Current and novel pharmacological therapeutic approaches in Post-Traumatic Stress Disorder. A brief review

1. Yehuda R, Hoge CW, McFarlane AC et al. Post-traumatic stress disorder. Nat Rev Dis Primers, 2015, 1:15057.10.1038/nrdp.2015.5727189040 Search in Google Scholar

2. Yehuda R, Lehrner A, Rosenbaum TY. PTSD and Sexual Dysfunction in Men and Women. J Sex Med, 2015, 12(5):1107-19.10.1111/jsm.1285625847589 Search in Google Scholar

3. Watson P. PTSD as a Public Mental Health Priority, Curr Psychiatry Rep, 2019, 21(7):61. Search in Google Scholar

4. Benjet C, Bromet E, Karam EG, Kessler RC, et al. The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium. Psychol Med. 2016, 46(2):327-43.10.1017/S0033291715001981486997526511595 Search in Google Scholar

5. Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res, 2009, 1293:13-23.10.1016/j.brainres.2009.03.044276167719332037 Search in Google Scholar

6. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev, 2006, 2006(1):CD002795.10.1002/14651858.CD002795.pub2699394816437445 Search in Google Scholar

7. Davidson JR. Remission in post-traumatic stress disorder (PTSD): effects of sertraline as assessed by the Davidson Trauma Scale, Clinical Global Impressions and the Clinician-Administered PTSD scale. Int Clin Psychopharmacol, 2004, 19(2):85-7.10.1097/00004850-200403000-0000515076016 Search in Google Scholar

8. Dieperink M, Erbes C, Leskela J et al. Comparison of treatment for post-traumatic stress disorder among three Department of Veterans Affairs medical centers, Mil Med, 2005, 170(4):305-8. Search in Google Scholar

9. Bernardy NC, Hoge CW, & Friedman MJ. VA/DoD Clinical Practice Guideline for the management of posttraumatic stress disorder and acute stress disorder. Washington, DC: United States Departments of Veterans Affairs and Defense, 2017, available at VA/DOD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder, accessed on 9th of June, 2021. Search in Google Scholar

10. American Psychological Association. (2017), Clinical practice guideline for the treatment of posttraumatic stress dis order (PTSD) in adults. American Psychological Association Guideline Development Panel for the Treatment of PTSD in Adults, available at: https://www.apa.org/ptsd-guideline/ptsd.pdf, accessed on 9th of June 2021. Search in Google Scholar

11. Rauch SL, Shin LM, Phelps EA. Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research-past, present, and future. Biol Psychiatry, 2006, 60(4):376-82.10.1016/j.biopsych.2006.06.00416919525 Search in Google Scholar

12. Rauch SL, Shin LM, Whalen PJ, Pitman RK. Neuroimaging and the neuroanatomy of PTSD. CNS Spectr, 1998, 3(suppl 2):30 – 41.10.1017/S1092852900007306 Search in Google Scholar

13. Horn SR, Charney DS, Feder A. Understanding resilience: New approaches for preventing and treating PTSD. Exp Neurol, 2016, 284(Pt B):119-132.10.1016/j.expneurol.2016.07.00227417856 Search in Google Scholar

14. Abdallah CG, Averill LA, Akiki TJ et al. The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder. Ann Rev Pharmacol Toxicol, 2019, 59:171-189.10.1146/annurev-pharmtox-010818-021701632688830216745 Search in Google Scholar

15. Rasmusson AM, Pineles SL. Neurotransmitter, Peptide, and Steroid Hormone Abnormalities in PTSD: Biological Endophenotypes Relevant to Treatment. Curr Psychiatry Rep, 2018, 20(7):52.10.1007/s11920-018-0908-9 Search in Google Scholar

16. Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci, 2009, 10(6):410-22.10.1038/nrn2648 Search in Google Scholar

17. Birnbaum S, Gobeske KT, Auerbach J, Taylor JR, Arnsten AF. A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry, 1999, 46(9):1266-74.10.1016/S0006-3223(99)00138-9 Search in Google Scholar

18. Fitzgerald JM, DiGangi JA, Phan KL. Functional Neuroanatomy of Emotion and Its Regulation in PTSD. Harv Rev Psychiatry, 2018, 26(3):116-128.10.1097/HRP.0000000000000185594486329734226 Search in Google Scholar

19. Quinones MM, Gallegos AM, Lin FV, Heffner K. Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review. Cogn Affect Behav Neurosci, 2020, 20(3):455-480.10.3758/s13415-020-00782-9768289432170605 Search in Google Scholar

20. Pan X, Wang Z, Wu X, Wen SW, Liu A. Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis. BMC Psychiatry, 2018, 18(1):324. doi: 10.1186/s12888-018-1910-9.10.1186/s12888-018-1910-9617386630290789 Search in Google Scholar

21. Speer KE, Semple S, Naumovski N, D’Cunha NM, McKune AJ. HPA axis function and diurnal cortisol in post-traumatic stress disorder: A systematic review. Neurobiol Stress, 2019, 11:100180.10.1016/j.ynstr.2019.100180658223831236437 Search in Google Scholar

22. Yehuda R, Flory JD, Bierer LM et al. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry, 2015, 77(4):356-64.10.1016/j.biopsych.2014.02.00624661442 Search in Google Scholar

23. Bandelow B, Baldwin D, Abelli M et al. Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry. 2017 Apr;18(3):162-214.10.1080/15622975.2016.1190867534177127419272 Search in Google Scholar

24. Zohar J, Yahalom H, Kozlovsky N et al. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies, Eur Neuropsychopharmacol, 2011, (11):796-809.10.1016/j.euroneuro.2011.06.00121741804 Search in Google Scholar

25. Southwick SM, Krystal JH, Bremner JD et al. Noradrenergic and serotonergic function in posttraumatic stress disorder. Arch Gen Psychiatry, 1997, 54(8):749-58.10.1001/archpsyc.1997.018302000830129283511 Search in Google Scholar

26. Kelmendi B, Adams TG, Yarnell S, Southwick S, Abdallah CG, Krystal JH. PTSD: from neurobiology to pharmacological treatments. Eur J Psychotraumatol, 2016, 7:31858.10.3402/ejpt.v7.31858510686527837583 Search in Google Scholar

27. Ramboz S, Oosting R, Amara DA et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A, 1998, 95(24):14476-81.10.1073/pnas.95.24.14476243989826725 Search in Google Scholar

28. Murrough JW, Czermak C, Henry S et al. The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding. Arch Gen Psychiatry, 2011, 68(9):892-900.10.1001/archgenpsychiatry.2011.91324483621893657 Search in Google Scholar

29. Zohar J, Fostick L, Juven-Wetzler A et al. Secondary prevention of chronic PTSD by early and short-term administration of escitalopram: a prospective random ized, placebo-controlled, double-blind trial. The Journal of clinical psychiatry, 2018, 79(2):16m10730. doi: 10.4088/JCP.16m10730.10.4088/JCP.16m1073028703951 Search in Google Scholar

30. Miner LH, Jedema HP, Moore FW, Blakely RD, Grace AA, Sesack SR. Chronic stress increases the plasmalemmal distribution of the norepinephrine transporter and the coexpression of tyrosine hydroxylase in norepinephrine axons in the prefrontal cortex. J Neurosci, 2006, 26(5):1571-8.10.1523/JNEUROSCI.4450-05.2006667548816452680 Search in Google Scholar

31. Krystal JH, Webb E, Cooney NL et al. Serotonergic and noradrenergic dysregulation in alcoholism: m-chlorophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects. Am J Psychiatry, 1996, 153(1):83-92.10.1176/ajp.153.1.838540598 Search in Google Scholar

32. Southwick SM, Krystal JH, Morgan CA et al. Abnormal noradrenergic function in posttraumatic stress disorder. Arch Gen Psychiatry, 1993, 50(4):266-74.10.1001/archpsyc.1993.018201600360038466387 Search in Google Scholar

33. Raskind MA, Peskind ER, Chow Bet al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med, 2018, 378(6):507-517.10.1056/NEJMoa150759829414272 Search in Google Scholar

34. Germain A, Richardson R, Moul DE et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans. J Psychosom Res, 2012, 72(2):89-96.10.1016/j.jpsychores.2011.11.010326796022281448 Search in Google Scholar

35. Brunet A, Saumier D, Liu A, Streiner DL, Tremblay J, Pitman RK. Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial, Am J Psychiatry, 2018, 175(5):427-433. Search in Google Scholar

36. van Zuiden M, Frijling JL, Nawijn L et al. Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients. Biol Psychiatry, 2017,81(12):1030-1040.10.1016/j.biopsych.2016.11.01228087128 Search in Google Scholar

37. Flanagan JC, Sippel LM, Wahlquist A, Moran-Santa Maria MM, Back SE. Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. J Psychiatr Res, 2018, 98:64-69.10.1016/j.jpsychires.2017.12.014580095129294429 Search in Google Scholar

38. Sippel LM, Allington CE, Pietrzak RH, Harpaz-Rotem I, Mayes LC, Olff M. Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities, Chronic Stress (Thousand Oaks), 2017, 1:247054701668799.10.1177/2470547016687996548228528649672 Search in Google Scholar

39. Pitman RK, Rasmusson AM, Koenen KC et al. Biological studies of post-traumatic stress disorder, Nat Rev Neurosci, 2012,13(11):769-87. Search in Google Scholar

40. Pennington DL, Abé C, Batki SL, Meyerhoff DJ. A preliminary examination of cortical neurotransmitter levels associated with heavy drinking in posttraumatic stress disorder. Psychiatry Res, 2014, 224(3):281-7.10.1016/j.pscychresns.2014.09.004425445025444536 Search in Google Scholar

41. Hill MN, Campolongo P, Yehuda R, Patel S. Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder. Neuropsychopharmacology, 2018, 43(1):80-102.10.1038/npp.2017.162571909528745306 Search in Google Scholar

42. Bitencourt RM, Pamplona FA, Takahashi RN. Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats. Eur Neuropsychopharmacol, 2008, 18(12):849-59.10.1016/j.euroneuro.2008.07.00118706790 Search in Google Scholar

43. Assareh N, Gururajan A, Zhou C, Luo JL, Kevin RC, Arnold JC. Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice. Behav Pharmacol, 2020, 31(6):591-596.10.1097/FBP.000000000000056532483052 Search in Google Scholar

44. García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules, 2020, 10(11):1575.10.3390/biom10111575769961333228239 Search in Google Scholar

45. Elms L, Shannon S, Hughes S, Lewis N. Cannabidiol in the Treatment of Post-Traumatic Stress Disorder: A Case Series. J Altern Complement Med. 2019, 25(4):392-397.10.1089/acm.2018.0437648291930543451 Search in Google Scholar

46. Berardi A, Schelling G, Campolongo P. The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings, Pharmacol Res. 2016, 111:668-678.10.1016/j.phrs.2016.07.02427456243 Search in Google Scholar

47. Bitencourt RM, Takahashi RN. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials. Front Neurosci, 2018, 12:502.10.3389/fnins.2018.00502606658330087591 Search in Google Scholar

48. Cannabidiol (CBD) Critical Review Report, World Health Organization, Expert Committee on Drug Dependence, Geneva, available at CANNABIDIOL (CBD) (who.int), accessed on 9th of June, 2021. Search in Google Scholar

49. Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology (Berl), 2021, 238(1):9-28.10.1007/s00213-020-05712-8779692433221931 Search in Google Scholar

50. Sartori SB, Singewald N. Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacol Ther, 2019, 204:107402.10.1016/j.pharmthera.2019.10740231470029 Search in Google Scholar

51. Cameron C, Watson D, Robinson J. Use of a synthetic cannabinoid in a correctional population for posttraumatic stress disorder-related insomnia and nightmares, chronic pain, harm reduction, and other indications: a retrospective evaluation. J Clin Psychopharmacol, 2014, 34(5):559-64.10.1097/JCP.0000000000000180416547124987795 Search in Google Scholar

52. Spindle TR, Cone EJ, Goffi E et al. Pharmacodynamic effects of vaporized and oral cannabidiol (CBD) and vaporized CBD-dominant cannabis in infrequent cannabis users. Drug Alcohol Depend, 2020, 211:107937.10.1016/j.drugalcdep.2020.107937741480332247649 Search in Google Scholar

53. Young MB, Norrholm SD, Khoury LM et al. Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA). Psychopharmacology (Berl), 2017, 234(19):2883-2895.10.1007/s00213-017-4684-8569375528741031 Search in Google Scholar

54. Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry. 2019 Sep 12; 10:650.10.3389/fpsyt.2019.00650675138131572236 Search in Google Scholar

55. Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R. The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol, 2011, 25(4):439-52.10.1177/0269881110378371312237920643699 Search in Google Scholar

56. Mithoefer MC, Wagner MT, Mithoefer AT et al. Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol, 2013, 27(1):28-39.10.1177/0269881112456611357367823172889 Search in Google Scholar

57. Jerome L, Feduccia AA, Wang JB et al. Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl), 2020, 237(8):2485-2497.10.1007/s00213-020-05548-2735184832500209 Search in Google Scholar

58. Illingworth BJ, Lewis DJ, Lambarth AT et al. A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. J Psychopharmacol, 2021, 35(5):501-511.10.1177/026988112096591533345689 Search in Google Scholar

59. Schenk S, Newcombe D. Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. J Clin Psychopharmacol, 2018, 38(6):632-638.10.1097/JCP.000000000000096230303861 Search in Google Scholar

60. Morgan L. MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t. Ann Gen Psychiatry, 2020, 19:33.10.1186/s12991-020-00283-6721863332435270 Search in Google Scholar

61. Jîtcă G, Ősz BE, Tero-Vescan A, Vari CE. Psychoactive Drugs-From Chemical Structure to Oxidative Stress Related to Dopaminergic Neurotransmission. A Review, Antioxidants (Basel), 2021,10(3):381.10.3390/antiox10030381800078233806320 Search in Google Scholar

62. de la Torre R, Farré M. Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans. Trends Pharmacol Sci, 2004, 25(10):505-8.10.1016/j.tips.2004.08.00115380932 Search in Google Scholar