Table 2.

Summary of human trials investigating the cognitive effects of plants of Salvia species

Study	Duration	Study design	Participants	Intervention	Main results
Alzheimer’s disease
Akhondzadeh et al. [80]	4 months	Double-blind, placebo-controlled study	30 patients completed trial with average age of 72 years	S. officinalis extract 60 drops/day or placebo 60 drops/day. Salvia extract was prepared as 1:1 in alcohol 45%	Over a 4-month period, people taking Salvia liquid drops experienced significantly better cognitive function (as measured by the Alzheimer’s Disease Assessment Scale, and Clinical Dementia Rating Scale) compared with adults taking placebo capsules
Perry et al. [79]	6 weeks	Open-label design	11 patients aged 76–95 years in whom a diagnosis of mild to moderate probable Alzheimer’s disease was established	Capsules contained 50 µL essential oil of S. lavandulaefolia plus 50 µL of sunflower oil GC analysis demonstrated 94 peaks, the major peaks were of borneol, camphene, camphor, 1,8-cineole and α-terpineol, with only a trace of thujone. Dosage—Week 1: one capsule at 8 a.m.; Week 2: one capsule at 8 a.m. and one capsule at 7 p.m.; Weeks 3–6: as above with one additional capsule at 12:30 p.m.	There were statistically significant reductions in neuropsychiatric symptoms and an improvement in attention from baseline to 6 weeks
Acute cognitive and mood effects
Tildesley et al. [82]	6 h	Double-blind, placebo-controlled study	Trial 1, 20 healthy adults with a mean age of 20 years; Trial 2, 24 healthy adults with a mean age of 23 years	In Trial 1, 20 participants received 50, 100 and 150 µL of a standardised essential oil extract of S. lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 µL of a standardised essential oil extract of S. lavandulaefolia and placebo GC-MS was performed and the terpene constituents were as follows (%): α-pinene, 6.5; camphene, 6.3; β-pinene, 5.4; myrlene, 1.9; limonene, 1.2; 1,8-cineole, 25.8; camphor, 24.4; caryophyllene, 1.2; terpinen-4-OL, 2.0; borneol, 3.3; α-terpineol, 2.8	In Trial 1, memory performance was enhanced for the 50-µL dose at 1- and 2.5-hour time points. The effect was also apparent following administration of the 100 µL dose at 2.5 h post-dose sessions. A dose-specific enhancement on delayed word recall was also observed for the 50 µL dose at 1 and 2.5 h post-dose In Trial 2, the immediate word recall effect at 1 hour was maintained, and this was coupled with improved memory performance at 4 h post-dose testing session for the same dose. No significant enhancement on either immediate or delayed word recall was found for either the lowest (25 µL) or the highest (150 µL) doses of Salvia
Tildesley et al. [81]	6 h	Double-blind, placebo-controlled study	24 healthy adults with a mean age of 23 years	Two identical capsules corresponding to a dose of either 0 (a sunflower oil placebo), 25 µL, or 50 µL of S. lavandulaefolia essential oil in sunflower oil	Administration of S. lavandulaefolia resulted in a consistent improvement for both the 25- and 50-µL dose on the ‘Speed of Memory’ factor. There was also an improvement on the ‘Secondary Memory’ factor for the 25-µL dose. Mood was consistently enhanced, with increases in self-rated ‘alertness’, ‘calmness’ and ‘contentedness’ following the 50-µL dose and elevated ‘calmness’ following 25 µL
Kennedy et al. [18]	4 h	Double-blind, placebo-controlled study	30 healthy adults with a mean age of 24 years	On each study day participants received 4 capsules of identical appearance, each containing either placebo or 150 mg of S. officinalis dried leaf. Drug dosages corresponded to either 0 mg (placebo), 300 or 600 mg of S. officinalis dried leaf	Both doses of Salvia led to improved ratings in mood in the absence of the stressor (that is, in pre-DISS mood scores) post-dose, with the lower dose reducing anxiety and the higher dose increasing ‘alertness’, ‘calmness’ and ‘contentedness’ on the Bond–Lader mood scales The reduced anxiety effect following the lower dose was, however, abolished by performing the DISS, with the same dose also being associated with a reduction of alertness during performance. Task performance on the DISS battery was improved for the higher dose at both post-dose sessions, but reduced for the lower dose at the later testing session
Scholey et al. [19]	6 h	Double-blind, placebo-controlled study	20 healthy, older-age adults with a mean age of 73 years	Each tablet contained either 167 or 333 mg of S. officinalis extract. Participants received oral doses of four pills, each combination of active and placebo pills corresponding to 0 (placebo), 167, 333, 666 or 1332 mg of the standardised sage extract depending on that day’s treatment The S. officinalis for the study was a standardised ethanolic (70%) extract of dried S. officinalis in an approximate concentration ratio of 7.5:1 leaf/extract	Compared with the placebo condition, 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
Moss et al. [83]	Not specified	Randomised, single-blinded study	135 healthy adults with a mean age of 22 years	S. officinalis aroma, S. lavandulaefolia aroma and no aroma (control). Five drops of the appropriate essential oil and 5 mL water were placed on the stone and left to diffuse into the testing cubicle	S. officinalis aroma group performed significantly better than the control group on the quality of memory and secondary memory primary outcome factors from the test battery. The Alert mood measure displayed significant differences between both aromas and the control condition
Kennedy et al. [22]	4 h	Double-blind, placebo-controlled study	36 healthy adults with a mean age of 24 years	A single soft gel capsule containing either 50 mL of S. lavandulaefolia essential oil plus olive oil, or a placebo capsule containing olive oil	The essential oil was a potent inhibitor of human AChE and consisted almost exclusively of monoterpenoids. Oral consumption led to improved performance of secondary memory and attention tasks, most notably at the 1-hour post-dose testing session, and reduced mental fatigue and increased alertness, which were more pronounced 4-hours post-dose

AChE acetylcholinesterase, DISS Daytime Insomnia Symptom Scale, GC gas chromatography, GC-MS gas chromatography-mass spectrometry