Drug abusers who progress to the second stage of addiction are subject to withdrawal when they initiate abstinence. Many drugs produce cognition-related withdrawal symptoms that may make abstinence more difficult. These include:
Nicotine provides a familiar example of cognitive changes in withdrawal. In both chronic smokers and animal models of nicotine addiction, cessation of nicotine administration is associated with deficits in working memory, attention, associative learning, and serial addition and subtraction (Bell et al., 1999
; Blake and Smith, 1997
; Davis et al., 2005
; Hughes, Keenan, and Yellin, 1989
; Jacobsen et al., 2006
; Mendrek et al., 2006
; Raybuck and Gould, 2009
; Semenova, Stolerman, and Markou, 2007
). Moreover, it has been shown that the severity of decreases in cognitive performance during periods of smoking abstinence predicts relapse (Patterson et al., 2010
; Rukstalis et al., 2005
). Although these deficits usually dissipate with time, a dose of nicotine will rapidly ameliorate them (Davis et al., 2005
)—a situation that may contribute to some relapses. Thus, chronic substance abuse can lead to cognitive deficits that are particularly pronounced during early periods of abstinence.
While the cognitive deficits associated with withdrawal from drugs are often temporary, long-term use can also lead to lasting cognitive decline. The nature of deficits varies with the specific drug, the environment, and the user’s genetic makeup (see Genes, Drugs, and Cognition on page 11). In general, however, they impair the ability to learn new patterns of thought and behavior that are conducive to successful response to treatment and recovery.
For example, long-term cannabis users have impaired learning, retention, and retrieval of dictated words, and both long-term and short-term users show deficits in - time estimation (Solowij et al., 2002
), although how long these deficits persist is not yet known. As another example, chronic amphetamine and heroin users show a deficits in a range of cognitive skills, including verbal fluency, pattern recognition, planning, and the ability to shift attention from one frame of reference to another (Ornstein et al., 2000
). The decisionmaking deficits resembled those observed in individuals with damage - to the prefrontal cortex, suggesting that both drugs alter function in that brain area (Rogers et al., 1999
A pair of recent studies suggests that some meth- amphetamine-induced cognitive losses may be partially recouped with extended abstinence (Volkow et al., 2001
; Wang et al., 2004
). Evaluated when abstinent for less than 6 months, chronic methamphetamine abusers scored lower than unexposed controls on tests of motor function, memory for spoken words, and other neuropsychological tasks. The deficits were associated with a comparative scarcity of dopamine transporters (proteins that regulate dopamine) and reduced cellular activity (metabolism) in the thalamus and NAc. When retested after 12 to 17 months of abstinence, the drug abusers’ motor function and verbal memory had risen to levels that approached those of the control group, and the gains correlated with a return toward normal transporter levels in the striatum and metabolic levels in the thalamus; however, other neuropsychological deficits remained, along with depressed metabolism in the NAc.
In another study, abusers of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) continued to score relatively poorly in tests of immediate and delayed recall of spoken words even after 2.5 years of abstinence (Thomasius et al., 2006
). In a study of polydrug abusers who had stated a primary preference for either cocaine or heroin, deficits in executive function—defined as changes in fluency, working memory, reasoning, response inhibition, cognitive flexibility, and decisionmaking—remained after up to 5 months of abstinence (Verdejo-García, and Pérez-García, 2007
An important question is whether nicotine’s cognitive benefit persists as smoking shifts from sporadic to chronic. In some studies with animals, chronic nicotine administration improved cognitive capacities such as attention, but other studies found that initial improvements waned with chronic treatment (Kenney and Gould, 2008
). Furthermore, several recent studies have shown that smoking and a past smoking history are associated with cognitive decline. For example, in one study with middle-aged men and women, smokers’ cognitive speed declined nearly twice as much as non-smokers’ over 5 years; in addition, declines in smokers’ cognitive flexibility and global cognition occurred at 2.4 times and 1.7 times the respective rates of nonsmokers (Nooyens, van Gelder, and Verschuren, 2008
). Recent quitters’ scores in these areas were similar to smokers’, and ex-smokers performed at levels intermediate between smokers and nonsmokers.
Similarly, in another study, smokers’ performance deteriorated more over 10 years than nonsmokers’ on tests of verbal memory and speed of visual searching; ex-smokers’ visual search speed slowed more than non-smokers’ as well (Richards et al., 2003
). Although some early studies suggested that smoking might retard the cognitive decline associated with Alzheimer’s disease (van Duijn and Hofman, 1991
), followup studies failed to confirm this, and others correlated smoking quantity and duration with higher risk for Alzheimer’s disease (Swan and Lessov-Schlaggar, 2007
Laboratory studies have demonstrated nicotine-related alterations in neuronal functioning that could underlie cognitive decline that persists even after prolonged abstinence. For example, rats’ self-administration of nicotine was associated with a decrease in cell adhesion molecules, a decrease in new neuron production, and an increase in cell death in the hippocampus (Abrous et al., 2002
). Such changes could result in long-lasting cognitive changes that contribute to poor decisionmaking and addiction.