Estrogenic regulation of limbic cannabinoid receptor binding
Open accessAbstract
Sex differences have been identified in many of the behavioral and physiological effects of cannabinoids. While estrogen has been linked to some of these variations, the effects of estrogen on cannabinoid receptor binding have not been characterized within regions of the brain specifically implicated in stress responsivity and emotional behavior. To examine sex differences, and the role of estradiol, in regulation of the cannabinoid receptor, we compared the binding site density of the cannabinoid receptor within the amygdala, hippocampus and hypothalamus in males, cycling females, ovariectomized (OVX) females and estradiol-treated OVX females (OVX+E). Our data reveal that males and OVX females have higher amounts of hypothalamic and lower amounts of amygdalar cannabinoid receptor binding relative to both cycling females and OVX+E females. Within the hippocampus, ovariectomy resulted in an upregulation of cannabinoid receptor binding. These data provide a putative biochemical mechanism mediating the observed behavioral and physiological sex differences in the effects of cannabinoids, particularly with respect to stress and emotional behavior.
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
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 animals, CB1 receptor levels are higher in males than females.
“Animal data showing higher CB1 receptor levels in male relative to female animals18, 56, 57”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rubino, T., Vigano', D., Realini, N., Guidali, C., Braida, D., Capurro, V., Castiglioni, C., Cherubino, F., Romualdi, P., Candeletti, S., et al. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301664 · Cited by 345 · see citing works
Cannabinoids in Clinical Practice
Williamson, E. M., & Evans, F. J. (2000) · Drugs · doi:10.2165/00003495-200060060-00005 · Cited by 283 · see citing works
Reich, C. G., Taylor, M. E., & McCarthy, M. M. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.05.013 · Cited by 244 · see citing works
de Fonseca, F. R., Cebeira, M., Ramos, J. A., Martín, M., & Fernández-Ruiz, J. J. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00585-0 · Cited by 243 · see citing works
Cannabinoid self‐administration in rats: sex differences and the influence of ovarian function
Fattore, L., Spano, M. S., Altea, S., Angius, F., Fadda, P., & Fratta, W. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707465 · Cited by 200 · see citing works
González, S. R., Bisogno, T., Wenger, T., Manzanares, J., Milone, A., Berrendero, F., Marzo, V. D., Ramos, J. A., & Fernández‐Ruíz, J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2406 · Cited by 196 · see citing works
Sex differences in antinociceptive and motoric effects of cannabinoids.
Tseng, A. H., & Craft, R. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01267-5 · Cited by 156 · see citing works
Estrogen recruits the endocannabinoid system to modulate emotionality.
Hill, M., Karacabeyli, E., & Gorzalka, B. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.02.003 · Cited by 141 · see citing works
Self-citationHippocampal CB1 Receptors Mediate the Memory Impairing Effects of Δ9-Tetrahydrocannabinol
Wise, L. E., Thorpe, A. J., & Lichtman, A. H. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.31 · Cited by 136 · see citing works
Gorzalka, B. B., Hill, M. N., & Chang, S. (2009) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.08.009 · Cited by 106 · see citing works
Self-citationMize, A. L., & Alper, R. H. (2000) · Brain Research · doi:10.1016/s0006-8993(00)01998-3 · Cited by 92 · see citing works
Craft, R. M., & Leitl, M. D. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.09.004 · Cited by 70 · see citing works
Diaz, S. V., Farhang, B., Hoien, J., Stahlman, M., Adatia, N., Cox, J. M., & Wagner, E. J. (2009) · Neuroendocrinology · doi:10.1159/000191646 · Cited by 50 · see citing works
Nguyen, Q. H., & Wagner, E. J. (2006) · Neuroendocrinology · doi:10.1159/000096996 · Cited by 46 · see citing works
Adolescent exposure to nicotine modifies acute functional responses to cannabinoid agonists in rats
Marco, E. M., Llorente, R., Moreno, E., Fernández, J. M. B., Guaza, C., & Viveros, M. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.04.012 · Cited by 37 · see citing works
Daniel, J. M., Winsauer, P. J., Brauner, I. N., & Moerschbaecher, J. M. (2002) · Behavioral Neuroscience · doi:10.1037/0735-7044.116.6.989 · Cited by 37 · see citing works
Kalbasi Anaraki, D., Sianati, S., Sadeghi, M., Ghasemi, M., Javadi, P., Ejtemaei Mehr, S., & Dehpour, A. R. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.02.055 · Cited by 22 · see citing works
Bonnin, A., Fern�ndez-Ruiz, J. J., Mart�n, M., de Fonseca, F. R. G., Hern�ndez, M. L., & Ramos, J. A. (1993) · Journal of Neural Transmission · doi:10.1007/bf01244868 · Cited by 16 · see citing works
SCHMOLESKY, M. T., Wang, Y., Creel, D. J., & Leventhal, A. G. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001113)427:2 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neumeister, 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 · see citing works
Amygdala FAAH and anandamide: mediating protection and recovery from stress
Gunduz-Cinar, O., Hill, M. N., McEwen, B. S., & Holmes, A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.08.008 · Cited by 229 · see citing works
Self-citationThe Impact of Exposure to Cannabinoids in Adolescence: Insights From Animal Models
Rubino, T., & Parolaro, D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.024 · Cited by 183 · see citing works
- Authors
- Riebe, C. J. N., Hill, M. N., Lee, T. T. Y., Hillard, C. J., & Gorzalka, B. B.
- Affiliations
- University of British Columbia (CA)
- Medical College of Wisconsin (US)
- Corresponding author
- Gorzalka, Boris B.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 35
- Issue
- 8
- Pages
- 1265-1269
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC2933663
- OpenAlex
- W2038447112
- Cited by
- 128
- References
- 19
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 3 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 7 · 2019: 2 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institute on Drug Abuse (R01DA009155, DA09155, DA022439, R21DA022439)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- estrogen, estradiol, cannabinoid receptors, sex differences, limbic system, amygdala, hippocampus, hypothalamus, ovariectomy, receptor binding density, stress responsivity, emotional behavior
- MeSH terms
- Amygdala, Animals, Estradiol, Female, Hippocampus, Hypothalamus, Limbic System, Male, Ovariectomy, Protein Binding, Rats, Sprague-Dawley, Estrous Cycle, Receptors, Cannabinoid, Rats, Cannabinoid Receptor Agonists
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