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MDMA
Systematic (IUPAC) name
(RS)-1-(benzo[d][1,3]dioxol-5-yl)-N-methylpropan-2-amine
Identifiers
CAS number 69610-10-2
ATC code none
PubChem 1615
ChemSpider 1556
Chemical data
Formula C11H15NO2 
Mol. mass 193.25 g/mol
SMILES eMolecules & PubChem
Synonyms (±)-1,3-benzodioxolyl-N-methyl-2-propanamine;
(±)-3,4-methylenedioxy-N-methyl-α-methyl-2-phenethylamine;
DL-3,4-methylenedioxy-N-methylamphetamine;
methylenedioxymethamphetamine
Pharmacokinetic data
Metabolism Hepatic, CYP450 extensively involved, especially CYP2D6
Half life 6–10 (though duration of effects is typically actually 3–5 hours)
Excretion Renal
Therapeutic considerations
Pregnancy cat. C[1]
Legal status Prohibited (S9) (AU) Schedule III (CA) CD Lic (UK) Schedule I (US)
Routes Oral, sublingual, insufflation, inhalation (vaporization), injection,[2] rectal
.MDMA (3,4-Methylenedioxymethamphetamine, commonly known as Ecstasy) is an entactogenic drug of the phenethylamine and amphetamine families.^ Drug Metab Dispos 26:1202–1212 [ PubMed ] Lyles J, Cadet JL (2003) Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Amphetamine; high quality methamphetamine; marijuana; methylenedioxymethamphetamine (MDMA); marijuana grown in water (hydroponic) .

^ In Europe as of 1997, MDMA was number two on the list of most commonly used illicit drugs (United Nations, 1997).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

.MDMA is considered unusual for its tendency to induce a sense of intimacy with others and diminished feelings of fear, anxiety, and depression.^ MDMA is considered unusual for its tendency to induce a sense of intimacy with others and diminished feelings of fear and anxiety.

^ National Public Radio (NPR)'s "All Things Considered" aired an interview of John Halpern, who spoke about the MDMA/cancer anxiety study.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug.

Some have suggested it might have therapeutic benefits in certain individuals. .Before it was made a controlled substance, MDMA was used as an augmentation to psychotherapy, often couples therapy, and to help treat clinical depression as well as anxiety disorders.^ Using MDMA in psychotherapy.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ Before it was made a controlled substance, MDMA was used as an augmentation to psychotherapy , often couples therapy , and to help treat clinical depression as well as anxiety disorders , the results of which are poorly documented.

^ Many factors, including total lifetime MDMA consumption, the duration of abstinence between uses, the environment of use, poly-drug use/abuse, quality of mental health , various lifestyle choices, and predispositions to develop clinical depression and other disorders may contribute to various possible health consequences.

.Clinical trials are now testing the therapeutic potential of MDMA for post-traumatic stress disorder (PTSD) and anxiety associated with terminal cancer.^ Explored in a controlled setting, MDMA can be therapeutic for victims of Post-Traumatic Stress Disorder ( PTSD ).
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Most recently, the Multidisciplinary Association for Psychedelic Studies (MAPS) has planned a conference in Israel for late August 1999, in order to facilitate possible MDMA research in the treatment of post-traumatic stress disorder (PTSD) at Ben-Gurion University of the Negev.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[3][4]
.MDMA is criminalized in most countries in the world under a United Nations (U.N.) agreement,[5] and its possession, manufacture, or sale may result in criminal prosecution, although some limited exceptions exist for scientific and medical research.^ MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances and other international agreements, although exceptions exist for research.

^ MDMA is criminalized in most countries in the world under a United Nations (U.N.) agreement, 3 and its possession , manufacture , or sale may result in criminal prosecution , although some limited exceptions exist for scientific and medical research .

^ New world trade agreements and the easing of formerly restrictive national and international borders have resulted in dramatic increases in cargo transshipping and personal travel, thereby complicating drug inspection and interdiction efforts at POE's.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

.MDMA is one of the most widely used recreational drugs in the world and is taken in a variety of contexts far removed from its roots in psychotherapeutic settings.^ MDMA was subsequently patented in 1914 (Merck, 1914), but with the outbreak of World War I received little investigational attention into the drug’s potential applications (Shulgin and Shulgin, 1991).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ "I love the world and the world loves me", affirmed one beneficiary of MDMA-assisted therapy.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.It is commonly associated with dance parties (or "raves") and electronic dance music.^ It is commonly associated with the rave or electronica subculture and related genres of music .

^ Mozart sounds great on Ecstasy, but high-energy all-night dance parties celebrated with techno-pop house music are more standard.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Ecstasy-fueled "rave" parties become dances of death for English youths.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

[6]
.There have been debates within scientific, health care, and drug policy circles about the risks of MDMA, specifically the possibility of neurotoxic damage to the central nervous system (CNS).^ Mapping toxicant-induced nervous system damage with a cupric silver stain: a quantitative analysis of neural degeneration induced by 3,4-methylenedioxymethamphetamine.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Whereas the first effect of MDMA appears to produce a REVERSIBLE depletion of 5-HT, the second is due to a NEUROTOXIC effect of the drug on serotonergic neurons or nerve terminals."
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ The protocol will submitted to FDA shortly after NIDA’s scientific meeting on MDMA, held at the National Institutes of Health campus in Bethesda, MD, on July 19-20.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine its therapeutic potential and its effects.^ Regulatory authorities in several locations around the world have approved scientific studies administering MDMA to humans to examine either its therapeutic potential, or, more commonly, simply its basic effects .

^ In 1953 and 1954 , the United States Army commissioned a study of toxicity and behavioral effects in animals of injected mescaline and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973 .

^ Alexander Shulgin, a Berkeley biochemist, is believed to have introduced the drug to the psychotherapeutic scene after self-administering the drug and testifying to MDMA’s rehabilitative potential (Shulgin and Shulgin, 1991; Shulgin and Nichols, 1978).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

[7]
.Continuing to study the substance in clinical trials, the Multidisciplinary Association for Psychedelic Studies released the following statement in October 2008, "We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects.^ We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Most recently, the Multidisciplinary Association for Psychedelic Studies (MAPS) has planned a conference in Israel for late August 1999, in order to facilitate possible MDMA research in the treatment of post-traumatic stress disorder (PTSD) at Ben-Gurion University of the Negev.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ Against formidable odds, the Multidisciplinary Association for Psychedelic Studies ( MAPS ) has been seeking funding and FDA-approval for controlled trials of MDMA-assisted therapy for PTSD. If these trials are successful, then MAPS hopes that MDMA could eventually become a prescription-medicine.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.”[8]

Contents

Terminology

.MDMA was first introduced clinically under the names "Adam" and "Empathy" when it was used in psychotherapy in the late 1970s and early to mid 1980s.^ MDMA was first introduced clinically under the names " Adam " and " Empathy " when it was used in psychotherapy in the late 1970s and early to mid 1980s .

^ Using MDMA in psychotherapy.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ By the early 1980s, over a thousand private psychotherapists in the USA were using MDMA in their clinical practice.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[9] Later on, upon making it into the recreational drug use scene, it came to be widely known as "Ecstasy", often abbreviated as "E", "X", or "XTC".[9] MDMA in its pure, powder, crystalline, or capsule form, is commonly referred to as "Molly"[10] and/or "Mandy/Mindy".

History

.MDMA was first synthesized in 1912 by Merck chemist Anton Köllisch.^ MDMA [3,4-methylenedioxy-methamphetamine: ' Ecstasy '] was first 1 synthesized in 1912 by the German pharmaceutical company Merck .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA has often been erroneously reported in the literature to have been synthesized in 1912 as an appetite suppressant by Merck Laboratories, Germany.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ MDMA was synthesized in 1912 and patented in Germany by Merck in 1914 but was not the subject of human research at that time.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.At the time, Merck was interested in developing substances that stopped abnormal bleeding.^ At the time, Merck was interested in developing substances that stopped abnormal bleeding .

^ MDMA was an intermediate compound in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time.

Merck wanted to evade an existing patent, held by Bayer, for one such compound: hydrastinine. .At the behest of his superiors Walther Beckh and Otto Wolfes, Köllisch developed a preparation of a hydrastinine analogue, methylhydrastinine.^ At the behest of his superiors Walther Beckh and Otto Wolfes , Köllisch developed a preparation of a hydrastinine analogue , methylhydrastinine .

.MDMA was an intermediate compound in the synthesis of methylhydrastinine, and Merck was not interested in its properties at the time.^ MDMA is listed on Merck's patent-application merely as a chemical intermediate "for products of potential pharmaceutical value".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Study findings also suggest that monkeys, like humans, may slowly lose interest in taking MDMA over time, and that this change of heart is not a sign of brain toxicity.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA was synthesized in 1912 and patented in Germany by Merck in 1914 but was not the subject of human research at that time.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[11] .On December 24, 1912 Merck filed two patent applications that described the synthesis of MDMA[12] and its subsequent conversion to methylhydrastinine.^ On December 24 , 1912 Merck filed two patent applications that described the synthesis of MDMA 8 and its subsequent conversion to methylhydrastinine.

^ MDMA was subsequently patented in 1914 (Merck, 1914), but with the outbreak of World War I received little investigational attention into the drug’s potential applications (Shulgin and Shulgin, 1991).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ MDMA [3,4-methylenedioxy-methamphetamine: ' Ecstasy '] was first 1 synthesized in 1912 by the German pharmaceutical company Merck .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[13]
Over the following 65 years, MDMA was largely forgotten. .Merck records indicate that its researchers returned to the compound sporadically.^ Merck records indicate that its researchers returned to the compound sporadically.

.In 1927, Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar and smooth muscles were similar to ephedrine's.^ In 1927 , Max Oberlin studied the pharmacology of MDMA and observed that its effects on blood sugar and smooth muscles were similar to ephedrine 's, but that, in contrast, MDMA did not appear to produce pupil dilation .

^ An overwhelming similarity observed in most cases of MDMA-induced renal failure is the onset of hyperthermia.
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ As observed in the single dose MDMA study, rats exposed to multiple MDMA doses displayed blunted ACTH responses and augmented prolactin responses to fenfluramine.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Researchers at Merck conducted experiments with MDMA in 1952 and 1959.^ Researchers at Merck conducted experiments with MDMA in 1952 and 1959 .

^ This study will be conducted with a level of formality and oversight that MAPS is implementing for the first time but that will become standard on all our MDMA research projects.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ We’re encouraged that a large national audience will learn of our efforts to conduct MDMA psychotherapy research.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[11] .In 1953 and 1954, the United States Army commissioned a study of toxicity and behavioral effects in animals of injected mescaline and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973.^ In 1953 and 1954 , the United States Army commissioned a study of toxicity and behavioral effects in animals of injected mescaline and several analogues, including MDMA. These originally classified investigations were declassified and published in 1973 .

^ Goldberg G. United States legislative controls and their effect on the revival of amphetamine.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ While MDMA has been considered a predominately serotonergic agent, certain adverse effects including cardiovascular stimulation and hyperthermia likely involve NE and DA mechanisms, respectively.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[14] .The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi, the Journal of the Pharmaceutical Society of Japan.^ The first scientific paper on MDMA appeared in 1958 in Yakugaku Zasshi , the Journal of the Pharmaceutical Society of Japan .

^ MDMA [3,4-methylenedioxy-methamphetamine: ' Ecstasy '] was first 1 synthesized in 1912 by the German pharmaceutical company Merck .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ We will submit the paper to a scientific journal after we respond to the critiques from colleagues and experts.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.In this paper, Yutaka Kasuya described the synthesis of MDMA, a part of his research on antispasmodics.^ PiHKAL describes the synthesis and systematic testing on human subjects of a range of novel or neglected phenethylamine research drugs.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Ricaurte explains how he determined he administered methamphetamine instead of MDMA to primates and describes research with genuine MDMA that didn’t cause dopamine reductions.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[15]
.MDMA first appeared as a street drug in the early 1970s after its counterculture analogue, MDA, became criminalized in the United States in 1970.^ Whereas the first effect of MDMA appears to produce a REVERSIBLE depletion of 5-HT, the second is due to a NEUROTOXIC effect of the drug on serotonergic neurons or nerve terminals."
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ In the 1970s methamphetamine became a Schedule II drug - a drug with little medical use and a high potential for abuse.

^ Tracking ecstasy trends in the United States with data from three national drug surveillance systems.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[16] .In the mid-1970s, Alexander Shulgin, then at University of California, heard from his students about unusual effects of MDMA; among others, the drug had helped one of them to overcome his stutter.^ Alexander Shulgin, a Berkeley biochemist, is believed to have introduced the drug to the psychotherapeutic scene after self-administering the drug and testifying to MDMA’s rehabilitative potential (Shulgin and Shulgin, 1991; Shulgin and Nichols, 1978).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ MDMA was subsequently patented in 1914 (Merck, 1914), but with the outbreak of World War I received little investigational attention into the drug’s potential applications (Shulgin and Shulgin, 1991).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ Whereas the first effect of MDMA appears to produce a REVERSIBLE depletion of 5-HT, the second is due to a NEUROTOXIC effect of the drug on serotonergic neurons or nerve terminals."
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

.Intrigued, Shulgin synthesized MDMA and tried it himself in 1976.^ In truth, MDMA was an unplanned side reaction that occurred while Merck was trying to synthesize Hydrastinin, a vasoconstrictor (Gamma, 1998).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ Dr Shulgin himself reportedly felt MDMA came closest to fulfilling his ambition of finding the perfect psychotherapeutic drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Ironically, Dr Shulgin had himself synthesized MDMA in 1965, but hadn't tried it, an error of omission he later did much to repair .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[17] .Two years later, he and David Nichols published the first report on the drug's psychotropic effect in humans.^ Whereas the first effect of MDMA appears to produce a REVERSIBLE depletion of 5-HT, the second is due to a NEUROTOXIC effect of the drug on serotonergic neurons or nerve terminals."
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ Previously published and new data from our laboratory at the National Institute on Drug Abuse (NIDA) will be included to supplement literature reports.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ But beyond the narrow physical effects of MDMA on the brain, it's hard enough for articulate humans who take insight-and-empathy drugs to verbalise their processes of introspection.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

They described "altered state of consciousness with emotional and sensual overtones" that can be compared "to marijuana, to psilocybin devoid of the hallucinatory component".[18]
.Shulgin took to occasionally using MDMA for relaxation, referring to it as "my low-calorie martini", and giving the drug to his friends, researchers, and other people whom he thought could benefit from it.^ MDMA has even been described as a drug that "could be all things to all people" (Dr Shulgin).
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.One such person was psychotherapist Leo Zeff, who had been known to use psychedelics in his practice.^ It was forgotten until the middle 1970s when it was rediscovered by the psychedelic therapy community and began to be used as an adjunct to psychotherapy by psychiatrists and therapists who were familiar with the field of psychedelic psychotherapy.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ By the early 1980s, over a thousand private psychotherapists in the USA were using MDMA in their clinical practice.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Zeff was so impressed with the action of MDMA that he came out of his semi-retirement to proselytize for it. .Over the following years, Zeff traveled around the U.S. and occasionally to Europe training other psychotherapists in the use of MDMA.[17][19][20] Among underground psychotherapists, MDMA developed a reputation for enhancing communication during clinical sessions, reducing patients' psychological defenses, and increasing capacity for therapeutic introspection.^ This session will also be used as a training session for Drs.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ The protocol will submitted to FDA shortly after NIDA’s scientific meeting on MDMA, held at the National Institutes of Health campus in Bethesda, MD, on July 19-20.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[citation needed]
.Due to the wording of the United Kingdom's existing Misuse of Drugs Act of 1971, MDMA was automatically classified in the UK as a Class A drug in 1977.^ In Europe as of 1997, MDMA was number two on the list of most commonly used illicit drugs (United Nations, 1997).
  • MAPS: MDMA and Renal Function 24 January 2010 17:52 UTC www.maps.org [Source type: Academic]

^ MDA , MDEA , MDMA and assorted psychedelic amphetamines had been outlawed in the UK since 1977.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Whereas the first effect of MDMA appears to produce a REVERSIBLE depletion of 5-HT, the second is due to a NEUROTOXIC effect of the drug on serotonergic neurons or nerve terminals."
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

.In the early 1980s in the U.S., MDMA rose to prominence as "Adam" in trendy nightclubs and gay dance clubs in the Dallas area.^ In the early 1980s, American production of MDMA beyond the research laboratory was effectively controlled by chemists known as the "Boston Group".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ By the early 1980s, over a thousand private psychotherapists in the USA were using MDMA in their clinical practice.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[21] .From there, use spread to raves in major cities around the country, and then to mainstream society.^ Possibly it's because by this time there's far less serotonin around for the reuptake pump to use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

The drug was first proposed for scheduling by the Drug Enforcement Administration (DEA) in July 1984[22] and was classified as a Schedule I controlled substance in the U.S. on May 31, 1985.[23]
.In the late 1980s MDMA, as "ecstasy", began to be widely used in the UK and other parts of Europe, becoming an integral element of rave culture and other psychedelic- and dance-floor-influenced music scenes, particularly house music, with sub-genres such as trance, techno, Madchester and Acid House being most popular.^ Now it's up to us to prove what we have been saying for decades, that MDMA and other psychedelics have remarkable healing potentials.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Confessions of a middle-aged Ecstasy eater (son introduces father) A series of letters on MDMA and cancer (daughter introduces father) A Family’s Perspective on the Use of MDMA (parents introduce daughter) .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Mozart sounds great on Ecstasy, but high-energy all-night dance parties celebrated with techno-pop house music are more standard.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Spreading along with rave culture, illicit MDMA use became increasingly widespread among young adults in universities and later in high schools.^ It may be testimony to the comparative safety of MDMA that millions of young people use MDMA in the absence of a manual or any training, education and supervision at all.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Most commonly today, teenagers and young adults take Ecstasy to rave .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Such receptor stimulation can trigger marked hyperactivity, especially in young MDMA users who rave.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.MDMA became one of the four most widely used illicit drugs in the U.S., along with cocaine, heroin, and marijuana.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Bermejo-Barrera P, Moreda-Piñeiro A, Moreda-Piñeiro J, Bermejo-Barrera A. Determination of lead in illicit drugs by electrothermal atomic absorption spectrometry using palladium as chemical modifier.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

[citation needed] According to some estimates as of 2004, only marijuana attracts more first time users in the U.S.[24]
.After MDMA was criminalized, most medical use stopped, although some therapists continued to prescribe the drug illegally.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Later Charles Grob initiated an ascending-dose safety study in healthy volunteers.^ Our Institutional Review Board (IRB) has approved our protocol designed as a Phase 1 study of the psychological effects of MDMA in healthy volunteers.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ On the one hand, it is designed as a Phase 1 randomized, placebo-controlled, double-blind study of the psychological effects of MDMA on healthy volunteers.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MAPS' Harvard study is considered restrained and Charles Grob is chastised for speaking of potential spiritual benefits!
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Subsequent legally-approved MDMA studies in humans have taken place in the U.S. in Detroit (Wayne State University), Chicago (University of Chicago), San Francisco (UCSF and California Pacific Medical Center), Baltimore (NIDA-NIH Intramural Program), and South Carolina, as well as in Switzerland (University Hospital of Psychiatry, Zürich), the Netherlands (Maastricht University), and Spain (Universitat Autònoma de Barcelona).^ The existing database of MDMA pharmacokinetic studies represents a curious situation where clinical findings are well-documented, while preclinical data are lacking.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ It is a state of bliss, a participation mystique, a connectedness with both the interior and exterior universes, which has come about after the ingestion of a psychedelic drug, but which is not necessarily repeatable with a subsequent ingestion of the same drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Three protocols for double-blind controlled trials were from researchers at, respectively, Harvard Medical School, UC San Francisco Medical School, and U. of New Mexico Medical School, and were all rejected.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[25]
.In 2010 the BBC reported that use of MDMA had decreased in the UK in previous years.^ Doctors report that one Englishman consumed an estimated 40,000 tablets of MDMA over a nine year period.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Of course, no data exist on MDMA users who have been using it for 50 years.
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ While there is nothing in the medical literature on the topic, this report draws on information about MDMA, heptatitis C, and drugs used to treat it.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.This is thought to be due to increased seizures and decreased production of the precursor chemicals used to manufacture MDMA. The availability of legal alternatives to MDMA such as mephedrone is also thought to have contributed to its decrease in popularity.^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ So unlike tryptophan-loading and/or 5-HTP-loading to increase neural levels of serotonin production, this "dopaminergic" precursor strategy typically doesn't work.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Interestingly, the use of interventions to increase the biosynthesis of serotonin prior to MDMA use tends to trigger an increased synaptic release of dopamine, thereby enhancing the user's euphoria.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[26]

Therapeutic use

.There have long been suggestions that MDMA might be useful in psychotherapy, facilitating self-examination with reduced fear.^ Schmued ( 2003 ) used a novel histological stain, Fluoro-Jade B, to examine neuronal damage produced by MDMA administration in rats.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ The findings summarized in Table 3 suggest that there is no scientific justification for using interspecies scaling to “adjust” MDMA doses between rats and humans.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ This should be tempered by the observation that there > have been no observable long-term behavioral effects in people who have > taken MDMA, but it is unfashionable to decapitate humans and examine their > brains' serotonergic neurons directly.
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

[27][28][29] .Indeed, some therapists, including Leo Zeff, Claudio Naranjo, George Greer, Joseph Downing, and Philip Wolfson, used MDMA in their practices until it was made illegal.^ George Greer, a psychiatrist in private practice in Santa Fe, N.M., ...concluded that 'the single best use of MDMA is to facilitate more direct communication between people involved in a significant emotional relationship....'
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.George Greer synthesized MDMA in the lab of Alexander Shulgin and administered it to about 80 of his clients over the course of the remaining years preceding MDMA's Schedule I placement in 1985.^ Of course, no data exist on MDMA users who have been using it for 50 years.
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ In Newsweek , J Adler ["High on 'Ecstasy", April 15 1985] likened his MDMA experience to "a year of therapy in two hours".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.In a published summary of the effects,[30] the authors reported patients felt improved in various, mild psychiatric disorders and other personal benefits, especially improved intimate communication with their significant others.^ I especially want to communicate that fact to you because you are playing a significant role in making it possible.” November 11, 2008.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The journal Movement Disorders has recently published two letters in response to a report of parkinsonism in a former ecstasy user , and include a reply from the authors of the case report.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Ironically, at a time when the loss of personal liberty entailed by prohibitionist drug laws is justified by the societal costs of illicit drug-taking, "psychiatric" drugs are clinically prescribed by physicians regardless of the likely effect of a medication on the personal relationships of the patient.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.In a subsequent publication on the treatment method, the authors reported that one patient with severe pain from terminal cancer experienced lasting pain relief and improved quality of life.^ Two applications submitted by individual physicians were for single case studies, one for a terminal cancer patient who had been successfully treated for pain with MDMA-assisted psychotherapy prior to the criminalization of MDMA and the other for a unipolar depression patient for whom all available treatments had been attempted without success.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The project offers MDMA-assisted psychotherapy and non-drug psychotherapy for advanced-stage cancer patients who are experiencing anxiety and other end-of-life issues not adequately treated by traditional means.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The UCLA newspaper the Daily Bruin featured a report on Charles Grob's research on psilocybin in people with cancer experiencing anxiety relating to their illness.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[31] .However, few of the results in this early MDMA psychotherapy were measured using methods considered reliable or convincing in scientific practice.^ These parameters will be measured before and after the MDMA-assisted psychotherapy to allow researchers to evaluate changes in various areas of the brain and body.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ This study is designed to identify process variables that may help explain how MDMA can be a useful adjunct to psychotherapy.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ For an excellent history of the early use of MDMA, see Pursuit of Ecstasy by Beck and Rosenbaum.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.For example, the questionnaires used might not have been sensitive to negative changes and it is not known to what extent similar patients might improve from chance or from psychotherapy.^ Third, the behavioral tests utilized in rat studies might not be sensitive enough to detect subtle changes in learning and memory processes.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[citation needed]
.The therapeutic potential of MDMA is currently being tested in several ongoing studies, some sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS).^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Against formidable odds, the Multidisciplinary Association for Psychedelic Studies ( MAPS ) has been seeking funding and FDA-approval for controlled trials of MDMA-assisted therapy for PTSD. If these trials are successful, then MAPS hopes that MDMA could eventually become a prescription-medicine.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ (WIRB) has made the decision not to provide institutional review board services for the Multidisciplinary Association for Psychedelic Studies (MAPS).
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Studies in the U.S., Switzerland, and Israel are evaluating the efficacy of MDMA-assisted psychotherapy for treating those diagnosed with post-traumatic stress disorder (PTSD) or anxiety related to cancer.^ Explored in a controlled setting, MDMA can be therapeutic for victims of Post-Traumatic Stress Disorder ( PTSD ).
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The MAPS-sponsored study in Israel evaluating MDMA-assisted psychotherapy for subjects with war-and terrorism-related posttraumatic stress disorder (PTSD) has full government approval and is now in the subject recruitment stage.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.In interviews, patients and researchers from the South Carolina PTSD pilot study report tendencies for some participants to have reduced disease severity after MDMA psychotherapy.^ Israeli MDMA/PTSD pilot study protocol .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Swiss MDMA/PTSD pilot study protocol .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Wired published a piece charting the progress of research into the therapeutic uses of psychedelic drugs, including the ongoing studies of MDMA-assisted psychotherapy in people with PTSD, psilocybin in people with OCD, and psilocybin in cancer patient with anxiety, as well as planned studies into MDMA-assisted therapy in people with anxiety associated with advanced stage cancer, and psilocybin and LSD in people with cluster headaches September 14, 2004.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[32][33] .MAPS reported statistically significant results.^ Preliminary data analysis suggests that the research will have statistically significant results in reduction of PTSD symptoms in the subject population.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Such a problem doesn't always bedevil today's lame " antidepressants ", the results of whose trials often struggle to reach statistical significance.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[34] .MDMA has also been anecdotally reported to temporarily alleviate the symptoms of obsessive compulsive disorder (OCD).^ In defiance of scepticism from medical orthodoxy, Dr Holland also provides supporting evidence to back up anecdotal reports that MDMA can induce temporary remission of symptoms in victims of otherwise intractable schizophrenia .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Safe, long-acting MDMA analogues may prove therapeutic in the treatment of social phobia , eating disorders and obsessive-compulsive disorder ( OCD ).
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Indeed supersensitive 5-HT1B autoreceptors are implicated in depression and obsessive compulsive disorder.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.The European Monitoring Centre for Drugs and Drug Addiction notes that although there are some reports of tablets being sold for as little as €1, most countries in Europe now report typical retail prices in the range of €3 to €9 per tablet.^ The Guardian published another report specifically noting the recent expansion of the MDMA/PTSD study to now accept people with combat-related PTSD .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Austrailia's United Press runs "Dealers lacing ecstasy with other drugs," reporting on the widespread adulteration of ecstasy tablets throughout the country.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Domestic monitor program: A partial report on retail level heroin purchases from calendar year 1992, including source areas, cost, purity, and composition.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

[35] .The United Nations Office on Drugs and Crime claimed in its 2008 World Drug Report that typical U.S. retail prices are higher, 10 to 20 dollars per tablet, or from 2 to 10 dollars per tablet if bought in batches.^ Monograph: World Drug Report - 2000.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ Austrailia's United Press runs "Dealers lacing ecstasy with other drugs," reporting on the widespread adulteration of ecstasy tablets throughout the country.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Over 20 million such tablets and capsules have reportedly been sold in New Zealand, currently the world leader in BZP consumption and export.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[36] MDMA is expensive in Australia, costing AU$40–AU$70 per tablet, but in the asian comunity it is AU$20-30 depending on the size. .In terms of purity data for Australian MDMA, the average is around 34%, ranging from less than 1% to about 85%.^ MAPS' MDMA/PTSD research now has preliminary data to share with PTSD researchers around the world.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Reputedly there is less serotonergic toxicity than MDMA; but there can still be a very noticeable comedown.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Grob subsequently decided to focus on the use of psilocybin, instead of MDMA, in cancer patients, on the accurate theory that psilocybin research would be less controversial than MDMA research.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

The majority of tablets contain 70–85 mg of MDMA. Most ecstasy enters Australia from different markets, the Netherlands, the UK, Asia and the U.S.[37]

Polysubstance use

.MDMA is occasionally known for being taken in conjunction with psychedelic drugs, such as LSD or psilocybin mushrooms, or even common drugs such as marijuana.^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA was commonly known as "Adam", an allusion to "being returned to the natural state of innocence before guilt, shame and unworthiness arose".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Intriguingly, the euphoria experienced by MDMA users doesn't take the form of uncontrolled manic excitement, even where the drug induces "behavioural activation".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.As this practice has become more prevalent, most of the more common combinations have been given nicknames, such as "candy flipping", for MDMA combined with LSD[38], "hippie flipping" when combined with psilocybin mushrooms, and "kitty flipping" when combined with ketamine.^ Among heavy "recreational" MDMA users, self-medicating or otherwise, the incidence of depression seems to be more common than healed minds or any enduring therapeutic benefit.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In common with amphetamine, MDMA inhibits the neuronal reuptake of dopamine, albeit more weakly than MDA .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Again, MDMA use increases sensitisation to the rewarding effects of euphoriant dopaminergics such as cocaine ; and once more, this is not inherently a sign of "brain damage".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Many users use mentholated products while taking MDMA for its cooling sensation while experiencing the drug's effects.^ MDMA users for up to 1 year after cessation of drug use.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ For many but not all users, a magical drug becomes just a feel-good drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Examples include menthol cigarettes, Vicks[39] and lozenges. This sometimes has deleterious results on the upper respiratory tract.[40]

Chemistry

An industrial scale methamphetamine and MDMA chemical factory in Cikande, Indonesia.
.Safrole, a colorless or slightly black oil, extracted from the root-bark or the fruit of sassafras plants is the primary precursor for all manufacture of MDMA. There are numerous synthetic methods available in the literature to convert safrole into MDMA via different intermediates.^ Typically, safrole or isosafrole are first converted to MDP2P. The essential oil safrole occurs naturally as the primary constituent of oil of sassafras.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ These primary precursor chemicals of MDMA are produced in India, China, Poland, Germany, and increasingly elsewhere.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[41][42][43][44] .One common route is via the MDP2P (3,4-methylenedioxyphenyl-2-propanone, also known as piperonyl acetone) intermediate.^ Skinner HF. Methamphetamine synthesis via reductive alkylation hydrogenolysis of phenyl-2-propanone with N-benzylmethylamine.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

This intermediate can be produced in at least two different ways. .One method is to isomerize safrole to isosafrole in the presence of a strong base and then oxidize isosafrole to MDP2P. Another, reportedly better[citation needed], method is to make use of the Wacker process to oxidize safrole directly to the MDP2P (3,4-methylenedioxy phenyl-2-propanone) intermediate.^ Clandestine production is easiest starting with MDP2P. MDP2P (3,4-methylenedioxyphenyl-2-propanone) is a commercial product used by the flavouring and fragrance industry.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Groups with access to MDP2P can make MDMA via a simple conversion process.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Typically, safrole or isosafrole are first converted to MDP2P. The essential oil safrole occurs naturally as the primary constituent of oil of sassafras.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

This can be done with a palladium catalyst. .Once the MDP2P intermediate has been produced, it is then consumed via a reductive amination to form MDMA as the product.^ MDMA is listed on Merck's patent-application merely as a chemical intermediate "for products of potential pharmaceutical value".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Thus, 5,7-DHT produces reductions in 5-HT cell firing that are attributable to cell death, but MDMA does not.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

Another method of synthesis of MDMA is addition of HBr to safrole and reaction of the adduct with methylamine.
MDMA Synthesis 1.svg
MDMA Synthese 2.svg
.Relatively small quantities of essential oil are required to make large numbers of MDMA pills.^ Requirement to Belong to the Group “Ecstasy Realty”: Because of the large number of sims owned by Ecstasy Realty and the difficulty of personally notifying each and every tenant, it is now mandatory for all tenants to belong to the group “Ecstasy Realty”.
  • Ecstasy Realty in Second Life 3 February 2010 15:31 UTC ecstasyrealty.com [Source type: General]

.The essential oil of Ocotea cymbarum typically contains between 80 and 94% safrole.^ Typically, safrole or isosafrole are first converted to MDP2P. The essential oil safrole occurs naturally as the primary constituent of oil of sassafras.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.This would allow 500 ml of the oil, which retails at between $20 and $100, to be used to produce an estimated 1,300 to 2,800 tablets containing approximately 120 mg of MDMA each.^ Doctors report that one Englishman consumed an estimated 40,000 tablets of MDMA over a nine year period.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Thirty years ago in the US (and 20 years ago in Switzerland), when MDMA was not a prohibited substance, therapists were free to use MDMA as a tool in therapy.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[45]

Pharmacology

.The mechanism of action of MDMA's unusual effects has yet to be fully understood, although it is generally thought that the primary relevant pharmacological characteristic of the drug is its affinity for the plasmalemmal membrane transport protein the serotonin transporter (SERT).^ MDMA caused marked decreases in [ 3 H]-paroxetine-labeled SERT binding but had no effect on any measures of reactive gliosis.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ While MDMA has been considered a predominately serotonergic agent, certain adverse effects including cardiovascular stimulation and hyperthermia likely involve NE and DA mechanisms, respectively.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Many drugs used clinically produce effects that are similar to those produced by MDMA. For instance, reserpine causes sustained depletions of brain tissue 5-HT, yet reserpine is not considered a neurotoxin (Carlsson 1976 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.The SERT is a part of serotonergic neurons and removes the neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) from the synapse via reuptake for termination and recycling purposes after action potentials.^ Taking MDMA causes both an increased neuronal reuptake inhibition of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) and also, critically, its increased synaptic release .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ These differ in their substrate affinities and inhibitor sensitivities: the MAO-A isoenzyme has a greater affinity than the MAO-B isoenzyme for serotonin, but mainly MAO-B is present in the serotonergic axonal terminals, where it breaks down "foreign" neurotransmitters.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ HT1B hetero receptors are located on the terminals of non serotonergic neurons.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Not only does MDMA inhibit the reuptake of serotonin through its action at the SERT, but it also reverses its action through a process known as phosphorylation.^ MDMA induces the release of noradrenaline (norepinephrine), and inhibits its reuptake.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Dual-action dopamine- and serotonin-releasers like MDMA are the latter, though they aren't always harmless.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ However, MDMA is small enough to be taken up by the serotonin reuptake transporter into the serotonergic cell.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[46] .This results in the transporter conversely releasing serotonin into the synapse from inside the cell instead.^ The number of serotonin transporter sites, structural protein elements on the presynaptic outer axonal membrane that recycle the released neurotransmitter, may be reduced too.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ After the directionality of the reuptake pump is reversed by MDMA, serotonin released into the synapse can't be recycled back into the cell; and so it diffuses away.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Synapse 28:313–321 [ PubMed ] Rothman RB, Baumann MH (2002) Therapeutic and adverse actions of serotonin transporter substrates.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.For the above reasons, MDMA is classified as a combination serotonin reuptake inhibitor (SRI) and serotonin-releasing agent (SRA), though it is typically only referred to as the latter, since its definition essentially includes SRI properties.^ Unfortunately, pre-treatment with high doses of dopamine reuptake inhibitors blunts MDMA-induced release of dopamine, though not to the same degree as SSRIs blunt MDMA-induced release of serotonin.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ As well as inducing a synaptic flood of serotonin, taking MDMA indirectly induces the release of extra dopamine in the mesolimbic reward centres.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ However, MDMA is small enough to be taken up by the serotonin reuptake transporter into the serotonergic cell.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.In addition to its actions on serotonin, MDMA causes the same effects on the norepinephrine transporter (NET) and dopamine transporter (DAT), thus inducing release of norepinephrine and dopamine as well, respectively,[47] and hence, it can also be called a norepinephrine-dopamine reuptake inhibitor (NDRI) and norepinephrine-dopamine releasing agent (NDRA), or, in full, as a serotonin-norepinephrine-dopamine releasing agent (SNDRA).^ Unfortunately, pre-treatment with high doses of dopamine reuptake inhibitors blunts MDMA-induced release of dopamine, though not to the same degree as SSRIs blunt MDMA-induced release of serotonin.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA induces the release of noradrenaline (norepinephrine), and inhibits its reuptake.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin release via serotonergic neuromodulation.^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ While MDMA has been considered a predominately serotonergic agent, certain adverse effects including cardiovascular stimulation and hyperthermia likely involve NE and DA mechanisms, respectively.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA triggers the release of the neurotransmitter acetylcholine via a histaminergic H1 mechanism.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[48] .Oxytocin is a hormone released following events like hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust.^ To thicken the plot further, MDMA triggers the release of hypothalamic arginine-vasopressin and oxytocin (the "cuddle hormone").
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Oxytocin is a nine amino-acid peptide hormone and neurotransmitter that promotes pair-bonding , trust and social recognition.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Release of oxytocin, the " cuddle hormone ", surges too via stimulation of the serotonin 5-HT(1A) receptors.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[49] .Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor.^ Release of oxytocin, the " cuddle hormone ", surges too via stimulation of the serotonin 5-HT(1A) receptors.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ As well as inducing a synaptic flood of serotonin, taking MDMA indirectly induces the release of extra dopamine in the mesolimbic reward centres.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ At doses of MDMA and 5,7-DHT which caused comparable 5-HT depletions, only 5,7-DHT increased GFAP. In a more recent study, Pubill et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

A placebo-controlled study in 15 human volunteers found that 100 mg MDMA increased blood levels of oxytocin and the amount of oxytocin increase was correlated with the subjective prosocial effects of MDMA.[50]

Pharmacokinetics

MDMA powder
.MDMA reaches maximal concentrations in the blood stream between 1.5 and 3 hours after ingestion.^ With oral MDMA dosing, peak concentration in the plasma follows after around two hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ When the high-affinity enzymes are saturated, a disproportionately large increase in blood- and brain MDMA-concentrations may occur if the user then takes more of the drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.It is then slowly metabolized and excreted, with levels decreasing to half their peak concentration over approximately 8 hours.^ With oral MDMA dosing, peak concentration in the plasma follows after around two hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Thus, there are still high MDMA levels in the body when the experiential effects have mostly ended, indicating that acute tolerance has developed to the actions of MDMA. Taking additional supplements of MDMA at this point therefore produces higher concentrations of MDMA in the blood and brain than might be expected based on the perceived effects.^ Acute effects of (±)-MDMA on core body temperature in rats.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ In response to these massive doses of MDMA, levels of GFAP were significantly elevated in various brain regions but these increases did not correlate with the degree of 5-HT depletions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Metabolites of MDMA that have been identified in humans include 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-dihydroxyamphetamine (DHA) (also called alpha-methyldopamine (α-Me-DA)), 3,4-methylenedioxyphenylacetone (MDP2P), and N-hydroxy-3,4-methylenedioxyamphetamine (MDOH).^ MDMA is metabolised via N-demethylation to the active metabolite MDA; MDA can itself induce a state of sensual euphoria, though in humans the conversion rate from MDMA in the body is low.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Mizrachi N, Burla R, Sonenfeld D, Goren Z. The separation and identification of 3,4-methylenedioxyamphetamine derivatives (MDA, MDMA, MDEA and MBDB) in tablets.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ Pakulniewicz KJ. The use of derivatives to identify N-hydroxy-3,4-methylenedioxyamphetamine by GC-FTIR. Proceedings of the American Academy of Forensic Sciences 1995, 1, 22.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

.The contributions of these metabolites to the psychoactive and toxic effects of MDMA are an area of active research.^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA is metabolised via N-demethylation to the active metabolite MDA; MDA can itself induce a state of sensual euphoria, though in humans the conversion rate from MDMA in the body is low.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Now, the researchers working to make MDMA an FDA/EMEA approved prescription medicine must follow guidelines laid out by these agencies.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.65% of MDMA is excreted unchanged in the urine (additionally 7% is metabolized into MDA) during the 24 hours after ingestion.^ During the binge dosing procedure, body temperatures were measured by insertion of a thermometer probe into the rectum, and 5-HT-mediated behaviors were scored every hour.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ The metabolism of MDMA and MDA generates a number of metabolites, some of which may be active [e.g., Escobedo et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Like other substrate-type releasers, MDMA and MDA bind to plasma membrane monoamine transporters and are translocated into the cytoplasm.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[51]
.MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine.^ O -demethylenation catalyzed by cytochrome P450 2D6 (CYP2D6) and (2) O -methylation catalyzed by catechol- O -methyltransferase (COMT) [reviewed by de la Torre et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ CYP2D6 Cytochrome P450 2D6, CYP3A4 cytochrome P450 3A4, COMT catechol- O -methyltransferase.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ A naturally-occurring fatty acid derivative, GHB is a metabolite of normal human metabolism.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.The metabolism may be primarily by cytochrome P450 (CYP450) enzymes (CYP2D6 (in humans, but CYP2D1 in mice), and CYP3A4) and COMT. Complex, nonlinear pharmacokinetics arise via autoinhibition of CYP2D6 and CYP2D8, resulting in zeroth order kinetics at higher doses.^ MDMA has a complex nonlinear pharmacokinetics.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The CYP2D6 enzyme is soon saturated even in efficient metabolisers.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The release of serotonin following an MDMA-induced reversal of the reuptake pump results in a stimulation of the 5-HT1B receptors and, at higher doses, increasingly of the 5-HT2A receptors as well.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.It is thought that this can result in sustained and higher concentrations of MDMA if the user takes consecutive doses of the drug.^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ First-time MDMA users occasionally feel confused or anxious before the dose-dependent dopamine-release kicks in.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Because the enzyme CYP2D6 is deficient or totally absent in some people[52], it was once hypothesized that these people might have elevated risk when taking MDMA. However, there is still no evidence for this theory and available evidence argues against it.^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Study findings suggest that when monkeys take doses of MDMA similar to those used by Ecstasy-using humans, there are no signs of harm to serotonin or dopamine cells.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Lazy and reluctant eaters who regularly take Ecstasy are at greater risk of vitamin and mineral deficiencies, and more vulnerable to MDMA-induced serotonergic damage, than matched controls.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[53] .It is now thought that the contribution of CYP2D6 to MDMA metabolism in humans is less than 30% of the metabolism.^ Ideology aside, humans can benefit from genetically enhanced neuroprotection no less than intoxicated rodents.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ CYP2D6 and COMT are both polymorphic in humans, and differential expression of CYP2D6 isoforms leads to interindividual variations in the metabolism of serotonergic medications (e.g., SSRIs) (Charlier et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Reputedly there is less serotonergic toxicity than MDMA; but there can still be a very noticeable comedown.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Indeed, an individual lacking CYP2D6 was given MDMA in a controlled clinical setting and a larger study gave MDMA to healthy volunteers after inhibiting CYP2D6 with paroxetine.^ Data from the safety study revealed no unusual risks and indicated that MDMA could be safely administered within a clinical research context.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Psychological Effects/Therapist-Training MDMA Protocol Cleared by FDA The FDA permitted us to proceed with our clinical investigation, " A Phase I Placebo-Controlled, Double-Blind Crossover Study to Assess Psychological Effects of MDMA when Administered to Healthy Volunteers ," also referred to as our MDMA/PTSD therapist training protocol.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Explored in a controlled setting, MDMA can be therapeutic for victims of Post-Traumatic Stress Disorder ( PTSD ).
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Lack of the enzyme caused a modest increase in drug exposure and decreases in some metabolites, but physical effects did not appear appreciably elevated.^ In response to these massive doses of MDMA, levels of GFAP were significantly elevated in various brain regions but these increases did not correlate with the degree of 5-HT depletions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Inducible enzyme isoforms increase both in amount and activity in response to drugs.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ It's known that stimulation of the dopamine D2-like receptor causes an increase in phosphatidylinositol hydrolysis by activating enzyme phospholipase C. Enhanced phosphatidylinositol hydrolysis is implicated in euphoric mania .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.While there is little or no evidence that low CYP2D6 activity increases risks from MDMA, it is likely that MDMA-induced CYP2D inhibition will increase risk of those prescription drugs that are metabolized by this enzyme.^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The CYP2D6 enzyme is soon saturated even in efficient metabolisers.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Selegiline also protects against MDMA-induced inhibition of tryptophan hydroxylase .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.MDMA-induced CYP2D inhibition appears to last for up to a week after MDMA exposure.^ Selegiline also protects against MDMA-induced inhibition of tryptophan hydroxylase .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA-induced depletion of cortical 5-HT up to 70% did not alter spatial navigation, skilled forelimb use, or foraging behavior in rats.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ However, the threshold dose for any lasting MDMA-induced toxicity is unknown; and the identity and precise mechanism of the chemical(s) causing the oxidative stress is unclear.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.MDMA and metabolites are primarily excreted as conjugates, such as sulfates and glucuronides.^ If systemic metabolism of MDMA is indeed necessary for neurotoxicity, the nature of any such possible toxic metabolite (s) is unknown: thioether conjugates of alpha-methyl dopamine have been mooted; and in 2009 neurotoxic thioether adducts of MDMA were detected in humans.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[54]
The (R)-enantiomer (top) and the (S)-enantiomer of MDMA
MDMA is a chiral compound and has been almost exclusively administered as a racemate. .However, an early uncontrolled report suggests that the (S)-enantiomer is significantly more potent in humans than the (R)-enantiomer[55][56] indicate that the disposition of MDMA is stereoselective, with the S-enantiomer having a shorter elimination half-life and greater excretion than the R-enantiomer.^ MDMA-induced love is no more everlasting than its older and fitness-enhancing counterpart.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In men, orgasm is more intense than normal but delayed: MDMA retains a residual sympathomimetic activity, triggering a detumescence of the male organ.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MBDB's chemical cousin beta-keto-MBDB (bk-MBDB, " Butylone ") is a more enjoyable and stimulating empathogen than MBDB. As of 2009, its human use is still extremely limited.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.For example, Fallon et al.[55] reported that the area under the blood plasma concentration versus time curve (AUC) was two to four times higher for the (R)-enantiomer than the (S)-enantiomer after a 40 mg oral dose in human volunteers.^ With oral MDMA dosing, peak concentration in the plasma follows after around two hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ At doses of MDMA and 5,7-DHT which caused comparable 5-HT depletions, only 5,7-DHT increased GFAP. In a more recent study, Pubill et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Similarly, the plasma half-life of (R)-MDMA was significantly longer than that of the (S)-enantiomer (5.8 ± 2.2 hours vs 3.6 ± 0.9 hours).^ With oral MDMA dosing, peak concentration in the plasma follows after around two hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The preferentially metabolised (+)- enantiomer ("mirror image") of MDMA is more active, more stimulating, more dopaminergic, more subjectively rewarding , and more neurotoxic than the (-)- enantiomer .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.However, because MDMA has dose dependent kinetics, it is likely that these half-lives would be higher at more typical doses (100 mg is sometimes considered a typical dose).^ In response to these massive doses of MDMA, levels of GFAP were significantly elevated in various brain regions but these increases did not correlate with the degree of 5-HT depletions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ See more articles cited in this paragraph Abnormal ACTH and prolactin responses to fenfluramine in rats exposed to single and multiple doses of MDMA. Psychopharmacology (Berl).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Given as the racemate, MDMA has a half-life of around 8 hours.^ The optimal adult dose of racemic MDMA is probably around 120-130mg [around 2mg/kg of body weight i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ With oral MDMA dosing, peak concentration in the plasma follows after around two hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA for PTSD LSD/Psilocybin for Anxiety Related to Life-threatening Illness Ibogaine for Drug Addiction Medical Marijuana Psychedelic Research Around the World .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

Drug interactions

.There are a number of reported potentially dangerous possible interactions between MDMA and other drugs.^ The discovery that MDMA is not always the harmless fun-drug that a number of its recreational users (understandably) first supposed has caused the medical establishment to demonise MDMA or dismiss its psychotherapeutic potential completely.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Critics of the drug-warrior mentality claim that MDMA's possible neurotoxicity served only as a pretext for banning it.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Researchers certainly aren't paid to report that some illegal drugs are potentially life-enhancing agents.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Several cases have been reported of death in individuals who ingested MDMA while taking ritonavir (Norvir), which inhibits multiple CYP450 enzymes.^ The Harvard Crimson reported on the MDMA/cancer anxiety study that will be taking place at McLean Hospital.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ We have incorporated what we have learned in revised versions of our MDMA/PTSD protocols and Case Report Forms (CRFs).
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ But beyond the narrow physical effects of MDMA on the brain, it's hard enough for articulate humans who take insight-and-empathy drugs to verbalise their processes of introspection.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Toxicity or death has also been reported in people who took MDMA in combination with certain monoamine oxidase inhibitors (MAOIs) such as phenelzine (Nardil), tranylcypromine (Parnate), or moclobemide (Aurorix, Manerix).^ In any event, the monoamine oxidase inhibitor selegiline [l-deprenyl/ Eldepryl ] appears to be neuroprotective at monoamine oxidase type-B-selective dosages i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ People who take such agents are stigmatised as "drug abusers".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ So what leaves so many "normal" Darwinian people - who are neither clinically depressed nor loved-up on MDMA - comparatively anhedonic and hypo dopaminergic?
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[57] .On the other hand, MAOB inhibitors like selegiline (Deprenyl; Eldepryl, Zelapar, Emsam) do not seem to carry these risks when taken at selective doses, and have been used to completely block neurotoxicity in rats.^ In any event, the monoamine oxidase inhibitor selegiline [l-deprenyl/ Eldepryl ] appears to be neuroprotective at monoamine oxidase type-B-selective dosages i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ On the other hand, deficits in 5-HT release are readily demonstrated in MDMA-pretreated rats when 5-HT systems are taxed by drug challenge or environmental stressors.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA's apologists aren't convinced that the neurotoxicity evidence is persuasive - except for MDMA taken at unrealistically high doses.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[58]
.People taking any type of serotonin reuptake inhibitor (SRI) on a chronic basis commonly find that the psychedelic and entactogenic effects of MDMA are near fully abolished, leaving merely stimulation instead.^ As well as inducing a synaptic flood of serotonin, taking MDMA indirectly induces the release of extra dopamine in the mesolimbic reward centres.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ While MDMA has been considered a predominately serotonergic agent, certain adverse effects including cardiovascular stimulation and hyperthermia likely involve NE and DA mechanisms, respectively.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Unlike SSRIs, L-tryptophan and 5-HTP can be taken chronically without blunting MDMA's effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Many people attempt taking a dose around 3x as high and this appears to work as a remedy for the problem to some degree.^ Unfortunately, pre-treatment with high doses of dopamine reuptake inhibitors blunts MDMA-induced release of dopamine, though not to the same degree as SSRIs blunt MDMA-induced release of serotonin.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Additionally, upon discontinuation of the prolonged administration of the SRI in question, such individuals may still not be able to properly experience the full desired effects of MDMA at normal doses for anywhere from a few weeks to as long as several months.^ This should take several additional months.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ If MDMA is taken several days in a row, amphetamine-like and eventually dysphoric effects start to predominate.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA at normal doses is only minimally active at the "psychedelic" 5-HT2A receptor owing to its (comparatively) bulky methyl group.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.There is a possible risk of experiencing serotonin syndrome if MDMA is combined with another serotonergic drug.^ Review Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MDMA is often reckoned a "serotonergic" drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In general, taking MAO-inhibiting agents with anything serotonergic is normally contraindicated because of the risk of the serotonin syndrome .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[59]
.Most people who die while under the influence of MDMA have also consumed significant quantities of at least one other drug in combination.^ As a crossover study, subjects will get placebo on one occasion and MDMA on the other.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Doctors report that one Englishman consumed an estimated 40,000 tablets of MDMA over a nine year period.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Schedule One is the most restricted of all drug categories i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.The risk of solely MDMA-induced death is overall relatively minimal.^ One novel and unlikely-sounding proposal to minimise MDMA-induced neurotoxicity is pretreatment with aspirin .
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[24]

Effects

.The primary effects attributable to MDMA consumption are predictable and fairly consistent amongst users.^ MDMA's primary effects wear off after some 3-4 hours.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Even so, some heavy MDMA users claim they don't experience any long-term adverse effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ For although MDMA is no infallible truth-serum, its effects on the human user might indeed be abused for sinister purposes by skilled interrogators.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Generally, users report feeling effects within 30–60 minutes of consumption, hitting a peak at approximately 1–1.5 hours, reaching a plateau that lasts about 2–3 hours, followed by a comedown of a few hours which may be accompanied by fatigue and minor effects.^ In retrospect, today's entire dreaming and waking consciousness may prove to be only minor variants on a theme whose motif can't be grasped from within.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ It has been suggested that the heavy MDMA user who discerns no long-lasting ill effects, and who displays minimal functional impairment, may still be subtly damaging his or her serotonergic "functional reserve".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Some users of cocaine report feelings of restlessness, irritability, and anxiety.

[60][61][62]

Subjective effects

The most common effects reported by users include:[63]
As well as:

Side effects

.In January 2001, an overview of the subjective side effects of MDMA was published by Liechti, Gamma, and Vollenweider in the journal Psychopharmacology.^ Liechti and Vollenweider 2001 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Neuropsychopharmacology 22:513–521 [ PubMed ] Liechti ME, Vollenweider FX (2001) Which neuroreceptors mediate the subjective effects of MDMA in humans?
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ The appeal of MDMA is related to its unique profile of psychotropic actions, which includes amphetamine-like stimulant effects, coupled with feelings of increased emotional sensitivity and closeness to others (Liechti and Vollenweider 2001 ; Vollenweider et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Their paper was based on clinical research conducted over several years involving 74 healthy volunteers.^ On Friday May 8, Valerie Mojeiko and Josh Sonstroem of MAPS Clinical Research Team, went to Vancouver to conduct a pre-study site visit.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Clinquest JO will bring several clinical research staff from Egypt to hear the presentation.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Amy and Todd, the clinical research monitors who are volunteering to help us implement pharmaceutical-level monitoring and checks and balances, were impressively professional.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.The researchers found that there were a number of common side effects and that many of the effects seemed to occur in different amounts based on gender.^ Dry mouth, appetite suppression and insomnia are common adverse side-effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ There are gender differences in response; proportionately to body-weight, women are normally more sensitive than men to the sub-acute and longer-term effects of MDMA, so their optimal dosage may be lower.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Quite aside from their different molecular mechanisms of action, however, there are striking differences in subjective effect between MDMA and "serotonergic" centrally active psychiatric medicines.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.The top side effects reported were difficulty concentrating, jaw clenching, grinding of the teeth during sleep, lack of appetite, and dry mouth/thirst (all occurring in more than 50% of the 74 volunteers).^ Dry mouth, appetite suppression and insomnia are common adverse side-effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Adverse side-effects tend to become more troublesome.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Yet down at the bottom of the social heap, there are proportionately far more crushed and wounded spirits than there are at the top.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Liechti, et al. also measured some of the test subjects for blood pressure, heart rate, and body temperature against a placebo control. .The increases were noticeable, but not dangerous and not statistically significant (this means that the changes they measured were not certain to be an effect of the drug instead of random chance).^ Clearly non-humans can't describe the effects on their consciousness of psychoactives, even though they can be taught to "discriminate" them - the so-called "animal model" of subjective drug effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ A: All addictive drugs have two things in common: they produce an initial pleasurable effect, followed by a rebound unpleasant effect.

^ Furthermore, MDMA administration rarely causes persistent changes in baseline measures of neural function, and deficits are most readily demonstrated by provocation of the 5-HT system by pharmacological (e.g., drug challenge) or physiological means (e.g., environmental stress).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[64][65]

After effects

Effects reported by users once the acute effects of MDMA have worn off include:
.When they occur, these after subacute effects are typically reported to last up to 3 to 7 days, with the exception of depression, which in some cases has become chronic.^ While tolerance to the high can occur, users can also become more sensitive to cocaines anesthetic and convulsant effects without increasing the dose taken.

^ The functional deficit the dip reflects may last ten days or more - in some cases possibly weeks or months.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ When addicted individuals stop using cocaine, they may become depressed.

Overdose

Upon overdose, the potentially serious serotonin syndrome, stimulant psychosis, and/or hypertensive crisis, among other dangerous adverse reactions, may come to prominence, the symptoms of which can include the following:
.Potential incarceration, hospitalization, institutionalization, and/or death, on account of extreme erratic behavior which may include acts of crime, accidental or intentional self-injury, and/or suicide, as well as illicit drug abuse, may ensue under such circumstances.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ In the 1970s methamphetamine became a Schedule II drug - a drug with little medical use and a high potential for abuse.

^ A synthetic drug, methamphetamine has a high potential for abuse and dependence.

Chronic use

.Some studies indicate that repeated recreational users of MDMA have increased rates of depression and anxiety, even after quitting the drug.^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The Boston Globe published "A Good Death" , an article that discussess the resurgence of interest in studying MDMA and psychedelic drugs to help people with cancer deal with anxiety and pain.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA increases the rate of transporter-mediated serotonin outflow.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[66][67] .In addition to this, some studies have indicated that repeated recreational users of MDMA may have impaired long-term memory[68] and cognitive function.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ MAPS is pleased to have the help of volunteers Scott Martin MD and Mili Ballard to coordinate this long-term follow-up study.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[69] .Many factors, including total lifetime MDMA consumption, the duration of abstinence between uses, the environment of use, poly-drug use/abuse, quality of mental health, various lifestyle choices, and predispositions to develop clinical depression and other disorders may contribute to various possible health consequences.^ Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.MDMA use has been occasionally associated with liver damage,[70] excessive wear of teeth,[71] and (very rarely) Hallucinogen persisting perception disorder.^ MDMA for 2 days; persistent anxiogenic effects of MDMA were associated with depletions of 5-HT in the amygdala, hippocampus, and striatum.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA-induced depletion of cortical 5-HT up to 70% did not alter spatial navigation, skilled forelimb use, or foraging behavior in rats.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[72]

Legal issues

.MDMA is legally controlled in most of the world under the UN Convention on Psychotropic Substances and other international agreements, although exceptions exist for research.^ Monograph: Multilingual dictionary of narcotic drugs and psychotropic substances under international control.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ To date, only cocaine and heroin have been subjected to comprehensive studies; however, this field is expected to expand to other controlled substances over the next decade.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ In the USA itself, the world's most celebrated psychedelic chemist and leading authority on MDMA has been stymied from conducting human research on Schedule One compounds after publishing his trailblazing autobiography-cum-cookery book.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Generally, the unlicensed use, sale or manufacture of MDMA are all criminal offenses.^ The inspectors focused on issues of diversion control and checked out the safe, the alarm system and the forms and procedures that will be used to track all of the MDMA and placebo capsules.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ It may be testimony to the comparative safety of MDMA that millions of young people use MDMA in the absence of a manual or any training, education and supervision at all.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ However, not all the problems of MDMA use can be blamed on Prohibition and the lethal mix of ignorance and criminality it spawns.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

United Kingdom

.In the UK, MDMA is a Class A drug under the Misuse of Drugs Act 1971 (Schedule 1 under the Misuse of Drugs Regulations 2001), making it illegal to sell, buy, or possess without a license.^ This license will permit her to possess and handle MDMA for the study.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Studies of MDMA can be lawfully conducted only under government license by ideologically-vetted researchers.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ See more articles cited in this paragraph Review Are interspecies comparisons in the toxicity of centrally acting drugs valid without brain concentrations?
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking.^ Penalties include a maximum of seven years and/or unlimited fine for possession; life and/or unlimited fine for production or trafficking.

^ In 2001, the maximum penalty for death from dangerous driving was raised to 15 years.
  • DUI Library: Foreign - Drunk Driving in Japan | DUI.com 15 September 2009 3:42 UTC www.dui.com [Source type: FILTERED WITH BAYES]

^ Penalties include fines, incarceration and license suspension.
  • DUI Library: Foreign - Drunk Driving in Japan | DUI.com 15 September 2009 3:42 UTC www.dui.com [Source type: FILTERED WITH BAYES]

.See list of drugs illegal in the UK for more information.^ For more information about Estate pricing changes, please see the Estate pricing change FAQ. .
  • Ecstasy Realty in Second Life 3 February 2010 15:31 UTC ecstasyrealty.com [Source type: General]

^ See more articles cited in this paragraph Review Are interspecies comparisons in the toxicity of centrally acting drugs valid without brain concentrations?
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Click here to see it for yourself: Ecstasy City For more information, click HERE .
  • Ecstasy Realty in Second Life 3 February 2010 15:31 UTC ecstasyrealty.com [Source type: General]

.In February 2009 an official independent scientific advisory board to the UK government recommended that MDMA be re-classified to Class B, but this recommendation was immediately rejected by the government (see Recommendation to downgrade MDMA).^ MAPS submitted the MDMA/PTSD protocol for review to the Independent Review Consulting Institutional Review Board (IRC-IRB), with the protocol to be discussed by the review board on January 2, 2003.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ For the last several months, another independent Institutional Review Board (IRB) has been reviewing Dr. Michael Mithoefer’s MAPS -sponsored MDMA/PTSD protocol.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ See more articles cited in this paragraph Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA. Brain Res.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

This 2009 report on MDMA stated:[73]
.
The original classification of MDMA in 1977 under the Misuse of Drugs Act 1971 as a Class A drug was carried out before it had become widely used and with limited knowledge of its pharmacology and toxicology.^ Worried that his life's work might be quite literally destroyed by the drug-warriors, Dr Shulgin acted to thwart the obscurantists before it was too late.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The review will focus on data obtained from rats since most preclinical MDMA research has been carried out in this animal model.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Since then use has increased enormously, despite it being a Class A drug.^ The price of using such drugs can be hypermasculine aggressiveness ["roid rage"], increased dominance behaviour and even a propensity to sexual violence.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.As a consequence, there is now much more evidence on which to base future policy decisions....^ Very speculatively, our future offspring may not merely be more loved by their caregivers, but much more "loveable" too.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ On MDMA, there's much more going on as well.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Now we wait until the IRB meeting at the end of August to see if there are more questions.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Recommendation 1: A harm minimisation approach to the widespread use of MDMA should be continued....^ Tragically, when MDMA is used to excess the outcome can be harmful, not healing.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Recommendation 6: MDMA should be re-classified as a Class B drug.

United States

.In the U.S., MDMA was legal and unregulated until May 31, 1985, at which time it was emergency scheduled to DEA Schedule I, for drugs deemed to have no medical uses and a high potential for abuse.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MDMA-induced incidence of these syndromes was apparently unknown in clinical practice prior to the drug's legal proscription.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.During DEA hearings to schedule MDMA, most experts recommended DEA Schedule III prescription status for the drug, due to beneficial usage of MDMA in psychotherapy.^ An important part of the MDMA-assisted psychotherapy drug development process is to assess whether therapists are administering the therapy in a uniform manner consistent with the treatment manual.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Could MDMA really become a prescription drug?
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ After all, MDMA-assisted psychotherapy really can promote healing in a unique manner unlike any other prescription medicine.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.The judge overseeing the hearings, Francis Young, also recommended that MDMA be placed in Schedule III. Nevertheless, the DEA classified MDMA as Schedule I.[74][75] In 2001, responding to a mandate from the U.S. Congress, the U.S. Sentencing Commission, resulted in an increase in the penalties for MDMA by nearly 3,000%,[76] despite scientific protest calling for a decrease in the penalties for MDMA possession and distribution.^ The testimony had little effect and the Sentencing Commission recommended substantial increases in penalties.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The legal record from DEA’s 1984-1988 MDMA scheduling hearings Testimony by Rick Doblin, Ph.D. and others before US Sentencing Commission hearing on MDMA, 3/19/01 Why MDMA Should Not Have Been Made Illegal by Marsha Rosenbaum and Rick Doblin Meeting agenda and video archives for "MDMA/Ecstasy Research: Advances, Challenges, Future Directions" - NIDA-sponsored conference, July 19-20, 2001.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[77] .The increase makes 1 gram of MDMA (four pills at 250 mg per pill's total weight regardless of purity, standard for Federal charges) equivalent to 1 gram of heroin (approximately fifty doses) or 2.2 pounds (1 kg) of marijuana for sentencing purposes at the federal level.^ MDMA is now, dose for dose, punished more heavily than heroin.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The optimal adult dose of racemic MDMA is probably around 120-130mg [around 2mg/kg of body weight i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ MAPS currently owns approximately 17 grams of MDMA. We are having the supply of MDMA reexamined for quality assurance.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[78] See also the RAVE Act of 2003.

World Health Organization

In 1985 the World Health Organization's Expert Committee on Drug Dependence recommended that MDMA be placed in Schedule I of the 1971 Convention on Psychotropic Substances, despite noting:[79]
No data are available concerning its clinical abuse liability, nature and magnitude of associated public health or social problems.
The decision to recommend scheduling of MDMA was not unanimous:[79]
One member, Professor Paul Grof (Chairman), felt that the decision on the recommendation should be deferred awaiting, in particular, the data on the substance's potential therapeutic usefulness and that at this time international control is not warranted.
The 1971 Convention has a provision in Article 7(a) that allows use of Schedule I drugs for "scientific and very limited medical purposes." The committee's report stated:[79][80]
.
The Expert Committee held extensive discussions concerning therapeutic usefulness of 3,4 Methylenedioxymethamphetamine.^ The Guardian published an extensive discussion of current and planned research into the therapeutic uses of MDMA and psychedelic drugs .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.While the Expert Committee found the reports intriguing, it felt that the studies lacked the appropriate methodological design necessary to ascertain the reliability of the observations.^ While the Expert Committee found the reports intriguing, it felt that the studies lacked the appropriate methodological design necessary to ascertain the reliability of the observations.

^ We believe that this financial distance from MAPS, and more so the rigor of the methodological design of the study itself, will enable the results of the study to be viewed by skeptics as more objective.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.There was, however, sufficient interest expressed to recommend that investigations be encouraged to follow up these preliminary findings.^ There was, however, sufficient interest expressed to recommend that investigations be encouraged to follow up these preliminary findings.

^ END QUOTE If anyone is interested I would be willing to find out if there has been any further research on MDMA and report any results of the research.
  • behigh.org - XTC FAQ 24 January 2010 17:52 UTC www.behigh.org [Source type: Academic]

^ However, there are currently no particular pharmacological treatments for the wide range of symptoms associated with these abused drugs.

To that end, the Expert Committee urged countries to use the provisions of article 7 of the Convention on Psychotropic Substances to facilitate research on this interesting substance.

Health concerns

While the short-term adverse effects and contraindications of MDMA are fairly well known, there is significant debate within the scientific and medical communities regarding possible long-term physical and psychological effects of MDMA.

Short-term health concerns

.Short-term physical health risks of MDMA consumption include hyperthermia,[81][82] and hyponatremia.^ Serious adverse effects of MDMA intoxication include cardiac arrhythmias, hypertension, hyperthermia, serotonin (5-HT) syndrome, hyponatremia, liver problems, seizures, coma, and, in rare cases, death (Schifano 2004 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ The authors theorized that delay-dependent impairments in the DNMTP procedure reflect MDMA-induced deficits in short-term memory, possibly attributable to 5-HT depletion.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[83] .Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive perspiration puts the body at further risk as the stimulatory and euphoric qualities of the drug may render the user oblivious to their energy expenditure for quite some time.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Diuretics such as alcohol may exacerbate these risks further.^ Though such a tactic is sensible enough in theory, excess preloading with 5-HTP may potentially precipitate or exacerbate the serotonin syndrome.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

Long-term effects on serotonin and dopamine

.MDMA causes a reduction in the concentration of serotonin transporters (SERTs) in the brain.^ Long-term MDMA-induced changes in the availability of the serotonin transporter may be reversible ; but it is unclear whether recovery is complete.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ SSRIs inhibit the binding of MDMA to the serotonin transporter.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Current theory suggests that MDMA causes serotonin release via a diffusion exchange mechanism involving the serotonin transporter, not by calcium-dependent exocytosis of the serotonin-containing secretory vesicles.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

The rate at which the brain recovers from serotonergic changes is unclear. .One study demonstrated lasting serotonergic changes occurring due to MDMA exposure[84].^ On the one hand, it is designed as a Phase 1 randomized, placebo-controlled, double-blind study of the psychological effects of MDMA on healthy volunteers.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Prolonged MDMA administration can even cause a long-lasting increase in the dopamine content of the nucleus accumbens, possibly indicating its disinhibition from normal serotonergic control.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ As a crossover study, subjects will get placebo on one occasion and MDMA on the other.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Other studies have suggested that the brain may recover from serotonergic damage.^ Previous studies suggest that war-related PTSD may be more prevalent and harder to cure than PTSD caused by other types of trauma, and out study may help to compare the effect of trauma etiology on treatment efficacy.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ It has been suggested that the heavy MDMA user who discerns no long-lasting ill effects, and who displays minimal functional impairment, may still be subtly damaging his or her serotonergic "functional reserve".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Study findings also suggest that monkeys, like humans, may slowly lose interest in taking MDMA over time, and that this change of heart is not a sign of brain toxicity.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[85][86]
.Some studies show that MDMA may be neurotoxic in humans.^ Some studies suggest that possible MDMA-induced neurotoxicity to the serotonin system can be largely prevented by taking a double dose of fluoxetine (Prozac) or another SSRI shortly after starting to "come down".
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Some of the most important Spanish newspapers and journals broke the news about the MDMA/cancer anxiety study, echoing the news report from the Washington Post.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[87][88] .Other studies, however, suggest that any potential brain damage may be at least partially reversible following prolonged abstinence from MDMA.[86][89] However, other studies suggest that SERT-depletion arises from long-term MDMA use due to receptor down-regulation, rather than true neurotoxicity.^ Prolonged receptor activation typically leads to receptor desensitisation and/or down-regulation.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Orally administered MDMA causes a long-term depletion of serotonin in rat brain.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[90] .Depression and deficits in memory have been shown to occur more frequently in long-term MDMA users.^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Long-term MDMA-induced changes in the availability of the serotonin transporter may be reversible ; but it is unclear whether recovery is complete.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Even so, some heavy MDMA users claim they don't experience any long-term adverse effects.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[91][92] .However, some recent studies have suggested that MDMA use may not be associated with chronic depression.^ Despite the risks of illicit MDMA use, some clinicians believe the drug may have therapeutic potential in the treatment of psychiatric disorders, such as post-traumatic stress disorder, and clinical studies with MDMA are underway (Doblin 2002 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ At doses of MDMA and 5,7-DHT which caused comparable 5-HT depletions, only 5,7-DHT increased GFAP. In a more recent study, Pubill et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Study findings suggest that when monkeys take doses of MDMA similar to those used by Ecstasy-using humans, there are no signs of harm to serotonin or dopamine cells.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[93][94]
.One study on MDMA toxicity, by George A. Ricaurte of Johns Hopkins School of Medicine, 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 not MDMA but methamphetamine, which is known to cause dopaminergic changes similar to the serotonergic changes caused by MDMA.[95] Ricaurte blamed this mistake on the chemical supply company that sold the material to his lab.^ MDMA could, after all, actually cause dopaminergic neurotoxicity and Parkinson’s Disease.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA, one dose every 2 h.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ He originally claimed that MDMA caused severe dopaminergic neurotoxicity in primates injected with a common recreational dose regimen of MDMA, and suggested that Ecstasy users could develop Parkinson’s.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.Most studies have found that levels of the dopamine transporter (or other markers of dopamine function) in MDMA users deserve further study or are normal.^ This study will be conducted with a level of formality and oversight that MAPS is implementing for the first time but that will become standard on all our MDMA research projects.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Interestingly, the use of interventions to increase the biosynthesis of serotonin prior to MDMA use tends to trigger an increased synaptic release of dopamine, thereby enhancing the user's euphoria.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Clinical studies designed to critically evaluate the long-term effects of MDMA are hampered by a number of factors, including comorbid psychopathology and polydrug abuse among MDMA users.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[96][97][98][99][100][101][102]

Purity and dosage of "ecstasy"

.Another concern associated with MDMA use is toxicity from chemicals other than MDMA in ecstasy tablets.^ Activation of the 5-HT2C receptors serves to mask expression of MDMA-induced hyperactivity, sometimes evidently more effectively than others.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ For an excellent history of the early use of MDMA, see Pursuit of Ecstasy by Beck and Rosenbaum.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Austrailia's United Press runs "Dealers lacing ecstasy with other drugs," reporting on the widespread adulteration of ecstasy tablets throughout the country.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

Due to its near-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.^ In response to these massive doses of MDMA, levels of GFAP were significantly elevated in various brain regions but these increases did not correlate with the degree of 5-HT depletions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Doctors report that one Englishman consumed an estimated 40,000 tablets of MDMA over a nine year period.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The MDMA dosing regimen caused significant depletions of tissue 5-HT in various brain regions, including hypothalamus.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Pills may contain other active substances meant to stimulate in a way similar to MDMA, such as amphetamine, methamphetamine, ephedrine, or caffeine, all of which may be comparatively cheap to produce and can help to boost overall profits.^ Ecstasy tablets often contain other psychoactive substances such as substituted amphetamines, caffeine, or ketamine, which can contribute to the overall effects of the ingested preparation (Parrott 2004 ).
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Blunts; methamphetamine; PCP; a mixture of marijuana and other substances within a cigar; Gamma hydroxybutyrate (GHB) .

^ Rats receiving either single or multiple MDMA injections displayed marked increases in anxiogenic behaviors in all three tests when compared to control rats.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.In some cases, tablets sold as ecstasy do not even contain any MDMA. Instead they may contain an assortment of presumably undesirable drugs and substances, such as paracetamol, ibuprofen, piperizines, talcum powder, etc.^ In any case, MDMA users themselves may find the magic of the initial drug-induced epiphany tends to fade with frequent use.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Over 20 million such tablets and capsules have reportedly been sold in New Zealand, currently the world leader in BZP consumption and export.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Taken in the absence of a dopaminergic psychostimulant, TFMPP does not feel akin to MDMA. Even combined with a dopaminergic, TFMPP's activation of the 5-HT2C receptors makes some users feel anxious.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[103]
.There have been a number of deaths attributed to PMA, a potent and highly neurotoxic hallucinogenic amphetamine, being sold as ecstasy.^ Prohibitionism and a consequent absence of quality-control means that the "Ecstasy" sold in clubs often contains liberal quantities of amphetamine.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[104][105] .PMA is unique in its ability to quickly elevate body temperature and heart rate at relatively low doses, especially in comparison to MDMA. Hence, a user who believes he is consuming two 120 mg pills of MDMA could actually be consuming a dose of PMA that is potentially lethal, depending on the purity of the pill.^ In response to these massive doses of MDMA, levels of GFAP were significantly elevated in various brain regions but these increases did not correlate with the degree of 5-HT depletions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Nor does experimental central MDMA perfusion trigger the toxicity-enhancing higher body temperatures likely from the peripheral route.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ The ability of MDMA to elevate body temperature is well-characterized in rats (Dafters 1995 ; Dafters and Lynch 1998 ; Nash et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.Not only does PMA cause the release of serotonin, but also acts as a monoamine oxidase inhibitor, MAOI.^ Thus agents acting directly or indirectly as 5-HT1B agonists can cause the release of dopamine in the striatum and nucleus accumbens.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In any event, the monoamine oxidase inhibitor selegiline [l-deprenyl/ Eldepryl ] appears to be neuroprotective at monoamine oxidase type-B-selective dosages i.e.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Unfortunately, pre-treatment with high doses of dopamine reuptake inhibitors blunts MDMA-induced release of dopamine, though not to the same degree as SSRIs blunt MDMA-induced release of serotonin.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.When combined with an MDMA-like substance, serotonin syndrome can result.^ Serotonin 5-HT2A antagonists like ketanserin (Sulfrexal) can inhibit the syndrome; but they aren't widely available on the street or average dance-floor.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Dual-action dopamine- and serotonin-releasers like MDMA are the latter, though they aren't always harmless.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Like an SSRI, MDMA occupies the serotonin transporter and prevents serotonin from binding, increasing its availability in the synapse.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[citation needed]

Harm assessment

.The chief executive of the UK Medical Research Council stated that MDMA is "on the bottom of the scale of harm", and was rated to be of lesser concern than alcohol, tobacco, as well as several classes of prescription medications, when examining the harmfulness of twenty popular recreational drugs.^ Among MDMA's "unlicensed" and independent researchers, there is a natural tendency to believe any agent that triggers such sublime states must essentially be good for you.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Sessa and Nutt have recently published an editorial in the Journal of Psychopharmacology, "MDMA, politics and medical research: Have we thrown the baby out with the bathwater?"
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA-related medical complications have risen more than 20-fold in recent years, consistent with increasing popularity of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.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.^ Weve also added a measure of suicidality required by the FDA for all studies using drugs that have psychological effects.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Seekers of sustainable ecstasy would be rash to fetishise any particular drug or family of pharmacological tools - however magnificent their acute action on the user.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Based on these factors, the study placed MDMA at number 18 in the list of 20 popular drugs.^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The Boston Globe published a lengthy piece on the MDMA/cancer anxiety study that will take place at Harvard University's McLean Hospital.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ The Harvard Crimson reported on the MDMA/cancer anxiety study that will be taking place at McLean Hospital.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

[106]
.David Nutt, chairman of the UK Advisory Council on the Misuse of Drugs, stated in the Journal of Psychopharmacology in January 2009 that ecstasy use compared favorably with horse riding in terms of risk, with ecstasy leading to around 30 deaths a year in the UK compared to about 10 from horse riding, and "acute harm to person" occurring in approximately 1 in 10,000 episodes of ecstasy use compared to about 1 in 350 episodes of horse riding.^ News coverage of a soon-to-be published research report in the journal Human Psychopharmacology vary in depth and accuracy, with some claiming "Even Low ecstasy use harms memory," or "Taking Ecstasy Once can Damage Memory" , while others provide more details suggesting that this is not the case.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ It is a state of bliss, a participation mystique, a connectedness with both the interior and exterior universes, which has come about after the ingestion of a psychedelic drug, but which is not necessarily repeatable with a subsequent ingestion of the same drug.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Here in the UK, suicide is the most common cause of death for men under 35 years old.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[107] Dr. Nutt notes the lack of a balanced risk assessment in public discussions of MDMA:[107]
The general public, especially the younger generation, are disillusioned with the lack of balanced political debate about drugs. .This lack of rational debate can undermine the trust in government in relation to drug misuse and thereby undermining the government’s message in public information campaigns.^ Alas application of means-ends rationality is rarely the norm in drug-policy debate or in psychiatric medicine.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.The media in general seem to have an interest in scare stories about illicit drugs, though there are some exceptions (Horizon, 2008).^ There's so much to be wary about illicit drugs and their use."
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ While there is nothing in the medical literature on the topic, this report draws on information about MDMA, heptatitis C, and drugs used to treat it.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Some areas are seeing an increase in the number of Hispanic and Native American meth users, though whites are still the most dominant users of the drug.

[108] .A telling review of 10-year media reporting of drug deaths in Scotland illustrates the distorted media perspective very well (Forsyth, 2001).^ The forensic analysis of illicit drugs has been the subject of a number of minor review articles and monographs over the past 10 years (1,2,3,4,5,6,7,8,9).
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ This review presents a 10 year survey of the detection and analysis of drugs of forensic interest, as published in the mainstream scientific literature from 1992 through 2001.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ An immense amount of analytical data has been published over the past 10 years for drugs of abuse.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

[109] During this decade, the likelihood of a newspaper reporting a death from paracetamol was in [sic] per 250 deaths, for diazepam it was 1 in 50, whereas for amphetamine it was 1 in 3 and for ecstasy every associated death was reported.
A spokesperson for the ACMD clarified that "The recent article by Professor David Nutt published in the Journal of Psychopharmacology was done in respect of his academic work and not as chair of the ACMD."[110]

Recommendation to downgrade MDMA to Class B in the UK (Feb 2009)

.In 2000, the UK Police Foundation issued the Runciman Report which reviewed the medical and social harms of MDMA and recommended: "Ecstasy and related compounds should be transferred from Class A to Class B."[111] In 2002, the Home Affairs Committee of the UK House of Commons, issued a report, The Government's Drugs Policy: Is it working?, which also recommended that MDMA should be reclassified to a Class B drug.^ Review Allometric issues in drug development.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Chemical structures of MDMA and related compounds .
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Monograph: World Drug Report - 2000.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

[112] .The UK government rejected both recommendations, saying that re-classification of MDMA would not be considered without a recommendation from the Advisory Council on the Misuse of Drugs, the official UK scientific advisory board on drug abuse issues.^ This exchange of letters was part of a package of material that MAPS sent today to members of NIDA’s National Advisory Council on Drug Abuse (NACDA) requesting that NACDA recommend to NIDA that it release information about the MDMA research of Dr. Ricaurte.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA's defenders would say that the same is true of lithium, penicillin or paracetamol, none of which are banned.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ This is not just because the magic should be sustainable without limit, but because postponing the onset of drug-induced reward minimises a medicine's "abuse-potential" without compromising its efficacy.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

[113]
.In February 2009, the UK Advisory Council on the Misuse of Drugs issued A review of MDMA ('ecstasy'), its harms and classification under the Misuse of Drugs Act 1971, which recommended that MDMA be re-classified in the UK from a class A drug to a class B drug.^ Review Allometric issues in drug development.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Review Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

[73]
From the Discussion section of the ACMD report on MDMA:
.Physical harms: (10.2) Use of MDMA is undoubtedly harmful.^ Tragically, when MDMA is used to excess the outcome can be harmful, not healing.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.High doses may lead to death: by direct toxicity, in situations of hyperthermia/dehydration, excessive water intake, or for other reasons.^ MDMA displays nonlinear kinetics in humans such that administration of increasing doses, or multiple doses, leads to unexpectedly high plasma levels of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Use of cocaine in a binge, during which the drug is taken repeatedly and at increasingly high doses, may lead to a state of increasing irritability, restlessness, and paranoia.

^ At such extraordinary doses of MDMA, excessive sympathetic activation and hyperthermia could cause physiological dysregulation sufficient to elicit nonspecific neuropathy.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.However, fatalities are relatively low given its widespread use, and are substantially lower than those due to some other Class A drugs, particularly heroin and cocaine.^ Other psychoactive drugs are used mainly for "unrecognised" and non-medical purposes.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ To date, only cocaine and heroin have been subjected to comprehensive studies; however, this field is expected to expand to other controlled substances over the next decade.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

^ Rathbone DA, Holt PJ, Bruce NC, Lowe CR. The use of recombinant DNA technology in the design of a highly specific heroin sensor.
  • Detection and Analysis of Drugs, A Forensic Literature Review 1992-2001 - [www.rhodium.ws] 15 September 2009 3:42 UTC www.designer-drug.com [Source type: Academic]

Although it is no substitute for abstinence, the risks can be minimised by following advice such as drinking appropriate amounts of water (see Annex E). .(10.3) Some people experience acute medical consequences as a result of MDMA use which can lead to hospital admission, sometimes with the requirement for intensive care.^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ If and when it becomes approved in some form, this protocol will be the first FDA-approved study of the therapeutic use of MDMA since MDMA was placed in Schedule 1 in 1985.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA users could be related to cannabis use rather than MDMA. Further experiments will be required to resolve the precise nature of neuroendocrine changes in MDMA users.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.MDMA poisonings are not currently increasing in number and are less frequent than episodes due to cocaine.^ Grob subsequently decided to focus on the use of psilocybin, instead of MDMA, in cancer patients, on the accurate theory that psilocybin research would be less controversial than MDMA research.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Reputedly there is less serotonergic toxicity than MDMA; but there can still be a very noticeable comedown.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ A new study of MDMA self-administration in monkeys found MDMA to be far less toxic than assumed from previous studies.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.(10.4) MDMA appears not to have a high propensity for dependence or withdrawal reactions although a number of users seek help through treatment services.^ From October 6-10, 2008, Michael Mithoefer MD, Annie Mithoefer BSN, and June May Ruse PhD, worked on the MDMA/PTSD treatment manual .
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Clinical studies designed to critically evaluate the long-term effects of MDMA are hampered by a number of factors, including comorbid psychopathology and polydrug abuse among MDMA users.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ Moreover, 5-HT axons and terminals remaining after MDMA treatment appear swollen and fragmented, suggesting structural damage.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

.(10.5) MDMA appears to have little acute or enduring effect on the mental health of the average user, and unlike amphetamines and cocaine, it is seldom implicated in significant episodes of paranoia.^ But either way, chronic heavy use of the methoxylated amphetamines or any other " club-drug " poses risks to the user's health.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Alas they soon return; the acute effects of MDMA are mostly all too reversible.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Yet some MDMA users feel, rightly or wrongly, they've been granted a tantalising glimpse of what true mental health may be like in centuries to come; and an insight into what the rest of us are missing.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.(10.6) There is presently little evidence of longer-term harms to the brain in terms of either its structure or function.^ There is no evidence of any harm caused to any of the subjects by administering research grade MDMA in a therapeutic setting.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

.However, there is evidence for some small decline in a variety of domains, including verbal memory, even at low cumulative dose.^ Surprisingly, perhaps, there is substantial evidence to indicate that some endogenous serotonergic pathways normally activate rather than suppress motor output.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Not even heroic doses of MDMA are likely to kill off serotonergic brain cells, though there have been unconfirmed reports of MDMA-induced apoptosis in mega-dosed rats.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Even pure , low-dose MDMA does not suit everybody.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

The magnitude of such deficits appears to be small and their clinical relevance is unclear. .The evidence shows that MDMA has been misused in the UK for 20 years but it should be noted that long-term effects of use cannot be ruled out.^ Long-term MDMA-induced changes in the availability of the serotonin transporter may be reversible ; but it is unclear whether recovery is complete.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Alas, adopting a prophylactic SSRI regimen isn't a realistic long-term option for frequent MDMA users either, or at least not if they intend to continue using their hugdrug of choice.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ Long-term supplementation with DHEA seems to have beneficial effect on libido, immune function and some forms of cognition.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.(10.7) Overall, the ACMD judges that the physical harms of MDMA more closely equate with those of amphetamine than of heroin or cocaine.^ MDMA is now, dose for dose, punished more heavily than heroin.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA-induced love is no more everlasting than its older and fitness-enhancing counterpart.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

^ In men, orgasm is more intense than normal but delayed: MDMA retains a residual sympathomimetic activity, triggering a detumescence of the male organ.
  • MDMA / Ecstasy : Utopian Pharmacology 24 January 2010 17:52 UTC mdma.net [Source type: FILTERED WITH BAYES]

.Societal harms: (10.8) MDMA use seems to have few societal effects in terms of intoxication-related harms or social disorder.^ An article in the New Zealand Herald about posttraumatic stress disorder (PTSD) in veterans mentions the use of MDMA for PTSD but makes some incorrect claims.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ Long-term effects of (±)-MDMA on tissue levels of 5-HT ( top panel ) and DA ( bottom panel ) in brain regions.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

^ While MDMA appears to have few long-term effects on cognition in rats, a growing body of evidence demonstrates that MDMA administration can cause persistent anxiety-like behaviors in this species (Fone et al.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

However, the ACMD notes the very small proportion of cases where ‘ecstasy’ use has been implicated in sexual assault. (10.9) Disinhibition and impulsive, violent or risky behaviours are not commonly seen under the influence of MDMA, unlike with cocaine, amphetamines, heroin and alcohol. .(10.10) The major issue for law enforcement is ‘ecstasy’s’ position, alongside other Class A drugs, as a commodity favoured by organised criminal groups.^ In addition, law enforcement officials have caught teens as young as 14- and 15-year-olds using and selling the drug.

^ Key relapse issues are similar to that of cocaine use and include other substance abuse and being around drug-using friends.

It is therefore generally associated with a range of secondary harms connected with the trafficking of illegal drugs.
The UK Home Office rejected the recommendation of its independent scientific advisory board to downgrade MDMA to Class B, "saying it is not prepared to send a message to young people that it takes ecstasy less seriously".[114][115]
The government's veto was criticized in scientific publications. .Colin Blakemore, Professor of Neuroscience, Oxford, stated in the British Medical Journal, "The government’s decisions compromise its commitment to evidence based policy".[116] Also in response, an editorial in the New Scientist noted "A much larger percentage of people suffer a fatal acute reaction to peanuts than to MDMA....^ As already noted, there is no new study specifically studying MDMA-assisted therapy in people with combat-related PTSD, and the military has not been involved in any step of this research so far.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MAPS submitted a lengthy written response to the WIRB letter, along with 14 letters of information and support from MDMA scientists around the world.
  • MDMA Research 3 February 2010 15:31 UTC www.maps.org [Source type: Academic]

^ MDMA-related medical complications have risen more than 20-fold in recent years, consistent with increasing popularity of the drug.
  • 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings 28 January 2010 0:22 UTC www.ncbi.nlm.nih.gov [Source type: Academic]

Sadly, perspective is something that is generally lacking in the long and tortuous debate over illegal drugs."[117]

Environmental concerns

Demand for safrole in the manufacture of MDMA is causing rapid and illicit harvesting of the Cinnamomum parthenoxylon tree in Southeast Asia, in particular the Cardamom Mountains in Cambodia[118].

See also

References

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Further reading

External links


Simple English

Redirecting to Ecstasy


Citable sentences

Up to date as of December 04, 2010

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