Depressive DisordersNeuroimaging & Brain MeasuresAyahuasca

The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging

This systematic review (s=28, 2016) concludes that ayahuasca seems to have low toxicity, but that the myriad reported therapeutic benefits stand in need of replication.

Authors

  • Jamie Hallak
  • Rafael dos Santos
  • José Carlos Bouso

Published

Journal of Psychopharmacology
meta Study

Abstract

Rationale

In recent decades, the use of ayahuasca (AYA) - a β-carboline- and dimethyltryptamine-rich hallucinogenic botanical preparation traditionally used by Northwestern Amazonian tribes for ritual and therapeutic purposes - has spread from South America to Europe and the USA, raising concerns about its possible toxicity and hopes of its therapeutic potential. Thus, it is important to analyze the acute, subacute, and long-term effects of AYA to assess its safety and toxicity.

Objectives

The purpose of this study was to conduct a systematic review of human studies assessing AYA effects on psychiatric symptoms, neuropsychological functioning, and neuroimaging.

Methods

Papers published until 16 December 2015 were included from PubMed, LILACS and SciELO databases following a comprehensive search strategy and pre-determined set of criteria for article selection.

Results

The review included 28 full-text articles. Acute AYA administration was well tolerated, increased introspection and positive mood, altered visual perceptions, activated frontal and paralimbic regions and decreased default mode network activity. It also improved planning and inhibitory control and impaired working memory, and showed antidepressive and antiaddictive potentials. Long-term AYA use was associated with increased cortical thickness of the anterior cingulate cortex and cortical thinning of the posterior cingulate cortex, which was inversely correlated to age of onset, intensity of prior AYA use, and spirituality. Subacute and long-term AYA use was not associated with increased psychopathology or cognitive deficits, being associated with enhanced mood and cognition, increased spirituality, and reduced impulsivity.

Conclusions

Acute, subacute, and long-term AYA use seems to have low toxicity. Preliminary studies about potential therapeutic effects of AYA need replication due to their methodological limitations.

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Research Summary of 'The current state of research on ayahuasca: A systematic review of human studies assessing psychiatric symptoms, neuropsychological functioning, and neuroimaging'

Introduction

Ayahuasca (AYA) is a botanical hallucinogen traditionally used in Amazonian ritual contexts and, more recently, as a sacrament within syncretic Brazilian religions such as Santo Daime and União do Vegetal (UDV). The brew combines Banisteriopsis caapi, which contains reversible monoamine oxidase A (MAO-A) inhibitors (β-carbolines such as harmine and tetrahydroharmine), with Psychotria viridis, a source of the serotonergic agonist dimethyltryptamine (DMT). When taken together, the β-carbolines allow orally ingested DMT to reach the central nervous system and produce psychoactive effects that typically peak around 1.5–2 hours and last roughly 4–6 hours. Previous human studies and reviews suggested AYA has moderate, short-lived physiological effects and that ritual consumption is not generally associated with psychopathology or cognitive deficits, but many earlier studies were limited by small samples, a focus on experienced ritual participants, or a lack of neuroimaging data. Dos Santos and colleagues set out to update and extend prior reviews by performing a systematic review of human studies published up to 16 December 2015 that assessed acute, subacute, and long-term effects of ayahuasca on psychiatric symptoms, neuropsychological functioning, and neuroimaging. The objective was to synthesise evidence on safety, tolerability, cognitive effects, neural correlates and preliminary therapeutic signals (for example antidepressive or antiaddictive effects), while noting methodological limitations that constrain causal inference and generalisability.

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Study Details

References (57)

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Serotonergic psychedelics temporarily modify information transfer in humans

Alonso, J. N., Romero, S., Mañanas, M. A. et al. · International Journal of Neuropsychopharmacology (2015)

Health status of ayahuasca users

Barbosa, P., Mizumoto, S., Bogenschutz, M. P. et al. · Drug Testing and Analysis (2012)

Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles

Tracy, D., Baumeister, D., Barnes, G. et al. · Therapeutic Advances in Psychopharmacology (2014)

Classic hallucinogens in the treatment of addictions

Bogenschutz, M. P., Johnson, M. W. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2016)

Therapeutic mechanisms of classic hallucinogens in the treatment of addictions: from indirect evidence to testable hypotheses

Bogenschutz, M. P., Pommy, J. A. · Drug Testing and Analysis (2012)

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Bouso, J. C., Fábregas, J. M., Antonijoan, R. M. et al. · Psychopharmacology (2013)

Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study

Bouso, J. C., González, D., Fondevila, S. et al. · PLOS ONE (2012)

Dimethyltryptamine (DMT): Subjective effects and patterns of use among Australian recreational users

Cakic, V., Potkonyak, J., Marshall, A. · Drug and Alcohol Dependence (2010)

67 cited
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
Show all 57 references
The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

Carhart-Harris, R. L., Leech, R., Shanahan, M. et al. · Frontiers in Human Neuroscience (2014)

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin

Carhart-Harris, R. L., Leech, R., Williams, T. M. et al. · British Journal of Psychiatry (2018)

202 cited
Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors

Carter, O., Burr, D. C., Pettigrew, J. D. et al. · Journal of Cognitive Neuroscience (2006)

Lysergic acid diethylamide: side effects and complications

Cohen, S. · Journal of Nervous and Mental Disease (1980)

Ayahuasca in adolescence: a preliminary psychiatric assessment

da Silveira, D. X., Doering-Silveira, E., Grob, C. S. et al. · Journal of Psychoactive Drugs (2005)

Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion

De Araujo, D. B., Ribeiro, S., Cecchi, G. A. et al. · Human Brain Mapping (2011)

Report on psychoactive drug use among adolescents using ayahuasca within a religious context

Doering-Silveira, E., Grob, C. S., Dobkin de Rios, M. et al. · Journal of Psychoactive Drugs (2005)

114 cited
Safety and Side Effects of Ayahuasca in Humans-An Overview Focusing on Developmental Toxicology

Dos Santos, R. G. · Journal of Psychoactive Drugs (2013)

Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

Dos Santos, R. G., Osório, F. L., Crippa, J. A. et al. · brazilian Journal of Psychiatry (2016)

130 cited
Assessment of addiction severity among ritual users of ayahuasca

Fábregas, J. M., González, D., Fondevila, S. et al. · Drug and Alcohol Dependence (2010)

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Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids

Gable, R. S. · Addiction (2006)

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)

Psychedelics and schizophrenia

González-Maeso, J., Sealfon, S. C. · Trends in Neuroscience (2009)

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)

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)

Psilocybin biases facial recognition, goal-directed behavior, and mood state toward positive relative to negative emotions through different serotonergic subreceptors

Kometer, M., Schmidt, A., Bachmann, R. et al. · Biological Psychiatry (2012)

Psilocybin-induced decrease in amygdala reactivity correlates with enhanced positive mood in healthy volunteers

Kraehenmann, R., Preller, K. H., Scheidegger, M. et al. · Biological Psychiatry (2015)

Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

Labate, B. C. · Journal of Psychoactive Drugs (2011)

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Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions

Liester, M. B., Prickett, J. I. · Journal of Psychoactive Drugs (2012)

Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence: qualitative results

Loizaga-Velder, A., Verres, R. · Journal of Psychoactive Drugs (2014)

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
Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Osório, F. L., Sanches, R. F., Macedo, L. et al. · brazilian Journal of Psychiatry (2015)

420 cited
The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network

Palhano-Fontes, F., Andrade, K. C., Tófoli, L.F. et al. · PLOS ONE (2015)

Effects of the South American psychoactive beverage ayahuasca on regional brain electrical activity in humans: a functional neuroimaging study using low-resolution electromagnetic tomography

Riba, J., Anderer, P., Jané, F. et al. · Neuropsychobiology (2004)

Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively

Riba, J., Rodríguez-Fornells, A., Barbanoj, M. J. · Psychopharmacology (2002)

70 cited
Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers

Riba, J., Urbano, G., Morte, A. et al. · Psychopharmacology (2001)

Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics

Riba, J., Valle, M., Urbano, G. et al. · Journal of Pharmacology and Experimental Therapeutics (2003)

Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson’s disease

Samoylenko, V., Rahman, M. M., Tekwani, B. L. et al. · Journal of Ethnopharmacology (2010)

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression a SPECT study

Sanches, R. F., Osório, F. L., Dos Santos, R. G. et al. · Journal of Clinical Psychopharmacology (2016)

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Acute Biphasic Effects of Ayahuasca

Schenberg, E. E., Alexandre, J. F. M., Filev, R. et al. · PLOS ONE (2015)

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Acute effects of lysergic acid diethylamide in healthy subjects

Schmid, Y., Enzler, F., Gasser, P. et al. · Biological Psychiatry (2015)

Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism

Schwarz, M. J., Houghton, P. J., Rose, S. et al. · Pharmacology Biochemistry and Behavior (2003)

93 cited
Exploring the therapeutic potential of Ayahuasca: acute intake increases mindfulness-related capacities

Soler, J., Elices, M., Franquesa, A. et al. · Psychopharmacology (2015)

Drug models of schizophrenia

Steeds, H., Carhart-Harris, R. L., Stone, J. M. · Therapeutic Advances in Psychopharmacology (2014)

Adverse Reactions to Psychedelic Drugs - A Review of the Literature

Strassman, R. J. · Journal of Nervous and Mental Disease (1984)

273 cited
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

Studerus, E., Kometer, M., Hasler, F. et al. · Journal of Psychopharmacology (2010)

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Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report

Szmulewicz, A. G., Valerio, M. P., Smith, J. M. · International Journal of Bipolar Disorders (2015)

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)

Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis

Vollenweider, F. X., Leenders, K. L., Maguire, P. et al. · Neuropsychopharmacology (1997)

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)

Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, peyote, ibogaine and ayahuasca

Winkelman, M. J. · Current Drug Abuse Reviews (2014)

Effects of psilocybin on time perception and temporal control of behaviour in humans

Wittmann, M., Carter, O., Hasler, F. et al. · Journal of Psychopharmacology (2007)

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