Neural Mechanisms Underlying Craving and the Regulation of Craving Hedy Kober and Maggie Mae Mell

9 Neural Mechanisms Underlying Craving and the Regulation of Craving Hedy Kober and Maggie Mae Mell Introduction Craving has long been considered a core feature of addiction (World Health Organization, 1955; O’Brien, Childress, Ehrman, & Robbins, 1998; Volkow et al., 2006; Sinha & Li, 2007; Kavanagh & Connor, 2012). Consistently, over the last two decades, a wealth of research has directly linked drug craving with drug taking and relapse (e.g., Heinz et al., 2005; Crits‐Christoph et al., 2007; Allen, Bade, Hatsukami, & Center, 2008; Shiffman et al., 2013; Kober, 2014 for review). On the basis of the accumulated evidence, the American Psychiatric Association recently added craving – defined as “a strong desire for drugs” – as a diagnostic criterion for substance‐related and addictive disorders in the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM‐5) (APA, 2013). Also defined as a “conscious, reportable urge” (Preston et al., 2009), craving can be experienced for a range of appetitive stimuli, including drugs – but also food, sex, and money. As such, craving is a very common phenomenon. In fact 94% of males and 100% of females report having experienced craving for a specific food at some point in their lives (Osman & Sobal, 2006).1 Nevertheless, in the context of substance use disorders, a failure to regulate craving can lead to dire outcomes, such as harmful drug use. In the next sections we will review craving’s central causal role in drug use and relapse and will consider the brain regions that underlie craving. Then we will review the role of the regulation of craving in reducing craving and in treatment for addiction, as well as the neural mechanisms that give rise to this ability. Craving and Drug Use Although this view has been challenged (e.g., Tiffany, 1990; Perkins, 2009; Wray, Gass, & Tiffany, 2013), the recent inclusion of craving as a diagnostic criterion in DSM‐5 (APA, 2013) cements it as a defining feature of addiction. Indeed, several The Wiley Handbook on the Cognitive Neuroscience of Addiction, First Edition. Edited by Stephen J. Wilson. © 2015 John Wiley & Sons, Ltd. Published 2015 by John Wiley & Sons, Ltd. 196 Hedy Kober and Maggie Mae Mell lines of evidence have linked drug craving to drug taking, across various legal and illegal drugs (e.g., alcohol, nicotine, cocaine). First, in retrospective studies, drug users often cite craving as the reason for continued use and relapse (e.g., Norregaard, Tonnesen, & Petersen, 1993). For example, as early as 1968, a study of cigarette smoker treatment outcomes reported that nearly half of those who had relapsed pointed to cravings as the main culprit (Peterson, Lonergan, Hardinge, & Teel, 1968). Similarly, craving was self‐reported as a cause of relapse by alcohol drinkers (Maisto, O’Farrell, Connors, McKay, & Pelcovits, 1988; Connors, Maisto, & Zywiak, 1998), cocaine users (McKay, Rutherford, Alterman, Cacciola, & Kaplan, 1995), and heroin users (Heather, Stallard, & Tebbutt, 1991). Second, prospective clinical studies have shown that craving is associated with subsequent drug use (e.g., Monti et al., 1990; O’Connor, Gottlieb, Kraus, Segal, & Horwitz, 1991; Weiss et al., 1997; Bordnick & Schmitz, 1998; Robbins & Ehrman, 1998; Allen et al., 2008; Robinson et al., 2011). Moreover, several studies have specifically shown that craving predicts drug taking and/or relapse following abstinence, including in cigarettes (Killen, Fortmann, Newman, & Varady, 1991; Killen, Fortmann, Kraemer, Varady, & Newman, 1992; Norregaard et al., 1993; Doherty, Kinnunen, Militello, & Garvey, 1995; Swan, Ward, & Jack, 1996; Killen & Fortmann, 1997; Etter & Hughes, 2006; Heffner, Lee, Arteaga, & Anthenelli, 2010; Berlin et al., 2013; Sweitzer, Denlinger, & Donny, 2013), cocaine (Weiss et al., 2003; Crits‐Christoph et al., 2007; Rohsenow, Martin, Eaton, & Monti, 2007; Paliwal, Hyman, & Sinha, 2008), methamphetamine (Hartz, Frederick‐Osborne, & Galloway, 2001; Galloway, Singleton, & Methamphetamine Treatment Project Corporate Authors, 2008), alcohol (Miller, Westerberg, Harris, & Tonigan, 1996; Bottlender & Soyka, 2004) and opioid drugs (Tsui, Anderson, Strong, & Stein, 2014). In one of the largest studies of this kind, 691 methamphetamine‐dependent users were assessed every week for eight weeks while undergoing outpatient treatment (Galloway et al., 2008). At each assessment, they reported their cravings for methamphetamine (0‐100 scale), reported any methamphetamine use in the past week, and provided urine samples (to biologically verify abstinence). The authors reported that, at each time point, cravings strongly predicted use by the following time point, such that every 1‐point increase in craving score increased the probability of methamphetamine use during the following week by 0.38%. Another study investigated the relationship between daily craving and cigarette smoking after an attempt to quit (Allen et al., 2008). Over a period of 30 days, female participants provided daily reports of craving and smoking. First, the authors reported that those who relapsed reported significantly higher craving on the quit date than those who abstained the entire period. In a second analysis, craving scores were standardized within participants to more accurately identify temporal variations in craving. Within these standardized scores, craving reports increased on the 4–5 days prior to relapse and peaked on the day of relapse (with very large effect sizes of d > 1.0). Third, ecological momentary assessment (EMA) studies with cigarette, marijuana, cocaine, ecstasy, heroin, and poly‐drug users have elegantly documented links between daily or hourly variations in craving and specific instances of drug use. In EMA studies (which are also referred to as “experience‐sampling”), participants are provided with handheld devices that allow them to report their cravings and urges during daily activities. Participants are typically prompted by random reminders, and also give reports when they experience a temptation to use and/or when they use drugs. EMA Neural Mechanisms Underlying Craving and the Regulation of Craving 197 studies are especially powerful, as they provide real‐life and real‐time data that are dif- ficult to reproduce in laboratory settings and are more reliable than retrospective reports. In one such study, Preston and colleagues used EMA over the course of 25 weeks to investigate the relationship between craving and cocaine use (Preston et al., 2009). They found that during periods of cocaine use, ratings of craving were significantly higher than during periods of (urine‐verified) abstinence. Focusing on the five hours before reports of cocaine use, they found that craving linearly increased until cocaine use. Other EMA studies have also shown that craving increases prior to drug taking (Shiffman, Paty, Gnys, Kassel, & Hickcox, 1996; Catley, O’Connell, & Shiffman, 2000; Hopper et al., 2006; Epstein, Marrone, Heishman, Schmittner, & Preston, 2010; Buckner, Crosby, Silgado, Wonderlich, & Schmidt, 2012; Marhe, Waters, van de Wetering, & Franken, 2013; Moore et al., 2014), correlates with drug taking (Litt, Cooney, & Morse, 2000), and predicts drug taking (Shiffman et al., 1997; Shiffman et al., 2002; O’Connell, Schwartz, Gerkovich, Bott, & Shiffman, 2004; Cooney et al., 2007; Johnson, Barrault, Nadeau, & Swendsen, 2009; Buckner et al., 2012; Holt, Litt, & Cooney, 2012). Although these findings do not establish that craving is necessary or sufficient to explain every instance of drug use and relapse, taken together they do suggest that craving is a powerful predictor and a likely causal factor in drug use and relapse (e.g., Shiffman et al., 1997). Cue‐Induced Craving Several researchers have begun to distinguish between two kinds of cravings: tonic or “background” craving, and phasic or “provoked” craving, also known as cue‐induced craving (Ferguson & Shiffman, 2009). The former type of craving is a slowly changing state; it is often induced by abstinence and fades over time. The latter kind is intense, acute, and episodic, and can be provoked by a wide range of internal and external/ situational cues associated with drug use. In real life, these cues include the sight of people using drugs, contact with people with whom one previously used drugs, and paraphernalia, situations, or locations previously associated with drug use (e.g., one’s favorite bar). In laboratory models of cue‐induced craving, cues include photographs or movies depicting drugs, drug use, and paraphernalia, in‐vivo presentation of such stimuli, imagery‐based or recalled scenarios of drug use, and even olfactory cues (e.g., cigarette smoke). To this date, more than 100 studies have examined this phenomenon in cigarette smokers, alcohol drinkers, opiate, cocaine, and marijuana users. An early meta‐analysis summarizing 41 such studies concluded that the presentation of drug‐ associated cues strongly and reliably induces the subjective experience of craving, along with a range of physiological responses such as increased heart rate and sweat response across all addicted groups (Carter & Tiffany, 1999). Drug cues are thought to lead to such reactions as a result of associative learning that took place during prior episodes of drug exposure (for discussion, see Niaura et al., 1988; Childress et al., 1993). Importantly, a growing body of work directly links cue‐induced craving to drug use. First, the presence of other drug users or of the drug itself has been linked to instances of drug

Load more