Lamiaceae Pharmacology Evidence suggests that alongside phenolic constituents, the psychotropic properties of the Lamiaceae reside in volatile constituents and, as a consequence, the essential oils they produce may also exert neurocognitive effects. Mints: Spearmint Spearmint may be a beneficial nutritional intervention for cognitive health. Recent studies show that compounds isolated from Mentha spicata are promising for neurodegenerative therapy. Spearmint contains vitamins, antioxidants, and vital nutrients. It is rich in limonene, carvone and congeners, and cineol. It's a potent antioxidant. It has carminative, anti-spasmodic, anti-oxidant, anti-depressant, anti-inflammatory, sedative and stimulant action. It's like the benefits of teas providing catechin, epicatechin with flavonoids like rutin and luteolin. It's also rich in rosmarinic acid, it's the highest of Lamiaceae (more than Rosemary). Based on available research, it appears that spearmint is well tolerated in recommended doses up to 500 milligrams daily or taken as a tea twice daily for 30 days. Extract doses seem higher. Studies point towards 1,8-cineole as a good candidate for NMDA antagonism, with a weaker AChE inhibitory effect. Cognitive function task scores suggest improved reasoning, significantly improved attention/concentration and planning from baseline after 30 d of treatment. Day one, subjects experienced acutely improved attention/concentration from pre- supplementation. It was well-tolerated and may improve certain aspects of cognitive function. Using spearmint as an extract improved quality of working memory and spatial working 1 memory accuracy, caused improvement in ability to fall asleep. Overall treatment effects were evident for vigor-activity, total mood disturbance, and alertness and behaviour following wakefulness, with trends observed for improvements after spearmint [1] https://doi.org/10.1089/acm.2016.0379 [2] https://doi.org/10.1016/j.nutres.2018.11.012 Peppermint While peppermint contains essential oils, terpenoids and flavonoids such as eriocitrin, hesperidin, and kaempferol 7-O-rutinoside, It's also a source of rosmarinic acid. "Peppermint (M. piperita) essential oil with high levels of menthol and menthone and characteristic in vitro AChE inhibitory, calcium regulatory, GABAA receptor and nicotinic receptor binding properties, beneficially modulated performance of demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive testing. These effects were only evident for the higher (100 μL) of the two doses investigated; raising the possibility that doses of this essential oil in excess of 100 μL would exert greater effects in terms of cognitive/mood enhancement." [1] https://doi.org/10.3390/nu10081029 Rosemary (now technically a Salvia) Rosmarinus officinalis is herb used for culinary and medicinal purposes that contains polyphenols such as rosmarinic acid, carnosic acid, and luteolin and other water- soluble phytochemicals that exert several effects on psychiatric diseases or neurological function including neuroprotective, cognitive properties, anti- depressive and anti-anxiety effects. R. officinalis EO (ROEO) has been reported to exhibit anti-proliferative, antioxidant and antibacterial activities, as well as improvement of cognition, mood, and memory function in healthy adults and improvement of locomotor activity in mice . 2 Data suggest potential beneficial properties of acute consumption of rosemary water in humans [1]. Rosemary tea administration exerts anxiolytic and antidepressant effects in mice and inhibits cholinesterase activity [2] inhalation of rosemary essential oil is reported to improve cognition, mood, and memory and has anxiolytic, anti-stress and neuronal cell differentiation induction effects. The presence of 1,8-cineole and rosmarinic acid and the absorption of these (and other) compounds may facilitate performance through cholinergic pathways. Serum levels of 1,8-cineole have previously been demonstrated to correlate with task performance following exposure to rosemary aroma. Rosemary polyphenols cause the regulation of several neurotransmitters (dopamine, norepinephrine, serotonin and acetylcholine) and gene expression [3] while the volatiles activate the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production [4] Carnosic acid and carnosol, which are major components of the rosemary extract, were able to promote markedly enhanced synthesis of NGF [5] In a study, an improved performance was observed in a task due to the olfactory impact of rosemary EO with increase in overall quality of memory. The combination of EOs from R. officinalis and M. piperita were reported to augment the memory and activity level of mice and dogs. Rosemary EO also possess moderate AChE inhibitory activity and can synergistically act with 2-pinene and 1,8-cineole. It also increases locomotor activity, motivate vigor, stimulate cerebral cortex, cause mood relaxation and increase alertness (Hongratanaworakit, 2009) [1] https://www.ncbi.nlm.nih.gov/pubmed/30318972 [2] https://www.ncbi.nlm.nih.gov/pubmed/25910439 [3] https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00657-2 [4] https://www.ncbi.nlm.nih.gov/pubmed/29273038 [5] https://www.ncbi.nlm.nih.gov/pubmed/14600414 Sages: Salvia officinalis 3 There is mounting evidence of beneficial cognitive and mood effects but although Salvia officinalis seems to have positive, acute, cognitive-enhancing and mood effects, its effects over longer-term ingestion require study [1]. A randomised placebo-controlled trial in healthy young participants found 300–600 mg encapsulated dried Salvia leaf improved mood and cognitive functions after a single dose Confirmed clinical pharmacological effects of Sage on humans so far include improvement of memory and cognitive functions, pain relief and significant improvement in blood glucose (including HbA1c and post-prandial glucose) and lipid profile (especially an increase of high- density lipoprotein, HDL) [2]. AChE inhibition via Salvia phenolic mono- and di-terpenes has been reported, suggesting beneficial effects in Alzheimer’s disease and for cognitive functions. A recent study noted a broad pharmacodynamic spectrum for Salvia officinalis, with specific effects seen on adrenergic α2A, muscarinic M3, and μ-opioid receptors, as well as on serotonin neurotransmission [3]. Biologically active substances in Salvia comprise mono-, di- and triterpenes like 1,8–cineol, carnosic acid, carnosol or ursolic acid as well as phenolic compounds including caffeic- or rosmarinic acid or flavonoids (e.g. quercetin). The highest binding affinities were seen for extracts prepared from freshly harvested Salvia officinalis in comparison to samples obtained from dried plants [1] https://dx.doi.org/10.1007%2Fs40268-016-0157-5 [2] https://www.ncbi.nlm.nih.gov/pubmed/30845696 [3] https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-019-25 49-x 4 Salvia lavandulaefolia (Spanish sage) In a placebo-controlled, double-blind, balanced, crossover study, mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-microl dose and elevated 'calmness' following 25 microl of oral essential oils from Salvia. These results represent further evidence that Salvia is capable of acute modulation of mood and cognition in healthy young adults. The data also suggest that previous reports of memory enhancement by Salvia may be due to more efficient retrieval of target material. [1] https://doi.org/10.1016/s0091-3057(03)00122-9 [2] https://doi.org/10.1016/s0091-3057(03)00122-9 [3] https://doi.org/10.1177/0269881110385594 Salvia sclarea (Clary Sage) S. sclarea extract had decent affinity for the 5-HT2A receptors and fairly good affinity for the D2 receptors. Clary sage oil has antidepressant-like effects and potent anti-stress effects. The antidepressant-like effect of clary oil is closely associated with modulation of the DAergic pathway while the anti-stress effect relies on DA/5-HT1A pathways [2] [1] https://doi.org/10.1016/j.jep.2010.04.035 Salvia elegans (Pineapple sage) Salvia elegans has antidepressant, anxiolytic and antihypertensive activity, popularly known as "mirto", is a shrub that has been widely used in Mexican traditional medicine for the treatment of different central nervous system diseases, principally, anxiety. It showed strong binding to mAChRs. It contains active flavanones like 5-O-(6-rhamnosylglucoside)-7- hydroxy-4'-methoxyflavanone and ursolic acid. Melissa officinalis Lemon balm treatments were generally associated with improvements in mood and/or cognitive performance [1] Improvements in feelings include “calm”, “secure”, “at ease”, 5 “satisfied”, “comfortable”, “self-confident”, “relaxed”, “content’, “steady” and “pleasant”. "Twenty healthy young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf, or a matching placebo, at 7-day intervals. Cognitive performance and mood were assessed before dose and at 1, 3, and 6 h after dose - data supported the cholinergic receptor-binding properties of M. officinalis and the fact that it acts on mood and cognition in a dose- and time-dependent manner [2] 60 drops/day of lemon balm extract exerted positive effects on cognition in Alzheimer’s Disease Has GABA transaminase inhibition activity via rosmarinic acid thus acting as an indirect GABAergic. Shown to improve mood and mental performance. These effects are believed to involve muscarinic and nicotinic acetylcholine receptors. Positive results have been achieved in a small clinical trial involving Alzheimer patients with mild to moderate symptoms. Lemon balm essential oil has an affinity for gamma-aminobutyric acid A (GABAA) receptors and exerts a net depressant effect on neuronal activity (commensurate with anxiolytic effects). Essential oils obtained from Melissa officinalis leaf showed high acetylcholinesterase and butyrylcholinesterase co-inhibitory activities. They also found that Melissa elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission. Lemon balm essential oil inhibited radioligands binding to the muscarinic M1, 5HT2A, histamine H3 receptors and GABAA receptor channel site. M. officinalis EO displayed broad receptor binding capacity in comparison to L. angustifolia EO, and showed affinity for binding with 5HT1A and the agonist binding site of GABAA receptors. A 50:50 mixture of Melissa and Lavender essential oils inhibited [3H] flunitrazepam binding, whereas the individual oils had no significant effect. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245564/ [2] https://www.ncbi.nlm.nih.gov/pubmed/12888775 Satureja spp . (Winter and summer savory) Satureja species are traditionally used for various diseases and complications such as gastrointestinal cramps, nausea, diarrhea, muscle pains, and infectious diseases. It has substantial AChE inhibitory (more potent than rosemary, less than Salvia officinalis) and antioxidant properties making it promising for cognitive decline. Flavonoids, tannins, acids and exudates are other known compounds in savory and includes hydroxycinnamic acids and derivatives, (+)-catechin, vanillic, and protocatechuic acids. Based on the presence of all these metabolites, pharmacological properties such as antioxidant, anti-inflammatory and analgesic, and anti-hypercholesterolemic activity have also been demonstrated. The main constituents of the essential oil (quite rich) were carvacrol and thymol. Extracts significantly 6 enhances male sexual behaviour on multiple measures. Oregano In humans, with a supercritical CO2 extract, "a single dose ... induced a state of wakeful relaxation, enhanced vigilance and improved concentration in addition to increased mental capacity but did not affect sleep structure" [1] A single dose increased calmness, vigilance, mental information processing capacity, with an increase in processing speed with the conclusion it "is safe and does not exhibit any adverse side effects at the dosages providing the functional benefits, a result that was also confirmed by behavioural studies". " in vitro profiling revealed that only [an] extract, but none of its constituents, showed the full range of desired activities, namely inhibition of the reuptake of all three monoamine neurotransmitters in addition to reversible inhibition of their inhibiting enzyme. Our data are in line with the well-studied phenomenon that mixtures of natural ingredients, especially phytochemicals, exert synergistic effects that are not present in single ingredients" Carvacrol also exerts several actions on the neuronal system including acetylcholinesterase inhibition as well as having anxiolytic and antidepressant properties having the ability to likely modulate mood and cognitive processes. It also modulates central neurotransmitter pathways, such as dopaminergic, serotonergic and GABAergic systems, an oregano extract acting as a triple reuptake inhibitor. It seems to cause a specific increase of DA levels in PFC and "ingested in low concentrations, it might determine feelings of well-being and could possibly have positive reinforcer effects." "Carvacrol is a monoterpenic phenol isolated from aromatic herbs including oregano and thyme. This aromatic phytochemical has anti-inflammatory, analgesic, antiarthritic, antiallergic, anticarcinogenic, antidiabetic, cardioprotective, gastroprotective, hepatoprotective, and neuroprotective properties. This monoterpenoid phenol regulates human ion channels transient receptor potential V3 and A1 causing a sensation of warmth. It is also known that carvacrol can activate PPAR and suppress COX-2 mediated inflammation. Dong et al. 7 demonstrated that enzyme cytochrome P450 2A6 (CYP2A6) is the predominant drug-metabolizing enzyme involved in the metabolism of carvacrol requesting attention when carvacrol is coadministrated with other compounds mainly undergoing CYP2A6-mediated metabolism. Orally administered carvacrol (12.5–50 mg/kg) induces antidepressant effects that seem to be mediated by the dopaminergic brain pathways in mice. Zotti et al. showed that carvacrol administration (12.5 mg/kg, by mouth [PO] for 7 days) can raise 5-HT and dopamine ranges in the hippocampus and prefrontal cortex" [1] https://www.teknoscienze.com/tks_article/animal-and-human-efficacy-data-of-a-brain- active-oregano-extract/ Sculletaria spp. (Skullcaps) S. lateriflora (American Skullcap) It had notable effects in reducing subjective anxiety scores [1] S. lateriflora may be superior to pharmaceutical anxiolytics in its ability to produce mood enhancing effects without side-effects such as a reduction in energy or cognition or causing fatigue [2] [1] https://pubmed.ncbi.nlm.nih.gov/12652886/ [2] https://pubmed.ncbi.nlm.nih.gov/23878109/ S. baicalensis (Baikal skullcap) S. baicalensis and it's primary active constituent baicalin has diverse pharmacological properties. In particular, baicalin seems to have promising CNS activity [1]. Antidepressant- and anxiolytic-like properties (the latter mediated through the activation of benzodiazepine binding site of GABAA receptors) 8 Inhibits prolyl oligopeptidase dose-dependently, having potential benefits for schizophrenia, bipolar affective disorder, and related neuropsychiatric diseases [2]. Can potentially be used to treat dopaminergic dysfunction-associated CNS diseases (incl. neurodegenerative and ADHD). It's able to protect dopaminergic neurons and modulate brain dopamine levels, thus serving as a potentially effective novel treatment for ADHD [3]. In schizophrenia, addition of baicalin (1.5g/day) to atypical antipsychotics led to greater improvements in both primary and secondary negative symptoms than those treated with antipsychotics alone - seems to have efficacy for predominant negative symptoms and in improving cognitive function [4]. Able to facilitate remyelination in various models of CNS disorders and suppress neuroinflammation [5] Baicalin can: - pass through the blood–brain barrier - stimulate neurogenesis - promote neural differentiation and inhibit neuronal apoptosis - inhibit neuroinflammation and oxidative stress - promote CNS myelin repair Shown to be relatively nontoxic when given orally [1] https://www.mdpi.com/2076-3425/8/6/104 [2] https://doi.org/10.1016/j.bmc.2008.04.067 [3] https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-019-0428-5 [4] https://www.academia.edu/97015688/Efficacy_and_safety_of_the_adjunctive_Baicalin_in_ schizophrenia_patients_with_negative_symptoms_and_cognitive_impairment_a_randomiz ed_pilot_study [5] https://nn.neurology.org/content/9/2/e1142.abstract 9