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An Introduction to the Complex Connection Between Cannabis and Schizophrenia
Chapter 1
An Introduction to the Complex Connection Between Cannabis and Schizophrenia Marc W. Manseau*, Michael T. Compton† *New York University School of Medicine, New York, NY, United States † Columbia University College of Physicians and Surgeons, New York, NY, United States
BACKGROUND AND HISTORY The Cannabis sativa plant has two main subspecies, sativa and indica, and contains more than 400 compounds, with approximately 80 of these classified as cannabinoids (Borgelt, Franson, Nussbaum, & Wang, 2013). People most often smoke parts of the plant to obtain psychoactive effects of the drug, but it can also be vaporized and inhaled or ingested orally in multiple forms (oil infusions, edible products, etc.). Having been cultivated for thousands of years, there are hundreds of different strains of Cannabis sativa (hereafter referred to as “cannabis”), making for a wide breadth of cannabinoid blends with corresponding subtly varying psychoactive effects when ingested. However, the principal cannabinoids thought to be responsible for psychoactive effects are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for most psychoactive effects from cannabis use, whereas CBD does not produce intoxication but may counteract some effects of THC. Many differences between strains of cannabis are likely explained by variation in THC and CBD content, as well as the ratio between the two cannabinoids, and there is evidence that the THC-to-CBD ratio has been increasing in cannabis strains over the past few decades (ElSohly et al., 2016). Cannabis is the most widely used illicit drug in the world, with about 13.1 million people (prevalence rate = 0.19%) globally meeting criteria for cannabis dependence in 2010, and with prevalence rates being highest among young adult males in higher income countries (Degenhardt et al., 2013). Furthermore, cannabis use rates have recently been stable on average worldwide, with about 3.8% of people estimated to have used cannabis in 2014, but use has generally been rising in the Americas over the past decade, following a long period of decline since the 1970s (United Nations Office on Drugs and Crime, 2016). The Complex Connection between Cannabis and Schizophrenia. http://dx.doi.org/10.1016/B978-0-12-804791-0.00001-X © 2018 Elsevier Inc. All rights reserved.
1
2 The Complex Connection between Cannabis and Schizophrenia
While it is not entirely clear what has contributed to recent increasing cannabis use in some global regions, changing social norms and legal status around cannabis use may be at least partially implicated. Since the 1961 United Nations' Single Convention on Narcotic Drugs (United Nations, 1962), cannabis cultivation, sale, and use has been illegal in most countries. In fact, suppressing cannabis production and distribution has been a major priority for the Drug Enforcement Administration's (DEA) efforts in the “War on Drugs” within the United States (US) (US Drug Enforcement Administration, 2017). However, more recently, many countries and states of the US have moved to decriminalize (reduce or remove criminal penalties) or legalize (remove criminal penalties and establish a system for taxation and regulation of production and distribution) recreational cannabis, and/or approve its legal use for medical purposes. Specifically, as of 2017, at least 40 countries and eight states of the US as well as the District of Columbia (DC) have removed some legal penalties for recreational cannabis use (covering more than 20% of the US population), while 29 states of the US and DC have allowed some form of medical cannabis use (Carnevale, Kagan, Murphy, & Esrick, 2017). However, many still strongly oppose legal cannabis access and use, and governments continue to restrict cannabis production and distribution, creating enormous controversy and ambivalence. For instance, cannabis remains classified as a schedule I substance (high potential for abuse; no currently accepted medical treatment use) by the Food and Drug Administration (FDA) and DEA on the federal level within the US. In 2013, the US Department of Justice under the Obama Administration decided not to pursue legal action against physicians “prescribing” medical cannabis in states that allow it, a decision that could be reversed under a new Presidential Administration. Presumably, recent shifts in legal regulation have been driven at least in part by changing public opinion toward cannabis use. Indeed, there is evidence within the US that attitudes are increasingly favoring arguments about the potential societal benefits of cannabis legalization over messages about public health risks (McGinty, Niederdeppe, Heley, & Barry, 2017). One reason for shifting attitudes about cannabis use could be related to changing perceptions about the availability of cannabis or risk of its use. For instance, there is evidence that state-level medical cannabis laws have led to perceptions of increased availability, and in turn to higher use, of cannabis among adults in the US (Martins et al., 2016). It is likely that increasing legalization efforts affect public perceptions and vice versa, creating political and social dynamics that support removing restrictions to cannabis access and increase use rates within many societies. However, there is strong reason for concern that cannabis use is not without substantial risks. Putting aside the physical health risks of inhaling cannabis smoke, there is evidence that cannabis exposure carries mental health risks, especially when used by youth or used heavily. For instance, when used regularly and/or in adolescence, cannabis use has been convincingly linked to cognitive and motivational problems, lower educational attainment, unemployment, use of more dangerous substances, and a range of
Introduction to Cannabis and Schizophrenia Chapter | 1 3
psychiatric symptoms. In addition, for those who have already developed psychiatric disorders (e.g., mood, anxiety, or psychotic disorders), cannabis use may be associated with poorer engagement in care, worse symptom control, and lower psychosocial functioning (Agosti, Nunes, & Levin, 2002; Fergusson, Boden, & Horwood, 2015; Wilkinson, Stefanovics, & Rosenheck, 2015). With this said, it must be recognized that many adults use cannabis sporadically or even regularly without significant detriment to their mental health.
CANNABIS AND PSYCHOSIS What about the topic of this book, the connection between cannabis use and psychosis? The relationship is indeed complex, and with a long and storied history. The cult classic film from the late 1930s, “Reefer Madness,” dramatized (and spurred on) longstanding public fear about the connection between cannabis use and psychosis. While controversial, such fear around this perceived connection may have contributed to increasing efforts to restrict legal access to cannabis (Barcott, 2015). Partially driven by a recognition that THC administration can transiently cause many symptoms of schizophrenia (i.e., positive, negative, and cognitive symptoms), the scientific literature over the past half-century has paid increasing attention to the role of cannabis use in the development of psychotic disorders. Chapters 10 and 11 address, respectively, two core aspects of the relationship between cannabis use and psychosis: whether cannabis use causes psychosisspectrum disorders and whether it leads to an earlier age at onset of psychosis (AOP). Specifically, Chapter 10 discusses the literature on cannabis use as an independent, causal risk factor in the development of schizophrenia and related psychotic disorders. While many studies have found a consistent and robust association between cannabis use and the development of psychotic disorders, the exact nature of this relationship has been controversial, with competing arguments for direct causation, reverse causation, and confounding (Manseau & Goff, 2015). Gilman and colleagues carefully and systematically review the literature on this topic, making a strong argument that cannabis use is an important component cause in the development of psychotic disorders, particularly among those who are biologically vulnerable to psychosis. While it is impossible to definitively demonstrate a causal relationship between cannabis use and schizophrenia in a controlled experiment, the authors demonstrate that the following causal criteria have been established in the literature: a strong and consistent association between cannabis use and psychosis; cannabis use commonly precedes the development of psychosis; there appears to be a dose-response relationship; confounding factors can be largely ruled out as entirely explaining the relationship; and there is a plausible biological mechanism for the relationship between cannabis use and the development of psychotic disorders. Chapter 11 covers the relationship between cannabis use and AOP. Similar to the discussion on cannabis use as an independent risk factor in the development
4 The Complex Connection between Cannabis and Schizophrenia
of psychotic disorders, the authors review the substantial literature showing a replicated, significant association between cannabis use and a younger AOP. The authors argue that cannabis use likely causes an earlier AOP by demonstrating that cannabis use often precedes the onset of psychotic symptoms (and indeed often prodromal symptoms), that there is a dose effect of cannabis use on AOP, and that while certain vulnerability factors do exist that predispose individuals to an earlier AOP in the setting of cannabis use, none of them likely completely confound the relationship between cannabis use and AOP. Aside from the discussion of the causation of schizophrenia and related disorders, cannabis is the most commonly used illicit substance among individuals with schizophrenia, and there is substantial evidence that its use in this population is associated with worsening psychotic symptoms, illness relapse, and decreased functioning over time (Clausen et al., 2014; Radhakrishnan, Wilkinson, & D'Souza, 2014). Chapter 12 addresses this very matter. That chapter describes the prevalence of cannabis use and cannabis use disorders among those with psychotic disorders, and explores the effects of cannabis use on the course and outcomes of psychosis-spectrum illnesses.
BRIEF OVERVIEW OF THE BOOK The remainder of the chapters in this book thoroughly explore various aspects of the relationship between cannabis and psychosis, from epidemiology to biological mechanisms to treatment, thereby providing important context to the core issues of causation and effects on the course of these devastating illnesses. Compton and Han address the epidemiology of cannabis use in the US in Chapter 2. This chapter is unique in that it reports the results of an original analysis of data from the 2002–2014 National Surveys on Drug Use and Health. It shows that cannabis use and use disorder rates have actually been decreasing recently among youth in the US, but increasing among adults. The trends, which will be interesting to continue to follow, have important public health implications related to the effects of tobacco use control efforts and perceived risk of cannabis on cannabis use rates. Chapter 3 reviews the biological effects of cannabinoids on the brain. The chapter includes an in-depth discussion of the natural endocannabinoid system, which has fascinating and important implications for psychosis, both in the context of cannabis use and entirely on its own (Muller-Vahl & Emrich, 2008; Manseau & Goff, 2015). The chapter also covers the biology of addiction as it applies to cannabis use, and the effects of cannabinoids on a wide array of brain functions. Chapter 4 provides a comprehensive overview of the effects of THC in the laboratory setting, by systematically reviewing the large literature on the psychoactive and cognitive effects of THC and related cannabinoids in human laboratory studies. Chapter 5 reviews the psychotomimetic and cognitive effects of cannabis use in the general (i.e., nonclinical) population. While cannabis use is an important
Introduction to Cannabis and Schizophrenia Chapter | 1 5
risk factor for the development of schizophrenia, the fact remains that a small proportion of people who use cannabis develop a full-threshold psychotic disorder. Solowij compiles evidence supporting the notion that cannabis use may be linked to transient and/or subclinical psychotic-like symptoms, cognitive deficits, and related functional impairment in a portion of the population. Chapter 6 provides an overview of the literature connecting cannabis use to schizotypy, thereby providing further evidence for the relationship between cannabis use and psychotic-like outcomes in the wider population of people not diagnosed with psychotic disorders. The discussion of the impact of cannabis use within populations at mounting risk for psychosis progresses further with Chapter 7, which addresses the effects of cannabis use in those at ultra-high risk (UHR) for psychosis. In this chapter, the authors review the effects of cannabis use on the illness course and outcomes of those at UHR for psychosis, including research on whether and how cannabis use influences the likelihood of progression to a full-threshold psychotic disorder. Chapter 8 describes the scientific literature on cannabis-induced psychotic disorders, providing further evidence that cannabis use can cause full-threshold psychotic syndromes, even if only transiently in some users. In this chapter, the author provides a broad overview of this topic, from epidemiology to diagnosis to management approaches. Chapter 9 addresses a new class of cannabinoid compounds, synthetic cannabinoids (SCs). In this chapter, the authors detail the emergence of SC use, which some have called an epidemic, and describe how and why SC use may lead to more immediate and serious psychotic symptoms than natural cannabis use. Chapters 10–12—on cannabis use as a component cause, a risk factor for earlier onset, and a poor prognostic indicator in the context of schizophrenia and related psychotic disorders—have already been introduced above. Chapter 13 addresses treatment approaches to cannabis use disorder among individuals with psychotic disorders. In this chapter, the authors discuss principles of pharmacological and psychosocial management of patients with comorbid psychotic and cannabis use disorders. However, recognizing the paucity of effective, evidence-based approaches to this all-too-common and impairing combination of disorders, they also discuss the critical research necessary for progress in the field. Finally, Chapter 14 discusses the exciting potential of CBD as a novel treatment for schizophrenia and related disorders. While recognizing that conclusions in the field remain preliminary, they delineate both animal and human studies that support the possible use of CBD as an effective, safe, and welltolerated antipsychotic compound. They also discuss legal barriers to further research on cannabinoids in general and CBD specifically.
CONCLUSIONS Cannabis sativa is the most commonly used illicit drug globally. In recent years, its possession is being increasingly decriminalized and even legalized
6 The Complex Connection between Cannabis and Schizophrenia
for both medical and recreational use in the US and worldwide. Among the mental health concerns related to the drug, there is mounting evidence of an intricate link between cannabis use and schizophrenia and related psychotic disorders. Cannabis use is more prevalent among people with schizophrenia than in the general population; young people who use cannabis are twice as likely to develop schizophrenia; premorbid cannabis use appears to hasten the onset of psychosis among those who develop a psychotic disorder; and cannabis use can induce schizophrenia-like symptoms in otherwise healthy individuals. At the same time, there is promising evidence to suggest that CBD, one of the many cannabinoid compounds found in the Cannabis sativa plant, could prove to be an effective antipsychotic to treat schizophrenia. This book provides an in-depth overview of the current state of knowledge on the role that cannabis plays in psychotic symptoms, psychotic disorders, and schizophrenia, covering both pathophysiological and pharmacological implications. It addresses wide-ranging topics including the epidemiology of cannabis use in the US, the risks associated with its use, the biological aspects of the drug and its effects on the brain, management of cannabis use disorder, and the pharmacological possibilities of using CBD to treat psychotic disorders.
Key Chapter Points ●
●
●
The Cannabis satvia plant contains many cannabinoids, including the principal psychoactive component, THC, as well as CBD. Cannabis is the most widely used illicit drug in the world, with over 13 million people globally meeting the criteria for cannabis dependence recently, and with prevalence rates being the highest among young adult males in higher income countries. Cannabis use rates have recently been stable on average worldwide, but use has generally been rising in the Americas over the past decade. There is mounting evidence of an intricate link between cannabis use and schizophrenia and related psychotic disorders. Cannabis use is more prevalent among people with schizophrenia than in the general population; young people who use cannabis are twice as likely to develop schizophrenia; premorbid cannabis use appears to hasten the onset of psychosis among those who develop a psychotic disorder; and cannabis use can induce schizophrenia-like symptoms in otherwise healthy individuals.
REFERENCES Agosti, V., Nunes, E., & Levin, F. (2002). Rates of psychiatric comorbidity among U.S. residents with lifetime cannabis dependence. American Journal of Drug and Alcohol Abuse, 28, 643–652. Barcott, B. (2015). Weed the people: The future of legal Marijuana in America. New York, NY: Time. Borgelt, L. M., Franson, K. L., Nussbaum, A. M., & Wang, G. S. (2013). The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy, 33, 195–209.
Introduction to Cannabis and Schizophrenia Chapter | 1 7 Carnevale, J. T., Kagan, R., Murphy, P. J., & Esrick, J. (2017). A practical framework for regulating for-profit recreational marijuana in US States: Lessons from Colorado and Washington. The International Journal on Drug Policy, 1–15. EPub. Clausen, L., Hjorthoj, C. R., Thorup, A., Jeppesen, P., Petersen, L., Bertelsen, M., et al. (2014). Change in cannabis use, clinical symptoms and social functioning among patients with first episode psychosis: a 5-year follow-up study of patients in the OPUS trial. Psychological Medicine, 44, 117–126. Degenhardt, L., Ferrari, A. J., Calabria, B., Hall, W. D., Norman, R. E., McGrath, J., et al. (2013). The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study. PLoS ONE, 8, e76635. ElSohly, M. A., Mehmedic, Z., Foster, S., Gon, C., Chandra, S., & Church, J. C. (2016). Changes in cannabis potency over the last 2 decades (1995-2014): Analysis of current data in the United States. Biological Psychiatry, 79, 613–619. Fergusson, D. M., Boden, J. M., & Horwood, L. J. (2015). Psychosocial sequelae of cannabis use and implications for policy: Findings from the Christchurch Health and Development Study. Social Psychiatry and Psychiatric Epidemiology, 50, 1317–1326. Manseau, M. W., & Goff, D. C. (2015). Cannabinoids and schizophrenia: Risks and therapeutic potential. Neurotherapeutics, 12, 816–824. Martins, S. S., Mauro, C. M., Santaella-Tenorio, J., Kim, J. H., Cerda, M., Keyes, K. M., et al. (2016). State-level medical marijuana laws, marijuana use and perceived availability of marijuana among the general U.S. population. Drug and Alcohol Dependence, 169, 26–32. McGinty, E. E., Niederdeppe, J., Heley, K., & Barry, C. L. (2017). Public perceptions of arguments supporting and opposing recreational marijuana legalization. Preventive Medicine, 99, 80–86. Muller-Vahl, K. R., & Emrich, H. M. (2008). Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia. Expert Review of Neurotherapeutics, 8, 1037–1048. Radhakrishnan, R., Wilkinson, S. T., & D'Souza, D. C. (2014). Gone to pot—a review of the association between cannabis and psychosis. Frontiers in Psychiatry, 5, 54. United Nations. (1962). Single convention on narcotic drugs, 1961. New York, NY: United Nations. United Nations Office on Drugs and Crime. (2016). World Dug Report 2016, Chapter 1: Cannabis. Vienna: United Nations. US Drug Enforcement Administration. (2017). Domestic cannabis eradication/suppression program. Washington, DC: US Drug Enforcement Administration. Available at: https://www.dea. gov/ops/cannabis.shtml Accessed 18.04.17. Wilkinson, S. T., Stefanovics, E., & Rosenheck, R. (2015). Marijuana use is associated with worse outcomes in symptom severity and violent behavior in patients with posttraumatic stress disorder. Journal of Clinical Psychiatry, 76, 1174–1180.
An Introduction to the Complex Connection Between Cannabis and Schizophrenia Marc W. Manseau*, Michael T. Compton† *New York University School of Medicine, New York, NY, United States † Columbia University College of Physicians and Surgeons, New York, NY, United States
BACKGROUND AND HISTORY The Cannabis sativa plant has two main subspecies, sativa and indica, and contains more than 400 compounds, with approximately 80 of these classified as cannabinoids (Borgelt, Franson, Nussbaum, & Wang, 2013). People most often smoke parts of the plant to obtain psychoactive effects of the drug, but it can also be vaporized and inhaled or ingested orally in multiple forms (oil infusions, edible products, etc.). Having been cultivated for thousands of years, there are hundreds of different strains of Cannabis sativa (hereafter referred to as “cannabis”), making for a wide breadth of cannabinoid blends with corresponding subtly varying psychoactive effects when ingested. However, the principal cannabinoids thought to be responsible for psychoactive effects are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is responsible for most psychoactive effects from cannabis use, whereas CBD does not produce intoxication but may counteract some effects of THC. Many differences between strains of cannabis are likely explained by variation in THC and CBD content, as well as the ratio between the two cannabinoids, and there is evidence that the THC-to-CBD ratio has been increasing in cannabis strains over the past few decades (ElSohly et al., 2016). Cannabis is the most widely used illicit drug in the world, with about 13.1 million people (prevalence rate = 0.19%) globally meeting criteria for cannabis dependence in 2010, and with prevalence rates being highest among young adult males in higher income countries (Degenhardt et al., 2013). Furthermore, cannabis use rates have recently been stable on average worldwide, with about 3.8% of people estimated to have used cannabis in 2014, but use has generally been rising in the Americas over the past decade, following a long period of decline since the 1970s (United Nations Office on Drugs and Crime, 2016). The Complex Connection between Cannabis and Schizophrenia. http://dx.doi.org/10.1016/B978-0-12-804791-0.00001-X © 2018 Elsevier Inc. All rights reserved.
1
2 The Complex Connection between Cannabis and Schizophrenia
While it is not entirely clear what has contributed to recent increasing cannabis use in some global regions, changing social norms and legal status around cannabis use may be at least partially implicated. Since the 1961 United Nations' Single Convention on Narcotic Drugs (United Nations, 1962), cannabis cultivation, sale, and use has been illegal in most countries. In fact, suppressing cannabis production and distribution has been a major priority for the Drug Enforcement Administration's (DEA) efforts in the “War on Drugs” within the United States (US) (US Drug Enforcement Administration, 2017). However, more recently, many countries and states of the US have moved to decriminalize (reduce or remove criminal penalties) or legalize (remove criminal penalties and establish a system for taxation and regulation of production and distribution) recreational cannabis, and/or approve its legal use for medical purposes. Specifically, as of 2017, at least 40 countries and eight states of the US as well as the District of Columbia (DC) have removed some legal penalties for recreational cannabis use (covering more than 20% of the US population), while 29 states of the US and DC have allowed some form of medical cannabis use (Carnevale, Kagan, Murphy, & Esrick, 2017). However, many still strongly oppose legal cannabis access and use, and governments continue to restrict cannabis production and distribution, creating enormous controversy and ambivalence. For instance, cannabis remains classified as a schedule I substance (high potential for abuse; no currently accepted medical treatment use) by the Food and Drug Administration (FDA) and DEA on the federal level within the US. In 2013, the US Department of Justice under the Obama Administration decided not to pursue legal action against physicians “prescribing” medical cannabis in states that allow it, a decision that could be reversed under a new Presidential Administration. Presumably, recent shifts in legal regulation have been driven at least in part by changing public opinion toward cannabis use. Indeed, there is evidence within the US that attitudes are increasingly favoring arguments about the potential societal benefits of cannabis legalization over messages about public health risks (McGinty, Niederdeppe, Heley, & Barry, 2017). One reason for shifting attitudes about cannabis use could be related to changing perceptions about the availability of cannabis or risk of its use. For instance, there is evidence that state-level medical cannabis laws have led to perceptions of increased availability, and in turn to higher use, of cannabis among adults in the US (Martins et al., 2016). It is likely that increasing legalization efforts affect public perceptions and vice versa, creating political and social dynamics that support removing restrictions to cannabis access and increase use rates within many societies. However, there is strong reason for concern that cannabis use is not without substantial risks. Putting aside the physical health risks of inhaling cannabis smoke, there is evidence that cannabis exposure carries mental health risks, especially when used by youth or used heavily. For instance, when used regularly and/or in adolescence, cannabis use has been convincingly linked to cognitive and motivational problems, lower educational attainment, unemployment, use of more dangerous substances, and a range of
Introduction to Cannabis and Schizophrenia Chapter | 1 3
psychiatric symptoms. In addition, for those who have already developed psychiatric disorders (e.g., mood, anxiety, or psychotic disorders), cannabis use may be associated with poorer engagement in care, worse symptom control, and lower psychosocial functioning (Agosti, Nunes, & Levin, 2002; Fergusson, Boden, & Horwood, 2015; Wilkinson, Stefanovics, & Rosenheck, 2015). With this said, it must be recognized that many adults use cannabis sporadically or even regularly without significant detriment to their mental health.
CANNABIS AND PSYCHOSIS What about the topic of this book, the connection between cannabis use and psychosis? The relationship is indeed complex, and with a long and storied history. The cult classic film from the late 1930s, “Reefer Madness,” dramatized (and spurred on) longstanding public fear about the connection between cannabis use and psychosis. While controversial, such fear around this perceived connection may have contributed to increasing efforts to restrict legal access to cannabis (Barcott, 2015). Partially driven by a recognition that THC administration can transiently cause many symptoms of schizophrenia (i.e., positive, negative, and cognitive symptoms), the scientific literature over the past half-century has paid increasing attention to the role of cannabis use in the development of psychotic disorders. Chapters 10 and 11 address, respectively, two core aspects of the relationship between cannabis use and psychosis: whether cannabis use causes psychosisspectrum disorders and whether it leads to an earlier age at onset of psychosis (AOP). Specifically, Chapter 10 discusses the literature on cannabis use as an independent, causal risk factor in the development of schizophrenia and related psychotic disorders. While many studies have found a consistent and robust association between cannabis use and the development of psychotic disorders, the exact nature of this relationship has been controversial, with competing arguments for direct causation, reverse causation, and confounding (Manseau & Goff, 2015). Gilman and colleagues carefully and systematically review the literature on this topic, making a strong argument that cannabis use is an important component cause in the development of psychotic disorders, particularly among those who are biologically vulnerable to psychosis. While it is impossible to definitively demonstrate a causal relationship between cannabis use and schizophrenia in a controlled experiment, the authors demonstrate that the following causal criteria have been established in the literature: a strong and consistent association between cannabis use and psychosis; cannabis use commonly precedes the development of psychosis; there appears to be a dose-response relationship; confounding factors can be largely ruled out as entirely explaining the relationship; and there is a plausible biological mechanism for the relationship between cannabis use and the development of psychotic disorders. Chapter 11 covers the relationship between cannabis use and AOP. Similar to the discussion on cannabis use as an independent risk factor in the development
4 The Complex Connection between Cannabis and Schizophrenia
of psychotic disorders, the authors review the substantial literature showing a replicated, significant association between cannabis use and a younger AOP. The authors argue that cannabis use likely causes an earlier AOP by demonstrating that cannabis use often precedes the onset of psychotic symptoms (and indeed often prodromal symptoms), that there is a dose effect of cannabis use on AOP, and that while certain vulnerability factors do exist that predispose individuals to an earlier AOP in the setting of cannabis use, none of them likely completely confound the relationship between cannabis use and AOP. Aside from the discussion of the causation of schizophrenia and related disorders, cannabis is the most commonly used illicit substance among individuals with schizophrenia, and there is substantial evidence that its use in this population is associated with worsening psychotic symptoms, illness relapse, and decreased functioning over time (Clausen et al., 2014; Radhakrishnan, Wilkinson, & D'Souza, 2014). Chapter 12 addresses this very matter. That chapter describes the prevalence of cannabis use and cannabis use disorders among those with psychotic disorders, and explores the effects of cannabis use on the course and outcomes of psychosis-spectrum illnesses.
BRIEF OVERVIEW OF THE BOOK The remainder of the chapters in this book thoroughly explore various aspects of the relationship between cannabis and psychosis, from epidemiology to biological mechanisms to treatment, thereby providing important context to the core issues of causation and effects on the course of these devastating illnesses. Compton and Han address the epidemiology of cannabis use in the US in Chapter 2. This chapter is unique in that it reports the results of an original analysis of data from the 2002–2014 National Surveys on Drug Use and Health. It shows that cannabis use and use disorder rates have actually been decreasing recently among youth in the US, but increasing among adults. The trends, which will be interesting to continue to follow, have important public health implications related to the effects of tobacco use control efforts and perceived risk of cannabis on cannabis use rates. Chapter 3 reviews the biological effects of cannabinoids on the brain. The chapter includes an in-depth discussion of the natural endocannabinoid system, which has fascinating and important implications for psychosis, both in the context of cannabis use and entirely on its own (Muller-Vahl & Emrich, 2008; Manseau & Goff, 2015). The chapter also covers the biology of addiction as it applies to cannabis use, and the effects of cannabinoids on a wide array of brain functions. Chapter 4 provides a comprehensive overview of the effects of THC in the laboratory setting, by systematically reviewing the large literature on the psychoactive and cognitive effects of THC and related cannabinoids in human laboratory studies. Chapter 5 reviews the psychotomimetic and cognitive effects of cannabis use in the general (i.e., nonclinical) population. While cannabis use is an important
Introduction to Cannabis and Schizophrenia Chapter | 1 5
risk factor for the development of schizophrenia, the fact remains that a small proportion of people who use cannabis develop a full-threshold psychotic disorder. Solowij compiles evidence supporting the notion that cannabis use may be linked to transient and/or subclinical psychotic-like symptoms, cognitive deficits, and related functional impairment in a portion of the population. Chapter 6 provides an overview of the literature connecting cannabis use to schizotypy, thereby providing further evidence for the relationship between cannabis use and psychotic-like outcomes in the wider population of people not diagnosed with psychotic disorders. The discussion of the impact of cannabis use within populations at mounting risk for psychosis progresses further with Chapter 7, which addresses the effects of cannabis use in those at ultra-high risk (UHR) for psychosis. In this chapter, the authors review the effects of cannabis use on the illness course and outcomes of those at UHR for psychosis, including research on whether and how cannabis use influences the likelihood of progression to a full-threshold psychotic disorder. Chapter 8 describes the scientific literature on cannabis-induced psychotic disorders, providing further evidence that cannabis use can cause full-threshold psychotic syndromes, even if only transiently in some users. In this chapter, the author provides a broad overview of this topic, from epidemiology to diagnosis to management approaches. Chapter 9 addresses a new class of cannabinoid compounds, synthetic cannabinoids (SCs). In this chapter, the authors detail the emergence of SC use, which some have called an epidemic, and describe how and why SC use may lead to more immediate and serious psychotic symptoms than natural cannabis use. Chapters 10–12—on cannabis use as a component cause, a risk factor for earlier onset, and a poor prognostic indicator in the context of schizophrenia and related psychotic disorders—have already been introduced above. Chapter 13 addresses treatment approaches to cannabis use disorder among individuals with psychotic disorders. In this chapter, the authors discuss principles of pharmacological and psychosocial management of patients with comorbid psychotic and cannabis use disorders. However, recognizing the paucity of effective, evidence-based approaches to this all-too-common and impairing combination of disorders, they also discuss the critical research necessary for progress in the field. Finally, Chapter 14 discusses the exciting potential of CBD as a novel treatment for schizophrenia and related disorders. While recognizing that conclusions in the field remain preliminary, they delineate both animal and human studies that support the possible use of CBD as an effective, safe, and welltolerated antipsychotic compound. They also discuss legal barriers to further research on cannabinoids in general and CBD specifically.
CONCLUSIONS Cannabis sativa is the most commonly used illicit drug globally. In recent years, its possession is being increasingly decriminalized and even legalized
6 The Complex Connection between Cannabis and Schizophrenia
for both medical and recreational use in the US and worldwide. Among the mental health concerns related to the drug, there is mounting evidence of an intricate link between cannabis use and schizophrenia and related psychotic disorders. Cannabis use is more prevalent among people with schizophrenia than in the general population; young people who use cannabis are twice as likely to develop schizophrenia; premorbid cannabis use appears to hasten the onset of psychosis among those who develop a psychotic disorder; and cannabis use can induce schizophrenia-like symptoms in otherwise healthy individuals. At the same time, there is promising evidence to suggest that CBD, one of the many cannabinoid compounds found in the Cannabis sativa plant, could prove to be an effective antipsychotic to treat schizophrenia. This book provides an in-depth overview of the current state of knowledge on the role that cannabis plays in psychotic symptoms, psychotic disorders, and schizophrenia, covering both pathophysiological and pharmacological implications. It addresses wide-ranging topics including the epidemiology of cannabis use in the US, the risks associated with its use, the biological aspects of the drug and its effects on the brain, management of cannabis use disorder, and the pharmacological possibilities of using CBD to treat psychotic disorders.
Key Chapter Points ●
●
●
The Cannabis satvia plant contains many cannabinoids, including the principal psychoactive component, THC, as well as CBD. Cannabis is the most widely used illicit drug in the world, with over 13 million people globally meeting the criteria for cannabis dependence recently, and with prevalence rates being the highest among young adult males in higher income countries. Cannabis use rates have recently been stable on average worldwide, but use has generally been rising in the Americas over the past decade. There is mounting evidence of an intricate link between cannabis use and schizophrenia and related psychotic disorders. Cannabis use is more prevalent among people with schizophrenia than in the general population; young people who use cannabis are twice as likely to develop schizophrenia; premorbid cannabis use appears to hasten the onset of psychosis among those who develop a psychotic disorder; and cannabis use can induce schizophrenia-like symptoms in otherwise healthy individuals.
REFERENCES Agosti, V., Nunes, E., & Levin, F. (2002). Rates of psychiatric comorbidity among U.S. residents with lifetime cannabis dependence. American Journal of Drug and Alcohol Abuse, 28, 643–652. Barcott, B. (2015). Weed the people: The future of legal Marijuana in America. New York, NY: Time. Borgelt, L. M., Franson, K. L., Nussbaum, A. M., & Wang, G. S. (2013). The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy, 33, 195–209.
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