Salvia

Other Names

bird's sagebroadleaf sagechaj gradinskichiaChinese sageclaryclary sagecommon sageCretan sageculinary sageDalmatian sageDan Shendanshendiviner's sageelelisphakosErba SaviaFranse theegarden sagegolden chiagolden sageGreek sageHeilsalbeiKaduljakitchen sageLabiataeLamiaceae (sage family)lelifagusmagic mintmashkodewashkmystic sageOrvosi zsályared sageredroot sageRyytisalviasacred herbSafakussageSalbeiSàleviasalieŠalvěj lékařskásálviaSalvia apianaSalvia columbariaeSalvia divinorumsalvia dulceSalvia fruticosaSalvia hispanicaSalvia lavandulifoliaSalvia miltiorrhizaSalvia officinalisSalvia rosmarinussalvia salvatrixSalvia sclareaSalviae Miltiorrhizae Radix et Rhizomasauge officinaleSelviashay al-jabalska Mariaska PastoraSpanish sagesphakosSzałwia lekarskathé de la GrèceTıbbi ada çayıtrue sagewhite sageШалфей лекарственныйقصعين مخزنيمريميةセージ丹參세이지

Synopsis

Salvia: A Comprehensive Reference

Overview and Scope

The name Salvia designates the largest genus within the mint family (Lamiaceae), encompassing an extraordinary breadth of botanical and pharmacological diversity. The genus Salvia encompasses about 900 shrub-like species of plants belonging to the mint family, Lamiaceae (Labiatae). In popular, scientific, and regulatory discourse, "Salvia" most commonly refers to one of three pharmacologically distinct species: Salvia officinalis L. (common sage or garden sage), used as a culinary herb and traditional medicine throughout the Mediterranean world; Salvia miltiorrhiza Bunge (Danshen or red sage), a cornerstone of Traditional Chinese Medicine with well-documented cardiovascular applications; and Salvia divinorum Epling & Játiva-M. (diviner's sage), a psychoactive plant from Oaxacan Mexico with a unique ethnobotanical history and distinctive neuropharmacology. This article provides a detailed treatment of all three species, clearly delineated by section.

Part I: Salvia officinalis L. — Common Sage

1.1 Botanical Identity and Taxonomy

Salvia officinalis, common sage or sage, is a perennial, evergreen subshrub, with woody stems, grayish leaves, and blue to purplish flowers. It is a member of the mint family (Lamiaceae) and native to the Mediterranean region, though it has been naturalized in many places throughout the world. It is native to Middle East and Mediterranean areas, but today has been naturalized throughout the world. The Old World type grows to approximately 60 cm (2 ft) tall and wide, with lavender flowers most common, though they can also be white, pink, or purple.

The genus name Salvia is widely held to derive from the Latin salvare, meaning "to save" — its common appellation, Salvia, derives from the Latin verb salvare, signifying "to save," a testament to its enduring reputation as a healing herb. Salvia officinalis L., also known as the "Salvation Plant," has been long used and well-documented in traditional medicine around the globe.

The species is closely related to Salvia fruticosa Mill. (three-lobed or Greek sage), which has a distinct but overlapping Mediterranean distribution and traditional use profile, and to Salvia lavandulaefolia (Spanish sage), which has been studied for cognitive effects. The botanical family Lamiaceae, which comprises around 230 genera and 7,100 species worldwide, is of great importance for medicine, cooking, cosmetics, and the cultivation of medicinal and aromatic plants.

1.2 Common Forms and Preparations

Salvia officinalis is available in a wide range of forms for both medicinal and culinary use. According to a 2016 EMA herbal monograph of Salvia officinalis L., folium, an aqueous infusion of Salvia officinalis is applied to the skin in traditional medicine for the relief of minor inflammation. The monograph also describes Salvia officinalis being consumed orally as a dry/liquid extract or tincture, for the treatment of heartburn, bloating, excessive sweating, and relief of inflammation of the mouth or throat. Comminuted herbal substance (the dried, cut leaf), and liquid extract (DER 1:1), with extraction solvent ethanol 70% V/V, are recognized preparation forms. Sage tincture is produced from 1 part of comminuted sage leaf and 10 parts of ethanol (70% V/V), and is a separate monograph in the European Pharmacopoeia.

Most medicinal uses of Salvia officinalis products in Europe are marketed in varied forms, at a daily dose of 1.5–2.5 g/day. In Spain, a dry extract of Salvia officinalis is marketed for the treatment of excessive sweating at a dose of 360 mg/day (equivalent to 500–800 mg of dried Salvia officinalis leaves). Beyond pharmaceutical preparations, sage species are popular herbal teas in the Mediterranean, for example S. fruticosa in Greece, Crete, and Turkey, and S. officinalis subsp. lavandulifolia in Spain.

1.3 Traditional and Historical Use

The use of S. officinalis in medicine extends to antiquity. It has been used over several millennia across a number of different cultures including Ayurvedic medicine, as well as early Greek and Chinese civilisations. Ancient civilizations, including the venerable Romans and Greeks, held sage in high esteem for its medicinal virtues. They employed it to address a broad spectrum of ailments, from digestive disturbances to the enhancement of memory.

In folk medicine, S. officinalis has been used for the treatment of different kinds of disorders including seizure, ulcers, gout, rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and hyperglycemia. Salvia officinalis has been used since ancient times for treating snakebites, increasing women's fertility, and more.

Persian physicians also incorporated the herb into formal medical systems. Persian physicians of the 10th century, like Avicenna, classified sage among warming herbs, prescribing it for excessive phlegm and digestive torpor. English herbalists subsequently documented multiple uses: English herbalist John Gerard included it in his 1597 Herball, noting that distilled water of sage was used to treat headaches, while powdered leaves poulticed on wounds accelerated healing.

Sage also had a significant culinary role. Since ancient times, Salvia spp. have been sold commercially not only for use in therapy but also as a spice to flavor meats such as pork, sausage, and poultry.

1.4 Key Constituents and Active Compounds

Salvia officinalis contains a chemically diverse array of bioactive molecules. Essential oils, non-volatile terpenes, flavonoids, and phenolic acids are proven to be the main active principles of S. officinalis that greatly contribute to its pharmacological properties.

Essential Oil Constituents

The composition of essential oils can vary widely, but the major components are mostly oxygenated monoterpenoids α-thujone, 1,8-cineole, and camphor. Principal components of the essential oil, in addition to thujone, are 1,8-cineole and camphor. Thujone exists as two isomers (α-thujone and β-thujone) and is responsible for both some of the herb's biological activities and its toxicological concerns (see Safety section).

Diterpenes and Triterpenes

Diterpenes and triterpenes — carnosic acid, carnosol, and ursolic acid — are also found to be present in Dalmatian sage. In addition, the leaves contain tannins, diterpene bitter principles, triterpenes, steroids, flavones, and flavonoid glycosides.

Phenolic Acids and Flavonoids

The most prevalent flavonoids include glycosides of luteolin, apigenin, hispidulin, and quercetin. Rosmarinic, salvianolic, caffeic, and sagerinic acids, and sagecoumarin are abundant phenolic acids of S. officinalis.

Strong bioactive compounds like phenolic acids (like rosmarinic acid and caffeic acid), flavonoids (like luteolin and apigenin), diterpenes (like carnosic acid and carnosol), triterpenes, and essential oils (like thujone and camphor) are found in sage.

1.5 Mechanisms of Action

Cholinergic System Modulation

A primary mechanistic hypothesis for the cognitive effects of S. officinalis is inhibition of acetylcholinesterase (AChE). Acetylcholine (ACh) levels in synaptic clefts are raised by rosmarinic acid's reversible inhibition of acetylcholinesterase (AChE). In Alzheimer's sufferers, this makes up for cholinergic deficiencies. Preclinical and clinical studies have demonstrated that the ingredients and essential oils of S. officinalis L., which are commonly utilized in European folk medicine to enhance memory, are advantageous for acute memory and attention in healthy young and old people. The majority of researchers concur that the cholinesterase inhibitory activity of Salvia species is responsible for the effects that have been observed.

In vitro assays have identified specific compounds as particularly potent: inhibitory potentials of secondary metabolites including rosmarinic acid, carnosic acid, and carnosol were investigated against acetylcholinesterase and butyrylcholinesterase. Elevated inhibitory effects on acetyl- and butyryl-cholinesterase of dihydrotanshinone I (IC50: 1.50 ± 0.02 and 0.50 ± 0.01 µg/mL, respectively), carnosol (IC50: 11.15 ± 0.05 and 3.92 ± 0.03 µg/mL), and carnosic acid (IC50: 31.83 ± 0.65 and 4.12 ± 0.04 µg/mL) were observed.

However, results in this area are not entirely consistent. One investigation observed no effects on serotonin re-uptake, very limited acetylcholinesterase (AChE) inhibition, and estrogenic activity in only one subfraction, which was lost in the total extract. Others, however, have also seen AChE inhibition of Salvia phenolic mono- and di-terpenes in mice, suggesting beneficial effects in Alzheimer's disease and for cognitive functions. Overall, results are contradictory and seem largely to depend on the manufacturing processes and/or plant species and plant parts used.

Anti-inflammatory Mechanisms

Sage's bioactive components work together to suppress inflammatory signaling pathways, especially NF-κB. By inhibiting IκB kinase (IKK), sage chemicals at 10–20 µM (such as rosmarinic acid and carnosic acid) stop IκB from being phosphorylated and degraded.

Neuroprotective Mechanisms

Carnosic acid inhibits fibril production and decreases plaque deposition in hippocampus neurons via binding to Aβ peptides. While carnosic acid increases mitochondrial Complex I activity, maintaining ATP generation, salvianolic acid scavenges ROS in neurons.

Antioxidant Activity

Research emphasizes the antioxidant properties of S. officinalis due to its flavonoids and phenolic acids. Rosmarinic acid in Salvia has antioxidant and anti-apoptosis effects and protects the neurons against the toxicity of Aβ.

1.6 Scientific Evidence by Area of Use

1.6.1 Cognitive Function and Alzheimer's Disease

Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated.

Clinical trials in Alzheimer's disease: The pivotal human trial in this area was conducted by Akhondzadeh et al. (2003). The objective of this study was to assess the efficacy and safety of Salvia officinalis extract in Alzheimer's disease (AD) at 4 months using a fixed dose. A randomized, double-blind, placebo-controlled trial was conducted in three centers. Patients with mild to moderate AD (n=36) with a score of ≤12 on the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-cog) and ≤2 on Clinical Dementia Rating (CDR) were randomized to placebo or fixed dose of Salvia officinalis extract. Over 16 weeks, the primary outcome measure was the change in ADAS-cog score. At 4 months, S. officinalis extract produced a significantly better outcome on cognitive functions than placebo (ADAS-cog: F = 4.77, d.f. = 1, P = 0.03; CDR-SB: F = 10.84, d.f. = 1, P < 0.003). This trial was notable for being small (n=36) and conducted at a single point in time, limiting generalizability.

Systematic review of cognitive trials: Eight clinical studies investigating the acute effects of S. officinalis on healthy subjects were included in a systematic review. Several botanical ingredients have been suggested to have benefits in the area of cognitive health; Salvia officinalis has shown anti-inflammatory effects and exhibited promising cognitive improvements in multiple human studies. One study demonstrated anti-inflammatory effects for S. officinalis across a broad set of in vitro models in human cells, and adds further evidence to support modulation of acetylcholine and monoamine neurotransmitter levels as mechanisms contributing to the benefits of the herb on cognitive health.

Evidence strength: Preliminary to moderate. Positive signals exist from small randomized trials and a systematic review, but all studies involve small sample sizes and the evidence base is insufficient to support a clinical recommendation for Alzheimer's disease treatment.

1.6.2 Menopausal Symptoms (Hot Flashes and Vasomotor Symptoms)

S. officinalis has been most extensively studied in clinical trials for the management of menopausal symptoms. The first placebo-controlled, confirmatory clinical trial showed efficacy for a Salvia officinalis preparation not only in the reduction of hot flashes but of other climacteric symptoms as well.

One double-blind, randomized, placebo-controlled clinical trial used the proprietary preparation Menosan® (a hydroalcoholic, thujone-free extract from freshly harvested S. officinalis leaves). Salvia officinalis improved not only vasomotor symptoms (Menopause Rating Scale [MRS] and Hot Flush Score [HFS] scores) but simultaneously exerted a positive impact on accompanying somato-vegetative and psychological symptoms, thus addressing a broad range of menopausal complaints. Salvia officinalis proved to be a valid option for women reluctant or contraindicated to HRT who seek a natural and safe alternative treatment of their vasomotor and other typical menopausal symptoms like alterations of mood and cognition.

An earlier double-blind randomized clinical trial enrolled 100 postmenopausal women with hot flashes. This double-blind randomized clinical trial was performed on 100 qualified postmenopausal women with hot flashes. The study women were divided into two groups daily treated with 3 salvia or placebo tablets (100 mg) for 8 weeks.

Additional evidence from a separate randomized trial found sleep benefits: study findings showed that the average post-intervention sleep score in common sage groups decreased 3.8 units when compared with pre-intervention, and this decline of sleep score was statistically significant. In the control group, after treatment, the sleep score average remained the same.

A 2023 systematic review and meta-analysis (Moradi et al., cited by NCCIH) further synthesized the evidence from multiple trials on hot flashes in postmenopausal women. Moradi et al. published "The effect of Salvia officinalis on hot flashes in postmenopausal women: a systematic review and meta-analysis" in the International Journal of Community Based Nursing and Midwifery.

Evidence strength: Moderate. Multiple small-to-medium RCTs and at least one placebo-controlled confirmatory trial support efficacy for hot flash reduction. Limitations include variable preparations, short trial durations, and small sample sizes across the evidence base.

1.6.3 Glycemic Control and Lipid Profile

S. officinalis has been investigated in type 2 diabetic patients for effects on blood glucose and lipid markers. A study was performed to investigate the hypoglycemic effect of Salvia officinalis on blood glucose, glycosylated hemoglobin (HbA1c), lipid profile, liver and kidney function tests in a double-blind clinical trial on 80 type II diabetic patients who had not reached ideal control of the disease. The case group received Salvia officinalis and the control group received placebo tablets three times a day for three months. Fasting blood sugar (FBS) and 2-hour postprandial (2hpp) glucose were checked at the beginning and every 2 weeks for three months; HbA1c, lipid profile, liver and kidney function tests were also measured at baseline and at the end of the trial.

Antihyperlipidemic effects have also been investigated: Kianbakht et al. investigated the "antihyperlipidemic effects of Salvia officinalis L. leaf extract in patients with hyperlipidemia: a randomized double-blind placebo-controlled clinical trial," published in Phytotherapy Research in 2011. A 2022 systematic review and meta-analysis published in the Journal of Complementary and Integrative Medicine evaluated the effect of S. officinalis on blood glycemic indexes and blood lipid profile in diabetic patients.

Preclinically, Salvia officinalis decoctions were investigated for antioxidant activity and inhibitory ability towards key enzymes with impact in diabetes and obesity (α-glucosidase, α-amylase, and pancreatic lipase). The S. officinalis decoction exhibited moderate inhibitory capacity against α-glucosidase.

Evidence strength: Preliminary. Small RCTs show signals for glycemic and lipid benefit, but the total clinical evidence base is limited and methodologically heterogeneous.

1.6.4 Antimicrobial Activity

Both in vitro and in vivo studies demonstrate its effectiveness against bacterial infections. The compounds in the Salvia genus exhibit antioxidant, antibacterial, anticancer, antimicrobial, anti-inflammatory, anti-dermatophyte, antiviral, antineoplastic, and anti-platelet aggregation properties. The antimicrobial evidence to date is largely preclinical; robust human trials for infectious indications have not been published.

1.6.5 Anti-inflammatory and Antioxidant Applications

Studies have revealed a wide range of pharmacological activities including anticancer, anti-inflammatory, anti-nociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects. The bulk of anti-inflammatory evidence rests on in vitro and animal studies; specific human trials targeting inflammatory outcomes as a primary endpoint are limited.

1.7 Dosage Forms and Reported Dosages

Oral medicinal use (Europe): Dry/liquid extract or tincture; typical daily dose of 1.5–2.5 g/day for dried leaf preparations. In Spain, dry extract at 360 mg/day (equivalent to 500–800 mg dried leaves) for excessive sweating.
Hot flash trials: 3 salvia tablets (100 mg each) daily for 8 weeks.
Alzheimer's disease trial (Akhondzadeh 2003): Fixed dose of 60 drops/day of Salvia officinalis extract.
Herbal infusion (tea): The EMA monograph recognizes aqueous infusion (tea) as a traditional form; preparation involves pouring hot boiled water on dried leaf and steeping.
Tincture: Produced from 1 part comminuted sage leaf in 10 parts ethanol (70% V/V), with a separate monograph in the European Pharmacopoeia.

1.8 Safety Considerations

Thujone Toxicity

The principal safety concern with S. officinalis preparations — particularly the essential oil — is the content of thujone (primarily α-thujone). The essential oil of Salvia officinalis L. contains constituents like thujone and camphor, which have toxic effects in high doses. Toxicological dose limits have been set based on the available toxicological data and other studies. The toxic effect appears to be of central nervous origin with convulsions as the main symptom. Based on existing data it can be concluded that because of the toxic properties of the essential oil, one should not exceed recommendations concerning the posology of sage leaf.

Sage oil is characterized by high levels of thujone. Consumption of sage oil in single-ingredient products involves a high risk of exceeding the maximum recommended daily intake of thujone. Thujone is toxic and may cause seizures at high doses as shown in animal studies and indicated from case reports.

The EMA and regulatory bodies have set limits on thujone exposure. The presence of thujone in sage leaf preparations mentioned in the monograph is restricted to a daily exposure of 6.0 mg/person for a maximum duration of 2 weeks. For adults, the upper limit for total daily intake of thujone from health products is 6 mg. The EMA's benefit-risk assessment of sage oil (as a standalone essential oil product) is explicitly negative: the benefit-risk analysis of sage oil is negative.

Anecdotal toxicity reports from overdosing exist, though establishing thujone as the sole causal agent has proved difficult: a number of anecdotal reports have been published concerning toxicity associated with overdosing with extracts of Salvia or Artemisia in humans; however, none of these confirms these effects to be due exclusively to thujone.

The EMA recommends that low-thujone chemotypes should be preferred. Thujone is reported to be neurotoxic and chemotypes with low content of thujone should be preferred.

Pregnancy and Lactation

Pure Salvia officinalis oil and extract consumption is contraindicated during pregnancy, due to its abortifacient and emmenagogic properties.

Reproductive and Genotoxicity Data Gaps

Tests on reproductive toxicity, genotoxicity, and carcinogenicity have not been performed with preparations of Salviae officinalis folium covered by the EMA monograph. A European Union list entry is not supported due to lack of adequate data on genotoxicity. These are significant evidence gaps acknowledged by regulatory authorities.

Drug Interactions

Given its activity on cytochrome P450 enzymes (implicated in preclinical data) and pharmacodynamic interactions via the cholinergic system, interactions with cholinesterase inhibitors used in dementia, anticonvulsant drugs, and sedatives are biologically plausible, though human pharmacokinetic interaction studies are limited.

Part II: Salvia miltiorrhiza Bunge — Danshen (Red Sage)

2.1 Botanical Identity and Source

Salvia miltiorrhiza (Labiatae, Lamiaceae), danshen, is an annual sage mainly found in China and neighboring countries. Danshen, the dried root or rhizome of Salvia miltiorrhiza Bunge, has been widely used in Asian countries for treating cardiovascular diseases, including coronary heart disease, myocardial infarction (MI), angina pectoris, and atherosclerosis. It is distinct from S. officinalis in its morphology (notable for its bright red roots), geographic distribution, chemical profile, and historical use.

2.2 Traditional and Historical Use

Salvia miltiorrhiza Bunge (Danshen) is an eminent medicinal herb that possesses broad cardiovascular and cerebrovascular protective actions and has been used in Asian countries for many centuries. Danshen has long been used for relieving blood stasis and improving blood circulation in East Asian medicines. The crude drug (dried root) and its preparations are currently used in China to treat patients suffering from heart attack, angina pectoris, stroke, and some other conditions.

Salvia miltiorrhiza Bunge (SM), known as Danshen, belongs to the family Labiatae and is widely used in TCM as a traditional natural medicine in clinics for several decades in various parts of China. SM is used to treat malignant tumors, neurological, metabolic disorders, lung diseases, cardiovascular diseases, inflammatory diseases, gynecological diseases, liver diseases, and renal diseases.

2.3 Key Constituents and Active Compounds

The chemical constituents from the root extract of SM are divided into two categories: liposoluble tanshinones and water-soluble phenolics, most of which have been identified and purified using various chromatographic and spectroscopic methods.

Lipophilic constituents — tanshinone I, tanshinone IIA, tanshinone IIB, cryptotanshinone, dihydrotanshinone, etc. — as well as hydrophilic constituents — danshensu, salvianolic acid A and B, protocatechuic aldehyde, etc. — contribute to the cardiovascular protective actions of Danshen, suggesting a potential synergism among these constituents. To date, the chemical constituents of Danshen have been well identified, including more than 30 lipophilic compounds that have a diterpene quinone structure (tanshinone I–VI, cryptotanshinone, isotanshinone I–II, Danshenol A, etc.) and more than 50 hydrophilic compounds that mainly have a phenolic acid structure (Danshensu, salvianolic acids, etc.).

2.4 Mechanisms of Action

In vivo and in vitro studies show that tanshinone IIA and salvianolate have a wide range of cardiovascular and other pharmacological effects, including antioxidative, anti-inflammatory, endothelial protective, myocardial protective, anticoagulation, vasodilation, and anti-atherosclerosis, as well as significantly helping to reduce proliferation and migration of vascular smooth muscle cells.

Tanshinone IIA, the most actively investigated constituent of Danshen, has been reported to possess a wide range of therapeutic effects in cardiovascular diseases; its anti-inflammatory effects include the downregulation of the Toll-like receptor 4 (TLR4)/NF-κB pathway and the inhibition of nitric oxide (NO), interleukin (IL)-1β, IL-6, and TNF-α.

Pharmacological examinations showed that the plant and its active ingredients, tanshinones and salvianolic acids, have anticoagulant, vasodilatory, increased blood flow, anti-inflammatory, free radical scavenging, mitochondrial protective, and other activities.

Miltirone, a diterpenoid of S. miltiorrhiza, has sedative activity and is a benzodiazepine receptor agonist. Purified tanshinone IIA and IIB are neuroprotective in cerebral ischemia and reperfusion.

2.5 Scientific Evidence by Area of Use

2.5.1 Cardiovascular Disease

Accumulating evidence suggests that Danshen and its components prevent vascular diseases, in particular atherosclerosis and cardiac diseases, including myocardial infarction, myocardial ischemia/reperfusion injury, arrhythmia, cardiac hypertrophy, and cardiac fibrosis.

Clinical use in China: Some clinical studies reported that S. miltiorrhiza preparations in combination with Western medicine were more effective for treatment of various cardiovascular diseases including angina pectoris, myocardial infarction, hypertension, hyperlipidemia, and pulmonary heart diseases. The majority of this clinical evidence comes from studies conducted in China, often in combination with other TCM preparations (notably "fufang danshen"), and most published trials lack the methodological rigor (double-blinding, clear randomization, independent outcomes assessment) of Western regulatory-grade trials.

Results from animal and cell disease models reveal that S. miltiorrhiza plays beneficial roles in improving cardiovascular conditions such as atherosclerosis, hypertension, and myocardial ischemia.

2.5.2 Dyslipidemia

While Danshen, and its preparations in pill and injection formulations, are widely used in China for the treatment of dyslipidemia and atherosclerotic cardiovascular disease, studies have elucidated favorable effects of Danshen usage in dyslipidemia. A meta-analysis of clinical efficacy (2024, PMC11597782) reviewed the evidence for Danshen as complementary therapy for dyslipidemia, with in silico mechanistic insights also provided.

Evidence strength: Moderate for cardiovascular protection in preclinical models and early-phase clinical studies conducted in China; insufficient by Western regulatory standards for standalone therapeutic claims, partly due to trial quality and co-administration with other agents.

2.5.3 Drug Interactions with Danshen

Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. A review summarized the effects of these bioactive components on the pharmacokinetics of co-medicated drugs with mechanistic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on published data from both in vitro and in vivo human studies. Danshen is recognized to interact with warfarin (increasing anticoagulant effect), with well-documented case reports and pharmacokinetic data; Danshen represents a traditional Chinese medicine that has a relatively high safety profile, but its interactions with anticoagulants are clinically significant and documented.

Part III: Salvia divinorum Epling & Játiva-M. — Diviner's Sage

3.1 Botanical Identity and Source

Salvia divinorum (Epling & Játiva-M.) is a member of the mint family (Lamiaceae) endemic to the Sierra Mazateca region of the Sierra Madre de Oaxaca of southern Mexico. Salvia divinorum (Latin: sage of the diviners; also called ska maría pastora, seer's sage, yerba de la pastora, magic mint, or simply salvia) is a species of plant in the sage genus Salvia, known for its transient psychoactive properties when its leaves, or extracts made from the leaves, are administered by smoking, chewing, or drinking (as a tea).

Salvia divinorum produces few viable seeds even when it does flower — no seeds have ever been observed on plants in the wild. For an unknown reason, pollen fertility is also comparatively reduced.

3.2 Traditional and Historical Use

It has a history of known ethnobotanical use by the Mazatec Indians extending several centuries, both in medicinal and spiritual practices. Mazatec shamans have a long and continuous tradition of religious use of S. divinorum to facilitate visionary states of consciousness during spiritual healing sessions.

For centuries, Mazatec shamans have cultivated and utilized the plant in religious ceremonies for divination, healing, and spiritual journeys, primarily consuming it by chewing fresh leaves or drinking infusions. In their rituals, the shamans use only freshly harvested S. divinorum leaves. They see the plant as an incarnation of the Virgin Mary, and begin the ritual with an invocation to Mary, Saint Peter, the Holy Trinity, and other saints.

The plant's existence was first described scientifically in the modern era: the American anthropologist Jean Bassett Johnson made expeditions to Mexico in the mid-to-late 1930s, observed the entheogenic use of Salvia divinorum by the Mazatecs there, and was the first to describe the existence of the plant in 1939. Subsequently, other researchers, including Blas Pablo Reko and Robert J. Weitlaner, also described the plant and its use in the 1940s and 1950s.

3.3 Key Constituent: Salvinorin A

Salvinorin A (chemical formula C₂₃H₂₈O₈) is a trans-neoclerodane diterpenoid and the known active constituent of Salvia divinorum. This compound is present in the dried plant at about 0.18%. Salvinorin A is not an alkaloid (meaning it does not contain a basic nitrogen), unlike most known opioid receptor ligands. Salvinorin A is the first documented diterpene hallucinogen.

Daniel Siebert identified salvinorin A as the active constituent of Salvia divinorum via self-experimentation in 1993 and published these findings in 1994. The chemical identification of the psychoactive principle of Salvia divinorum was completed simultaneously by Ortega and Valdés in the early 1980s.

Six new diterpenoids were isolated from S. divinorum: salvinorins D–F and divinatorins A–C. Other compounds from S. divinorum did not bind to the kappa opioid receptor (KOR), suggesting that salvinorin A is the plant's active principle.

Similar to many psychoactive herbs, Salvia divinorum synthesizes and excretes its active constituent (salvinorin A) via trichomes, of the peltate-glandular morphology, located just beneath the cuticle (subcuticular) layer. By mass, salvinorin A "is the most potent naturally occurring hallucinogen." It is active at doses as low as 200 µg.

3.4 Mechanism of Action

Research has shown that salvinorin A is a potent and selective κ-opioid (kappa-opioid) receptor agonist. Salvinorin A, the active ingredient of Salvia divinorum, is a selective kappa-opioid receptor agonist, and hence points to a different mechanism of action compared to serotonin 2A receptor agonists. This pharmacological profile is unique among classical psychedelics, which predominantly act at the serotonin 5-HT2A receptor.

Reports of the perceptiotropic effects that accompanied use of this material led to phytochemical investigations which yielded a novel neoclerodane diterpenoid, salvinorin A. This compound was found to possess extremely high affinity and selectivity for the kappa opioid receptors and was determined to bind in a unique manner different from classic opioids. While S. divinorum and salvinorin A both produce pronounced perceptotropic effects (i.e., mixed hallucinogenic and dissociative effects), they have also been shown to attenuate drug-seeking behavior.

Salvia divinorum contains the highly selective kappa-opioid receptor agonist salvinorin A; this compound produces visual hallucinations and synesthesia.

3.5 Psychoactive Effects and Preparations

The leaves contain the potent compound salvinorin A and can induce a dissociative state and hallucinations. Users typically experience altered perceptions, vivid hallucinations, and a changed sense of self, though effects are usually short-lived. The route of administration significantly affects the onset and duration of effects; smoking concentrated extracts produces a much more rapid and intense experience than traditional chewing.

Traditional preparation, as used by Mazatec communities, involves chewing fresh leaves or drinking infusions. Smoking extracts of salvia appears to be the most common form of use among recreational users, similar to smoking cannabis.

3.6 Scientific and Clinical Evidence

S. divinorum and salvinorin A remain largely at the preclinical research stage for any therapeutic application. The toxicity of Salvia divinorum is currently poorly understood. Salvia divinorum and its active constituent salvinorin A are not approved for medical use in the United States. While early studies have examined potential applications of kappa-opioid agonism in depression, drug addiction, and pain, no human clinical trials have established efficacy or safety for any medical condition. The evidence base is at present confined to receptor pharmacology and preclinical studies.

Salvinorin A and the other diterpenoids of the plant are not detected by conventional drug screening methods.

3.7 Regulatory and Legal Status

Neither Salvia divinorum nor salvinorin A are listed in any of the Schedules of the United Nations Drug Conventions. However, national and subnational regulation varies significantly. In recent years, both Salvia divinorum and its active principle salvinorin A have become controlled under drugs legislation in Belgium, Denmark, Italy, Latvia, Lithuania, Romania, and Sweden, in Australia and Japan, as well as in a number of states of the US. Canada added Salvia divinorum and salvinorin A to its Controlled Drugs and Substances Act, making sale or possession illegal without authorization. In the United Kingdom, salvia became outlawed in 2016 under the Psychoactive Substances Act. In Mexico, the plant's country of origin, salvia remains legal at the federal level. It is not listed as a prohibited narcotic in Mexico, and local Mazatec communities continue to use it in traditional practices.

Cross-Species Summary: Body Systems and Health Areas

Nervous system / Cognition: S. officinalis — cholinesterase inhibition, memory and attention (multiple small RCTs, systematic reviews); S. divinorum — profound, short-acting dissociative/hallucinogenic effects via κ-opioid receptor agonism (pharmacological research only); S. miltiorrhiza — neuroprotection in ischemia (preclinical, limited clinical data).
Endocrine / Reproductive system: S. officinalis — reduction of hot flashes and menopausal vasomotor symptoms (moderate RCT evidence); contraindicated in pregnancy due to abortifacient/emmenagogic properties.
Cardiovascular system: S. miltiorrhiza — anticoagulation, vasodilation, anti-atherosclerosis, myocardial protection (extensive preclinical data, clinical use in China).
Metabolic / Endocrine (glycemia, lipids): S. officinalis — preliminary clinical evidence for reduced fasting blood glucose, HbA1c improvement, and lipid-lowering effects in type 2 diabetes and hyperlipidemia.
Immune / Infectious: S. officinalis — antimicrobial and antifungal activity demonstrated in vitro and in animal models; oral and pharyngeal anti-inflammatory effects recognized by EMA.
Gastrointestinal system: S. officinalis — traditional use for heartburn, bloating, and diarrhea recognized in EMA monograph; direct clinical trial evidence is limited.

References

Health Conditions

Health conditions that Salvia may help support.

No conditions available.

Body Systems

Body systems that Salvia may help support.

No body systems available.