Why MDMA to Treat PTSD?

This is the second in a series of three blogs examining the use of MDMA as a psychedelic medicine. The first installment, "The History of MDMA", was published on March 9th. In this installment, we will consider the condition that is Posttraumatic Stress Disorder (PTSD) and why MDMA may be well-suited to provide treatment when it is embedded in a specialized protocol under clinical supervision. In the third installment, we will discuss the FDA’s Expanded Access or Compassionate Use program and how The Pearl Psychedelic Institute is the first site in the United States to begin this program and how it will be conducted.


References to the human psychological ravages of war can be found in historical literature dating back more than 2,000 years to Ancient Greece. However, it was not until 1980 with the release of the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) that the formal diagnosis of Posttraumatic Stress Disorder (PTSD) was recognized by the medical community. Since that time, psychotherapeutic and pharmacological treatments for PTSD have evolved to try and address the myriad symptoms and challenges presented by this condition that is often chronic, severe and life-threatening. However, research demonstrates that less than 50% of adults respond to conventional PTSD treatments and the only pharmacological interventions that are approved by the FDA for PTSD are the SSRIs Paxil and Zoloft. “If you’re a combat veteran with multiple tours of duty, the chance of a good response to these drugs is 1 in 3, maybe lower,” said John Krystal, chairman of psychiatry at Yale University and a director at the VA’s National Center for PTSD. “That’s why there’s so much frustration and interest in finding something that works better.” This blog will examine 3,4-Methylenedioxymethamphetamine, MDMA, and how it works in the brain and why it is showing some promise in treating the symptoms of PTSD when it is used in conjunction with a specialized psychotherapy protocol being administered by trained, qualified professionals.


History

Although there have been mentions in historical literature about the destructive power of war experiences going back to 50 B.C., formal attempts to address the psychological wreckage being witnessed in veterans was not begun in the United States until the Civil War. The term “nostalgia” was previously used to describe the anxiety and sleeplessness that many veterans reported and the term “Soldier’s heart” or “irritable heart” reflected the medical thinking during the Civil War that perhaps the disturbing symptoms (trouble breathing, rapid pulse, anxiety) were the result of a physiological injury sustained in combat. This was echoed in European reports of “railway spine” where due to the increase in rail travel at the time, victims of railway accidents typically suffered “concussion of the spine” and it was suspected that this is what caused their “fear, fright and alarm” in the months and years following the accident. However, this conceptualization did not last as more evidence emerged that those suffering with this condition were possibly responding to a deep psychological wounding that may or may not have involved physiological injury.


In World War I, the term “shell shock” was prominent and the belief that exposure to the roar and explosive destruction from big guns was the cause but many soldiers who had not been exposed to shelling were also reporting symptoms of debilitating sleep and anxiety problems and the condition was then referred to as “war neuroses.” In World War II, the US Army formally recognized the condition as “battle fatigue” or “Combat Stress Reaction” (CSR) and it is estimated that half of the discharges during World War II were due to CSR. The term “thousand-yard stare” also became popular during World War II as a description of the vacant or unfocused gaze of the soldier who has reacted to the horrors of war with an emotional detachment that is psychologically protective but results in detriments to functioning. However, this term is also used at times to describe the dissociative “not all there” look of victims of other types of traumatic experience.


“'If you’re a combat veteran with multiple tours of duty, the chance of a good response to these drugs is 1 in 3, maybe lower,' said John Krystal, chairman of psychiatry at Yale University and a director at the VA’s National Center for PTSD.”

Recent History

The initial Diagnostic and Statistical Manual of Mental Disorders (DSM-I) was published by the American Psychiatric Association in 1952 and it listed “gross stress reaction” as a diagnosis that was meant to include normal people who had been exposed to combat or disaster-related trauma and the title suggested that this condition would be relatively short-lived and remit within 6 months which would then require another diagnosis. Almost inexplicably, the DSM-II, which was published in 1968, removed this diagnosis and replaced it with something called “adjustment reaction to adult life” which came nowhere near capturing the suffering of those individuals traumatized in combat and/or life experiences. Finally, after researching Vietnam War veterans, Holocaust survivors and survivors of sexual abuse and domestic violence, the DSM-III, published in 1980, elucidated the clear link between traumatic experience exposure to the complex, long-term effects that were now being referred to as Posttraumatic Stress Disorder (PTSD).


Since that time, a lot has been learned about PTSD. For one thing, it is much more common in the population than it was originally thought to be with an estimated 15 million adults in the United States suffering from PTSD during a given year. About 8 of every 100 women (8%) and 4 of every 100 men (4%) develop PTSD sometime in their lives although it is estimated that 60% of men and 50% of women will experience at least one trauma in their lives. Not everyone who experiences trauma will develop PTSD and research has shown that if the victim can access and experience caring support following a traumatic exposure, that is likely the single most important mitigating factor. However, factors such as previous traumatic exposures, episodic vs. chronic exposures, proximity, predictability and the degree of invasiveness and injury all can influence the severity of the pathological response to trauma.


“For one thing, it is much more common in the population than it was originally thought to be with an estimated 15 million adults in the United States suffering from PTSD during a given year. About 8 of every 100 women (8%) and 4 of every 100 men (4%) develop PTSD sometime in their lives although it is estimated that 60% of men and 50% of women will experience at least one trauma in their lives.”

The Science Behind PTSD

I have been employed in mental health positions since 1989 and been a licensed psychologist for over 20 years and I am convinced that at least 80% of every diagnosis I have encountered is, at its root, a problem with poorly integrated trauma. Varied diagnoses such as Major Depressive Disorder, Obsessive-Compulsive Disorder, Generalized Anxiety Disorder, Oppositional Defiant Disorder in children and adolescents and many others can trace their etiology to traumatic experience. Somewhere in the patient’s history is one or more traumatic losses or experiences (often abuse, neglect, accidents) and then to meet the demands of life, they develop maladaptive coping skills (avoidance, aggression, withdrawal, etc) that usually lead to various mental health diagnoses. In many of the diagnoses that involve a significant genetic component, such as bipolar disorder and schizophrenia, trauma is usually the most common factor that seems to influence a carrier with a genetic predisposition to eventually develop and express the disorder. In addition, there was a study that looked at Iraq War veterans and their PTSD and the results indicated that those who developed the most severe combat-related PTSD cases were the ones that had a history of childhood abuse and developmental trauma.


One of the most important things that science has learned about trauma and how it affects the human organism is that the negative and pathological effects are due to brain biology rather than one’s “character” or “toughness” or “weakness.” In normal information processing, the human brain receives information from the five senses and this information is sent to the thalamus (which is sort of like the cook in the kitchen) and the thalamus is receiving and organizing this sensory information which helps orient the person to what is happening to them in time and space. If there is no danger or threat contained in this sensory information, it is then sent to the prefrontal cortex for processing where it is categorized based on our past experiences, language is assigned to the information and context is provided so that a narrative emerges about what is happening. It is then eventually encoded as a memory and stored in the frontal lobe of the brain where it can be recalled should we want or need recall and it usually will not impinge on consciousness in a way that can interfere or disrupt functioning.


Information processing during a traumatic experience is quite different. When the thalamus receives the sensory information during a traumatic experience, the perceived danger and threat triggers two almond-shaped structures known as the amygdalae and when these are activated, the organism automatically and instantaneously gets ready to fight, run away or freeze. Once this happens, the higher order brain processing “goes offline” and the brain reverts to more primitive modes of processing information. As a result, the sensory information does not go through the normal processing, encoding and storage and instead, gets improperly stored in the brain in a highly charged, fragmented state. As a result, traumatic memories can often involuntarily impinge on the patient’s consciousness in the form of intrusive images, nightmares and flashbacks. A sound or a smell or any other reminder of the trauma that is encountered out in the world will automatically trigger the fight, flight or freeze response and this is often what leads to PTSD sufferers isolating and avoiding engaging with the world. This automatic triggering of the amygdalae is also a primary reason why PTSD patients have difficulty tolerating conventional PTSD therapies and often flee or end treatment.

“One of the most important things that science has learned about trauma and how it affects the human organism is that the negative and pathological effects are due to brain biology rather than one’s “character” or “toughness” or “weakness.””


Why MDMA

One of the reasons why MDMA-assisted therapy has promise in the treatment of PTSD is what it is able to facilitate biochemically in the brain and when MDMA is used in conjunction with a specialized psychotherapy protocol, evidence seems to indicate that healing can occur. In the preparatory sessions leading up to a session where MDMA is administered, great care is taken to build trust and rapport with the patient, to learn about the patient’s trauma history and how it has affected their life and to prepare them for the effects of the MDMA. When MDMA takes effect in the brain, the amygdalae are basically de-activated by about 95% and when this happens, it allows traumatic memories to emerge. MDMA does not make encountering this traumatic material easy or pleasant, but it shuts off the fight, flight or freeze reaction so that the patient can be more emotionally and intellectually available to engage with the traumatic material. MDMA also activates the prefrontal cortex so that when this trauma material is allowed to emerge, it can go through the processing that should have taken place when the trauma was originally occurring if the person had not been in automatic fight, flight or freeze mode. The trauma material is then organized, language is assigned to it so that it can take on a narrative form and then it is encoded and stored like a normal memory. There is no amnesia or forgetting about the trauma but it tends to become a memory of something that happened to the person and not an intrusive, overwhelming, visceral identifier of that person. MDMA also stimulates the release of two hormones, prolactin and oxytocin, which bring about a state of deep relaxation and empathy/connectedness, respectively, and this can further encourage the therapeutic healing process.

In the context of a specialized psychotherapy protocol for PTSD, MDMA may help create conditions in the brain of the PTSD sufferer that encourage healing by inducing a biochemical state that allows the patient to effectively process and store traumatic memories. There is still much to learn about MDMA and the other psychedelics and their healing capacities but results from the Phase 2 and ongoing Phase 3 studies seem to indicate that MDMA-assisted therapy could provide some hope for the millions of people suffering from PTSD in the United States. On a larger and more future-oriented scale, if we can find a treatment that can successfully mitigate the damaging effects of trauma, it could also signal a leap in being able to more effectively treat patients that are suffering from other trauma-related mental illnesses that do not meet criteria for PTSD. If there was someday a way to eliminate the underlying driver (poorly integrated trauma) of the maladaptive behaviors that underlie most mental illnesses, then it stands to reason that the more conventional psychological interventions for those mental illnesses could become more effective.


“There is still much to learn about MDMA and the other psychedelics and their healing capacities but results from the Phase 2 and ongoing Phase 3 studies seem to indicate that MDMA-assisted therapy could provide some hope for the millions of people suffering from PTSD in the United States.”

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