PET Imaging Studies in Drug Abuse Research

There is overwhelming evidence that addiction is a disease_of the brain (Leshner, 1997). Yet public perception that addiction is a reflection of moral weakness or a lack of willpower persists. The insidious consequence of this perception is that we lose sight of the fact that there are enormous medical consequences of addiction including the fact that a large fra'ction of the total deaths from cancer and heart disease are caused by smoking addiction. Ironically the medical school that educates physicians in addiction medicine and the cancer hospital that has a smoking cessation clinic are vanishingly rare and efforts at harm reduction are frequently met with a public indignation. Meanwhile the number of people addicted to substances is enormous and increasing particularly the addictions to cigarettes and alcohol. It is particularly tragic that addiction usually begins in adolescence and becomes a chronic relapsing problem and there are basically no completely effective treatments. Clearly we need to und$rstand how drugs of abuse affect the brain and we need to be creative in using this information to develop effective treatments. Imaging technologies have played a major role in the conceptualization of addiction as a disease of the brain (Fowler et al., 1998a; Fowler et al., 1999a). New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology and medicine. This topic cuts across the medical specialties of neurology, psychiatry, cancer and heart disease because of the high medical, social and economic toll that drugs of abuse, including and especially the legal drugs, cigarettes and alcohol, take on society. In this chapter we will begin by highlighting the important role that chemistry has played in making it possible to quantitatively image the movement of drugs as well as their effects on the human brain. This will be followed by highlights of PET studies of the acute effects of the psychostimulant drugs cocaine and methylphenidate (ritalin) and studies of the chronic effects of cocaine and of tobacco smoke on the human brain. This chapter concludes with the description of a study which uses brain imaging coupled with a specific pharmacological challenge to address the age-old question of why some people who experiment with drugs become addicted while others do not. The Importance of Chemistry The ability to isolate and monitor specific chemical changes in the …