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MDMA-Assisted Psychotherapy as an Intervention for People Suffering from Post-Traumatic Stress Disorder

Stefan Bumol

October 10, 2008

·      What is PTSD and how is it treated now?

 

Post-Traumatic Stress Disorder (PTSD) is a psychological disorder that can develop in people who have experienced a terrifying ordeal that involved physical harm or the threat of physical harm to one’s self or others.  PTSD results from a variety of incidents including rape, torture, natural disasters, abuse, and accidents and was first brought to public attention in relation to war veterans and postwar psychological trauma.  Most people suffering from PTSD repeatedly relive their trauma through conscious flashbacks of the events or in nightmares while sleeping.  These symptoms can have significant impact on the quality of life for people suffering from PTSD.  PTSD can occur at any age, and the National Institutes of Health estimates that PTSD affects 7.7 million American adults (http://www.nimh.nih.gov/health/publications/anxiety-disorders/nimhanxiety.pdf).

 

          PTSD is a complex biopsychosocial condition that is identified by a combination of symptoms including fear and hyperarousal, intrusive re-experiencing of traumatic experiences, and numbing and withdrawal.  Current treatments for PTSD may involve some form of psychotherapy and/or the use of anti-anxiety drugs such as benzodiazepines.  While these treatments are effective for some, others do not find relief of their symptoms from such treatments (http://www.maps.org/research/mdma/ptsd_study/treatment-manual/053005/intro.html).   

 

·      What is MDMA?

 

3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive amphetamine known to produce a variety of physiological and psychological effects.  Made a Schedule I drug in 1985, MDMA has a history as both a popular street drug (known under the slang terms ecstasy, X, E, XTC, and rolls among others), but was also used in psychotherapy before it became Schedule I.  MDMA is known for its euphoric and stimulant effects, and people primarily use MDMA recreationally to cause emotional openness, euphoria, stimulation, and a reduction of critical and cynical thoughts.  It is believed that MDMA primarily works by the presynaptic release and depletion of serotonin in the brain (and to a lesser extent dopamine) by not allowing for its reuptake into neurons.  A common dose of MDMA ranges from 75-125 mg, and the primary effects of MDMA last three to four hours with continued effects up to six hours.  Many users report a “crash” after the effects have subsided that can lead to a depressed mood.  It is most well known for its high prevalence in rave dance culture. (http://www.erowid.org/chemicals/mdma/mdma_basics.shtml). 

 

o  Brief History

 

MDMA was first synthesized in 1912 and patented by the pharmaceutical company Merck but was not initially tested for uses because it was only created as a precursor to another drug the company was developing.  MDMA was researched by the CIA and the Army in 1953 and 1954 as a possible truth serum but proved unsuitable for this purpose.  The substance began to be used by the psychotherapeutic community in the late 1970’s but as its availability and abundance increased, the DEA eventually cracked down and made MDMA a Schedule I controlled substance in 1985 despite outcry from many in the psychotherapeutic community http://www.a1b2c3.com/drugs/x_01.htm).  Despite appeals in regards to potential therapeutic use, MDMA remains a Schedule I drug today.  In 2001, the Multidisciplinary Association for Psychedelic Studies, (MAPS) a nonprofit research and educational organization, received permission from theUS Food and Drug Administration to sponsor human testing of MDMA for the treatment of PTSD.  MAPS consists of many of the same doctors and researchers that had originally fought to keep MDMA available to doctors in the 1980’s FDA approval of MDMA as a prescription drug.  The first clinical trials using MDMA-assisted psychotherapy began in 2004 (http://thedea.org/drughistory.html) and there are currently studies underway or being reviewed in the United States, Switzerland, Israel, and Canada (http://www.maps.org/mdma/index.html). 

 

·      Why MDMA-Assisted Psychotherapy?

 

The premise behind MDMA-assisted psychotherapy is that patients who are under the influence of MDMA during a psychotherapy session may be more open to the therapeutic process. MDMA is also not physically addictive.  MDMA is not a therapy by itself, but when used as a tool in psychotherapy it can help patients indirectly overcome the neurobiological changes associated with PTSD by lessening or eliminating the stress reactions to triggers of flashbacks and the chronic hyperarousal associated with PTSD.  MDMA in theory then, can improve rapport between therapist and patient by creating an atmosphere of hope and encouragement.  Patients are less likely to feel overwhelmed by their emotions during a session and can hopefully restructure their intrapsychic framework so as to develop a greater behavioral and emotional response to the stimuli that trigger PTSD symptoms.  Biologically, MDMA is known to decrease activity in the left amygdale, which is reported to cause a reduction in fear and defensiveness (http://www.maps.org/research/mdma/ptsd_study/treatment-manual/053005/intro.html).  These data, combined with anecdotal and uncontrolled research conducted by therapists prior to 1985 suggest a potential for the efficacy of this treatment.

 

·      Objections to the Use of MDMA in Psychotherapy

 

While some in the psychiatric and scientific community support the studies currently underway, there are others who deem MDMA too dangerous to even be considered as a treatment.  MDMA, as a stimulant, is known to increase heart rate and under certain conditions and dosages it can cause an unsafe rise in body temperature leading to hyperthermia/hyperpyrexia (essentially heatstroke) which can be fatal.  One significant problem in regards to MDMA’s safety concerns is its prevalence as a street drug.  Illicit ecstasy tablets sold on the streets often contain other psychoactive substances such as amphetamine or other stimulants (Parrott, 2004).  Also, of the deaths associated with MDMA, many people had multiple other drugs in their systems, so it is difficult to discern the actual cause of death (http://thedea.org/statistics.html).  Beyond deaths attributable to MDMA, there is also concern in the scientific community that prolonged use of MDMA can cause lasting neurological damage (http://thedea.org/neurotoxicity.html).

 

 

·      MDMA in Scientific Literature

 

Since MDMA is a Schedule I substance, the vast majority of scientific literature available has to do with its pharmacological effects on the human body as well as its effects on other animals.  In fact, the studies being sponsored by MAPS testing the efficacy of MDMA-assisted psychotherapy as an intervention are truly the first of their kind in a controlled clinical setting.  In order for MDMA to be a viable treatment (and to be approved as a prescription drug), it must be effective and it also must be proven that it is safe for consumption in the psychotherapeutic context. 

 

o  Efficacy Studies

 

Greer and Tolbert (1985) conducted a study of 29 individuals who underwent a single MDMA-assisted psychotherapy session.  The session appeared physically safe for all 29 participants and only one participate experienced any psychological difficulties lasting longer than a few days.  All nine participants with a DSM-III diagnosis reported a significant benefit, and two reported lasting remission of complications.  The researchers concluded that the best use of MDMA is to “facilitate direct communication between people involved in a significant emotional relationship” (page 326).  Some of the study participants who had mild alcohol or other substance abuse issues also reported decreased use of such substances after experiencing MDMA.  In a follow up report, Greer and Tolbert (1998) outlined a more concrete protocol to be used in conjunction with MDMA-assisted psychotherapy.  They advocated for attention to the setting of the therapeutic session and found that since MDMA did not significantly distort perception under low doses that the learning that takes place during these sessions can more easily be applied to the patient’s lives after the session has ended.  While this study seems promising on the surface, it was not strongly controlled and the data is based off of subjective reports from participants. 

 

In 2001 MAPS conducted a comprehensive literature review of MDMA and found that members of the Swiss Medical Soceity for Psycholytic Therapy conducted therapy with MDMA on 171 patients between 1988 and 1993.  In a follow-up survey, it was found that 85.1% of the 121 responding patients reported good or slight improvement during therapy  (http://www.maps.org/mdma/protocol/mdmareview.pdf). 

 

o  Safety and Pharmacology Studies

 

McKenna and Peroutka (1990) reported that MDMA causes an acute, but reversible, depletion of 5-HT (serotonin).  Additionally, they reported that MDMA may have long term effects on the nervous system indicative of serotonergic neurotoxicity.  This study is in agreement with multiple other studies that suggest possible long term  effects of MDMA usage in animals.  The problem is, however, that there is evidence that MDMA does not interact in the same way in all animals.  It has been found that rats and healthy humans had differing behaviorial responses to MDMA (Vollenweider, Remensberger, Hell, & Geyer, 1999). 

In an overview of MDMA neurotoxicity studies, Curran (2000) reports that MDMA has been known to cause serotonergic neuronal toxicity in all animal species tested but that in humans such a causal link is not as easily identified.  More simply put, there just simply is not enough long term data from humans to truly know if the depletion of serotonin caused by MDMA has a lasting effect on humans.  In another review, Morgan (2000) claims that chronic and heavy recreational use of MDMA leads to sleep disorders, depressed mood, and memory problems.  To add to the complexity of this issue, Gamma, Buck, Berthold, and Vollenweider (2001) reported no difference in cognitive performance based on an index of regional cerebral blood flow using positron emission tomography between MDMA users who had taken on average 270 ecstasy tablets over their lifetime and those who had never used MDMA.  In another review of existing literature, it was also found that “no demonstration of functional or behavioral abnormalities in rats and primates, in spite of a great deal of evidence of the reduction of both serotonin levels and serotonin nerve terminals when high doses of MDMA were administered (Greer & Tolbert, 1998, page 374).

 

 

·      Ongoing Studies

 

As stated earlier, MAPS is currently sponsoring pilot studies in the United States, Switzerland, Israel, and Canada.  These studies are highly controlled and have advanced protocols.  The US study, being conducted by Michael Mithoefer includes 21 subjects with PTSD symptoms who have not responded to other therapies.  The protocol called for two MDMA-assisted psychotherapy sessions as part of a larger psychotherapy course with the option of a third session as well (http://www.maps.org/research/mdma/protocol/ib_mdma_new08.pdf).   MAPS has reported that as of July 18, 2008 the last subject in the US study had completed her third and final experimental session. This initial study will be followed by another study to evaluate patient outcomes one year after treatment.  While no data from the study has been published to date, the initial data suggests this method of MDMA-assisted psychotherapy has had some efficacy that could warrant further clinical trials in the future (http://www.maps.org).  Donna Kilgore, one of the participants of the US study and a rape victim who suffered from PTSD, claims to be symptom-free a year after her two MDMA sessions (http://www.washingtonpost.com/wp-dyn/content/article/2007/11/20/AR2007112001777_pf.html).

 

·      Conclusion

 

While a large amount of scientific study has been done to better understand MDMA, many unanswered questions still remain.  While scientists generally agree that long-term exposure to high doses of MDMA can lead to lasting neurological damage, it is unclear if such damage truly has an effect on behavior.  So much of the data collected is taken from subjects who use the street, often impure, form of MDMA that it even further clouds results.  On top of all of that, the nature of studying and evaluating the effects of psychoactive substances on the brain and mind is highly subjective. 

The therapeutic use of MDMA is also hampered by its notoriety as a street drug and also by highly sensationalist studies.  In one case, Ricaurte ,Yuan, Hatzidimitriou, Cord, and McCann (2002) even published a study in Science claiming severe neurotoxicity in primates after a single common recreational dose.  It turned out that the researchers had not even administered MDMA to the primates but had instead given them methamphetamine.  Clearly, much more research is needed on MDMA to truly understand its full long-term effects as well as its mechanisms of action.  It appears that the current studies being sponsored by MAPS use relatively low doses of MDMA compared to many of the studies conducted on animals and street users, which decreases the possibility of negative physiological effects.  Research into this area should proceed with caution, but with positive initial reports, this area of therapeutic intervention should not be overlooked simply because of the notoriety of MDMA.

 

References

 

Curran, H.V. (2000).  Is MDMA (`Ecstasy') Neurotoxic in Humans? An Overview of Evidence                and of Methodological Problems in Research. Neuropsychobiology, 42, 34-41.

 

Gamma, A., Buck, A., Berthold, T., & Vollenweider FX. (2001).  No difference in brain   activation during cognitive performance between Ecstasy (MDMA) users and controls: a          [H2(15)O]-PET study. Journal of Clinical Psychopharmacology, 21(1), 66-71.

 

Greer, G., & Tolbert R.  (1986).  Subjective reports of the effects of MDMA in a clinical setting.              Journal of Psychoactive Drugs, 18(4), 319-27.

 

Greer, G.R., & Tolbert, R. (1998).  A method of conducting therapeutic sessions with MDMA. 

Journal of Psychoactive Drugs, 30(4), 371-9.

 

McKenna, D.J., & Peroutka, S.J. (1990).  Neurochemistry and neurotoxicity of 3,4-            methylenedioxymethamphetamine (MDMA, 'ecstasy'). Journal of  Neurochemistry,           54(1), 14-22.

 

Morgan, M.J. (2000).  Ecstasy (MDMA): a review of its possible persistent psychological             effects. Psychopharmacology, 152(3), 230-48.

 

Parrott, A.C. (2004).  Is ecstasy MDMA? A review of the proportion of ecstasy tablets     containing MDMA, their dosage levels, and the changing perceptions of purity.                                  Psychopharmacology, 173(3-4), 234-41.

 

Ricaurte, G.A., Yuan, J., Hatzidimitriou, G., Cord, B.J., & McCann, U.D. (2002).  Severe            Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of             MDMA (“Ecstasy”). Science, 297:2260-2263.

 

Vollenweider, F.X., Remensberger, S., Hell, D., & Geyer, M.A. (1999).  Opposite effects of 3,4-            methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus             healthy humans. Psychopharmacology, 143(4), 365-72.

 

http://www.a1b2c3.com/drugs/x_01.htm

 

http://www.erowid.org/chemicals/mdma/mdma_basics.shtml

 

http://www.nimh.nih.gov/health/publications/anxiety-disorders/nimhanxiety.pdf

 

http://www.maps.org

 

http://www.maps.org/mdma/index.html

 

http://www.maps.org/research/mdma/ptsd_study/treatment-manual/053005/intro.html

 

http://www.maps.org/research/mdma/ptsd_study/treatment-manual/053005/intro.html

 

http://www.maps.org/mdma/protocol/mdmareview.pdf

 

http://www.maps.org/research/mdma/protocol/ib_mdma_new08.pdf

 

http://thedea.org/statistics.html

 

http://thedea.org/neurotoxicity.html

 

http://thedea.org/drughistory.html

 

http://www.washingtonpost.com/wp-dyn/content/article/2007/11/20/AR2007112001777_pf.html  

 

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