Skip to content

Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration.

Caitlyn C Costa, Aoife S Weiss, Caroline M Limbaker, Anna E Kirkland, Lindsay M Squeglia, Carmela M Reichel, Rachel D Penrod, Jordan S Carter

Neuroscience May 25, 2026 DOI: 10.1016/j.neuroscience.2026.03.031 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Male and female Sprague Dawley rats at adolescence (post-natal day 36-57), young adulthood (post-natal day 177-210), and middle adulthood (post-natal day 360-393)
Interventions Vaporized THC cannabis extract citicoline
Duration 14 days forced exposure (adolescence) or 20 days self-administration (young and middle adulthood), with testing before and after exposure
Topics Cannabis
Keywords Citicoline Cognitive deficits Memory Pattern separation
Key findings Vaporized THC or cannabis extract impaired spatial pattern separation in rats at all ages during early abstinence, and citicoline administration rescued these deficits.

Abstract

Rates of cannabis use continue to rise, however, the neurocognitive effects are not fully characterized. Deficitsin memory processes, especially in adolescents, have been reportedfollowing exposure toΔ9-tetrahydrocannabinol (THC), the main psychoactive componentin cannabis. Treatments addressing these deficits have been unsuccessful. Here, we test the hypothesis that vaporized THC/cannabis extract will impair spatial pattern separation at several ages, as assessed by the spontaneous location recognition (SLR) task. We also test the hypothesis that citicoline, a compound with memory-modulating effects, will restore THC-induced deficits in SLR. At three age points (adolescence post-natal day [PND] 36-57, young adulthood PND 177-210, and middle adulthood PND 360-393), male and female Sprague Dawley rats were longitudinally testedon the SLR task before (SLR PRE) and after (SLR POST) vaporized THC or cannabis extract exposure. This occurred via forced exposure (14 days, adolescence) or self-administration (20 days, young and/or middle adulthood). During the SLR POST, subjectsreceived saline or citicoline injections. At all ages, rats demonstrated robust performance of the SLR PRE task. During early abstinence from THC/cannabis vapor exposure, rats had impaired SLR POST performance that was rescued by citicoline administration, particularly when given during memory encoding/consolidation.Vehicle-exposed rats had intact SLR POST performance, hich was not changed by citicoline.This study is the first to demonstrate THC-induced deficits in pattern separation. While these deficits are present during early abstinence, SLR performance recovers during prolonged abstinence. Furthermore, our results indicate thatciticoline may repair THC-induced cognitivedeficits, though the mechanism requires further exploration.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

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

Citations in the library

Explore topics