Ecstasy has become increasingly popular among young adults, especially within the young adult dance scene at parties known as “raves.” Ecstasy or 3,4-methylenedioxymethamphetamine, also known as MDMA, gives users a euphoric feeling, often making them feel closer to other people, thus giving it the name, the “love drug” (Ramcharan, Meenhorst, Otten, Koks, de Boer, Maes, and Beijnen, 1998). Patented in 1914 as an appetite suppressant, MDMA was banned in the 1980s (Henry, Jeffreys, and Dawling, 1992). Many users today assume that MDMA is relatively safe and only causes slight impairments to functioning; however, research shows that use of MDMA can have neurotoxic effects. Studies indicate that ambient temperatures can induce toxicity, and MDMA use can cause a decrease in 5-HT (one type of serotonin receptor) axons and axon terminals (Malberg and Lewis, 1998). When regeneration of 5-HT axons does occur, it is often abnormal (Green and Goodwin, 1996; Hatzidimitriou, McCann, and Ricaurte, 1999).
Kalat (2001) states that low serotonin release can cause an increase in aggressive behavior. Studies show that monkeys with low levels of serotonin turnover display an increase in aggressive behavior. This also may be true for humans with similar serotonin deficiencies: low serotonin has also been found in persons attempting suicide. However, it is not conclusive that low serotonin is responsible for aggression as it is for impulsiveness. Mice given the choice of a small but more frequent reward or a larger reward with a longer waiting period chose the small but frequent reward. Serotonin levels not only affect aggression and impulses but thermoregulation as well (Ramcharan, Meenhorst, Otten, Koks, de Boer, Maes, and Beijnen, 1998). In studies of tissue distribution in MDMA users, the brain and liver showed the highest levels of MDMA (Ramcharan, et al, 1998).
In a study of the effects of ambient temperature and neurotoxicity on MDMA, it was found that a change in the ambient temperature of as little as 2° Celsius (C) can cause neurotoxicity (Malberg and Lewis, 1998). In the study, rats were treated with either MDMA or saline. Ambient temperatures were controlled at 20°, 22°, 24°, 26°, 28°, or 30° C, core temperature was measured, and after two weeks, the rats were killed, and 5-HT and 5-hydroxyindole acetic acid levels were analyzed for toxicity (Malberg and Lewis, 1998). It was found that in rats that were treated with saline, the core temperature was not affected by the ambient temperature; however, in the MDMA treated rats, hypothermia was produced in ambient temperatures of 20° and 20° C, and hyperthermia was verified in the MDMA-treated rats in an ambient temperature of 28°-30° C (Malberg and Lewis, 1998).
No changes in neurotransmitter levels were found in the saline-treated rats that were in an ambient temperature of 24°-40° C; however in the MDMA treated rats, depletions of 5-HT and 5-HIAA levels occurred with 24° C being the “breaking point.” As the ambient temperature increased, the more depletion of serotonin receptors was found (Malberg and Lewis, 1998). It seems that MDMA causes neurotoxicity with increased ambient temperatures. Caution is needed since many users take MDMA at “rave” parties where the environment is very warm, and the users are often dancing, drinking alcohol, and not replacing lost fluids. Thus, one of the environments that MDMA use is most popular, raves, could also be one of the elements that increases the neurotoxicity of the drug.
In another study (Hatzidimitriou, McCann, and Ricaurte, 1999), monkeys were studied to find if 5-HT deficits continued after seven years of being treated with MDMA. Previous studies were done 18 months after MDMA had been administered. Monkeys were treated with either saline or MDMA and killed at either two weeks or seven years following administration of saline or MDMA. The monkeys treated with saline showed no significant changes in 5-HT axon density, thus ruling out axon degeneration caused by aging. In MDMA-treated monkeys, significant reductions of 5-HT axon densities occurred in many areas of the brain, including the cerebral cortex, hippocampal formation, striatum, amygdaloid complex, hypothalamus, thalamus, and raphe nuclei. Of those areas, all except the hypothalamus, thalamus, and raphe nuclei, showed significant loss in 5-HT axon density at two weeks, and when there was recovery after seven years, it was rarely full recovery and often the recovery was abnormal. After seven years, the hypothalamus had complete recovery to damaged 5-HT axons, most of the nuclei of the thalamus had complete recovery in the seven-year monkeys, and the raphe nuclei showed no loss of cell bodies or 5-HT axons at either two weeks or seven years in the MDMA-treated monkeys (Hatzidimitriou, McCann, and Ricaurte, 1999). Hatzidimitriou, et al., state that there could be several factors to explain the regeneration in some areas of the brain and not in others. One explanation is the proximity of the axons to the cell bodies, the myelination of the fibers, and the size of the lesion caused by MDMA. In the occipital lobe and the primary visual cortex, reduction occurred in fibers in layer IVC. Even after seven years, the layer was still unrecognizable as a distinctive layer. In the hippocampal formation, the subiculum showed the most decrease in 5-HT axons, with an 80 percent loss remaining even after seven years (Hatzidimitriou, McCann, and Ricaurte, 1999).
Boot, McGregor, and Hall (2000) state that the most long-term damage is done to the 5-HT axons of the cortex, hippocampus, and striatum. There is an argument in the studies aforementioned. One argument is that the laboratory animals have the MDMA injected, while many human users of MDMA take the drug orally. The injection of MDMA in monkeys is far more neurotoxic than oral ingestion in humans (Boot, McGregor, and Hall, 2000). Another argument is that low densities of 5-HT axons might be the cause of MDMA use.
There have been links between low 5-HT concentrations and impulsiveness (Boot, McGregor, and Hall, 2000). Boot, McGregor, and Hall (2000) also state that heavy users of MDMA have EEG patterns similar to patterns of people who are aging or experiencing dementia.
Research shows that severe degeneration of parts of the brain can occur after a single dose of MDMA in rats (Green and Goodwin, 1996). Yet, there are cases of individuals who have survived massive overdoses of MDMA.
In one case, a 30-year old man, who was reported to have taken 50 tablets of MDMA in addition to alcohol and oxazepam, was admitted to the hospital comatose and convulsing. With the exception of an increase in the enzyme creatine phosphokinase (CPK), (probably convulsion induced), the subject had a complete recovery in two days (Ramcharan, et al, 1998). Although the literature does not state whether or not there was significant reduction in his 5-HT axons or axon terminals, perhaps the dosage was not as lethal as it could have been. The man took the dosage at home in a cool and relaxed atmosphere where the ambient temperature did not increase to the levels indicative of toxicity (Ramcharan, et al, 1998). The literature does not indicate if the individual was taking any prescription drugs in prescribed dosages. Studies (Malberg and Lewis, 1998) have shown that fluoxetine (Prozac) can prevent MDMA from entering 5-HT neurons. Although rats in the experiment still suffered from hyperthermia, there was no evidence of neurotoxicity with a fluoxetine pretreatment. Despite this individual’s survival of such high doses of MDMA, due to the neurotoxicity of MDMA, and its effects on 5-HT axons and axon receptors, there could also be long-term psychological problems due to impairment of serotonin processing, including depression, aggression, and impulsiveness. Studying the effects of MDMA in humans is difficult. MDMA cannot be administered to humans in a research situation, and the means of administration to animals is often different from that of humans, so frequently studies must be done on individuals and self-reports. Even when examined in a scientific situation, results may be inconsistent. If people obtain MDMA illegally, and it is not a natural-based drug, ingredients and the levels of the ingredients are likely inconsistent, thus making it difficult to determine exactly at what levels neurotoxicity occurs, and if perhaps other chemicals might be reacting with MDMA. In the mean time, more research needs to be done to determine the effects of MDMA on humans, and the effects selective serotonin reupkate inhibitors such as fluoxetine have on the decrease of the toxicity of MDMA.
References
Green, R. &Goodwin, G. (1996, June). Ecstasy and neurodegeneration: ecstasy’s long term effects are potentially more damaging than its acute toxicity. British Medical Journal [Online serial], 312(7045):1493, Retrieved March 24, 2001 from the World Wide Web: http://web7.infotrac.galegroup.com/itw/I...0_A18456698&dyn=70!ar_fmt?sw_aep=nu_ma
Hatzidimitriou, G., McCann, U., & Ricaurte, G. (1999, June). Altered Serotonin Innervation Patterns in the Forebrain of Monkey Treated with (+/-)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery. The Journal of Neuroscience [Online serial], 19(12):5096-5107, Retrieved March 24, 2001 from the World Wide Web: http://www.jneurosci.org/cgi/content/ful...d=QID_NOT_SET&stored_search=&FIRSTINDE>
Henry, J., Jeffreys, K., & Dawling, S. (1992, Aug). Toxicity and deaths from 3,4-methylenedioxymethamphetamine (“ecstasy”). The Lancet [Online serial], 340(8816): 384(4), Retrieved March 24, 2001 from the World Wide Web: http://web7.infotrac.galegroup.com/itw/I...0_A12554376&dyn=98!ar_fmt?sw_aep=nu_ma
Kalat, J. (2001). Biological Psychology (7th ed.). Belmont
Malberg, J & Seiden, L. (1998, July). Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)=Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat. The Journal of Neuroscience [Oneline serial], 18(13):5086-5094, Retrieved March 24, 2001 from the World Wide Web: http://www.jneurosci.org/cgi/content/ful...d=QID_NOT_SET&stored_search=&FIRSTINDE>
Ramcharan, S., Meenhorst, P.L., Otten, J.M.M.B., Koks, C.H.W., de Boer, D., Maes, R.A.A., & Beijnen, J.H. (1998, Dec.). Survival After Massive Ecstasy Overdose. Journal of Toxicology: Clinical Toxicology [Online serial], 36 (7): 727, Retrieved March 24, 2001 from the World Wide Web: http://web7.infotrac.galegroup.com/itw/i...0_A53499521&dyn=49!as_fmt?sw_aep=nu_ma