Nora Volkow

PET imaging for addiction medicine

Positron emission tomography (PET) has been shown to be an effective imaging technique to study neurometabolic and neurochemical processes involved in addiction. That is, PET has been used to research neurobiological differences in substance abusers versus healthy controls and the pharmacokinetics and pharmacodynamics of abused drugs. Over the past years, the research scope has shifted to investigating neurobiological effects of abstinence and treatment, and their predictive power for relapse and other clinical outcomes. This chapter provides an overview of PET methodology, recent human PET studies on drug addiction and their implications for clinical treatment.

Gender Differences in Brain Activation by Food Stimulation

The increasing prevalence of obesity worldwide and associated morbidity and mortality highlights the need to understand the neurobiological and functional mechanisms underlying eating behaviors. Gender is a relevant factor since women are reported to have higher rates of obesity than men. To tap into the neurobiological underpinnings of eating behavior, we developed a food stimulation paradigm to be used for imaging and showed that the presentation of food that could not be consumed in normal weight subjects was associated with increased metabolic activity in the orbitofrontal cortex, which is a brain region involved with conditioning, salience attribution, and motivation. Women had greater activation in the anterior prefrontal and the orbitofrontal cortex than men during food stimulation. Using the same food stimulation paradigm, we found blunted activation of brain regions involved with inhibitory control in women when compared with men, which suggests a possible neurobiological mechanism for the gender differences in this behavior. Understanding the mechanism(s) contributing to gender differences in overeating behaviors may provide a scientific basis for pharmacological and behavioral approaches to its prevention and treatment.

Studies of the Brain Cannabinoid System Using Positron and Single-Photon Emission Tomography

Studies using radiolabeled cocaine in conjunction with positron emission tomography (PET) have been conducted since 1989 to image cocaine-binding sites in the human brain (1). Among other findings, they have demonstrated that the concentration of these sites is decreased in chronic cocaine abusers (2), and that > 50% of the binding sites in striatum must be occupied for subjects to experience a high (3). Similar studies of marihuana were for many years hampered by the unsuitability of radiolabeled forms of THC for PET studies (4–5), and the unavailability of other in vivo imaging agents for cannabinoid receptors. However, recent developments in medicinal chemistry have made new agonists and antagonists available with high affinity for the cannabinoid receptor. This has led to the synthesis of [123I]AM 281, the first radioligand able to visualize the brain cannabinoid CB1 receptor by ex vivo autoradiography and single-photon emission computed tomography (SPECT) (6–8). Other radiotracers for cannabinoid receptor imaging with SPECT and PET will probably soon become available. This chapter briefly reviews these developments, together with the results of PET studies of the effects of marihuana and other abused drugs on brain blood flow and metabolism.