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Long-term consequences of a single treatment of mice with an ultra-low dose of Delta9-tetrahydrocannabinol (THC).

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

Behavioural Brain Research January 20, 2010 DOI: 10.1016/j.bbr.2009.09.021 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal experimental study Peer reviewed
Population ICR mice
Intervention Delta9-tetrahydrocannabinol (THC)
Dose 0.002 mg/kg
Duration At least 5 months
Topics Cannabis
Key findings A single extremely low dose of THC (0.002 mg/kg) in ICR mice induced cognitive deficits lasting at least 5 months, detected across tests of spatial navigation and spatial and non-spatial recognition. The authors suggest these deficits may stem from a common upstream process such as attention or motivation. The same dose also produced sustained ERK1/2 activation in the cerebellum.

Abstract

A single administration of an extremely low dose (0.002 mg/kg) of Delta9-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.

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Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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