Gli psichedelici: quanto è efficace e sicuro il loro possibile impiego in psichiatriae psicoterapia? Lo stato delle evidenze

Titolo Rivista PNEI REVIEW
Autori/Curatori Francesco Dente
Anno di pubblicazione 2023 Fascicolo 2023/1
Lingua Italiano Numero pagine 17 P. 89-105 Dimensione file 1110 KB
DOI 10.3280/PNEI2023-001006
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FrancoAngeli è membro della Publishers International Linking Association, Inc (PILA)associazione indipendente e non profit per facilitare (attraverso i servizi tecnologici implementati da CrossRef.org) l’accesso degli studiosi ai contenuti digitali nelle pubblicazioni professionali e scientifiche

Nell’ultimo decennio la ricerca sull’utilizzo terapeutico degli psichedelici ha subito un’impennata, soprattutto per quanto riguarda la loro poten- ziale applicazione nel trattamento dei disturbi psichiatrici. In questi studi è stata indagata la sicurezza e l’efficacia delle varie sostanze psichedeliche, come gli psichedelici classici (psilocibina, ayahuasca e LSD) la ketamina e l’MDMA. Gli studi si sono focalizzati nel trattamento di diversi disturbi psi- chiatrici come la depressione, le dipendenze da sostanza e la sindrome da stress post-traumatico (PTSD). Inoltre, grazie allo sviluppo delle tecniche di neuroimaging è possibile indagare come queste sostanze modulino i di- versi network cerebrali, e come esse sembrino effettuare i loro meccanismi terapeutici. In questo articolo, verranno descritti gli aspetti generali delle diverse sostanze psichedeliche, dalla classificazione ai diversi meccanismi farmacologici sottolineando le differenze tra psichedelici classici e non. Inol- tre, verranno analizzate le diverse componenti della psicoterapia assistita da psichedelici con particolare riguardo alle variabili del set e del setting. Infi- ne, verrà effettuata una revisione della letteratura riguardante gli studi più importanti dell’ultimo decennio sul tema del trattamento di ansia e depres- sione con psichedelici classici e ketamina, dipendenze da sostanze trattate con psichedelici classici e ketamina e trattamento della sindrome da stress post-traumatico con MDMA.;

Keywords:Psichedelici, Psicoterapia-assistita da psichedelici, Setting, Psilo- bicina, Ketamina, MDMA.

  1. Aday J.S., Davis A.K., Mitzkovitz C.M., Bloesch E.K., & Davoli C.C. (2021). Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects. ACS Pharmacology & Translational Science, 4(2), 424–435.
  2. Anis N.A., Berry S.C., Burton N.R., & Lodge D. (1983). The dissociative ana- esthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. British Journal of Pharmacology, 79(2), 565–575.
  3. Baggott M.J., Coyle J.R., Siegrist J.D., Garrison K.J., Galloway G.P., & Men- delson J.E. (2016). Effects of 3,4-methylenedioxymethamphetamine on socio- emotional feelings, authenticity, and autobiographical disclosure in healthy vo- lunteers in a controlled setting. Journal of Psychopharmacology, 30(4), 378–387. DOI: 10.1177/026988111562634
  4. Belser A.B., Agin-Liebes G., Swift T.C., Terrana S., Devenot N., Friedman H.L., Guss J., Bossis A., & Ross S. (2017). Patient Experiences of Psilocybin-Assisted Psychotherapy: An Interpretative Phenomenological Analysis. Journal of Huma- nistic Psychology, 57(4), 354–388. DOI: 10.1177/002216781770688
  5. Bogenschutz M.P., Forcehimes A.A., Pommy J.A., Wilcox C.E., Barbosa P., & Strassman R.J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology, 29(3), 289–299. DOI: 10.1177/026988111456514
  6. Carbonaro T.M., Bradstreet M.P., Barrett F.S., MacLean K.A., Jesse R., John- son M.W., & Griffiths R.R. (2016). Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Journal of Psychopharmacology, 30(12), 1268–1278. DOI: 10.1177/026988111666263
  7. Carhart-Harris R.L., Murphy K., Leech R., Erritzoe D., Wall M.B., Ferguson B., Williams L.T.J., Roseman L., Brugger S., De Meer I., Tanner M., Tyacke R., Wolff K., Sethi A., Bloomfield M.A.P., Williams T.M., Bolstridge M., Stewart L., Morgan C., Newbould R.D., Feilding A., Curran H.V., & Nutt D.J. (2015). The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontane- ous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity. Biological Psychiatry, 78(8), 554–562.
  8. Carvalho M., Carmo H., Costa V.M., Capela J.P., Pontes H., Remião F., Carvalho F., & Bastos M.D.L. (2012). Toxicity of amphetamines: an update. Archives of Toxicology, 86(8), 1167–1231.
  9. Cohen L., Athaide V., Wickham M.E., Doyle-Waters M.M., Rose N.G.W., & Hohl
  10. C.M. (2015). The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review. Annals of Emergency Medicine, 65(1), 43-51.e2.
  11. Cottler L.B., Leung K.S., & Abdallah A.B. (2009). Test-re-test reliability of DSM-IV adopted criteria for 3,4-methylenedioxymethamphetamine (MDMA) abuse and dependence: a cross-na- tional study. Addiction, 104(10), 1679–1690.
  12. Dakwar E., Nunes E.V., Hart C.L., Foltin R.W., Mathew S.J., Carpenter K.M., Choi C.J. “Jean”, Basaraba C.N., Pavlicova M., & Levin F.R. (2019). A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. American Journal of Psychiatry, 176(11), 923–930.
  13. Dakwar E., Nunes E.V., Hart C.L., Hu M.C., Foltin R.W., & Levin F.R. (2018). A sub- set of psychoactive effects may be critical to the behavioral impact of ketamine on cocaine use disorder: Results from a randomized, controlled laboratory study. Neuropharmacology, 142, 270–276.
  14. Kometer M., Schmidt A., Jancke L., & Vollenweider F.X. (2013). Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations. Journal of Neuroscien- ce, 33(25), 10544–10551. DOI: 10.1523/JNEUROSCI.3007-12.201
  15. Krystal J.H., Abdallah C.G., Sanacora G., Charney D.S., & Duman R.S. (2019). Ketamine: A Paradigm Shift for Depression Research and Treatment. Neu- ron, 101(5), 774–778.
  16. Liechti M.E., & Vollenweider F.X. (2001). Which neuroreceptors mediate the subjective effects of MDMA in humans? A summary of mechanistic studies. Hu- man Psychopharmacology: Clinical and Experimental, 16(8), 589–598.
  17. Masters R.E.L., & Houston J. (1972). The varieties of psychedelic experience. New York: Holt, Rinehart and Winston.
  18. Mitchell J.M., Bogenschutz M., Lilienstein A., Harrison C., Kleiman S., Par- ker-Guilbert K., Ot’alora G. M., Garas W., Paleos C., Gorman I., Nicholas C., Mithoefer M., Carlin S., Poulter B., Mithoefer A., Quevedo S., Wells G., Klaire S.S., Van DerKolk B., Tzarfaty K., Amiaz R., Worthy R., Shannon S., Woolley J.D., Marta C., Gelfand Y., Hapke E., Amar S., Wallach Y., Brown R., Hamilton S., Wang J.B., Coker A., Matthews R., De Boer A., Yazar-Klosinski B., Emerson A., & Doblin R. (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine, 27(6), 1025–1033.
  19. Mithoefer M.C., Feduccia A.A., Jerome L., Mithoefer A., Wagner M., Walsh Z., Hamilton S., Yazar-Klosinski B., Emerson A., & Doblin R. (2019). MDMA-assi- sted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharma- cology, 236(9), 2735–2745.
  20. Katalinic N., Lai R., Somogyi A., Mitchell P.B., Glue P., & Loo C.K. (2013). Ketamine as a new treatment for depression: A review of its efficacy and adverse effects. Australian & New Zealand Journal of Psychiatry, 47(8), 710–727. DOI: 10.1177/000486741348684
  21. Johnson M.W., Griffiths R.R., Hendricks P.S., & Henningfield J.E. (2018). The abuse potential of medical psilocybin according to the 8 factors of the Control- led Substances Act. Neuropharmacology, 142, 143–166.
  22. Johnson M.W., Garcia-Romeu A., Cosimano M.P., & Griffiths R.R. (2014). Pilot study of the 5-HT 2A R agonist psilocybin in the treatment of tobac- co addiction. Journal of Psychopharmacology, 28(11), 983–992. DOI: 10.1177/026988111454829
  23. Johnson M., Richards W., & Griffiths R. (2008). Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology, 22(6), 603–620. DOI: 10.1177/026988110809358
  24. Hartogsohn I. (2017). Constructing drug effects: Ahistory of set and setting. Drug Scien- ce, Policy and Law, 3, 205032451668332. DOI: 10.1177/2050324516683325
  25. Haijen E.C.H.M., Kaelen M., Roseman L., Timmermann C., Kettner H., Russ S., Nutt D., Daws R.E., Hampshire A.D.G., Lorenz R., & Carhart-Harris R.L. (2018). Predicting Responses to Psychedelics: A Prospective Study. Frontiers in Pharmacology, 9, 897.
  26. Grof S. (2009). LSD: doorway to the numinous: the groundbreaking psychedelic research into realms of the human unconscious. Rochester, VT: Park Street Press. Grunebaum, M. F., Galfalvy, H. C., Choo, T.-H., Keilp, J. G., Moitra, V. K., Parris, M. S., Marver, J. E., Burke, A. K., Milak, M. S., Sublette, M. E., Oquendo, M. A., & Mann, J. J. (2018). Ketamine for Rapid Reduction of Suici- dal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. American Journal of Psychiatry, 175(4), 327–335.
  27. Vollenweider F.X., & Kometer M. (2010). The neurobiology of psychedelicdrugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11(9), 642–651.
  28. Grof S. (1980). LSD psychotherapy. Pomona, Calif: Hunter House.
  29. Griffiths R.R., Johnson M.W., Carducci M.A., Umbricht A., Richards W.A., Richards B.D., Cosimano M.P., & Klinedinst M.A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with li- fe-threatening cancer: A randomized double-blind trial. Journal of Psychopharma- cology, 30(12), 1181–1197. DOI: 10.1177/026988111667551
  30. Gorman I., Nielson E.M., Molinar A., Cassidy K., & Sabbagh J. (2021). Psyche- delic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practi- ce. Frontiers in Psychology, 12, 645246.
  31. Garcia-Romeu A., Griffiths R.R., & Johnson M.W. (2014). Psilocybin-occasio- ned mystical experiences in the treatment of tobacco addiction. Current Drug Abu- se Reviews, 7(3), 157–164. DOI: 10.2174/1874473708666150107121331
  32. Flanagan T.W., & Nichols C.D. (2018). Psychedelics as anti-inflammatory agen- ts. International Review of Psychiatry, 30(4), 363–375. DOI: 10.1080/09540261.2018.148182
  33. Feduccia A.A., & Mithoefer M.C. (2018). MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Progress in Neuro-Psychopharmacology and Biological Psychiatry, 84, 221–228.
  34. Ketamine enhances novel object recognition memory reconsolidation via the BDNF/TrkB pathway in mice. Physiology & Behavior, 242, 113626.
  35. Fan, J.-F., Tang, Z.-H., Wang, S.-Y., Lei, S., Zhang, B., & Tian, S.-W. (2021).
  36. Vollenweider F.X., Vollenweider-Scherpenhuyzen M.F.I., Bäbler A., Vogel H., & Hell D. (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action: Neuro Report, 9(17), 3897–3902. DOI: 10.1097/00001756-199812010-0002
  37. Watts R., Day C., Krzanowski J., Nutt D., & Carhart-Harris R. (2017). Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treat- ment-Resistant Depression. Journal of Humanistic Psychology, 57(5), 520–564. DOI: 10.1177/002216781770958
  38. Zarate C.A., Singh J.B., Carlson P.J., Brutsche N.E., Ameli R., Luckenbaugh D.A., Charney D.S., & Manji H.K. (2006). A Randomized Trial of an N-methyl-D-a- spartate Antagonist in Treatment-Resistant Major Depression. Archives of General Psychiatry, 63(8), 856.
  39. Zeifman R.J., Singhal N., Breslow L., & Weissman C.R. (2021). On the Relation- ship between Classic Psychedelics and Suicidality: A Systematic Review. ACS Phar- macology & Translational Science, 4(2), 436–451.
  40. Zhou W., Wang N., Yang C., Li X.-M., Zhou Z.-Q., & Yang J.-J. (2014). Keta- mine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontalcortex. European Psychiatry, 29(7), 419–423.
  41. Diazgranados N., Ibrahim L., Brutsche N.E., Newberg A., Kronstein P., Kha- life S., Kammerer W.A., Quezado Z., Luckenbaugh D.A., Salvadore G., Ma- chado-Vieira R., Manji H.K., & Zarate C.A. (2010). A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar De- pression. Archives of General Psychiatry, 67(8), 793.
  42. Díaz J.L. (2010). Sacred plants and visionary consciousness. Phenomenology and the Cognitive Sciences, 9(2), 159–170.
  43. Deane G. (2020). Dissolving the self: Active inference, psychedelics, and ego-dissolution. Philosophy and the Mind Sciences, 1(I), 1–27.
  44. De Vos, C. M. H., Mason, N. L., & Kuypers, K. P. C. (2021). Psychedelics and Neuro- plasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. Frontiers in Psychiatry, 12, 724606.
  45. De La Torre R., Farré M., Ortuño J., Mas M., Brenneisen R., Roset P.N., Segura J., & Camí J. (2000). Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans: Non-linear pharmacokinetics of MDMA. British Journal of Clinical Pharmacology, 49(2), 104–109.
  46. Daws R.E., Scott G., Soreq E., Leech R., Hellyer P.J., & Hampshire A. (2020). Opti- misation of functional network resources when learning behavioural strategies for perfor- ming complex tasks. Neuroscience. [Preprint] DOI: 10.1101/2020.06.17.156570
  47. Davis A.K., Barrett F.S., May D.G., Cosimano M.P., Sepeda N.D., Johnson M.W., Finan P.H., & Griffiths R.R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 78(5), 481.
  48. Das R.K., Gale G., Walsh K., Hennessy V.E., Iskandar G., Mordecai L.A., Brandner B., Kindt M., Curran H.V., & Kamboj S.K. (2019). Ketamine can reduce harmful drin- king by pharmacologically rewriting drinking memories. Nature Communications, 10(1), 5187.
  49. Nichols D.E. (1986). Differences Between the Mechanism of Action of MDMA, MBDB, and the Classic Hallucinogens. Identification of a New Therapeutic Class: Entactogens. Journal of Psychoactive Drugs, 18(4), 305–313. DOI: 10.1080/02791072.1986.1047236
  50. Nichols D.E. (2004). Hallucinogens. Pharmacology & Therapeutics, 101(2), 131–181.
  51. Nour M.M., Evans L., Nutt D., & Carhart-Harris R.L. (2016). Ego-Dissolution and Psychedelics: Validation of the Ego-Dissolution Inventory (EDI). Frontiers in Human Neuroscience, 10, 269.
  52. Palhano-Fontes F., Barreto D., Onias H., Andrade K.C., Novaes M.M., Pes- soa J.A., Mota-Rolim S.A., Osório F.L., Sanches R., Dos Santos R.G., Tófoli L.F., De Oliveira Silveira G., Yonamine M., Riba J., Santos F.R., Silva-Junior A.A., Alchieri J.C., Galvão-Coelho N.L., Lobão-Soares B., Hallak J.E.C., Ar- coverde E., Maia-de-Oliveira J.P., & Araújo D.B. (2019). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomi- zed placebo-controlled trial. Psychological Medicine, 49(4), 655–663. DOI: 10.1017/S003329171800135
  53. Papakostas, G. I., Salloum, N. C., Hock, R. S., Jha, M. K., Murrough, J. W., Ma- thew, S. J., Iosifescu, D. V., & Fava, M. (2020). Efficacy of Esketamine Augmenta- tion in Major Depressive Disorder: A Meta-Analysis. The Journal of Clinical Psychia- try, 81(4).
  54. Phelps J. (2017). Developing Guidelines and Competencies for the Training of Psychedelic Therapists. Journal of Humanistic Psychology, 57(5), 450–487. DOI: 10.1177/002216781771130
  55. Quednow B.B., Kometer M., Geyer M.A., & Vollenweider F.X. (2012). Psilocy- bin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ke- tanserin in Healthy Human Volunteers. Neuropsychopharmacology, 37(3), 630–640.
  56. Radiske A., Rossato J.I., Gonzalez M.C., Köhler C.A., Bevilaqua L.R., & Camma- rota M. (2017). BDNF controls object recognition memory reconsolidation. Neurobio- logy of Learning and Memory, 142, 79–84.
  57. Richards W.A. (2017). Psychedelic Psychotherapy: Insights From 25 Years of Research. Journal of Humanistic Psychology, 57(4), 323–337. DOI: 10.1177/002216781667099
  58. Rowland L.M., Astur R.S., Jung R.E., Bustillo J.R., Lauriello J., & Yeo R.A. (2005). Selective Cognitive Impairments Associated with NMDA Receptor Blocka- de in Humans. Neuropsychopharmacology, 30(3), 633–639.
  59. Sassano-Higgins S., Baron D., Juarez G., Esmaili N., & Gold M. (2016). A REVIEW OF KETAMINE ABUSE AND DIVERSION: Review: Ketamine. Depression and Anxiety, 33(8), 718–727.
  60. Schenk S. (2009). MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research. Neuropsychobiology, 60(3–4), 130–136. DOI: 10.1159/00025354
  61. Schlag A.K., Aday J., Salam I., Neill J.C., & Nutt D.J. (2022). Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology, 36(3), 258–272.
  62. Smigielski L., Kometer M., Scheidegger M., Krähenmann R., Huber T., & Vol- lenweider F.X. (2019). Characterization and prediction of acute and sustained respon- se to psychedelic psilocybinin a mindfulness group retreat. Scientific Reports, 9(1), 14914.
  63. Sripada R.K., King A.P., Garfinkel S.N., Wang X., Sripada C.S., Welsh R.C., & Liberzon I. (2012). Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. Journal of Psychiatry and Neuroscience, 37(4), 241–249.
  64. Vizeli P., & Liechti M.E. (2017). Safety pharmacology of acute MDMA administra- tion in healthy subjects. Journal of Psychopharmacology, 31(5), 576–588. DOI: 10.1177/026988111769156

Francesco Dente, Gli psichedelici: quanto è efficace e sicuro il loro possibile impiego in psichiatriae psicoterapia? Lo stato delle evidenze in "PNEI REVIEW" 1/2023, pp 89-105, DOI: 10.3280/PNEI2023-001006