Further Reading

Stanton, does the latest discovery about the effects of cocaine disprove your theory?

Stanton,

What effects do these results have on your theories?

Thanks in advance,
Joel Becker

Science Slots Piece In Cocaine Addiction Puzzle

LONDON (Reuters) - U.S. scientists have come a little closer to understanding cocaine addiction, throwing a lifeline to addicts who fear that even if they do kick the habit a relapse is inevitable.

Researchers at the Yale University School of Medicine found that repeated use of cocaine triggered the production of a new gene in the brain and that the gene, delta-FosB, stayed in the brain long after cocaine use had stopped.

"A cocaine addict is addicted because of the many changes the drug produces in the brain. Some of these changes persist even after years of abstinence," Eric Nestler, professor of psychiatry and neurobiology at Yale, told Reuters. "Our findings help us understand addiction, so that eventually we can better treat it," said Nestler, whose research was published in Wednesday's science journal Nature.

Nestler and his team found that chronic users of cocaine had high levels of delta-FosB in one area of the brain. "What we showed is that when delta-FosB builds up in this particular nerve cell type, then there is an increased sensitivity to cocaine," Nestler told Reuters. "However good cocaine felt before, it feels better now."

With infrequent users of cocaine, delta-FosB is only produced in small amounts. With addicts, it accumulates to a greater extent and becomes a potent biological factor. Addiction to cocaine, or other drugs, is believed to be partly caused by biological changes. "There has been the sense that there is perhaps some kind of switching of the brain. We think delta-FosB may be one part of the switch," Nestler said. He admits research into cocaine addiction is at a very primitive stage but says understanding the part played by delta-FosB could point the way to improved treatment.

Understanding the role of delta-FosB in turning a casual user of cocaine into a chronic addict is a step on the way to understanding the biological processes of addiction. Delta-FosB is also produced in the brain by repeated exposure to substances such as heroin, nicotine, alcohol and PCP or angel dust.

Nestler and his team used genetically engineered mice and found the animal's responsiveness to cocaine rose dramatically when the delta-FosB gene was turned on in brain regions important for the formation of addiction. But the role of delta-FosB is just one piece in the puzzle that is cocaine addiction. "We know of other genes that do the same thing in different parts of the brain," Nestler said.

Nestler said one day it might be possible to neutralize the more persistent neurobiological changes associated with drug addiction.


Dear Joel

Great question! This is an example of science in reverse. It's part of the NIDA program to discover explanations for behavior that contradict the actual course of this behavior.

As I wrote to Alan Leshner when the NIDA had a conference to explain the biology of heroin addiction, these putative neurological mechanisms explain nothing of what we observe to be the standard use of heroin and cocaine. In particular, organisms repeatedly exposed to cocaine (or heroin, or alcohol) do not show a tendency to continue their addictions. They are most often characterized by a reaction against the habit (so that most cocaine users who encounter problems cut back or quit using cocaine or — even in the case of animals — readily shift behavior when other rewards are made readily available to them).

Also, please note that this putative explanation for addiction actually reverses decades of pharmacological theorizing — these standard explanations have focussed on the lessening impact of repeated drug infusions (the process of tolerance) that supposedly require the addict to use more of the substance to gain the accustomed effects. The current research instead maintains that repeated use leads to greater sensitivity and responsiveness.

It is true that an addicted individual finds the effects of a drug powerful, reassuring, and appealing, and that their very familiarity and predictability are critical elements in their appeal. But is that why people become and remain drug addicts? All regular and repeated experiences become ingrained through habit and repetition — and all powerful experiences produce both satiation and greater sensitivity to their effects from practice.

Biological explanations for familiar processes that nonetheless do not deal with the critical elements in why people either continue, or instead resist and escape, habitual but life-destroying rewards do not advance addiction theory, and instead mislead us from what matters in addiction. As the researchers note, addicts are harmed by a "fear that even if they do kick the habit a relapse is inevitable." But their own theory supports exactly this self-defeating belief system.

Stanton