by Carl Hart
I pondered this and other questions as I rode the subway back to my lab. Why was my data so inconsistent with the stories told by the other panelists? Was I out of touch with the way people use drugs in the real world? Maybe the doses that I tested were too low, I thought. I had intentionally started off with low doses to ensure the safety of my research participants. At that point, the largest dose I had given was 20 mg, which is considerably lower than doses reportedly used by methamphetamine addicts. Perhaps the individuals described by the prosecutor and police officer used much larger doses than those tested in my studies. This might explain our disparate conclusions. I also thought about how methamphetamine is typically used outside the lab—snorted, injected, or smoked. This ensures that the drug hits the brain more quickly and produces more intense effects. In my studies, it was swallowed. When taken this way it produces the least intense effects. Given these caveats, I questioned whether the data collected in my studies was relevant to the situation in the real world. I figured the hysteria about methamphetamine had to reflect something about reality and that my studies, up until that point, had not captured it.
Over the next seven years, I went about trying to resolve this issue. I searched the human literature to see if anyone had studied larger methamphetamine doses when the drug was snorted, smoked, or injected. There was virtually nothing. I thought about José Martí’s famous quote in his 1882 essay “On Oscar Wilde”: “A knowledge of different literatures is the best way to free one’s self from the tyranny of any of them.” So I read the literature on animal studies looking for information that might be relevant to human addiction. These studies showed that the drug caused extensive damage to certain brain cells and produced severe learning and memory problems. Aha, I got it! Finally, here was some data that was in line with popular anecdotes about methamphetamine. But as I looked more closely it became clear that the animal results had serious limitations and might not be applicable to people. For one, the amounts of methamphetamine given to animals are far more than amounts taken by methamphetamine addicts. If one gave similarly high doses of caffeine or nicotine to animals, the same serious toxic effects would be seen. But when animals were given methamphetamine doses comparable to those used by people, the destructive effects were not observed. During my graduate education, the notion that methamphetamine damaged brain cells was an unquestioned fundamental truth in drug research. Now this basic belief needed to be qualified, making it difficult to extrapolate to people.
Next, I studied the literature on the long-term effects of methamphetamine in addicts. These were people who had used the drugs for many years. In these studies, abstinent methamphetamine addicts and a control group (usually non–drug users) completed a comprehensive set of cognitive tests over the course of several hours, and the results were compared to determine whether the cognitive functioning of the methamphetamine addicts was normal. Of course, normality is a relative concept that is determined by not only comparing performance of the methamphetamine group with the performance of a control group but also comparing the methamphetamine group’s scores with those from a normative dataset, taking into consideration the individual’s age and level of education. These requirements are important because they allow us to take into account the relative contribution of age and education in terms of the individual’s score and adjust the score accordingly. Simply stated, it would be inappropriate to compare the vocabulary scores of a sixteen-year-old high school dropout with those of a twenty-two-year-old college graduate. The older college graduate would be expected to outperform the younger dropout.
With members of my lab at an end-of-year celebration.
Study after study found that methamphetamine addicts had severe cognitive impairment. In one study by Sara Simon and colleagues, the apparent impairments were so bad that it led them to warn: “The national campaign against drugs should incorporate information about the cognitive deficits associated with methamphetamine. . . . Law enforcement officers and treatment providers should be aware that impairments in memory and in the ability to manipulate information and change points of view (set) underlie comprehension . . . methamphetamine abusers will not only have difficulty with inferences . . . but that they also may have comprehension deficits . . . the cognitive impairment associated with [methamphetamine abuse] should be publicized. . . .”7 As I read this and similar papers more critically, I noticed something intriguing. While it was true that the controls had outperformed methamphetamine addicts on a few tests, the performance of the two groups wasn’t different on the majority of tests. More important, when I compared the cognitive scores of the methamphetamine addicts in the Simon study against scores in a larger normative dataset, none of the methamphetamine users’ scores were outside the normal range.8 This meant that the cognitive functioning of the methamphetamine users was normal. This should have tempered the researchers’ conclusions and prevented them from stating such dire warnings. What’s more, the methamphetamine literature was filled with similar unwarranted conclusions; as a result, the apparent methamphetamine addiction–cognitive impairment link has been widely publicized—numerous articles have appeared in scientific journals and the popular press.
The reporting of brain imaging findings has been especially misleading. On July 20, 2004, for example, the New York Times printed an article titled, THIS IS YOUR BRAIN ON METH: A “FOREST FIRE” OF DAMAGE. It stated, “People who do not want to wait for old age to shrink their brains and bring on memory loss now have a quicker alternative—abuse methamphetamine . . . and watch the brain cells vanish into the night.” This conclusion was based on a study that used magnetic resonance imaging (MRI) to compare brain sizes of methamphetamine addicts with non-drug-using healthy people.9 The researchers also looked at the correlation between memory performance and several brain structural sizes. They found that methamphetamine users’ right cingulate gyrus and hippocampus were smaller than those of controls by 11 and 8 percent, respectively. Memory performance on only one of four tests was correlated with hippocampal size (that is, individuals with larger hippocampal volume performed better). As a result, the researchers concluded, “chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance.” This interpretation, as well as the one printed in the Times article, is inappropriate for several reasons.
First, brain images were collected at only one time point for both groups of participants. This makes it virtually impossible to determine whether methamphetamine use caused “cerebral deterioration,” because there might have been differences between the groups even before methamphetamine was ever used. Second, the non–drug users had significantly higher levels of education than methamphetamine users (15.2 versus 12.8 years, respectively); it is well established that higher levels of education lead to better memory performance. Third, there were no data comparing methamphetamine users with controls on any memory task. This, in itself, precludes the researchers from making statements regarding impaired memory performance caused by methamphetamine. Nonetheless, the only statistically significant cognitive finding was a correlation of hippocampal volume and performance on one of the four tasks. This finding is the basis for the claim that methamphetamine users had memory impairments, because the hippocampus is known to play a role in some long-term memory; but other brain areas are also involved in processing long-term memory. The size of these other areas was not different between the groups. Finally, the importance on everyday functioning of the brain differences is unclear because an 11 percent difference between individuals, for example, is most likely within the normal range of brain structure sizes.
This example is not unique. The brain imaging literature is replete with a general tendency to characterize any brain differences as dysfunction caused by methamphetamine (as well as other drugs), even if differences are within the normal range of human variability.10 It would be like comparing the brains of police officers who have less education with those of college professors who
have obtained a PhD, and concluding that the officers are cognitively impaired as a result of any differences that might be noted. This simplistic thinking is the main thrust behind the notion that drug addiction is a brain disease. It certainly isn’t a brain disease like Parkinson’s disease or Alzheimer’s disease. In the case of these illnesses, one can look at the brains of affected individuals and make pretty good predictions about the illness involved. We are nowhere near being able to distinguish the brain of a drug addict from that of a non–drug addict.
Because the literature wasn’t as informative as I’d hoped, I wrote and received a grant to study larger methamphetamine doses in individuals snorting the drug. These laboratory studies detailed the immediate and short-term effects of the drug on measures of cognitive functioning, mood, sleep, blood pressure, heart rate, and the drug’s addictiveness. I tested doses up to 50 mg, which were, at the time, the largest doses tested in people. All of the drug doses were given in a double-blind manner—the research participants didn’t know whether they were getting placebo or real methamphetamine, nor did the medical staff monitoring the sessions. The research participants were carefully selected to make sure they were in excellent medical condition. All were addicted to methamphetamine and used more than 100 mg of the drug on a weekly basis. I wanted to make sure that I was not exposing them to more drug in the lab than they used outside the lab. Similar to the cocaine studies I had previously conducted, we intentionally recruited people who were not seeking treatment, because we felt it was unethical to give methamphetamine to someone trying to stop using.
In the first experiment, we simply had research participants snort one dose of methamphetamine while our medical team carefully monitored their vital signs for twenty-four hours. We also asked the participants to do cognitive tests and rate their mood before and several hours after the drug was given. The findings were consistent with data from our previous studies when we gave the drug by mouth.11 Participants reported feeling more euphoric and their cognitive functioning was improved. These effects lasted about four hours. The drug also caused significant increases in blood pressure (BP) and heart rate that lasted for up to twenty-four hours. The maximum levels were about 150/90 (BP) and 100 (beats per minute). While these elevations were undoubtedly significant, they were well below levels obtained when most people are engaged in a vigorous activity such as physical exercise. Another finding was that the drug reduced the amount of time our participants slept.12 For example, when they took placebo, participants got about eight hours of sleep on that evening. But when the 50 mg dose was given, they got only six hours of sleep. Together, the results indicated that a large snorted dose of methamphetamine produced expected effects. The drug didn’t keep people up for consecutive days, it didn’t dangerously elevate their vital signs, nor did it impair their judgment. Around the same time, other researchers were studying the drug when it was injected or smoked and they were getting similar results.13
The human laboratory data were at odds with anecdotal reports and conventional wisdom. Maybe I hadn’t asked the right question. One of the most popular beliefs about methamphetamine is that it is highly addictive, more so than any other drug. In the next set of experiments, I set out to address this issue. Under one condition, I gave methamphetamine addicts a choice between taking a big hit of methamphetamine (50 mg) or five dollars in cash. They took the drug on about half of the opportunities. But when I increased the amount of money to twenty dollars, they almost never chose the drug.14 I had gotten similar results with crack cocaine addicts in an earlier study.15 This told me that the addictive potential of methamphetamine was not as had been claimed; its addictiveness wasn’t extraordinary. My results also showed me that methamphetamine addicts, just like crack addicts, can and do make rational decisions, even when faced with a choice to take the drug or not. This was consistent with the literature assessing cognitive functioning of methamphetamine users, but as noted above, only if you looked carefully.16
Still, the popular view of methamphetamine remained unchanged. Most media portrayals continued to emphasize unrealistic effects and exaggerate the harms associated with the drug. For example, in January 2010, NPR ran a story titled, “This Is Your Face on Meth, Kids.” The story described a California sheriff who was trying to stop young people from experimenting with methamphetamine. With the help of a programmer, he developed a computer program that digitally altered teenagers’ faces to show them what they would look like after using methamphetamine for six, twelve, and thirty-six months. These young people watched their images change from those of healthy, vibrant individuals to faces marred by open scabs, droopy skin, and hair loss. They were told that these were the physiological effects of using methamphetamine. Ninety percent of individuals who tried methamphetamine once, they were also told, would become “addicted.” How could such inaccurate information be given to naive students, let alone be reported on NPR, I thought.
There is no empirical evidence to support the claim that methamphetamine causes one to become physically unattractive. Of course, there have been the pictures of unattractive methamphetamine users in media accounts about how the drug is ravaging some rural town. You may have also seen the infamous “meth mouth” images (extreme tooth decay). But consider this: methamphetamine and Adderall are essentially the same drug. Both drugs restrict salivary flow, leading to xerostomia (dry mouth), one proposed mechanism of meth mouth. Adderall and generic versions are used daily and frequently prescribed—each year they are among the top one hundred most prescribed drugs in the United States—yet there are no published reports of unattractiveness or dental problems associated with their use. The physical changes that occurred in the dramatic depictions of individuals before and after their methamphetamine use are more likely related to poor sleep habits, poor dental hygiene, poor nutrition and dietary practices, and media sensationalism. With regard to the addictiveness of methamphetamine, the best available information clearly shows that the majority of people who try methamphetamine will not become addicted.17
The media and general public were not the only ones caught up in the methamphetamine hysteria. Many scientists were also bamboozled. From 2006 to 2010, I was a member of an NIH grant review committee. The committee was composed of about forty scientists with diverse expertise. One of our main tasks was to evaluate the scientific merits of research grant proposals submitted by drug abuse scientists. We frequently reviewed proposals seeking funds to study methamphetamine. Many of the proposals argued that the drug produced brain damage, while others pointed to the cognitive impairments caused by methamphetamine. They seemed to have accepted, as a foregone conclusion, that any use of this drug was destructive. These arguments were compelling to some on the review committee. The problem was that they were not supported by evidence; instead they were misrepresentations of the data. I am not suggesting that the scientists who wrote the grants did this intentionally. I don’t think they did. I do believe, however, that the scientists understood quite well the mission of their proposed funder—National Institute on Drug Abuse (NIDA)—and this understanding shaped their grant proposal.
NIDA’s mission “is to lead the Nation in bringing the power of science to bear on drug abuse and addiction.” Drug abuse and addiction are only limited and negative aspects of the many effects produced by drugs. Of course, drugs like methamphetamine produce other effects, including positive ones such as improved cognitive performance and mood, but that isn’t a part of NIDA’s mission. And scientists seeking research money from NIDA are well aware that they must emphasize the negative effects of drugs in order to get funded. Upton Sinclair’s famous quote aptly describes this situation: “It is difficult to get a man to understand something when his salary depends upon his not understanding it.”18 Consider also that NIDA funds more than 90 percent of all research on the major drugs of abuse. This means that the overwhelming majority of information on drugs published in the scientific literature, textbooks, and popular press is biased toward the negative a
spects of drug use.
I am not suggesting that the negative consequences of drug use shouldn’t be the focus of research funded by NIDA. Focusing on the pathological aspects of drug use is extremely important for developing effective treatments for drug addiction. But the current disproportionate focus on the bad effects of drugs tends to leave us with a skewed perspective. It has helped to create an environment where certain drugs are deemed evil and any use of these drugs is considered pathological. As I have repeatedly pointed out throughout this book, most people who use any drug do so without problems. This is not an endorsement for the legalization of drugs. It’s just a fact. The near-exclusive focus on the negative effects of drugs has also contributed to a situation where there is an unwarranted and unrealistic goal of eliminating certain types of drug use at any cost. Too often marginalized groups absorb the bulk of the cost. It has been well documented that certain minority communities have been particularly affected by our zeal to get rid of certain drugs. The human cost of this misguided approach is incalculable, as hundreds of thousands of men and women, including my own family members, languish in prison as a result.
In an effort to draw attention to the misinterpretations that plague the methamphetamine scientific literature, I wrote a critical review article that assessed more than fifty peer-reviewed research studies on the short- and long-term effects of the drug on brain and cognitive functioning.19 I concluded that methamphetamine addicts were overwhelmingly within the normal range on both measures. But, despite this fact, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as clinically significant abnormalities.