By Erez Jacob Ofer. Tel Aviv University. I want to thank Dr. Zahava Solomon for giving me the opportunity to explore this topic. A literature review of posttraumatic stress disorder and MDMA therapy was assessed in order to find scientific evidence for the claim made by researchers, clients, and clinicians that MDMA therapy may help victims with unremitting posttraumatic stress disorder. Although more research is necessary regarding MDMA and PTSD, several studies and therapeutic anecdotes reveal that MDMA, as an adjunct to psychotherapy, is a promising and powerful tool that may further assist clinicians to heal their clients.
Posttraumatic Stress Disorder or PTSD was first officially recognized in 1980 with the publication of the third edition of the Diagnostic and Statistical Manual of Mental Disorders, or the DSM-III (American Psychiatric Association, 1980, pg. 236). According to Kessler, Chiu, Demler, and Walters (2005), PTSD is characterized as a debilitating anxiety disorder in which the victim may suffer from symptoms such as hyperarousal, flashbacks, and avoidance behaviors. Kessler et al. (2005) describe PTSD as a major, worldwide public health problem, and claim that in the United States alone, it is estimated that between 6%-10% of the population suffers from a lifetime of PTSD. PTSD is often a chronic illness that is associated with high rates of psychiatric and medical comorbidity, suffering, disability, drug abuse, and suicide (Kessler et al., 2005). It has also been estimated that between 75,000 and 225,000 U.S. soldiers returning from war in Iraq and Afghanistan will suffer from PTSD (Tanielian and Jaycox, 2008).
Researchers and military psychologists had been interested in combat stress reaction for many years prior to the publication of the DSM-III. In fact, Scott (1990) points out that the writers of the DSM-I in 1952 included an entry for “gross stress reaction”, which they described as a temporary condition under extreme environmental stress that would disappear once the individual was removed from the stressful situation. Yet it wasn’t until the publication of the DSM-II that there was a clearer guideline for diagnosing a patient with PTSD (American Psychiatric Association, 1980, pg. 236). According to Golub (1985), many combat veterans during the Vietnam War came back with intense cases of persistent combat shock with long-lasting symptoms that had not been present prior to the war such as depression, anxiety, and outbursts of rage, to name a few. Furthermore, Golub (1985) states that the staggering number of psychiatric casualties from the Vietnam War lead to new research and a new diagnosis criterion for the condition described as Post-traumatic Stress Disorder.
In the DSM-IV, published in 1994, there were several changes made to the diagnostic criteria section for Post-traumatic Stress Disorder. First of all, the actual disorder had a minor name change, from Post-traumatic Stress Disorder in the DSM-III to Posttraumatic Stress Disorder in the DSM-IV. Most importantly though were the changes detailing the criterion section for Posttraumatic Stress Disorder. For example, in the DSM-III, section A. of the Diagnostic Criteria for Post-traumatic Stress Disorder lists the “Existence of a recognizable stressor that would evoke significant symptoms of distress in almost everyone.” However, under the DSM-IV criterion for PTSD, the editors redefine Section A. so that “The person has been exposed to a traumatic event in which both of the following were present: (1) the person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others. (2) the person’s response involved intense fear, helplessness, or horror. Note: In children, this may be expressed instead by disorganized or agitated behavior.” Also, the DSM-III does not include Acute Stress Disorder, which was later included in the DSM-IV.
Acute Stress Disorder is similar to PTSD except that its onset may be immediately following the trauma and can last up to 4 weeks, whereas PTSD according to the DSM-IV occurs when the duration of symptoms last longer than one month. The changes made between DSM-III and DSM-IV are of utmost importance because they redefine the disorder, in turn, redefining for some victims their status as suffering from PTSD or not. In the year 2000, the DSM-IV-TR was introduced and with the upcoming version of the DSM-V, there is much debate regarding yet another redefining entry for Posttraumatic Stress Disorder. McNally (2009) mentions several valid points that need to be addressed. For example, he suggests that the phrase under Criterion A1 “was confronted”, in regards to a traumatic stressor, be removed. He brings up the case of the traumatic events of 9-11, in which he argues that there must be a psychobiological difference between those that developed PTSD like symptoms from watching the event on television in comparison to those that actually experienced the event first hand, at or near ground zero.
It appears to me that as the collection of PTSD research by leading experts, clinicians, psychiatrists, psychologists, and traumatologists continues to grow, the closer the PTSD research community is coming to an actual consensus as to what does and does not constitute PTSD. The most common examples of people who do suffer from and are diagnosed with PTSD are individuals who have survived extremely stressful, life threatening conditions such as military combat, terrorist attacks, captivity, torture, vehicle accident, physical, sexual, and child abuse, rape, assault, and natural disasters (Herman, 1992). The term unremitting PTSD is the occurrence of intrusive recollections such as flashbacks, avoidance and numbing behavior patterns, and hyper-arousal for longer than the duration of one month (American Psychiatric Association, 2000).
What is interesting to note is that not every person who experiences a situation in which PTSD is a common result, does in fact, develop PTSD. There are individuals who have been raped, soldiers who have undergone near death combat experiences, and so forth, that do not develop PTSD. They may develop delayed-onset PTSD, or they may never develop PTSD. So one of the biggest questions the PTSD research community is investigating is how effective are the current treatments available, and arguably more important, are there any preventative measures to be taken immediately following the trauma to prevent the onset of PTSD. And the answer is an affirmative yes; there are several available options for both preventative measures as well as treatments once PTSD has developed, all with varying results. Feldner, Monson, and Friedman (2007) discuss several available options and their efficacy.
One example of such preventative treatment is CISD, or Critical Incident Stress Debriefing, in which the intervention takes place immediately following the traumatic event (Feldner et al., 2007). The mechanism of action behind said intervention is that the victim verbally expresses on a cognitive and emotional level their experience of the trauma almost immediately after the event, in turn, according to Feldner et al. (2007) “reducing stress, rumination, and strain on homeostatic bodily mechanisms and facilitating meaning-making about the event” (p. 87). However, the problem lies in the fact that not every person responds equally well to each treatment. Although preventative measures such as CISD sound ideal in theory, Feldner et al. (2007) cite several peer-reviewed studies of CISD that do not find such interventions to be effective against preventing PTSD in trauma victims. One study showed that CISD maintains PTSD symptoms while another study surprisingly found that CISD might in fact trigger PTSD in individuals who, had they not undergone CISD intervention, would not have eventually succumbed to PTSD.
Feldner et al. (2007) also mention three other such post trauma prevention programs including Risk Targeting Intervention, Stepped Collaborative Care, and Psychobiological treatments, which I will briefly describe. Feldner et al. (2007) explain risk-targeting intervention as an attempt to lessen anxiety symptoms amongst at-risk individuals, citing the famous experiment in which sexually assaulted women were either shown or not shown an informative film before undergoing a gynecological examination. Interestingly enough, after a 6-week period, women shown the film showed a lower rate (33%) of PTSD symptoms in comparison to the group of women who had not received the visual intervention (72%). Another such preventative measure is Stepped Collaborative Care, in which the symptoms of the victim are carefully monitored by professionals and then the level of care for the patient is adjusted according to the needs of their stabilizing or destabilizing condition. Results from a Stepped Collaborative Care study showed no increase in PTSD symptoms while individuals who did not receive the care showed a 6% increase in PTSD symptoms. One final prevention technique mentioned by Feldner et al. (2007) is that of the psychobiological approach, in which the pharmacologist attempts to understand and alter the mechanism of action in the stress regions of the brain. Recent neuroscience research shows that the dominant mechanism of action regarding a person’s stress response occurs in the amygdala, the hippocampus, and medial prefrontal cortex regions of the brain (mPFC) (Friedman, M. J., 2002). By understanding the neuroscience underlying the mechanisms of action, several pharmacologists have attempted to target those regions with hormones and drugs in order to prevent the development of PTSD immediately following a traumatic event. For example, Schelling et al. (2001) administered hydrocortisone to a group of heart surgery patients, and in comparison with the placebo group that did not receive hydrocortisone therapy, 31 months postsurgery, the hydrocortisone group showed an 11% PTSD rate while the placebo group had a 64% PTSD rate. Other experiments have been conducted using b adrenergic antagonists (b-blockers), as well as the administration of benzodiazepines immediately following a traumatic event, all with varying results. All four of the pre-PTSD approaches are meant to prevent the onset of PTSD, so once a person is already diagnosed with posttraumatic stress disorder, these preventative measures are somewhat irrelevant.
So the question is, if PTSD cannot be completely prevented as of yet, what types of treatment options currently exist for people who do develop PTSD? And the answer is several, with the most widely used approaches including psychotherapy, pharmacology, or a combination of both. Psychotherapy approaches include cognitive behavioral therapy (CBT) with an emphasis in Prolonged Exposure, Cognitive Processing Therapy, Eye Movement Desensitization and Reprocessing (EMDR), and psychodynamic psychotherapy (Mithoefer et al., 2010). Popular pharmacologic approaches include the use of selective serotonin reuptake inhibitors (SSRI’s), benzodiazepines, and a collection of at least 22 other individual drugs in seven different drug classes, including antipsychotics, alpha-adrenergic antagonists, and anti-convulsants (Mithoefer et al., 2010). Due to the fact that between 25% and 50% of individuals undergoing clinical trials for psychotherapy and pharmacotherapy treatments do not show signs of improvement, Mithoefer et al. (2010) believe that it is important to keep searching for new therapies with less treatment failure rates.
MDMA Therapy
MDMA, or 3,4-Methylenedioxymethamphetamine, is a phenylisopropylamine derivative characterized by several unique psychopharmacological effects (Mithoefer et al., 2010). It was invented in 1912 by the pharmaceutical company Merck and bears structural and pharmacological similarities to the psychedelic mescaline and the stimulant amphetamine (Mithoefer et al., 2010). MDMA, better known as its street name “ecstasy”, was used in the 1970’s as an adjunct to psychotherapy sessions, and during the 1980’s, was popularized amongst the party scene known as “raves.” Moreover, once MDMA became considered a major party drug in 1985, its status became illegal and was classified as a schedule 1 controlled substance (Mithoefer, et al., 2010). It is interesting to note that several other currently illegal drugs such as barbiturates, LSD, amphetamines, and nitrous oxide, have also been used by researchers and psychiatrists dating back to as early as the 1940’s (Mithoefer, et al., 2010.) In fact, there exists a field of psychotherapy known as psychedelic therapy in which patients undergo a prolonged therapy session under the influence of psychedelic drugs such as LSD or psilocybin in order to better understand their sub-conscious processes (Grof, S, 1968).
Harris et al. (2002) describe MDMA and other 3,4-methylenedioxy substituted phenethylamines as “entactogens”, being a new class of pharmacological agents whose affects partially overlap those of psychostimulants, such as amphetamines, and serotonergic hallucinogenics, like LSD. Reported effects of entactogens include enhanced feelings of closeness to others, empathy, well being, and insightfulness with rarely any hallucinogenic experiences (Harris et al., 2002). According to Mithoefer et al. (2010), MDMA users tend to report feeling a decrease in fear while simultaneously experiencing a state of clear headedness and an alert state of consciousness. Users also report feeling a 2-4 hour experience characterized by an increase in euphoria, well-being, sociability, self-confidence, and extroversion (Greer and Tolbert, 1998).
The use of MDMA has become very controversial within the past two decades. One study found that in the year 2000, 8.2% of 12th graders in the United States reported using MDMA within the past year (Harris et al., 2002). In 2003, a sensationalist report was published by the prestigious journal Science claiming that the use of MDMA causes severe dopaminergic and moderate serotonergic neurotoxicity in primates after a single common recreational dose. Almost one year later, it was revealed that the researchers had in fact accidentally administered (+) –methamphetamine instead of MDMA, and the article was almost immediately retracted (Ricaurte et al., 2002). However, the social stigmas of using MDMA and the fear of extreme brain damage even after one recreational use have tainted the reputation of MDMA. Since MDMA is still illegal in the U.S. and other western nations, there exists a danger to the consumer when buying black market ecstasy, since it is often impure. For example, the website EcstasyData.org, which is an independent lab pill testing program, reports that mislead ecstasy consumers were actually ingesting caffeine, MDPV, 5-MeO-DiPT, Methamphetamine, TFMPP, Procaine, Methylsulfonylmethane, MDE, BZP, Cocaine, Lidocaine, and several other drugs, instead of pure MDMA.
The more I began immersing myself in the topic of MDMA therapy, the more questions I began to ask. “What exactly is MDMA therapy?” “How do you do it?” “Should it be conducted in a medical office, a private clinic, or the clients home?” and “Is a psychiatrist needed to administer the MDMA or is a therapeutic dose harmless enough for a therapist to monitor?” All of these questions and many more are thoughtfully answered in the Greer and Tolbert (1998) report A Method of Conducting Therapeutic Sessions with MDMA. Greer and Tolbert draw from their several years of experience conducting MDMA therapy between the years 1980-1985, before it became a controlled substance. Greer and Tolbert (1998) suggest the importance of fulfilling the proper “set and setting”, as was described by Stanislav Grof, one of the leading experts in LSD therapy. According to Grof, “The term set includes the expectations, motivations, and intentions of the subject in regard to the session…the preparation and programming for the session…the specific technique of guidance used during the drug experience. The term setting refers to the actual environment, both physical and interpersonal, and to the concrete circumstances under which the drug is administered” (Greer and Tolbert, 1998, p. 371).
Before the actual therapy session was conducted, Greer and Tolbert (1998) would have clients fill out a questionnaire asking them questions like how they had heard about MDMA therapy, what are the motives for wanting to try MDMA therapy, what are the clients fears and expectations, and what is the clients background and medical condition. Greer and Tolbert referred to themselves as “sitters”, meaning that the clients were there to explore themselves on a deeply personal level and that their active role as therapist was to attend to the needs of the client during the session. Clients were advised to schedule their appointment on a day that would be followed by another free day so that they would have time to integrate and process their experience, since common side effects of grieving are anxiety, sadness, and physical pain (Greer and Tolbert, 1998). Greer and Tolbert (1998) also mention an interesting case of a second generation Holocaust survivor who after a few MDMA therapy sessions was finally able to shed the intense sorrow and negativity she had felt for the majority of her life before.
MDMA has several known physiological, subjective, and pharmacological effects on the human body and in recent years, many studies have been published about MDMA and MDMA therapy. An article published by Johansen and Krebs (2009) entitled How Could MDMA (ecstasy) Help Anxiety Disorders? A Neurobiological Rationale found three main neurobiological explanations for how MDMA’s pharmacological effects, coupled with psychotherapy, could help people suffering from extreme anxiety disorders, including PTSD: 1.) MDMA increases the levels of oxytocin, which could improve therapeutic allegiance; 2.) MDMA increases activity in the ventromedial prefrontal region and decreases activity in the amygdala, which could improve emotional regulation and decrease avoidance; 3.) MDMA increases the release of norepinephrine and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations (Johansen and Krebs, 2009). Harris et al. (2002) also found that MDMA increases levels of prolactin, DHEA, and plasma cortisol.
One of the experiments with the most promising results is the Mithoefer et al. (2010) study entitled The Safety and Efficacy of +(-)3,4-methylenedioxymethamphetamine Assisted Psychotherapy in Subjects with Chronic, Treatment-Resistant Posttraumatic Stress Disorder: The First Randomized Controlled Pilot Study sponsored by MAPS, the Multidisciplinary Association for Psychedelic Studies. Subjects had an average of 19 years of PTSD symptoms based on the DSM-IV-TR criteria and 15/20 of the subjects had undergone other multiple medication trials and psychotherapies, to no avail. The therapeutic dosage of MDMA used in scientific literature for MDMA therapy lies between 1.5-2.0 mg/kg and is usually taken in a capsule form by mouth. Volunteers in the Mithoefer et al. (2010) study were given either an inactive placebo, or a 120mg capsule The onset is anywhere between 45-75min, followed by a peak at around 2-2.5h after ingestion, with the effect lasting between 4-5h total. Some volunteers in the Mithoefer et al. (2010) study were also given a supplemental dose, which made the effects last between 5-6h. Mithofer et al. (2010) found that MDMA causes increases in pulse, body temperature, and blood pressure. Subjects administered with MDMA, and not placebo, reported side effects such as jaw tightness, nausea, feeling cold, dizziness, and impaired balance (Mithoefer et al., 2010). The Mithoefer et al. (2010) study found several interesting results. 10 out 12 (83.3%) of the subjects who had received MDMA therapy no longer met DSM-IV criteria for PTSD in comparison to the placebo 2 out of 8 (25%). Three of the twenty subjects in the experiment had been unable to work because of the debilitating nature of PTSD, but after their experience with MDMA, all three were able to work again. Mithoefer et al. (2010) also examine their research and in the discussion section include an analysis of the strengths and weakness of the experiment. Finally, they suggest that more research be done on MDMA and its effectiveness in the fight against PTSD.
Based on the auspicious U.S. findings of the Mithoefer et al. (2010) study, MAPS has launched several other studies around the globe including Australia, Canada, Israel, Jordan, Spain, and Switzerland. Since I am currently living in Israel, I decided to investigate the Israeli study, and on a wintry early morning, hopped on the train from Tel Aviv to nearby Beer Yaakov, home of the Beer Yaakov Mental Health Center where the clinical trials are currently taking place. The clinical investigator for the project in Israel is Professor Moshe Kotler and after a weeklong attempt to get in touch with him, I was referred to his colleague, Dr. Sergio Marchevsky. Dr. Marchevsky was very helpful, providing me with several resources and answering any of my many questions. From my hour-long interview with him, I was able to gather several interesting facts about the current study. Dr. Marchevsky believes that most people do not receive the proper treatment immediately following the trauma and that 85% of individuals would positively react to CBT. During the trial, clients take the MDMA, close their eyes, wait 40 minutes, and are instructed to let their mind do the work. He says that patients enjoy the MDMA therapy because they receive a lot of care from the therapist. The therapy itself is the patient’s experience, not the actual meeting with the therapist. The patient is encouraged after an hour to speak with the therapist about the experience and the therapist is there to help facilitate the patient’s journey. Unfortunately, I was unable to watch an exemplary MDMA therapy sessions in action because it is against protocol.
Discussion
One study found that the response rate to pharmacotherapy was 20-22% higher than the placebo group, while another study found that about 30% of subjects taking SSRI’s achieve full remission from PTSD after a 12 week period. These reviews represent the severe need for new research to be done in the field of pharmacotherapy in order to find more effective techniques to help victims of PTSD, such as MDMA therapy (Mithoefer et al., 2010). Although there are several treatments for PTSD currently available like CBT and SSRI’s, there are still many people who suffer from unremitting PTSD. There is a copious amount of evidence including clinical trials and personal anecdotes suggesting that MDMA therapy is very beneficial to individuals suffering from unremitting posttraumatic stress disorder, both short and long-term. There are still many questions that need to be answered on psychological, pharmacological, clinical, cultural, sociological, and political levels, so that the individual who has undergone every legal form of treatment currently available, and still struggles daily from PTSD, will have easy, affordable access to an innovative treatment that may very well be the means to an end of a seemingly interminable life sentence of suffering.
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http://www.ecstasydata.org/results.php
