Implications of Adolescent Cannabis Use
Introduction
Schizophrenia is a chronic, intensely debilitating, and often severe disease that affects roughly one percent, or 3.2 million people in the United States. Schizophrenia is also the costliest to treat, exceeding $155 billion dollars yearly and costing the US over $44,000 per individual (Casper & Joukov, 2018). Schizophrenia is also one of the leading causes of disability worldwide. Schizophrenia is characterized by distinct symptoms and subcategories which act primarily on the central nervous system. For a person to be properly diagnosed they must exhibit both negative symptoms (social withdrawal, indecision, apathy, and flat affect, etc.) and positive symptoms (hallucinations and delusions). While treatments exist for Schizophrenia, they are not ideal and often include strong antipsychotics, which are not effective in treating negative symptoms and can lead to increased chances of diabetes, obesity, and heart disease. While the disability of schizophrenia is well understood, the cause of the disease is less so (Casper & Joukov, 2018).
In the absence of a well-rounded explanation, and with a lack of effective treatment, researchers and physicians have been searching for possible causes and risk factors since the discovery of schizophrenia over 100 years ago. But not unlike the disease itself, conclusions as to what causes the disease vary widely from genetics to neurodevelopment, to prenatal infection, gestational diabetes, and paternal. Schizophrenia is an aberration, so it comes as no surprise that researchers are again looking into a new risk factor; cannabis use. Specifically, the correlation between adolescent cannabis use and the development of schizophrenia later on. However, even here, there remains indecision as to whether cannabis use is a real risk factor, how cannabis affects the brain, and if cannabis affects the brain at all.
Heavy Cannabis Use Alters Adolescent Brain Development
Cannabis is the most widely used, and by far the most misused, drug available, and with the current optimism surrounding cannabis culture, as well as legality increasing access, many consider cannabis to be safe. However, there remains a population at great risk when it comes to using cannabis regularly. Adolescents, whose bodies are still working to develop crucial structures, and connections in the brain, are at the largest risk. Over the past decade cannabis use of people under the age of 18 has increased nearly twenty-fold, which is alarming when considering schizophrenia as a repercussion (Casper & Joukov, 2018).
Grey Matter and Synaptic Pruning
As the adolescent brain undergoes changes like synaptic pruning, chronic cannabis use comes at the risk of inducing over-pruning, leaving the brain at greater risk of developing schizophrenia. The loss of cortical grey matter, is also included in this brain damage. A loss of grey matter leads to hypo-functioning in areas of the brain that involve memory, speech, perception, and decision making. Chronic cannabis use not only leaves the brain at risk for psychosis but also inhibits cognition and causes inhibition (Kumra et al, 2012).
Frontal Cortex and GABA Hypofunction
Further implications of frequent cannabis use during adolescence include damage to the frontal cortex. Cannabis use prevents the normal development of the frontal cortex, leading to GABA (Gamma-aminobutyric acid) hypofunction, which inhibits the neurotransmitter in doing its job, which would normally be regulating the communication between neurons and reducing excitability. This puts the brain at risk for not only developing schizophrenia, but also schizoaffective disorder, a disorder that categorized psychosis in addition to mood disorder symptoms. Schizoaffective disorder can sometimes be more severe than schizophrenia alone (Renard et al, 2018).
Mesolimbic Dopamine System
Chronic cannabis exposure has further consequences for the developing brain, as GABA function has a direct relationship to the mesolimbic dopamine system. With GABAergic neurotransmission hypofunctioning, little is left to regulate the dopaminergic system:
attenuated GABAergic function in the PFC may cause abnormalities in the synchronization of gamma-band, prefrontal neuronal activity, and sub-cortical dopaminergic transmission, which may, in turn, lead to schizophrenia-like symptoms such as hallucinations as well as pathological affective and cognitive deficits. (Kumra et al, 2012)
Dopamine dysregulation has been long considered to be a contributing factor to the development of schizophrenia by some, it’s overproduction, no longer hindered by GABAergic neurotransmission, could increase the severity of schizophrenia (Renard et al, 2018). It is important to recognize also that the risk of developing schizophrenia in adolescence increases with use: if used (cannabis) between one and 10 times, there is a 130% increase in the likelihood of psychosis; if used between 10 and 50, there is a 200% increase in the likelihood; and if used more than 50 times before the age of 18, there is a 600% increase in the likelihood of developing schizophrenia (Arseneault et al, 2002). By preventing crucial aspects neurodevelopment from occurring when and how they should, the changes in the brain, loss of grey matter, hypofunctioning GABAergic neurotransmission, and dopamine dysregulation, leave all adolescents at risk for schizophrenia or schizoaffective disorder, and not just those predisposed, the consequences of which could be life-altering.
Adolescents Genetically Predisposed
Knowing how cannabis use in adolescence changes the brain help to understand how those changes might lead to schizophrenia. However, some researchers argue that those changes alone are not significant enough to lead to psychosis in an otherwise healthy young person (i.e. if that young person is at no genetic risk, and are not showing prodromal symptoms of schizophrenia). But for those who are either, and often for those who have both a genetic history and early symptoms, the risk becomes frighteningly high, with the likelihood doubling and even tripling, compared to an adolescent with no additional predisposition (Mustonen et al, 2018).
Considering the way cannabis changes the brain, and then applying those changes to someone already very likely to develop schizophrenia, it is easy to see why cannabis use is riskier for someone predisposed. Adolescents, “with prodromal symptoms and cannabis use had double the incidence of psychosis” and those with “both parental psychosis and cannabis use have been shown to have a greater risk for psychotic outcomes” (Mustonen et al, 2018).
Acutely aware that cannabis can trigger a first-time episode of psychosis, or trigger a new episode in people who already have schizophrenia, some lawmakers suggest we increase the age limit until well after the brain has finished developing (somewhere between 25 and 27). Lawmakers also suggest taking steps to prevent people who are at risk of or have schizophrenia from being able to purchase cannabis. The concern increases as the legality of cannabis is changes (Casper & Joukov, 2018).
Further concerning is that cannabis use in adolescents before the age of fifteen could trigger early-onset schizophrenia (onset before 18). Early-onset schizophrenia is one of the most serious consequences of adolescent cannabis use, as early-onset schizophrenia is typically a more severe form of the disease, and significantly harder to treat, often leading to treatment resistance and little to no control over psychotic symptoms. As a consequence of adolescent cannabis use reduced grey matter, and reduced total brain volume in the left superior parietal cortex, leads to deficits in attention, focus, and memory For those likely to develop schizophrenia changes to the brain can be more devastating than schizophrenia alone might be, especially if the onset occurs before age 18 (Kumra et al, 2012). Chronic cannabis use may also increase the severity of some symptoms like visual hallucinations (Casper & Joukov, 2018). Because of these conclusions, cannabis use among those predisposed should be highly discouraged.
Reverse Causation
A final, and, less agreed upon, consideration is that cannabis use has little to no effect on the brain. Power et al (2014) argue that, “it is a well-established fact that cannabis use is much higher among schizophrenic patients than the general population” many young people are self-medicating to manage prodromal symptoms before they even know what those symptoms are. This argument contradicts the idea that cannabis is the risk factor, suggesting instead that schizophrenia is, in fact, a risk factor for cannabis use. “This would mean that the association between schizophrenia and cannabis use is not simply one of an environmental risk factor, but rather involves gene-environment correlation, as individuals choose and shape their own environment based on their own innate preferences,” (Power et al, 2014). For many people with the disease, self-medication is common, and there exists a false perception that cannabis, and other substances, may help control symptoms (Casper & Joukov, 2018).
This concept seeks to contradict previous ideas and suggests that the causal relationship between cannabis and schizophrenia is overestimated, as bidirectionality has not been taken into consideration. The bidirectional approach further suggests that prodromal adolescents are also more likely to experiment with drugs, including cannabis (Power est al, 2014).
Included in this bidirectional argument Power, et al (2014) noted the strong possibility of a “shared genetic aetiology” where cannabis and genetic risk variants interact, going so far as to question if cannabis use itself is heritable, or if some of the same genes that increase the risk of schizophrenia development also increase the likelihood of cannabis use. Despite what evidence exists against reverse causation (i.e. neurodevelopmental changes), a true causal link between cannabis and schizophrenia remains controversial, as findings can “always be hampered by confounding variables and/or reverse causality bias” (Vaucher et al, 2018). Reverse causation, while acknowledged as a possibility, is often dismissed in favor of preventive medicine and programs. While a definitive, causal link, between cannabis and schizophrenia, cannot be established, it remains important to stay cautious, regardless of how much a risk factor cannabis truly is. When considering this link, it is important to remember that schizophrenia has the potential to be gravely disabling, and so, disregarding significant risk seems unethical (Marconi et al, 2016).
Conclusion and Discussion
Where there has been a large push for cannabis legalization there has also been push back from physicians, who are wary of the potential risks cannabis allows for. However, a cannabis economy remains consistently alluring “…and legalizing cannabis has some potential benefits, such as increases government revenue, decreasing violence, and providing relief for certain medical conditions” (Casper & Joukov, 2018). Nevertheless, these benefits need to be weighed again possible negative outcomes, like the possibility of increased rates of schizophrenia, which is not only a costly disease, managed primarily by Medicaid, but it is also a disabling condition which has the potential to devastate persons and their families.While no true conclusion is available, the science suggests that adolescent cannabis use has very real neurodevelopmental consequences for all people younger than 18.
Chronic cannabis exposure can lead to damage to the frontal cortex, reduced grey matter, the over-pruning of synapses, GABAergic neurotransmission hypofunction, and dopamine dysregulation, all of which can be seen in those who have already developed schizophrenia, allowing researchers to tentatively call cannabis a risk factor for the development of schizophrenia or schizoaffective disorder (Renard et al, 2018; see also Kumar et al, 2012). Adolescents who are at genetic risk (i.e. parental/familial psychosis) are at an even higher risk and these neurodevelopmental changes have more serious consequences for this subgroup, including the possibility of treatment-resistant early-onset schizophrenia (Kumar et al, 2012). Other possibilities do exist, as people with schizophrenia are more likely to use cannabis (Power et al, 2014). Regardless, it is unlikely that adolescents aged fifteen or younger are self-medicating, even if they have a high probability of developing schizophrenia.
Despite the disagreement, researchers continue to explore the link between cannabis and schizophrenia. Yet, the best option is to remain cautious, and discourage youth, especially if they have genetic or familial history of schizophrenia, or if they are displaying prodromal symptoms like occasional voice-hearing or new social withdrawal, from experimenting with cannabis. Where legality is concerned, stricter regulations should be instituted to prevent people with schizophrenia from accessing cannabis, but most importantly, increasing the required age to purchase past 21 as the brain is still considered adolescent until nearly 28.
Unfortunately, for those schizophrenics who want it, it will always be possible to attain cannabis from illegal sources, this is the same for adolescents under the age requirement. Cannabis is particularly difficult drug to contend with, given its main stream usage, generally optimistic perception, and increasing legality, which puts preventable programs in a tough spot.
How do you prevent something that is, theoretically, impossible to contain? Ideas like requiring a psychological evaluation for the legal purchase of cannabis, creating a database of those already diagnosed, seem like a violation of privacy, given the existing stigmatization and discrimination surrounding schizophrenia. A solution to the problem is nearly as difficult to come to as the understanding of the problem in the first place. Which is why the question of cannabis and schizophrenia remains so controversial. The goal, however, is always to prevent disability and improve quality of life, so even if researchers continue to disagree, a more mainstream, well established, and truthful look at cannabis and the risk factor it poses to the developing brain, could save many young people from a psychotic future.
References
Arseneault, L., Cannon, M., Poulton, R., Murray, R., Caspi, A., & Moffitt, T.E. (2002). Cannabis Use in Adolescence and Risk for Adult Psychosis: longitudinal prospective study. BMJ 325, 1212-1213. https://doi:10.1136/bmj.325.7374.1212
Caspar, S. & Joukov, A. (2018). The Implications of Marijuana Legalization on the Prevalence and Severity of Schizophrenia. Health Matrix: Journal of Law-Medicine, 28(1), 175-200.
Kumra,S., Robinsion, P., Tambyraja, R., Jensen, D., Schimunel, C., Houri, A., Reis, T., Lim, K. (2012). Parietal Lobe Volume Deficits in Adolescents With Schizophrenia and Adolescents With Cannabis Use Disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 51(2), 171-180. https://doi.org/10.1016/j.jaac.2011.11.001
Marconi, A., Di Forti, M., Lewis, C., Murray, R., & Vassos, E. (2016). Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. Schizophrenia Bulletin, 42(5), 1262–1269. https://doi.org/10.1093/schbul/sbw003
Mustonen, A., Niemelä, S., Nordström, T., Murray, G., Mäki, P., Jääskeläinen, E., & Miettunen, J. (2018). Adolescent Cannabis Use, Baseline Prodromal Symptoms and the Risk of Psychosis. The British Journal of Psychiatry, 212, 227–233. https://doi.org/10.1192/bjp.2017.52
Power, R., Verweij, K.J.H, Zuhair, M., Montgomery, G.W., Henders, A.K., Heath, A.C., Madden, P.A.F, Medland, S.E., Wray, N.R., & Martin, M.G. (2014). Genetic Predisposition to Schizophrenia Associated with Increased Use of Cannabis.[1]
Renard, J., Rushlow, W.J., Laviolette, S.R. (2018). Effects of Adolescent THC Exposure on the Prefrontal GABAergic System: Implications for Schizophrenia-Related Psychopathology. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00281
Vaucher, J., Keating, B.J., Lasserre, A.M., Gan, W., Lyall, D.M., Ward, J., Smith, D.J., Pell, J.P., Sattar, N., Paré, G., &, Holmes, M.V. (2018). Cannabis Use and Risk of Schizophrenia: a Mendelian randomization study. Molecular Psychiatry, 22, 1287-1292. https://doi.org/10.1038/mp.2016.252
[1] No doi available
