Quantitative changes in hippocampal structure following long-term exposure to Δ9-tetrahydrocannabinol: possible mediation by glucocorticoid systems

Philip W. Landfield, Lisa B. Cadwallader, Sharon Vinsant

Research output: Contribution to journalArticlepeer-review

128 Scopus citations


Although cannabinoids exert strong effects on brain function, there have been no extensive analyses of the long-term effects of cannabinoids on mammalian brain structure. Consequently, we conducted quantitative light and electron microscopic studies on the brains of rats treated chronically with Δ9-tetrahydrocannabinol (THC) (5× weekly for 8 months - approximately 30% of the life-span). In these studies, we found significant THC-induced changes in hippocampal structure: specifically, THC-treated animals exhibited decreased neuronal density and increased glial cell reactivity (i.e. an increase of cytoplasmic inclusions). In addition, we confirmed prior reports of THC-induced increases in adrenal-pituitary activity, since both adrenocorticotropic hormone (ACTH) and corticosterone were elevated substantially during an acute stress. However, the animals appeared to be only minimally affected behaviorally by the doses used (highest dose: 8 mg/kg) and no effects of THC were observed on several ultrastructural variables, including synaptic density. The observed hippocampal morphometric effects of chronic THC are similar to apparent glucocorticoid-dependent changes that previously have been found to develop in rat hippocampus during normal aging. Given that cannabinoids and steroids are similar in chemical structure in several respects, therefore, the present results seem to raise the possibility that chronic THC exposure may alter hippocampal anatomical structure by interactions with, or mimicry of, aderenal steroid activity.

Original languageEnglish
Pages (from-to)47-62
Number of pages16
JournalBrain Research
Issue number1-2
StatePublished - Mar 8 1988

Bibliographical note

Funding Information:
This research was supported by Grant DA 03637 from the National Institute of Drug Abuse. We thank Leslie Shown for highly skilled and valuable technical assistance, Dr. J.C. E!dridge for important technical consultation, and Sheree Icenhower for excellent assistance with the manuscript.


  • Adrenocorticotropic hormone (ACTH)
  • Behavior
  • Corticosterone
  • Glial reactivity
  • Hippocampus
  • Morphometrics
  • Neuronal density
  • Δ-Tetrahydrocannabinol

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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