The danger of stimulants

Stimulant drug abuse packs a triple-whammy to people's decision-making abilities, hampering their reasoning and increasing impulsive and compulsive behaviors, according to research presented at APA's 2011 Annual Convention by Trevor W. Robbins, a behavioral and clinical neuroscientist at the University of Cambridge in England.

These three tendencies all have slightly different origins in the brain, he said, but they all contribute to the story of stimulant drug addiction—clouding people's judgment during the early stages of addiction, and then making it harder for them to quit.

"These drug abusers ... have poisoned their frontal cortex and produced decision-making deficits," Robbins said.

Poor judgment

During the early stages of stimulant use, people often make a bad bet—underestimating the number of times they can use cocaine, for example, before becoming dependent. This tendency may be explained in part by the fact that stimulant drug use itself makes people worse gamblers, according to one study by Robbins and his colleagues, published in Neuropsychopharmacology (Vol. 2, No. 4).

In the study, the researchers asked four groups of participants—18 chronic amphetamine users, 13 opiate users, 10 people with orbitofrontal cortex lesions and 10 people with dorsolateral or medial prefrontal cortex lesions—to play a computer game known as the Cambridge Gambling Task. In the game, the computer presents participants with an array of 10 red and blue boxes, and asks them to guess which color box is hiding a yellow square. So, for instance, if the computer presents participants with six red boxes and four blue ones, a smart participant would bet on the red boxes, since that's probably where the yellow square is hiding. Then, the computer asks participants to bet a proportion of their points on the correctness of their answer.

The stimulant users performed poorly on the task—making decisions slowly and often making the wrong decision. In addition, the longer the participants had been abusing the drug, the worse their decision-making.

Opiate users, in comparison, showed slowed performance but generally made the correct bet. Among the participants with brain damage, only the ones with orbitofrontal cortex damage showed a pattern of impaired and slowed decision-making.

In a follow-up study, the researchers depleted serotonin levels among healthy participants and found that the participants made poorer decisions, but their decision-making speed was not slowed.

"This suggests that, among amphetamine users, their poor decision-making may be associated with orbitofrontal damage and with reduced serotonin function in that region, as methamphetamine addicts have been shown to have reduced signs of serotonin function in the orbitofrontal cortex post mortem," said Robbins.

Flexibility

In addition to poor decision-making, stimulant drug use seems to make people less able to adapt when the rules of a game change, according to a study published by Robbins and his colleagues in Nature (Vol. 380, No. 6,569). In a procedure similar to the Wisconsin Card Sort Test, the researchers presented monkeys with two icons on a computer screen each showing a line and a shape, and the monkey had to touch one of the icons and avoid touching the other one. However, the "rule" was then changed so that the icon that was previously wrong became correct and vice versa.

Following small lesions in the orbitofrontal cortex, the monkeys did not adapt to the new rule, and persisted in choosing the formerly rewarded icon, the researchers found.

This tendency struck Robbins and his colleagues as similar to that of people with obsessive-compulsive disorder. So, in a study in press in Neuroimage, they compared the richness of the orbitofrontal cortex connections in the brains of people with OCD and those with a history of stimulant use, and found that both groups had reduced connectivity in the ventromedial and superior areas of the orbitofrontal cortex.

"In both cases, this reduction in connectivity was negatively correlated with compulsive behavior," said Robbins. "The more compulsive they were, the less connectivity they had."

In another study, in press in Biological Psychiatry, Robbins and his colleagues showed that activity in the striatum, a brain region connected to the orbitofrontal cortex, was reduced during "reversal learning" in stimulant-dependent individuals and was also related to their cognitive inflexibility. Researchers ameliorated this loss of activity and cognitive inflexibility by giving stimulant-dependent participants pramipexole, which acts like dopamine in the brain and is often used to control the symptoms of Parkinson's disease.

Impulsivity

People who are more impulsive to begin with are probably more likely to try drugs, said Robbins. Stimulants, however, seem to amplify that trait, according to a study he conducted with colleagues published in Biological Psychiatry (Vol. 68, No. 8). They found that non-drug abusing siblings of cocaine addicts tended to score higher than average on the Barratt Impulsiveness Scale, agreeing with statements such as "I do things without thinking" and "I change jobs often." The cocaine-addicted study participants scored even higher.

Robbins and his colleagues further tested chronic stimulant users' and their siblings' impulsive tendencies by giving them the stop signal reaction time test—a game where a computer prompts you to press a particular key, but as soon as you get into the rhythm of pressing it, a beep sounds, telling you to cancel your response. Both stimulant drug users and their siblings were much slower to respond to the beep than the control group.

"Their siblings clearly have some sort of predisposition to impulsivity parallel to their drug-taking siblings, which means that the impulsivity can't simply be a result of drug abuse and is a personality trait which may you vulnerable to stimulant abuse. Of course, abusing the drug probably makes things worse, possibly through toxic effects in the prefrontal cortex circuits that mediate self-control," Robbins said.

Taken together, the findings suggest that stimulant drugs may produce changes in people's prefrontal cortices that make them more likely to continue using drugs, said Robbins. However, new medications may help people at the early stages of addiction regain control of their lives.