After more than a decade of drug abuse, including a run with methamphetamine, 20-year-old college dropout Nic Sheff wrote in his journal:

How the hell did I get here? It doesn’t seem that long ago that I was on the water-polo team. I was an editor of the school newspaper, acting in the spring play, obsessing about which girls I liked, talking Marx and Dostoevsky with my classmates. The kids in my class will be starting their junior years of college. This isn’t so much sad as baffling. It all seemed so positive and harmless, until it wasn’t. (Sheff, 2005)

Nic’s father, David Sheff, chronicles the story of his son’s addiction in his harrowing memoir, A Beautiful Boy. Nic’s involvement with drugs began early in his life—his father found marijuana in his backpack when he was just 12 years old. David became increasingly devastated as he witnessed his son’s transition from a bright energetic boy to a drug addict. Each time Nic remained sober for an extended period, David had hope that his son had finally turned a corner, only to be disappointed by yet another relapse.

After cleaning up his act, Nic was accepted into Manchester College, far away from his San Francisco home and all of the drug-related cues that had kept leading him into relapse. Elated to pick up his son after his first full year of college, David’s excitement turned to panic when he looked at Nic and saw the telltale signs that Nic was definitely using drugs again—pale skin, unkempt hair, a vibrating body, gyrating jaw, and darting eyes. Nic’s old habits were evident that painful summer, as he would disappear for weeks without contacting his parents. Consequently, David was certain that Nic was somewhere on the street abusing methamphetamine. He feared he would never see his son again.

Somehow, Nic found enough sobriety in the next couple of years to write his own memoir, Tweak: Growing up on Methamphetamine. “Tweaking,” a word that usually refers to minor alterations, is anything but a minor alteration in the context of drug use. In this most dangerous stage of methamphetamine abuse, the user has reached the end of a binge—several days of continuous use without sleeping, accompanied by an emotional tsunami of irritability and paranoia—and can no longer get satisfaction from the drug. During a tweak, methamphetamine users have been known to engage in dangerous behavior, threatening and hurting friends or loved ones and committing crimes (Sheff, 2008).

Behind the Scenes

What changes in Nic’s brain accompanied his transition from a highly functioning child to a methamphetamine addict? Animal research has established that amphetamine and methamphetamine alter neurons that secrete the neurotransmitter dopamine into the striatum. Dopamine is a neurochemical involved in reward and motor systems and is one of the most investigated neurochemicals in addiction research. Addiction, in Nic’s case, involved an uncontrollable desire to consume methamphetamine. Addiction, as you’ll learn throughout this chapter, is the compulsive dependence on a behavior or substance—a complex response that involves many neurochemicals.

Specifically, research suggests that chronic methamphetamine use leads to a type of toxicity characterized by decreased numbers of dopamine-sensitive (dopaminergic) synaptic endings, as well as lower dopamine levels in the brain (Berman, O’Neill, Fears, Bartzokis, & London, 2008). In one study, rats that received high-dose methamphetamine injections showed a 35% reduction in dopaminergic synaptic endings relative to control rats that received saline injections (Pubill, Canudas, Pallàs, Camins, Camarasa, & Escubedo, 2003). This study provided evidence that methamphetamine restructures the dopaminergic neural circuits that keep the brain’s movement, emotions, and thoughts running smoothly.

Using magnetic resonance imaging (MRI), researchers have found evidence that the human brain is similarly affected by the use of methamphetamine. In one study, autopsied brains of methamphetamine users showed up to 97% lower dopamine levels in an area of the striatum known as the caudate nucleus, relative to the autopsied brains of control subjects (Moszcynska et al., 2004). In a positron emission tomography (PET) study that imaged human subjects’ living brains, Nora Volkow and her colleagues at the National Institute on Drug Abuse (NIDA) reported reduced availability of a specific subtype of dopamine receptor in chronic methamphetamine users, compared with non-drug-abusing control subjects (Volkow et al., 2001).

In these types of studies of drug abusers, researchers use a control (non-drug-abusing) group of subjects as the comparison group (since it is typically not possible to conduct a controlled study in which individuals participate once before they are drug abusers and again after they are drug abusers). Brain differences observed between the drug-abusing group and the non-drug-abusing control group are generally interpreted as evidence of the changes that drug abuse causes in the brain.

Other researchers have observed less gray matter in limbic structures such as the cingulate cortex, as well as white matter hypertrophy, or enlargement, and smaller hippocampal volumes, in methamphetamine addicts compared with non-drug-abusing control subjects. Chronic methamphetamine abuse is associated with a pattern of abnormal brain structure that is comparable in effect size to deficits observed in schizophrenia (see Chapter 13) and early dementia (see Chapter 5) (Thompson et al., 2004).

What behavioral patterns are associated with these findings of abnormal brain structure? Research on humans has identified positive relationships between striatal dopamine receptor availability and impulsiveness (Lee et al., 2009). Even when they stop taking the drug, methamphetamine users demonstrate impaired response inhibition and decision-making (Paulus et al., 2002; Salo et al., 2002). Early in the abstinence period, users experience a range of troubling symptoms including fatigue, decreased pleasure, agitation, vivid dreams, irritability, anxiety, and poor concentration. Most of these patients also experience cravings for the drug (McGregor et al., 2005). These withdrawal symptoms (those troubling symptoms that emerge once the drug use ceases) make it especially difficult for users like Nic to continue to abstain from drug use.