Do Opiates Permanently Alter the Brain?
> 9/14/2007 1:39:43 PM

One of the best possible dissuasions against drug use is that it causes irreparable brain damage. But determining whether a specific drug actually does make permanent changes is very difficult.  A recent article in the Journal of Neuropsychiatry takes on this complex problem by surveying the entire field of opiate addiction. By looking at the larger experimental picture, we can see that cognitive tests have offered contradictory evidence, but that new brain imaging technology may offer a way out of the confusion.

While the extensive and disjointed list of previous opiate studies compiled by Dr. Michele Martin for this article is overwhelming, a little effort organizing allows us to see that research tended to focus on a combination of three types of users and one of two methods of observation. Scientists most commonly compare current users, abstinent users, and replacement drug users by either brain scans or cognitive impairment tests.

Many studies have reported cognitive impairment in all three types of opiate users, but the large variety of the alleged impairments calls their accuracy into question. Much of recent research has concentrated on comparing opiate abusers or never-users to those regulating their addiction with methadone. While some researchers found that methadone users suffered only from verbal or episodic memory deficits, Doctors Darke, Sims, McDonald, and Wickes found that users performed worse on information processing, attention, short-term visual memory, delayed visual memory, short-term verbal memory, long-term verbal memory, and problem solving tasks.

The veracity of these wide-ranging findings is threatened by the fact that those on methadone, especially those with the most cognitive impairment, had much higher levels of other mental health problems and other addictions. Doctor J. Vassileva sought to remove other addictions from the equation by studying heroin addicts in Bulgaria, where polysubstance abuse is exceedingly rare. Dr. Vassileva did not find the range of deficiencies that previous researchers found, but did discover notable impairments in the ability of abstinent addicts to sacrifice short-term benefits for long-term gains.

Dr. Vassileva’s study avoids another potential problem with previous studies— it includes truly abstinent subjects instead of those on methadone. Studies have shown that methadone users have worse episodic memory if they take one large does a day instead of two, and they perform worse in a variety of tasks compared to those taking the alternative drug buprenorphine. This calls into question not only the viability of including methadone users in studies, but also the safety of methadone as a replacement drug.

Tests of cognitive impairment have been inconclusive. Fortunately, recent advances in imaging technology have opened up new ways to directly measure the lasting impact of opiate use on the brain. Refined PET scans revealed that opiates targeted multiple different receptors. Now that the technology has fully matured,  receptor-specific PET ligands have allowed scientists to identify three general stages of brain degeneration over the course of the addiction. Stage 1 involves damage to the cerebellum causing restlessness and a slight loss of motor control. Stage 2 brings tremors and myoclonic jerks of major muscle groups. Stage 3 brings extended spasms, fevers, and even death. Each of these stages involves a noticeable change in the flow of blood to relevant areas of the brain. Unfortunately, these brain scans have not yet been able to prove whether or not permanent brain damage occurs. While one study found that blood flow levels started returning to normal after three weeks of detoxification, another study by Drs. Botelho, Relvas, and Abrantes noticed no such improvement after 10 weeks.

While the survey article in Neuropsychiatry helps to identify the blurry spots in our view of opiate recovery, it cannot give answers but only point out the tasks others must undertake and the pitfalls they must avoid. Future researchers must isolate or fully understand the effect of methadone and comorbid disorders before assuming that the impairments in those no longer using heroin are purely the residuals of heroin. A cautionary tale of rushing to attribute damage to opiates— the observation that some former heroin addicts suffer from toxic spongiform encephalopathy. Only after it was noticed that this occurred in outbreaks did scientists suspect that the brain damage was actually caused by toxic adulterates slipped in by shady drug dealers. Some of the researchers in the studies above pointed out another major flaw in their own studies: Certain brains are more drawn to drugs in the first place, requiring a comparison of before and after to detect any changes. To make sure that these original brain differences are taken into account, future studies should scan and test subjects before their first drug abuse. It is costly and time consuming to follow subjects without knowing which ones will eventually turn into addicts, but such research is necessary. Now that the holes in our knowledge of opiate addiction have be outlined, we hope that they can be filled.

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