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?”, speaking out against the effects of politics and regulation on medical research with MDMA and in favor of more basic and medical research. In their editorial, Sessa and Nutt discuss the costs to the research enterprise imposed by regulation of MDMA, and proposes at least three avenues of further research. The piece is provocative and uneven, but makes for encouraging reading for supporters of MDMA psychotherapy research.
By Ilsa Jerome
November 2007
Recently Sessa and Nutt published an editorial in the Journal of Psychopharmacology that argues that political involvement and regulation of MDMA has undermined the research enterprise by preventing scientists from readily conducting research with the drug (Sessa and Nutt 2007). Though aspects of their case are flawed or incomplete, their general point stands and can be extended from MDMA to other drugs, as LSD.
Sessa and Nutt recount the history of MDMA, including its use in psychotherapy, its escape from this context and its scheduling. They describe early anecdotal accounts and one early research study (Greer and Tolbert 1986). They note that placing MDMA in schedule 1 in part on the basis of lack of research supporting medical use itself curtails any research that might mitigate the lack of data. Sessa and Nutt consider several areas of psychological and psychiatric research that could benefit from conducting research with MDMA in humans, including investigations into the effects of serotonin on mood, assessing low-dose MDMA as an antidepressant and investigating the efficacy of MDMA-assisted psychotherapy, noting that studies of MDMA-assisted psychotherapy are already underway. They conclude by noting that all research with MDMA and other scheduled drugs is hampered by legal control, whether the research in question seeks to demonstrate the therapeutic potential of MDMA or some potentially negative effect, as the nature and trajectory of an MDMA “hangover.” Finally, Sessa and Nutt argue that the “war on drugs” results in a war on science.
Sessa and Nutt construct a strong case for the costs to researchers of restrictions produced by tight control, and note that any number of research questions are made inappropriately difficult to answer owing to these restrictions. However, some elements of their case rest on flawed assumptions, or they poorly present and describe the data supporting their case.
For instance, MDMA is a potent serotonin releaser, but it may not be the best choice for use in research studies of serotonin suppletion, as it also releases norepinephrine and dopamine (Battaglia et al. 1988; Setola et al. 2003). Other drugs, like fenfluramine, also elevate serotonin, yet do not elevate mood (Bond et al. 1995). The authors could have made a far stronger case for human MDMA research by noting the lack of research into its reportedly unique effects on how we feel and think about others (social cognition), the effects that drew some researchers to assign MDMA to a new drug class, the “entactogens.” There are no studies investigating even the simplest behavioral or pharmacological mechanisms for any of the unique effects of the drug.
Though correct in noting the lack of strong support for the existence of long-term effects of ecstasy use in moderate users, they do not seem to realize that long-term effects in heavy ecstasy users include both changes in estimated serotonin uptake sites and impaired cognitive function. While current research strongly suggests the transience of reduced brain serotonin sites, it is less clear in the case of impaired cognitive function (see for exampleReneman et al. 2006; Thomasius et al. 2006). While it is possible and perhaps even likely that the common practice of using other drugs plays a role in impairing memory in heavy ecstasy users, most studies find that the impairment lasts longer than changes in brain serotonin uptake sites.
Sessa and Nutt offer little basis in support of performing an investigation of low-dose MDMA as an anti-depressant. At the 10 to 25 mg doses they propose using, it seems likely that MDMA would not release sufficient serotonin, norepinephrine or dopamine to promote an immediate increase in mood, and is liable to be acting as a conventional selective serotonin uptake inhibitor. It is even possible that prolonged daily administration might produce some of the same heart problems that occurred after using fenfluramine or some anti-migraine drugs by activating 5HT2B receptors, though MDMA activity at this receptor is far smaller than its actions on any of the three monoamine transporters. Studies examining the use of MDMA in psychotherapy seem more fruitful.
Finally, they might have built a stronger case by educating readers on the difficulties of conducting research with restricted compounds, as the hurdles are not necessarily apparent for people working outside these areas of research. These difficulties make conducting research costly, and it may also make researchers uncomfortable or feel stigmatized for their interest in studying MDMA or other scheduled psychoactives.
Despite these problems, the case for the costs of political interference to medical and neuroscience research, and the arguments in support of continued human MDMA research remain provocative and strong. Preventing further research with MDMA from occurring on account of its legal status, Sessa and Nutt conclude, may prevent the development of exciting discoveries in psychiatry and neuroscience, including spotting a potential treatment for mental disorders.
References
Battaglia G, Brooks BP, Kulsakdinun C, De Souza EB (1988) Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites. Eur J Pharmacol 149: 159-163.
Bond AJ, Feizollah S, Lader M (1995) The effects of d-fenfluramine on mood and performance, and on neuroendocrine indicators of 5-HT function. J Psychopharmacol 9: 1-8.
Greer G, Tolbert R (1986) Subjective reports of the effects of MDMA in a clinical setting. J Psychoactive Drugs 18: 319-327.
Reneman L, Schilt T, de Win MM, Booij J, Schmand B, van den Brink W, Bakker O (2006) Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users. J Psychopharmacol 20: 389-399.
Sessa B, Nutt DJ (2007) MDMA, politics and medical research: Have we thrown the baby out with the bathwater? J Psychopharmacol 21: 787-791.
Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL (2003) 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Mol Pharmacol 63: 1223-1229.
Thomasius R, Zapletalova P, Petersen K, Buchert R, Andresen B, Wartberg L, Nebeling B, Schmoldt A (2006) Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: the longitudinal perspective. J Psychopharmacol 20: 211-225.