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Newsgroups: alt.drugs
From: an13187@anon.penet.fi (H-Man)
Subject:  MDMA article
Message-ID: <1993Jul3.005415.4993@fuug.fi>
Date: Wed, 30 Jun 1993 02:04:54 GMT

[some bs deleted -cak]

                          JAMA(R) 1992; 268: 1505-1506
 
                    September 23, 1992 / September 30, 1992
 
SECTION: MEDICAL NEWS & PERSPECTIVES
 
LENGTH: 1565 words
 
TITLE:  Ecstasy -Fueled 'Rave' Parties Become Dances of Death for English
Youths
 
AUTHOR: Teri Randall
 
TEXT:
   THE ILLEGAL designer drug  ecstasy  -- promoted by some as a safe, nontoxic
means to "warm, loving relaxation" -- has killed at least 15 young people in
England in the last 2 years and caused severe toxicity in numerous patients,
experts report from that country's National Poisons Unit.  In almost every
case, a recreational dose of the drug had been taken at a dance club or
party where crowds danced vigorously in popular, all-night dance sessions
called "raves." 
 
   In most of the serious cases reported, the users had collapsed
unconscious or started to convulse while dancing.  By the time they were
noticed and taken to emergency departments, their body temperatures had
soared as high as 110 degrees F (43.3 degrees C), their pulses were racing,
and their blood pressures were plummeting.  These patients with severe
toxicity usually developed disseminated intravascular coagulation,
rhabdomyolysis, and acute renal failure.  Despite treatment, death sometimes
ensued from 2 to 60 hours after admission, usually due to severe
hyperthermia accompanied by disseminated intravascular coagulation.
 
   Severe or fatal reactions of this type are virtually undocumented in the US
drug abuse literature concerning  ecstasy  (also known as  MDMA  for its
chemical name, 3,4-methylenedioxymethamphetamine).  But this pattern of illness
has recently become all too familiar in British medical journals (J R Soc Med.
1991; 84:371; J R Soc Med. 1992;85:61; BMJ. 1992;305:5,6,29; BMJ.
1992;305:309-310; and Lancet. 1992;339:677-678).
 
   The most recent report, published 6 weeks ago, describes seven fatalities,
all associated with rave dances (Lancet. 1992;340:384-387).  The report also
describes seven cases of unexplained hepatotoxicity (including one death)
attributed to a history of  ecstasy  use.
 
   According to the authors, the pattern of illness and the amounts of  MDMA
ingested rule out the possibility of an overdose.  In most cases the user had
taken only a few tablets or capsules.  By comparison, one analytically
documented  MDMA  overdose -- allegedly 42 tablets taken at home -- was
accompanied by no symptoms other than a "hangover" with tachycardia and
hypertension.  The patient's plasma  MDMA  level was 7.72 mg/L, which is six to
70 times greater than the plasma levels measured in the fatal cases.
 
   John Henry, MD, consulting physician for the National Poisons Unit at Guy's
Hospital, London, England, and lead author of the most recent Lancet report,
says that prolonged, vigorous dancing (which may itself be an effect of
 MDMA)  may compound the pharmacologic effects of the drug.  The
amphetamine-derived  MDMA  has been shown to increase body temperature in rats,
presumably by interfering with serotonin metabolism in the brain.
 
   Higher ambient temperatures seem to intensify this effect, and the hot,
poorly ventilated environments of some nightclubs, together with inadequate
fluid replacement, may be sufficient to elevate body temperature to lethal
levels in susceptible individuals, Henry suggests.
 
   The finding has relevance for the international medical community because
the rave culture is now being exported to the United States and other
countries (see accompanying article).  Henry urges physicians to be aware of
the drug's pharmacologic effects when it is combined with this type of
dancing.  Cases of severe hyperthermia or unexplained jaundice or
hepatomegaly should suggest possible  MDMA  toxicity, he says.
 
   For the patient who is taken acutely ill, medical treatment is urgent and
includes control of convulsions, measurement of core temperature, rapid
rehydration, active cooling measures, and possibly use of the antispasmodic
drug dantrolene (Anaesthesia. 1991; 47:686-687).
 
A 'Cultural Reformulation'
 
   Of great interest to Henry is how the drug has been adopted by, and has
perhaps even catalyzed, the new rave culture in England -- similar, he says, to
the Acid Test parties of the 1960s and the use of LSD (lysergic acid
diethylamide) and amphetamines.  The drug's association with the rave scene has
led to its enormous popularity in England.  An estimated half-million people in
that country have taken  MDMA,  he says, most of them young people.
 
    MDMA  use had been widespread in both the United States and England
throughout the 1980s, but in a much different context, and with different
outcomes.  Users usually took it while they were alone or with a small group of
people.  Ninety percent of users in one US study said the drug made them feel
euphoric, more verbal, and closer to other individuals.  Some called it the
"love drug."
 
   In a study done at Stanford (Calif) University School of Medicine in 1987 --
at the peak of the drug's popularity in the United States -- 39% of the
undergraduates reported they had used  MDMA  at least once (N Engl J Med.
1987;317:1542-1543).
 
   In the late 1980s, the drug was "'reformulated,'" Henry says, "not in the
pharmacologic sense, but in the cultural sense." The rave scene in England
provided a "new 'formula,' a new package, a new culture." And it is this new
cultural context that has, unfortunately, provided a real-life showcase for
 ecstasy's  previously unknown lethal potential.
 
   Before this "reformulation," the handful of reported fatalities were mostly
cardiac arrhythmias in individuals with underlying natural disease (JAMA. 1987;
257:1615-1617).
 
   Many users did experience adverse effects, however.  In a 1986 study, 29
volunteers were given 75 mg to 150 mg (a "recreational dose") of pure  MDMA  by
psychotherapists (J Psychoactive Drugs. 1986;18:319-327).  All 29 experienced
undesirable physical symptoms: 28 lost their appetite, 22 had trismus or
bruxism, nine had nausea, eight had muscle aches or stiffness, and three had
ataxia.  Sweating was common, and tachycardia and hypertension were recorded.
Afterward, 23 people noted fatigue for hours or days, and 11 had insomnia.
 
   The mechanism by which  MDMA  elevates body temperature is still a matter of
speculation, although experts suspect it involves the drug's interference with
serotonin metabolism in the brain.  In experimental animals,  MDMA  stimulates
the release of this neurotransmitter from serotonergic neurons, particularly
from those in the dorsal raphe.  Under normal conditions, released serotonin is
taken up into the terminal endings of the cells that released it.  But in the
presence of  MDMA,  this reuptake process is altered, leaving the nerve cells
depleted of serotonin.
 
   The waters are muddied, however, when one looks at clinical experience.
Some experts have argued that there is no clinical evidence that people who use
MDMA  develop such typical symptoms of serotonin depletion as disorders of
sleep, mood, and sexual function (Arch Gen Psychiatry. 1990;47:288-289).
 
   Lewis Seiden, PhD, professor of pharmacology at the University of Chicago,
Ill, conducted extensive research on the neurotoxicity of  MDMA  in the
mid-1980s.  When he heard of the recent reports of fatalities associated with
the use of the drug in English nightclubs, he was reminded, he says, of a
well-established phenomenon in amphetamine research called "aggregation
toxicology": One solitary rat or mouse given an injection of amphetamine will
survive.  But several animals, confined in a small cage and given the identical
dose of amphetamine, will die.
 
   Over the years, one of several proposed explanations for this phenomenon has
been amphetamine-induced hyperthermia, Seiden says.
 
   On the other hand, one "can't make the assumption the MDMA is just a
fancy form of amphetamine," points out Steven Karch, MD, research director
of the Trauma Center at the University Medical Center of Southern Nevada,
Las Vegas. "The molecules are very close structurally [figure].  But then
again, all stimulants look roughly the same."
 
   Seiden also speculates that because  MDMA  is such a potent
serotonin-releasing agent in the brain, it might also effect
serotonin-releasing cells elsewhere in the body.  Ninety percent of the
serotonin in the body is located outside the brain, much of it in the gut
and mast cells, he says. 
 
The Long Road to Rave
 
    MDMA  has a long, controversial history that spans nearly a century, says
Karch, who is also editor of the Forensic Drug Abuse Advisor.
 
   The patent for MDMA was initially granted in 1914 to E. Merck in
Darmstadt, Germany, as an appetite suppressant.  The compound's toxicology
wasn't systematically studied until the early 1950s, under a US Army
contract with a group at the University of Michigan, Ann Arbor.  The results
of these studies were eventually declassified and published in 1973, when it
was revealed that MDMA is somewhat less toxic than MDA (another amphetamine
derivative), but more toxic than the hallucinogen mescaline (Toxicol Appl
Pharmacol. 1973;25:299-309). 
 
   No pharmaceutical company has ever made  MDMA,  nor has the Food and Drug
Administration approved it.  A small number of psychiatrists have advocated its
use in therapy, based on the belief that it lowers patients' defenses and
promotes trust and confidence.
 
   In 1985, after several studies showed neurotoxicity in animals, the Drug
Enforcement Agency classified  MDMA  as a Schedule I compound.  Schedule I
compounds, such as heroin and LSD, are believed by the agency to have a high
potential for abuse and no currently accepted medical use.
 
GRAPHIC: Figure, Structural formulas of amphetamine, methamphetamine, and  MDMA
 ("Ecstasy" ).
 
SECTION: MEDICAL NEWS & PERSPECTIVES
 
LENGTH: 493 words
 
TITLE: 'Rave' Scene,  Ecstasy  Use, Leap Atlantic
 
AUTHOR: Teri Randall
 
TEXT:
   THE BRITISH rave counterculture, and its liberal use of ecstasy (MDMA) ,
has become a hot export to the United States, wrapped in a high-tech music
and video package and supported by low-tech laboratories that illicitly
produce the drug stateside.
 
   An August 19, 1992, article by United Press International says that a
clamp-down on rave parties by British authorities has inspired several English
rave promoters to move their business to the United States.  Staged in empty
warehouses or open fields outside San Francisco or Los Angeles, their parties
are drawing thousands of young Californians on designated weekend nights.
 
   Partygoers -- attired in Cat in the Hat-hats and psychedelic jumpsuits --
pay $ 20 at the door to dance all night to heavily mixed, electronically
generated sound, surrounded by computer-generated video and laser light
shows.  They pay another $ 3 to $ 5 for "smart drinks" -- amino acid-laced
beverages that reputedly enhance energy and alertness.  And for another $
20, those so inclined can purchase an ecstasy tablet (see accompanying
article). 
 
   Many observers can't help but draw comparisons to the LSD-laced "human
be-ins" of a quarter-century ago.  The scene has come full circle, they add,
noting that several Los Angeles raves have been hosted by Timothy Leary's son.
The elder Leary, a former Harvard professor who advocated the use of LSD
(lysergic acid diethylamide) three decades ago, has made several appearances at
his son's raves, calling them "high-tech Acid Tests."
 
   Large raves also have been staged in New York, NY, and other urban
centers in the United States.  Their popularity is increasing in parts of
India, Indonesia, Belgium, and New Zealand, and a promoter is working to
popularize the scene in Sweden, United Press International reports.
 
   So far, there appear to be no published reports of death or severe toxicity
caused by  MDMA  use.
 
   Most of the  MDMA  available in England is supplied by clandestine
laboratories in the Netherlands.  In the United States, the drug is made
predominantly on the West Coast by small-scale operators, says Joseph Bono,
supervisory chemist, special testing, Drug Enforcement Agency.
 
   The synthesis of  MDMA  requires minimal knowledge of chemistry.  Illicit
laboratories are often set up in kitchens, mobile trailers, or garages with
little concern for cleanliness.  Reactions may be set up in cookie jars.  Solid
products may be removed with coffee filters; and the coffee filter may be
thrown back into the reaction vessel for a second synthesis step (J Forensic
Sci. 1988;33:576-587).  Bono detects a lot of contaminants and by-products
in the samples that reach his laboratory for analysis.
 
   "We're not dealing with Smith, Kline, and French here.  We're dealing with
people who are just interested in turning out a product," Bono says.  "If it
assays at 50% as opposed to 100% or 95%, they don't really care.  And what is
that other 50%?  Who knows?"