The Complex Connection between Cannabis and Schizophrenia

Michael T. Compton, Marc Manseau

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128051832
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

The Complex Connection between Cannabis and Schizophrenia provides an in-depth overview of the current state of research into the role that cannabis plays in schizophrenia, covering both the pathophysiological and the pharmacological implications. It addresses the epidemiology of cannabis use and the risks associated with its use, the biological aspects of the drug, its effects on the brain and the pharmacological possibilities of using cannabidiol to treat schizophrenia.

It is the only book on the market devoted exclusively to examining the links between this very commonly used (and misused) drug and a specific set of devastating psychiatric illnesses, providing a comprehensive guide to our current understandings of this relationship.

Marijuana is the most commonly used illicit drug globally, and is becoming increasingly decriminalized and even legalized worldwide. Among the numerous mental-health concerns related to the drug, there is mounting evidence of an intricate link between cannabis use and schizophrenia and related psychotic disorders. At the same time, there is promising evidence to suggest that cannabidiol, one of the many compounds found in cannabis that activates the brain's cannabinoid receptors, could prove to be an effective antipsychotic to treat schizophrenia.

• Synthesizes existing knowledge about the confusing, but crucial, relationship between cannabis use and schizophrenia symptoms
• Provides a comprehensive overview of the neurobiological mechanisms of cannabis use and its effects on the brain, including an exploration of the endocannabinoid system
• Examines the promising evidence suggesting cannabidiol as an effective antipsychotic treatment for schizophrenia
• Aids readers studying the neurobiological underpinning of cannabis addiction and psychosis in determining directions for their own future research

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

Abstract

The Cannabis sativa plant contains many cannabinoids, including the principal psychoactive component, Δ⁹-terahydrocannabinol (THC), as well as cannabidiol (CBD). Cannabis is the most commonly used illicit drug globally. In recent years, its possession is being increasingly decriminalized and even legalized for both medical and recreational use in the United States 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. At the same time, there is early, promising evidence to suggest that CBD may be an effective and well-tolerated antipsychotic agent. This book provides an in-depth overview of the current state of research on the role that cannabis plays in psychosis and psychotic disorders, comprehensively covering a wide range of topics, from epidemiology to pathophysiology to treatment implications.

Keywords

Cannabis; Marijuana; Psychosis; Psychotic disorders; Schizophrenia

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).

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 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 psychosis-spectrum 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 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...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Chapter 1: An Introduction to the Complex Connection Between Cannabis and Schizophrenia
• Chapter 2: The Epidemiology of Cannabis Use in the United States
• Chapter 3: Cannabinoids and the Brain: The Effects of Endogenous and Exogenous Cannabinoids on Brain Systems and Function
• Chapter 4: Psychotomimetic and Cognitive Effects of Δ9-Tetrahydrocannabinol in Laboratory Settings
• Chapter 5: Psychotomimetic and Cognitive Effects of Cannabis Use in the General Population
• Chapter 6: The Association Between Cannabis Use and Schizotypy
• Chapter 7: Effects of Cannabis Use in Those at Ultra-High Risk for Psychosis
• Chapter 8: Cannabis-Induced Psychotic Disorders
• Chapter 9: Synthetic Cannabinoids and Synthetic Cannabinoid-Induced Psychotic Disorders
• Chapter 10: Cannabis Use as an Independent Risk Factor for, or Component Cause of, Schizophrenia and Related Psychotic Disorders
• Chapter 11: Cannabis Use as a Determinant of Earlier Age at Onset of Schizophrenia and Related Psychotic Disorders
• Chapter 12: The Prevalence and Effects of Cannabis Use Among Individuals With Schizophrenia and Related Psychotic Disorders
• Chapter 13: The Treatment of Cannabis Use Disorder Among Individuals With a Psychotic Disorder
• Chapter 14: Cannabidiol as a Potential Novel Therapeutic Agent for Psychotic Disorders
• Index