The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Reductions in circulating endocannabinoid levels in individuals with post-traumatic stress disorder following exposure to the world trade center attacks
Open accessAbstract
Endocannabinoid (eCB) signaling has been identified as a modulator of adaptation to stress, and is integral to basal and stress-induced glucocorticoid regulation. Furthermore, interactions between eCBs and glucocorticoids have been shown to be necessary for the regulation of emotional memories, suggesting that eCB function may relate to the development of post-traumatic stress disorder (PTSD). To examine this, plasma eCBs were measured in a sample (n=46) drawn from a population-based cohort selected for physical proximity to the World Trade Center (WTC) at the time of the 9/11 attacks. Participants received a structured diagnostic interview and were grouped according to whether they met diagnostic criteria for PTSD (no PTSD, n=22; lifetime diagnosis of PTSD=24). eCB content (2-arachidonoylglycerol (2-AG) and anandamide (AEA)) and cortisol were measured from 8 a.m. plasma samples. Circulating 2-AG content was significantly reduced among individuals meeting diagnostic criteria for PTSD. The effect of reduced 2-AG content in PTSD remained significant after controlling for the stress of exposure to the WTC collapse, gender, depression and alcohol abuse. There were no significant group differences for AEA or cortisol levels; however, across the whole sample AEA levels positively correlated with circulating cortisol, and AEA levels exhibited a negative relationship with the degree of intrusive symptoms within the PTSD sample. This report shows that PTSD is associated with a reduction in circulating levels of the eCB 2-AG. Given the role of 2-AG in the regulation of the stress response, these data support the hypothesis that deficient eCB signaling may be a component of the glucocorticoid dysregulation associated with PTSD. The negative association between AEA levels and intrusive symptoms is consistent with animal data indicating that reductions in AEA promote retention of aversive emotional memories. Future work will aim to replicate these findings and extend their relevance to clinical pathophysiology, as well as to neuroendocrine and molecular markers of PTSD.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“AEA levels have been shown to be reduced in PTSD patients (Hill et al., 2013;Neumeister et al., 2013) and depressed patients with high anxiety scores (Hill, Miller, Carrier, Gorzalka, & Hillard, 2009;Hill, Miller, Ho, Gorzalka, & Hillard, 2008).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Hill et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The development of a Clinician-Administered PTSD Scale
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995) · Journal of Traumatic Stress · doi:10.1002/jts.2490080106 · Cited by 5,024
Reliability and validity of a brief instrument for assessing post-traumatic stress disorder
Foa, E. B., Riggs, D. S., Dancu, C. V., & Rothbaum, B. O. (1993) · Journal of Traumatic Stress · doi:10.1002/jts.2490060405 · Cited by 2,537
The endogenous cannabinoid system controls extinction of aversive memories
Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., Hermann, H., Tang, J., Hofmann, C., Zieglgänsberger, W., et al. (2002) · Nature · doi:10.1038/nature00839 · Cited by 1,728
Di, S., Malcher‐Lopes, R., Halmos, K. C., & Tasker, J. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04850.2003 · Cited by 820
Breslau, N., Davis, G. C., Peterson, E. L., & Schultz, L. R. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00933-1 · Cited by 582
Enzymatic pathways that regulate endocannabinoid signaling in the nervous system
Ahn, K., McKinney, M. K., & Cravatt, B. F. (2008) · Chemical Reviews · doi:10.1021/cr0782067 · Cited by 529
Patel, S., Roelke, C. T., Rademacher, D. J., Cullinan, W. E., & Hillard, C. J. (2004) · Endocrinology · doi:10.1210/en.2004-0638 · Cited by 475
Self-citationStructured Clinical Interview for DSM-IV (SCID)
Kübler, U. (2013) · Springer eBooks · doi:10.1007/978-1-4419-1005-9_66 · Cited by 445
Status of Glucocorticoid Alterations in Post‐traumatic Stress Disorder
Yehuda, R. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04979.x · Cited by 409
Self-citationEnhancing Cannabinoid Neurotransmission Augments the Extinction of Conditioned Fear
Chhatwal, J. P., Davis, M., Maguschak, K. A., & Ressler, K. J. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300655 · Cited by 376
Hill, M. N., McLaughlin, R. J., Pan, B., Fitzgerald, M. L., Roberts, C. J., Lee, T. T. Y., Karatsoreos, I. N., Mackie, K., Viau, V., Pickel, V. M., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0496-11.2011 · Cited by 375
Self-citationNeumeister, A., Normandin, M. D., Pietrzak, R. H., Piomelli, D., Zheng, M. Q., Gujarro-Anton, A., Potenza, M. N., Bailey, C. R., Lin, S. F., Najafzadeh, S., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.61 · Cited by 361
Ishac, E. J. N., Jiang, L., Lake, K. D., Varga, K., Abood, M. E., & Kunos, G. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15639.x · Cited by 352
Endogenous cannabinoid signaling is essential for stress adaptation
Hill, M. N., McLaughlin, R. J., Bingham, B., Shrestha, L., Lee, T. T. Y., Gray, J. M., Hillard, C. J., Gorzalka, B. B., & Viau, V. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914661107 · Cited by 349
Self-citationHill, M. N., & Tasker, J. G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.12.030 · Cited by 346
Self-citationHill, M. N., Miller, G. E., Carrier, E. J., Gorzalka, B. B., & Hillard, C. J. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.03.013 · Cited by 328
Self-citationFast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling
Evanson, N. K., Tasker, J. G., Hill, M. N., Hillard, C. J., & Herman, J. P. (2010) · Endocrinology · doi:10.1210/en.2010-0285 · Cited by 324
Self-citationGunduz-Cinar, O., MacPherson, K. P., Cinar, R., Gamble-George, J., Sugden, K., Williams, B., Godlewski, G., Ramikie, T. S., Gorka, A. X., Alapafuja, S. O., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.72 · Cited by 307
Hill, M. N., McLaughlin, R. J., Morrish, A. C., Viau, V., Floresco, S. B., Hillard, C. J., & Gorzalka, B. B. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.114 · Cited by 304
Self-citationCohen, H., Liu, T., Kozlovsky, N., Kaplan, Z., Zohar, J., & Mathé, A. A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.230 · Cited by 299
Plasma neuropeptide-Y concentrations in humans exposed to military survival training
Morgan, C. A., Wang, S., Southwick, S. M., Rasmusson, A., Hazlett, G., Hauger, R. L., & Charney, D. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00239-5 · Cited by 298
Patel, S., Roelke, C. T., Rademacher, D. J., & Hillard, C. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03916.x · Cited by 297
Self-citationCampolongo, P., Roozendaal, B., Trezza, V., Hauer, D., Schelling, G., McGaugh, J. L., & Cuomo, V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900835106 · Cited by 294
Yehuda, R., Cai, G., Golier, J. A., Sarapas, C., Galea, S., Ising, M., Rein, T., Schmeidler, J., Müller-Myhsok, B., Holsboer, F., et al. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.02.034 · Cited by 294
Self-citationSerum Endocannabinoid Content is Altered in Females with Depressive Disorders: A Preliminary Report
Hill, M., Miller, G., Ho, W.-S., Gorzalka, B., & Hillard, C. (2008) · Pharmacopsychiatry · doi:10.1055/s-2007-993211 · Cited by 292
Self-citationKrystal, J. H., & Neumeister, A. (2009) · Brain Research · doi:10.1016/j.brainres.2009.03.044 · Cited by 264
Hariri, A. R., Gorka, A. X., Hyde, L. W., Kimak, M. A., Halder, I., Ducci, F., Ferrell, R. E., Goldman, D. A., & Manuck, S. B. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.10.047 · Cited by 264
Post-traumatic stress disorder and smoking: A systematic review
Fu, S. S., McFall, M., Saxon, A. J., Beckham, J. C., Carmody, T. P., Baker, D. G., & Joseph, A. M. (2007) · Nicotine & Tobacco Research · doi:10.1080/14622200701488418 · Cited by 260
Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD
Rasmusson, A. M., Hauger, R. L., Morgan, C. A., Bremner, J. D., Charney, D. S., & Southwick, S. M. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00185-7 · Cited by 255
Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans
Dlugos, A., Childs, E., Stuhr, K. L., Hillard, C. J., & de Wit, H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.100 · Cited by 248
Self-citationYehuda, R., Brand, S. R., & Yang, R.-K. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.027 · Cited by 244
Self-citationPlasma and Cerebrospinal Fluid Interleukin-6 Concentrations in Posttraumatic Stress Disorder
Baker, D. G., Ekhator, N. N., Kasckow, J. W., Hill, K. K., Zoumakis, E., Dashevsky, B. A., Chrousos, G. P., & Geracioti Jr., T. D. (2001) · Neuroimmunomodulation · doi:10.1159/000049028 · Cited by 238
Hill, M. N., & McEwen, B. S. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.11.001 · Cited by 235
Self-citationElevated levels of serum interleukin-1β in combat-related posttraumatic stress disorder
Spivak, B., Shohat, B., Mester, R., Avraham, S., Gil‐Ad, I., Bleich, A., Valevski, A., & Weizman, A. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00375-7 · Cited by 216
Hauer, D., Schelling, G., Gola, H., Campolongo, P., Morath, J., Roozendaal, B., Hamuni, G., Karabatsiakis, A., Atsak, P., Vogeser, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062741 · Cited by 200
Hillard, C. J., Weinlander, K. M., & Stuhr, K. L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.020 · Cited by 190
Self-citationRapid elevations in limbic endocannabinoid content by glucocorticoid hormones in vivo
Hill, M. N., Karatsoreos, I. N., Hillard, C. J., & McEwen, B. S. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.03.005 · Cited by 170
Self-citationDissociation of within- and between-Session Extinction of Conditioned Fear
Plendl, W., & Wotjak, C. T. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6038-09.2010 · Cited by 162
Depression-like phenotype following chronic CB1 receptor antagonism
Beyer, C. E., Dwyer, J. M., Piesla, M. J., Platt, B. J., Shen, R., Rahman, Z., Chan, K., Manners, M. T., Samad, T. A., Kennedy, J. D., et al. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.03.020 · Cited by 160
The Endocannabinoid System and the Treatment of Mood and Anxiety Disorders
Hill, M. N., & Gorzalka, B. B. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709789824624 · Cited by 155
Self-citationRiebe, C. J. N., & Wotjak, C. T. (2011) · Stress · doi:10.3109/10253890.2011.586753 · Cited by 149
Sajdyk, T. J., Johnson, P. L., Leitermann, R. J., Fitz, S. D., Dietrich, A. D., Morin, M., Gehlert, D. R., Urban, J. H., & Shekhar, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0659-07.2008 · Cited by 147
Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder
Sah, R., Ekhator, N. N., Strawn, J. R., Sallee, F. R., Baker, D. G., Horn, P. S., & Geracioti, T. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.04.037 · Cited by 145
Neuroendocrinology of Post-Traumatic Stress Disorder
Pervanidou, P., & Chrousos, G. P. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)82005-9 · Cited by 143
Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks
Sarapas (2011) · PubMed · doi:10.3233/dma-2011-0764 · Cited by 143
Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks
Sarapas, C., Cai, G., Bierer, L. M., Golier, J. A., Galea, S., Ising, M., Rein, T., Schmeidler, J., Müller-Myhsok, B., Uhr, M., et al. (2011) · Disease Markers · doi:10.1155/2011/328054 · Cited by 143
Self-citationMotion Sickness, Stress and the Endocannabinoid System
Choukèr, A., Kaufmann, I., Kreth, S., Hauer, D., Feuerecker, M., Thieme, D., Vogeser, M., Thiel, M., & Schelling, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010752 · Cited by 140
Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain
Hansen, H. S. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.03.022 · Cited by 140
Atsak, P., Hauer, D., Campolongo, P., Schelling, G., McGaugh, J. L., & Roozendaal, B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200742109 · Cited by 140
Patel, S., Carrier, E. J., Ho, W. ‐. V., Rademacher, D. J., Cunningham, S., Reddy, D. S., Falck, J. R., Cravatt, B. F., & Hillard, C. J. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400377-jlr200 · Cited by 124
Self-citationBellocchio, L., Gómez, E. S., Quarta, C., Metna‐Laurent, M., Cardinal, P., Binder, E., Cannich, A., Delamarre, A., Häring, M., Martín‐Fontecha, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218573110 · Cited by 118
Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus
Gamber, K. M., Macarthur, H., & Westfall, T. C. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.04.017 · Cited by 107
Cannabimimetic effects of osteopathic manipulative treatment.
McPartland, J. M., Giuffrida, A., King, J., Skinner, E., Scotter, J., & Musty, R. E. (2005) · PubMed · Cited by 102
Association between posttraumatic stress disorder and inflammation: A twin study
Plantinga, L., Bremner, J. D., Miller, A. H., Jones, D. P., Veledar, E., Goldberg, J., & Vaccarino, V. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.01.081 · Cited by 99
Neumeister, A. (2013) · Depression and Anxiety · doi:10.1002/da.22031 · Cited by 47
Mangieri, R. A., Hong, K., Piomelli, D., & Sinha, R. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1518-3 · Cited by 43
Hauer, D., Weis, F., Campolongo, P., Schopp, M., Beiras-Fernandez, A., Strewe, C., Giehl, M., Toth, R., Kilger, E., & Schelling, G. (2012) · Reviews in the Neurosciences · doi:10.1515/revneuro-2012-0058 · Cited by 33 · cited 2×
“…to acute stress, or low basal eCB contents in the circulation, have been related to excessive stress-induced activation of the HPA axis (Chouker et al., 2010; Dlugos et al., 2012) and negative long-term outcomes following exposure to stressful events, such as cardiac surgery (Hauer et al., 2012).”
Background
Cited by
Sorted by citations
Post-traumatic stress disorder.
Yehuda, R., Hoge, C. W., McFarlane, A. C., Vermetten, E., Lanius, R. A., Nievergelt, C. M., Hobfoll, S. E., Koenen, K. C., Neylan, T. C., & Hyman, S. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.57 · Cited by 870
Self-citationNeurobiological Interactions Between Stress and the Endocannabinoid System
Morena, M., Patel, S., Bains, J. S., & Hill, M. N. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.166 · Cited by 698
Self-citationPractical considerations in medical cannabis administration and dosing
MacCallum, C. A., & Russo, E. B. (2018) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2018.01.004 · Cited by 663
Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?
Hillard, C. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.130 · Cited by 449
Self-citationHill, M. N., Campolongo, P., Yehuda, R., & Patel, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.162 · Cited by 250
Self-citation
Metadata
- Authors
- Hill, M. N., Bierer, L. M., Makotkine, I., Golier, J. A., Galea, S., McEwen, B. S., Hillard, C. J., & Yehuda, R.
- Affiliations
- University of Calgary (CA)
- James J. Peters VA Medical Center (US)
- Columbia University (US)
- Rockefeller University (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Hill, Matthew N.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 38
- Issue
- 12
- Pages
- 2952-2961
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3870889
- OpenAlex
- W2024564598
- Cited by
- 256
- References
- 56
- Citations by year
- 2026: 8 · 2025: 27 · 2024: 24 · 2023: 22 · 2022: 15 · 2021: 28 · 2020: 24 · 2019: 22 · 2018: 28 · 2017: 16 · 2016: 10 · 2015: 19 · 2014: 10 · 2013: 2
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute of Mental Health (MH-41256, R37MH041256, R01MH041256, R56MH077321)
- National Institute on Drug Abuse (R01DA026996, DA026996)
- National Center for Research Resources (5 M01RR00071, M01RR000071)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- post-traumatic stress disorder, endocannabinoids, 2-arachidonoylglycerol, anandamide, cortisol, September 11 attacks, World Trade Center, intrusion symptoms, emotional memory, stress response, plasma biomarkers
- MeSH terms
- Aged, Alcoholism, Amides, Arachidonic Acids, Ethanolamines, Ethnicity, Female, Glycerides, Humans, Hydrocortisone, Male, Middle Aged, Neuropsychological Tests, Oleic Acids, Palmitic Acids, Psychiatric Status Rating Scales, Sex Characteristics, Stress Disorders, Post-Traumatic, Terrorism, Polyunsaturated Alkamides, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
