Cited by 168Psychedelics and Drug StudiesNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

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

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Cameron, Lindsay P., Benson, Charlie J., DeFelice, Brian C., Fiehn, Oliver, Olson, David E.·2019·ACS Chemical Neuroscience

Abstract

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. 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). 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. 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.

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  • The effects of psychoplastogens on structural plasticity in the PFC may explain why they have demonstrated efficacy in many preclinical rodent behavioral tests involving PFC circuitry including the forced swim test and fear extinction learning.

    “This may explain why they have demonstrated efficacy in many preclinical rodent behavioral tests involving PFC circuitry including the forced swim test and fear extinction learning (151, 194–197).”
  • Low doses of DMT produce beneficial effects in rodent behavioral paradigms relevant to treating depression and PTSD comparable to high doses.

    “we demonstrated that low doses of DMT produce beneficial effects in rodent behavioral paradigms relevant to treating depression and PTSD comparable to high doses”

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  1. U.S. National Library of Medicine. Depression: How effective are antidepressants? https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087089/ (accessed October 2018).
  2. Vaidya V. A.; Marek G. J.; Aghajanian G. K.; Duman R. S. (1997) 5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex. J. Neurosci. 17, 2785– 2795. 10.1523/JNEUROSCI.17-08-02785.1997. 9092600 PMC6573109 · DOI · Paper page

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Authors
Cameron, L. P., Benson, C. J., DeFelice, B. C., Fiehn, O., & Olson, D. E.
Affiliations
  • University of California, Davis (US)
  • King Abdulaziz University (SA)
Corresponding author
Olson, David E.
Venue
ACS Chemical Neuroscience
Published
2019-03-04
Volume
10
Issue
7
Pages
3261-3270
ISSN
1948-7193 (ISSN-L)
OpenAlex
W2919894573
Cited by
168
References
72
Citations by year
2026: 18 · 2025: 21 · 2024: 27 · 2023: 23 · 2022: 38 · 2021: 16 · 2020: 15 · 2019: 9 · 2012: 1
FWCI
22.77
Type
journal article
Language
en
Open access
Locations
  • ACS Chemical Neuroscience (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK104351, U24 DK097154)
  • Division of Graduate Education (1650042)
  • Department of Biochemistry and Molecular Medicine, University of California, Davis (NA)
  • Department of Chemistry, University of California, Davis (NA)
  • Genome Center, University of California, Davis (NA)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
N,N-dimethyltryptamine, DMT, psychedelic microdosing, antidepressant-like effects, anxiety, fear extinction learning, working memory, social interaction, weight gain, serotonergic psychedelics, mood disorders
MeSH terms
Affect, Animals, Antidepressive Agents, Anxiety, Behavior, Animal, Depression, N,N-Dimethyltryptamine, Extinction, Psychological, Fear, Female, Hallucinogens, Male, Rats, Sprague-Dawley, Rats

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