Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans

Klumpers, Floris; Denys, Damiaan; Kenemans, J Leon; Grillon, Christian; van der Aart, Jasper; Baas, Johanna MP

doi:10.1177/0269881111431624

Cited by 73Memory and Neural MechanismsCannabis and Cannabinoid ResearchNeurotransmitter Receptor Influence on Behavior

Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans

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Klumpers, Floris, Denys, Damiaan, Kenemans, J Leon, Grillon, Christian, van der Aart, Jasper, Baas, Johanna MP·2012·Journal of Psychopharmacology

DOI 10.1177/0269881111431624PMC PMC3454470

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Abstract

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB(1) receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB(1) or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-)clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB(1) agonist.

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Authors: Klumpers, F., Denys, D., Kenemans, J. L., Grillon, C., van der Aart, J., & Baas, J. M.
Affiliations: Utrecht University (NL)
Royal Netherlands Academy of Arts and Sciences (NL)
National Institutes of Health (US)
Experimental Psychology and Helmholtz Institute, Utrecht University, Utrecht, the Netherlands
ORCID: Klumpers, Floris
Denys, Damiaan
Kenemans, J Leon
Grillon, Christian
Baas, Johanna MP
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 2012-02-20
Volume: 26
Issue: 4
Pages: 471-478
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881111431624
PMC: PMC3454470
OpenAlex: W1974340846
Cited by: 72
References: 57
Citations by year: 2026: 3 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 4
FWCI: 3.28
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Funders: National Institutes of Health
National Institute of Mental Health (ZIAMH002798)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: delta-9-tetrahydrocannabinol, D-cycloserine, NMDA receptor, CB1 receptor, cannabinoid receptor agonists, skin conductance response, fear-potentiated startle, extinction retention, anxiety disorders, healthy volunteers
MeSH terms: Adolescent, Adult, Conditioning, Psychological, Cycloserine, Double-Blind Method, Extinction, Psychological, Fear, Female, Humans, Male, Reflex, Startle, Dronabinol

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Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans

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