Post traumatic stress disorder is a mental health condition that is characterized by a dysfunctional norepinephrine (NE) system, which prohibits an individual's ability to successfully integrate new information to past traumatic memories. Common treatments that are currently offered for PTSD patients are: cognitive processing therapy, prolonged exposure therapy, eye movement desensitization and reprocessing, stress inoculation training, or pharmacological options such as SSRIs and SNRIs. Patient feedback from previously mentioned modes of treatment have revealed that even after a patient undergoes psychotherapy their PTSD remains a chronic illness. Oftentimes when a patient experiences PTSD their symptoms may run comorbid with depression and other mental illnesses as well. Due to the fact that each patient’s neuroanatomy responds differently to medications, each case of PTSD is treated uniquely. Which prompts the need for further neuroscience and psychology research to develop novel approaches for PTSD treatments. A few non-traditional developments that are in the works is bilateral phasic activation of the locus coeruleus that resets spatial memories and the reviewal of psychedelic assisted psychotherapy.
Within the recent publication of, “Locus Coeruleus Phasic, But Not Tonic, Activation Initiates Global Remapping in a Familiar Environment” conducted by Grella et al., researchers proposed a network reset and potential memory updating by unilateral glutamate locus coeruleus (LC) activation. The neural networks reviewed in this study were of lab rats that were conditioned to an open field in (Environment A). The rats momentarily returned to the colony for 20 minutes and were reintroduced to Environment A (A/A) or taken to Environment B (A/B). Before placement in the “B” environment, the rats were given clonidine infusions and produced the familiar “A” environment map in the dentate gyrus (DG). The immediate early gene (IEG) data collected for DG, CA1, and CA3 was reviewed within both groups of rats. The ipsilateral phasic activation paired with glutamate activated the LC and reset the familiar A/A spatial map in the DGS. Researchers then closely reviewed the pyramidal cells of CA1 and CA3, which revealed a bilateral phasic activation paired with glutamate activates the LC to generate a global reset. Researchers conclude that the LC episodic memory signal is underlined by a failure to switch between memory encoding and memory retrieval of new space maps in DGS, CA1, and CA3. These research findings reveal a deeper understanding of the mechanisms in PTSD and the development of future treatments that interfere a traumatic memory with a positive one, during memory reconsolidation in efforts to reduce fear.
In a separate study by Krediet et al., “Reviewing the Potential of Psychedelics for the Treatment of PTSD,” researchers examined the redevelopment of psychedelics in psychotherapy. A population of PTSD patients can not tolerate the re-experience of traumatic memories during therapy, which causes high nonresponse rates and treatment dropout. The substance-assisted psychotherapy approach uses MDMA or ketamine as a means to catalyze psychotherapy. Substance-assisted psychotherapy reduces the fear response of anxiety-provoking trauma and increases a patient's interpersonal trust with their therapist. Ketamine possesses antidepressant properties and acts through the glutamatergic signaling pathway that was similarly previewed by Grella et al. The glutamate system is essential in the reconsolidation of memory as well as the extinction of learning. When ketamine is administered at the beginning of a mindfulness-based cognitive therapy session in doses of 0.5 mg/kg over a period of 40 minutes, patients experienced enhanced levels of fear extinction. MDMA was also reviewed in this study and is capable of decreasing the overactive amygdala activity in PTSD patients. According to researchers, patients who experienced 2-3 sessions of MDMA-assisted psychotherapy with doses ranging from 75-125 mg show sustained reductions in PTSD symptoms in follow up non-drug psychotherapy sessions. These long-term treatment effects persisted over a 3.5-year period that demonstrated higher effect size and lower dropout rates than FDA approved treatments for paroxetine and sertraline. Concerns for neurotoxicity and abuse liability are curbed from the medically supervised component of substance-assisted psychotherapy. Although MDMA and ketamine hold promise for use within a substance-assisted psychotherapy framework, further clinical trials must be explored. One may also take note that monitored prescription of MDMA or ketamine in controlled dosages cannot be compared to excessive use from unknown sources.
The preview of these two recent research studies conducted by Grella et al., and Krediet et al. demonstrate new non-traditional frameworks that deserve to be further explored for the future of PTSD treatments.
Works Cited
Grella, Stephanie L., et al. “Locus Coeruleus Phasic, But Not Tonic, Activation Initiates Global Remapping in a Familiar Environment.” The Journal of Neuroscience, vol. 39, no. 3, 2019, pp. 445-455, https://doi.org/10.1523/JNEUROSCI.1956-18.2018
Krediet, Erwin, et al. “Reviewing the Potential of Psychedelics for the Treatment of PTSD.” The International Journal of Neuropsychopharmacology, vol. 23, no. 6, Oxford University Press, 2020, pp. 385–400, https://doi.org/10.1093/ijnp/pyaa018.
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