Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral disturbances. While its pathogenesis is complex, increasing evidence supports the role of an imbalance between excitatory and inhibitory (E/I) neuronal activity in disease progression. E/I imbalance contributes to synaptic impairment, network hypersynchrony, and ultimately cognitive deterioration. Despite advances in understanding AD pathophysiology, no highly effective or disease-modifying treatments are currently available. This review explores the pharmacological properties of linalool, a monoterpene found in high concentrations in Lavandula angustifolia and in Cannabis sativa L. as minor component, which has demonstrated several neuromodulatory effects. Unlike current AD therapies that typically target cholinergic or NMDA-mediated mechanisms in isolation, linalool exerts a multi-target action that may help restore E/I balance. These effects also underlie its well-established anxiolytic and sedative properties, though their therapeutic relevance extends beyond behavioral symptoms to include the modulation of neuronal network function in neurodegeneration. We also examine studies on lavender extracts, rich in linalool, with the potential to influence sleep regulation, neuronal excitability, and cognitive function. Finally, we discuss the emerging role of cannabis extracts and the potential entourage effect of linalool and phytocannabinoids in targeting neuronal excitability. Overall, the findings discussed in the present review highlight linalool-containing phytocomplexes as promising candidates for supportive or complementary strategies in managing E/I imbalance and cognitive decline in AD.

Exploring Linalool-Based Phytotherapy for Excitatory/Inhibitory Imbalance in Alzheimer's Disease: A Review of Lavender and Cannabis Therapeutic Effects on Sleep, Seizures, and Cognition

Roviello G.;
2026

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral disturbances. While its pathogenesis is complex, increasing evidence supports the role of an imbalance between excitatory and inhibitory (E/I) neuronal activity in disease progression. E/I imbalance contributes to synaptic impairment, network hypersynchrony, and ultimately cognitive deterioration. Despite advances in understanding AD pathophysiology, no highly effective or disease-modifying treatments are currently available. This review explores the pharmacological properties of linalool, a monoterpene found in high concentrations in Lavandula angustifolia and in Cannabis sativa L. as minor component, which has demonstrated several neuromodulatory effects. Unlike current AD therapies that typically target cholinergic or NMDA-mediated mechanisms in isolation, linalool exerts a multi-target action that may help restore E/I balance. These effects also underlie its well-established anxiolytic and sedative properties, though their therapeutic relevance extends beyond behavioral symptoms to include the modulation of neuronal network function in neurodegeneration. We also examine studies on lavender extracts, rich in linalool, with the potential to influence sleep regulation, neuronal excitability, and cognitive function. Finally, we discuss the emerging role of cannabis extracts and the potential entourage effect of linalool and phytocannabinoids in targeting neuronal excitability. Overall, the findings discussed in the present review highlight linalool-containing phytocomplexes as promising candidates for supportive or complementary strategies in managing E/I imbalance and cognitive decline in AD.
2026
Istituto di Biostrutture e Bioimmagini - IBB - Sede Napoli
Alzheimer's disease
cannabis
entourage effect
excitatory/inhibitory imbalance
lavender
linalool
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/573522
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