β-caryophyllene, a CB2-selective phytocannabinoid, differentially modulates attention and inhibitory control in low- and high-performing young and aged mice.

Williams M N, Patel N T, Fleischel E J, Wimmer M E, Ward S J, Parikh V

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Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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6 authors.

Williams M NDepartment of Psychology and Neuroscience, Temple University, 1701 N. 13th Street, Philadelphia, PA, 19122, USA.

Patel N TDepartment of Psychology and Neuroscience, Temple University, 1701 N. 13th Street, Philadelphia, PA, 19122, USA.

Fleischel E JDepartment of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.

Wimmer M EDepartment of Psychology and Neuroscience, Temple University, 1701 N. 13th Street, Philadelphia, PA, 19122, USA.

Ward S JCenter for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.

Parikh VDepartment of Psychology and Neuroscience, Temple University, 1701 N. 13th Street, Philadelphia, PA, 19122, USA. vinay.parikh@temple.edu.

Funding

NCCIH NIH HHS 3R01 AT010778-02S1

6 · The paper itself

Abstract

rationaleEvidence suggests that modulation of cannabinoid signaling via CB2 receptors regulates neuroinflammation and confers neuroprotection, positioning these receptors as promising targets for age-related cognitive decline. However, there are limited studies that have directly explored the effects of acute CB2 receptor activation on cognitive domains impacted in aging.

objectiveThis study examined the impact of β-caryophyllene (BCP), a sesquiterpene with putative CB2 receptor agonist properties, on executive function and recognition memory in young and aged mice.

methodsYoung (2 mo) and aged (15 mo) male and female C57BL/6J mice were trained in an operant go/no-go (GNG) visual discrimination task. Animals trained to criterion were injected with BCP (0, 25, 50, or 100 mg/kg; i.p.) using a within-subjects design. BCP effects were also tested in novel object recognition (NOR) and object location recognition (OLR) paradigms.

resultsAged mice required more sessions than young mice to acquire GNG contingencies but performed equivalently post-acquisition. Acute BCP induced dose-dependent impairments in attentional control, with moderate-to-high doses (50 and 100 mg/kg) reducing go trial performance independent of age or sex, while inhibitory control (no-go trial performance) remained unaffected. In contrast, low-dose BCP (25 mg/kg) selectively enhanced inhibitory control in aged low-performing mice but not in young or high-performing aged mice. Low-dose BCP improved NOR but not OLR performance.

conclusionsAcute BCP produces domain- and dose-specific cognitive effects, with low doses enhancing inhibitory control in cognitively vulnerable aged mice. These rapid effects likely arise from neuromodulatory rather than delayed anti-inflammatory mechanisms, warranting further validation of CB2 receptor dependence.

Indexed as

AgingAttentionCannabinoidsCB2 ReceptorsInhibitory ControlMemoryMice

Identifiers

PMID42149199

DOI10.1038/npp.2017.278

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