Can MDMA Cure Post Traumatic Stress Disorder (PTSD).

Introduction

The entactogen MDMA overlaps with the chemical structure of methamphetamine and mescaline and has biological effects similar to epinephrine, dopamine, and serotonin. 

It increases the release of monoamines through the reversal of transporter proteins and reuptake inhibition specifically serotonin and norepinephrine. Not only does it block reuptake of serotonin and norepinephrine it enhances the release as well and inhibits VMAT preventing the packaging of monoamines into vesicles making more available for release. It also modulates glucocorticoids through the HPA axis, decreases amygdala and hippocampal activity, increases oxytocin, and increase prefrontal cortex activity. 

Medical Use

MDMA started out as a therapeutic agent to enhance blood clotting for surgical procedures and trauma. Turns out it does not work very well for that indication, who would have thought. It’s currently listed as a schedule I substance (defined as having no accepted medical use, high abuse potential, and lack of accepted safety). 

It was later discovered to have “empathogenic effects” helping individuals who use the medication to feel more connected to their fellow human beings. After all isn’t that what we are all after? A deep connection to others and people who truly understand us. The original name for the drug was empathy, but that has changed over the years to molly and escstcy. Personally, I like names that describe what a drug does, and empathy or empath is just so much more marketable don’t you think?

Why PTSD is a Big Problem

With several recent wars in both Iraq and Afghanistan, America has a PTSD problem with many combat veterans returning home and requiring treatment. If you ever treated patients with PTSD than you know it’s difficult and the therapy can be intense. Many patients are unable to sit with the discomfort required to reconsolidate these memories. Having worked at the VA for one year I was surprised by the number of vets with non-combat related PTSD. Honestly, they the vast majority of my cases were people who had accidents while working or in training and subsequently developed PTSD. 

The idea is we need methods to enhance the efficacy and speed of trauma focused psychotherapies. What better way to do that than with empathy a medication that enhances feelings of connection. The basic idea being the patient would be given MDMA and then undergo psychotherapy and by using the medication it can influence fear extinction and memory reconsolidation. There are many mechanisms at play including effects on dopamine, serotonin, BDNF, cortisol, and oxytocin. 

The concept of using a psychedelic drug to enhance the effects of psychotherapy is not a new concept, and was done for years using LSD and other compounds. What is different now, is we are trying to put the scientific rigor behind the studies to prove that it works better than placebo, and to learn more about the mechanism of action. 

I want to point out that the main benefit of all these psychedelic medications seems to be enhanced neuroplasticity and the ability to form new connections in critical neurocircuits much easier than would otherwise be possible. 

Benefits of MDMA Assisted Psychotherapy

-Increase blood flow to the vmPFC decreasing activation of the amygdala largely responsible for the fear response 

-Enhance the production of BDNF which improves the long-term potentiation and memory consolidation 

-Elevate the stress hormone cortisol which interacts with glucocorticoid receptors in the hippocampus to improve memory 

-Elevates the prosocial neuropeptide oxytocin which decreases activation of the amygdala and enhances connection with the therapist

-Increased levels of dopamine which can destabilize the old memories and help with reconsolidation of new ones 

-Increased serotonin levels resulting in prosocial and positive affective states. 

The goal of PTSD treatment is to prevent the patient from being held hostage by these memories. We want to destabilize the old memories, modify them, and reconsolidate the new memories. The trauma still occurred, but the patient no longer has the same fear reaction to the traumatic memories. 

MDMA-Assisted Therapy proved to be highly effective in individuals with severe PTSD. 

-In this study investigators gave patients with PTSD 120-180 mg of MDMA along with a trauma focused psychotherapy. There were significant rates of both response and remission compared to placebo. 

-MDMA was well tolerated 

-It was granted breakthrough status by the FDA 

-This was a big deal in the news and media outlets 

-It needs to be replicated to confirm the results 

Potential Adverse Effects of MDMA 

-Potential for abuse and diversion (probably no take homes) 

-Possible hyperthermia or hyponatremia (more common in the recreational use environment than clinical) 

-People often engage in prolonged physical activity in hot environments and do not consume enough water this results in dehydration and possible hyperthermia (think large dance party)

-In the opposite case the person overcompensates and overconsumes water diluting their blood and causing hyponatremia. Excess of anything can cause problems and water is no exception. 

Blue Monday and Black Tuesday 

-Use of MDMA can cause low mood, irritability, and fatigue. It can occur for days after recreational use. 

-In the clinical setting, fatigue, anxiety, low mood, headaches, and nausea can occur in the week after treatment 

   Why It’s Important to Thrive and Not Just Survive

We Spend a significant amount of time as doctors monitoring for adverse outcomes. 

We use the absence of disease as an indicator of health. 

But the mere absence of disease is not enough to proclaim good health. 

If we only monitor for the absence of disease, we miss the things that are most important in our patients’ daily lives. 

The things I’ve found to be most important in my life, and often lacking in my patient’s lives are…

Being happy, having a sense of purpose and meaning, and having good relationships which are sometimes ignored if overt signs and symptoms of disease are not present. 

Being “well” is a state of complete mental, physical, and social wellbeing. 

Having a purpose in life is associated with reduced mortality risk, so is life satisfaction. Things like loneliness and social isolation are associated with increased mortality.

When these needs are met people not only live longer but they live with intention. 

Let’s Look beyond the absence disease 

 

The Loneliness Epidemic and Avoidant Personality Disorder 

Although loneliness has always been a friend of mine (Backstreet boys 1997), there is an epidemic of loneliness across all age groups. 

We live in a world where we are all more connected with each other through technological advances and social media, yet people feel more disconnected than ever. 

The COVID-19 pandemic did make this any better, 36% of all Americans, including 61% of young adults and 51% of mothers with young children feel loneliness is a significant problem in their lives. 

The question is are people feeling lonely because they are suffering from avoidant personality disorder?

Epidemiology

The prevalence of APD is 2.36% in the general population, and it appears to occur equally in males and females. 

Definitions and Criteria for diagnosis

Let’s start with a definition of what avoidant personality disorder is and how it can impact a person’s life. 

This is part of the cluster C personality disorders often thought of as the anxious/fearful personality disorders. These individuals experience excessive social anxiety, severe feelings of inferiority and inadequacy, and while they desire close relationships, they avoid the feared stimulus instead living in self-imposed social isolation. 

Other key criteria include: 

-patterns of social inhibition 

-hypersensitivity to rejection or criticism 

-it must be present by early adulthood 

This affects all areas of life and should be a pervasive pattern. It’s not something that is isolated or situational.  

DSM-5 Criteria: 4 out of 7 are required to make a diagnosis 

  1. Avoids occupational activities that involve significant interpersonal contact because of fears of criticism, disapproval, or rejection. 
  2. Unwilling to engage in relationships unless they are certain of being liked. (They will look for social cue or indicators of interest before committing and often attempt to read other minds) 
  3. Shows restraint in relationships for fear of being ridiculed or shamed 
  4. You are preoccupied with being criticized or rejected 
  5. The person is inhibited in new interpersonal situations because of feelings of inadequacy 
  6. The person will view themselves as socially inept, inferior to others, or unappealing to others. 
  7. The person is reluctant to take personal risks for fear of embarrassment 

It’s important to keep in mind this diagnosis is largely unchanged since DSM-III and are primarily viewed through a psychoanalytic lens. The key difference between avoidant personality disorder and social anxiety is these feelings are pervasive throughout the person’s life, where in social anxiety they are limited to social situations. Although some believe these are the same disorder with many of the criteria overlapping. Avoidant patients tend to read more into things and are constantly looking for any indication from others that supports their theory that they are defective or inadequate. 

Other personality disorders can have rejection sensitivity and sensitivity to criticism, this is often seen in narcissistic personality disorder. We are all sensitive to criticism in certain situations it’s not necessarily pathological. 

Treatment: 

This largely focuses on psychotherapy and sometimes medication if other comorbid psychiatric disorders are identified. Some of the psychotherapy techniques that are effective include social skills training, cognitive behavioral therapy, and exposure therapy. These are also good cases for psychoanalysis if the person can commit to that form of therapy. 

Conclusion :

Could Some of the Loneliness people are experiencing be due to avoidant personality disorder?

-Possibly, but it’s only going to be a small percentage considering the prevalence of avoidant personality disorder is 2.36%. 

-Loneliness has many contributing factors and encouraging people to spend less time connecting digitally and more time connecting face to face is a good place to start. 

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