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Some Therapeutic uses of Ecstasy?

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.

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