3,4-Methylenedioxymethamphetamine (MDMA, "Ec- stasy") is a ring-substituted phenethylamine with a chemical structure related both to mescaline and methamphetamine. MDMA possesses a distinctive and unique psychological profile characterized by a specificity to act over the human emotional sphere (Shulgin & Nichols 1978) without notably affecting other psychological functions, such as visual per- ception or cognitive process (Harris et al. 2002; Tancer & Johanson 2001; Carni et al. 2000; Vollenweider et al. 1998). Because of this unusual quality, a new pharmacological category, entactogens, has been established to denote MDMA and some other chemically-related compounds (Hermle et al. 1993; Nichols 1986).
MDMA was first synthesized by the pharmaceutical company Merck in 1912 as a precursor of a haemostatic drug called methylhydrastinin, but it was not tested at that time either in humans or animals (Freudenmann, Öxler & Bernschneider-Reif 2006). In the 1950s, the U.S. army assayed a number of phenethy lamines, including MDMA, in toxicological animal studies (Hardman, Haavik, & Seevers 1973) but there are no references regarding its use in military human experiments. This research remained secret until publication in 1973. At the beginning of the 1970s, the former Bureau of Narcotics and Dangerous Drugs (now the Drug Enforcement Administration- DEA) found MDMA for the first time being used on the street (Gaston & Rasmussen 1972) but the first scientific references regarding its pharmacological profile did not appear until the end ofthat decade (Anderson et al. 1978; Shulgin & Nichols 1978), some years after its rediscovery by the chemist Alexander Shulgin (Shulgin & Shulgin 1991).
From the rediscovery of MDMA until its prohibition in the U.S. in 1985, MDMA was widely used as an adjunct to the psychotherapeutic process (Grinspoon & Bakalar 1986), although no formal controlled studies were undertaken. It has been estimated that during this period around 500,000 doses of MDMA were administered in psychotherapeutic settings (Rosenbaum & Doblin 1991) and that about 4,000 people were introduced to the therapeutic use of MDMA just by Leo Zeff, Ph.D., the "Secret Chief and leader of the underground therapeutic use of MDMA, (Stolaroff 1997; Shulgin & Shulgin 1991).
The inclusion of MDMA in the list of Schedule I controlled substances shut down all legal use, though in recent years there is a resurgence in the scientific investigation of the psychotherapeutic potential of MDMA (Check 2004; Doblin 2002), with studies investigating MDMA-assisted psychotherapy in subjects with PTSD approved in the U.S ., Switzerland and Israel and one study at Harvard Medical School approved to investigate MDMA-assisted psychotherapy in subjects with anxiety associated with advanced-stage cancer patients (Allen 2006).
Before the prohibition of MDMA in 1985, it was used by a wide range of psychotherapists to treat diverse psychological disorders, including psychosis and anxiety, in individuals and couple therapy as well in group therapy (Grinspoon & Bakalar 1986; Greer 1985). MDMA was also useful in reducing physical pain secondary to some kinds of cancer (Greer & Tolbert 1998). Most clinicians agreed that it was most useful in the treatment of sequelae secondary to psychological trauma, such as child abuse or war stress (Greer 1985).
The only quantitative data regarding the efficacy of MDMA were provided by Greer & Tolbert (1998, 1990, 1986) in their publications describing MDMA-assisted psychotherapy in 80 patients. Greer and Tolbert found that 90% of their patients reported positive experiences with lasting beneficial effects that remained at the one-year follow-up. Of those 90%, one third had experienced just one dose of MDMA, another third had experienced two doses, and the last third had taken more than two doses. In a followup utilizing a self-report questionnaire mailed to 171 patients treated by psychiatrists with MDMA and/or LSD-assisted psychotherapy in Switzerland between 1988 and 1993 (121 or 71% of questionnaires were returned with data), Gasser (1996, 1995) found that 65% of these respondents reported "good improvement" and 26% "slight improvement" after a course of LSD or MDMA-assisted therapy. Treatment consisted on average of three years of therapy with 70 nondrug sessions and seven sessions with MDMA or LSD.
Anecdotal accounts of MDMA-assisted therapy exist in print and in other media, including documents and testimony at the hearings on the scheduling of MDMA ( www.maps.org/deamdma; Greer & Tolbert 1998; Grinspoon & Bakalar 1986; Wolf son 1986). Lastly, psychotherapeutic models using MDMA as an adjunct to the psychotherapeutic process in the treatment of depression (Riedlinger & Montagne 2001; Riedlinger & Riedlinger 1994), schizophrenia (Holland 2001), and posttraumatic stress disorder (PTSD) (Bouso 2001) have been proposed.
The therapeutic potential of MDM A consists in temporarily reducing or eliminating anxiety and fear, thus helping subjects gain access to their emotions and internal conflicts without the overwhelming fear normally associated with these emotions and memories. This ameliorative effect simultaneously helps subjects access these traumatic emotions and communicate them to a therapist, thus enhancing both the therapeutic alliance and the psychotherapeutic process (Greer & Tolbert 1998; Grinspoon & Bakalar 1986; Greer 1985). Since it enhances both introspection and the strength of the therapeutic alliance- the most important variables predicting therapeutic outcome (Alexander & Luborsky 1986)- MDMA seems an ideal tool for use in the psychotherapeutic process, especially for the treatment of PTSD (Bouso 2001).
