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Taffe Lab: MDMA

(+/-)3,4-Methylenedioxymethampetamine (MDMA, "Ecstasy")

MDMA/Ecstasy molecule

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Current projects in the laboratory focus on cognitive, thermoregulatory and reinforcing effects of exposure to MDMA.

Phase III: Interest in the reinforcing properties of MDMA Search PubMed is related to the observation that despite considerable structural similarity between the amphetamines, recreational use patterns for MDMA differ considerably from, e.g., d-amphetamine or d-methamphetamine. Nevertheless it is clear that some users develop repetitive, compulsive use patterns more consistent with stimulant addiction. Our goal is to understand why MDMA is less compulsively abused and the mechanisms by which use may transition to compulsive intake.

Phase II: Interest in the thermoregulatory impact of MDMA is further enhanced by evidence from Emergency Department reports and examinations of neurotoxic dosing in rodents. Many MDMA-related ED visits and fatalities feature significant and malignant elevations in body temperature Search PubMed . It is relatively unknown how MDMA dose, individual liabilities and environmental conditions may interact to produce thermo-critical events. Similarly, the impact of less critical thermoregulatory disturbances on post-MDMA consequences are not well understood.

In repeated-dosing "neurotoxicity" studies in rodents, the magnitude of the serotonergic insult depends in some part on the change in body temperature that is produced Search PubMed . MDMA appears to produce a poikilothermic state rather than unidirectional hyperthermia in rodents. Acute or lasting influences of body temperature alterations associated with MDMA had not been well characterized in the nonhuman primate models prior to our studies. Our goal was to evaluate the acute and sustained effects of MDMA on thermoregulation in the macaque to refine our understanding of the conditions under which lasting behavioral effects are or are not produced. Our ongoing studies have found that monkey temperature responses to acute MDMA are insensitive to stereoisomer and ambient temperature (Taffe et al, 2006; Von Huben et al., 2007); both results appear to differ from rodent responses. Furthermore, MDMA suppresses activity in monkeys whereas it increases activity in rats. Nevertheless, the consistent hyperthermia under normal laboratory conditions indicated that our negative cognitive results were not due to a failure of MDMA to cause body temperature elevation.

Phase I: Interest in the cognitive impact of MDMA stemmed from two lines of evidence. First, human recreational users of Ecstasy exhibit a range of neuropsychological disturbance even after prolonged intervals of abstinence from Ecstasy Search PubMed . Second, repeated dosing with MDMA over short intervals (e.g., twice per day for four days) results in selective reductions in serotonin terminal markers in many nonhuman species including both Old World and New World monkeys Search PubMed . Our goal was to determine if the established neuropsychological disturbances in abstinent Ecstasy users is attributable to MDMA.  We found no lasting cognitive changes following a typical "neurotoxicity" regimen which did produce the expected decrease in serotonin in cortex and hippocampal regions (Taffe et al, 2001, 2002, 2003). This led to a question of whether monkeys experienced body temperature changes akin to those found so necessary in rodent models to produce neurotoxicity.

MDMA/Ecstasy Publications

Dutta, R.R., Taffe, M.A. and Mandyam, C.D. Chronic administration of amphetamines disturbs development of neural progenitor cells in young adult nonhuman primates.  Progress in Neuropsychopharmacology & Biological Psychiatry, 2018, 85:46-53. [ Publisher Site ][ PubMed ]

Aarde, S.M., Huang, P-K  and Taffe, M.A. High Ambient Temperature Facilitates The Acquisition Of 3,4-Methylenedioxymethamphetamine (MDMA) Self-Administration. Pharmacol Biochem Behav, 2017 Dec, 163:38-49. [ Publisher Site ][ PubMed ]

Vandewater, S.A., Creehan, K.M. and Taffe, M.A. Intravenous self-administration of entactogen-class stimulants in male rats. Neuropharmacology, 2015, 99:538-545. [ Publisher Site ][ PubMed ]

Aarde, S.M., Miller, M.L. Creehan, K.M., Vandewater, S.A. and Taffe, M.A. One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and Methylone. Drug Alcohol Depend, 2015, 151:151-158. [ Publisher Site ][ PubMed ]

Creehan, K.M., Vandewater, S.A. and Taffe, M.A. Intravenous self-administration of mephedrone, methylone and MDMA in female rats. Neuropharmacology, 2015, 92:90-97. [ Publisher Site ][ PubMed ]

Miller, M.L., Creehan, K.M., Angrish, D., Barlow, D.J., Houseknecht, K.L., Dickerson, T.J. and Taffe, M.A. Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone), Drug Alcohol Depend, 2013, 127(1-3):248-253 Epub 2012 Jul 23.[ PubMed Abstract ] [ Publisher Link ]

Huang,P.K.,  Aarde, S.M., Angrish, D., Houseknecht, K.L., Dickerson, T.J. and Taffe, M.A. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats, Drug Alcohol Depend, 2012, [ PubMed Abstract ][ Publisher Link ]

Taffe, M.A. Δ9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys, Neuroscience, 2012, 201:125-133 Nov 29 2011 [Epub ahead of print] [ PubMed Abstract ] [ Publisher Link ]

Gilpin, N.W., Wright Jr., M.J., Dickinson, G., Vandewater, S.A., Price. J.U., and Taffe, M.A. Influences of activity wheel access on the body temperature response to MDMA and Methamphetamine, Pharmacol Biochem Behav, in press  [ PubMed Abstract ] [ Publisher Link ][ RequestPDF ]

Crean, R.D., Davis, S.A. and Taffe M.A. Oral administration of (±)3,4-methylenedioxymethamphetamine and (+)methamphetamine alters temperature and activity in rhesus macaques, Pharmacol Biochem Behav, 2007, 87(1): 11-19. [ PubMed Abstract ] [ Publisher Link ]. [ RequestPDF ]

Von Huben, S.N., Lay, C.C., Crean, R.D., Davis, S.A., Katner, S.N. and Taffe M.A. Impact of ambient temperature on hyperthermia induced by (±)3,4-methylenedioxymethamphetamine in rhesus macaques, Neuropsychopharmacology, 2007, 32(3):673-681. Epub 2006 Apr 12. [ PubMed Abstract ] [ Publisher Link ]. [ RequestPDF ]

Crean, R.D., Davis, S.A., Von Huben, S.N., Lay, C.C., Katner, S.N. and Taffe M.A. Effects of (±)3,4-methylenedioxymethamphetamine, (±)3,4-methylenedioxyamphetamine and methamphetamine on temperature and activity in rhesus macaques, Neuroscience, 2006, 142(2):515-525.Epub 2006 Jul 28 [ PubMed Abstract ] [ Publisher Link ]. [ RequestPDF ]

Taffe, M.A., Lay, C.C., Von Huben, S.N., Davis, S.A., Crean, R.D. and Katner, S.N. Hyperthermia induced by 3,4-methylenedioxymethamphetamine in rhesus monkeys, Drug Alcohol Depend, 2006, 82(3):276-281 [ PubMed Abstract ] [ Publisher Link ]. [ RequestPDF ]

Taffe, M.A., Huitrón-Resendiz, S., Schroeder, R., Parsons, L.H., Henriksen, S.J. and Gold, L.H. (2003). MDMA exposure alters cognitive and electrophysiological sensitivity to rapid tryptophan depletion in rhesus monkeys, Pharmacol Biochem Behav, 76(1):141-152. [ PubMed Abstract ] [ Publisher Link ] [ RequestPDF ]

Taffe, M.A., Davis, S.A., Yuan, J., Schroeder, R., Hatzidimitriou, G., Parsons, L.H., Ricaurte, G.A., and Gold, L.H. (2002) Cognitive performance of MDMA-treated rhesus monkeys: Sensitivity to serotonergic challenge, Neuropsychopharmacology, 27(6):993-1005. [ PubMed Abstract ] [ Publisher Link ] [ Request PDF ]

Taffe, M.A., Weed, M.R., Davis, S., Huitrón-Resendiz, S., Schroeder, R., Parsons, L.H., Henriksen, S.J. and Gold, L.H. (2001) Functional consequences of repeated (±)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys, Neuropsychopharmacology, 24(3):230-239 [ PubMed Abstract ] [ Publisher Link ] [ RequestPDF ]

MDMA research in The Taffe Laboratory was previously supported by USPHS Grant R01 DA024105 and R01 DA018418.