Highlights of recently published NIDA-supported studies

Long-Term Cocaine Abuse Linked With Impaired Heart Function

Long-term regular cocaine abuse impairs cardiac left ventricular function in African-Americans, say NIDA-funded researchers Dr. Shenghan Lai and colleagues at The Johns Hopkins Medical Institutions. Magnetic resonance imaging of heart muscle contractions disclosed lower pumping efficiency in areas of the left ventricular wall among 32 African-Americans who abused cocaine compared with 14 nonabusers. The study participants, men and women aged 25 to 54, were all in good health with no signs of heart disease; the findings suggest that prolonged exposure to the drug may cause subclinical impairment that increases risk for cardiac events. Acute cocaine abuse has previously been associated with several cardiac complications, including arrhythmia, ruptured aorta, heart attack, and sudden death.
American Journal of Cardiology 97(7):1085-1088, 2006. [Abstract]

Bupropion Reduces Meth's Subjective Effects and Cue-Induced Craving

A small placebo-controlled trial produced evidence that the antidepressant bupropion may be useful for treating methamphetamine addiction. Drs. Thomas Newton and Richard De La Garza at the University of California, Los Angeles, and Dr. John Roach and colleagues, at the University of Texas, San Antonio, divided 20 methamphetamine-addicted individuals into two groups for 6 days of treatment: one group received bupropion (150 mg/d) throughout the trial and the other, placebo. At baseline and the end of the trial each participant received three infusions; one of an inert vehicle and two of methamphetamine (15mg and 30 mg), spaced over 2 hours. Before and at frequent intervals after each infusion, participants reported on their subjective reactions. Compared to baseline, those who received bupropion experienced reduced highs and slightly decreased cravings at the end of the trial, while those who received placebo experienced significantly more craving.
Neuropsychopharmacology 31(7):1537-1544, 2006. [Full Text]

Cocaine Can Mobilize Stored Dopamine

Cocaine increases dopamine levels primarily by preventing the neurochemical from being transported back into its releasing cell, leaving more outside the neuron, where it contributes to the drug's euphoric effects. Dr. R. Mark Wightman and colleagues of the University of North Carolina at Chapel Hill and Dr. George Augustine of Duke University have recently shown that cocaine also can tap into an intracellular dopamine reserve pool. As far back as the 1970s, some researchers suspected this could occur, but they could not confirm it. Now, thanks to advances in molecular genetics and techniques to study neurotransmission, scientists have learned in studies with mice that proteins called synapsins, under the control of three genes, lock up the reserve pool by tethering its vesicles to the neuron's internal structural framework. When the cell is called upon to release extraordinary amounts of the neurotransmitter, a chemical reaction relaxes the synapsin's grasp on reserve pool vesicles, allowing them to join the releasable pool. "Although this extra mechanism is definitely not the most important action of cocaine, it points to a way that the drug can switch dopamine cells into a sustained-release mode, promoting the activation that dopamine exerts on its target neurons," says Dr. Wightman.
The Journal of Neuroscience 26(12):3206-3209, 2006. [Full Text]

Researchers Develop a New Tracer for Cannabinoid Receptor

Cannabinoid receptors appear to play a role in several conditions—including schizophrenia, depression, obesity, and drug abuse—but a radiolabel has not been available for imaging them in the brain. Drs. Andrew G. Horti and Dean F. Wong and colleagues at the Johns Hopkins Medical Institutions synthesized a new chemical (11C-JHU75528) for this purpose. The tracer readily entered the brains of mice and baboons and bound specifically to cannabinoid receptors (CB1), unlike candidates tested in prior research. The chemical also did not induce any noticeable side effects in the animals. The researchers have also successfully tested 11C-JHU75528 in preliminary human imaging studies and are hopeful that they will someday be able to use it to clarify the relationship between CB1 and specific aspects of drug abuse and other neurological conditions.
Journal of Nuclear Medicine 47(10):1689-1696, 2006. [Full Text]

Volume 21, Number 5 (March 2008)