Download PDF
Pharmacopsychiatry 2021; 54(04): 191-199
DOI: 10.1055/a-1486-7386
Review

The Potential Role of Psychedelic Drugs in Mental Health Care of the Future

Gerhard Gründer 
1   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
2   OVID Health Systems GmbH, Berlin, Germany
,
Henrik Jungaberle 
2   OVID Health Systems GmbH, Berlin, Germany
3   MIND Foundation gGmbH, Berlin, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), or dimethyltryptamine (DMT), as well as psychoactive drugs that trigger phenomenologically- related experiences like 3,4-methylenedioxymethamphetamine (MDMA) and ketamine, belong to the most promising treatment approaches in contemporary psychiatry. Psychedelic-assisted psychotherapy is not only a new treatment paradigm in psychopharmacology, but it also requires a redefinition of psychotherapeutic processes and the contextualization of psychopharmacological interventions within a new treatment infrastructure. Crucial for future practice and research in the field are (1) informed patient referral and co-treatment practices, (2) screening (e. g., choosing the right patients for these therapies), (3) the dosing preparation sessions, (4) the assisted dosing sessions as well as after-care procedures such as (5) psychological integration and (6) supporting the development of structured patient communities. Definition of future treatment delivery infrastructures and requirements for therapist training are further challenges for research and practice. Finally, the implementation of psychedelic-assisted psychotherapy in routine mental health care must be embedded into public communication about the potential and risks of these innovative therapeutic approaches. This paper provides a synopsis of challenges for practitioners, researchers, and regulators to be addressed in the approval processes of psychedelics.



Publication History

Received: 15 February 2021
Received: 06 April 2021

Accepted: 13 April 2021

Article published online:
12 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Heifets BD, Malenka RC. Disruptive psychopharmacology. JAMA Psychiatry 2019; 76: 775-776
    CrossrefPubMedGoogle Scholar
  • 2 Mithoefer MC, Feduccia AA, Jerome L. et al. MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology 2019; 236: 2735-2745
    CrossrefPubMedGoogle Scholar
  • 3 El-Seedi HR, De Smet PAGM, Beck O. et al. Prehistoric peyote use: Alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas. J Ethnopharmacol 2005; 101: 238-242
    CrossrefPubMedGoogle Scholar
  • 4 Nichols DE, Walter H. The history of psychedelics in psychiatry. Pharmacopsychiatry 2020; DOI: 10.1055/a-1310-3990. Online ahead of print
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Guttmann E. Artificial psychoses produced by mescaline. J Ment Sci 1936; 82: 203-221
    CrossrefPubMedGoogle Scholar
  • 6 Nayak S, Johnson MW. Psychedelics and psychotherapy. Pharmacopsychiatry 2020; DOI: 10.1055/a-1312-7297. Online ahead of print
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Gouzoulis-Mayfrank E, Schreckenberger M, Sabri O. et al. Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG. Neuropsychopharmacology 1999; 20: 565-581
    CrossrefPubMedGoogle Scholar
  • 8 Vollenweider FX, Leenders KL, Scharfetter C. et al. Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology 1997; 16: 357-372
    CrossrefPubMedGoogle Scholar
  • 9 Stoll WA. 11. Lysergsäure-diäthylamid, ein Phantastikum aus der Mutterkorngruppe. Schweiz Arch Neurol Psychiatr 1947; 60: 279-323
    PubMedGoogle Scholar
  • 10 Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2: 349-352
    CrossrefPubMedGoogle Scholar
  • 11 Kuhn R. Über die Behandlung depressiver Zustände mit einem Iminodibenzylderivat (G 22355). Schweiz Med Wochenschr 1957; 87: 1135-1140
    PubMedGoogle Scholar
  • 12 Delay J, Deniker J. Neuroleptic effects of chlorpromazine in therapeutics of neuropsychiatry. J Clin Exp Psychopathol 1955; 16: 104-112
    PubMedGoogle Scholar
  • 13 Sternbach LH. The benzodiazepine story. J Med Chem 1979; 22: 1-7
    CrossrefPubMedGoogle Scholar
  • 14 Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry 2017; 4: 409-418
    CrossrefPubMedGoogle Scholar
  • 15 Trivedi MH, Rush AJ, Wisniewski SR. et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am J Psychiatry 2006; 163: 28-40
    CrossrefPubMedGoogle Scholar
  • 16 Rush AJ, Trivedi MH, Wisniewski SR. et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006; 354: 1231-1242
    CrossrefPubMedGoogle Scholar
  • 17 Rush AJ, Trivedi MH, Wisniewski SR. et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163: 1905-1917
    CrossrefPubMedGoogle Scholar
  • 18 Alboni S, van Dijk RM, Poggini S. et al. Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment. Mol Psychiatry 2017; 22: 552-561
    CrossrefPubMedGoogle Scholar
  • 19 Madsen MK, Fisher PM, Burmester D. et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. GM. Neuropsychopharmacology 2019; 44: 1328-1334
    CrossrefPubMedGoogle Scholar
  • 20 Mertens LJ, Preller KH. Classical psychedelics as therapeutics in psychiatry — current clinical evidence and potential therapeutic mechanisms in substance use and mood disorders. Pharmacopsychiatry 2021; Online ahead of print DOI: 10.1055/a-1341-1907.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Hartogsohn I. Constructing drug effects: A history of set and setting. Drug Science, Policy and Law 2017; 3 205032451668332 DOI: 10.1177/2050324516683325.
    CrossrefPubMedGoogle Scholar
  • 22 Carhart-Harris RL, Roseman L, Haijen E. et al. Psychedelics and the essential importance of context. J Psychopharmacol 2018; 32: 725-731
    CrossrefPubMedGoogle Scholar
  • 23 Vollenweider FX, Preller KH. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci 2020; 21: 611-624
    CrossrefPubMedGoogle Scholar
  • 24 Olson DE. The subjective effects of psychedelics may not be necessary for their enduring therapeutic effects. ACS Pharmacology & Translational Science 2020; DOI: 10.1021/acsptsci.0c00192.
    CrossrefPubMedGoogle Scholar
  • 25 Yaden DB, Griffiths RR. The subjective effects of psychedelics are necessary for their enduring therapeutic effects. ACS Pharmacology & Translational Science 2020; DOI: 10.1021/acsptsci.0c00194.
    CrossrefPubMedGoogle Scholar
  • 26 Zinberg NE. Drug, Set, and Setting: The Basis for Controlled Intoxicant Use. New Haven: Yale University Press; 1986
    Google Scholar
  • 27 Gage SH, Sumnall HR. Rat Park: How a rat paradise changed the narrative of addiction. Addiction 2019; 114: 917-922
    CrossrefPubMedGoogle Scholar
  • 28 Swanson LR. Unifying theories of psychedelic drug effects. Front Pharmacology 2018; 9: 172
    CrossrefPubMedGoogle Scholar
  • 29 Garcia-Romeu A, Richards WA. Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. Int Rev Psychiatry 2018; 30: 291-316
    CrossrefPubMedGoogle Scholar
  • 30 Wolff M, Evens R, Mertens LJ. et al. Learning to let go: a cognitive-behavioral model of how psychedelic therapy promotes acceptance. Front Psychiatry 2020; 11: 5
    CrossrefPubMedGoogle Scholar
  • 31 Majić T, Jungaberle H, Schmidt T. et al. Psychotherapie mit adjuvanter Gabe von serotonergen psychoaktiven Substanzen—Möglichkeiten und Hindernisse. Fortschritte Neurol Psychiatr 2017; 85: 383-392
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Trope A, Anderson BT, Hooker AR. et al. Psychedelic-assisted group therapy: a systematic review. J Psychoactive Drugs 2019; 51: 174-188
    CrossrefPubMedGoogle Scholar
  • 33 Hutten NRPW, Mason NL, Dolder PC. et al. Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study. Eur Neuropsychopharmacol 2020; 41: 81-91
    CrossrefPubMedGoogle Scholar
  • 34 Lea T, Amada N, Jungaberle H. et al. Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders. Psychopharmacology 2020; 237: 1521-1532
    CrossrefPubMedGoogle Scholar
  • 35 Kaertner LS, Steinborn MB, Kettner H. et al. Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing. Scientific Reports 2021; 11: 1941
    CrossrefPubMedGoogle Scholar
  • 36 Hofmann A. LSD My Problem Child—Insights/Outlooks. Oxford: Oxford University Press; 2018
    Google Scholar
  • 37 Busch AK, Johnson WC. L.S.D. 25 as an aid in psychotherapy; Preliminary report of a new drug. Dis Nerv Syst 1950; 11: 241-243
    PubMedGoogle Scholar
  • 38 Carhart-Harris RL. How do psychedelics work?. Curr Opin Psychiatry 2019; 32: 16-21
    CrossrefPubMedGoogle Scholar
  • 39 Gasser P, Holstein D, Michel Y. et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis 2014; 202: 513-520
    CrossrefPubMedGoogle Scholar
  • 40 Liechti ME. Modern clinical research on LSD. Neuropsychopharmacology 2017; 42: 2114-2127
    CrossrefPubMedGoogle Scholar
  • 41 Belser AB, Agin-Liebes G, Swift TC. et al. Patient experiences of psilocybin-assisted psychotherapy: an interpretative phenomenological analysis. J Humanist Psychol 2017; 57: 354-388
    CrossrefPubMedGoogle Scholar
  • 42 Griffiths RR, Johnson MW, Richards WA. et al. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology 2011; 218: 649-665
    CrossrefPubMedGoogle Scholar
  • 43 Millière R. Looking for the self: phenomenology, neurophysiology and philosophical significance of drug-induced ego dissolution. Front Hum Neurosci 2017; 11: 245
    CrossrefPubMedGoogle Scholar
  • 44 Orlinsky DE. The “generic model of psychotherapy” after 25 years: evolution of a research-based metatheory. J Psychother Integration 2009; 19: 319-339
    CrossrefPubMedGoogle Scholar
  • 45 Orlinsky DE, Grawe K, Parks BK. Process and outcome in psychotherapy: Noch einmal. In: Handbook of Psychotherapy and Behavior Change. 4th ed. Oxford: John Wiley & Sons, Oxford; 1994: 270-376
    Google Scholar
  • 46 Mithoefer MC, Mithoefer A, Jerome L. et al. A Manual for MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder. Version 8.1., May 22, 2017, https://s3-us-west-1.amazonaws.com/mapscontent/research-archive/mdma/TreatmentManual_MDMAAssistedPsychotherapyVersion+8.1_22+Aug2017.pdf, Access: March 22nd, 2021
    PubMed
  • 47 Phelps J. Developing guidelines and competencies for the training of psychedelic therapists. J Humanist Psychol 2017; 57: 450-487
    CrossrefPubMedGoogle Scholar
  • 48 Grof S. LSD Psychotherapy. 2nd ed Hunter House; 1994
    Google Scholar
  • 49 Nielson EM, Guss J. The influence of therapists’ first-hand experience with psychedelics on psychedelic-assisted psychotherapy research and therapist training. J Psychedel Studies 2018; 2: 64-73
    CrossrefPubMedGoogle Scholar
  • 50 Luoma JB, Sabucedo P, Eriksson J. et al. Toward a contextual psychedelic-assisted therapy: perspectives from acceptance and commitment therapy and contextual behavioral science. J Context Behav Sci 2019; 14: 136-145
    CrossrefPubMedGoogle Scholar
  • 51 Labate BC, Jungaberle H. The Internationalization of Ayahuasca. Labate BC, Jungaberle H. Münster: LIT Verlag; 2011
    Google Scholar
  • 52 Letcher A. Mad thoughts on mushrooms: discourse and power in the study of psychedelic consciousness. Anthropol Conscious 2007; 18: 74-98
    CrossrefPubMedGoogle Scholar
  • 53 Aday JS, Bloesch EK, Davoli CC. 2019: a year of expansion in psychedelic research, industry, and deregulation. Drug Science, Policy and Law 2020; 6: 205032452097448
    CrossrefPubMedGoogle Scholar
  • 54 Jungaberle H, Thal S, Zeuch A. et al. Positive psychology in the investigation of psychedelics and entactogens: a critical review. Neuropharmacol 2018; 142: 179-199
    CrossrefPubMedGoogle Scholar
  • 55 Aday JS, Davoli CC, Bloesch EK. Psychedelics and virtual reality: parallels and applications. Ther Adv Psychopharmacol 2020; 10: 2045125320948356
    CrossrefPubMedGoogle Scholar
  • 56 Walsh Z, Thiessen MS. Psychedelics and the new behaviourism: considering the integration of third-wave behaviour therapies with psychedelic-assisted therapy. Int Rev Psychiatry 2018; 30: 343-349
    CrossrefPubMedGoogle Scholar
  • 57 Aday JS, Mitzkovitz CM, Bloesch EK. et al. Long-term effects of psychedelic drugs: A systematic review. Neurosci Biobehav Rev 2020; 113: 179-189
    CrossrefPubMedGoogle Scholar
  • 58 Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alc Abuse 2017; 43: 55-60
    CrossrefPubMedGoogle Scholar
  • 59 Breeksema JJ, Niemeijer AR, Krediet E. et al. Psychedelic treatments for psychiatric disorders: a systematic review and thematic synthesis of patient experiences in qualitative studies. CNS Drugs 2020; 34: 925-946
    CrossrefPubMedGoogle Scholar
  • 60 Roseman L, Haijen E, Idialu-Ikato K. et al. Emotional breakthrough and psychedelics: validation of the Emotional Breakthrough Inventory. J Psychopharmacol 2019; 33: 1076-1087
    CrossrefPubMedGoogle Scholar
  • 61 Carhart-Harris RL, Leech R, Williams TM. et al. Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin. Br J Psychiatry 2012; 200: 238-244
    CrossrefPubMedGoogle Scholar
  • 62 Bouso JC, dos Santos RG, Alcázar-Córcoles MÁ. et al. Serotonergic psychedelics and personality: A systematic review of contemporary research. Neurosci Biobehav Rev 2018; 87: 118-132
    CrossrefPubMedGoogle Scholar
  • 63 MacLean KA, Johnson MW, Griffiths RR. Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. J Psychopharmacol 2011; 25: 1453-1461
    CrossrefPubMedGoogle Scholar
  • 64 Wagner MT, Mithoefer MC, Mithoefer AT. et al. Therapeutic effect of increased openness: Investigating mechanism of action in MDMA-assisted psychotherapy. J Psychopharmacol 2017; 31: 967-974
    CrossrefPubMedGoogle Scholar
  • 65 Griffiths RR, Richards WA, McCann U. et al. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 2006; 187: 268-292
    CrossrefPubMedGoogle Scholar
  • 66 Mackenzie R. What can neuroscience tell us about the potential of psychedelics in healthcare? How the neurophenomenology of psychedelics research could help us to flourish throughout our lives, as well as to enhance our dying. Curr Drug Abuse Rev 2014; 7: 136-145
    CrossrefPubMedGoogle Scholar