Thursday, February 14, 2008

Fighting Fire with Fire

An introduction to anti-craving drugs

The early neurobehavioral research on addiction has been vindicated by the development of anti-craving drugs and new drugs for depression.

On the other hand, the psychopharmacology of addiction is not much studied in med school, and all but unknown among the general populace. Even the treatments now in existence are woefully underutilized. Moreover, there are good reasons to question whether these drugs are being prescribed with sufficient care and forethought in cases where they are being used. Legitimate, unanswered questions exist about pharmacotherapy for addictive disorders.

The most important effect--the reregulation of brain receptor arrays with time--is little understood. And we cannot say with certainty whether messing with Mother Nature’s receptors, in some cases, might disrupt other finely tuned immunological or neurological systems in the body. Finally, there is the possibility of side effects years down the road, which obviously cannot be predicted based on current studies. What we already know is that the “bodymind,” as Candace Pert refers to it, is a delicate and astonishingly complicated piece of organic machinery.

Researchers are confronted with the perpetual dilemma of designing out, or designing down, the side effects of any new class of drugs. The historical record of drugs like Thorazine, and darker cases like Oraflex and thalidomide, are reminders of the potential pitfalls of development races and corner-cutting practices in the pharmaceutical industry. The pharmacological sciences and the people who work in them are inextricably linked to the drug companies that sell the end products of any neurochemistry that yields marketable new medications. It cannot be otherwise: Market considerations drive much of the research. By 1990, the American pharmaceutical industry had surpassed the federal government’s National Institutes of Health as the world’s principal source of biomedical research and development funding. One of the stiffest challenges facing managed health care in the future will be the matter of evaluating the effectiveness of medications for addiction.

Fighting fire with fire brings scientists face to face with the problems posed by the blood-brain barrier, that superfine mesh of cells that protects the brain from unwelcome molecular intruders. Bacteriologists discovered the barrier more than two centuries ago, when they learned that dyes injected into the body stained all the organs except the brain. Normally, the capillary-rich barrier of cells is so densely packed that the only way to penetrate the tight junctions between them is by means of special transporter molecules. These specialized molecules act as chauffeurs for the amino acids, hormones, and other compounds that must pass regularly and consistently into the brain. These transporter molecules can be fussy about riders, and the only way around that is to use molecules so tiny that they are measured in units of atomic mass called “Daltons.”

Knowing this, biochemists have worked toward discovering extremely small molecules, and this is partly why so few effective psychoactive drugs come along. While scientists have had some luck with small-molecule approaches to treating epilepsy, schizophrenia, and certain mood disorders, there is no reason to assume a small molecule can always be found to fit the bill.

Current work centers on tricking existing transporter molecules into ferrying artificial cargos into the brain. Pills that easily penetrate the blood-brain barrier are rare, special, and capable of causing a host of problematic side effects. If Zyban demonstrated that there were good reasons to be hopeful about future anti-craving drugs, then the diet drugs Redux and “fen-phen” demonstrated to critics of the drug industry what seemed to be a reversion to type—unsafe drugs released to the public without sufficient attention to dangerous side effects. Eli Lilly’s earlier caution about moving forward with serotonin boosting drugs as anti-obesity medications—as anti-craving drugs for food addicts--soon came to look like a wise decision.

--Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction © Dirk Hanson 2008, 2009.

Related posts:

Chantix and Suicide
What is Drug Craving?
Naloxone and "Receptorology"
Topamax for Alcoholism: A Closer Look


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