Effects of MDMA On The Human Body - Long-term Adverse Effects - Serotonergic Changes - Possible Neuroprotective Strategies

Possible Neuroprotective Strategies

There are a number of factors that have been shown to protect animals from long-term MDMA-induced serotonin changes. These include dose, temperature, antioxidants, and SSRIs. Some MDMA users have attempted to use analogous strategies to decrease their risks of long-term serotonin changes, although there is uncertainty as to how well this works in people.

The most obvious strategy is reducing dose. Long-term serotonergic changes are dose dependent in animals. Taking higher or repeated doses of MDMA is therefore likely to increase chances of similar changes in people. Although the threshold dose to cause toxicity is unknown in humans, lower doses are almost certainly less risky.

Studies in rats also find that environments or activities that increase the animals' body temperature increase serotonergic changes. However, this finding has not been replicated in primates, possibly because rodents are less able to regulate body temperature than primates. Nonetheless, it is possible that higher body temperature also increases serotonergic changes in people.

Antioxidants may decrease possible MDMA-induced serotonergic changes. Studies in rats have shown that injections of ascorbic acid, alpha lipoic acid, or some other radical scavengers are effective in reducing oxidative stress caused by MDMA. (Erowid, 2001) It has been speculated that humans may be able to similarly achieve protection using a combination of antioxidants, such as Vitamin A, C, and E or multivitamins including selenium, riboflavin, zinc, carotenoids, etc. may help reduce oxidative damage. No published studies have confirmed that this works. In addition, many of these vitamins, though, are water soluble, and are quickly excreted from the body. The typical MDMA user is psychoactive for 4–6 hours and may not have an appetite from the time of taking until the following sleep cycle or many hours later. Damage occurs in the absence of these antioxidants.

There are problems in trying to translate studies of neuroprotection with antioxidants from animal studies to humans. The effective doses of antioxidants given to these animals are much higher than humans would ever take both in its method of administration (injected vs. oral) and in its dosage. Both the neurotoxic and neuroprotective effects may be maximized in these animal studies, and it is not possible to know what doses or patterns of use (if any) would produce the same effects in people.

Selective serotonin reuptake inhibitors (SSRIs) have been shown to decrease or block MDMA neurotoxicity in rodents, even if they are given several hours after MDMA. Because of this, some MDMA users administer an SSRI while, or shortly after taking MDMA, in an attempt to prevent possible neurotoxicity. These SSRIs are typically antidepressants such as fluoxetine or sertraline. The theory of some scientists is that SSRIs prevent dopamine or a neurotoxic MDMA metabolite from entering through the serotonin reuptake transporter, where it is theorized that it may contribute to formation of reactive oxygen species, including hydrogen peroxide. There are several concerns with taking SSRIs with MDMA. On a practical level, administration of SSRIs will block the desired effects of the drug if taken too early. This blocking effect can last several weeks, depending on the half-life of the SSRI. In addition, MDMA and the SSRI will often mutually reduce each other's metabolism, causing them to last longer in the body. Theoretically, this might increase risk of overdosing on the SSRI, leading to serotonin syndrome. Although this appears to occur rarely (if ever), it is considered a theoretical possibility.

More significant risks occur if MDMA is taken with some other prescription drugs, including antidepressants that act as monoamine oxidase inhibitor. This can lead to serotonin syndrome and the possibility of life-threatening hypertension.

Many users also attempt to replenish the hypothesized deficit of serotonin that is thought to follow the use of MDMA by administering 5-HTP, in an attempt to reduce the depressed mood and unpleasant symptoms in the days following MDMA usage (including the immediate "come-down" and what is known as "suicide Tuesday" or "mid-week blues"). The serotonin precursor 5-HTP, which is commercially available as a dietary supplement, supplies the user with more of the raw materials to synthesize the neurotransmitter, theoretically reducing the negative psychological effects of depleted serotonin. (Note that normal dietary sources of serotonin precursors may have less than normal effects if tryptophan hydroxylase levels have been reduced by MDMA.) Varied reports indicate that the perceived impact of pre-loading is dependent upon a number of factors and while it has not been shown to reliably increase the subjective effects of MDMA, your mileage may vary.