The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD.

Summary

This study aims to investigate the effects of MDMA on prefrontal and amygdala activation, and to explore the relationship between these MDMA-induced neural changes and the acute behavioral effects of the drug in patients with PTSD.

Timeline

Start

2024-05

Primary completion

2028-01

Completion

2028-01

Outcome

Outcome not reported

Stopped (Business): “Funding ended.”

Publications

• Background Haagen JF, Smid GE, Knipscheer JW, Kleber RJ. The efficacy of recommended treatments for veterans with PTSD: A metaregression analysis. Clin Psychol Rev. 2015 Aug;40:184-94. doi: 10.1016/j.cpr.2015.06.008. Epub 2015 Jun 27.
• Background Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995 Dec;52(12):1048-60. doi: 10.1001/archpsyc.1995.03950240066012.
• Background Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW, Milad MR, Liberzon I. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci. 2012 Nov;13(11):769-87. doi: 10.1038/nrn3339. Epub 2012 Oct 10.
• Background Abad S, Camarasa J, Pubill D, Camins A, Escubedo E. Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits. Mol Neurobiol. 2016 Dec;53(10):7271-7283. doi: 10.1007/s12035-015-9618-z. Epub 2015 Dec 21.
• Background 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 Apr;25(4):439-52. doi: 10.1177/0269881110378371. Epub 2010 Jul 19.
• Background Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Martin SF, Yazar-Klosinski B, Michel Y, Brewerton TD, Doblin R. 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 Jan;27(1):28-39. doi: 10.1177/0269881112456611. Epub 2012 Nov 20.
• Background Shin LM, Rauch SL, Pitman RK. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci. 2006 Jul;1071:67-79. doi: 10.1196/annals.1364.007.
• Background Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010 Jan;35(1):169-91. doi: 10.1038/npp.2009.83.
• Background Lanius RA, Bluhm R, Lanius U, Pain C. A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation. J Psychiatr Res. 2006 Dec;40(8):709-29. doi: 10.1016/j.jpsychires.2005.07.007. Epub 2005 Oct 7.
• Background Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007 Oct;164(10):1476-88. doi: 10.1176/appi.ajp.2007.07030504.
• Background Carhart-Harris RL, Wall MB, Erritzoe D, Kaelen M, Ferguson B, De Meer I, Tanner M, Bloomfield M, Williams TM, Bolstridge M, Stewart L, Morgan CJ, Newbould RD, Feilding A, Curran HV, Nutt DJ. The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories. Int J Neuropsychopharmacol. 2014 Apr;17(4):527-40. doi: 10.1017/S1461145713001405. Epub 2013 Dec 17.
• Background Hysek CM, Domes G, Liechti ME. MDMA enhances "mind reading" of positive emotions and impairs "mind reading" of negative emotions. Psychopharmacology (Berl). 2012 Jul;222(2):293-302. doi: 10.1007/s00213-012-2645-9. Epub 2012 Jan 27.
• Background Kirkpatrick MG, Lee R, Wardle MC, Jacob S, de Wit H. Effects of MDMA and Intranasal oxytocin on social and emotional processing. Neuropsychopharmacology. 2014 Jun;39(7):1654-63. doi: 10.1038/npp.2014.12. Epub 2014 Jan 22.
• Background Hysek CM, Schmid Y, Simmler LD, Domes G, Heinrichs M, Eisenegger C, Preller KH, Quednow BB, Liechti ME. MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci. 2014 Nov;9(11):1645-52. doi: 10.1093/scan/nst161. Epub 2013 Oct 4.
• Background Wardle MC, de Wit H. MDMA alters emotional processing and facilitates positive social interaction. Psychopharmacology (Berl). 2014 Oct;231(21):4219-29. doi: 10.1007/s00213-014-3570-x. Epub 2014 Apr 12.
• Background Baggott MJ, Kirkpatrick MG, Bedi G, de Wit H. Intimate insight: MDMA changes how people talk about significant others. J Psychopharmacol. 2015 Jun;29(6):669-77. doi: 10.1177/0269881115581962. Epub 2015 Apr 28.
• Background Baggott MJ, Coyle JR, Siegrist JD, Garrison KJ, Galloway GP, Mendelson JE. Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting. J Psychopharmacol. 2016 Apr;30(4):378-87. doi: 10.1177/0269881115626348. Epub 2016 Feb 15.
• Background Carhart-Harris RL, Murphy K, Leech R, Erritzoe D, Wall MB, Ferguson B, Williams LT, Roseman L, Brugger S, De Meer I, Tanner M, Tyacke R, Wolff K, Sethi A, Bloomfield MA, Williams TM, Bolstridge M, Stewart L, Morgan C, Newbould RD, Feilding A, Curran HV, Nutt DJ. The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level-Dependent Resting State Functional Connectivity. Biol Psychiatry. 2015 Oct 15;78(8):554-62. doi: 10.1016/j.biopsych.2013.12.015. Epub 2014 Jan 10.
• Background Liechti ME, Vollenweider FX. Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies. Hum Psychopharmacol. 2001 Dec;16(8):589-598. doi: 10.1002/hup.348.
• Background Ramos L, Hicks C, Kevin R, Caminer A, Narlawar R, Kassiou M, McGregor IS. Acute prosocial effects of oxytocin and vasopressin when given alone or in combination with 3,4-methylenedioxymethamphetamine in rats: involvement of the V1A receptor. Neuropsychopharmacology. 2013 Oct;38(11):2249-59. doi: 10.1038/npp.2013.125. Epub 2013 May 16.
• Background Heinrichs M, Domes G. Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans. Prog Brain Res. 2008;170:337-50. doi: 10.1016/S0079-6123(08)00428-7.
• Background Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ. Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration. Soc Neurosci. 2009;4(4):359-66. doi: 10.1080/17470910802649470.
• Background Thompson MR, Hunt GE, McGregor IS. Neural correlates of MDMA ("Ecstasy")-induced social interaction in rats. Soc Neurosci. 2009;4(1):60-72. doi: 10.1080/17470910802045042. Epub 2008 May 23.
• Background Kirkpatrick MG, Francis SM, Lee R, de Wit H, Jacob S. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans. Psychoneuroendocrinology. 2014 Aug;46:23-31. doi: 10.1016/j.psyneuen.2014.04.006. Epub 2014 Apr 19.
• Background Kamilar-Britt P, Bedi G. The prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA): Controlled studies in humans and laboratory animals. Neurosci Biobehav Rev. 2015 Oct;57:433-46. doi: 10.1016/j.neubiorev.2015.08.016. Epub 2015 Sep 25.
• Background Parrott AC. The psychotherapeutic potential of MDMA (3,4-methylenedioxymethamphetamine): an evidence-based review. Psychopharmacology (Berl). 2007 Apr;191(2):181-93. doi: 10.1007/s00213-007-0703-5. Epub 2007 Feb 13.
• Background Quirk GJ, Mueller D. Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology. 2008 Jan;33(1):56-72. doi: 10.1038/sj.npp.1301555. Epub 2007 Sep 19.
• Background Mueller D, Porter JT, Quirk GJ. Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction. J Neurosci. 2008 Jan 9;28(2):369-75. doi: 10.1523/JNEUROSCI.3248-07.2008.
• Background Southwick SM, Bremner JD, Rasmusson A, Morgan CA 3rd, Arnsten A, Charney DS. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry. 1999 Nov 1;46(9):1192-204. doi: 10.1016/s0006-3223(99)00219-x.
• Background Bailey CR, Cordell E, Sobin SM, Neumeister A. Recent progress in understanding the pathophysiology of post-traumatic stress disorder: implications for targeted pharmacological treatment. CNS Drugs. 2013 Mar;27(3):221-32. doi: 10.1007/s40263-013-0051-4.
• Background Connor TJ. Methylenedioxymethamphetamine (MDMA, 'Ecstasy'): a stressor on the immune system. Immunology. 2004 Apr;111(4):357-67. doi: 10.1111/j.0019-2805.2004.01847.x.
• Background Ekman, P. and W.V. Friesen, Measuring facial movement. Environmental psychology and nonverbal behavior, 1976. 1(1): p. 56-75.
• Background Harris RJ, Young AW, Andrews TJ. Morphing between expressions dissociates continuous from categorical representations of facial expression in the human brain. Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21164-9. doi: 10.1073/pnas.1212207110. Epub 2012 Dec 3.
• Background Dziobek I, Rogers K, Fleck S, Bahnemann M, Heekeren HR, Wolf OT, Convit A. Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET). J Autism Dev Disord. 2008 Mar;38(3):464-73. doi: 10.1007/s10803-007-0486-x. Epub 2007 Nov 8.
• Background Cami J, Farre M, Mas M, Roset PN, Poudevida S, Mas A, San L, de la Torre R. Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor performance and subjective effects. J Clin Psychopharmacol. 2000 Aug;20(4):455-66. doi: 10.1097/00004714-200008000-00010.
• Background Dumont GJ, Verkes RJ. A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers. J Psychopharmacol. 2006 Mar;20(2):176-87. doi: 10.1177/0269881106063271.
• Background Vollenweider FX, Gamma A, Liechti M, Huber T. Psychological and cardiovascular effects and short-term sequelae of MDMA ("ecstasy") in MDMA-naive healthy volunteers. Neuropsychopharmacology. 1998 Oct;19(4):241-51. doi: 10.1016/S0893-133X(98)00013-X.
• Background Liechti ME, Gamma A, Vollenweider FX. Gender differences in the subjective effects of MDMA. Psychopharmacology (Berl). 2001 Mar 1;154(2):161-8. doi: 10.1007/s002130000648.
• Background Kuypers KP, Ramaekers JG. Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine. J Psychopharmacol. 2005 Nov;19(6):633-9. doi: 10.1177/0269881105056670.
• Background Grob CS, Danforth AL, Chopra GS, Hagerty M, McKay CR, Halberstadt AL, Greer GR. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Arch Gen Psychiatry. 2011 Jan;68(1):71-8. doi: 10.1001/archgenpsychiatry.2010.116. Epub 2010 Sep 6.

Drugs

Indications