1 Introduction
1.1 MDMA
was originally developed as a pharmaceutical product,
patented in 1913 by Merck as a slimming product, but
never marketed.
1.2 Ecstasy
resurfaced in the 1980s as a tool in experimental
psychotherapy, particularly in resolving relationship
and marital difficulties, before the drug was declared
illegal in the USA following an increase in recreational
use.
1.3 Ecstasy
users are attracted to the drug by the warmth and
empathic feelings it induces, and by the energy provided
by the stimulant effects of the drug. It acts by dramatically
increasing the release of serotonin, at a dangerously
high level frequently leading to neurotoxicity and
long-term depletion of serotonin function. For that
reason, most ecstasy users find they are unable to
repeat the effects of their first experiences, and
keep increasing the dosages used in vain attempt to
do so.
1.4 When
the drug effects subside, the user is left feeling
low and depressed. Many researchers fear the long-term
effects of mass ecstasy use and the long term implications
for psychiatric resources.
2 Side
effects
2.1 Ecstasy
has been linked to a number of sudden deaths, largely
due to complications arising from acute hyperthermia,
and occasionally from excessive/compulsive water drinking.
2.2 There
are a number of reports linking acute liver failure
with one time or moderate/regular ecstasy use, requiring
transplantation to avoid fatality.
2.3 Ecstasy
use has been shown to cause serotonergic neurotoxicity
in both laboratory animals and in humans, leading
to a reduction in serotonin levels as the cells which
secrete the neurotransmitter are killed. This has
potential long-term mental health consequences including
severe depression, impaired memory and cognitive function,
and increased tendency to violent behaviour.
2.4 Other
reported complications include chest pains, pneumomediastinum
and gastric artery perforation. Further side effects
are reported from fake or quasi-legal preparations
masquerading as ecstasy.
2.5 Summary:
In view of the severe side effects associated with
use of MDMA, the drug is unlikely to be approved for
therapeutic use. It is possible that analogues could
be developed to provide a drug with the desired effects
- therapeutic or recreational - while minimising the
acute and long-term health consequences, at some point
in the future.
3 Ecstasy
and Pain Relief
3.1 There
is a scarcity of research into ecstasy and pain, however
some reports suggest MDMA could increase the pain
threshold in rats.
3.2 Nencini
et al reported that repeated injetions could potentiate
the analgesic effect of morphine, concluding "a
functional consequence of repeated MDMA administration
in rats was to enhance morphine-induced antinociception
in association with reductions in brain and cervical
spinal cord 5-HT.". Crisp et al, finding
the pain-relieving effect of MDMA was blocked by a
serotonin antagonist, concluded: "These
findings suggest that the antinociceptive effects
of MDMA are serotonergically mediated."
3.3 The
only report of pain relief in humans is from Greer
and Tolbert, who reported a case history of a man
using ecstasy for relief of pain resulting from myeloma.
3.4 Summary:
There is very little scientific evidence available,
as few studies have investigated the antinociceptive
effect of ecstasy. However the limited research which
has been published does provide some evidence to support
the proposition that ecstasy can have pain-relieving
activity, and no evidence to the contrary.
4 Ecstasy and Anxiety/Depression
4.1 Animal
Studies: Studying mice, Lin et al reported "The
results indicate that MDMA has anxiogenic-like properties
at lower doses and anxiolytic-like at higher doses."
Maldonado et al similarly reported "Overall,
the behavioral profile found in the light/dark test
indicates an anxiogenic-like activity of MDMA in mice.".
4.2 In
rats, Morley et al reported "MDMA
increased anxiety-related behaviours in the emergence
and elevated plus-maze tests at all dose levels...
These results indicate that MDMA has both anxiogenic
and anxiolytic effects depending upon the test situation
employed."
4.3 Human
Studies: Vollenweider et al reported ecstasy to
induce "an effective state of
enhanced mood, well-being, and increased emotional
sensitiveness, little anxiety, but no hallucinations
or panic reactions." Adverse consequences
after 24 hours included "lack
of energy and appetite, feelings of restlessness,
insomnia, jaw clenching... difficulty concentrating,
and brooding"
4.4 Morgan
reported that no differences were found on anxiety
scales between ecstasy users, non-ecstasy-using polydrug
users, and matched non-drug using controls. He reported,
however, that ecstasy users were "more
psychologically disturbed and impulsive than nondrug
controls," and committed more errors
on the matching familiar figures test of cognitive
function. In a 2000 review, he reported "There
is growing evidence that chronic, heavy, recreational
use of ecstasy is associated with sleep disorders,
depressed mood, persistent elevation of anxiety, impulsiveness
and hostility, and selective impairment of episodic
memory, working memory and attention. There is tentative
evidence that these cognitive deficits persist for
at least 6 months after abstinence, whereas anxiety
and hostility remit after a year of abstinence."
"Some of these problems may remit
after abstinence, but residual neurotoxicity and decline
of serotonergic function with age may result in recurrent
psychopathology and premature cognitive decline."
4.5 In
a double blind placebo-controlled study, Hermle et
al reported "The majority of
the psychotropic effects resembled those that have
already been described in anecdotal reports. The substance
produced a partially controllable state of enhanced
insight, empathy, and peaceful feelings. All subjects
displayed a general stimulation with increased psychomotor
drive, logorrhea, and facilitation of communication.
One of the fourteen volunteers developed a toxic psychosis.
One volunteer displayed a dysphoric reaction, one
suffered from episodes of anxiety for some days after
the experiment."
4.6 Parrott
et al studying 12 regular heavy ecstasy users, 16
occasional light users and 22 controls reported: "Heavy
Ecstasy users reported significantly higher scores
than controls on... paranoid ideation, psychoticism,
somatisation, obsessionality, anxiety, hostility,
phobic anxiety, altered appetite and restless sleep,
together with greater... impulsiveness."
They cautioned "However, since
repeated MDMA can cause serotonergic neurotoxicity
in laboratory animals and man, these problems may
reflect reduced serotonin activity induced by regular
ecstasy use." In a study of current
users, former users and controls, Wareing et al reported
"there were significant group
differences on the measures of anxiety (users were
more anxious)" Gamma et al, studying
EEG responses reported "Ecstasy
users had higher levels of state depressiveness, emotional
excitability and a trend-level increase in state anxiety."
4.7 McCann
& Ricaurte reported "recreational" use
of ecstasy to have produced long term adverse neuropsychiatric
consequences in vulnerable persons, including "panic
disorder" after a single dose. They also found
that prozac (fluotexine) does not block the subjective
effects of ecstasy, but may inhibit the neurotoxic
effects of the drug. The same team later reported
"MDMA users had lower scores
on personality measures of impulsivity (p = .004)
and indirect hostility (p = .009)",
and that "many of the adverse
neuropsychiatric consequences noted after MDMA involve
behavioral domains putatively influenced by brain
serotonin (e.g., mood, cognition and anxiety)."
They concluded: "Although the
large majority of individuals who have used MDMA recreationally
do not develop acute complications, as the popularity
of MDMA has increased, so have reports of adverse
nonpsychiatric and psychiatric consequences associated
with use of the drug." In a 1999 study,
they reported "MDMA users reported
more positive and fewer negative emotions and physical
symptoms following m-CPP than controls, and were significantly
less likely to report an m-CPP (serotonin
agonist)-induced panic attack."
4.8 Gouzoulis
et al reported "The widely used
recreational drugs (MDMA, Ecstasy) and (MDE, Eve)
occupy an intermediate position between stimulants
and hallucinogens. Besides stimulation similar to
that caused by amphetamines, they usually induce a
pleasant, easily controllable emotional state with
relaxation, fearlessness and feelings of happiness,
but they sometimes also have stronger, hallucinogenic,
effects.", however, they also noted
"Complications are rare, but
potentially devastating ([long-lasting anxiety and
depressive syndromes in chronic users, fatalities
with hyperpyrexia, rhabdomyolysis and DIC syndrome
(disseminated instravascular coagulation), possible
hepatotoxicity]."
4.9 Studying
drug use among 3075 students, Webb et al found no
relationship between drug use and (high) anxiety levels
as measured on the hospital anxiety depression scale.
Williamson et al studied adverse effects among a sample
of 158 stimulant users. Reported adverse effects included
anxiety problems, depression, mood swings, feelings
of paranoia, and panic attacks, with sleep and appetite
disturbances the most common. Depression and paranoid
feelings associated with stimulant use were reported
by half the subjects, many stating that these were
mild, although 35% of ecstasy users reported having
had at least one 'severe' adverse effect. Drugs differed
in the likelihood and reported severity of adverse
effects. Amphetamine use was associated with significantly
more adverse effects and with more severe adverse
effects than Ecstasy or cocaine.
4.10 In
our 1994/98 IDMU Regular Users Surveys, subjects who
reported suffering anxiety attacks were likely to
spend more on ecstasy than other drug users, although
this difference failed to achieve statistical significance
(p<0.1). "Paranoia" was associated with
more frequent ecstasy use (p<.001), as were memory
problems (p<.01), apathy and laziness (p<.01).
However, "stress relief" was associated
with more frequent (p<.001) or prolonged (p<.01)
ecstasy use, but no association either way with "antidepressant/happiness"
reports.
5 Ecstasy
and Agoraphobia
5.1 Pallanti
et al described "three patients
whose panic disorder began during recreational use
of MDMA (Ecstasy) and was subsequently complicated
by agoraphobic avoidance that continued autonomously
after cessation of the drug. Their panic disorder
responded well to serotoninergic antidepressant drugs."
5.2 Kuntze
reported a case history of an ecstasy user suffering
agoraphobic anxiety disorder.
6 Summary
- Therapeutic Use
6.1 Pain:
There is very little scientific evidence available,
as few studies have investigated the antinociceptive
effect of ecstasy. However the limited research which
has been published does provide some evidence to support
the proposition that ecstasy can have pain-relieving
activity, and no evidence to the contrary.
6.2 Endometriosis/Uterine
function: No studies have been published which
have investigated the potential use of ecstasy in
the treatment of endometriosis, or any other uterine
disorder. Given the presence of serotonergic cells
in the uterine lining, it is possible that the drug
could have some effect, either directly or secondary
to release of ovarian steroid hormones, however the
nature of any potential effect is unknown, but might
even exacerbate the condition.
6.3 Mental
Health Effects: There is very little support for
the proposition that ecstasy can be used as a treatment
for anxiety or depression. Animal studies suggest
that ecstasy may have differential effects, increasing
anxiety at lower doses, but decreasing it higher doses.
6.4 The
majority of human studies suggest that ecstasy users
tend to have higher levels of anxiety and depression
than users of other drugs, or non-using controls,
that these reactions can in many cases be severe,
and may persist for up to 12 months following cessation
of use.
6.5 Severe
depression is widely-associated with the serotonin
depletion caused by heavy or prolonged use of ecstasy.
Regular ecstasy use is also associated with impairment
of memory and cognitive function.
6.6 Although
particular individuals may consider ecstasy to be
of benefit in reducing stress and inducing a feeling
of well-being, these effects only persist as long
as the drug is taken.
6.7 Case
studies have documented several individuals who have
developed agoraphobic conditions following recreational
ecstasy use.
6.8 There
are anecdotal reports that ecstasy may provide some
unique relief for certain neurological conditions
such as Parkinsonism.
