Review and Critique: Methamphetamine Mice Study Falls Far Short

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special to Drug War Chronicle by John Calvin Jones, Ph.D., JD

(Editor's Note: This article was submitted with full scholarly citations. We edited them out for reasons of brevity and style. Anyone wishing the fully annotated version of the article can request it by sending an email to psmith@drcnet.org.)

On August 14, both the newswires and the Society of Neuroscience announced that Dr. Jacqueline McGinty and her colleagues made some new, important, scientific findings about the "long-term consequences of methamphetamine use." McGinty found some of the neurological effects (i.e. brain damage) that methamphetamine causes, the society claimed. In a study titled, "Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice," researchers claim that after a mere four doses of methamphetamine, they could measure residual brain damage in mice over nine months later. The researchers then conclude, reasoning by analogy, that use of methamphetamine by humans will lead to brain damage that harkens Parkinson's disease.

http://stopthedrugwar.org/files/methbrainscans.gif
NIDA brain scans
At a most basic level, there are methodological, political, and ethical questions about the validity and propriety of the study and the authors' conclusions. First, McGinty et al. injected the mice with mega doses of methamphetamine, not doses comparable to what recreational or addicted users take.

Second, after claiming that glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine, McGinty depleted the GDNF in one set of mice, administered the meth to them and then concluded that the meth (not their chemical imbalance) caused brain damage. Given that the brains of humans are not altered to lower their GDNF, why should we believe the findings are applicable to people who use meth?

Third, for over a hundred years, the federal government has produced and/or supported research that parrots the government position to vilify certain drugs and those populations who use them. More poignantly, the state of South Carolina and the Medical University of South Carolina where McGinty works has recently been on the frontlines of the prosecution of the war on drugs, as opposed to addressing drug use issues as a medical matter.

In this respect, this latest piece, funded by both the US Army (which compels soldiers to consume amphetamines) and NIDA, compels us to question the research project itself, let alone its supposed results and speculative conclusions.

McGinty and her co-authors purport to tell us that typical doses of methamphetamines can have serious, long-lasting, deleterious effects on brain function to the point of causing Parkinson's disease or Parkinson's-like neurological impairment and disorder. However, instead of giving mice comparable doses as consumed by regular or infrequent meth users, McGinty et al. gave one set of mice four mega doses of methamphetamine.

Four times, McGinty's team injected mice with 10mg of meth per kg body weight, the latter three injections coming at two hour intervals after the first. If a person followed the same regime, how much meth would she take following the McGinty binge? For a 110 pound woman (50 kg), at 10mg per kg, she would be injected with 500 mg of meth -- and then injected three more times over a period of six hours.

The obvious question is, "would four doses of 500mg of meth in six hours be a lot of meth for a 50kg woman?" McGinty fails to provide any mention on the propriety of their dosage and or how common it is for people to enjoy such mega doses. Though one might find a wide range of opinion as to what constitutes either a normal or mega-dose of methamphetamine, the evidence is relatively clear as to how much meth humans regularly consume.

The DEA references an un-cited NIDA report of 2006 which declares, "In some cases, abusers forego food and sleep while indulging in a form of binging known as a "run," injecting as much as a gram of the drug every 2 to 3 hours over several days until the user runs out of the drug or is too disorganized to continue." For some curious reason, the NIDA report has no citations or references to bolster its claim about superhuman meth addicts who need as much as a gram at a time.

Conversely, according to the drug information web site Erowid, a large dose of meth, taken intravenously, would be 50 mg. For even a regular user, 50 mg would generate a high from one to three hours and the user would have another two to four hours to come down.

Hence, if we follow the dictates of Erowid, where a regular meth user might go seven hours between hits, we see that McGinty and company gave mice 10 times what a regular user needs and then re-administered the mega dose three more times within less than seven hours.

The mice in McGinty's study were given unadulterated meth. There have been other documented cases of unadulterated meth use. During the time of the German Third Reich, German soldiers were given Pervitin (which had 3mg of methamphetamine) and later another drug which contained Pervitin called D-IX. D-IX had three significant psychoactive substances, cocaine (5mg), methamphetamine (3mg), and 5mg of a morphine extract. Soldiers and their commanders were advised to take only two pills (either the Pervitin or later the D-IX) per day as necessary to stave off sleepiness.

To compare then, while German soldiers weighing roughly 75kg (165 lbs.) were taking not more than 12 mg of meth (orally) per day (two pills with three mg each, twice a day), lab mice were injected with relatively 250 times as much, in one day. To ingest two hundred times too much water, coffee, aspirin, heroin, alcohol, etc. within a six hour period is enough to kill anyone. That some researchers found evidence that defective mice would show a sign of brain damage many months after what should have been a life ending meth binge is unremarkable.

And by no means were McGinty and her team without any guide as to how much meth other American scientists administer in their animal studies. In sharp contrast with McGinty et al., researchers at UCLA (2007) gave groups of monkeys a range from .2mg/kg to .06mg/kg of meth, no more than three times per day. But they did expose their animals to meth more often than McGinty did. The monkeys in the UCLA study were doped up 9-12 times per week for 6-8 weeks. What were the study's conclusions? The researchers concluded that while such meth exposure correlated strongly with behavioral changes, anti-social and more aggressive actions, the brains of the monkeys did NOT show extensive neurodegeneration. If one set of mammals were exposed to meth for a longer period, yet did not show the same types of disease as reported by McGinty et al., what can we conclude except that she poisoned her mice with mega doses of meth?

It is easy to argue that McGinty and colleagues simply have produced another junk-science, pro-government Drug War propaganda piece. Recent history is filled with examples of similar efforts, with equally dubious results:

  • In 1974 Dr. Robert Heath of Tulane University poisoned monkeys with carbon monoxide smoke produced by burning marijuana. Though Dr. Heath claimed that the marijuana itself produced brain damage, later investigation showed that Heath forced the monkeys to inhale the equivalent of smoke from 63 joints in five minutes and 30 joints a day for 90 days!

  • In 1989, without any scientific evidence, Dr. Ira Chasnoff published a "study" where he proclaimed to have found a new phenomenon, the "crack baby." Years later, however, when he and other neurologists approached the topic with some rigor and control, Chasnoff declared that there were no developmental effects from in utero cocaine exposure. Claiming that poverty, not crack, was the greatest determinant of brain development, Chasnoff wrote:

    "Their average developmental functioning level is normal. [In utero cocaine exposed children] are no different from other children growing up. They are not the retarded imbeciles [that] people talk about."

  • In 2002, NIH sponsored researcher, George Ricaurte, announced to the world in an article published in Science magazine that recreational use of ecstasy (MDMA) leads to brain damage and that ecstasy use by teens would lead to Parkinson's or other neuropsychiatric diseases in later life. Like McGinty and Co., Ricaurte's team poisoned monkeys with massive doses of ecstasy that they claimed were standard doses -- in fact Ricaurte had no references as to define what a baseline dose should be. Voices opposed to the drug war responded immediately, attacking the methodology and conclusions of Ricaurte's work. One year later, after Ricaurte discovered that he had not actually administered MDMA (!), Science itself retracted the article.

  • In the early 1990s, at the same hospital whence McGinty and her team hail, the Medical University Hospital in Charleston, South Carolina, doctors and nurses on the maternity ward elected to work as an arm of the state in prosecuting the drug war -- and perpetuated the crack baby myths and stereotypes about crack and African-Americans at the same time.

    The Medical University Hospital instituted a policy of reporting on and facilitating the arrest of pregnant, primarily African-American, patients who tested positive for cocaine. For four years, many African-American women were dragged out publicly from the hospital in chains.

    The medical staff, working in collaboration with the prosecutor and police, conducted an "experiment" to see if arrests would reduce drug use by pregnant women. All but one of the thirty women arrested pursuant to the policy were African-American. The white nurse who implemented and ran the program admitted that she believed that mixing of the races was against God's will and noted in the medical records of the one white woman they arrested that she "lived with her boyfriend who is a Negro." Despite claims to the contrary by hospital staff and the South Carolina Attorney General, most of the arrested mothers were never offered any drug treatment before being taken to jail.

So with this history, we must contextualize McGinty's study and what she claims is the serious social need both to study meth and to warn us of its ills. In recent interviews, McGinty told reporters that:

"Methamphetamine intoxication in any young adult may have deleterious consequences later in life, though [the consequences might] not be apparent until many decades after the exposure. These studies speak directly to the possibility of long-term public health consequences resulting from the current epidemic [sic] of methamphetamine abuse among young adults."

What is the basis for McGinty, a medical doctor and researcher, proclaiming that South Carolina, or the United States, is suffering from a "meth epidemic"? Let us start with a medical definition of an epidemic. As a baseline medical definition, an epidemic refers to the occurrence of more cases of a disease than would be expected in a community or region during a given time period. Included in the idea of an unexpectedly high rate of affliction, we expect to see abnormal or higher rates of mortality.

The threat of disease epidemics in crowded, densely populated or unsanitary conditions is particularly well illustrated in military history. On many occasions a germ has been as important as the sword or gun in determining the outcome of a war. The Spanish conquest of Mexico owes much of its success to an epidemic of smallpox that destroyed about half of the Aztec population. The typhoid bacillus killed thousands during the American Civil War (1861-1865) and the Boer War (1899-1902) in South Africa. Further, the mortality rate from epidemic typhus increases with age. Over half of untreated persons age 50 or more die from typhus.

Other examples of epidemics include the Spanish flu and Bubonic plague. In 1918, some estimates find that 28% of all Americans were affected with the Spanish Flu. And the mortality rate associated with that flu outbreak was 2.5%. The Bubonic plague (or Black plague) has been responsible for great pandemics. The first spread occurred from the Middle East to the Mediterranean basin during the fifth and sixth centuries AD, killing approximately 50% of the population there. The second pandemic afflicted Europe between the 8th and 14th centuries, destroying nearly 40% of the population.

So while in the medical context, the use of the term epidemic is reserved for contagious diseases and or ailments associated with mortality, McGinty insists on using the inflammatory language in relation to a behavior that in no way is contagious -- though arguably addictive for some individual users -- and does not demonstrate excessive or high mortality rates.

According the 2006 edition of the annual study by the University of Michigan, Monitoring the Future (funded by the NIDA), less than 1% of American teens use meth monthly. Another recent NIDA report (2003) found that in some parts of Nebraska, nearly six percent of arrestees across five select counties tested positive for methamphetamine. But in raw numbers, that same study found that only 32 people out of a population of 644,000 were both arrested and tested positive for meth.

In December 2001, the federal National Drug Intelligence Center reported that meth use in South Carolina was far below that of other states. That said, in 2004, a total of 500 people sought treatment for meth addiction in South Carolina. That is, 500 people in a population of over 4.3 million -- or little more than 12 in 100,000 residents of the state.

To compare, in an area of the country where meth is supposedly a visible problem, the Midwest, not even a rural state like Nebraska can show meth use rates of over 1% for the general population. Similarly, given that South Carolina has meth use rates below the national average, and the nation does not show teen meth use at even 1%, where is the evidence of a meth epidemic? Given the federal government's own data on meth use, McGinty's insistence on a meth epidemic is simply not credible.

Similarly, the mortality rates in South Carolina have remained relatively steady over the past 15 years and trend lines show decreasing mortality. In 1998, the State of South Carolina reported zero drug deaths / overdoses in teens. The same was true in 2004 (the last year that data is available).

When McGinty cannot get the basics right, exaggerates or inflates claims, and repeats old drug war propaganda -- as applied to a new drug -- there is little reason to believe her research is credible.

Permission to Reprint: This article is licensed under a modified Creative Commons Attribution license.
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meth report

Wow. Great article! One of the reasons I don't trust research, blindly.

It is being twisted more and more, each year, to tout the researchers beliefs, instead of scientific evaluation!!

no need

There is really no need to test rats for the damage done by methamphetamine. Had you written this article on MDMA, I would have applauded your efforts. Somehow, that methyl-dioxy makes all the difference.

Who believes that crank is a good thing? That drug really needs to be heavily regulated and supervised. I'm not in favor of any kind of totalitarian policies, but something needs to be done about that drug.

That is possibly the worst substance you could have chosen for this article. Legitimate research protocol is an important question, but it is irresponsible to address this question in relation to methamphetamines.

A better article would be on the vested interests in public perception of caffeine. Why is it so socially acceptable? Why don't motorists involved in accidents and people injured on job sites get tested for caffeine? For that matter, why do so many people get liscences who so clearly should never be behind the wheel of an automobile?

You want to talk about how money affects politics? This is a good subject. Methamphetamines deserve the reputation. Maybe, just maybe, somehow this drug has its place, but I doubt it. I find it hard to imagine how people could draw any other conclusion but that we are all much better off without it.

good research

--That is possibly the worst substance you could have chosen for this article. Legitimate research protocol is an important question, but it is irresponsible to address this question in relation to methamphetamines.

It is not irresponsible to denounce any illegitimate research. It is important to know how harmful meth actually is, medically speaking. It certainly seems to be a horribly harmful drug, but we shouldn't just demonize it to the extreme at the cost of ACTUALLY DOING REAL RESEARCH ON IT! Illegitimate research to support drug war propaganda does not aid anyone in truly understanding the harmfulness of a drug.

real research

I see what you mean. All the same, I would prefer to see questions about such research into more promising drugs. There really isn't much need to demonize methamphetamine.

On the other hand, hysteria doesn't help much. The crystal meth crisis would be better dealt with through public outreach, clinics, and 12 step groups than through drug war activity.

There doesn't need to be propaganda for meth. It lives up to its reputation. I am just not nearly as concerned about propaganda that accurately portrays truly dangerous substances as much as I am concerned with propaganda that associates these with relatively harmless or even beneficial drugs. In particular, I am concerned with the relationship between methamphetamine and MDMA.

Either way, it is important to have research we can trust. So much of it either seems to be a form of drug war propaganda, or propaganda funded by drug dealers, chemists, growers, etc.

I wouldn't say that the researcher in the article was making mountains out of mole hills, but perhaps those mountains are more like the blue ridge than the rockies.

I've personally seen enough of drugs like crack, cocaine, meth, and heroin to feel that perhaps there is a need for law enforcement of one kind or another.

I'd love to see such an article on MDMA, 2-CB, or any and all of the Shulgin compounds. I'd also love to see some reliable research on cannabis. These drugs are shrouded in misinformation and are routinely misrepresented. This is an issue that I feel deserves some clarification with regard to health issues, public opinion, and the role of legislation and law enforcement are critical in terms of human rights and injustice.

I still feel that meth was a bad choice for this issue. I feel strongly about that. I just feel like it's of the essence to focus on drug war issues that involve drugs that might have promise. Bringing meth in just seems to confuse the issue.

Couldn't have said it better

"I still feel that meth was a bad choice for this issue. I feel strongly about that. I just feel like it's of the essence to focus on drug war issues that involve drugs that might have promise. Bringing meth in just seems to confuse the issue."

Maybe I am confused, but what is the point either pro or con to this article? Agreed, the researcher may have gone overboard, but are you proposing that meth is somehow a good thing?

Meth blog

Review and Critique

Everyone needs to be aware that extrapolating data from studies done on other animal species to our own human specie, because of the different physiologies, is dangerous and unscientific. From a 2004 speech, Acting Commissioner of the FDA, Lester M. Crawford, D.V.M., Ph.D., acknowledged that, even after all the preclinical animal testing, 92% of new drugs are rejected in the first phase of human clinical trials. Of the last 8% about 50% of those will be rejected by phase 3 of the human clinical trials. This means that 96% of new drugs that passed the tests in other animal species are rejected when tested in our own. This is not science this is bad gambling. Because of the different physiologies between different species it is not possible to determine, with any accuracy, which specie will react like our own when given certain substances. The fact that it is not possible to extrapolate data freely from mice to rats is a strong indicator of how dangerous and futile it is to try to extrapolate data from mice or rats to humans. Experiments on other animal species to provide health benefits for our own is fraudulent, cruel and dangerous and should be banned.

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