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Cited by 1,052Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchPharmacological Receptor Mechanisms and Effects

The DOI matches its Crossref record; 64 of the 68 references it cites were found in a registry or an index.

Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain

Glass, M, Faull, R.L.M, Dragunow, M·1997·Neuroscience
DOI 10.1016/s0306-4522(96)00428-9
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Abstract

The anatomical distribution and density of cannabinoid receptors in the human brain was studied in one fetal (33 weeks gestation), two neonatal (aged three to six months) and eight adult (aged 21-81 years) human cases using quantitative receptor autoradiography following in vitro labelling of sections with the synthetic cannabinoid agonist [3H]CP55,940. Cannabinoid receptors were distributed in a heterogeneous fashion throughout the adult human brain and spinal cord. The allocortex contained very high concentrations of cannabinoid receptor binding sites in the dentate gyrus, Ammons's horn and subiculum of the hippocampal formation; high concentrations of receptors were also present in the entorhinal cortex and amygdaloid complex. Cannabinoid receptor binding sites were also present throughout all regions of the neocortex, where they showed a marked variation in density between the primary, secondary and associational cortical regions: the greatest densities of receptors were present in the associational cortical regions of the frontal and limbic lobes, with moderate densities in the secondary sensory and motor cortical regions, and with the lowest densities of receptors in the primary sensory and motor cortical regions. Relatively high concentrations of cannabinoid receptors were consistently seen in cortical regions of the left (dominant) hemisphere, known to be associated with verbal language functions. In all of the cortical regions, the pattern and density of receptor labelling followed the neocortical laminar organization, with the greatest density of receptors localized in two discrete bands--a clearly delineated narrow superficial band which coincided with lamina I and a deeper broader, conspicuous band of labelling which corresponded to laminae V and VI. Labelling in the intervening cortical laminae (II-IV) showed lower densities, with a well delineated narrow band of label in the middle of laminae IV in the associational cortical regions. The thalamus showed a distinctive heterogeneous distribution of cannabinoid receptors, with the highest concentration of receptors localized in the mediodorsal nucleus, anterior nuclear complex, and in the midline and intralaminar complex of nuclei, i.e. in thalamic nuclei which have connectional affiliations with the associational cortical areas. The basal ganglia showed a distinctive heterogeneous pattern of receptor binding, with the very highest concentrations in the globus pallidus internus, moderate concentrations in the globus pallidus externus and ventral pallidum, and moderately low levels of binding throughout the striatal complex. In the midbrain, some of the highest levels of cannabinoid receptor binding sites in the human brain were present in the substantia nigra pars reticulata, with very low levels of labelling in all other midbrain areas. The highest densities of cannabinoid receptor binding in the hindbrain were localized in the molecular layer of the cerebellar cortex and the dorsal motor nucleus of the vagus, with moderate densities of receptors in the nucleus of the solitary tract. The spinal cord showed very low levels of receptor binding. Studies on the distribution of cannabinoid receptors in the fetal and neonatal human brain showed similar patterns of receptor distribution to that observed in the adult human brain, except that the density of receptor binding was generally markedly higher, especially in the basal ganglia and substantia nigra. The pattern of cannabinoid receptor labelling in the striatum showed a striking patchy pattern of organization which was especially conspicuous in the fetal brain. These results show that cannabinoid receptor binding sites in the human brain are localized mainly in: forebrain areas associated with higher cognitive functions; forebrain, midbrain and hindbrain areas associated with the control of movement; and in hindbrain areas associated with the control of motor and sensory functions of the autonomic nervous system. (AB

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Citations

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Research works printed but not linked: 9

  1. Bidaut-Russell, 1989, Opioid and cannabinoid analgetics both inhibit cyclic AMP production in the rat striatum, Adv. Biosci., 75, 165
  2. Campbell, 1986, Delta-9-tetrahydrocannabinol differentially affects sensory-evoked potentials in the rat detate gyrus, J. Pharmac. exp. Ther., 239, 941
  3. Chen, 1993, Transient concentration of cannabinoid receptors in the cortex subplate zone during kitten post-natal development, Soc. Neurosci. Abstr., 19, 305
  4. Devane, 1988, Determination and characterisation of a cannabinoid receptor in rat brain, Molec. Pharmac., 34, 605
  5. Dewey, 1972, The effects of chronic administration of trans-delta-9-tetrahydorcannibinol on behaviour and the cardiovascular system of dogs, Archs int. Pharmacodyn. Thér., 198, 118
  6. Edery, 1972, Structure activity relationships in the tetrahydrocanabinol species, Arzneimittel-Forshch., 22, 1995
  7. Howlett, 1985, Cannabinoid inhibition of adenylate cyclase. Biochemistry of response in neuroblasta cell membrane, Molec. Pharmac., 27, 429
  8. Howlett, 1986, Involvement of Gi in the inhibition of adenylate cyclase by cannabinoid drugs, Molec. Pharmac., 29, 307
  9. Mendelson, 1976, Operant acquisition of marijuana by men, J. Pharmac. exp. Ther., 198, 42

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Metadata

Authors
Glass, M., Faull, R. L. M., & Dragunow, M.
Affiliations
University of Auckland (NZ)
Corresponding author
Faull, R.L.M
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
1997-02
Volume
77
Issue
2
Pages
299-318
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/s0306-4522(96)00428-9
OpenAlex
W2037811574
Cited by
1,052
References
68
Citations by year
2026: 28 · 2025: 40 · 2024: 34 · 2023: 39 · 2022: 56 · 2021: 53 · 2020: 52 · 2019: 48 · 2018: 46 · 2017: 49 · 2016: 37 · 2015: 41 · 2014: 39 · 2013: 37 · 2012: 42
FWCI
11.26
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
Keywords
cannabinoid receptors, human brain, receptor distribution, receptor density, fetal brain, neonatal brain, hippocampal formation, neocortex, cortical laminar organization, thalamus, basal ganglia, midbrain, spinal cord, globus pallidus internus, globus pallidus externus, ventral pallidum, striatum, amygdala, entorhinal cortex, hemispheric lateralization, CP55,940
MeSH terms
Adult, Aged, Aged, 80 and over, Autoradiography, Brain, Brain Chemistry, Brain Mapping, Cannabinoids, Coloring Agents, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Myelin Sheath, Pregnancy, Receptors, Drug, Spinal Cord, Receptors, Cannabinoid

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