This Is Your Brain on Drugs

High-tech imaging reveals the chemistry of addiction

Drug intoxication produces characteristic waveform signatures in the mammalian brain. The search for specific biological markers in the brain was made possible by positron emission tomography, better known as the PET scan. The idea is simple: Doctors inject test subjects with radioactively tagged glucose, which passes the blood-brain barrier with ease. The more electrochemically active portions of the brain burn extra glucose for energy. By noting precisely where the tagged glucose has gone, and converting that information into a digital two-dimensional array, a PET scan serves as a neurobiological map of brain activity in response to specific stimuli. Functionally, PET scans are pictures of the brain, showing specific areas that “light up” during the performance of a task, or in response to a drug.

Neuroimaging techniques like nuclear magnetic resonance imaging, or MRI, provide another level of detail. With MRIs, scientists could study the brain as a living work in progress. They could create a three-dimensional picture of the brain, with the sagittal, transaxial and coronal planes all visible at once—almost a brain hologram. For the first time, addiction scientists could watch areas of the brain light up with activity under the influence of specific mood-altering chemicals.

Two areas were of particular interest. One was the nucleus accumbens, which was involved in the regulation of dopamine and serotonin synthesis. The other was the locus ceruleus—a tiny area of the brain saturated with cells involved in the production and release of the neurotransmitter norepinephrine. Norepinephrine is another important neurotransmitter in the story. It is also known as noradrenaline, and is essentially identical to adrenaline (the latter also called, confusingly, epinephrine). For practical purposes, the four terms are essentially synonymous.

Alcohol, cocaine, the opiates, and other drugs made these two areas of the brain bloom with activity on the MRI and PET scans. These snapshots of your brain on drugs specifically showed that psychoactive drugs of abuse, the ones that altered mood and emotion, did so at the very sites in the brain known to be involved in regulating emotional states. As a general rule, the same areas of the brain tended to light up no matter what addictive drug was under study. Whether it was a molecule of rapture, or a molecule of sorrow, sooner or later it went surging through the brain’s limbic system--a diffuse aggregation of mid-brain structures involved with emotion, memory, mood, sleep, and a host of specific behaviors ranging from appetite to risk-taking.

That the subjects also showed characteristic brain activity when they quit doing drugs was of equal interest. Dr. Kenneth Blum and his coworkers at the University of Texas Health Science Center demonstrated that certain waveforms occur in the locus ceruleus when abstinent addicts experience cravings. The locus ceruleus helps control levels of the original “fight or flight” chemical, norepinephrine, and when an addict in withdrawal panics, the locus ceruleus lights up like the Fourth of July.

Other studies of the nucleus accumbens showed abnormal firing rates in scanned addicts who were deep into an episode of craving. Drug hunger in abstinent addicts, it appeared, was not all in the head, or strictly psychological. Cravings have a biological basis.