In recent years the recreational use of Methamphetamine (MDMA or Ecstasy) had risen greatly. It has been linked to the “rave” lifestyle. Ravers use the drug to heighten their experience while partying and dancing to electronic music. Persons outside of the rave scene who enjoy the euphoria the drug produces also employ it. Because of this Methylenedioxymetamphetamine is currently one of the most popular drugs in the Western world. Clearly research on the effects of this drug is needed to guard against uneducated use by the masses, which may have disastrous consequences.
Oral administration of MDMA results in a massive increase of extra cellular serotonin. Serotonin is a neurotransmitter, which will increase feelings of happiness and euphoria. This increase in available serotonin produces what is generally described as an extremely enjoyable high. But what are the consequences? Does one have the ability to recover from this surge of serotonin, or are MDMA users asking for the depression that is generally associated with low serotonin levels?
The objective of the article entitled “Electrophysiological Evidence of Serotonergic Impairment in Long-Term MDMA (‘Ecstasy’) Users,” is to report findings on experiments completed to determine if Methamphetamine (MDMA) use causes long-term impairment to the serotonin (5-HT) system of rats (2-4), dogs, and non-human primates. (5-7). This evidence is coupled with observation of 5-HT impairment in human recreational users of MDMA. The evidence presented in this article shows whether or not this 5-HT dysfunction in human users was caused by the users’ use of ecstasy. The research was undertaken because there is ambiguity about causation.
Does ecstasy use impair serotonergic function, or are those with such dysfunction more prone to use MDMA? A series of related experiments were undertaken by Rodney J. Croft, Ph. D. Anthony Klugman, M. D. , Torsten Baldeweg, M. D and John H. Gruzelier, Ph. D. the authors of the aforementioned article. Their findings were published in The American Journal of Psychology, issue # 158, volume 10, in October of 2001. (1) In their experiment 22 long-term MDMA users, 19 long-term cannabis users, and 20 drug-nave comparison subjects were evaluated in an attempt to determine the effect MDMA use has on serotonergic function in humans.
In order to acquire the necessary data measurements were made with EEGs (electroencelphalagrams,) to measure brain activity in the frontal cortex where serotonin is very important. EOGs (electrooculograms) were used to measure eye movements. These movements were calculated as the difference between voltages above and below the left-eye. In order to measure the serotonin an auditory intensity dependence function was employed. 5-HT in the primary auditory cortex (the part of the brain used to process sound stimulus) is thought to operate as a protective mechanism by attenuating cortical response to loud auditory stimuli.
This means that auditory stimuli and the subjects’ response to said stimuli is a good measurement of serotonin levels. (15,19). An example of this would be if the response to a 100 deci-bell noise would not be proportionately larger than the response to a noise with only 60 deci-bells. This is a particularly good way to measure 5-HT levels in MDMA users because neocortex is one the primary areas of MDMA-related damage in non-human primates. (5-7). I extrapolated that similar damage is likely to occur in humans because I know humans are closely related physiologically to the aforementioned primates.
The researchers screened the subjects in telephone interviews and excluded the ones who reported having suffered from neurological disturbances (these persons would bias the results because the sample would not longer be representational of the average healthy MDMA user. ) Also excluded were subjects who took or had taken psychotropic medication, for the same reason. The MDMA group was composed of persons who said they had used MDMA on at least 20 occasions. The comparison group was made up of subjects who had never used MDMA and didn’t use cannabis regularly.
The last group, the cannabis group if they had used cannabis at least twice a week for at least a two-year period, and MDMA only irregularly. The subjects all signed consent forms and were administered the National Adult Reading Test (21) to obtain estimated IQ. They were then fitted with an electrode cap using tin electrodes. ) and were then placed in an electrically shielded sound-attenuated booth, to see what their hearing thresholds were. The subjects then filled out a series of questionnaires about personality and drug use. At the same time the intensity dependence paradigm was run.
Duration=15 minutes. ) The data was collected an analyzed. The Kruskal-Wallis nonparametric test was used to test for differences between the intensity dependence slopes of the three groups. They then used the Nondirectional Mann-Whitney tests to do the post-hoc analyses. To make sure that the group differences were from MDMA user’s MDMA use and not other variables, data for the MDMA group were analyzes with a multiple regression in which N1/P2 slope was the criterion and the total MDMA consumption (tablets), frequency of MDMA use (tablets per month), age, and sex were the predictor variables.
The variable “total MDMA tablets used” was transformed to normality by using the square root function (yielding t_total) and “frequency of use” was transformed by using the natural log (yielding t_frequency. ) A correlation analysis was performed to determine if t_total and t_frequency were related. So what was the outcome recorded by the statistical and data analysis? Well, significant positive relations were found between MDMA users’ N1/P2 slopes and total MDMA consumption, independent of frequency of use, but not frequency of MDMA consumption independent of total consumption. In addition t_total did not correlate with t_frequency.
This data showed that regular users of MDMA exhibited lower active levels of 5-HT when compared to the drug-nave control group, and the regular users of cannabis. The experimenters concluded this to suggest 5-HT impairment in MDMA users is related to the total amount of MDMA consumed. This evidence is indicative that MDMA users have more serotonergic impairment than do non-users. Because a lot of MDMA users are also marijuana users, it was important to show that MDMA would affect 5-HT independent of cannabis use. (20) This experiment showed that impairment of 5-HT levels was unrelated to cannabis use.
The evidence also showed that it is total MDMA consumption and not frequency of use that effects 5-HT levels in the brain. It doesn’t matter how frequently or infrequently the drug is employed, it is a cumulative effect of all tablets consumed. This evidence is very convincing because it concurs with the findings of other experiments demonstrating 5-HT impairment in human MDMA users. (9-12) More importantly, the evidence falls in line with the research conducted on animals on MDMA and 5-Ht levels. (6-8). This research showed that MDMA use caused serotonergic impairment in animals.
There is strong evidence that the 5-HT deficits observed in earlier studies in humans were caused by subjects’ use of MDMA. The convergence of evidence on this topic is very convincing. The data is not, of course, perfect. There could be inaccuracies in the self-reported drug histories of the subjects. Inaccurate estimations of drug use by drug users do not seem unlikely. The article indicates that such inaccuracies would not affect interpretation because the inaccurate estimates would affect relations only with frequency of use, which there was shown to be no provable correlation anyway.
The total consumption of tablets, which was the important variable, would be unchanged. Makes sense to me. The results cannot be fully trusted as fact, because full experimental protocol was not employed in this research. Causation can’t be proved just from correlation, because there are always other elements and factors involved. The authors of the article supported their conclusion that total MDMA consumption directly affects 5-HT levels by saying “As frequency of MDMA use did not relate to either total consumption or to measures of subjects’ 5-HT levels, we believe causation to be most parsimonious explanation of the results.
I too feel that that causation is a likely and probable explanation. The frequency of use was not indicated to affect anything; it doesn’t matter if there were inaccuracies in the reporting of said frequency. The rest of the evidence seems to be fairly un-biased. Does this mean that MDMA makes users depressed? Such an extrapolation cannot be asserted with full confidence at this point in time. There are too many other factors. The cognitive impairment found in other studies to be present in MDMA users (10, 23-28) are not necessarily caused by lowered levels of 5-HT.
The impairment could be related to premorbid abilities, or use of other drugs or combinations of drugs. (20) However, I do agree with the researchers when they assert that abnormally low levels of 5-HT have a large role in depression, aggression, and violent suicide. This has been deduced theoretically (15) and predicted 5-HT deficits in groups with the aforementioned characteristics have been demonstrated empirically (29, 30).
Depression has been treated rather successfully with drugs that increase levels of serotonin, which indicates that the deficit of this neurotransmitter played a role in the depression. 0). There is also extensive case-study evidence of observed depression and other psychopathology in patients following both acute and long-term exposure to MDMA. Because of the convergence of both empirical and case-study evidence on this topic, I see a clear relationship between 5-HT levels and incidence of depression. This article shows us that there is a strong correlation and a likely causal relationship between MDMA use and lowered 5-HT levels, independent of other variables.
Therefore, the medical and psychological communities should take evidence that suggests a link between 5-HT deficit and MDMA use very seriously indeed. I would not recommend ecstasy as a recreational drug because I feel that the decreased levels of serotonin incurred by its use and possible subsequent depression is not worth the high. The second article I reviewed is entitled “Methamphetamine self-administration by humans. ” It was written by Carl L. Hart, Amie S. Ward, Margaret Haney, Richard W. Foltin, and Marian W. Fischman and published in The American Journal of Psychopharmacology, Issue # 157, pages 75-81, October 2001. Methamphetamine is a stimulant commonly found in “ecstasy” tablets sold on the street. Ecstasy tablets are rarely pure MDMA, but rather a mix of a number of stimulants. The goal of this article is to determine what are the reinforcing effects of methamphetamine in humans-that is, why is oral methamphetamine a positive reinforcer in humans?
In this study the researchers were attempting to characterize methamphetmine’s reinforcing effects in human research participants under controlled laboratory conditions. They wanted to see why people continue to orally self-administer MA despite wildly known indications that the drug is harmful. This also wanted to know if people would self-administer solely to achieve greater subjective positive effects (does it depend on how good the high is? ) In order to reach their goal, the researchers set up an experiment to figure out why MA worked as a positive reinforcer for humans.
