A Clinical Plan for MDMA (Ecstasy) in the Treatment of Posttraumatic Stress Disorder (PTSD): Partnering with the FDA

Doblin, Rick

doi:10.1080/02791072.2002.10399952

Cited by 82 publications

(71 citation statements)

References 27 publications

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“…Hundreds of sessions were conducted with Adam and the drug subsequently gained recognition among some clinicians for the treatment of depression, physical and psychological pain, and relationship problems [42,59]. Proponents of MDMA for psychotherapeutic purposes have made some advances recently and studies are ongoing to determine whether MDMA is beneficial for veterans with post-traumatic stress disorder and for terminally ill cancer patients with anxiety [41,163].…”

Section: Historymentioning

confidence: 99%

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Piper

2007

Neurotoxicology and Teratology

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The entactogen ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug among college, high school, and, occasionally, middle school students. Preclinical research examining the acute and long-term effects of MDMA has predominately been conducted in reproductively mature subjects but there has been increasing interest in adolescent and in utero exposure. This review examines the acute and long-term responses to MDMA during perinatal, adolescent, and adult periods. The ability of MDMA to alter core body temperature emerges gradually during ontogeny while a reduction in body weight is evident at all ages. Learning and workingmemory are also altered independent of the developmental stage of exposure. Current evidence suggests adults are more sensitive to the long-term serotonin depletions following MDMA but younger ages also exhibit substantial and rapid neuroplasticity. Sexually dimorphic MDMA responses have been identified for the acute hyperthermic and motoric effects of MDMA with pubescent males being especially susceptible. Several physiological, behavioral, and neurochemical MDMA issues requiring further study are also outlined. Keywords±3; 4-methylenedioxymethamphetamine; Adolescence; Anxiety; Depression; Learning; SerotoninThe phenylethylamine ±3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug best known as ecstasy. MDMA has several other street names including Adam, baby slits, chocolate chips, clarity, doctor, essence, kleenex, and roll [77]. Although ecstasy has some similarities with both stimulants and hallucinogens, MDMA is an entactogen. Entactogen means "touching within" based on the drug's subjective effects [110]. MDMA also causes long term changes in several markers of the integrity of the serotonin (5-HT) neurotransmitter system [58]. There have been several excellent recent reviews on MDMA toxicology, pharmacokinetics, pharmacodynamics, and neurobehavioral consequences [30,37,113,157], but none have systematically addressed the intricate effects of MDMA during development.Ecstasy use is not restricted to limited subpopulations, that is fans of techno music and "raves" [173] or male homosexuals [73,81], as MDMA has expanded into the general population [124,148,170] and especially young people [52,78,170,172]. Over one hundred pregnant women in Toronto called a substance abuse helpline between 1998 and 2000 to inquire Corresponding Author: Brian J. Piper, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003-7710, Tel: (413) 545-0996, bpiper@nsm.umass.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers...

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Section: Historymentioning

confidence: 99%

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Piper

2007

Neurotoxicology and Teratology

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“…Recreational users of MDMA, researchers, and the press have challenged the utility and validity of studies from the animal literature while anecdotal and empirical evidence suggests that public health messages regarding MDMA toxicity continue to be met with some skepticism ( . Furthermore, consideration of MDMA's therapeutic potential is gaining increasing acceptance from the United States Food and Drug Administration (FDA) as witnessed by current clinical trials exploring MDMA's efficacy in the treatment of refractory posttraumatic stress disorder and cancer-associated anxiety (Newton 2001;Doblin 2002;Kohn 2004;Crittenden 2005;Marsa 2005).…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging research in human MDMA users: a review

Cowan

2006

Psychopharmacology

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Rationale Determining whether, under what circumstances, and to what extent 3,4-methylenedioxymethamphetamine (MDMA) exposure produces chronic changes in human brain function is a critical public health issue. MDMA is a widely used recreational drug commonly sold as "Ecstasy". Because findings from the animal literature have indicated that specific dosage regimens of MDMA can produce longlasting alterations in serotonergic function, existing studies of MDMA effects in humans have examined brain serotonin (5-HT) transporters (5-HTT) and receptors or have examined brain structures or functions potentially affected by MDMA. Objectives The objectives of this review are to provide a background for interpreting human MDMA neuroimaging research, to examine existing neuroimaging data regarding the rationale for and limitations to human MDMA research, and to provide suggestions for improving the design and interpretation of future neuroimaging approaches. Results Of the existing neuroimaging studies in human MDMA users, few experimental designs have been replicated across different research groups. Only investigations employing nuclear imaging methods to assay brain 5-HTT levels have been replicated across methods and research laboratories. These studies have found reduced levels of the 5-HTT in recently abstinent MDMA users with some evidence for normalization of 5-HTT levels with prolonged abstinence. However, the sensitivity of these methods is unknown.Conclusions The current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure. Future study designs might benefit from improved sample homogeneity, increased length of MDMA abstinence, longitudinal study design, test-retest measures, serotonergic specificity, and multimodal approaches.

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“…It is important to gain insights into such mechanisms if we are to create rational arguments regarding the abuse liability of MDMA. In addition, because clinical studies are underway to investigate the utility of MDMA in treating post-traumatic stress disorder (Doblin, 2002), new knowledge regarding the drug effects on sensory physiology is critical for establishing the drug's therapeutic potential.…”

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confidence: 99%

MDMA (3,4-Methylenedioxymethamphetamine)-Mediated Distortion of Somatosensory Signal Transmission and Neurotransmitter Efflux in the Ventral Posterior Medial Thalamus

Starr

Page

Waterhouse³

2008

J Pharmacol Exp Ther

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MDMA (3,4-methylenedioxymethamphetamine, Ecstasy) is reported to enhance tactile sensory perception, an effect that is believed to contribute to its popularity as a recreational drug. To date, no literature exists that addresses the neurophysiological mechanisms underlying the effects of MDMA on somatosensation. However, MDMA interactions with the serotonin transporter protein (SERT) are well known. The rat trigeminal somatosensory system has been studied extensively and receives serotonergic afferents from the dorsal raphe nucleus. Given that these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that short-term lowdose MDMA administration (3 mg/kg i.p.) led to a significant increase in 5-hydroxytryptamine (5-HT) efflux in the ventral posterior medial (VPM) thalamus, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We further evaluated the potential for MDMA to modulate whisker-evoked discharge (WED) of individual neurons in this region. After surgically implanting stainless steel 8-wire multichannel electrode bundles, we recorded spike train activity from single cells of halothane-anesthetized rats while mechanically activating the whisker pathway. We found that short-term low-dose MDMA (3 mg/kg i.p.) increased the spontaneous firing rate but reduced the magnitude and duration of WED in individual VPM thalamic neurons. It is noteworthy that the time course of drug action on neuronal firing patterns was generally consistent with increased 5-HT efflux as shown from our microdialysis studies. Based on these results, we propose the working hypothesis that MDMA may "distort" rather than enhance tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.

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A Clinical Plan for MDMA (Ecstasy) in the Treatment of Posttraumatic Stress Disorder (PTSD): Partnering with the FDA

Abstract: The following article was originally published in the April-June 2002

Cited by 82 publications

References 27 publications

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

Neuroimaging research in human MDMA users: a review

MDMA (3,4-Methylenedioxymethamphetamine)-Mediated Distortion of Somatosensory Signal Transmission and Neurotransmitter Efflux in the Ventral Posterior Medial Thalamus

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