Undoing Addiction in the Brain's Reward Sector

NEUROMEDICINE

New treatments for addiction could result from studies of ibogaine, an alkaloid derived from a West African shrub.

Animal tests and anecdotal evidence in humans have indicated that ibogaine reduces cravings for alcohol and other drugs of abuse. Now, researchers at the University of California, San Francisco, have confirmed these findings in rodents and determined that ibogaine interacts with the brain's reward circuits.

Ibogaine, which has hallucinogenic and neurotoxic side effects, has not been approved by the Food & Drug Administration. But some clinicians outside the U.S. use ibogaine to limit patients' withdrawal symptoms and craving for alcohol and other drugs, UCSF reports. Neuroscientists Dorit Ron and Patricia H. Janak and colleagues now provide evidence that backs the clinicians' faith in the compound [J. Neurosci., 25, 619 (2005)].

The researchers confirmed previous findings that ibogaine reduces ethanol consumption in rats. They also showed that ibogaine limits relapse effects after alcohol withdrawal in rats.

The neuroscientists then set out to determine how ibogaine works. They knew that drugs of abuse, including alcohol, induce neural changes in the ventral tegmental area, which is involved in the brain's reward mechanisms. The researchers also knew that glial cell line-derived neurotrophic factor (GDNF) diminishes response to such drugs. So they reasoned that ibogaine acts by ramping up production of GDNF in the ventral tegmental area. Results from cellular studies and tests the researchers conducted in rats and mice support this hypothesis.