Ecstasy use and mental health.

There’s been a news story claiming that ecstasy use causes depression. The research this story is based on has apparently never been published, suggesting that it was of such low quality that even in an age of anti-drug hysteria no scientific publication felt it was worth printing. However, the basic finding (that ecstasy users are more likely to have emotional problems) does in fact appear to be true.

In a large longitudinal German study (tracking about 2,500 people over time) it was found that, at the end of the study, 68% of those reporting having used “ecstasy” at least once also reported having suffered from a DSM-IV psychological disorder at some point in their lives.[18] (DSM-IV is a mental health diagnostic manual.) However, the researchers report that in about 90% of these cases, the person was diagnosed with a mental disorder before their first use of ‘ecstasy.’ It is likely that MDMA (and other drug use) can trigger or worsen psychiatric problems, but in at least the vast majority of cases, psychiatric problems are more likely to be the cause of the drug use, not the other way around. ‘Ecstasy’ users, statistically speaking, are not normal to start with.

• Visit the Mental Health page for more information.

“But I know people that are stupid/emotionally unstable from using ‘ecstasy’…doesn’t that mean they’ve been brain damaged?!”

Not necessarily. The nervous system tries to correct for unusual levels of activity, often by ‘turning the volume down’ (or up) on different systems. In the case of coffee drinkers, your brain makes itself less sensitive to caffeine, creating tolerance (and in many cases, mild dependence.) If you take a lot of acetaminophen, your body eventually works to counteract it, which can lead to ‘rebound’ headaches (the headache coming back if you stop taking acetaminophen.) This phenomenon of your brain trying to compensate for unusual factors (such as drugs) is called neuroadaptation, and is one cause of drug tolerance (needing more to have the same effect) and physical dependence. Neuroadaptation is not damage! It is a constant, normal, and entirely controlled process by which your brain tries to keep itself running smoothly.

Sometimes neuroadaptation can be manipulated in useful ways: SSRI antidepressants like Prozac, Zoloft, Paxil, etc. work partly by getting your brain to change its sensitivity to serotonin (for those drugs the process is somewhat slow, which is why it takes several weeks for an SSRI to become fully effective against depression.)

However, in the case of recreational drug use, this effect is almost always disruptive: You take a drug for a brief period, your brain tries to compensate, and then when the drug is gone your brain is off-balance again, now over-compensating. It will return to normal, but the process can take days, weeks, in some cases even months. In the case of MDMA, your brain makes itself less sensitive to serotonin to try to compensate for all the serotonin the drug releases. Fully re-setting its sensitivity levels after even a single use of MDMA can take weeks, even months from a very high dose. If you use MDMA frequently, your brain doesn’t have enough time to re-set and gets pushed further and further from normal levels of serotonin sensitivity. In extreme cases, this can apparently lead to users becoming seriously depressed, anxious, unmotivated, poor memories, etc.

It’s quite understandable that people are afraid of brain damage when they experience this sort of mental disruption; the average person has never been told that there were any other possible explanations, in spite of virtually all of us being familiar with the basic phenomenon in the form of ‘needing that first cup of coffee in the morning to get going’ and the like. My position is not that people don’t get seriously screwed up by frequent use of MDMA; only that the cause is unlikely to be actual permanent damage. Given a break from use of a few months, even the most severely ‘e-tarded’ user should find themselves greatly improved as the brain slowly returns to its normal ‘volume settings.’ (For more information and an animation of one process of neuroadaptation, visit MDMA At Work.)

Conclusions

I absolutely believe that MDMA can be neurotoxic in humans. There’s just no reason to believe that it is at a sane dosage/under normal circumstances, and your odds can be greatly improved with a little common sense: Don’t mix drugs, be aware of overheating dangers, and take some antioxidants.

What I would consider safe usage of MDMA?

• A single dose. Taking multiple full doses in an evening may not be safe. As a single dose, however, even doses high enough to just about knock you on your ass (in the 2 mg/kg range) are probably safe. (‘Safe’ in the sense that driving a car is safe; relative, not absolute safety.)

• A safe environment. That means either moderate (‘room temp’) air temperatures or avoiding high levels of activity (dancing.)

• No drug mixing, including alcohol. Not all drugs can increase risk, but unless you’re sure you know what you’re doing, it’s best not to be on other drugs while high on MDMA.

MDMA-related injuries and deaths are in most cases actually overheating injuries and deaths. MDMA does not normally cause significant increases in body temperature in humans; a significant increase in body temp is abnormal and should be treated immediately.

The role of overheating in MDMA neurotoxicity can hardly be exaggerated; no animal experiment has ever produced neurotoxicity at any dose of MDMA at normal human body temperature. In the infamous Ricaurte “Ecstasy Parkinsonism” monkey experiment, his animals reached body temperatures of as high as 107F. More typically, experimental animals that develop MDMA neurotoxicity reach body temperatures of about 39C (103F). Although the exact mechanisms of MDMA neurotoxicity are at best imperfectly understood, damage is clearly a result of the combination of the unusual strain placed on the neurons by drug exposure being greatly amplified by overheating. I do not anticipate human neurotoxicity at any likely voluntarily taken dose of MDMA in the absence of significant and prolonged hyperthermic response.

Origin of the Species

The research leading to this final document involved a comprehensive review of English-language MDMA research from the 1950s to present; well over a thousand journal articles detailing numerous animal and human experiments, field reports from doctors, opinions of experts, etc. ‘Library research’ of this sort is a rather thankless and tedious task, but when you get to the end, you’ve really gotten to the end; no opinion is left unconsidered, no research left unexamined. I compiled my notes, discussed and argued with other academics, contacted researchers for more information in some cases, etc. This document expresses and makes the case for the final opinion that my research brought me to: That moderate recreational use of MDMA does not present a credible risk for neurotoxicity. It is not a comprehensive discussion of the totality of the research (although most brain scan work, pro and con, has been included.)

Conspicuously lacking is detailed coverage of the numerous generic sorts of ‘ecstasy users not as mentally sharp’ type of research. This was not done as a way to avoid evidence against my position; rather it is because the quality of such research has been so consistently poor as to not merit detailed examination. The typical work in this category makes the following chain of assumptions:

1. People who use ‘ecstasy’ were (prior to their drug use) just like non-drug users.

2. The people we recruit are representative of the larger user population.

3. No other drugs that the volunteers use will affect results.

4. There are no differences in sleep patterns, sub-clinical psychiatric disturbances or any other environmental factors that could affect test performance.

5. Any differences that are found must be due to permanent damage. Neuroadaptation (such as the brain scan research amply demonstrates the existence of) will not be considered.

Assumption 1 has been disproven; pre drug-use rates of mental illness in ecstasy users are higher than those of non-drug users as well as users of other categories of drugs. Assumption 2 cannot easily be disproven, but is unlikely to be true. Assumption 3 is disproven by the unremarkable fact that when concurrent use of marijuana is controlled for, differences in cognitive performance (such as word recall) mostly or entirely vanish. 4. Ravers (attendees of all-night dance parties) are usually the recruitment pool for volunteers, which brings a rather unlikely assumption of otherwise equivalent lifestyles between ecstasy users and non-users. 5. That MDMA causes transient disruptions of memory is well established anecdotally, and should be inferred from research identifying neuroadaptive changes in available serotonin receptor densities in both experimental animals and humans following recent MDMA exposure. Researchers in the ‘ecstasy users have worse memories’ field tend to ignore this problem. Those that do make some effort to control this effect usually do no more than ask volunteers not to use for two weeks and give urine test for drugs the day of testing. However, all research indicates that MDMA can subtly affect the mind for at least 3-4 weeks, and urine drug tests only detect use within the past few days.

A less obvious problem in such human research is subject bias. When testing a new medication, you can’t let the people who you’re testing it on know if they’re getting the real drug or a sugar pill, because expectations can produce a powerful placebo effect; people who expect to feel better inevitably do feel better. Any sort of expectation of what the results will be by the test subjects will throw off those same results. This sort of problem is especially great when testing drug users for cognitive effects, because not only do they know if they’re in the control group or not, they probably have some idea of what the researchers expect the result to be. (For instance, just about anybody you recruit for an MDMA study knows that they are expected to have memory problems.) How can you control for this sort of bias? The honest answer is you can’t, although you can at least try not to promote a bias. The most flagrant act of fraud I’ve seen in this category was a researcher who, before testing some ‘ecstasy’ users to see if they were different from non-users, told them that their MDMA use caused untreatable brain damage that would impair their performance. It takes balls of steel to deliberately shape experimental results like that, but not everybody working in this field has a high sense of scientific integrity.

In the end, I hold a dim view of the genre. Besides, why try to guess at serotonergic damage from behavior when we have perfectly capable brain-scanning technology to directly examine the serotonin system? For these reasons of both quality and directness of the measurement technique this page almost exclusively examines brain scan work. At the end of the day, I am wholly unmoved when Billy Bob the psychologist publishes an article claiming evidence of neurotoxicity because his ecstasy-using volunteers were not identical to his non-drug using volunteers. There is an ocean of confounds that must be bridged to make such conclusions credible, especially in light of the strong evidence of no permanent structural changes in user’s brains. The quality of retrospective human research has, however, been increasing over the years; with luck, the future may bring more substantive work.