Neuropharmacology of the Neuropsychiatric Symptoms of Dementia and Role of Pain: Essential Oil of Bergamot as a Novel Therapeutic Approach.

Int J Mol Sci. 2019 Jul 6;20(13). pii: E3327. doi: 10.3390/ijms20133327.


Author Information: Scuteri D1, Rombolà L1, Morrone LA1, Bagetta G2, Sakurada S3, Sakurada T4, Tonin P5, Corasaniti MT6. 1 Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende, Italy. 2

Preclinical and Translational Pharmacology, Department of Pharmacy, Health Science and Nutrition, University of Calabria, 87036 Rende, Italy. giacinto.bagetta@unical.it. 3

Department of Physiology and Anatomy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. 4

Daiichi College of Pharmaceutical Sciences-First Department of Pharmacology Fukuoka, Fukuoka 815-8511, Japan. 5 Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy. 6 Department of Health Sciences, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.


Aging of the population makes of dementia a challenge for health systems worldwide. The cognitive disturbance is a serious but not the only issue in dementia; behavioral and psychological syndromes known as neuropsychiatric symptoms of dementia remarkably reduce the quality of life. The cluster of symptoms includes anxiety, depression, wandering, delusions, hallucinations, misidentifications, agitation and aggression. The pathophysiology of these symptoms implicates all the neurotransmitter systems, with a pivotal role for the glutamatergic neurotransmission. Imbalanced glutamatergic and GABAergic neurotransmissions, over-activation of the extrasynaptic N-methyl-D-aspartate (NMDA) receptors and alterations of the latter have been linked to the development of neuropsychiatric symptoms experienced by almost the entire demented population. Drugs with efficacy and safety for prevention or long term treatment of these disorders are not available yet. 


Aromatherapy provides the best evidence for positive outcomes in the control of agitation, the most resistant symptom. Demented patients often cannot verbalize pain, resulting in unrelieved symptoms and contributing to agitation. Bergamot essential oil provides extensive preclinical evidence of analgesic properties. Incidentally, the essential oil of bergamot induces anxyolitic-like effects devoid of sedation, typical of benzodiazepines, with a noteworthy advantage for demented patients. These data, together with the reported safety profile, form the rational basis for bergamot as a neurotherapeutic to be trialed for the control of behavioral and psychological symptoms of dementia.


PMID: 31284573 PMCID: PMC6651821 DOI: 10.3390/ijms20133327