Long-term consequences of a single treatment of mice with an ultra-low dose of Δ9-tetrahydrocannabinol (THC)

Haitham Amal, Lilach Fridman-Rozevich, Roey Senn, Anastasia Strelnikov, Mikhal Gafni, Ora Keren, Yosef Sarne*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


A single administration of an extremely low dose (0.002 mg/kg) of Δ9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to ICR mice induced long-term cognitive deficits that lasted for at least 5 months. The behavioral deficits were detected by several tests that evaluated different aspects of memory and learning, including spatial navigation and spatial and non-spatial recognition. Our findings point to possible deficits in attention or motivation that represent a common upstream cognitive process that may affect the performance of the mice in the different behavioral assays. Similar ultra-low doses of THC (3-4 orders of magnitude lower than doses that are known to evoke the acute effects of THC) also induced sustained activation of extracellular-regulated kinase (ERK1/2) in the cerebellum, indicating that a single injection of such low doses of the cannabinoid drug can stimulate neuronal regulatory mechanisms. The relevance of these findings to the behavioral consequences of chronic exposure to marijuana is discussed.

Original languageAmerican English
Pages (from-to)245-253
Number of pages9
JournalBehavioural Brain Research
Issue number2
StatePublished - 20 Jan 2010
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the Israel Anti-drug-Authority and by the Israel Science Foundation (grant no. 180/04 ).


  • Cannabinoid drugs
  • Cognitive deficits
  • Extracellular-regulated kinase (ERK)
  • Learning and memory
  • Marijuana
  • Recognition tests
  • Spatial learning tests
  • Δ-Tetrahydrocannabinol (THC)


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