Beyond Fear

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Beyond Fear: Research on the Effects of MDMA

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  • Companies emphasized trade names (like Heroin on left) and they patented many chemical processes (patent for MDMA on right)
  • Companies emphasized trade names (like Heroin on left) and they patented many chemical processes (patent for MDMA on right)
  • Companies emphasized trade names (like Heroin on left) and they patented many chemical processes (patent for MDMA on right)
  • Beyond Fear

    1. 1. Beyond Fear: TheEffects of MDMA inHumansMatthew Baggott, Ph.D.University of ChicagoPhoto by Simon Webster
    2. 2. About MeWorked on the firstfederally fundedMDMA dosing study in1998Helped MAPS get FDApermission to giveMDMA to patientsHave studied, inhumans: MDMA,MDA, LSD,stimulants...
    3. 3. About this researchUniversity of Chicago: Harriet de Wit, MatthewKirkpatrick, Megan WardleCalifornia Pacific Medical Center: JohnMendelson, Gantt Galloway, Jeremy Coyle,Kathleen GarrisonUCSF: Reese Jones
    4. 4. About this researchUniversity of Chicago: Harriet de Wit, MatthewKirkpatrick, Megan WardleCalifornia Pacific Medical Center: JohnMendelson, Gantt Galloway, Jeremy Coyle,Kathleen GarrisonUCSF: Reese JonesUniversity of Basel: Cédric Hysek, MatthiasLiechti
    5. 5. Location of thediscovery of LSDby SandozChemist AlbertHofmann
    6. 6. Why Basel?Location of thediscovery of LSDby SandozChemist AlbertHofmann
    7. 7. • 1856, Perkin discovers mauveine, the firstsynthetic dye.• 1863, Bayer company founded as a dyemaker in Wuppertal• 1865, BASF (Baden Aniline and SodaFactory) founded in Mannheim, with factoryon the Rhine river• 1886, Sandoz founded in BaselBefore drugs there were dyes
    8. 8. • 1886, aniline dye derivativeacetanilide sold as analgesic /antipyretic “Antifebrin”• 1891, methylene blue used totreat malaria• 1935, “Prontosil”, a red dye,sold as the first antibioticMany dyes have biological effects(Wikipedia)
    9. 9. Patent law protected the processnot the resulting chemical
    10. 10. Use trade namesPatent law protected the processnot the resulting chemical
    11. 11. Use trade namesPatent law protected the processnot the resulting chemicalPatent many processes(Freudenmann,Öxler,&Bernschneider-Reif2006)
    12. 12. In what wayscan drugs likeMDMAfunction likedyes?MDMA(„Ecstasy‟)
    13. 13. Overview
    14. 14. OverviewMDMA does something novel•not a typical stimulant (drunken/sedated effects)•not a typical hallucinogen (consistently positive)How does it work?•Neurochemistry: Serotonin, oxytocin,norepinephrine•Psychology: Prosocial effects, authenticity•Reduced anxiety may not be the core effect(Focus here is on acute (short term) effects)
    15. 15. How We Measure Drug Effects
    16. 16. How We Measure Drug Effects
    17. 17. How We Measure Drug Effects
    18. 18. How We Measure Drug Effects38358
    19. 19. MDMA is not a typical stimulant(Sedative-like effects)
    20. 20. N = 29 (15 M)Time (Hr)VASScore(-pre)-20-100102030Clear headed0 1 2 3 4 5 6Confused0 1 2 3 4 5 6Drunken0 1 2 3 4 5 6ConditionPlaceboMDMAN = 29 (15 M)MDMA is not a typical stimulant(Sedative-like effects)
    21. 21. MDMA is not a typical hallucinogen(Consistent positive social effects)
    22. 22. Time (Hr)VASScore(-pre)-50510152025Closeness to others0 1 2 3 4 5 6Kind0 1 2 3 4 5 6Loving0 1 2 3 4 5 6ConditionPlaceboMDMAMDMA is not a typical hallucinogen(Consistent positive social effects)N = 29 (15 M)
    23. 23. How does it work? Neurochemistry
    24. 24. Serotonin transporter (SERT) isimportant to MDMA effects
    25. 25. Serotonin transporter (SERT) isimportant to MDMA effectsTime (hours)ClosenesstoOthers(0-100)102030405060700 1 2 3 4 5 6conditionPlaceboMDMA
    26. 26. Serotonin transporter (SERT) is alsoimportant to MDMA effectsClosenesstoOthers(0-100)Time (hours)102030405060700 1 2 3 4 5 6conditionPlaceboMDMAFirst CitalopramCital-MDMA
    27. 27. MDMA increases Oxytocin
    28. 28. 2004006008001000Time (hours)Oxytocin(pg/ml)-1 1 2 3 4PlaceboMDMA2004006008001000CmaxOxytocin(pg/ml)PlaceboMDMAAUCOxytocin(pg*hrs/ml)0500100015002000MDMA increases Oxytocin* ** *(Baggott et al. submitted)N=16 (8F, 8M)
    29. 29. Sociability = i1 + cDose + e1Sociability = i2 + c’Dose + bOxytocin + e2Oxytocin = i3 + aDose+ e3Oxytocin partly mediates MDMAeffects on self-report sociability(MacKinnon et al. 2007; Preacher and Hayes 2004)MDMAorPlaceboSociability, 2.5 HrOxytocin,2 Hra bcab = 0.36 (95%CI 0.06 – 0.87)
    30. 30. Blood levels after MDA or MDMAMDAMDMAMDA T1/2 : 9.7 3.2 hMDMA T1/2 : 8.1 2.1 h
    31. 31. Tolerance Development
    32. 32. Tolerance Development
    33. 33. Tolerance Development
    34. 34. Tolerance Development
    35. 35. Tolerance Development
    36. 36. Tolerance Development
    37. 37. Tolerance Development
    38. 38. Tolerance Development
    39. 39. Tolerance DevelopmentHypotheticalPlot showingNo Tolerance
    40. 40. Tolerance: MDA < MDMA
    41. 41. Tolerance: MDA < MDMA
    42. 42. (Hyseketal.2011)ReducingNorepinephrine‟sRoleinMDMAReducingSerotonin‟sRoleinMDMAPhysical Self-report
    43. 43. (Hyseketal.2011)ReducingNorepinephrine‟sRoleinMDMAReducingSerotonin‟sRoleinMDMAPhysical Self-report
    44. 44. (Hyseketal.2011)ReducingNorepinephrine‟sRoleinMDMAReducingSerotonin‟sRoleinMDMAPhysical Self-report
    45. 45. (Hyseketal.2011)ReducingNorepinephrine‟sRoleinMDMAReducingSerotonin‟sRoleinMDMAPhysical Self-report
    46. 46. ReducingNorepinephrine‟sRoleinMDMAReducingSerotonin‟sRoleinMDMAPhysical Self-report><
    47. 47. How does it work? Psychology
    48. 48. Hypothesized MDMA Effect Hypothesized BenefitImproved mood Positive mood encourages changesin cognitive models about theworldIncreased interpersonalconnectionImproved couples therapy;facilitation of therapeutic alliance;more rapid therapy with fewersessions requiredReduced fear response Allows difficult/negative emergentmaterial to be re-evaluatedEntactogenic (“touching within”) Deeper contact with true self;recognition of positive aspects ofself(adapted from Parrott 2007)How does it work? Psychology
    49. 49. Hypothesized MDMA Effect Hypothesized BenefitImproved mood Positive mood encourages changesin cognitive models about theworldIncreased interpersonalconnectionImproved couples therapy;facilitation of therapeutic alliance;more rapid therapy with fewersessions requiredReduced fear response Allows difficult/negative emergentmaterial to be re-evaluatedEntactogenic (“touching within”) Deeper contact with true self;recognition of positive aspects ofself(adapted from Parrott 2007)How does it work? Psychology
    50. 50. MDA(n = 12)MDMA(n = 16)
    51. 51. Hypothesized MDMA Effect Hypothesized BenefitImproved mood Positive mood encourages changesin cognitive models about theworldIncreased interpersonalconnectionImproved couples therapy;facilitation of therapeutic alliance;more rapid therapy with fewersessions requiredReduced fear response Allows difficult/negative emergentmaterial to be re-evaluatedEntactogenic (“touching within”) Deeper contact with true self;recognition of positive aspects ofself(adapted from Parrott 2007)How does it work? Psychology
    52. 52. Time (Hr)VASScore(-pre)-50510152025Closeness to others0 1 2 3 4 5 6Kind0 1 2 3 4 5 6Loving0 1 2 3 4 5 6ConditionPlaceboMDMAInterpersonal feelingsN = 29 (15 M)
    53. 53. Interpersonal Perception
    54. 54. Trustworthiness-3 SD
    55. 55. Trustworthiness-1.5 SD
    56. 56. Trustworthiness0 SD
    57. 57. Trustworthiness1.5 SD
    58. 58. Trustworthiness3 SD
    59. 59. Perceptions of TrustworthinessPredicted Trustworthiness (SD units)PercievedTrustworthiness(1-7Scale)345-3 -2 -1 0 1 2 3PlaceboMDMA
    60. 60. Perceptions of TrustworthinessPredicted Trustworthiness (SD units)PercievedTrustworthiness(1-7Scale)345-3 -2 -1 0 1 2 3PlaceboMDMA
    61. 61. Predicted Trustworthiness (SD units)PercievedTrustworthiness(1-7Scale)345-3 -2 -1 0 1 2 3PlaceboMDMACitalopramCitalopram-MDMAPerceptions of Trustworthiness
    62. 62. Hypothesized MDMA Effect Hypothesized BenefitImproved mood Positive mood encourages changesin cognitive models about theworldIncreased interpersonalconnectionImproved couples therapy;facilitation of therapeutic alliance;more rapid therapy with fewersessions requiredReduced fear response Allows difficult/negative emergentmaterial to be re-evaluatedEntactogenic (“touching within”) Deeper contact with true self;recognition of positive aspects ofself(adapted from Parrott 2007)How does it work? Psychology
    63. 63. Does MDMA really reducefear/anxiety?
    64. 64. Does MDMA really reducefear/anxiety?It significantly decreased anxiety in onestudy but not in two others, using theSTAI-S(Liechti & Vollenweider 2000; Liechti et al. 1998; Hasler etal. 2008)It increased anxiety scores in females butnot males, using the EWL Apprehension-anxiety(Liechti et al. 2001)It increased anxiety, more in females thanmales, using a VAS (Bedi and de Wit 2011)
    65. 65. MDMA increases anxiety in ourstudiesN = 29 (15 M)Time (hr)VASScore(-pre)-15-10-5051015Anxious0 1 2 3 4 5 6Relaxed0 1 2 3 4 5 6ConditionPlaceboMDMAN = 29 (15 M)
    66. 66. AnxiousN = 16 (8 M)Time (Hr)VASScore(-pre)-1001020Anxious0 1 2 3 4 5 6Loving0 1 2 3 4 5 6ConditionPlaceboMDMA
    67. 67. Time (Hr)VASScore(-pre)-1001020Anxious0 1 2 3 4 5 6Loving0 1 2 3 4 5 6ConditionPlaceboMDMAAnxious and More Loving ?N = 29 (15 M)
    68. 68. Anxious and More Loving ?• One possibility: a „Tend-and-befriend‟response to threat• Science has traditionally focused on a„fight-or-flight‟ response to stress, butmammals often seek safety and comfortwith others.(Taylor 2006)
    69. 69. Prediction: people should not be sociallyanxious
    70. 70. N = 12Prediction: people should not be sociallyanxiousTime (Hr)VASScore(-pre)-20-100102030Anxious0 1 2 3 4 5 6
    71. 71. N = 12Time (Hr)VASScore(-pre)-20-100102030Anxious0 1 2 3 4 5 6Time (hrs)SocialAnxiety-0.8-0.6-0.4-0.20.00 1.5 2 2.5 24PlaceboMDMA
    72. 72. N = 12Anxious but not anxious about peopleTime (Hr)VASScore(-pre)-20-100102030Anxious0 1 2 3 4 5 6Time (hrs)SocialAnxiety-0.8-0.6-0.4-0.20.00 1.5 2 2.5 24PlaceboMDMA
    73. 73. Hypothesis: Anxiety may be greatest ininexperienced people left alone
    74. 74. Hypothesis: Anxiety may be greatest ininexperienced people left aloneChicagoBaselSF
    75. 75. Hypothesized MDMA Effect Hypothesized BenefitImproved mood Positive mood encourages changesin cognitive models about theworldIncreased interpersonalconnectionImproved couples therapy;facilitation of therapeutic alliance;more rapid therapy with fewersessions requiredReduced fear response Allows difficult/negative emergentmaterial to be re-evaluatedEntactogenic (“touching within”) Deeper contact with true self;recognition of positive aspects ofself(adapted from Parrott 2007)How does it work? Psychology
    76. 76. How do you measure feelingsof deeper contact with one‟strue self?
    77. 77. How do you measure feelingsof deeper contact with one‟strue self? Authenticity:The operation of one‟s true self without impediment1. Awareness: knowing and trusting own motives, feelings, desires,and self-relevant cognitions.2. Unbiased Processing of self-relevant information: lack ofinterpretive distortions in processing of self-relevant information(e.g., not being defensive)3. Behavior: acting in accordance with own values, preferences, andneeds; not acting „„falsely‟‟ for others or rewards.4. Relational Orientation: acting with openness, sincerity, and truthin relationships with close others.(Goldman & Kernis, 2002; Sheldon, Ryan et al. 1997)
    78. 78. Feelings of Authenticityare increased by MDMASelf-reportAuthenticity3.03.23.43.63.8Placebo MDMA6M6F
    79. 79. OverviewMDMA does something novel•not a typical stimulant (drunken/sedated effects)•not a typical hallucinogen (consistently positive)How does it work?•Neurochemistry: Serotonin, oxytocin,norepinephrine•Psychology: Prosocial effects, authenticity•Reduced anxiety may not be the core effect(Focus here is on acute (short term) effects)
    80. 80. Drugs, like dyes, can serveas tools to see things that aredifficult to see
    81. 81. (Methylene blue and Mycobacterium tuberculosis, Wikipedia)
    82. 82. (Acerbi, Lampos, Garnett, Bentley 2013)Emotion Expression in 20th Century Books
    83. 83. Photo by Simon WebsterThank You!Slides at slideshare.net/mattbagg/beyond-fear

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