Anxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Palliative & End-of-Life DistressSchizophreniaNeuroimaging & Brain MeasuresChronic PainDepressive Disorders

Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences

This review (2015) looks at the influence of subjective (therapeutic) effects on the (treatment) outcomes of psychedelic experiences. This is put in context of the neuronal mechanism of psychedelics, but that relationship is still something that we know little about.

Authors

  • Tomislav Majic

Published

Journal of Clinical Psychopharmacology
meta Study

Abstract

Interest in the therapeutic potential of psychedelic substances has recently resumed. During an early phase of human psychedelic research, their therapeutic application in different pathologies had been suggested, and the first evidence for efficacy was provided. The range of recent clinical applications of psychedelics spans from cluster headaches and obsessive-compulsive disorder to addiction and the treatment of fear and anxiety in patients suffering from terminal illness, indicating potentially different therapeutic mechanisms. A variety of approaches in psychotherapy emphasize subjective experiences, such as so-called peak experiences or afterglow phenomena, as differentially mediating therapeutic action. This review aims to re-evaluate earlier and recent concepts of how psychedelic substances may exert beneficial effects. After a short outline of neurophenomenological aspects, we discuss different approaches to how psychedelics are used in psychotherapy. Finally, we summarize evidence for the relationship between subjective experiences and therapeutic success. While the distinction between pharmacological and psychological action obviously cannot be clear-cut, they do appear to contribute differently from each other when their effects are compared with regard to pathologies.

Available with Blossom Pro

Research Summary of 'Peak experiences and the afterglow phenomenon: when and how do therapeutic effects of hallucinogens depend on psychedelic experiences'

Introduction

Over the past two decades there has been a renewed scientific interest in hallucinogenic substances such as psilocybin and ketamine. Majić and colleagues place this revival against a history in which psychedelics were used both to model psychosis and as therapeutic tools; modern neuroimaging and improved methodological standards have prompted fresh hypotheses about their mechanisms. Earlier work emphasised that psychedelic-assisted therapy produces altered states of consciousness (ASCs), including intense mystical or peak experiences and a subsequent ‘‘afterglow’’, and proposed these subjective phenomena as central to therapeutic benefit. More recent approaches have also posited pharmacological, experience-independent mechanisms, particularly in the case of ketamine. This review aims to re-evaluate historical and contemporary concepts about how psychedelics may produce therapeutic effects. Majić and colleagues focus primarily on classical serotonergic hallucinogens and include specific reference to ketamine, while excluding MDMA and ibogaine from detailed consideration. They outline neurophenomenological issues, survey therapeutic models and clinical applications, and examine the evidence linking particular subjective experiences (for example, mystical peak experiences and afterglow periods) to clinical outcomes.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Full Text PDF

Full Paper PDF

Pro members can view the original manuscript directly in the browser.

Study Details

References (45)

Papers cited by this study that are also in Blossom

Treatment of acute opioid withdrawal with ibogaine

Alper, K. R., Lotsof, H. S., Frenken, G. M. N. et al. · The American Journal on Addictions (2010)

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)

Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis

Carhart-Harris, R. L., Leech, R., Erritzoe, D. et al. · Schizophrenia Bulletin (2012)

241 cited
Therapeutic infusions of ketamine: do the psychoactive effects matter?

Dakwar, E., Anerella, C., Hart, C. L. et al. · Drug and Alcohol Dependence (2014)

Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases

Gasser, P., Holstein, D., Michel, Y. et al. · Journal of Nervous and Mental Disease (2014)

594 cited
Serotonin research: contributions to understanding psychoses

Geyer, M. A., Vollenweider, F. X. · Trends in Pharmacological Sciences (2008)

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance

Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)

Show all 45 references
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

DPT as an adjunct in psychotherapy of alcoholics

Grof, S., Soskin, R. A., Richards, W. A. et al. · Pharmacopsychiatry (1973)

Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Halberstadt, A. L., Geyer, M. A. · Neuropharmacology (2011)

Psychological and cognitive effects of long-term peyote use among Native Americans

Halpern, J. H., Sherwood, A. R., Hudson, J. I. et al. · Biological Psychiatry (2005)

Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament

Halpern, J. H., Sherwood, A. R., Passie, T. et al. · Medical Science Monitor (2008)

Psychedelic Agents in Creative Problem-Solving: A Pilot Study

Harman, W. W., McKim, R. H., Mogar, R. E. et al. · Psychological Reports (1966)

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)

Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V. et al. · Journal of Psychoactive Drugs (2007)

154 cited
Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)

A clinical study of LSD treatment in alcoholism

Ludwig, A., Levine, J., Stark, L. et al. · American Journal of Psychiatry (1969)

158 cited
Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)

Factor analysis of the mystical experience questionnaire: A study of experiences occasioned by the hallucinogen psilocybin

MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)

350 cited
Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Moreno, F. A., Wiegand, C. B., Taitano, E. K. et al. · Journal of Clinical Psychiatry (2006)

Broadband Cortical Desynchronization Underlies the Human Psychedelic State

Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J. et al. · Journal of Neuroscience (2013)

427 cited
A review of the clinical effects of psychotomimetic agents

Osmond, H. · Annals of the New York Academy of Sciences (2010)

296 cited
The pharmacology of lysergic acid diethylamide: a review

Passie, T., Halpern, J. H., Stichtenoth, D. O. et al. · CNS Neuroscience and Therapeutics (2008)

The pharmacology of psilocybin

Passie, T., Seifert, J., Schneider, U. et al. · Addiction Biology (2002)

The peak experience variable in DPT-assisted psychotherapy with cancer patients

Richards, W. A., Rhead, J. C., Dileo, F. B. et al. · Journal of Psychedelic Drugs (2012)

Effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in Santo Daime members

Santos, R. G., Landeira-Fernandez, J., Strassman, R. J. et al. · Journal of Ethnopharmacology (2007)

Unauthorized Research on Cluster Headache

Sewell, R. A. · Preprints (2008)

Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression

Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)

Hallucinogenic drugs in psychiatric research and treatment: perspectives and prospects

Strassman, R. J. · Journal of Nervous and Mental Disease (1995)

93 cited
Prediction of psilocybin response in healthy volunteers

Studerus, E., Gamma, A., Kometer, M. et al. · PLOS ONE (2012)

Psychometric evaluation of the altered states of consciousness rating scale (OAV)

Studerus, E., Gamma, A., Vollenweider, F. X. · PLOS ONE (2010)

Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada

Thomas, G., Lucas, P., Rielle Capler, N. et al. · Current Drug Abuse Reviews (2013)

The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)

Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)

Cited By (84)

Papers in Blossom that reference this study

The effects of psilocybin therapy versus escitalopram on cognitive bias: A secondary analysis of a randomized controlled trial

Henry, J., Giribaldi, B., Nutt, D. J. et al. · European Neuropsychopharmacology (2025)

Safety, tolerability and subjective effects of vaporized N,N-Dimethyltryptamine: A randomized double-blind clinical trial

Wießner, I., Falchi-Carvalho, M., Laborde, S. et al. · European Neuropsychopharmacology (2025)

Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression

Wall, M. B., Demetriou, L., Giribaldi, B. et al. · American Journal of Psychiatry (2025)

2 cited
Effects of psychedelics in older adults: A prospective cohort study

Kettner, H., Roseman, L., Gazzaley, A. et al. · The American Journal of Geriatric Psychiatry (2024)

12 cited
The ego in psychedelic drug action - ego defenses, ego boundaries, and the therapeutic role of regression

Buchborn, T., Kettner, H., Kartner, L. et al. · Frontiers in Neuroscience (2023)

History repeating: guidelines to address common problems in psychedelic science

Van Elk, M., Fried, E. I. · Therapeutic Advances in Psychopharmacology (2023)

94 cited
Show all 84 papers
Dynamic Functional Hyperconnectivity after Psilocybin Intake is Primarily Associated with Oceanic Boundlessness

Mortaheb, S., Fort, L. D., Mason, N. L. et al. · Biological Psychiatry (2023)

20 cited
Harnessing placebo: Lessons from psychedelic science

Pronovost-Morgan, C., Hartogsohn, I., Ramaekers, J. G. · Journal of Psychopharmacology (2023)

Dose-response relationships of LSD-induced subjective experiences in humans

Prugger, J., Hirschfeld, T., Majic, T. et al. · Neuropsychopharmacology (2023)

19 cited
Dosing and Therapeutic Conduct in Administration Sessions in Substance-Assisted Psychotherapy: A Systematized Review

Thal, S. B., Wieberneit, M., Sharbanee, J. M. et al. · Journal of Humanistic Psychology (2023)

4 cited
On the need for metaphysics in psychedelic therapy and research

Sjöstedt-Hughes, P. · Frontiers in Psychology (2023)

Altered States of Consciousness During Ceremonial San Pedro Use

Bohn, A., Kiggen, M. H. H., Uthaug, M. V. et al. · International Journal for the Psychology of Religion (2022)

Psychedelic Identity Shift: A Critical Approach to Set And Setting

Devenot, N., Seale-Feldman, A., Smith, E. et al. · Kennedy Institute of Ethics Journal (2022)

28 cited
The Altered States Database: Psychometric data from a systematic literature review

Prugger, J., Derdiyok, E., Dinkelacker, J. et al. · Scientific Data (2022)

Being no one, being One: The role of ego-dissolution and connectedness in the therapeutic effects of psychedelic experience

Kałużna, A., Schlosser, M., Gulliksen Craste, E. et al. · Journal of Psychedelic Studies (2022)

35 cited
Scoping Review of Experiential Measures from Psychedelic Research and Clinical Trials

Herrmann, Z., Earleywine, M., De Leo, J. et al. · Journal of Psychoactive Drugs (2022)

Towards an understanding of psychedelic-induced neuroplasticity

Calder, A. E., Hasler, G. · Neuropsychopharmacology (2022)

Neural Mechanisms and Psychology of Psychedelic Ego Dissolution

Stoliker, D., Egan, G. F., Friston, K. J. et al. · Pharmacological Reviews (2022)

Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling

Henningfield, J. E., Coe, M. A., Griffiths, R. R. et al. · Neuropharmacology (2022)

Virtual Reality as a Moderator of Psychedelic-Assisted Psychotherapy

Sekula, A. D., Downey, L., Puspanathan, P. · Frontiers in Psychology (2022)

19 cited
Great Expectations: Recommendations for improving the methodological rigor of psychedelic clinical trials

Aday, J. S., Heifets, B. D., Pratscher, S. D. et al. · Psychopharmacology (2021)

Day trip to hell: A mixed methods study of challenging psychedelic experiences

Johnstad, P. G. · Journal of Psychedelic Studies (2021)

43 cited
Novel Treatment Approaches for Substance Use Disorders: Therapeutic Use of Psychedelics and the Role of Psychotherapy

Johnson, M. W., Gründer, G., Betzler, F. et al. · Current Addiction Reports (2021)

Neuropsychological Functioning in Users of Serotonergic Psychedelics - A Systematic Review and Meta-Analysis

Basedow, L. A., Riemer, T. G., Reiche, S. et al. · Frontiers in Pharmacology (2021)

Psychedelics for Brain Injury: A Mini-Review

Khan, S. I., Carter, G. T., Aggarwal, S. K. et al. · Frontiers in Neuroscience (2021)

LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model

Wießner, I., Falchi, M., Palhano-Fontes, F. et al. · Psychological Medicine (2021)

Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment: The Case of Takiwasi Center

Rush, B., Marcus, O., García, S. et al. · Frontiers in Pharmacology (2021)

19 cited
A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

Sumner, R. L., Chacko, E., Mcmillan, R. et al. · Journal of Psychopharmacology (2021)

51 cited
Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice

Palhano-Fontes, F., Gorman, I., Nielson, E. M. et al. · Frontiers in Psychology (2021)

Dose-response relationships of psilocybin-induced subjective experiences in humans

Hirschfeld, T., Schmidt, T. T. · Journal of Psychopharmacology (2021)

LSD alters dynamic integration and segregation in the human brain

Luppi, A. I., Carhart-Harris, R. L., Roseman, L. et al. · NeuroImage (2021)

141 cited
Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

McCulloch, D. E-W., Madsen, M. K., Stenbæk, D. S. et al. · Journal of Psychopharmacology (2021)

Mood and cognition after administration of low LSD doses in healthy volunteers: A placebo controlled dose-effect finding study

Hutten, N. R. P. W., Mason, N. L., Dolder, P. C. et al. · European Neuropsychopharmacology (2020)

95 cited
Isness: Using Multi-Person VR to Design Peak Mystical Type Experiences Comparable to Psychedelics

Glowacki, D. R., Wonnacott, M. D., Freire, R. et al. · Association for Computing Machinery (2020)

32 cited
Subacute Effects of the Psychedelic Ayahuasca on the Salience and Default Mode Networks

Pasquini, L., Palhano-Fontes, F., Araújo, D. B. · Journal of Psychopharmacology (2020)

Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination

Jiménez-Garrido, D. F., Gómez-Sousa, M., Ona, G. et al. · Scientific Reports (2020)

Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Wolff, M., Evens, R., Mertens, L. J. et al. · Frontiers in Psychiatry (2020)

Persisting Reductions in Cannabis, Opioid, and Stimulant Misuse After Naturalistic Psychedelic Use: An Online Survey

Garcia-Romeu, A., Davis, A. K., Griffiths, R. R. et al. · Frontiers in Psychiatry (2020)

121 cited
Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)

Neuropharmacological modulation of the aberrant bodily self through psychedelics

Ho, J. T., Preller, K. H., Lenggenhager, B. · Neuroscience and Biobehavioral Reviews (2020)

REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Cessation and reduction in alcohol consumption and misuse after psychedelic use

Garcia-Romeu, A., Davis, A. K., Fire Erowid et al. · Journal of Psychopharmacology (2019)

211 cited
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

Johnson, M. W., Hendricks, P. S., Barrett, F. S. et al. · Pharmacology and Therapeutics (2019)

Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions

Richards, W. A., Garcia-Romeu, A. · International Review of Psychiatry (2018)

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression

Roseman, L., Demetriou, L., Wall, M. B. et al. · Neuropharmacology (2018)

143 cited
Psychedelics, meditation, and self-consciousness

Milliere, R., Carhart-Harris, R. L., Roseman, L. et al. · Frontiers in Psychology (2018)

Effects of psilocybin therapy on personality structure

Erritzoe, D., Roseman, L., Nour, M. R. et al. · Acta Psychiatrica Scandinavica (2018)

219 cited
Psychedelics promote structural and functional neural plasticity

Ly, C., Greb, A. C., Cameron, L. P. et al. · Cell Reports (2018)

Out of the box: A psychedelic model to study the creative mind

Kuypers, K. P. C. · Medical Hypotheses (2018)

Unifying theories of psychedelic drug effects

Swanson, L. R. · Frontiers in Pharmacology (2018)

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

Reiche, S., Hermle, L., Gutwinski, S. et al. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018)

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

82 cited
Psychedelics, personality and political perspectives

Nour, M. R., Evans, J., Carhart-Harris, R. L. · Journal of Psychoactive Drugs (2017)

164 cited
5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Bryson, A., Carter, O., Norman, T. et al. · International Journal of Neuropsychopharmacology (2017)

18 cited
Phenomenology, Structure, and Dynamic of Psychedelic States

Preller, K. H., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Classical hallucinogens and neuroimaging: A systematic review of human studies: hallucinogens and neuroimaging

Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · Neuroscience and Biobehavioral Reviews (2016)

Psychedelics in the treatment of unipolar mood disorders: a systematic review

Rucker, J., Young, A. H., Jelen, L. A. et al. · Journal of Psychopharmacology (2016)

The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens

Canal, C. E., Murnane, K. S. · Journal of Psychopharmacology (2016)

Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Tófoli, L. F., De Araujo, D. B. · International Review of Neurobiology (2016)

LSD-induced entropic brain activity predicts subsequent personality change

Lebedev, A. V., Kaelen, M., L€ Ovd En, M. et al. · Human Brain Mapping (2016)

292 cited
Psychedelics

Nichols, D. E. · Pharmacological Reviews (2016)

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca

McKenna, D., Riba, J. · Current Topics in Behavioral Neurosciences (2016)

Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

Kometer, M., Vollenweider, F. X. · Behavioral Neurobiology of Psychedelic Drugs (2016)

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.