Cannabis Use Disorder: The Grim Reality of Cannabis Addiction
Nick Beebe
Illustrations by: Hannah Maver, Nick Beebe
Instead of using logical reasoning, or really any reasoning at all, my tanning-devout middle school health teacher often remarked that any use of drugs would kill us all. Her one brief Powerpoint devoted to cannabis was heavily structured on the assumption that it would act as a gateway drug before eventually leading to death. On the contrary, young users of the drug often view cannabis as nothing more than a Saturday night ritual at Natty Light-sponsored basement gatherings. Suffice it to say, the reality of cannabis appears to be clouded by a diverse array of perspectives, some of which likely stem from the drug’s stigmatized past. Though cannabis hasn’t been demonstrated as a direct cause of death, it can lead to a decreased quality of life and the emergence of addiction: cannabis use disorder (CUD). Cannabis — also referred to as marijuana, weed, and pot — is heavily touted for its delivery of altering effects without any apparent aftereffects, compared to drugs like alcohol, cocaine, and heroin. As such, cannabis is the most popular illicit psychoactive drug in all US states and every country [1]. While cannabis legalization in the U.S. becomes more widespread and its use normalized, it is crucial to acknowledge the expanding scientific literature that pertains to cannabis use disorder (CUD).
Research on CUD clearly signifies that cannabis can spark addiction, though this simple fact is continually undermined by the public. Epidemiologist Dr. Deborah Hasin of Columbia University links public ignorance of CUD to 25-year-old findings that dismissed the disorder as incredibly rare [2]. Twenty-five years ago, however, the common cannabis was 700-2000% less concentrated and obtaining the drug was nowhere near as simple as sending a dealer a Snapchat [3]. While cannabis addiction is by no means inevitable for all of the drug’s users, the potential for CUD to manifest noticeably increases in individuals who both extensively and continually administer the drug. In fact, there’s a 9% likelihood of transitioning from any cannabis use to complete cannabis dependence, though a number of additional factors can influence this rate [1]. With cannabis legalization on the rise — both medical and recreational — the likelihood of use is bound to consequently increase. In 2008, 72.8% of surveyed American drug users reported using cannabis, while 53.3% of this same group stated it is the only drug they use [4]. Due to a vast increase in cannabis potency and initial exposure at younger ages, there has also been a rise in overall cannabis use and reported CUD, in addition to cannabis-induced emergency room visits [2]. It is important to note that cannabis use disorder is preventable, and users should stay aware of their usage to avoid spiraling into substance abuse. Ultimately, the expansion of preventative intervention, grounded in sufficient CUD and cannabis research, is vital.
THE NEUROBIOLOGY OF CANNABIS USE
It is critical to understand how cannabis can alter brain chemistry and structure, especially as uncertainty surrounds both the acute and chronic effects of cannabis use on the central nervous system (CNS: the brain and spinal cord) [1]. The most popular method of cannabis administration has always been inhalation by smoking. However, other methods, like edibles or “dabs,” have steeply risen within the past decade, allowing users to consume even higher doses of THC [2]. Needless to say, when exploring the neural impacts of cannabis and ∆9-tetrahydrocannabinol (THC, the primary element of a cannabis high), it appears that cannabis isn’t exactly what popular culture makes it out to be.
Cannabis Inside the Body: Endocannabinoid System (ECS)
To best understand CUD, one must inspect the physiological pathway of cannabis in the body. Upon the first inhale (or “hit”), THC, the main cannabinoid of cannabis, enters the bloodstream and circulates within the body. Cannabinoids are a group of compounds that share chemical structures to naturally found components of cannabis; humans produce natural cannabinoids in the body, like AEA and 2-AG, but not the ones that come from cannabis, like THC, CBD, CBG, CBV, and THCVA [5]. Think of all cannabinoids as the same type of candy made by different brands — they are mere equivalents in regards to structure and function; it is where they come from that differs (either from the body or cannabis). The endocannabinoid system (ECS), a metropolis of self-made cannabinoids binding to appropriate body-spanning receptors, meticulously works to mediate the presence of cannabinoids — whether produced internally or externally [6]. These receptors, CB1R (cannabinoid 1 receptors), facilitate processes related to appetite, learning, anxiety, depression, schizophrenia, neurodegeneration, and addiction [7]. Despite being denoted as the peacekeeping switchboard of the body, the remarkability of the ECS has often been downplayed due to its association with cannabis.
Anandamide (AEA) is a neurotransmitter that acts as a ligand in the ECS, meaning it has the vital task of biological signaling — invoking a certain response cascade — like all cannabinoids that interact with CB1R. Ligands and receptors act much like Rube Goldberg machines: once a ligand molecule binds to a receptor, the receptor initiates a signalling pathway as a result of the ligand’s presence. As such, ligands, and the processes they control, are highly specialized and lead to specific outcomes. AEA, when at low levels in the body, correlates with increased appetite, anxiety, depression, and hypertension [6]. Due to their similarity in structure and role, it wouldn’t be a stretch to expect such feelings from low AEA to low THC as well (a notable example being “munchies”). THC in cannabis is able to infiltrate the ECS by resembling AEA, again due to their similar shape — hence both being classified as cannabinoids [7]. With the excessive usage of cannabis, THC’s mimicry of AEA overstimulates dopamine release, leading to an overtly euphoric state for an individual with minimized groundedness; this process also inhibits the emission of the neurotransmitter glutamate, which, as a result, promotes drug-seeking behaviors [8]. However, THC abuses this system into producing streams of dopamine for a “good feeling,” meaning the brain is activating the reward system for a behavior (i.e. smoking) that the pathway would not typically reward [3]. With constant stimulation of dopamine comes the body’s natural expectation of that constant amount of THC. This is what drives the formation of cannabis addiction.
Cannabis Inside the Body: The Brain
With the prolonged use of cannabis also comes a lower quantity of CB1R, which fortunately respawn with continued abstinence [3,9]. CB1R are heavily concentrated within the striatum, hippocampus, amygdala, and prefrontal cortex regions of the brain [1]. The latter three brain regions all experience decreases in size with increased cannabis administration, rendering them most vulnerable to manipulation by cannabis use [3,10]. The striatum, part of the brain’s reward system, releases dopamine when an individual performs actions that keep them alive (i.e. eating, drinking water, exercising). As the hippocampus is most involved with one’s long-term memory, cannabis can inhibit one from being able to clearly pull upon recollections of the past, even leading its users to develop false memories at a higher rate [11]. Historically, long-term memory problems for cannabis users appear to be relatively rare; but, recent findings dispute this, remarking that CB1R density was restored in subjects recovering from addiction in all brain regions except the memory-related hippocampus [1,9]. The amygdala, just to the side of the hippocampus, controls feelings of fear, stress, and anxiety; cannabis’ impact on this structure may explain why many experience paranoia while getting high [12]. Lastly, the prefrontal cortex (PFC), responsible for executive functioning, presides over processes including decision-making, impulsivity control, and social behavior, much like the brain’s moral compass. It has also been determined that the overstimulation of CB1R — when excess cannabinoids flood the body — directly interferes with proper PFC development [13].
The prolonged use of cannabis has also been linked to decreased grey matter [1]. Grey matter is the information processing component of the brain, found right on its surface — the more grey matter, the healthier the brain since greater brain function is promoted. Grey matter and the intensity of cannabis use have an inverse relationship with each other: the more intense the cannabis use, the lower the available grey matter [14]. Furthermore, the neurons that occupy grey matter function abnormally in people with CUD and those whose cannabis use is heavy, but not definitively indicative of CUD. In experimental trials with rats, brain exposure to “high doses” of THC for 90 days or more reduced both the quantity of neurons within grey matter and their capabilities, even months after a rat’s final “hit” [3]. Because these findings were observed in rats, a species that is not vastly dissimilar from us genetically speaking, further research should directly explore the impact of THC on neuronal structures in humans.
EXTENSIVE CANNABIS USE
When it comes to understanding humans, rodents truly act as great models given the similarities in the length of our genomes and the genes we share. One recent study with rats found that after rats were conditioned to become high, those exposed to THC-rich vapor were led to consistent THC use [12]. On average, each THC rat self-administered a peak of 18 puffs on the experiment’s tenth day, before use slowly decreased for the rest of the experiment. Notably, however, consumption of THC by these rats still remained considerably higher than the other groups (exposed to CBD or a control vapor). Eighteen THC puffs may sound like nothing more than a frat boy’s breakfast, but it’s essential to understand that these are rats, a mere fraction the size of humans. Needless to say, this observed behavior ties directly to the significant psychiatric burden of CUD. These rats, upon THC exposure, went from hardly ingesting the vapor at all to taking in shockingly large amounts; this is addiction [12,3]. CUD is characterized by physiological, behavioral, and cognitive symptoms that lead cannabis use to become one’s utmost priority [15]. Cannabis inevitably became high-priority to the rats in this study, just as it does for many of its human users.
With CUD also comes risks of depression, anxiety, poor executive functioning, and subpar stress management; these make up some of the aforementioned cognitive and behavioral symptoms of CUD [3,4,2]. Though some might report feeling happier while high — caught in glittering rushes of dopamine and shuffling Tame Impala tracks — studies have repeatedly failed to determine this link in the long run. Rather, studies lend credence to the notion that cannabis actually makes depression and anxiety worse [3,16,1]. In fact, less than half of medical cannabis users report being relieved of any depressive symptoms at all. Numerous studies have consistently highlighted cannabis’ role in instigating mental health problems, rather than treating them — specifically connecting cannabis use to the development of depression and suicidal tendencies, most evident in young users [15]. Historically, once a state legalizes cannabis, prescriptions for antidepressants drop tremendously, meaning it is likely that many suffering from depression are led to cannabis for treatment, regardless of its lack of efficacy [2]. This relationship is clearly in dire need of clarification and attention in forthcoming literature, as cannabis has been found not to help, but rather, worsen conditions like depression and anxiety.
FACTORS THAT INFLUENCE ONE’S RELATIONSHIP WITH CANNABIS
In 2015, nearly one-third of American cannabis users were diagnosed with CUD the year prior, a percentage similar to substance abuse amongst heroin (25%) and cocaine (36.5%) users [3]. On a global scale, approximately 13 million individuals have been found to meet the criteria for a CUD diagnosis from a 2015 UN report [1]. Clearly, it is imperative to investigate the myriad of neurobiological and interpersonal factors that influence one’s level of cannabis use and vulnerability to CUD development as both are issues for many around the world. So how do we know if someone is at greater risk for CUD, aside from just observing extensive cannabis use? Admittedly, there is a tremendous complexity underlying the individual differences that diversify humankind, a phenomenon commonly referred to as “nature vs. nurture.” Nature refers to one’s genetics inherited from both of their parents, and nurture refers to one’s upbringing and the environment in which they’ve developed; it gets complicated when elements of an individual that seem solely nature-driven or solely nurture-driven are influenced by the other. An example of nature might be the flaming red hair someone is born with, as hair color results from the genes they’ve inherited from their parents. On the other hand, an example of nurture might be developing a Boston accent. This is because it’s probably not in your DNA to develop a certain dialect, but rather, it comes from who you grew up around and how they spoke to you. In the context of cannabis and CUD, the following can be explored through the lenses of nature and nurture: genetic precursors, age at exposure, gender identity, ancestral background, and sexuality.
Genetics and Cannabis
Genetics don’t directly correspond to destiny, perhaps best noted in the 1997 cult classic Gattaca. Given how complex our genomes are, it can be quite hard to link specific genetic markers to certain conditions and complex traits like CUD. Cannabis use disorder is understood to be a polygenic disorder, meaning it’s caused by a combination of several genes. However, genome-wide association studies (GWAS) that compare genetic codes between many individuals have failed to locate overlapping genetic risk loci (genes that act as “markers” for something, CUD in this case). Recent findings suggest the potential for cannabis abuse and dependence is approximated to be anywhere from 21% to 78% inheritable from one’s parents [3]. This estimate is likely so wide due to the diversity of genetic precursors that have been identified from past studies, signaling more research is needed to reach certainty and a refined range of heritability. One well-studied mutation exists within chromosome 1’s FAAH gene, which affects how the brain deals with addiction and reward. This mutation is directly involved with the decreased production of AEA (the “bliss molecule”) which affects the ECS and drug response centers while increasing risk of CUD development [17,18]. Any negative impact to these regions ultimately alters the brain’s chemistry and the subsequent well-being of the individual. Furthermore, variation in the gene responsible for coding CB1R (cannabinoid receptors) has been associated with cannabis dependence [7]. Clearly, the middle ground between genetics and cannabis dependence is one that requires tremendous examination in the immediate future.
Ancestral Background and Cannabis
One’s ancestral background can also be a key component of CUD development; people with certain backgrounds appear more likely to develop the disorder than others. The most common primary illicit drug used by Whites, other than alcohol, is opiates, followed by cannabis. In comparison, cannabis has been found to be the most commonly used drug amongst Blacks, Latinos, Asians, and Pacific Islanders [19]. The gravitation towards cannabis by all is likely perpetuated by societal factors, that can be strengthened by genetic factors to result in CUD.
As it turns out, recent epidemiological studies have determined that adolescents identifying as White, multiracial, or Native American are more likely to use cannabis than adolescents of Pacific Islander, Latino, Black or Asian backgrounds. Native American adults and adolescents who live on reservations report the highest levels of cannabis use amongst all groups in the United States, with over 20% of Natives reporting cannabis abuse or dependence [20,19]. Further, Black Americans have been noted as having a greater risk of developing cannabis use disorder than Whites [21]. However, Whites, compared to Blacks, have a much harder time ending cannabis use, reporting an average of 5.5 lifetime quit attempts, compared to 2.1 for Blacks [22]. Another study determined that cases of CUD grew noticeably higher among Blacks and Native Americans compared to Whites from 2005 to 2013. [19]. But what accounts for these variabilities in cannabis abuse vulnerability across different groups?
It can be hypothesized that the high rates of CUD in Native and Black Americans spring from White-led dehumanization starting with the stealing of Native land to establish the New World. It is possible that this systemic oppression, violence, and consequent daily stress may drive these groups’ vulnerability to cannabis addiction. Additionally, with regard to the education received by marginalized groups, one study hypothesizes that a blatant lack of smaller class sizes for disadvantaged — often minority — students increases the risk of drug use nationwide. Smaller classes allow for higher academic achievement and a sense of belonging, while larger classes allow many students to slip through the cracks, feeling unnoticed with lower engagement, driving cannabis to potentially act as a means of coping with their position [21].
In the end, these findings should inspire more studies and more action when it comes to linking ancestral background and CUD, especially for individuals of mixed descent as they are considered in very few studies. If we know that certain populations are vulnerable to CUD development, what can we do to help them — instead of doing nothing?
Age at Cannabis Exposure
As with other drugs, the age of one’s initial exposure to cannabis is closely linked to the severity of its later effects. Typically, first exposures to cannabis during youth highly increases the likelihood of future cannabis use [19]. Despite an overall dearth of research on the relationship between development and cannabis use, developmental research on cannabis has consistently scrutinized the period of adolescence.
Late adolescence through one’s early twenties is the highest-risk window of developing CUD, meaning that any cannabis exposure during or before this time poses a potential threat [3,16,19]. The age of one’s first exposure to cannabis has also continuously decreased as the drug’s acceptance by the general public increases [16]. Since the human brain continues to develop well into the twenties, adolescence is regarded as a sensitive period of emotional vulnerability because cannabis interferes with several systems of the brain that hold a stake in psychotic and affective disorders [3,18]. One study has even found that individuals who started using cannabis during adolescence experience greater structural differences in the brain compared to those who started using the drug as adults, exemplifying the true malleability of a young, developing brain — especially as one in six who start using cannabis in adolescence will be dependent on it by young adulthood [10,15]. Furthermore, anyone who heavily utilizes cannabis before the age of 17 is five times more likely to abuse other substances later in life [16]. By allowing CUD to go unnoticed, many, especially vulnerable adolescents, can face CUD and additional substance abuse which effective education could have prevented.
Gender Identity and Cannabis
The popular “stoner” trope has often been tied to those that identify as male, which, interestingly enough, is strongly backed by research. Men experience greater odds of abusing and experiencing cannabis dependence, especially when they are young upon initial use and possess limited education [19]. Although there is a high number of men with cannabis dependence, the severity of CUD for women is greater; this is also the case for many other substance abuse disorders [3]. Individuals with transgender and non-binary identities were found to report a higher prevalence of cannabis use than their cisgender peers, though there is not yet a strong-enough consensus on the severity of CUD for these individuals. Amongst transgender populations, transgender men report higher usage rates of cannabis than transgender women, but non-binary individuals report more cannabis use than both of the aforementioned groups [23,24].
Men may be drawn towards cannabis because it can facilitate closeness, allowing for conventional gender expectations to be defied so that they can express themselves without fear of demasculinization [23]. Ultimately, though, the ways in which gender influences cannabis use are complex: this intersection is largely dependent on social, cultural, and political contexts [23]. In other words, variability of cannabis use in gender groups may be due to socially constructed differences rather than biological ones. It is possible, though, that biology might play into cannabis use gender differences. For example, the nucleus accumbens, a brain region that engages one in rewarding behaviors, has been demonstrated to exhibit a smaller response to drug stimuli in female rats than in male rats [25]. In other studies, where male and female rats are given the choice between a reward of food or cocaine, more females opted for cocaine than males [25]. However, there’s a dearth of studies pertaining to the sex differences of human neural mechanisms in drug-taking behavior which would be critical to consider when understanding CUD development on the basis of sex [26]. Because cannabinoids largely concentrate in fat tissue, and biological women physiologically tend to have more fat tissue, it was once posited that it would take females more cannabis to reach the same ‘level’ of high as men [26]. However, a study published this year directly contradicts this theory, determining that when men and women smoked identical cannabis cigarettes (joints), THC concentrations in the blood of females were higher, even when they smoked less [27]. However, both of these studies point to the absence of ample testing on this subject and argue this interplay should further be analyzed.
Sexuality and Cannabis
Similar to the complex entity of gender, sexuality often has close ties to one’s relationship with cannabis. As such, some studies have been able to identify variance in cannabis use amongst those with differing sexualities. In one study, queer women utilized cannabis, in any form, more than three times the average heterosexual woman, with bisexual women, particularly, using it the most [28]. Heterosexual men, on average, utilized cannabis more than men that identify as bisexual. However, gay men utilized cannabis significantly more often than heterosexual men [28]. Considering that more men suffer from CUD than women, it’s reasonable to infer that gay men both utilize cannabis and experience CUD at a very high rate [3,19]. Inevitably, this variation in CUD could stem from the brain’s cortical thickness — how much of the brain there actually is. Thinning of the cortical surface has been linked to impulsivity, leading to urges taking precedence over logic, even being linked to conditions like ADHD and bipolar disorder [30]. Homosexual men were noted as having slightly thinner cerebal cortices than heterosexual men, on average, along with other significant differences in various structural volumes [29]. It is clear that prejudice, discrimination, and stigma contribute to an increased risk of substance abuse and mental health problems for queer people, though this relationship is in need of greater investigation [28].
ENDING CANNABIS USE
Withdrawal
Studies of cannabis withdrawal syndrome (CWS) have been quite limited, though research on the topic should, and will likely, persist following its inclusion in the DSM-5 (a recently revised diagnostic manual that assesses mental disorders) and increasing legalization [1,3,10]. When the DSM-IV was published in 2000, very little was known about cannabis withdrawal, which helped bolster the widespread myth that cannabis couldn’t be addictive. Even today, many professionals, along with the public, remain naïve to the existence of cannabis withdrawal [2].
CWS consists of anxiety, irritability, restlessness, depression, anger, shakiness, nausea, sweating, stomach pain, and even boredom, as well as disturbances to one’s appetite, sleep, and weight [1,22]. The significance of CWS has been greatly disputed, though its range of symptoms vastly impair in one’s daily life [1]. The assemblage of withdrawal symptoms that many face should come as no surprise given how far the endocannabinoid system (ECS) internally spans; undoubtedly, the negative sensations following the end of cannabis use affirm the importance of a properly functioning ECS. The human body likes stability and predictability, so when one’s use of cannabis goes from persistent to nonexistent, the body (and ECS) is thrown into high alert. Further, relapse is common for many, as these withdrawal symptoms are so undesirable and difficult to endure. As found by patient observation in a Yale University-funded addiction facility, the most common reasons for relapse included negative moods, anxiety, cravings, boredom, stress, and trauma. Similarly, the presence of these psychological withdrawal symptoms are tied to worse outcomes for many patients with substance abuse disorders, though how this occurs specifically with individuals with CUD requires more investigation [31]. Ultimately, given how many cannabis users CWS affects, it would be inhumane to continue to essentially ignore what those suffering from CWS are facing, by not providing CWS (or CUD) with proper recognition or research [3].
Treatment
Although there are millions of people who suffer from CUD, there are no FDA-approved pharmacotherapies to aid with CUD or CWS. It has been hypothesized that therapies for both CUD and CWS should target the ECS, taking advantage of the great similarity between AEA and THC. But, such suggestions remain largely speculative as the role of cannabis in the field of medicine is considerably controversial [32]. Fortunately, psychosocial therapy has been found to help quell cravings by improving grey matter volume and the connectivity between different cortices of the brain [3]. Another promising approach is the administration of cannabidiol, also known as CBD. CBD, interestingly enough, comes from cannabis, but it doesn’t produce the “high” that many look to THC for. There is also no indication of addictive properties in CBD, which is especially important for someone living with CUD [3]. CBD, in the complete absence of THC, has been found to greatly reduce the desire for cannabis within recovering users, as well as the paranoia and memory impairment it induces [3,12]. However, more studies must corroborate the potential for CBD to help one through CUD/CWS, as the substance, classified as an unregulated supplement, has only recently come into light as a potential treatment option [9].
LOOKING TO THE FUTURE
It’s likely that the information available on CUD has been limited by the sociopolitical quagmire of the US. Until this gap of research is closed, a true understanding of the extent of cannabis’s control over brain growth will remain obstructed [3]. Of the studies that do exist, however, there is a clear need for standardization of metrics, especially as the development of CUD is likely linked more to cannabis potency than one’s duration of use [1]. Additionally, taboos surrounding addiction must be eliminated in order for individuals to have open, honest, and evidence-based dialogues that allow substance abuse to be combatted head-on. Rather than try to entirely prevent individuals from experimenting with drugs without explanation, revised education about addictive substances, like cannabis, is urgently needed [16]. This means rejuvenating the mundane middle school health class with critical, current information to teach students how to avoid substance abuse and, if applicable, manage addiction. State legislators should also deeply contemplate the various risk factors for CUD when it comes to the passage of medical and recreational cannabis laws [2].
Although cannabis hasn’t been proven to be as physically dangerous as other substances like alcohol, cocaine, and opiates, it can be incredibly dangerous on neurological and psychological levels. Ultimately, proper education on cannabis, CUD, and CWS, is desperately needed for all, from the doctors who will diagnose CUD and CWS to the teenagers attending daily smoke circles. CUD is entirely preventable and cannot be disregarded any longer. Cannabis is addictive and requires further research and recognition, especially when it comes to CUD (and consequent CWS). More research on cannabis and its effects on human users are in dire need as countless states progress with legalization. In the end, being able to “outsmoke” everyone at the party isn’t something to be admired. It’s problematic. A plant can, in fact, throw your life off track, despite how “natural” it may seem; after all, aren’t tobacco, alcohol, opium, cocaine, and meth derived from plants, too?
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