MDMA, politics and medical research: Have we thrown the baby out with the bathwater?

Sessa, Ben; Nutt, David

doi:10.1177/0269881107084738

Cited by 39 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it must be emphasized that these observations derived from a subject who used very high and (unusually) frequent doses of MDMA might have little relevance to subjects who receive very low, infrequent doses of the drug for possible therapeutic purposes (Sessa and Nutt, 2007).…”

Section: Implications For Possible Use Of Mdma In Psychiatrymentioning

confidence: 98%

“…Although the drug can cause some degree of methamphetaminelike euphoria (Dumont and Verkes, 2006), ecstasy users report other (still not well defined) pleasurable experiences that appear to be distinct from those of methamphetamine (Kish, unpublished observations). In addition, MDMA is now being tested in a clinical trial for the treatment of post-traumatic stress disorder (Mithoefer, 2007) and the suggestion has been made that the drug, because of its ability to cause release of serotonin (see Kish, 2002), might have some clinical utility in mood disorders (Sessa and Nutt, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study

Fitzmaurice

Chang

et al. 2008

J Psychopharmacol

View full text Add to dashboard Cite

Evidence that the widely used methamphetamine analog MDMA (3,4-methylenedioxymethamphetamine, ecstasy) might damage brain serotonin neurones in humans is derived from imaging investigations showing variably decreased binding of radioligands to the serotonin transporter (SERT), a marker of serotonin neurones. However, in humans, it is not known whether low SERT binding reflects actual loss of SERT protein itself. As this question can only be answered in post-mortem brain, we measured protein levels of SERT and that of the rate-limiting serotonin-synthesizing enzyme tryptophan hydroxylase (TPH) in autopsied brain of a high-dose MDMA user. As compared with control values, SERT protein levels were markedly (-48% to -58%) reduced in striatum (caudate, putamen) and occipital cortex and less affected (-25%) in frontal and temporal cortices, whereas TPH protein was severely decreased in caudate and putamen (-68% and -95%, respectively). The magnitude of the striatal SERT protein reduction was greater than the SERT binding decrease typically reported in imaging studies. Although acknowledging limitations of a case study, these findings extend imaging data based on SERT binding and suggest that high-dose MDMA exposure could cause loss of two key protein markers of brain serotonin neurones, a finding compatible with either physical damage to serotonin neurones or downregulation of components therein.

show abstract

Section: Implications For Possible Use Of Mdma In Psychiatrymentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study

Fitzmaurice

Chang

et al. 2008

J Psychopharmacol

View full text Add to dashboard Cite

show abstract

“…Recently Sessa and Nutt (2007) suggested that MDMA might be used as a psychotherapeutic agent. We concurred with them that the doses proposed would be unlikely to produce an acute adverse effect (Green et al 2008).…”

mentioning

confidence: 99%

MDMA: On the translation from rodent to human dosing

et al. 2009

View full text Add to dashboard Cite

The recent paper in this journal by Goni-Allo et al. (2008) was a welcome addition to the literature on the effects of MDMA in rodents because it examined functional changes and related them to the systemic exposure (e.g., plasma concentrations) of the drug. Such pharmacodynamicpharmacokinetic (or quantitative pharmacology) studies are vital if we are to attempt to relate preclinical findings to the possible acute and long-term consequences of human ingestion of MDMA. The debate on whether preclinical findings on the serotonergic neurotoxicity induced by MDMA in the rodent brain can be extrapolated to human recreational usage has engaged scientists' minds for around 20 years. Concerns have been raised as to whether the administered dose of MDMA typically used to cause neurotoxicity in rats allows any translational projections to be made as to the doses required to produce similar damage in the brains of humans following recreational use of the drug. These concerns are discussed in this short article.In order to extrapolate doses used in animal studies to those in man it has been suggested by some (McCann and Ricaurte 2001) that the technique of interspecies scaling (Mordenti and Chappell 1989) should be used. Based on similar exposure (AUC, Css) to MDMA in rats and humans, this proposes that using the equation D human ¼D animal W human =W animal ð Þ 0:7 (where D is dose in milligram and W is weight in kilogram) allows calculation of equivalent doses in animals and humans. Accordingly, the dose of 20 mg/kg in rats becomes equivalent to a human dose of 280 mg (4 mg/kg) or somewhat over three ecstasy tablets. Other investigators (Sessa and Nutt 2008) have intimated that a dose of (for example) 20 mg/kg given by intraperitoneal injection to rats can be directly extrapolated and therefore proposed that a similar oral dose is required by human users to achieve a similar effect. So, a 20 mg/kg dose in rats is deemed "equivalent" to a 1,400 mg dose (20 mg/kg× 70 kg body weight) which is around 20 ecstasy tablets.Of course, neither of these approaches has been shown to be valid for MDMA. Furthermore, the common practice of relating the pharmacological response directly to the administered dose is basically flawed. In examining the pharmacodynamics of a specific compound, factors like bioavailability, active metabolites, plasma protein binding differences, and pattern of systemic exposure can all play a major role in determining the onset, intensity, and duration of final effect. Since the exposure patterns of MDMA and active metabolite(s) can vary markedly between species, they confound any simple interpretation on a drug effect at any specific dose in one species producing a quantitatively similar effect in another, since it is impossible for all of the administered substance (at any stated dose) to be responsible for the observed pharmacological effect. For intelligent interpretation of any data collected, it is important at the very least to have a measurement of "exposure" of parent and potentially active metabolites ...

show abstract

“…22 The drug's historical link to recreational use as ecstasy maintains a negative legacy for many people. This controversy was starkly illustrated by the recent dismissal of the UK government's Chair of the Advisory Council on the Misuse of Drugs (ACMD) in the wake of comments made concerning a review of scientific evidence about the relative harm and safety of MDMA.…”

Section: Mdma For Ptsd Z Opinionmentioning

confidence: 99%

Could MDMA be useful in the treatment of post‐traumatic stress disorder?

Sessa¹

2011

Prog Neurol Psychiatry

Self Cite

View full text Add to dashboard Cite

In recent studies, 3,4‐methylenedioxymethylamphetamine (MDMA) has shown promise in the treatment of post‐traumatic stress disorder (PTSD) as an adjunct to post‐trauma psychological therapy. However, because of historical associations with its use as the recreational drug ecstasy, MDMA research remains a controversial subject. Dr Sessa discusses these controversies and describes a UK‐based MDMA/PTSD currently in development. Copyright © 2011 John Wiley & Sons, Ltd.

show abstract

MDMA, politics and medical research: Have we thrown the baby out with the bathwater?

Cited by 39 publications

References 25 publications

Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study

Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study

MDMA: On the translation from rodent to human dosing

Could MDMA be useful in the treatment of post‐traumatic stress disorder?

Contact Info

Product

Resources

About