Species of Salvia (sage) have a long-standing reputation in European medical herbalism, including for memory enhancement. In recent controlled trials, administration of sage extracts with established cholinergic properties improved cognitive function in young adults.
This randomised, placebo-controlled, double-blind, balanced, five-period crossover study investigated the acute effects on cognitive performance of a standardised extract of Salvia officinalis in older adults.
Materials and methods
Twenty volunteers (>65 years of age, mean = 72.95) received four active doses of extract (167, 333, 666 and 1332 mg) and a placebo with a 7-day wash-out period between visits. Assessment involved completion of the Cognitive Drug Research computerised assessment battery. On study days, treatments were administered immediately following a baseline assessment with further assessment at 1, 2.5, 4 and 6 h post treatment.
Compared with the placebo condition (which exhibited the characteristic performance decline over the day), the 333-mg dose was associated with significant enhancement of secondary memory performance at all testing times. The same measure benefited to a lesser extent from other doses. There also were significant improvements to accuracy of attention following the 333-mg dose. In vitro analysis confirmed cholinesterase inhibiting properties for the extract.
The overall pattern of results is consistent with a dose-related benefit to processes involved in efficient stimulus processing and/or memory consolidation rather than retrieval or working memory efficiency. These findings extend those of the memory-enhancing effects of Salvia extracts in younger populations and warrant further investigation in larger series, in other populations and with different dosing regimes.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Aggleton JP, Brown WB (1999) Episodic memory, amnesia and the hippocampal–anterior thalamic axis. Behav Brain Sci 22:425–486
Akhondzadeh S, Noroozian N, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M (2003) Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther 28:1–7
Bartram T (1998) Bartram’s encyclopaedia of herbal medicine. Robinson, London
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Gardiner JM, Richardson-Klavehn A (2000) Remembering and knowing. In: Tulving E, Craik FIM (eds) Handbook of memory. Oxford University Press, New York, pp 229–244
Herholz K, Weisenbach S, Kalbe E, Diederich NJ, Heiss WD (2005) Cerebral acetylcholine esterase activity in mild cognitive impairment. NeuroReport 8:1431–1434
Howes MJR, Perry NSL, Houghton PJ (2003) Plants with traditional uses and activities relevant to the management of Alzheimer’s disease and other cognitive disorders. Phytother Res 17:1–18
Imanshahidi M, Hosseinzadeh H (2006) The pharmacological effects of salvia species on the central nervous system. Phytother Res 20:427–437
Kennedy DO, Scholey AB (2005) The psychopharmacology of European herbs with cognition enhancing properties. Curr Pharm Des 12:4613–4623
Kennedy DO, Scholey AB, Wesnes K (2001a) Differential, dose-dependent changes in cognitive performance and mood following acute administration of ginseng to healthy young volunteers. Nutr Neurosci 4:399–412
Kennedy DO, Scholey AB, Wesnes KA (2001b) Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng combination to healthy young volunteers. Nutr Neurosci 4:399–412
Kennedy DO, Scholey AB, Tildesley NTJ, Perry EK, Wesnes KS (2002a) Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 72:953–964
Kennedy DO, Scholey AB, Wesnes KA (2002b) Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav 75:739–751
Kennedy DO, Wake G, Savelev S, Tildesley NTJ, Perry EK, Wesnes KS, Scholey AB (2003) Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology 28:1871–1881
Kennedy DO, Pace S, Haskell C, Okello EJ, Milne A, Scholey AB (2005) Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology 31:845–852
Keppel G (1991) Design and analysis. Prentice-Hall, New Jersey
Mantle D, Pickering AT, Perry EK (2000) Medicinal plant extracts for the treatment of dementia: a review of their pharmacology, efficacy and tolerability. CNS Drugs 13:201–213
McKeith I, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, Cicin-Sain A, Ferrara R, Spiegel R (2000) Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 356:2031–2036
Miyazawa M, Watanabe H, Kameoka H (1997) Inhibition of acetylcholinesterase activity by monoterpenoids with a p-menthane skeleton. J Agric Food Chem 45:677–679
Muir JL (1997) Acetylcholine, aging, and Alzheimer’s disease. Pharmacol Biochem Behav 56:687–696
Ogura H, Kosasa T, Kuriya Y, Yamanishi Y (2000) Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butylcholinesterase in vitro. Methods Find Exp Clin Pharmacol 22:609–613
Perry N, Court G, Bidet N, Court J, Perry E (1996) European herbs with cholinergic activities: potential in dementia therapy. Int J Geriatr Psychiatry 11:1063–1069
Perry EK, Pickering AT, Wang WW, Houghton PJ, Perry NSL (1999) Medicinal plants and Alzheimer’s disease: from ethnobotany to phytotherapy. J Pharm Pharmacol 51:527–534
Perry N, Howes M, Houghton P, Perry E (2000a) Why sage may be a wise remedy: effects of Salvia on the nervous system. In: Kintzios SE (ed) Sage: the genus Salvia. Harwood, Netherlands, pp 207–223
Perry NSL, Houghton PJ, Theobald A, Jenner P, Perry EK (2000b) In-vitro inhibition of erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 53:1347–1356
Perry NSL, Houghton PJ, Sampson J, Theobald AE, Hart S, LisBalchin M (2001) In-vitro activities of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer’s disease. J Pharm Pharmacol 53:1347–1356
Perry NSL, Houghton PJ, Jenner P, Keith A, Perry EK (2002) Salvia lavandulaefolia essential oil inhibits cholinesterase in vivo. Phytomedicine 9:48–51
Perry NSL, Bollen C, Perry EK, Ballard C (2003) Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav 75:651–659
Randall DC, Shneerson JM, File SE (2005) Cognitive effects of modafinil in student volunteers may depend on IQ. Pharmacol Biochem Behav 82:133–139
Savelev S, Okello E, Perry NSL, Wilkins RM, Perry E (2003) Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Biochem Pharmacol Behav 75:661–668
Savelev S, Okello EJ, Perry EK (2004) Butyryl and acetylcholinesterase inhibitory activities in essential oils of salvia species and their constituents. Phytotherapy Res 18:315–324
Scholey AB (2002) Attention. In: Perry EK, Ashton H, Young AH (eds) Neurochemistry of consciousness. Benjamins, Amsterdam, pp 43–63
Scholey AB, Kennedy DO (2002) Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand. Hum Psychopharmacol Clin Exp 17:35–44
Scholey AB, Kennedy DO (2004) Cognitive and physiological effects of an “energy drink”: an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions. Psychopharmacology 176:320–330
Scholey AB, Harper S, Kennedy DO (2001) Cognitive demand and blood glucose. Physiol Behav 73:585–592
Scholey A, Kennedy D, Wesnes K (2005) The psychopharmacology of herbal extracts: issues and challenges. Psychopharmacology 179:705–707
Seamans JK, Yang CR (2004) The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol 74:1–58
Tildesley NTJ, Kennedy DO, Perry EK, Ballard CG, Savelev S, Wesnes KA, Scholey AB (2003) Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Biochem Pharmacol Behav 75:669–674
Tildesley NTJ, Kennedy DO, Perry EK, Ballard CG, Wesnes KA, Scholey AB (2005) Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiol Behav 83:699–709
Wesnes K (2003) The cognitive drug research computerised assessment system: application to clinical trials. In: De Deyn P, Thiery E, D’Hooge R (eds) Memory: basic concepts, disorders and treatment. Uitgeverij Acco, Leuven, pp 453–472
Wesnes KA, Ward T, McGinty A, Petrini O (2000) The memory enhancing effects of a Ginkgo-biloba/Panax ginseng combination in healthy middle aged volunteers. Psychopharmacology 152:353–361
Funding for this study was provided by a grant from Oxford Natural Products Ltd. The company (which no longer exists) had no further role in the study design, collection, analysis, and interpretation of data and writing of the reports. Specifically, the company was not involved in the original concepts and systematic review of existing trial evidence, the design, the choice of investigators, the control of allocation schedule, the conduct of the trial, the collection and monitoring of data, the analysis and interpretation, and the writing and approval of the report. The authors are grateful to the Newcastle branch of the Alzheimer’s Society for assisting the involvement of volunteers.
This study formed part of a Ph.D. funded by Oxford Natural Products Ltd.
About this article
Cite this article
Scholey, A.B., Tildesley, N.T.J., Ballard, C.G. et al. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology 198, 127–139 (2008). https://doi.org/10.1007/s00213-008-1101-3
- Cognitive decline
- Age-related memory decline
- Alzheimer’s disease