, and heroin, the potency of THC in cannabis products obtained through interdiction seizures has increased from approximately 3 percent in the 1980s to 12 percent or higher in 2014 [78]. As a result, the cannabis available today may be more hazardous than earlier studies reflect. Whereas an average-sized cannabis “joint” contains 10–15 percent THC, butane hashish oil, a concoction of hashish oil infused with butane, can contain up to 90 percent THC [63]. Long-term cannabis users can develop dependence and withdrawal requiring chemical dependency treatment [63, 79, 80].
Historically, about 9 percent of regular cannabis users became addicted. By comparison, 15 percent of alcohol users, 32 percent of nicotine users, and 26 percent of opiate users become addicted [57, 63, 64, 81]. However with the advent of high potency cannabis products, cannabis use disorders are rising in prevalence. The National Institute on Drug Abuse recently released data that suggests that 30 percent of those who use cannabis may have some degree of cannabis use disorder [82].
Early cannabis exposure alters brain reward pathways, thus facilitating the subsequent use of other drugs. If cannabis use starts in childhood, one in six starters will become addicted. Daily users of cannabis are at the highest risk for developing cannabis dependence. Twenty-five to fifty percent of these users will become addicted [57]. While there has been controversy about this, cannabis is very likely a gateway drug because of the high potency of contemporary strains [57]. The earlier a child is exposed to cannabis, the greater the risk of cocaine and heroin use and drug dependence as an adult. Today, the number of adults with substance abuse disorders is increasing. Increasing access and availability of high potency cannabis products will only exacerbate this trend [63, 81].
Some reports have suggested that the legalization of cannabis products would curtail opiate use and opioid overdose death. However in Colorado, heroin-related deaths have doubled since 2011 when statewide; 79 deaths were observed compared to 2015 when 160 heroin-related deaths occurred. Pueblo County in particular was in the highest percentile of heroin use by county and also ranked as having statistically higher cannabis use [83].
Chronic users of cannabis who become dependent develop an uncomfortable withdrawal syndrome that can interfere with cessation of use, even when the user is motivated to quit. Withdrawal symptoms include irritability, nervousness, insomnia, restlessness, depression, decreased appetite and other physical discomfort [57].
Cannabis-Related Violence and Death
Death by suicide has also been observed among cannabis users. Multiple studies have documented a relationship between cannabis use and suicidality [67], and cannabis use is considered to be an important risk factor for suicidal behaviors [84].
The Veterans Administration conducted a cross-sectional, multisite study of 3233 Iraq/Afghanistan-era veterans. Cannabis use disorder was significantly associated with both current suicidal ideation (P < .0001) as well as a lifetime history of suicide attempts (P < .0001) compared to veterans with no lifetime history of having a CUD. This difference in those with CUD and those not diagnosed with CUD persisted even after adjusting for gender, PTSD, depression, alcohol use disorder, other drug use, childhood sexual abuse, and combat exposure [75, 85].
A large longitudinal study in Australia and New Zealand including over 2000 adolescents found an almost seven times increase in suicide attempts in daily cannabis users compared with non-users [86]. Dugre et al. studied 1136 recently discharged psychiatric patients followed at 4 and 10-week time intervals and evaluated them for cannabis, alcohol, and cocaine use as well as episodes of violence between 1992 and 1995. Persistency of cannabis use was associated with an increased risk of subsequent violence, significantly more so than with alcohol or cocaine [87].
Many proponents of the legalization of cannabis argued for the safety of the drug by noting no deaths were associated with it compared to opiates, cocaine, and alcohol. However, lethal consequences have been observed due to the increasing risk of psychosis. When recreational cannabis became legal, cannabis cookies, candies, and drinks infused with THC soon became popular. Many new consumers were not aware of the potent THC content in edibles [78]. In September 2012, an 18-year-old male smoked potent cannabis and subsequently fatally stabbed himself 20 times. In April 2014, a Wyoming college student jumped to his death from a Denver hotel balcony after eating more than the recommended serving of an edible product. That same month, a Denverite shot and killed his spouse in front of their three children after consuming edibles [78].
Studies show that the persistency of cannabis use following acute psychiatric discharge is predictive of violence [87]. Moulin et al. found cannabis use disorder to be a significant risk factor for violent behavior. In this study, 265 patients with early psychosis (dichotomized by presence or absence of violent behavior) were followed prospectively for 36 months. Cannabis use was linked to impulsivity and lack of insight. A cannabis use disorder diagnosis was made in 61 percent of subjects engaging in violence compared to 23 percent of non-users. Subjects who began using cannabis at a younger age, were more violent. Preventive strategies could be developed on the basis of such patient profiles [88].
Cannabis consumption has increased with its legalization as well as the perception that it is an innocuous substance. Hospital emergency departments continue to see a rise in patients presenting with cannabis-related adverse events. For example, the University of Colorado Hospital Emergency Department found a more than threefold increase in cannabis-associated emergency department visits from 2012 to 2016. This has placed a new burden on the healthcare system resulting from costly workups and hospitalizations [89].
Potential Psychiatric Benefits of CBD
Most of the psychiatric complications secondary to whole plant cannabis are related to the psychoactive cannabinoid THC and not CBD [90]. The expanding literature on CBD provides promising evidence that it is useful in the treatment of several psychological conditions. For example, the use of whole plant cannabis with high THC and low CBD concentrations has been associated with reduction of hippocampal volume, which increases the risk of impaired memory and new learning. Higher CBD to THC ratios may have a role in neuroprotection [91]. A number of studies have suggested that CBD may mitigate THC-induced psychosis [92–95]. CBD alone has antipsychotic effects. This was demonstrated in a study of healthy volunteers who experienced a reduction in ketamine-induced depersonalization with CBD treatment [96]. In a single case report of a patient with schizophrenia who could not tolerate conventional antipsychotics, a significant reduction in psychotic symptoms was observed after the patient received high-dose CBD for 4 weeks, with a recurrence of symptoms after the CBD was discontinued [97]. CBD given to patients with either acute paranoid schizophrenia or schizophreniform psychosis resulted in reduced psychotic symptoms, similar to what was observed with conventional antipsychotic drugs but with a significantly more tolerable side effect profile [98]. Finally, Gomes and colleagues demonstrated that CBD diminished the catalepsy induced by haloperidol, supporting its potential benefit as an adjuvant in the treatment of psychotic disorders [99]. These preliminary findings are promising and support the need for additional larger-scale randomized controlled trials in an effort to the establish efficacy of CBD in the treatment of psychotic disorders.
Zuardi and colleagues discovered that CBD has anxiolytic properties in study participants exposed to stressful situations [100]. CBD has also demonstrated superior efficacy compared to placebo in the treatment of generalized anxiety disorder [101]. Evidence also supports the potential benefit of CBD in the treatment of post-traumatic stress disorder. In one study, CBD reduced subjective anxiety and autonomic arousal, as measured by skin conductance response [102]. Another study involving the dual-step administration of the partial NMDA agonist D-cycloserine and CBD showed a disruption of reconsolidation of traumatic memories [103]. Finally, a double-blind, placebo-controlled trial demonstrated that CBD administration led to an enhanced consolidation of fear extinction when administered after extinction suggesting that CBD may be useful in the treatment of all anxiety disorders, including PTSD [104].
The role of CBD in the treatment of addictions has also been examined. Morgan and colleagues found that smokers treated with CBD reduced the number of cigarettes that they smoked by 40%. The number of cigarettes smoked by the placebo group was unchanged [105]. CBD may also have some utility in reducing opioid-seeking behavior and also diminish the reward-facilitating effects associated with opioid use [106]. However, much more research is required to fully determine CBD’s role in addiction medicine. While the growing body of clinical studies support the efficacy of CBD as an adjuvant as well as a monotherapy for psychiatric conditions, a recent Cochrane review concluded that there were insufficient high-quality studies to draw a reliable conclusion regarding efficacy, despite no reports of adverse events. Currently, the lack of regulation, testing, and contamination of CBD products demands that practitioners exercise an abundance of caution when making clinical decisions for a vulnerable patient population. Furthermore, studies of Epidiolex, the first FDA-approved CBD product for the treatment of refractory seizures, have demonstrated other potential adverse reactions such as hepatic transaminase elevations and hepatocellular injury. Drug-drug interactions with CBD are also a concern. For example, concomitant use of valproate and CBD can synergistically elevate hepatic enzymes. CBD dosages should be adjusted when combined with strong inhibitors or inducers of CYP3A4 and CYP2C19 to ensure efficacy and avoid excessive amounts of CBD being absorbed. Somnolence and sedation can occur with its use and patients must not drive or operate machinery until they have gained sufficient experience with CBD dosing. Suicidal ideation and behavior have been reported with the use of CBD. Decreased appetite, diarrhea, fatigue, and insomnia are other identified side effects [107].
An abundance of caution must be exercised when making clinical decisions for a vulnerable patient population. Because most studies demonstrate more harm than benefit with regard to whole plant cannabis in the treatment of psychiatric conditions, the American Psychiatric Association has taken the position that there is currently no scientific evidence to support the use of cannabis as an effective treatment for any psychiatric illness [108].
Conclusion
Across the country, states are contending with a truly novel situation. Public opinion, expressed through ballot initiatives to amend state constitutions, has resulted in the introduction of a new treatment in the absence of well-designed research and FDA approval. This new treatment includes an unusual and likely unhealthy route of administration (i.e., smoking). Whole plant cannabis is consumed, despite the fact that it is composed of hundreds of individual compounds with various psychoactive and non-psychoactive properties.
In the absence of rigorous scientific data, dispensaries are now distributing cannabis and cannabis products to large numbers of individuals. Yet physicians, who are the gatekeepers of this process under state law, lack adequate information on which to base their judgment if they choose to discuss cannabis as a treatment option with their patients.
The practice of medicine must remain evidence-based under most circumstances. Physicians should carefully consider their ethical and professional responsibilities before issuing a cannabis recommendation to a patient. A physician should not advise a patient to seek a treatment option about which the physician has inadequate information regarding composition, dose, side effects, or appropriate therapeutic targets and patient populations.
With regard to psychiatric conditions, there remains limited evidence that cannabis is effective in treating serious mental illnesses [108]. In most states legalizing cannabis for medicinal purposes, tax revenue has been earmarked for research. Until this research yields reliable information about the safety and efficacy of individual cannabinoids, mental health professionals should largely avoid making recommendations for cannabis products and simply stay abreast of advancing science.
Cannabis Use and Psychosis, Mood, and Anxiety Disorders
Introduction
In the past decade, more than two-thirds of US states and the District of Columbia have legalized medical marijuana, and more than one-third of these have also legalized cannabis for recreational use. This has significantly expanded availability and public access to an increasingly wide array of cannabis products that have significantly higher potency than the cannabis available pre-legalization [109–113]. A number of research studies have reported an association between cannabis use and psychotic disorders as well as mood and anxiety disorders [114]. In most of these studies, the associations were based on the use of much lower potency cannabis products available prior to legalization. Also, methodological limitations of most previous studies did not enable determination of whether the relationship between cannabis use and psychiatric disorders was causal. This chapter will briefly summarize results of previous studies examining the association between cannabis use and psychiatric disorders including a recent meta-analysis [115] and emerging research on the effects of higher potency cannabis use on mental health problems.
This chapter will first examine recent trends in the potency of available cannabis products and rates of use in the post-legalization environment in the United States. We will then review studies addressing the association between cannabis use and psychotic, mood, and anxiety disorders. Conclusions regarding the relationship between cannabis use and psychiatric disorders are based on the weight of evidence drawn from current research.
Increasing Cannabis Potency Post-legalization
In the 1960s, both cannabis plant material (marijuana) and resin (hashish) contained 3% THC or less [109], with a very modest increase in potency through the mid-1990s. In 1995, the average THC content in samples confiscated by the DEA was 4%, and only 0.6% of the samples were high potency, containing more than 12% THC. In 2014, shortly after Colorado and Washington became the first two states to legalize recreational cannabis, the average THC content of DEA-confiscated samples was 11.8%, and 41.2% of the samples contained more than 12% THC [110]. Among samples of cannabis legally for sale in Washington State between 2014 and 2016, cannabis flower had an average THC content of 20.6% [111]. The cannabis industry also produces highly concentrated cannabis products including “shatter,” “wax,” and other concentrates, including butane hash oil (BHO) containing 70–90% THC [112], with some crystalline products advertised as 99.9% THC [113].
From a public health standpoint, it very concerning that the market share for concentrates has increased after legalization. In Washington state, the market share for concentrates, averaging 69% THC, increased by 150% in the 2 years after recreational cannabis sales began, reaching 21.2% of total cannabis sales in 2016 [111]. Concerns about the increasingly widespread access and availability of high potency cannabis products is further heightened, given how little is known about the health risks, including the potential impact on mental health, associated with their use.
Post-legalization Trends in the Prevalence and Frequency of Cannabis Use
In the United States, past-year cannabis use among a sample of over 36,000 adults rose from 4.1% in 2001 to 9.5% in 2013. The increase was most dramatic in the 18–29 age group, with past-year use increasing from 10.5% in 2001 to 21.2% in 2013 [116]. Among 12th grade students, annual use peaked at 51% in 1979. It dropped throughout the 1980s, and in 1992, only 22% of 12th graders reported using cannabis in the prior year [117]. Use then increased by the late 1990s, declined slightly through the mid-2000s, and increased gradually between 2008 and 2015 [117, 118]. Across all grade levels, there was no significant change in the rate of lifetime or current marijuana use between 2015 and 2017 [118]. In 2018, 36% of 12th graders reported past-year cannabis use [117].
The prevalence and frequency of use are also increasing in many other parts of the world, most notably in westernized countries, including Canada, Australia, New Zealand, and western Europe [119]. In New Zealand, nearly 80% of participants in one cohort reported using cannabis at least once by age 30, and 59% reported using before age 18 [120]. In a UK cohort, 27% of 16-year-olds reported ever using cannabis, and 3.3% reported using more than 60 times [121]. In the Australian Twin Registry (ATR), the percentage of participants who reported ever using cannabis rose from 30% in 1993 to 69% in 2009 [122]. Age of first use also decreased from 21 years to 18 years over the same time period, and the prevalence of frequent use (greater than 100 times) increased from 4.9% to 15.2% [122].
Impact of Medical Legalization
Recent data from Canada raises concerns that many individuals who use medical cannabis, even for legally authorized medical conditions, increase the amount and frequency of their use after obtaining medical authorization. Sixty-five percent of medical cannabis users in a 2011–2012 Canadian survey reported increasing their cannabis consumption after obtaining a medical marijuana license; half of these reported large increases in use [123]. In a 2017 survey, 22% of medical cannabis users reported that their cannabis use had increased “a lot” since obtaining legal access to medical cannabis [124].
Additional research is needed to determine factors that may be contributing to the reported increases in cannabis use. These may include greater addictive potential of high potency cannabis, development of tolerance, or other factors. Additional research is also needed to evaluate whether the use of high potency cannabis has a greater impact on pre-existing psychiatric disorders and/or a greater risk of causing mental health problems compared to lower potency cannabis. The following section examines results of studies that have addressed the relationship between cannabis use and psychiatric conditions. Although causation cannot be determined based on results of individual studies, causation can be inferred when (1) consistent findings from multiple reports show a strong association with a large effect size, (2) the exposure consistently precedes the outcome, (3) there is a dose-response relationship between the exposure and outcome, and (4) there is a plausible biological explanation tying the exposure to the outcome [125, 126]. Evidence comes from both cross-sectional epidemiological studies and longitudinal population studies.
These principles are used to evaluate the current body of research and determine what the weight of evidence tells us about the relationship between cannabis use and psychosis, mood, and anxiety disorders.
What Does Research Tell Us About Cannabis Use and Mental Illness?
Cannabis, Psychosis, and Schizophrenia
In 1987, Andreasson and colleagues famously published follow-up data from a survey of more than 45,000 Swedish men who had undergone a compulsory medical examination for conscription in 1969–1970. The men were followed in the national health register through 1983. Compared to non-users, people who reported using 11–50 times at conscription had a relative risk of 3.0 for later developing schizophrenia. Relative risk was doubled (RR = 6.0) in those who reported using more than 50 times, supporting a dose-response relationship [127]. Subsequent secondary analyses of these data also supported a strong dose-response relationship between cannabis use and later development of schizophrenia, both in subjects who used cannabis only and those who used cannabis plus other drugs. There was no relationship between cannabis use and the later development of other psychotic disorders [128]. A recent meta-analysis of more than 50 studies reported that more than 1/3 (34%) of individuals with a cannabis-induced psychosis later developed schizophrenia [115].
Most other studies have examined the relationship between cannabis use and psychosis more generally, not limited to the diagnosis of schizophrenia. The early developmental stages of psychosis (EDSP) study collected 4-year follow-up data on 2437 participants who were aged 14–24 at the time of recruitment. Participants who reported using cannabis five or more times at study entry had more than double the risk of having two or more psychotic symptoms at follow up, compared to those who had used 0–4 times [129]. This finding suggests that young people who start using cannabis under age 25 may be vulnerable to developing psychosis even at low levels of exposure. Additionally, this study found a statistically significant linear relationship between the amount of cannabis use at baseline and the subsequent risk of psychotic symptoms. Participants who used less than once a month had no greater risk of developing psychosis than non-users. A gradation of increasing risk was found in participants whose use ranged from approximately weekly (OR = 1.50) to 3–4 times per week (OR = 2.44) [129].
Another important finding of this study was the increased risk associated with cannabis use among participants who had mild psychotic symptoms at baseline. Among those with no psychotic symptoms at baseline, people who had used cannabis (≥5 times) had a 6% difference in risk of psychosis at follow-up compared to non-users. However, participants who did have mild psychotic symptoms at baseline and who used cannabis had a 25% difference in their risk of subsequent psychosis compared to those who had psychotic symptoms at baseline but did not use cannabis [129]. Other studies have had similar findings. One study in a population at ultra-high risk (UHR) for psychosis based on clinical criteria found that people with early-onset and frequent cannabis use were more likely than non-users to transition to psychosis. Those who started using before age 15 and used at least once per week were at the highest risk [130]. There is a plausible biological explanation for increased vulnerability in adolescents, given that THC binds to CB1 receptor and may interfere with CB1’s regulatory role in the development of the prefrontal cortex during rapid brain development occurring throughout adolescence [131]. These findings indicate that youth who have any psychotic symptoms should avoid even infrequent cannabis use.
Cannabis use in people with a possible genetic predisposition to psychosis was examined in one study of siblings of patients with psychotic disorders. In this group, cannabis users had a fourfold increase in the odds of developing psychosis compared to non-users (OR 4.1) [132].
A 2007 meta-analysis, based on seven studies available at the time, confirmed concerns about cannabis use in both adolescents and adults. Compared to individuals who had never used cannabis, those reporting any cannabis use had increased risks for psychotic symptoms (OR = 1.41) and for a psychotic disorder (OR = 2.58). Furthermore, the six studies that analyzed the effect of frequency of use (with the highest frequencies defined as >50 times to daily, depending on the study) all found dose-response relationships between frequency of use and risk of psychosis [133]. Only one of the seven studies included collected data exclusively on adolescent cannabis use [134]; three more included young adults [128, 129, 135]. The remaining three studies reported primarily on adults [136–138], indicating that even in adulthood, cannabis use increases the risk of psychosis.
A more recent epidemiologic survey study was conducted on nearly 18,000 young adults in the Netherlands [139], where cannabis use was allowed in certain “coffee shops” beginning in 1976 [140] and where some of the highest-potency products in Europe are available [141]. This study found that both positive symptoms (such as hallucinations and paranoia) and negative symptoms (such as avolition and social withdrawal) of psychosis were worse in the heaviest cannabis users, who spent more than €25 per week on cannabis. For positive symptoms, ORs compared to non-users increased from 1.7 in light users to 3.0 in the heaviest users, and for negative symptoms these ORs were 1.3 and 3.4, respectively. This study also found an increased odds of positive symptoms in people who began using cannabis before age 12 (OR = 3.1). People who started using between ages 12 and 15 had a slightly increased risk that did not reach statistical significance, while people who started using between ages 15 and 18 had an equivalent risk to those who started after age 18. A similar trend was seen for negative symptoms, with subjects who started use before age 12 having an OR of 1.7 [139].
Cannabis use has been associated with a variety of poor outcomes when used by people with pre-existing psychotic disorders [142], including greater risk of relapse [143] and longer duration of hospitalizations [144]. Compared to people with psychotic disorders who do not use cannabis, those with regular ongoing cannabis use have more positive psychotic symptoms [145], greater thought disturbance [146], and more hostility [146]. Cannabis use among people with psychotic disorders has also been linked to increased risk of death from accidents (SHR = 1.59) and all-cause mortality (HR = 1.24) [147].
A prospective study of first episode psychosis patients in South London found former regular cannabis users who quit had the lowest relapse rate (24%), while people who continued to use high-potency cannabis had the highest rate (58%) [148]. There were also significant effects of cannabis use on number of relapses and time to relapse [148], as well as length of relapse [149]. Some of these effects were mediated by negative effects of cannabis use on medication adherence [149].
Clearly, much more research is needed to understand the relationship between risk of psychosis and cannabis potency, especially with regard to the extremely high THC concentrations found in cannabis concentrates (e.g., BHO, shatter, wax, etc.) increasingly available post-legalization, about which little is known. Some studies suggest that CBD may have a protective effect against elevated risk of psychosis driven by THC [150–153]. Post-legalization trends in commercially marketed cannabis have seen dramatic increases in THC concentration, while CBD content has been removed or significantly reduced in most commercial cannabis products [114].
Taken together, the body of current research addressing relationship between cannabis use and psychosis strongly suggests that cannabis use is causally related to risk of psychosis. This risk is particularly elevated in adolescents and young adults using high-potency products. This conclusion is based on the consistent findings from multiple studies reporting cannabis use preceding the onset of psychosis, many of which show a dose-response relationship. Given the strong evidence for a dose-response relationship between frequency of cannabis use and psychotic symptoms, it is not surprising that emerging data indicate a higher risk for psychosis with higher potency products [140]. Emerging data also support a growing clinical concern that heavy or regular cannabis use – especially during adolescence – may precipitate earlier onset of psychotic disorders [154, 155]. Results from a recent meta-analysis showed that more than a third of individuals who experience psychosis related to cannabis use go on to later develop schizophrenia [115]. In individuals with pre-existing psychotic symptoms, cannabis use may worsen the risk for chronic symptoms [148, 149].
In summary, there is considerable evidence that cannabis use, especially in young people, can increase risk of psychosis in a dose-related manner. There is currently insufficient evidence to determine whether cannabis plays a causal role in the development of schizophrenia. However, there is growing evidence that cannabis use may precipitate earlier onset of schizophrenia in those who have other risk factors for developing the disorder [114, 115].
Cannabis and Mood and Anxiety Disorders
Compared to the research on psychosis and cannabis use, the current body of research examining the relationship between cannabis use and mood and anxiety disorders is more modest.
The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) surveyed more than 43,000 adults in 2001–2002 and again 3 years later. Data were collected on multiple psychiatric disorders, including major depression, bipolar disorder, and several anxiety disorders. At the baseline assessment, past-year cannabis use frequency of weekly or greater was associated with an increased overall risk for bipolar disorder (OR 2.62), depression (OR 2.27), and anxiety disorders (OR 2.20), as well as each specific anxiety disorder examined [156]. An even larger population-based survey, the National Survey on Drug Use and Health (NSDUH), gathered data from over 527,000 adolescent and adult participants between 2006 and 2015. A study examining the relationship between cannabis use and major depressive episodes found that in both age groups, participants with past-year cannabis use had a higher rate of past-year major depressive episodes than non-using participants [157].
One cohort study, focusing on adolescent use, found an increased risk of depression and anxiety at age 21 for all cannabis users who used every few days or more, but those whose use started at age 14 or earlier had a threefold increased risk (OR 3.4), while those who started after age 14 had a lower risk (OR = 2.3). Symptoms of anxiety or depression at age 14 did not predict later cannabis use (between ages 14 and 21) [158]. Results from another cohort showed that for young women, cannabis use at age 14–15 predicted anxiety/depression at age 20–21. Adolescent depression/anxiety did not predict later cannabis use for either sex [159].
Several systematic reviews and meta-analyses have examined this relationship as well. An early systematic review, published in 2003, concluded that there was evidence for a modest association between adolescent cannabis use and later depression [160]. Another, several years later, included all age groups and found a modestly increased risk (OR = 1.49) for depressive symptoms in people who used weekly or more, compared to non-users, using pooled data [133]. A meta-analysis of 31 studies with prospective cohort or cross-sectional designs found increased risks for anxiety in cannabis users (OR = 1.24) and people with cannabis use disorders (OR = 1.68) [161]. A recently published meta-analysis showed that adolescent-onset cannabis users, compared to non-users, had modestly but significantly increased risk (OR = 1.37) of depression in young adulthood as well as increased risk for suicidal ideation (OR = 1.50) and suicide attempts (OR = 3.46). The pooled risk (OR = 1.18) for anxiety was not statistically significant [162].
A few studies have explored the relationship between cannabis use and specific anxiety disorders, with mixed results. One study using NESARC data analyzed rates of specific anxiety disorders (panic disorder with and without agoraphobia, social phobia, specific phobia, and generalized anxiety disorder). Each of the individual disorders was associated with cannabis use, with ORs ranging from 1.74 for social phobia to 3.57 for panic disorder with agoraphobia [156]. A retrospective secondary analysis of NESARC data examined the temporal relationships between cannabis use and anxiety disorders. Results showed that for both adolescent- and adult-onset cannabis users, generalized anxiety disorder and panic disorder emerged after cannabis use, while social phobia and specific phobia emerged prior to cannabis use [163].
A study examining the relationship between cannabis use and adult mental health outcomes also reported that regular cannabis use was associated with higher risk of developing generalized anxiety disorder, but not social phobia, in young adulthood [164]. Similar findings were reported in another cohort study showing a twofold increase (OR = 2.2) in depression among participants who reported using cannabis more than 60 times lifetime, compared to non-users [121]. A longitudinal twin study found that adolescent identical twins who reported using cannabis more than 100 times were significantly more likely to develop major depressive disorder as young adults compared to the identical twin who reported less frequent or no use (OR 1.98) [122].
Although there is some variability across studies in definitions of “early onset” and “heavy use,” the current weight of evidence, based on consistent, convergent findings from these studies taken together, provides substantial empirical evidence that regular or frequent cannabis use, especially during adolescence, significantly increases the risk of developing depression and/or generalized anxiety disorder by young adulthood [165–169]. Preliminary findings from at least two of these studies also suggest that adolescents who significantly reduce or discontinue cannabis use may reduce their risk of developing major depression or generalized anxiety disorder to a level of risk similar to non-users [164, 170].
There is also consistent evidence that cannabis users, compared to non-users, who have pre-existing mood (depression, bipolar disorder) and/or anxiety disorders generally have a more severe and chronic course of illness and poorer response to treatment. In a study of 300 psychiatric outpatients with depression, cannabis users had significantly less improvement in depression symptom severity at 6-month follow-up compared to non-users [171]. Another study gathered data from 330 young women who were using cannabis. Those who reduced or stopped using cannabis during treatment (for depression) had significantly greater improvement in depression severity based on Beck Depression Inventory (BDI) scores, compared to participants who continued using cannabis at baseline levels [172].
Although the literature on cannabis use and bipolar disorder is scant, one large epidemiologic survey study found that individuals with bipolar disorder who reported any past year cannabis use, compared to non-users, had persistently higher subscale scores for mania and hallucinations/delusions, but not depression, throughout the 12-month study [173]. A 2-year prospective study of patients with bipolar disorder showed that bipolar patients who continued to use cannabis three or more times per week had significantly less symptom improvement and lower rates of clinical remission compared to non-users and less frequent cannabis users [174]. A large 2-year prospective observational study of European adults reported significantly higher rate of suicide attempts among current cannabis users with bipolar disorder (6.9%) compared to those who had never used cannabis (3.0%) and previous cannabis users (4.4%) [175]. A nationwide Danish national registry study of individuals diagnosed with schizophrenia, bipolar disorder, unipolar depression, or personality disorder found that current cannabis use disorder was associated with an increased risk of completed suicide in people with bipolar disorder (HR = 1.86) [176].
- 1.
Regular cannabis use during adolescence significantly increases the risk of developing major depressive disorder and/or generalized anxiety disorder in young adulthood.
- 2.
Among individuals with major depressive disorder and bipolar disorder, regular ongoing cannabis use may interfere with treatment response and reduce likelihood of clinical remission.
- 3.
Regular cannabis use in individuals diagnosed with major depression, bipolar disorder, or schizophrenia is associated with increased suicidal ideation, suicide attempts, and completed suicides.
Conclusion
- 1.
There is substantial evidence that cannabis use causally increases risk of psychosis in a dose-response fashion, especially in adolescents and individuals with pre-existing psychotic symptoms or risk factors including family history of schizophrenia. Adolescents in general should be educated about the neurotoxic effects of cannabis use during adolescence, including at least quadrupled risk of psychosis even in individuals without any family history of schizophrenia or other risk factors for developing psychosis. In part this is related to rapid brain development that occurs throughout adolescence from ages 10–24. Adolescents and young adults with any prior history of psychotic symptoms are at especially high risk and should be strongly discouraged from using cannabis. Although there is currently insufficient evidence to determine whether cannabis plays a causal role in the development of schizophrenia, there is growing evidence that cannabis use, especially during adolescence, may precipitate earlier onset of schizophrenia in individuals who have a family history or other risk factors for schizophrenia.
- 2.
Among individuals diagnosed with major depression, bipolar disorder or schizophrenia, there is robust evidence that regular cannabis use is associated with a more severe and chronic course of illness, less robust response to treatment, and lower rates of remission. Individuals with these and other psychiatric conditions should be routinely screened for cannabis use and provided with research-based psychoeducation about the aforementioned risks associated with ongoing cannabis use and potential benefits of discontinuing or significantly reducing cannabis use in terms of clinical improvement and response to treatment for a co-occurring psychiatric disorders and reduced risk of suicidality.
Marijuana and Suicide: Case-Control Studies, Population Data and Potential Neurochemical Mechanisms
Introduction
Suicide is clearly one of the most complex outcomes in behavioral research. It is both multifactorial, involving a large number of independent variables, and unpredictably episodic. Whereas most behavioral disorders which qualify for a DSM-V diagnosis can exhibit patterns over time which facilitate monitoring of symptoms in affected individuals, day to day or year to year, suicidal thoughts have been known to appear spontaneously 1 day and be gone the next [177, 178]. Even a history of depression is not a reliable predictor of suicidal ideation in college age young adults [179]; thus, parsing out the pre-existing risk factors for completed suicides can be very difficult. Suicidal ideation itself is also not consistently predictive [180]; rather, it is a prior suicide attempt which is the single most reliable marker of suicide completion [181, 182] and, as such, is the focus of much research.
This chapter will examine case-control publications on marijuana’s impact on suicide risk in the context of what is known about the typical impact of other recreational drugs, along with demographic variables known to influence suicidal outcomes. Population data will be presented for marijuana use and suicide rates, and the potential neurobiological mechanisms for marijuana’s impact will be explored.
The Impact of Recreational Drugs on Suicide Risk
Almost all recreational drugs are associated with an increased risk of suicide attempts when used to excess, and marijuana is no exception to this theme. Wong et al. [183] found a significant association with suicidality in US youth for each of ten substances used (heroin, methamphetamine, steroids, cocaine, ecstasy, hallucinogens, inhalants, alcohol, tobacco, and marijuana). O’Boyle and Brandon [184] identified suicide attempters as being significantly more likely to abuse multiple drugs, including alcohol, than non-attempters. The increased risk has been estimated to increase significantly for each additional drug used [185].
As with most behavioral outcomes, the role of drug use in precipitating the behavior rather than being a response to an underlying psychiatric disorder must be evaluated. This relationship has not been clarified for all recreational drugs, though the elevated suicide risk for some are high enough to eclipse the risk typically conveyed by depression, for example. Thus, although heroin addicts most often die from accidental overdoses [186], suicide attempts have been self-reported by 42% of a very large cohort of heroin users. Their risk of completed suicide is elevated as much as 14-fold [187], whereas the risk conveyed by depression alone has been estimated to be 6.1-fold [188, 189]. Abstinence from heroin in former addicts has been shown to be protective and polydrug use enhanced the suicide risk [190]. For cocaine users, the risk of suicide has been reported to be as high as ninefold [191]. Fowler et al. [192] found that fully 53% of suicide cases in the San Diego Suicide Study had received a substance abuse diagnosis of one type of another. Binge alcohol use has appeared to increase the risk for suicide attempts by a somewhat more modest factor of 1.3–2.6-fold [193], but it is primarily CNS depressants like alcohol, opiates, barbiturates, and benzodiazepines, which significantly increase the risk of a suicide attempt on the day of use [194].
Case-Control Studies Specific to Marijuana
Research on marijuana’s role in suicide has been building substantially over the past decade. Most published reports controlled for a variety of demographic variables known to impact suicide risk, but only one specifically corrected for a prior history of mood disorders [195], finding the risk for suicide attempts to be elevated by 7.5-fold in 168 Irish adolescent marijuana-users as compared to controls. A large prospective study (over 2500 subjects) launched in stages in New Zealand and Australia from 1977 to 1992 reported the risk of suicide attempts at some point in the teen or young adult years was elevated 6.9-fold in those who were using marijuana daily by age 17 [196]. Completed suicides was evaluated for 6445 subjects in Denmark [197], finding the risk for suicide was elevated 5.3-fold in those with a cannabis use disorder as compared to control subjects.
Earlier work was suggestive of a substantial impact, but the studies were often not conclusive because they were small (increasing marijuana use preceded suicides in the small Micronesian Island of Truk [198]), unadjusted for covariates [199], the association diminished to a nonsignificant trend after adjustment for covariates [200], or marijuana use was completely unrelated to suicide after adjusting for covariates, as seen in a study of adolescents in Switzerland [201]. Case-control data from the US National Mortality Followback Survey in 1993, revealed an increased risk of suicide in marijuana users, 2.3-fold for males and 4.8-fold for females [202]. Similarly, Pedersen et al. [203] reported that Norwegian subjects who used cannabis 11 or more times in the past year were 2.9-fold more likely to attempt suicide after adjusting for confounding covariates.
A lack of association was reported in 2009 by Price et al. [204] in a large study of mortality in Swedish transcripts, who found that correcting for potentially confounding variables, rendered an association between suicide and marijuana use nonsignificant. Here, it should be mentioned that the investigators corrected for smoking of cigarettes, which holds the potential for creating what is known as a collider variable [205], whereby two supposedly independent variables actually interact to obscure real associations with the dependent variable (the outcome). In this case, it was the tobacco versus marijuana use that created potential collider variables, since most cannabis users also smoke tobacco and cannabis use is known to have a reverse gateway effect by leading to a tobacco habit [206]. Correcting for tobacco use can therefore substantially reduce the apparent impact of marijuana.
In Nova Scotia, Rasic et al. [207] found that marijuana-only use was predictive of depression without suicidal features, possibly because the marijuana-only users were found to use it infrequently. Similarly, Arria et al. [179] found that cannabis use disorder was not predictive of suicide ideation in students attending college, although the trend of the association was positive and the study was not adequately powered to detect less than about a 3.5-fold relative risk.
One of the most effective means to adjust for genetic background and confounding environmental effects is to study the differential impact of marijuana in twins. Agrawal and colleagues [208] analyzed an updated Australian twin registry and found that members of identical and non-identical twin pairs who frequently used marijuana (defined as more than 100 times of use) were at a more than 3.6-fold increased odds of reporting suicidal ideation lasting more than 1 day and a more than sixfold odds of engaging in a suicide attempt (here, the non-identical twin comparison only, in part due to small sample size of identical twins) than their non-using twin. Because the impacts were generally similar in the non-identical and identical twin pairs (with an exception being a difference in attempts), they concluded that genetic factors played a relatively small role in mediating the effects seen.
A meta-analysis by Borges et al. [209] included the most well constructed of these studies and many others, finding the average increase in risk for suicide attempt was 3.2-fold for heavy users. The definition of heavy use in the meta-analysis varied from as low as less than once per month to daily or near-daily use. If the analysis had been restricted to near-daily or daily use, the effect size might have approached that of the Silins et al. [196] study of a 6.9-fold increased risk as seen from Fig. 4 in the Borges et al.’s meta-analysis. It should also be noted that the meta-analysis included studies of lower potency marijuana than that available today, as well as non-Caucasian ethnic groups. Chandra et al. [210] have documented the changing potency, from an average of 4% for the dry-leaf product in 1995 to an average of 17% in 2017. Other factors in the study-to-study variabilities seen in this meta-analysis are the differences in ethnic and gender vulnerability to suicide. Although recent publication of youth suicides in 21 low- and middle-income countries confirms that the impact of marijuana use to increase suicide risk extends across many ethnic group [211], Caucasian males of combined age groups exhibit more than double the risk for completed suicides of African-American males and more than triple the risk of Caucasian females, with African American female risk lower yet [212]. Individuals of Hispanic descent also have a notably lower risk than Caucasians (https://www.nimh.nih.gov/health/statistics/suicide.shtml). Yet, as reviewed by Sellers et al. [212], the data for suicide attempts in adolescents shows trends opposite to that of completed adult [213] suicides: females are more likely to attempt suicide than males; Latino and African American adolescents are more likely to attempt suicide than Caucasians.
A more recent meta-analysis by Gobbi et al. [214] restricted the inclusion of studies to those which were longitudinal, assessed marijuana use prior to age 18, and included a follow-up periods from 18–32 years. In those who began using marijuana before age 18, the adjusted odds ratio (OR) for attempting suicide by age 32 was found to be 3.46. No determination of the effect for degree of usage or strength of product was reported.
The impact of marijuana use on groups already at risk for suicide is a particular concern, and here, attention should first be focused on those with post-traumatic stress disorder (PTSD). Several investigators have demonstrated that among veterans and active duty personnel who suffer from PTSD, those who use marijuana make less progress overcoming their symptoms and have worse outcomes [215], including suicidal events [216–219]. Allan et al. [216] found that marijuana use in current and former military personnel with PTSD predicted suicidal thoughts within 1 month and suicide attempts within 11 months, in a model that incorporated age, sex, baseline opiate, and alcohol and marijuana use. The impact of marijuana was significant in those with elevated PTSD symptoms at baseline and was proportional to the number of days using marijuana per month. Because veterans and active duty personnel often have been exposed to potentially confounding variables of high impact, the adjustment factors should be noted here. One study which controlled for age, race, service sector, and combat exposure, found past 6-month cannabis use to be associated with severity of PTSD, depression, and suicidality in veterans [217]. In terms of the degree of risk posed, a diagnosed cannabis use disorder was found to be associated with a 3.1-fold increased risk of suicidal self-injury in a group of veterans, some with and some without a PTSD diagnosis, after adjusting for after adjusting for sex, age, sexual orientation, combat exposure, traumatic life events, traumatic brain injury, depression, alcohol use disorder, non-cannabis drug use disorder, and the baseline risk posed by posttraumatic stress disorder [218]. However, the risk for suicide attempts has also been reported to be higher, increased eightfold in post-deployment veterans with a cannabis use disorder, after controlling for PTSD severity, pre-deployment suicide attempts, depression, pain, non-cannabis drug use, and gender [219].
The importance of the timing of marijuana’s use relative to suicide events was addressed by Sellers et al. [212], who found that “day-of” use was a risk factor for both suicidal ideation and attempts in adolescents. In contrast, Bagge and Borges [194] reported that acute use of marijuana in the 24-hour period prior to a suicide attempt showed a trend to be protective in their unadjusted model, though when adjusted for other drug use, was not associated with risk; whereas past 24-hour use of recreational and prescription drugs that have CNS depressant actions (sedatives/anxiolytics, opioids, and alcohol) increased risk for suicide attempt. Stimulants showed a similar timing effect to that of marijuana, but the co-use of stimulants and marijuana resulted in the loss of significance in the adjusted models. The discrepancy between the two studies could relate to any of the following likely factors that distinguish the Sellers et al. study [212]: the bias inherent through selecting only subjects who were part of a teen alcohol use study (all were users, though not daily users); the much younger average age of the subjects; the 78% Caucasian ethnic distribution; the 80% proportion of females; the 32% proportion of subjects who were transgender; or the fact that the average 90 day use of marijuana was 15 days, which would likely indicate the majority were not addicted to marijuana.
Because both cannabis use and stimulant use over the long term are clearly associated with risk for suicide, one interpretation of the work of Bagge and Borges [194] is that the withdrawal from one or the other class of drug is likely a period of risk. It also should be kept in mind that mini-withdrawal episodes can happen within the course of 1 day as concentrations of active drug levels fall when a user may be too busy with other activities to keep their blood levels up. Vandrey et al. [220] have shown that withdrawal symptoms are already fairly pronounced by the time 24 hr. have elapsed.
Population Data on Suicide and Marijuana Use
In contrast to case-control studies, analysis of population level data cannot control for variables specific to individuals, such as pre-existing mood disorders, and must instead examine demographic data for populations available from public databases. But the advantage of studying health outcomes in whole populations is to confirm that case-control results are discernable in larger, unselected groups. The general public and many scientists regard effects observable at the population level as the necessary confirmation of importance to public health. A good example of this perspective can be found in the schizophrenia field, where numerous case-control findings for the association of marijuana use with the development of schizophrenia have often been discounted in the absence of corroborating trends in whole population-level data for the nation [221–223].
Plots of age-adjusted suicide rates, unemployment rates, and percent who used marijuana, other drugs, or who engaged in binge drinking (on a monthly basis, age 12 and older) in the United States and Colorado for 2-year averages starting from the year 2000 through 2015. Daily veteran suicide rates are also shown for the United States (upper plot). The identification of the symbols and lines for the lower plot are the same as shown in the upper plot. Data for drug and alcohol use was obtained from NSDUH reports (www.SAMHSA.gov); for unemployment from the Bureau of Labor Statistics) http://beta.bls.gov; for suicide in the general population, from the CDC, www.CDC.gov and for veteran suicides, from a report issued by the Veterans Affairs Administration. Note that data for other drug use, binge drinking, and daily suicides of veterans were not available for 2015
Potentially Confounding Demographic Variables
Among the many well-studied associations, some have high impact but have not changed in a manner that could explain the increase in suicide rates over recent time. For example, the proportion of gun-owning households in a clear factor in completed suicides [224] but has not significantly changed during the 15-year period covered by this study [225], and non-firearm suicides has increased at a higher rate over the past 10 years than have firearm suicides (http://webappa.cdc.gov/sasweb/ncipc/dataRestriction_inj.html). The rate of treatment of depression with antidepressants is another potential factor but has been found by others to have no discernible impact on suicide rates [226], and the antidepressant treatment rate remained flat from 2007 through 2010 [227] a time period encompassing the significant upturn in the national suicide rate. Federal funding for suicide prevention is undoubtedly important [228], and the Substance Abuse and Mental Health Services Administration (SAMHSA) increased the funding significantly over the years 2000–2015, going up roughly tenfold since the year 2004 (www.hhs.gov). Divorce is a well-accepted risk factor, but divorce rates have been declining for the past 35 years, most notably from 2008 through 2011 [229] during which time the slope in the suicide rate changed direction to head higher (Fig. 4.1). Teen suicide attempts stemming from overuse of social media [230] and its attendant abusive content have definitely increased, but the proportion of teen suicides as a fraction of the total increase seen by the end of 2015 was small (10%, http://webappa.cdc.gov/sasweb/ncipc/dataRestriction_inj.html).
Certain other influential variables either exhibited no change over recent time or changed in a direction inconsistent with their effect on suicide, for example, the proportion of the population living at high altitude [231, 232] and pathological gambling [233–235]. Colorado, as the bell weather state for impacts of altitude effects, experienced most of its population growth in the relatively low altitude front range during the period 2007–2015, and pathological gambling did not change discernibly across the country over the same time period [235].
As much as many aspects of life in the countryside may seem protective for suicide, rural rates of suicide are nearly double the per capita rates in urban environments [236]. Examining the degree of urbanization revealed a net increase in urbanization from 2001 through 2011 [237]; thus a flight of citizens to rural residences could not explain the increase in suicides during this span of time. Furthermore, as the population shifted to more urbanization, a shift toward more marijuana and other drug use was occurring in rural areas, a trend which would be expected to diminish the urban/rural gradient in suicide. For both urban and rural populations, marijuana was the most common cause of a substance use disorder [238]. In fact, Habecker et al. [239] found that urban and rural populations in Nebraska had become similar in profile with respect to ease of access to marijuana and other drugs with the following exceptions: women had markedly better access in to marijuana and prescription pills in rural than in urban areas and less access to methamphetamine and heroin in rural than in urban areas; white non-Hispanics had markedly better access to methamphetamine and heroin in rural than in urban environments. In contrast, Bukky [240] found at the national level, an urban-rural distinction was not present for marijuana, other illicit drugs or prescription drugs. Regardless, the increasing suicide rate in our country is unlikely to be driven by urban-rural distinctions, because urbanization increased during this time period, and residing in urban centers carries a lower risk of suicide than rural areas, though it remains possible the factors which increase rural risk may interact more strongly with the drug use increases seen in rural areas over time.
Two factors that changed markedly from 2007 to 2015, and in a direction consistent with increasing suicide risk, are unemployment and marijuana use. A study in the United Kingdom during the economic recession of 2008 attributed 40% of the suicides there to being unemployed [241]. The case-control, register-based, and population data on unemployment affecting suicide risk [241–245] show an impact ranging from two- to fourfold on completed suicides, thus somewhat less than the impact of marijuana as reviewed above. Others have found that the impact of unemployment most is strongly felt when it is of longer duration, showing greatest association when mass layoffs are occurring and exerting greatest impact at about 15–26 weeks [246]. Unemployment benefits often cease after 26 weeks, so it may be the anticipation of this event that becomes particularly problematic. The recession of 2008 fulfilled most of the high impact criteria for unemployment.
The Data on Suicide and Marijuana Use Rates Nationally and in Select States, 2000–2015
Figure 4.1 illustrates the plots of suicide in the general population and in veterans, marijuana use, unemployment, binge use of alcohol, and other drug use rates. Although binge alcohol use and other drug use did not change in a manner consistent with the increase in suicide rates, including these variables is important in order to illustrate that marijuana use is not acting as a proxy measure for binge alcohol or other drug consumption, but rather exhibits its own unique profile over time and prevalence. For example, the daily or near-daily use rate of marijuana by those aged 12 and over was 3.5% by 2015 [247], as compared to 0.33% using heroin in the past year (NSDUH reports, www.SAMHSA.gov).
Multiple linear regression of these dependent and independent variables yields a highly significant regression coefficient estimate for marijuana use rate predicting suicide in the general population, to the exclusion of the other variables (r = 0.925, p <0.000) and for unemployment predicting suicide in veterans (r = 0.885, p <0.000). It should be noted that for a small proportion of veterans, it is clear the impact of unemployment on suicide did outlast the elevation of the unemployment (cross-marked curve versus light gray curve in Fig. 4.1). In other words, it remains possible that not only did impact of unemployment outlast the recession for this population; it may also have done so for a portion of the general population.
Equivalent plots for state-level data in Colorado (lower panel, Fig. 4.1) show more variation as would be expected for a smaller population, but the results are very similar: marijuana use rates predicted the suicide rate to the exclusion of other variables (r = 0.828, p <0.000).
Chronology of changes in marijuana drug policy, changes in marijuana use, and changes in suicide rates in Colorado and the United States. (a) The growth of registered medical marijuana users in Colorado during the year 2009, with key events depicted by the arrows. Colorado had legalized medical marijuana in 2001, but the regulations were stringent. The first easing of restrictions followed the news of the upcoming Ogden memo, which eventually would indicate the federal government would not enforce the law on medical marijuana dispensaries [248]. Next, the ruling of a district court lifting a five patient per caregiver cap was not contested. Finally, the Ogden memo was released in October 2009. By 2010, the adult medical marijuana users grew in number to represent ~ 1.4% of the total adult population. (b) An increase in the slope of regression for age-adjusted suicide rates and for the percent who used marijuana monthly (aged 12 and older), after the Ogden memo was issued. The scales of the graph for Colorado and the United States are the same, but the ranges depicted are different to allow for the enlargement and easier viewing of the change in slope. The data source for state suicides was www.CDC.gov and for marijuana use rates www.samhsa.gov.
High marijuana use states (arranged in order from lower to higher use)
Montana | Massachusetts | Maine | Washington | D.C. | ||||||
Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | |
Marijuana use rate | 0.834 | 0.000 | 0.464 | 0.018 | 0.563 | 0.006 | 0.717 | 0.000 | ex | |
Unemployment rate | ex | 0.535 | 0.008 | 0.478 | 0.015 | 0.341 | 0.031 | ex | ||
Binge alcohol use rate | ex | ex | ex | ex | 0.599 | 0.024 | ||||
R2 | 0.673 | 0.733 | 0.675 | 0.823 | 0.359 | |||||
Power | 0.999 | 0.999 | 0.995 | 0.999 | 0.662∗ | |||||
Oregon | Alaska | Vermont | Rhode Island | Colorado | ||||||
Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | |
Marijuana Use | 0.912 | 0.000 | 0.477 | 0.085 | 0.886 | 0.000 | ex | 0.828 | 0.000 | |
Unemployment rate | ex | ex | ex | 0.836 | 0.000 | 0.222 | 0.093 | |||
Binge alcohol use rate | ex | ex | ex | ex | ex | |||||
R2 | 0.831 | 0.227 | 0.769 | 0.676 | 0.836 | |||||
Power | 1.000 | 0.493∗ | 0.999 | 0.999 | 0.998 | |||||
Low marijuana use states (arranged in order from lower to higher use)
Utah | Alabama | Iowa | North Dakota | Kansas | ||||||
Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | Estimate | P-value | |
Marijuana use rate | 0.794 | 0.004 | ex | 0.733 | 0.003 | 0.452 | 0.091 | ex | ||
Unemployment rate | 0.591 | 0.023 | ex | ex | ex | ex | ||||
Binge alcohol use rate | ex | 0.905 | 0.000 | ex | ex | ex | ||||
R2 | 0.526 | 0.818 | 0.537 | 0.204 | ||||||
Power | 0.903 | 1.000 | 0.970 | 0.443∗ | ||||||
Mississippi | Louisiana | Texas | South Dakota | Tennessee | ||||||
Estimate | P-value | Estimate | P-values | Estimate | P-value | Estimate | P-value | Estimate | P-value | |
Marijuana use rate | ex | ex | 0.939 | 0.000 | ex | 0.505 | 0.000 | |||
Unemployment rate | 0.468 | 0.047 | ex | ex | 0.527 | 0.043 | 0.804 | 0.000 | ||
Binge alcohol use rate | 0.454 | 0.053 | ex | ex | ex | ex | ||||
R2 | 0.609 | 0.882 | 0.278 | 0.882 | ||||||
Power | 0.973 | 1.000 | 0.604∗ | 1.000 | ||||||
Potential Mechanisms of Marijuana’s Effect
Indirect Mechanisms
Marijuana increases risk for several behavioral disorders which themselves greatly increase the risk for suicide. The data are most strong for a causal role of marijuana use in the development of schizophrenia, showing a four- to fivefold increased risk [250, 251] with heavy use of products that are of moderate THC strength by today’s standards (≤15%). Schizophrenia itself is associated with an increased risk for suicide of approximately 3.1-fold as compared to the general population (adjusted O.R. for age, etc.), a risk calculated based on proportion of suicides with schizophrenia versus the general population [252], with a lifetime risk of committing suicide of about 5% [253, 254]. The risk is highly dependent upon the age group and time since first diagnosis [255], decreasing markedly for those who survive 5 years past diagnosis and are beyond their 20s, as compared to the rates in the general population for the same age. Consistent with a mechanism involving the psychotic disorder itself, Waterreus et al. [256] found that once psychosis is activated, cannabis use does not further increase the risk for suicide.
The research on marijuana triggering bipolar disorder is not yet as extensive as the literature on its relationship with schizophrenia, though a large study conducted in the United State shows weekly use of low to moderate strength marijuana raises the risk for bipolar disorder by 2.6-fold when corrected for covariates [257], very similar to the 2.7-fold increased risk with weekly use seen for psychotic disorders like schizophrenia [250]. Bipolar disorder is reported to be associated with a sixfold risk of suicide versus the general population in a meta-analysis [258], and a similar risk when compared to the risk of unaffected siblings in a large Swedish study (6.8-fold, see Fig. 4.1 of publication) [259].
The risk for major depression with marijuana use is less than for schizophrenia and bipolar disorder, with ≥100 times of use (about equivalent to weekly use over a 2 year period) approximately doubling the risk in a study of twins [208]. Major depression itself is associated with a 6.1-fold increased risk for suicide [188, 189] and variously reported to carry a lifetime risk of completed suicides of 3.4–8.6% in the United States [260, 261].
Obviously, all of the studies cited above are influenced by the efficacy of psychopharmacological treatment in normalizing behavior and the proportion of patients who comply with treatment. The direction of the effect is not always as expected in that antidepressants are variously reported to increase suicide risk in adolescents [262]; increase risk of attempts in a wide age group, but not completed suicides [263]; increase risk primarily in the first several days after commencing a prescription [264, 265]; and decrease in the overall risk, but with a warning about monitoring the initial period of treatment [266]. In general, antipsychotic treatment is regarded as offering modest protection from suicide and suicidal behaviors [267–270], with clozapine being the most effective and approved by the FDA for suicidal indications in patients with schizophrenia [271], but there are also some reports of negative impacts of antipsychotic drugs on suicide risk in the short term [272]. Lithium and valproic acid may be the most successful examples of the psychopharmacological agents for preventing suicide when used to treat bipolar disorders [273–275].
Direct Mechanisms, Both Chronic and Acute
Studies of a more direct mechanism for marijuana’s impact on neurobiology have pointed towards a role for dopamine. Dunlop and Nemeroff [276] concluded that dopamine is important to a wide variety of pleasurable experiences and almost all abused drugs increase dopamine extracellular levels in the nucleus accumbens, long considered an integral part of the mesolimbic reward circuitry (reviewed by Ikemoto and Panksepp [277]). Dopamine, along with other stress-related biochemicals elevated by drug use, may exacerbate emotional distress and sensitivity to stressful stimuli [278]. Cocaine exerts similar effects on dopamine release in both animal and human models (as reviewed by Francis et al. [279]). Similar trends have also been reported for specific cannabinoid receptor-1 (CB1) agonists in animal models [280, 281] and in humans [282]. Even endogenous cannabinoids can upregulate dopaminergic neurotransmission in the striatum [283].
Indeed, chronic elevation of extracellular dopamine is thought to underlie the process of addiction (reviewed by Uhl et al. [284]), and therefore, extended use of marijuana can be expected to lead to depletion of dopamine in the reward centers of the brain [285], an outcome that would be consistent with loss of pleasure in everyday life. Paradoxically, there is inconsistent evidence that this long-term dopamine depletion from abuse of recreational drugs mirrors what happens in major depression, as reviewed in 2009 by Martin-Soelch [286]. More recently, Schneier et al. [287] found that extracellular dopamine in the ventral striatum does not appear to be lower in those with major depression.
Despite inconsistent parallels in dopamine levels between the anhedonia of drug addiction and depression, psychological testing coupled with fMRI data shows patterns in marijuana users that are consistent with depression. Zimmermann [288] demonstrated lower emotion regulation capacity in cannabis users (abstinent for 28 days) arising from increased prefrontal activation and diminished prefrontal-amygdala connectivity while expressing negative affect. In particular, marijuana users show decreases in regulation of emotion when the craving is strong, illustrating how poorly regulated motivational urges overwhelm cognitive control. Blum et al. [289] examined the question of experiencing pleasure derived from natural rewards such as social interaction and found a blunting of the reward experienced by users. All of these impacts, while not directly studied as a putative mechanism of marijuana’s impact on suicide, are known to influence suicidal ideation and urges.
Both the indirect hypothetical mechanisms, via the chronic mental illnesses the use triggers, and the direct mechanism of dopamine depletion, require chronic use to see an effect. Is there any evidence of an acute impact of marijuana use, and if so, what mechanism could possibly explain such an effect?
Acute onset of suicidal ideation has most often been seen following oral ingestion ∆9- THC ([290]; reviewed by Koppel et al. [291]). Suicidal ideation was observed in 1 out of 14 subjects administered with a liquid form of pure ∆9- THC (20 mg doses) over a period of 3 days in a clinical setting [292]. This unexpected outcome preceded their subsequent testing of the CB1 “inverse agonist” Rimonobant, but Rimonobant was withdrawn from the market before the study was completed because it had also been linked to an increased risk for suicidal ideation in prior studies [293]. This side effect of an inverse agonist should not be interpreted as being contradictory to the results for the direct agonist effects of ∆9- THC. Being a partial agonist, ∆9- THC [294] could theoretically interfere with the full agonist action of endogenous cannabinoids, potentially leading to a neurophysiologic end result similar to Rimonobant’s.
Why oral ingestion may be associated with suicidal urges more frequently could have something to do with first-pass metabolism by the liver following ingestion but not following smoking. The most striking difference in metabolites is the production by liver enzymes of significant amounts of 11-hydroxy-THC [295], a metabolite reported to be more psychoactive than ∆9- THC itself. Some reports have even suggested that ∆9- THC may in part be a pro-drug and it is 11-hydroxy-THC which is the primary psychoactive agent, based on the potency of its effect and the rapid onset of psychiatric and cardiac symptoms with its administration [296]. A percentage of the subjects studied by Lemberger et al. (66%, [297]) found the first exposure to 11-hydroxy-THC was quite unpleasant at its peak effect, while none reported that ∆9- THC in the same dose was unpleasant. It is the unpleasant nature of the high reported which would obviously be a concern for suicidal behaviors. In point of fact, Favrat et al. [298] reported that higher levels of 11-hydroxy-THC were associated with more severe psychotic symptoms following oral ingestion of ∆9- THC by two subjects.
The neurochemical basis for these acute effects on suicidal behaviors obviously requires much more research. One finding that holds promise to explain the rapid development of suicidal urges is the activation of the kynurenine pathway seen in postmortem samples of suicide victims or in blood samples from those who have attempted or contemplated suicide [298–302]. This activation is evident in ratios of the kynurenine, the first product of the pathway, to tryptophan, the initial substrate for the pathway [302]; is evident in the ratio of intermediate metabolites (quinolinate/picolinate) which could be indicated of higher flux through the pathway [301]; and is also evident in the elevation of a downstream metabolites, nicotinamide, in postmortem brain tissue of bipolar patients who have committed suicide [303] and quinolinate, in blood samples of those who have attempted suicide [304].
Cytokines which activate the kynurenine pathway have been shown to be elevated in those with suicidal behaviors [304], specifically IL6 [305] and TNF-α [306]. TNF-α is required for the induction of one of the two enzymes that initiate the kynurenine pathway, indoleamine 2,3-dioxygenase, IDO [307]. Although cannabinoids tend to depress the immune system [308, 309], including reductions in IL-6 and TNF-α that have been elevated by other agents [310, 311], administration of ∆9- THC under basal conditions primes immune cells for a subsequent TH-2 response when stimulated; thus, IL-6 and TNF-α (as part of a TH-2 response) would be elevated. Another potential mechanism is via another initiating enzyme of the pathway, tryptophan 2–3-dioxygenase. Decades ago, biochemists Poddar and Gosh [312] discovered that ∆9- THC activates tryptophan-2.3-dioxygenase (TDO2) in an animal model. This mode of activating of kynurenine synthesis would be unlikely to occur through cytokine signaling because unlike IDO, TDO2 is thought to be regulated independently of the cytokine system (reviewed by Miller et al. [296]).
Conclusions
The potential for suicidal behaviors is clearly the most severe mental health risk from marijuana use. Even unsuccessful suicides leave traumatic emotional scars on the individual and their loved ones. The circle of harm is wide. As a culture, we need to find routes to minimize suicidal thoughts and urges to begin with, and if minimizing the use of a drug associated with suicide risk is one strategy, it should be embraced as an easier route to prevention than attempting to solve many other complex social forces which increase suicide risk.
Preliminary evidence for marijuana’s causal role in suicide can be seen in the acute onset in a clinical setting; in the significant increase in risk when a prior history of a mood disorder is corrected for; and in the existence of at least two plausible biological mechanisms. Thus, the continued rise in marijuana use across the broad age group of 12+ represents an ongoing public health concern. Suicide attempts may be most common in teens and young adults [313] but completed suicides in the United States peak in middle age or later [213]. Prevention goals should therefore be geared toward a widespread decrease in marijuana use across all age groups.
Cannabis Use Disorder, Treatment, and Recovery
Progression of the Disease
During an assessment or treatment, one of the common activities is to ask a patient to craft a timeline of their disease and its impact. This allows treatment professionals, patients, and families to understand the progressive nature of the disease as well as the parts of life that started to unravel because of use. For some, this begins a difficult conversation because life did not feel “unmanageable” for a lengthy period of time. An individual might have started using and continued to use cannabis without significant consequence, such as getting arrested, hangovers, fighting with family, overdose, or losing a lob. In some states, cannabis is legal for both recreational and medicinal use and might have slowed the impact of consequences. On average, adults seeking treatment have been daily users for more than 10 years and tried to quit more than six times [314].This would mean that use has become a daily way of life, integrated into the routines and patterns of life. Friends, family, and a person’s social network may accept it as common place and find it difficult to consider needing treatment for cannabis.
Oftentimes to challenge a current stage of change (such as precontemplation), it might take a lengthy period of time or numerous negative situations or outcomes, to agree that one’s life has become disorderly and requires intervention [315, 316]. Again, for cannabis, this might take longer because of legalization, a minimized perspective of the drug’s impact, the role it plays in popular culture or less adverse feedback from friends and family.
Once an individual becomes open to the idea of treatment, at any level, the approach to treatment parallels that of other substances, it is imperative to use an objective evaluation of the disease and pursue placement in the appropriate level of care. The most respected criteria have been developed by the American Society of Addiction Medicine (ASAM) which cover six (6) dimensions that are affected by the disease.
These criteria were developed in the 1980s so there could be a nationally standardized set of criteria to evaluate the care provided to treat addiction. Currently, it is used in 30 states [317] to assist in diagnosis and placement.
Once these dimensions are evaluated by a trained professional, an individual can be placed in an appropriate level of care, ranging from detoxification to outpatient treatment. The challenge with cannabis is that the potentially slower progression of the disease paired with minimization of consequences can cause people to underestimate the impact of use. This drug can be called a “dream killer,” so sometimes measuring someone’s lack of ambition is difficult versus the impairment in relationships, finances, and the repetitive return to use. This is usually expressed in their stage of change, as precontemplation (“it’s not a problem for me”)/Dimension 4, which can be a difficult perspective to challenge [315, 316].
Professionals refer to this mental state as “amotivational syndrome” which is associated with long-term cannabis use. It presents as detachment, blunted affect, and impaired executive functioning [318]. A person would have little desire to engage in activities, have a sense of apathy, and have poor concentration. If an individual has experienced significant mental health problems (i.e., psychosis, increased anxiety, or depression), they may be more likely to agree to an intervention or treatment.
Marijuana Anonymous is a mutual aid group, an organization and 12-step program for people with a common desire to maintain abstinence from marijuana. It is a fellowship of people who share experience, strength, and hope. Founded in 1989, teachings and meetings can be located on their website marijuana-anonymous.org [319]. Groups such as this, can help challenge an individual’s perspective that suggests cannabis use is “no big deal.”
In the Marijuana Anonymous basic text questions like, “How did marijuana use keep me from realizing my potential?” or “How did my marijuana use keep me from doing what I wanted to do with my life?” suggest the nuanced concerns specific to long-term cannabis use [319]. As well as the distinctly different question of “Did I ever experience confusion, paranoia, and fear associated with my using?” A story told by a woman in treatment, suggested that she was waking at 4:30 am in order to clean the house and get high, then continued to use almost every 2 hours to stay high until she went to bed. The picture one might conjure of this type of user might not be a full-time working woman, wife, and mother of a one-year-old. She shared that she was unable to stop on her own, had been hiding her secret for months, and began questioning her partner’s loyalty as well as job decisions.
We who are marijuana addicts know the answer to this question. Marijuana controls our lives! We lose interest in all else; our dreams go up in smoke. Ours is a progressive illness often leading us to addictions to other drugs, including alcohol. Our lives, our thinking, and our desires center around marijuana—scoring it, dealing it, and finding ways to stay high.
Based on our own experiences, we who seek recovery in MA generally consider ourselves to be marijuana addicts. Whether or not our addiction is psychological, physical, or both, matters little. When it comes to the use of marijuana, we have lost the power of choice. It is strictly up to the individual to decide whether he or she feels addicted to marijuana. MA has no opinion about marijuana itself one way or another. Marijuana Anonymous exists solely to provide a means of recovery to the suffering addict who seeks help [320].
In order to assess impairement or “unmanageablity” it might require referencing the law. For example, in states where the adult use of cannabis is legal, it is worthy to note that if an adult is found using in front of children, having children test positive for THC (at birth or through second hand smoke/contact) or break state safety laws pertaining to cannabis, they can be charged with child endangerment [321]. Most users would argue that because it is legal, they aren’t breaking any laws. They are often mislead about the permitted parameters of possession, storage, and consumption. The cannabis industry goes as far to market its product to treat symptoms of pregnancy, such as nausea or pain, but fail to highlight that as soon as children, born or unborn, are involved, it becomes an illegal practice.
Mental Health
The use of cannabis can affect the mental health and thought patterns of an individual. Cannabis-induced psychosis typically refers to acute symptoms like paranoia, delusions, disorganized thinking, and hallucinations; however a growing body of evidence suggests that the higher-potency forms of cannabis such as “extracts” or “concentrates” can lead to these symptoms persisting even after use is discontinued, leading to a permanent shift in an individual’s mental health and wellness. When and individual is in these states of impaired thinking, or if that impairment has become permanent, they are often times at a much higher risk of causing harm to self or others [322–325]. The most obvious example is impaired driving, but thought disorders can lead to violent behaviors to both self and others.
There has long raged a fierce debate about the link between cannabis and violence; we encourage our reader to move past this argument that is near impossible to fully prove in one way or another and to remember that impaired thinking/thought disorders are absolutely causal to acts of harming self and/or others. Since cannabis-induced psychosis is understood and can be severe, we must acknowledge the association between harmful and potentially harmful behaviors and cannabis use.
While we lack solid research at this early stage, those in the field of SUD treatment and professionals who work with the cannabis-dependent patient will often cite the increased potency and presence of THC (Tetrahydrocannabinol) in the marketplace as a major contributor to their patient’s psychosis. To illustrate the radical shift, one must remember that the majority of our valid research relies on cannabis that contains under 10% THC and often some level of CBD (Cannabidiol) which is thought to mute the effects of THC on mental health. Products being produced as of this publication, such as “distillates” have been tested to be as pure as 99% THC with no trace of CBD. The majority of evidence we point to for “high-potency” marijuana comes from an ongoing study taking place in England and published regularly in The Lancet journal, this study, and most other countries, consider “high-potency” marijuana to be anything above 10% THC [326]. As the body of research grows, it does suggest that higher concentrations of THC are associated and or lead to higher instances of psychosis [326].
It is imperative to address potential barriers for effective treatment, like severe and pervasive illness including thought disorders. Treatment providers can use pharmacological interventions to treat as much of the symptomology as possible in order to begin and improve treatment outcomes. Examples could include the use of antipsychotics or mood stabilizers; even though symptoms might be a result of the effects of intoxication, it is helpful to stabilize an individual as quickly as possible so they can participate in their care. With this in mind, understand that treating mental health symptoms are made much more difficult if the patient continues their use. If the THC is causal or a contributing factor to the mental health conditions being treated, it should be removed in order to more successfully treat the symptoms of these conditions.
Money and Resources
Helping patients recognize the amount of money and time they are spending on cannabis also seems to be an effective way of helping them see the severity of their use. It is not uncommon to see individuals spending a concerning portion of their time and resources getting and using cannabis. Highlighting this can help them evaluate the importance of discontinuing use.
Behaviors
The cannabis-dependent individual often normalizes their use because they have cultivated a peer group for whom the same level of use is the norm. It is important to help them step back from this kind of sample group bias by helping them see destructive/concerning behaviors for what they are. The individual who waits outside of a dispensary for it to open at 9 am may easily justify this because they are there with friends doing the same and everyone just wants to take advantage of the “happy hour” sale being offered before noon. When asked to compare this to those waiting for a liquor store to open in the morning, they may be able to better see the concern.
Driving under the influence of cannabis is mistakenly considered by many users to improve their driving skills; this is categorically false. As a society, we recognize the harm caused by impaired driving under other substances and can draw this comparison to help them understand the severity of their actions. If patients are resistant to even this idea, which many are, a comparison to distracted driving may help to move them to a place of better understanding.
Citing examples of less socially unacceptable behaviors can be challenging but may help us build a case to the patient. Consuming cannabis in association with entertainment (concerts, movies, recorded music) is a long-standing past time that many report enhances the experience. Our concern for the dependent person is often an inability to enjoy these activities when not under the influence. For example, a glass of wine with dinner can contribute to the overall experience for some but an insistence that one be drunk to enjoy the same meal would be of concern. Discussing the ability to enjoy and engage without cannabis can often lead to important realizations for individuals. If they are unable to enjoy their favorite band, food, sex, the company of others, recreation, etc. without cannabis and if this can be pointed out, they will often see the flawed thinking and can open them up to treatment.
Cultural Considerations
The use of cannabis spans almost every culture and social group on earth, as does problem use. While there have long been religious groups for whom cannabis is a part of their tradition such as the Sandhu or Aghori in India or the Rastafarian tradition of the Jamaican islands to name a few, cannabis use is more prevalent in certain cultures outside of religious tradition.
For many in the Unites States, cannabis use has a long standing cultural and even familial tradition. When the dependent person is faced with treatment, it is important to remember that they are often being asked to remove themselves from their established culture, and this poses a unique challenge. Since few other mood-altering substances play such a large role in cultures and families, we often forget to address this specific barrier to treatment and recovery with patients. A comprehensive treatment and recovery plan will help patients learn to remain integrated with these important social groups without using cannabis. We suggest that the professional involved spend a good deal of time engaging and learning from the patient rather than dictating to them. It is important for the treatment provider to listen to their concerns in this area, recognize the cultural impact and collaborate for recovery focused solutions rather than give broad instructions that will often come across as dismissive and can impact therapeutic rapport. For providers who have little or no background inside of these social groups and or families in which cannabis use is the norm, it is very important to listen, learn, and engage.
Differences Between Adolescents and Adults
Adolescents may be able to recognize the severity of their use and need for interventions better than adults for several reasons. As there is extremely limited use for FDA-approved cannabis-derived medications in adolescents, almost all of their use is illicit and illegal. This simple reality often helps them understand that their use is not controlled. We also know a great deal about the negative consequences of youth use in regard to mental health, cognitive development, and even physical health and development. The simple reality is that delaying use in younger populations will lead to a much lower likelihood of problem use later in life. The younger the individual, the higher the level of concern and the more aggressive the intervention. This is reason enough to treat cannabis use early and for the appropriate length of time.
Detoxification
Many people decide to stop using because of life events, health concerns, challenges by friends, or family or work reasons. But a significant reason why people return to use of a substance is to avoid the experience of withdrawal. Cannabis withdrawal, which is now defined in the DSM 5 and ICD-10 Codes (F12.23), can represent an uncomfortable, drawn out experience [327, 328]. Symptoms of withdrawal include irritability, anger, or aggression; nervousness or anxiety; sleep difficulty; decrease in appetite or weight loss; restlessness; depressed mood; and at least one of the following symptoms that cause discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache [327]. Note that many individuals who are dependent are doing so to “treat” the abovementioned conditions; this reality can pose a challenge to the provider. For example, the opiate, addict would be unlikely to report using their drug of choice to “treat” the vomiting associated with detoxification from opiates whereas the cannabis addict just “uses cannabis to help sleep.” If an individual is not honest about their use with providers, these symptoms can frequently be misdiagnosed as other mood or medical disorders. This can lead to mistaking a diagnosable substance use disorder and/or encourage medical providers to add additional habit-forming medications to treat reported symptoms. Anecdotally, individuals in treatment report that sleep disturbances are the most frustrating symptom and can lead to a quick return to use of cannabis, if sleep is not addressed. This is one hallmark of cannabis treatment that is different than other substances; many of the symptoms of withdrawal do not have FDA-approved medications to help assist during the withdrawal period.
Acute withdrawal symptoms begin to present within the first 24 hours, peaking at 4 days and persisting for 16 days with long-term withdrawal lasting up to 1 month from the last use of cannabis [329]. Symptoms can include craving, restlessness, nervousness and sleeplessness, irritability, depression, anger, strange dreams, loss of appetite, and headache. Research indicates that withdrawal symptoms can be twice as difficult for women. Treatment studies suggest that if withdrawal symptoms can be reduced or alleviated, people will be less likely to resume cannabis use and could have better treatment outcomes.
Knowing that individuals have a better chance of recovery if they are being treated by professionals that understand specific concerns of cannabis intoxication and withdrawal, it is imperative that treatment be of the highest quality, with knowledgeable professionals and address specific cannabis withdrawal and common comorbid psychiatric disorders.
Treatment
The term treatment can range from inpatient detoxification to outpatient services, as well as mutual aid groups. Because of the uncomfortable, dysregulating, lengthy withdrawal period, it is best to have a person participate in an organized treatment plan. It does not mean that treatment has to be costly or remove an individual from their home environment, but it is imperative that the whole person be addressed within the care planning.
A recent study suggested that clinical trials of various treatments included psychotherapy, motivation enhancement therapy, cognitive behavioral therapy, and contingency management. Results suggested a combination of these produced the best abstinence outcomes, with modest rates of abstinence that decline post treatment [330].
Cognitive behavioral therapy (CBT) identifies thoughts, feelings, and behaviors that influence the use of substances. This treatment focuses on the pursuit of adaptive prosocial behaviors, cognitive restructuring, cost-benefit analysis, and modeling. It often includes the use of homework to improve coping skills and self-efficacy. Almost two decades ago, Stephens, Roffman, and Simpson conducted the first CBT treatment for cannabis use disorder [331]. Today, there are currently evidence-based programs that treat cannabis use disorder, both from an abstinence or harm-reduction [332].
Motivational enhancement therapy (MET) incorporates aspects of motivational interviewing (MI) and uses nonjudgmental feedback to challenge current thoughts and behaviors, decreasing ambivalence, and establishing collaborative goals. A hallmark of this approach is eliciting “change talk” to alter future behaviors. Researchers tested brief models (one or two sessions), gender-specific programs, and hybrid programs (9 sessions). Each demonstrating decreases in use, with better outcomes the longer an individual stayed in treatment [330, 333].
Contingency management (CM) targets a behavior and, based on operant conditioning, increases or decreases it using reinforcement. The use of vouchers, desired rewards for abstinence, negative UA, or attendance in groups is a regular practice [330, 333].
Results from clinical trials show moderate rates in reduction of use, but difficulty with sustained abstinence [330]. These rates are similar to other substances but surmised that a return to use of cannabis is often dismissed or minimized because “weed is no big deal,” “it’s medicine,” or that it’s “legal.”
Presently and in the future, it will be important to develop effective treatment that incorporates appropriate technology. Suggesting what we know from recovery, the individual needing treatment will severely underestimate the need for treatment and we know that the longer an individual can stay in treatment the better the outcome. It is likely that given the prominent role that cannabis plays in popular culture and likely in the patient’s daily life, that justification of a return to use will be easier for them than for those addicted to other substances. We must remember that there is significant societal pressure for many to return to use and to minimize it.
The most effective treatment includes not only the patient, but their social network. This can include family, friends, community members, employers, and/or any stakeholders in the individual’s world. If approved with legal releases, these people can provide history, financial or emotional support, and accountability for the patient. Between 40% and 70% of a person’s risk for developing a substance use disorder is genetic, but other risks include raised in a home with substance use, neighborhood where drug and alcohol are used, and associating with peers who use. One can see that these risks need to be addressed in order to support an individual’s chances of recovery.
Substance Abuse Mental Health Association (SAMSHA) developed eight aspects of life that comprise the “whole person,” and it is suggested that no matter what treatment is provided it address addiction; co-occurring and medical; grief, loss and trauma; social and relationships; financial, education, legal; spiritual; health, fitness and leisure; and recovery environment. If each of these aspects are addressed a person will have a chance of a rich and full recovery life.
Medication-assisted therapy (MAT) is one way that medical concerns, addiction, and mental health can be addressed. Currently, the FDA has not approved any medications for the treatment of cannabis use disorder. Although early research has indicated that pharmacological interventions, added to the previously described treatment modalities, may improve treatment outcomes [330]. This combination of treatment highlights biological, psychological and social aspects of care.
Marijuana Anonymous is a fellowship of men and women who share our experience, strength, and hope with each other that we may solve our common problem and help others to recover from marijuana addiction.
They follow a process of identifying how their lives have become unmanageable and making a life worth living.
- 1.
We admitted we were powerless over marijuana, that our lives had become unmanageable.
- 2.
Came to believe that a Power greater than ourselves could restore us to sanity.
- 3.
Made a decision to turn our will and our lives over to the care of God, as we understood God.
- 4.
Made a searching and fearless moral inventory of ourselves.
- 5.
Admitted to God, to ourselves, and to another human being the exact nature of our wrongs.
- 6.
Were entirely ready to have God remove all these defects of character.
- 7.
Humbly asked God to remove our shortcomings.
- 8.
Made a list of all persons we had harmed and became willing to make amends to them all.
- 9.
Made direct amends to such people wherever possible except when to do so would injure them or others.
- 10.
Continued to take personal inventory and when we were wrong promptly admitted it.
- 11.
Sought through prayer and meditation to improve our conscious contact with God, as we understood God, praying only for knowledge of God’s will for us and the power to carry that out.
- 12.
Having had a spiritual awakening as the result of these steps, we tried to carry this message to marijuana addicts and to practice these principles in all our affairs.
The most imperative aspect of seeking treatment is that it be trauma integrated, for those that have experienced adverse childhood experiences, or trauma as adults. This means that providers need to be aware of reactivity to trauma triggers and the brain’s response. Many programs understand that substances are used to numb the effect of trauma and distract from emotional pain; cannabis use is no different than any other substance, in this way. It is often used as an analgesic for emotional pain. Programs must integrate addiction, mental health, and trauma treatment simultaneously.
Cultural Differences Between Cannabis and Other Substances
The role that cannabis plays in pop culture and even fashion is dramatically different than any other drug with the exception of alcohol, the most destructive of all addictive substance we know. It is difficult to believe the devastating aspects of alcohol because it is accepted and used at much higher rates than other substances; culture plays a significant role in shaping this message. It is easy to see the parallels with cannabis and alcohol, but harder for users to see this with cannabis and other drugs. There is an understanding that most other substances of abuse are potentially destructive and damaging; however, with cannabis this reality is challenged in popular culture. Consider the amount of entertainment that both normalizes and glorifies use of this specific substance and compare that to other substances; have you ever seen anyone wearing a methamphetamine hat, or an album cover with heroin pictured? There is even an entire genre of film defined as “stoner film” in which cannabis use and abuse is central to the theme and activities. Some of the most recognizable celebrities and role models in the country are involved in the cannabis industry and or promote its use.
Understand that this deep cultural integration poses additional challenges to treating cannabis addiction. While we are typically asking patients to move away from behaviors that are understood to be destructive with other substances, asking them to do the same with cannabis is in many ways asking them to move away from much of content of their lives from music to film to peers, in effect, their identity.
To an extent, cannabis differs from alcohol in this regard. While alcohol is much more widely used and accepted, it is still understood that alcoholism is a real threat to some people and that alcohol abuse and misuse can have devastating consequences. For many who live inside a culture of cannabis, they have seldom been exposed to messages about their drug of choice that are negative and when they are, their entire community tends to rally around the idea that the information must be false or dismiss the message as old-fashioned. Given the recent changes in cannabis laws, there has been a great deal of money spent to both normalize its use as well as counter arguments that threaten that use. Many of today’s users believe cannabis to be a necessary and even life-giving part of their world and will push back on ideas contrary to that construct. With this in mind, know that for the addicted person to come to a point where they are willing to ask for help they have in effect stepped out of their entire world view and recognize the problem as serious enough that they are willing, at least in moments of desperation, to see that the lens through which they see almost everything might be fractured.
Stigma
Now that we understand how difficult it can be for the cannabis user to admit they have a problem and the immense social pressures not to seek help, we must consider what common reactions occur in the professional community as well as in circles of recovery. Many professionals remain uneducated on the severity of cannabis use disorder that is fueled by a MUCH more potent product than the plant of years past. As such, they underestimate the severity of the problem and can make it more difficult for the individual seeking help. It is commonly believed and repeated that “no one has ever died from weed.” This factually untrue statement, in itself, draws a comparison to other substances and ranks the cannabis addicted person below other addicts. Statements from professionals that uphold this fallacy or contribute to them feeling “less than” can be extremely harmful. Saying things like “it’s just weed,” “there are no other serious drugs involved,” or “you can’t be physically addicted to marijuana” can be all the reason a potential patient might walk away from help.
Conversely, by acknowledging the courage it takes to ask for help and recognizing what a major shift in thinking is required to make this admission, professionals may be able to enhance their motivation.
Changing Perspective
There is an old adage inside of recovery circles; “all someone needs to do is change everything.” While it might seem trite this simple bit of advice is the goal of the recovering person and everything we can do to help them work towards realizing it is helpful. For many of our patients working toward abstinence, we should remember that they very likely have not experienced or do not remember experiencing many daily situations that we all face and emotions we all feel without cannabis to mute or enhance those experiences. Remember that for many of our patients simply eating a meal without a ritual of cannabis use may feel impossible, not to mention listening to their favorite band, or watching a film. Since they were often engaged in their addiction throughout all aspects of daily life, it will be a learned skill to do so without cannabis. We can help by preparing them for this reality, listening as they process, and helping them identify and execute solutions. Things as simple as a poster on the wall, a shirt they see in public or a song that comes on might trigger their healing brains to crave cannabis starting a cycle that can often lead to relapse. Recognizing that these social cues will trigger them and developing action plans around those triggers can be very helpful. A patient in early recovery from cannabis addiction might tell us something that seems simple or absurd or unnecessary. People might clean out their music collection in order to avoid triggers, redecorate, and avoid certain foods or forms of entertainment. By recognizing the significant step that actions like these can represent, we will be better prepared to walk through these events and tasks with them. It is important to remember that for the cannabis addict triggers exist everywhere and old activities should be replaced by new ones that support their recovery and change. Helping them to identify the things that need to change and supporting those changes can help them in their journey to just “change everything” a daunting task when considered as a whole but one that is made much easier by putting one foot in front of the other, doing what they can in the moment and taking it one day at a time.
Summary
As the numbers of cannabis-dependent people increases, so does the number of those in recovery from cannabis addiction. This is good news for those working toward solutions with the addicted patient, we have more resources than ever before to aid in their assimilation into a community of recovery from cannabis addiction. As mentioned before, Marijuana Anonymous (MA) can be a powerful community to aid in one’s recovery. Today, there are meetings taking place all over the world at all hours of the day; the closer one is to a metropolitan setting the more MA meetings exist as well a virtual meetings. It is crucial that those in early recovery find a community in which they can thrive without cannabis. For some that may be religious traditions, for others groups that base their recovery around sports or recreational activities. As of this writing there is a national group called SAFE entertainment (www.soberafe.com) that works to create safe sober zones at concerts, music festivals, and sporting events. Since the use of cannabis is heavily associated with live music events organizations like this allow individuals in recovery to still engage in activities, they are passionate about, in a safe way. It is important for professionals to remember that recovery isn’t just the absence of substance, it can be the addition of a great deal and by adding social opportunities for those in early recovery we can aid in their efforts to remain abstinent.