Saturday, March 29, 2008

Amphetamine Blues

How meth addiction happens.

If alcohol’s impact on brain cells is wide-ranging and diffuse, and marijuana’s impact is selective and subtle, the impact of cocaine and amphetamine is much more straightforward. “There is certainly lots of evidence for common neurological mechanisms of reward across a wide variety of drugs,” said Dr. Robert Post, chief of the biological psychiatry branch at NIMH.

Animals will readily administer cocaine and amphetamine, Dr. Post once explained to me, but when researchers surgically block out areas of the brain that are dense with dopamine receptors, the picture changes dramatically. “The evidence definitely incriminates dopamine in particular,” said Dr. Post. “In animal models, if you make selective lesions in the dopamine-rich areas of the brain, particularly the nucleus accumbens in the limbic system, the animals won’t self-administer either amphetamine or cocaine.”

When you knock out large slices of the nucleus accumbens, animals no longer want the drugs. So, one cure for addiction has been discovered already—but surgically removing chunks of the midbrain won’t do, of course.

At the heart of the meth high is a chemical paradox. The entire range of stimulative effects hits the limbic system within seconds of being inhaled or inject, and the focused nature of the impact yields an astonishingly pleasurable high.

But the long-term result is exactly the opposite. The body’s natural stock of these neurotransmitters starts to fall as the brain, striving to compensate for the artificial flooding of the reward center, orders a general cutback in production. At the same time, the receptors for these neurotransmitters become excessively sensitive due to the frequent, often unremitting nature of the stimulation.

The release of dopamine and serotonin in the limbic structure called the nucleus accumbens lies at the root of active drug addiction. It is the chemical essence of what it means to be addicted. The pattern of neural firing that results from this surge of neurotransmitters is the “high.” Dopamine is more than a primary pleasure chemical—a “happy hormone,” as it has been called. Dopamine is also the key molecule involved in the memory of pleasurable acts. Dopamine is part of the reason why we remember how much we liked getting high yesterday.

One reason why amphetamine addicts will continue to use, even in the face of rapidly diminishing returns, is simply to avoid the crushing onset of withdrawal. Even though the drug may no longer be working as well as it once did, the alternative--the psychological and physical cost of withdrawal--is even worse. When addicts talk about “chasing a high,” the metaphor can be extended to the losing battle of neurotransmitter levels. In the jargon used by Alcoholics Anonymous, addicts generally have to get worse before they can get better.

Speed, then, is diabolically well suited to the task of artificially stimulating the limbic reward pathway. Molecules of amphetamine displace dopamine and norepinephrine in the storage vesicles, squeezing those two neurotransmitters into the synaptic gap, and keeping them there, where they repeatedly stimulate their receptors. By mechanisms less well identified, cocaine accomplishes the same feat. Speed also interferes with the return of dopamine, norepinephrine, and serotonin molecules to their storage sacs, a procedure known as reuptake blocking—the same mechanism by which the so-called selective serotonin reuptake inhibitors (SSRI) antidepressants increase the availability of serotonin in the brain.

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


sicntired said...

I've been addicted to opiate drugs for over 35 years.I now find myself in the unenviable position of needing painkilling drugs for a spinal degeneration that has me in severe pain.Because of concerns over addiction,I cannot find a doctor that will prescribe the medication necessary to manage my pain.Although there may be a cure for addiction somewhere down the road.There are a lot of people(addicts)that would prefer death to sobriety.I mention this only because I think that sometimes,in the pursuit of a better world.We create cures that are worse than the original disease.The quest for the annihilation of addiction has cost many people dearly.Although a cure is laudable,there are excesses in the name of sobriety that have been far worse than the addiction that they are trying to prevent.Abuse is the enemy here.Let's not try to cure everyone when only a very small percentage will ever need help.

Dirk Hanson said...

"Let's not try to cure everyone when only a very small percentage will ever need help."

I couldn't agree more. A major failing of the so-called war on drugs is the inability to distinguish between casual use and non-stop abuse. The pursuit of a cure for addiction only makes sense if we manage to distinguish active addiction from recreational use.

Moreover, I don't believe pain-killing drugs should ever be withheld from medical patients who clearly require them, regardless of past history.

student said...

i have been studying the addiction to amphetamines and would like permission to use some of your stories in my presentation. Thank you.

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