Anxiety DisordersMicrodosingDepressive DisordersDMT

Chronic, Intermittent Microdoses of the Psychedelic N, N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents

This rat study (n=35) investigated the effects of microdosing DMT (1mg/kg) in rats and found that a chronic (∼2 months), intermittent (every third day) microdosing regimen facilitated fear extinction learning and reduced depressive immobility in the forced swim test without producing the anxiety-like effects characteristic of a high dose.

Authors

  • David Olson
  • Lindsay Cameron

Published

ACS Chemical Neuroscience
individual Study

Abstract

Introduction

Drugs capable of ameliorating symptoms of depression and anxiety while also improving cognitive function and sociability are highly desirable. Anecdotal reports have suggested that serotonergic psychedelics administered in low doses on a chronic, intermittent schedule, so-called “microdosing”, might produce beneficial effects on mood, anxiety, cognition, and social interaction.

Methods

Here, we test this hypothesis by subjecting male and female Sprague Dawley rats to behavioral testing following the chronic, intermittent administration of low doses of the psychedelic N,N-dimethyltryptamine (DMT).

Results

The behavioral and cellular effects of this dosing regimen were distinct from those induced following a single high dose of the drug. We found that chronic, intermittent, low doses of DMT produced an antidepressant-like phenotype and enhanced fear extinction learning without impacting working memory or social interaction. Additionally, male rats treated with DMT on this schedule gained a significant amount of body weight during the course of the study.

Discussion

Taken together, our results suggest that psychedelic microdosing may alleviate symptoms of mood and anxiety disorders, though the potential hazards of this practice warrant further investigation.

Available with Blossom Pro

Research Summary of 'Chronic, Intermittent Microdoses of the Psychedelic N, N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents'

Introduction

Mood and anxiety disorders are major contributors to global disability and current treatments are often slow to act and ineffective for many patients. Serotonergic psychedelics such as LSD, psilocybin and DMT have been explored as experimental therapeutics, but it is unclear whether full hallucinogenic doses are required for clinical benefit. Anecdotal reports of ‘‘microdosing’’—regular, subhallucinogenic doses administered on an intermittent schedule—claim improvements in mood, anxiety, cognition and sociability, yet there are almost no peer-reviewed studies that systematically test these claims. Cameron and colleagues set out to model psychedelic microdosing in rats to determine which behaviours are sensitive to chronic, intermittent low doses of DMT. They compared the effects of a repeated low-dose regimen (1 mg/kg DMT administered intraperitoneally every third day for several weeks) with known outcomes of a single high (10 mg/kg) dose, and assessed a battery of behavioural, structural and molecular endpoints relevant to mood, anxiety, cognition, sociability and metabolism. The study aimed to establish whether subhallucinogenic repeated dosing produces antidepressant- or anxiolytic-like effects and to characterise accompanying neurobiological changes.

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

Create a free account to open full-text PDFs.

Study Details

References (24)

Papers cited by this study that are also in Blossom

Psychedelics as Medicines: An Emerging New Paradigm

Nichols, C. D., Nichols, D. E., Johnson, M. W. · Clinical Pharmacology and Therapeutics (2016)

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA

Grob, C. S., Mithoefer, M. C., Brewerton, T. D. · Lancet Psychiatry (2016)

The therapeutic potential of psychedelic drugs: past, present, and future

Carhart-Harris, R. L., Goodwin, G. M. · Neuropsychopharmacology (2017)

Psychedelic Drugs in Biomedicine

Kyzar, E. J., Nichols, C. D., Gainetdinov, R. R. et al. · Trends in Pharmacological Sciences (2017)

Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT)

Cameron, L. P. · ACS Chemical Neuroscience (2018)

Powerful substances in tiny amounts An interview study of psychedelic microdosing

Johnstad, P. G. · Nordic Studies on Alcohol and Drugs (2018)

121 cited
Microdosing psychedelics: personality, mental health, and creativity differences in microdosers

Anderson, T., Petranker, R., Rosenbaum, D. et al. · Psychopharmacology (2019)

142 cited
A systematic study of microdosing psychedelics

Polito, V., Stevenson, R. J. · PLOS ONE (2019)

197 cited
Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting

Prochazkova, L., Lippelt, D. P., Colzato, L. S. et al. · Psychopharmacology (2018)

Show all 24 references
The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial

Yanakieva, S., Polychroni, N., Family, N. et al. · Psychopharmacology (2018)

Psychedelics promote structural and functional neural plasticity

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

Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression

Cameron, L. P., Benson, C. J., Dunlap, L. E. · ACS Chemical Neuroscience (2018)

The Effects of Hallucinogens on Gene Expression

Martin, D. A., Nichols, C. D., Nichols, Á. C. D. · Current Topics in Behavioral Neurosciences (2017)

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)

Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats

Horsley, R. R., Páleníček, T., Kolin, J. et al. · Behavioural Pharmacology (2018)

3,4-Methylenedioxymethamphetamine facilitates fear extinction learning

Young, M. B., Andero, R., Ressler, K. J. et al. · Translational Psychiatry (2015)

Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine

Dunlap, L. E., Andrews, A. M. · ACS Chemical Neuroscience (2018)

Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans

Rodríguez-Fornells, A., Ribeiro, S., Sanches, R. F. et al. · European Neuropsychopharmacology (2015)

118 cited
Prophylactic Ketamine Attenuates Learned Fear

Mcgowan, J. C., Lagamma, C. T., Lim, S. C. et al. · Neuropsychopharmacology (2017)

Cited By (38)

Papers in Blossom that reference this study

1 cited
Single-dose 1cp-LSD administration for canine anxiety: a pilot study

Alberto Henríquez-Hernández, L., Hernández-Álvarez, E., García-Serrano, I. et al. · Veterinary Research Communications (2024)

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT)

Witowski, C. G., Hess, M. R., Jones, N. T. et al. · European Journal of Pharmacology (2024)

Effects of DMT on mental health outcomes in healthy volunteers

Timmermann, C., Zeifman, R. J., Erritzoe, D. et al. · Scientific Reports (2024)

29 cited
Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics

Jaster, A. M., González-Maeso, J. · Molecular Psychiatry (2023)

The risk of chronic psychedelic and MDMA microdosing for valvular heart disease

Tagen, M., Mantuani, D., Van Heerden, L. et al. · Journal of Psychopharmacology (2023)

Therapeutic mechanisms of psychedelics and entactogens

Heifets, B. D., Olson, D. E. · Neuropsychopharmacology (2023)

A non-hallucinogenic LSD analog with therapeutic potential for mood disorders

Lewis, V., Bonniwell, E. M., Lanham, J. K. et al. · Cell Reports (2023)

102 cited
Show all 38 papers
Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior

Galvão-Coelho, N. L., De Meiroz Grilo, M. L. P., de Sousa, G. M. et al. · Frontiers in Behavioural Neuroscience (2022)

Towards an understanding of psychedelic-induced neuroplasticity

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

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

Madrid-Gambin, F., Gomez-Gomez, A., Busquets-Garcia, A. et al. · Biomedicine & Pharmacotherapy (2022)

Repeated low doses of LSD in healthy adults: A placebo-controlled, dose-response study

de Wit, H., Molla, H. M., Bershad, A. K. et al. · Addiction Biology (2022)

Evaluating the Potential Use of Serotonergic Psychedelics in Autism Spectrum Disorder

Markopoulos, A., Inserra, A., De Gregorio, D. et al. · Frontiers in Pharmacology (2022)

30 cited
Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study

Marschall, J., Fejer, G., Lempe, P. et al. · Journal of Psychopharmacology (2021)

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)

Psychedelic-Inspired Approaches for Treating Neurodegenerative Disorders

Olson, D. E. · Journal of Neurochemistry (2021)

Serotonergic Psychedelics in Neural Plasticity

Torregrossa, M. M., Lu, J., Lukasiewicz, K. et al. · Frontiers in Molecular Neuroscience (2021)

Improving cognitive functioning in major depressive disorder with psychedelics: a dimensional approach

Kuiperes, Z., Schreiber, R. · Neurobiology of Learning and Memory (2021)

Psychedelic-inspired drug discovery using an engineered biosensor

Dong, C., Ly, C., Dunlap, L. E. et al. · Cell (2021)

42 cited
A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics

Savalia, N., Shao, L-X,, Kwan, A. C. · Trends in Neuroscience (2021)

98 cited
Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action

Dos Santos, R. G., Hallak, J. E., Baker, G. et al. · Journal of Psychopharmacology (2021)

Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

Kaertner, L. S., Steinborn, M. B., Kettner, H. et al. · Scientific Reports (2021)

112 cited
The History of Psychedelics in Psychiatry

Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)

Psilocybin and LSD Have No Long-Lasting Effects in an Animal Model of Alcohol Relapse

Meinhardt, M. W., Güngör, C., Skorodumov, I. et al. · Neuropsychopharmacology (2020)

Neural correlates of the DMT experience assessed with multivariate EEG

Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)

Acute Subjective and Behavioral Effects of Microdoses of Lysergic Acid Diethylamide in Healthy Human Volunteers

Bershad, A. K., Schepers, S. T., Bremmer, M. P. et al. · Biological Psychiatry (2019)

Your Personal Research Library

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

Chronic, Intermittent Microdoses of the... — Research Summary & Context | Blossom