Also, serious adverse events in MDMA users may be an interaction of the drug with a preexisting medical condition. Risk of adverse event after MDMA consumption is thought to be increased by preexisting cardiovascular problems, such as cardiomyopathy, hypertension, viral myocarditis, and congenital cardiac conduction abnormalities (such as Wolff–Parkinson–White, Romano–Ward, Brugada, and Jervell and Lange–Nielsen Syndromes).
Serious adverse events in MDMA users may also be caused by drugs sold as “ecstasy”, but which are not actually MDMA. Dangerous overheating, sometimes fatal, is associated with drugs such as PMA or 4-MTA. To help mitigate risks associated with the consumption of MDMA, certain organizations have created screening test kits to prevent the consumption of more harmful substances such as PMA, Methamphetamine, 2C analogs, BZP and TFMPP.
An important cause of death following MDMA use is hyponatremia, low blood sodium levels as a result of drinking too much water.While it is important to avoid becoming dehydrated, especially when out dancing in a hot environment, there have been a number of users suffering from water intoxication and associated hyponatremia (dilution of the blood that can cause swelling of the brain). Although many cases of this clearly involved individuals drinking large amounts of water, there are cases where there is no evidence of excessive water consumption. Their cases may be caused by MDMA inducing release of the antidiuretic hormone vasopressin by the pituitary gland. The action of vasopressin on the renal tubules leads to the retention of water, resulting in users producing less urine. (This is unrelated to having difficulty passing urine, a phenomenon known colloquially as E-wee).Hyponatremia also affects marathon runners and bodybuilders, who have been known to die from similar causes, as a result of drinking too much water and sweating out too much salt. It affects women more than men.
Hyponatremia is preventable by drinking fluid containing sodium, such as that contained in sports drinks (typically ~20mM NaCl).
The primary acute risks of taking MDMA resemble those of other stimulant amphetamines. The second most important cause of death from MDMA use is hyperthermia, core body temperature rising too high until the major organs shut down at about 42°C. This is comparatively more problematic than blood salt imbalance, harder to treat and to avoid. MDMA-related hyperthermia may occur as a symptom of serotonin syndrome, which is where too much serotonin is released into the brain. This can occur with MDMA if too much 5HTP or other serotonergic drugs are consumed together. 50–200 mg of 5HTP is believed by some users to make MDMA work better and last longer, but anecdotally more than 300 mg 5HTP may increase risk of serotonin syndrome, which can lead into lethal hyperthermia if it becomes too severe. It has been suggested that hyperthyroidism may also increase risk of MDMA-related hyperthermia.
Note that this is different from normal hyperthermia. Dance parties are an obvious hyperthermia risk environment, the venue often being hot and crowded, and the attending public dancing whilst on stimulant drugs. Ideally the temperature inside the dance rooms should be maintained in the range 24–27°C; MDMA affects the body’s ability to regulate temperature and it is easy to become either too hot or too cold if the temperature is outside of this range.
Mild hyperthermia and/or dehydration can occur from dancing too long, and users may recover with administration of fluids and rest in a cooler environment. However, if the user expresses concern about how hot they feel, or if their body temperature is still rising even when they have stopped dancing and are in a cooler environment, and their skin is hot and dry to the touch, then they may be developing more dangerous drug-induced hyperthermia, and these cases should be taken to and handled by a medical professional immediately. Treatment is most effective the sooner it is given, as with all adverse drug reactions. Hyperthermia is a particular concern if MDMA use is combined with other substances, such as 5HTP, or if additional stimulants are involved, such as methamphetamine or cocaine. MDMA is also implicated in affecting the mechanism of uncoupling protein (UCP), more specifically UCP3 in mitochondria which can lead to the abnormal thermogenic response.
In animal studies, a combination of prazosin (α1 adrenergic antagonist) and pindolol (5-HT1A antagonist/beta blocker) quickly and completely terminates drug-induced hyperthermia. Another drug, the migraine medicine pizotyline has also been shown to be useful in treating MDMA overdose in animals. However, neither of these treatments are approved for use in humans.
MDMA appears to decrease heat loss in the body by causing constriction of blood vessels near the skin. In addition, it can increase heat production by muscles and the brain. These effects may be amplified in people who become dehydrated and are therefore unable to cool by sweating. On top of this, MDMA can mask the body’s normal thirst and exhaustion responses, particularly if a user is dancing or is otherwise physically active for long periods of time without hydration. Because of these effects, MDMA can temporarily reduce the body’s ability to regulate its core temperature so that high-temperature surroundings (e.g. clubs) combined with physical exertion may lead to hyperpyrexia if precautions are not taken to remain cool. Sustained hyperpyrexia may lead to rhabdomyolysis, which in turn can cause renal failure and death. Depending on the initial cause of rhabdomyolysis, it may be successfully treated with dantrolene if diagnosed early enough, but often the characteristic symptoms may not be apparent until the condition is already severe.
MDMA-induced hyperthermia may be treated with dantrolene.
Due to the difference between the recreational dose and the lethality dose, it is extremely rare for a death to be accredited just to the consumption of MDMA. While a typical recreational dose is roughly 100–150 mg (often being measured by eye and dealt with as fractions of a gram), this dose is often then repeated but remains well below the lethal dose. Consumption of the drug can be self-reinforcing while under the influence, and overdoses can occur.
The standard treatment for MDMA overdose given in hospitals includes a range of drugs such as cyproheptadine or chlorpromazine but these are often of limited efficacy. MDMA overdose mainly results in hyperthermia and hyponatremia, which leads onto convulsions from the hyponatremia and rhabdomyolysis (toxic muscle breakdown) from the hyperthermia. These complications can be treated; benzodiazepines such as diazepam or lorazepam are used to control convulsions and dantrolene blocks rhabdomyolysis.
It’s been argued that “the seriousness of the effects can be dependent on environmental factors other than the drug concentration”, as blood concentrations of the drug spanned a large range in cases of death in MDMA users. This not-with-standing, “most of the cases of serious toxicity or fatality have involved blood levels… up to 40 times higher than the usual recreational range.”
Quoted from Dr. Julie Holland: “Not only are MDMA related cases a small percentage of all drug-related emergency room visits, but a large percentage of MDMA cases are not life-threatening. In a recent study conducted by the physicians in the Emergency Department of Bellevue, (Rella, Int J Med Toxicol 2000; 3(5): 28) regional hospital ecstasy cases phoned into the New York City poison control center were analyzed. There were 191 cases reported during the years 1993 to 1999 inclusive. This is a rate of fewer than thirty cases per year. 139 cases (73%) were mild and experienced minor or no toxicity. The most commonly reported symptoms were increased heart rate (22%), agitation (19%), and nausea and vomiting (12%). In these seven years, only one ecstasy-related death was reported, which was due to hyperthermia, or overheating.
Other adverse effects
MDMA users almost always experience bruxism (teeth grinding) and trismus (jaw clenching) as a short-term effect from the drug. Many users of MDMA alleviate this by using chewing gum, or chewing on improvised mouth guards (such as a small plastic glow stick or pacifier). Temporary jaw ache often results from jaw clenching or excessive chewing. Some users consume supplemental magnesium tablets to relax the jaw muscles and relieve clenching, although this practice has not been formally studied. In extreme cases, MDMA use has been associated with excessive wear of teeth and resulting dental problems.
Liver damage, which may have an immunological cause, has been seen in a small number of users. It is not clear to what extent liver toxicity is caused by MDMA or other compounds found in ecstasy tablets. Animal studies suggest MDMA can cause liver damage and that the risk and extent of liver damage is increased by high body temperature.
While there has been an urban legend that having an allergy to penicillin or related antibiotics means one is allergic to MDMA, this myth is baseless, as the two drugs are far too different for an allergy to one to translate into an allergy to the other.
In very rare cases, MDMA has been associated with serious neurological problems such as subarachnoid hemorrhage, intracranial bleeding, or cerebral infarction. Similar problems have been noted with amphetamines. The mechanisms are thought to involve the short-term hypertension leading to damage of cerebral blood vessels, especially in patients with pre-existing conditions such as arteriovenous malformations or cerebral angiomas.
While users sometimes report increased sexual desire, there are many reports of difficulty achieving both erection and orgasm while on the drug. It has been said that, “[MDMA] is a love drug but not a sex drug for most people.” This is the rationale behind the use of sextasy (combining MDMA with Viagra).
The combination of MDMA and low doses of viagra has been shown to prevent MDMA related serotonin depletion in rats. It even has a preventative effect 24 hours later by increasing resistance to MDMA-related oxidative stress