International Society for Traumatic Stress Studies

Are We Entering a New Era of PTSD Treatment Development?

Posted 28 May 2013 in StressPoints by Alexander Neumeister, MD - Recipient of the 2012 ISTSS Robert S. Laufer Award for Outstanding Scientific Achievement

In a sharp distinction from other medical disorders such as cancer, coronary artery disease and diabetes, which have objective biological tests for diagnosis, severity of illness, and response to treatment, biological markers cannot yet independently confirm the assessment of posttraumatic stress disorder (PTSD).

Current procedures for diagnosing PTSD rely on self-report screening measures and clinical interviews. Treatment has been limited to symptom management rather than targeting the biological etiology. This is a major concern, because PTSD is associated with occupational and social disability, as the core symptoms of re-experiencing, avoidance/numbing, and hyperarousal, as well as commonly comorbid psychiatric and medical conditions, are highly distressing and disruptive, and deleteriously affect functioning and quality of life.

Our group has been conducting a number of functional neuroimaging studies using state-or-the-art positron emission tomography (PET) and functional and structural magnetic resonance (MR) imaging to study the dimensional representation of the complex and multi-faceted phenotype of PTSD. This conceptually novel approach is in line with the National Institute of Mental Health’s Research Domain Criteria (RDoC) dimensional approach to classifying psychopathology and identifying novel targets for intervention.

Where are we currently in our efforts? Several key findings emerge from these studies. First, in vivo neuroimaging provides a foundation upon which to develop and validate informative biomarkers of PTSD vulnerability, as well as to guide the rational development of the next generation of evidence-based treatments for PTSD. Second, we have been able to collect evidence suggesting that novel neurochemical systems, i.e. the brain endocannabinoid system or opioid receptor system play a key role in the etiology of PTSD, and provide targets for evidence-based treatment developments. Besides improved understanding of the impact of trauma on brain function, we are now getting closer to the ultimate goal to offering targeted treatments to individuals with PTSD, based upon their own individual brain function. Therefore, symptoms management, while important in the acute phase of the illness might be replaced with aims to correct the neurobiological underpinnings of PTSD which hopefully will result in faster and more profound and long-lasting recovery.

One example for our ongoing efforts in generating the next generation of PTSD treatments has been stimulated by the observation that plant-derived cannabinoids provide relief for the haunting nightmares and other symptoms of PTSD and is consistent with the high rates of cannabis abuse among PTSD patients. This attempt at self-medication with cannabis with its primary psychoactive constituent tetrahydrocannabinol (THC) is misguided, however, because direct activation of CB1 receptors with plant-derived cannabinoids (a) leads to a rapid down-regulation of the eCB signaling system, thus aggravating the condition it seeks to treat, and (b) can result in tolerance and addiction.

Figure 1 (click here to enlarge)

However, mechanisms that enhance eCB signaling (Figure 1.) could become of therapeutic relevance by promoting a novel, evidence-based treatment for PTSD with the potential to prevent both the behavioral (anxiety, impaired extinction) and molecular adaptations to trauma (increased CB1 receptor expression) associated with PTSD. Blockade of eCB metabolism by inhibiting the eCB-degrading enzyme fatty acid amid hydrolase (FAAH) has been shown to magnify AEA-mediated CB1 signaling and produce a more circumscribed and beneficial spectrum of biological effects than those caused by direct CB1 receptor activation. Although not yet demonstrated in humans, such compounds may be therapeutically helpful to specifically enhance extinction and treat anxiety and therefore may emerge as useful in the treatment of PTSD.

As mentioned before, we are entering a new era of PTSD treatment, based on neuroscience evidence, and ongoing efforts of our group and many others are promising that we will be able to provide more efficient targeted treatments to trauma survivors in the near future.

About the Author

Alexander Neumeister, MD, is a professor of psychiatry and radiology at the New York University School of Medicine and the director of the Molecular Imaging Program for Anxiety & Mood Disorders. In 2012, Dr. Neumeister was the recipient of the ISTSS Robert S. Laufer Award for Outstanding Scientific Achievement in recognition of his exceptional contributions to research in the field of traumatic stress.