Newsgroups: alt.psychactives,alt.drugs From: rjesse@oracle.uucp (Robert Jesse) Subject: MDMA: Neurotoxicity and Safety Discussion Message-ID: <1994Feb26.223506.27127@oracle.us.oracle.com> Date: Sat, 26 Feb 1994 22:35:06 GMT at Oracle Corporation. The opinions expressed are those of the user and not necessarily those of Oracle. Here is some material that was recently submitted for inclusion in a future revision of the MDMA FAQ - I thought it may be of interest to some people sooner rather than later. If you have any corrections or constructive comments, you could send them to me and to Jon Taylor, the author and maintainer of the MDMA FAQ . Thanks. ps: note that these sections of text are not intended to stand alone. the FAQ contains important information - dosing, contraindications, etc. - that is not replicated here. ----------------------------------------------------------------------------- Neurotoxicity and Safety Discussion =================================== Neurotoxicity? -------------- One claimed effect of MDMA use is lowered brain serotonin levels. One study (Peroutka) found no evidence for this, but at least two others (Ricaurte) have found significantly reduced serotonin metabolite levels, the most recent study showing a 30% average difference between the control group of non-MDMA users and the experimental group consisting of people who had used MDMA about 75 times each, on average. What does this mean for users? Anecdotal evidence from years of legal and illegal use suggests that this is not of much concern for most people. Some folks, however, report periods of depression after using MDMA, on rare occasion severe depression. Considering that a primary action of many antidepressant drugs (MAOIs, SSRIs) is to increase brain serotonin levels, a connection between MDMA use and subsequent depression is not unbelievable. Psychological factors - sadness at returning to an ordinary state of consciousness after ecstasy - may also account for feeling down for a while. In any event, most users report the opposite: feelings of well-being or gentle euphoria in the days following an MDMA session. To get a better understanding of why the serotonin system may be critical to normalcy for some individuals and less so for others, see Listening to Prozac by Peter D. Kramer (Viking 1993). The entire book is worthwhile, but note pages 134-136 especially. There is solid experimental evidence that MDMA, administered in large doses and/or repeatedly, causes partial loss of serotonergic neurons in laboratory animals. Uncertain is whether this loss is permanent, reversible, or important. One study found in the rat nearly 100% recovery within a year. In another study (Ricaurte), non-human primates were dosed with MDMA and their brains were examined for morphological changes. Ricaurte found that there was no effect after 2.5 mg/kg oral doses given every two weeks, for a total of eight doses. But after a single oral dose of 5 mg/kg, he observed a 20% reduction in serotonergic neurons, only in the thalamus & hypothalamus. There appeared to be some regrowth over time, not necessarily complete, and also some "collateral sprouting" - growth of other types of neurons in the reduced serotonin areas. Note that in all of the animal studies, even when there are quite large serotonin system reductions (up to 90% in high MDMA dose rat studies), no behavioral deficits are observed. It is also uncertain how these studies would extrapolate to humans - the human brain may well be more or less sensitive, or sensitive in different areas, compared with other animals. In any case, what is known is that there are no reported cases that link behavior changes in humans with MDMA-induced serotonin system changes or neuronal loss. And, the long-term human behavior changes that are noted (in studies and from anecdotal case reports) are generally regarded as positive - lowered impulsiveness and hostility, improved social/interpersonal functioning, changes in religious/spiritual orientation or practice, etc. One of the reasons so little is known about the lasting effects of MDMA on the human brain is that no subjects (to date) have recorded their drug use history, then volunteered their brains for post-mortem study. If you would like to consider doing this, you can get donor information at 1-800-UM-BRAIN. Studies with live human subjects are also underway - both volunteers and donations are needed. One good source of current info is the Multidisciplinary Association for Psychedelic Studies (MAPS) - see "Organizations" at the end of the FAQ. Immune System ------------- Some users of MDMA report an apparent decrease in resistance to disease, especially with frequent MDMA use. It is unknown how much of this may be due to the pharmacological "body load" of MDMA, to staying up all night and dancing, to increased physical contact with people with colds, to suppressed appetite and poor nutrition, etc. Preventive Measures ------------------- A fundamental precaution is to stay well hydrated. Drink water frequently during the MDMA session, and moreso if you're physically active. Under the influence, time can pass surprisingly quickly. It is useful if trip guides or trip buddies remind each other to drink water often. For those who are concerned about the possibility of serotonin level or serotonin system changes in humans with therapeutic doses of MDMA, some researchers reckon changes can be lessened or prevented by taking antioxidants. In an article titled "Phenethylamines, Free Radicals, and Antioxidants" (MAPS Newsletter, Volume IV Number 1), author Brian Leibovitz suggests in Table 1 taking as a preventive measure the following: 5 mg B-Carotene; 2 grams Bioflavonoids; 100 mg Coenzyme Q10; 2-4 grams L-Ascorbic acid; 1 gram L-Carnitine; 2 grams N-Acetylcysteine (NAC); 250 ug Selenium, and 1,000 IU Vitamin E. "There is nothing magic about the doses listed; it is my best estimate based on present knowledge in nutrition." If you don't feel like buying out the local vitamin store, taking a subset of these (even just the ascorbic acid - vitamin C) could well be helpful. And, if you're really concerned, recent non-human animal research suggests that most or all of the serotonin system reduction may be prevented by taking Prozac (fluoxetine) 0-6 hours after taking the MDMA (see McCann and Ricuarte in J. Clinical Psychopharmacology, 13 (3):pp. 214-217, 1993). One might speculate that other SSRI drugs (Zoloft, Paxil) may work too. Note, however, that some people report that Prozac taken before or in the early part of an MDMA session lessens some of the desirable effects of the MDMA. Behavioral Safety Concerns -------------------------- As noted, a primary psychological effect of MDMA is to make the user feel "safe", at peace with the world, pleasantly reconciled to things as they are, and things however they will be. This can remarkably diminish one's ability to make "sound" judgements during the session. Examples: - It becomes easy to want to prolong the MDMA state by taking more and more of the drug, beyond what you would judge wise or worthwhile when not under its influence. - It becomes easier to have unsafe sex. You may "forget", judge that the risk of infection is very small, or feel that infection wouldn't be such a terrible thing after all. If you think you might have sex while on MDMA, it may help you and your partner to stay safe if you lay out safer sex supplies before dosing in a place you'll be sure to see them later, and agree beforehand that you'll use them if the occasion arises. Another danger stems from MDMA's lessening of the awareness of pain (whether through chemical analgesia, or through psychological analgesia). Combined with the extra energy the drug gives, it becomes easy to sustain bruises, blisters, or other tissue damage from extensive dancing, hiking, climbing, etc., without noticing it until after the damage is done. Under MDMA, it may seem "right" to make immediate changes in relationships (increasing or decreasing commitment) of all kinds. The new points of view appreciated during an MDMA session are one of the drug's most prized benefits, but it is probably unwise to actually make lasting relationship changes until you have a chance to see how you would feel about them after the drug and its afterglow wear off. Conclusion? ----------- One take on all this information is that there are a great many questions unanswered by research as yet. Thus a conservative, prudent assumption is that the risk of some kind of subtle neurological "damage" in humans from MDMA use is not zero. Yet there is no empirical evidence of neurological harm in humans (and there is considerable evidence of psychological benefits) - this in many years of legal use (before 1986 in the US), and quite widespread illegal use since then. Given any non-zero risk, it makes sense to examine the benefit side of the equation, and take the drug only when you expect to get some tangible positive outcome from it that you feel makes taking the risk worthwhile.