Editing Post-traumatic stress disorder (section)

== Research ==
Most knowledge regarding PTSD comes from studies in high-income countries.<ref name="FodorUnterhitzenberger2014">{{cite journal |vauthors=Fodor KE, Unterhitzenberger J, Chou CY, Kartal D, Leistner S, Milosavljevic M, Nocon A, Soler L, White J, Yoo S, Alisic E |title=Is traumatic stress research global? A bibliometric analysis |journal=[[European Journal of Psychotraumatology]] |volume=5 |issue=1 |pages=23269 |year=2014 |pmid=24563730 |pmc=3930940 |doi=10.3402/ejpt.v5.23269}}</ref>

To recapitulate some of the neurological and neurobehavioral symptoms experienced by the [[veteran]] population of recent conflicts in Iraq and Afghanistan, researchers at the [[Roskamp Institute]] and the James A Haley Veteran's Hospital (Tampa) have developed an animal model to study the consequences of [[mild traumatic brain injury]] (mTBI) and PTSD.<ref name="Ojo2014">{{cite journal |vauthors=Ojo JO, Greenberg MB, Leary P, Mouzon B, Bachmeier C, Mullan M, Diamond DM, Crawford F |title=Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury |journal=[[Frontiers in Behavioral Neuroscience]] |volume=8 |pages=213 |date=December 2014 |pmid=25002839 |pmc= 4067099 |doi=10.3389/fnbeh.2014.00213 |doi-access=free}}</ref> In the laboratory, the researchers exposed mice to a repeated session of unpredictable stressor (i.e. predator odor while restrained), and physical trauma in the form of inescapable foot-shock, and this was also combined with a mTBI. In this study, PTSD animals demonstrated recall of [[traumatic memories]], anxiety, and an impaired social behavior, while animals subject to both mTBI and PTSD had a pattern of disinhibitory-like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. In comparison with other animal studies,<ref name="Ojo2014" /><ref name="Poulos 2014">{{cite journal |vauthors=Poulos AM, Reger M, Mehta N, Zhuravka I, Sterlace SS, Gannam C, Hovda DA, Giza CC, Fanselow MS |title=Amnesia for early life stress does not preclude the adult development of posttraumatic stress disorder symptoms in rats |journal=[[Biological Psychiatry]] |volume=76 |issue=4 |pages=306–14 |date=August 2014 |pmid=24231200 |pmc=3984614 |doi=10.1016/j.biopsych.2013.10.007}}</ref> examination of [[Neuroendocrine cell|neuroendocrine]] and [[neuroimmune system|neuroimmune]] responses in plasma revealed a trend toward increase in [[corticosterone]] in PTSD and combination groups.

[[Stellate ganglion]] block is an experimental procedure for the [[Treatments for PTSD|treatment of PTSD]].<ref name="StatPearls SGBs">{{cite journal |vauthors=Piraccini E, Munakomi S, Chang KV |title=Stellate Ganglion Blocks |year=2020 |pmid=29939575 |url=https://www.ncbi.nlm.nih.gov/books/NBK507798/ |journal=StatPearls |publisher=StatPearls Publishing LLC}}</ref>

Researchers are investigating a number of experimental FAAH and MAGL-inhibiting drugs in hopes of finding a better treatment for anxiety and stress-related illnesses.<ref name="ECS_Stress_Related">{{cite journal |vauthors=Hill MN, Patel S |title=Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses |journal=[[Biology of Mood & Anxiety Disorders]] |volume=3 |issue=1 |pages=19 |date=October 2013 |pmid=24286185 |pmc=3817535 |doi=10.1186/2045-5380-3-19 |doi-access=free }}</ref> In 2016, the FAAH-inhibitor drug [[BIA 10-2474]] was withdrawn from human trials in France due to adverse effects.<ref name="BIA_10_2474">{{cite web |title=New clues to why a French drug trial went horribly wrong |url=https://www.science.org/content/article/new-clues-why-french-drug-trial-went-horribly-wrong |publisher=[[Science (journal)|Science]] |vauthors=Feldwisch-Drentrup H |access-date=11 December 2019 |date=July 2002}}</ref>

Evidence from clinical trials suggests that [[MDMA-assisted psychotherapy]] is an effective [[Treatments for PTSD|treatment for PTSD]].<ref>{{cite journal | vauthors = Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora GM, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R | title = MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study | journal = Nature Medicine | volume = 27 | issue = 6 | pages = 1025–1033 | date = June 2021 | pmid = 33972795 | pmc = 8205851 | doi = 10.1038/s41591-021-01336-3 }}</ref><ref>{{cite journal | vauthors = Singleton SP, Wang JB, Mithoefer M, Hanlon C, George MS, Mithoefer A, Mithoefer O, Coker AR, Yazar-Klosinski B, Emerson A, Doblin R, Kuceyeski A | title = Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder | journal = Frontiers in Psychiatry | volume = 13 | pages = 947622 | date = 2023 | pmid = 36713926 | pmc = 9879604 | doi = 10.3389/fpsyt.2022.947622 | doi-access = free }}</ref> On August 9, 2024, the FDA issued a letter stating that a further trial was necessary to ascertain that the benefits of MDMA-assisted psychotherapy outweighed the potential harms.<ref>{{Cite journal |last=Reardon |first=Sara |date=2024-08-13 |title=FDA rejects ecstasy as a therapy: what's next for psychedelics? |url=https://www.nature.com/articles/d41586-024-02597-x |journal=Nature |language=en |doi=10.1038/d41586-024-02597-x|pmid=39143279 }}</ref> Positive findings in clinical trials of MDMA-assisted psychotherapy might be substantially influenced by expectancy effects given the unblinding of participants.<ref>{{cite journal | vauthors = Muthukumaraswamy SD, Forsyth A, Lumley T | title = Blinding and expectancy confounds in psychedelic randomized controlled trials | journal = Expert Review of Clinical Pharmacology | volume = 14 | issue = 9 | pages = 1133–1152 | date = September 2021 | pmid = 34038314 | doi = 10.1080/17512433.2021.1933434 | s2cid = 235215630 }}</ref><ref>{{cite journal | vauthors = Burke MJ, Blumberger DM | title = Caution at psychiatry's psychedelic frontier | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1687–1688 | date = October 2021 | pmid = 34635858 | doi = 10.1038/s41591-021-01524-1 | s2cid = 238635462 }}</ref> To prevent this confounding factor, it has been suggested that future trials compare MDMA against an active placebo.<ref>{{Cite web |last=Fong |first=Benjamin Y. |date=2024-08-12 |title=FDA rejects MDMA-assisted therapy for PTSD treatment – a drug researcher explains the challenges psychedelics face |url=https://theconversation.com/fda-rejects-mdma-assisted-therapy-for-ptsd-treatment-a-drug-researcher-explains-the-challenges-psychedelics-face-236383#:~:text=In%20June%202024,%20an%20FDA,for%20the%20treatment%20of%20PTSD. |access-date=2024-09-30 |website=The Conversation |language=en-US}}</ref> There is a lack of trials comparing MDMA-assisted psychotherapy to existent first-line treatments for PTSD, such as trauma-focused psychological treatments, which seems to achieve similar or even better outcomes than MDMA-assisted psychotherapy.<ref>{{cite journal | vauthors = Halvorsen JØ, Naudet F, Cristea IA | title = Challenges with benchmarking of MDMA-assisted psychotherapy | journal = Nature Medicine | volume = 27 | issue = 10 | pages = 1689–1690 | date = October 2021 | pmid = 34635857 | doi = 10.1038/s41591-021-01525-0 | s2cid = 238636360 | url = https://hal.archives-ouvertes.fr/hal-03414583/file/Halvorsen%20et%20al%20-%202021%20-%20Challenges%20with%20benchmarking%20of%20MDMA-assisted%20psychotherapy.pdf }}</ref>

=== Psychotherapy ===
Trauma-focused psychotherapies for PTSD (also known as "exposure-based" or "exposure" psychotherapies), such as prolonged exposure therapy (PE), eye movement desensitization and reprocessing (EMDR), and cognitive-reprocessing therapy (CPT) have the most evidence for efficacy and are recommended as first-line treatment for PTSD by almost all clinical practice guidelines.<ref name="Examining military population and t">{{cite journal |vauthors=Straud CL, Siev J, Messer S, Zalta AK |title=Examining military population and trauma type as moderators of treatment outcome for first-line psychotherapies for PTSD: A meta-analysis |journal=[[Journal of Anxiety Disorders]] |volume=67 |pages=102133 |date=October 2019 |pmid=31472332 |pmc=6739153 |doi=10.1016/j.janxdis.2019.102133}}</ref><ref>{{cite journal |vauthors=Hamblen JL, Norman SB, Sonis JH, Phelps AJ, Bisson JI, Nunes VD, Megnin-Viggars O, Forbes D, Riggs DS, Schnurr PP |title=A guide to guidelines for the treatment of posttraumatic stress disorder in adults: An update |journal=[[Psychotherapy (journal)|Psychotherapy]] |volume=56 |issue=3 |pages=359–373 |date=September 2019 |pmid=31282712 |doi=10.1037/pst0000231 |s2cid=195829939 |url=http://orca.cf.ac.uk/131829/1/CPG%20Review%20of%20Guidelines%20111218.%20CC%20edit%2003_02_19%20revision%20clean.pdf}}</ref><ref>{{cite journal |vauthors=Kline AC, Cooper AA, Rytwinksi NK, Feeny NC |title=Long-term efficacy of psychotherapy for posttraumatic stress disorder: A meta-analysis of randomized controlled trials |journal=[[Clinical Psychology Review]] |volume=59 |pages=30–40 |date=February 2018 |pmid=29169664 |pmc=5741501 |doi=10.1016/j.cpr.2017.10.009}}</ref> Exposure-based psychotherapies demonstrate efficacy for PTSD caused by different trauma "types", such as combat, sexual-assault, or natural disasters.<ref name="Examining military population and t"/> At the same time, many trauma-focused psychotherapies evince high drop-out rates.<ref>{{cite journal |vauthors=Goetter EM, Bui E, Ojserkis RA, Zakarian RJ, Brendel RW, Simon NM |title=A Systematic Review of Dropout From Psychotherapy for Posttraumatic Stress Disorder Among Iraq and Afghanistan Combat Veterans |journal=[[Journal of Traumatic Stress]] |volume=28 |issue=5 |pages=401–9 |date=October 2015 |pmid=26375387 |doi=10.1002/jts.22038|s2cid=25316702 }}</ref>

Most systematic reviews and clinical guidelines indicate that psychotherapies for PTSD, most of which are trauma-focused therapies, are more effective than pharmacotherapy (medication),<ref>{{cite journal |vauthors=Merz J, Schwarzer G, Gerger H |title=Comparative Efficacy and Acceptability of Pharmacological, Psychotherapeutic, and Combination Treatments in Adults With Posttraumatic Stress Disorder: A Network Meta-analysis |journal=[[JAMA Psychiatry]] |volume=76 |issue=9 |pages=904–913 |date=June 2019 |pmid=31188399 |pmc=6563588 |doi=10.1001/jamapsychiatry.2019.0951}}</ref> although there are reviews that suggest exposure-based psychotherapies for PTSD and pharmacotherapy are equally effective.<ref>{{Cite book |vauthors=Forman-Hoffman V, Middleton JC, Feltner C, Gaynes BN, Weber RP, Bann C, Viswanathan M, Lohr KN, Baker C, Green J |url=http://www.ncbi.nlm.nih.gov/books/NBK525132/ |title=Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update |date=2018 |publisher=Agency for Healthcare Research and Quality (US) |series=AHRQ Comparative Effectiveness Reviews |location=Rockville, MD |pmid=30204376}}</ref> Interpersonal psychotherapy shows preliminary evidence of probable efficacy, but more research is needed to reach definitive conclusions.<ref>{{cite journal |vauthors=Althobaiti S, Kazantzis N, Ofori-Asenso R, Romero L, Fisher J, Mills KE, Liew D |title=Efficacy of interpersonal psychotherapy for post-traumatic stress disorder: A systematic review and meta-analysis |journal=[[Journal of Affective Disorders]] |volume=264 |pages=286–294 |date=March 2020 |pmid=32056763 |doi=10.1016/j.jad.2019.12.021 |s2cid=211111940}}</ref>