A newly published, DoD funded, study published in Biological Psychiatry is reviewed by Ann Trafton, a science writer from MIT, in an article posted by MedicalXpress titled 'Blocking a newly identified memory pathway could prevent PTSD'.
For reference, the article is found in PubMed as:
Stress Enables Reinforcement-Elicited Serotonergic Consolidation of Fear Memory.
Conclusion: Stress bolsters the consequences of aversive reinforcement, not by simply enhancing the neurobiological signals used to encode fear in unstressed animals, but rather by engaging distinct mechanistic pathways. These results reveal that predictions from classical associative learning models do not always hold for stressed animals and suggest that 5-HT2CR blockade may represent a promising therapeutic target for psychiatric disorders characterized by excessive fear responses such as that observed in PTSD.
Baratta MV, Kodandaramaiah SB, Monahan PE, Yao J, Weber MD, Lin PA, Gisabella B, Petrossian N, Amat J, Kim K, Yang A, Forest CR, Boyden ES, Goosens KA.
Biol Psychiatry. 2015 Jul 2. pii: S0006-3223(15)00533-8. doi: 10.1016/j.biopsych.2015.06.025. [Epub ahead of print]
PMID: 26248536
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Cited by (Google Scholar)
As I am not a neuroscientist and this study is very complex, I can only provide a basic overview (mostly paraphrased) of the research then conclude by showing how psilocybin appears to play a promising role in treating PTSD by its effect on the amygdala. Hopefully some "heroic investigators" will follow up on these new insights.
An animal subjected to chronic stress prior to experiencing a traumatic event engages a distinctive brain pathway that encodes traumatic memories in the amygdala (amygdala plays a key role in fear consolidation) more strongly than in unstressed animals. Serotonin promotes the process of memory consolidation in animals that go on to developed PTSD symptoms following chronic stress and a traumatic event. By blocking the amygdala cells' interactions with serotonin after trauma, the stressed animals did not develop PTSD symptoms.
Chronic stress causes cells in the amygdala to express many more 5-HT2C receptors, which bind to serotonin. Then, when a traumatic experience occurs, this heightened sensitivity to serotonin causes the memory to be encoded more strongly. It may be possible to weaken these memories by using serotonin-blocking drugs to interfere with the reconsolidation process (note: SSRIs do the opposite).
Ki Goosens, the senior author of the study, stated "there's no biological evidence to support the use of SSRIs for PTSD." She continued, "The consolidation of traumatic memories requires this serotonergic cascade and we want to block it, not enhance it," she adds. "This study suggests we should rethink the use of SSRIs in PTSD and also be very careful about how they are used, particularly when somebody is recently traumatized and their memories are still being consolidated, or when a patient is undergoing cognitive behavior therapy where they're recalling the memory of the trauma and the memory is going through the process of reconsolidation."
So where does psilocybin fit in as a treatment for PTSD in light of this new information?
The dorsal raphe nucleus is the largest serotonergic nucleus and provides a substantial proportion of the serotonin innervation to the forebrain. Ten percent of the axons from the nucleus raphe dorsalis of the rat have been shown to project to the amygdala. Dorsal raphe serotonergic activity is required for the stress enhancement of fear in a stimulus-dependent manner. During this study inhibition of the serotonergic dorsal raphe during conditioning was sufficient to prevent stress related enhancement of fear by blocking memory consolidation in the amygdala.
Psilocybin reduces the dorsal raphe nucleus cell firing rate thus resulting in decreased serotonin release in terminal projection fields such as the amygdala. Further more, psilocybin decreases amygdala reactivity during emotion processing which is associated with an increase of positive mood in healthy volunteers. Psilocybin works on the 5HT2A receptors which are abundant in the amygdala. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states.
Since psilocybin is essentially non-addicting, has less toxicity than caffeine, and, as shown above, plays a key role in inhibiting the release of serotonin from the dorsal raphe nucleus as well as decreasing the reactivity of the amygdala to negative stimuli, it is a primary candidate for a Clinical Trial to treat PTSD.
Note: there is an article citing the article above by Baratta et al. that demonstrates how a 5-HT2CR blockade (put another way, serotonin 2C receptor antagonism) improves fear discrimination and subsequent safety signal recall that would be helpful for those with PTSD since their capacity to discriminate between safety and danger, which is fundamental for survival, is disrupted. The article as found in PubMed:
Serotonin 2C receptor antagonist improves fear discrimination and subsequent safety signal recall.
Foilb AR, Christianson JP.
Prog Neuropsychopharmacol Biol Psychiatry. 2015 Sep 4;65:78-84. doi: 10.1016/j.pnpbp.2015.08.017. [Epub ahead of print]
PMID: 26344640
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