Ecstasy

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Ecstasy Pills

Ecstasy is a psychoactive drug known for its association with raves, dancing, and euphoria. Its chemical name is MDMA or 3,4-methylenedioxymethamphetamine. Typically, ecstasy is sold in the form of pills which commonly are found to be impure and may not even contain MDMA at all. The drug has been used for recreational purposes but is also being studied for its use in psychotherapy, particularly for the treatment of PTSD (post-traumatic stress disorder).

1 History
2 Illegality
3 Effects
- 3.1 Mode of action
- 3.2 Subjective effects
4 Health Concerns
5 Slang Terms

[edit] History

MDMA was first synthesized in the 1890s and later patented by Merck pharmaceuticals on December 24, 1912, but it wasn't until the mid 1970s that articles related to its psychoactivity began showing up in scholarly journals. In the late '70s and early '80s MDMA was used as a psychotherapeutic tool and also started to become available on the street. Its growing popularity led to it being made illegal in the United States in 1985 and its popularity has continued to increase since then.

[edit] Illegality

MDMA is illegal in the United States (Schedule I) and in most other countries. It is also listed as Schedule I in the International Convention on Psychotropic Substances, an international drug control treaty.

[edit] Effects

[edit] Mode of action

MDMA's unique effects can be attributed to an array of pharmacological changes which occur in the brain which are yet to be fully understood. One of the primary components in producing effects is the drug's higher affinity for SERTs than serotonin itself. SERTs are the part of the serotonergic neuron which removes serotonin from the synapse to be recycled or stored for later use. Not only does MDMA inhibit the reuptake of serotonin, but it reverses the action of the transporter so that it begins pumping serotonin into the synapse from inside the cell. This usually causes the serotonin storage vesicles to be emptied after only a few hours with a standard recreational dose. In addition, MDMA has a partial affinity for blocking the reuptake of dopamine and a smaller affinity still for blocking that of norepinephrine as well as other neurotransmitters in smaller quantities.

MDMA's unique empathic/enactogenic effects have recently been attributed to the release of oxytocin, a hormone usually released in large quantities following such activities as orgasm and childbirth. Essential in facilitating bonding and the establishment of trust, absent the release of this hormone, the subjective "loved-up" feelings of closeness and connectedness with others would be significantly less pronounced.

[edit] Subjective effects

The primary effects of MDMA include an increased awareness of the senses, feelings of openness, euphoria, empathy, love, happiness, heightened self-awareness, feeling of mental clarity and an increased appreciation of music and movement. Some users, depending on the purity and kind of the pill, will feel lighter and stronger and will be able to do things that they cannot do sober. Examples are increased athletic ability and being able to do heavy lifting. Tactile sensations are enhanced for some users, making physical contact with others more pleasurable. Other side effects, such as jaw clenching and elevated pulse, are common. Some users report effects similar to those of softer stimulants such as caffeine, and a few report effects comparable to harder stimulants such as cocaine. Alexander Shulgin stated that the single best use of MDMA was to facilitate more direct communication between people involved in significant emotional relationships.[citation needed] Psychiatrist George Greer came to the same conclusion in his report on the first 29 subjects administered MDMA in his practice, with the MDMA having been synthesized in Shulgin's lab.

[edit] Health Concerns

While the short term side effects and contraindications of MDMA are fairly well known, there is significant debate within the scientific and medical community over the long term effects and the possibility for physical harm arising from MDMA use.

[edit] Government studies

The chief executive of the UK Medical Research Council stated MDMA was "on the bottom of the scale of harm," and the Science & Technology Committee rated it of lower concern than for alcohol, tobacco, and cannabis, when examining the harmfulness of any given drug. The UK study placed great weight on the risk for acute physical harm, the propensity for physical and psychological dependency on the drug, and the negative familial and societal impacts of the drug. On these factors, the study places MDMA relatively low, which reflects its lower score in comparison to the risks of alcohol.

[edit] Physical

The short-term health risks of taking MDMA include hypertension, dehydration and hyperthermia. In the raving subculture, use of MDMA can increase the risks of dehydration and hyperthermia, as the drug's stimulatory effects can mask the body's normal sense of exhaustion and thirst. The risk of hyperthermia may be increased by a high fat diet, but more importantly MDMA is implicated in affecting the mechanism of uncoupling protein (UCP), more specifically UCP3 in mitochondria.

MDMA affects the regulation of the body's internal systems. Continuous dancing without sufficient breaks or drinks can lead to dangerous overheating and dehydration, and serves to significantly enhance the drug's neurotoxic action. Drinking too much water without adequate salt can cause hyponatremia or water intoxication, although this is less common than overheating.

Hypertension is a risk in some users due to the increase in heart rate and blood pressure. This risk increases as dose increases which can lead to overstimulation of the heart and ultimately death.

[edit] Neurological overview

It has been established that MDMA affects the brains of humans and lower primates differently, especially in terms of long-term changes. In both animals, MDMA causes a reduction in the concentration of serotonin transporters (SERTs) in the brain. Baboons who were given a neurotoxic dose of MDMA only showed partial regrowth of SERTs when scanned a year later. In contrast, human studies differ in that those who had never used ecstasy were indistinguishable in PET brain scan studies from former ecstasy users. However, the same study also concluded that the reduction in memory performance due to heavy, prolonged MDMA use may be long-lasting.

Although oxidative stress (see neurotoxicity theory below) may cause SERTs to degrade faster than they are able to be replaced, the serotonin axon itself seems to have been spared, which indicates that neurotoxicity may not be the means by which SERT count was reduced. It is possible that excess serotonin in the synapse due to MDMA, especially if uses occur within a short period, causes the serotonin cells to produce fewer SERTs, a phenomenon which has already been demonstrated with other serotonin-depleting drugs. MDMA use may also cause a decrease in the number of serotonin receptors on the dendrite of the neuron. (See down-regulation theory below.)

For a detailed and comprehensive explanation of this topic, see TheDea.org's evaluation of studies.

[edit] Receptor down-regulation

One theory of SERT-depletion arising out of long-term MDMA use is receptor down-regulation which is one form of synaptic plasticity. When any neurotransmitter is present in excess for prolonged periods of time, the brain responds in an attempt to reestablish its own natural neuro-electrical balance. Weekly use of MDMA over a prolonged period may actually cause serotonin receptors to retreat into the dendrite of serotonin nerve cells, in addition to enticing serotonin cells lower its own SERT count. The change in synaptic serotonin concentration due to recreational MDMA use is at the extreme end of what is even possible in the brain and therefore, down-regulation could occur fairly easily with regular use.

This process causes the brain to become desensitized to the neurotransmitters present in the synapses and therefore also to the effects of MDMA itself. Therefore, in addition to a generally decreased quality of mood between doses, greater amounts of MDMA are required to achieve the same level of desired effects. It is this cycle that is often believed to be the cause of long-term emotional problems among regular ecstasy users.

[edit] Neurotoxicity

Under another theory, MDMA is considered neurotoxic in humans. While the method of this toxicity has not been definitively established, the current leading theory is that the metabolism of MDMA-induced dopamine release leads to the lipid peroxidation of serotonergic neurons. This occurs when MAO-B breaks up dopamine into free radicals capable of damaging cells, leading to a reduction in SERT count and possibly damage or destruction of the axon itself, thus interfering with the integrity of the brain's serotonin network

Normally, the brain is able to protect itself from oxidative stress, but it is believed that the aforementioned damage can be attributed to MDMA's unique interaction with serotonin transporters. Not only does MDMA reverse the normal functioning of the transporter in which case serotonin is pumped out of the cell, but once the stored serotonin has been depleted, the transporter begins to take up dopamine which has been shown to be toxic to serotonin cells by itself. Once MAO oxidizes dopamine inside the serotonin cell, the damage is greatly magnified. Several studies have demonstrated that such damage in the brain is reversible after prolonged abstinence from the drug. In severe cases, however, the possibility for recovery of cognitive functions may be much more limited.

Neurotoxicity of serotonergic neurons would occur in selective areas of the human brain as serotonin cells are highly concentrated in certain areas such as the neocortex and hippocampus. Although some studies have demonstrated this, the rate at which this damage occurs is disputed.

U.S. government-funded studies performed by George Ricaurte at Johns Hopkins University, which have demonstrated catastrophic brain damage occurring due to MDMA exposure, have been widely discredited by the scientific community. The second study on the subject, which claimed that a single recreational dose of MDMA could cause Parkinson's Disease in later life due to severe dopaminergic stress, was actually retracted by Ricaurte himself after he discovered his lab had administered methamphetamine, a known neurotoxin, and not MDMA.

Antioxidants have been shown to prevent the neurotoxicity of MDMA in rats. In one study, intravenous administration of alpha lipoic acid completely blocked the neurotoxic effects of MDMA. No scientific experiment has been performed to date with human subjects, although some users report that taking various combinations of antioxidants before, during, and after using MDMA serves to moderate the subsequent mood-dip and improve recovery time.

The administration of an SSRI in rats prior to the administration of MDMA has been shown to completely block neurotoxicity. This is due to the binding of such medications with SERTs. However, administering an SSRI prior to administration of MDMA also completely or partially blocks the desired effects of the latter, something a large number of users prescribed an SSRI have reported. As a compromise it has been shown that administration of an SSRI 3-4 hours after MDMA, at which time the primary effects will have tapered off significantly, markedly limits neurotoxicity overall despite some axonal damage having already occurred. Once again, no such scientific experiment has been performed on human test subjects, and potential complications may still exist.

It should also be noted that the production and introduction into the active brain of serotonin is a much lengthier process than is that of dopamine. Therefore, users who redose once the serotonergically-induced effects of MDMA have mostly diminished are likely not stimulating the release of serotonin at all as a single recreational dose of MDMA is likely to have depleted these rather limited reserves. The subsequent effects of redosing are therefore due almost entirely to the action of increased dopamine in the brain, and therefore, once again, neurotoxicity is significantly enhanced.

[edit] Psychological

MDMA use commonly results in a rebound period of poor mood or possibly depression commonly known as a "comedown", the length and severity of which depends on the user, the dose and the total duration of MDMA's activity in the body. Heavy or frequent use may precipitate lasting depression and anxiety in vulnerable users, particularly those prone to depression or other mental disorders as well as anyone in a state of crisis in their life.

"Redosing" in an attempt to extend MDMA's desired effects has been shown to substantially increase neurotoxicity as well as the undesired physical side effects associated with MDMA use such as trisma and bruxia, which are caused by MDMA's partial dopaminergic affinity. The longer MDMA is active and being metabolized in the brain, the greater the neurotoxic damage and the greater the risk of short-term emotional problems. The more occasions MDMA is used, the greater the chances of long-term problems. Deficits in memory have been shown in long term MDMA users.

A recent University of Louisiana study found no significant relationship between depression and recreational ecstasy use. The preliminary results from an ongoing Dutch study also indicate that the very moderate use of Ecstasy alleviates symptoms of depression by 28% and improved users' overall mental state. These users also appear to be free of neurological injury of any kind.

[edit] Drug interactions

Individuals who have stopped taking any type of SSRI after prolonged medication may not be able to experience the desired effects of MDMA for as long as several months following discontinuation of the medication. This is due to the fact that SSRIs decrease the brain's sensitivity to the presence of serotonin as the brain seeks to reestablish a normal neuro-electrical balance.

Most people who die while under the influence of Ecstasy have also consumed significant quantities of at least one other drug. The risk of MDMA-induced death overall is very low.

The use of MDMA can be dangerous when combined with other drugs (particularly monoamine oxidase inhibitors (MAOIs) and antiretroviral drugs, in particular ritonavir). Combining MDMA with MAOIs can precipitate hypertensive crisis, as well as serotonin syndrome which can be fatal. MAO-B inhibitors such as deprenyl do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.

[edit] Purity

Due to its' nearly-universal illegality, the purity of a substance sold as Ecstasy is unknown to the typical user. The MDMA content of tablets varies widely between regions and different brands of pills and fluctuates somewhat each year.

Pills often contain other active substances meant to stimulate in a way similar to MDMA. These substances commonly include amphetamine, methamphetamine, ephedrine, and caffeine, all of which may be comparatively cheap to produce and can help to boost profit overall. Due to many users' inability to discern subtle pharmacological differences between substances, this practice is widely ignored by the market. In some cases, tablets sold as Ecstasy do not even contain any MDMA, chemicals in the Ecstasy Family, or even any kind of stimulant drug. Instead they may contain an assortment of presumably undesirable drugs such as acetaminophen, ibuprofen, or ketamine amongst others.

Scientific surveys of seized Ecstasy pills in the United Kingdom and Europe indicate that purity levels are generally high, and that adulterants are rare. Although the US government's Office of National Drug Control Policy reports that over 55% of ecstasy pills seized in the United States in 2007 were laced with methamphetamine, it is unknown what percentage of a tablet on average the drug constitutes.[6] It should also be noted that as a general rule, tablets seized do not necessarily represent the entire market accurately, as it is impossible to know how many of each tablet are being consumed and what each contains.

A full and proper characterization of ecstasy pills requires advanced lab techniques, such as high performance liquid chromatography-mass spectrometry (usually referred to as HPLC-MS), gas chromatography-mass spectrometry (usually referred to as GC-MS) and gas chromatography-infrared spectroscopy (usually referred to as GC-IRD). Ecstasydata.org, a non-profit organization, uses such techniques to analyze MDMA pills for a fee.

DanceSafe, among other companies, provides home testing kits to verify the contents of MDMA pills. PillReports.com and Trancesafe.com each provide the results of home testing kits in addition to the suspected contents when a test has not been performed.

[edit] PMA

There have been a number of deaths in which PMA, a potent and highly neurotoxic hallucinogenic amphetamine, has been sold as Ecstasy. PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA.[53] Hence, a user who believes he is consuming 2 120mg pills of MDMA is actually consuming a dose of PMA that is potentially lethal, depending on the purity of the pill. Not only does PMA cause the release of serotonin, but also acts as an MAO-A inhibitor. When combined with an ecstasy-like substance, serotonin syndrome can result.

While both PMA and MDMA are currently Schedule I in the U.S, PMA was scheduled more than 10 years before MDMA.[54][55] Additionally, both drugs were rescued from obscurity by the same man, Alexander Shulgin, who at the time was synthesizing new psychoactive chemicals having been granted a license by the DEA to conduct autonomous research.

Between the late 1970s and early 1990s, virtually no PMA-related deaths were reported worldwide. It was not until safrole, one of the key ingredients in the original method of MDMA synthesis, was made more difficult to acquire that PMA began to be seen in batches of ecstasy pills in any notable quantity.

PMA is almost never sought after as a drug of choice, and this would not be practical to assume for several reasons. One reason is because it is so rare, another is that those who are aware of its existence are usually equally familiar with its unique hazards. The psychological effects of PMA as compared to MDMA are also quite different. PMA lacks the empathogenic qualities of MDMA, and depending on the analogue ingested, may only produce physical stimulation absent of any euphoria (see PMA).

[edit] Slang Terms