Salvinorin

432.47

432.46

200-835-2

T56W91NG6J

DTXSID80232584

Colorless crystals from methanol|White powder

109.11000

1.82

white

1.3±0.1 g/cm3

235-238 °C

563.8±50.0 °C at 760 mmHg

2℃

1.548

DMSO: ≥10mg/mL

−20°C

2.16X10-10 mm Hg at 25 deg C (est)

D22 -45.3° (c = 8.530 in CHCl3); D25 -41° (c = 1 in CHCl3)

Henry's Law constant = 5.6X10-13 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 1.2X10-10 cu cm/molec-sec at 25 °C (est)

UN 1648 3 / PGII

3

11-20/21/22-36

22-24/25-36/37-16

QL6127142

F,Xn

Stable under recommended storage conditions.

P210-P261-P302 + P352 + P312-P304 + P340 + P312-P337 + P313-P403 + P235

H225-H302 + H312 + H332-H319

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.|Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains.|Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: General industrial hygiene practice.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Water quality data compiled from the Retrieval (STORET) Data Warehouse and the USGS National Water Information System (NWIS) reports sediment monitoring data for various chemicals but does not include salvinorin A at this time(1).

IDENTIFICATION AND USE: Salvinorin A forms colorless crystals or white powder. It is a traditional medicine used by the Mazatec people of Oaxaca, Mexico. In traditional medicine, the leaves are used for divination and for treatment of anemia and excretory functions. Currently, neither Salvia divinorum nor any of its constituents, including salvinorin A, are controlled under the federal Controlled Substances Act (CSA). Neither Salvia divinorum nor its active constituent salvinorin A has an approved medical use in the U.S. However, both the plant and its preparations are becoming increasingly popular among non-traditional users. HUMAN STUDIES: Salvinorin A is a potent and selective kappa opioid receptor agonist. The use of the parent plant Salvia divinorum may cause diuresis, nausea, and dysphoria. Smoking the extract was described as the preferred form of administration. Subjective effects were described as intense but short-lived, appearing in less than 1 min and lasting 15 min or less. They included psychedelic-like changes in visual perception, mood and somatic sensations, and importantly, a highly modified perception of external reality and the self, leading to a decreased ability to interact with oneself or with one's surroundings. ANIMAL STUDIES: Rats were anesthetized and administered salvinorin A at 1600 ug/kg or vehicle. Recordings were made of galvanic skin response, electrocardiogram, temperature, and pulse pressure for 100 minutes. No effects were seen on cardiac conduction, temperature, or galvanic skin response. A nonsignificant rise was seen in pulse pressure. In rats, salvinorin A (80-640 ug/kg) did not affect short-term memory, but it impaired spatial long-term memory. Episodic and aversive memories were impaired by salvinorin A (160-640 ug/kg). Overall, animal studies of salvinorin A show a rapid onset of action and short distribution and elimination half-lives as well as a lack of evidence of short- or long-term toxicity.

Salvinorin A is a chemical constituent of Salvia divinorum, commonly known as seer sage(1). Salvia divinorum is a perennial herb in the mint family native to certain areas of the Sierra Mazateca region of Oaxaca, Mexico; Salvinorin A is found primarily in the leaves, and to a lesser extent in the stems of the plant(2).

Salvinorin A's production, illicit use(1), and administration in traditional medicine(2) may result in its release to the environment through various waste streams(SRC). Currently, neither Salvia divinorum nor any of its constituents, including salvinorin A, are controlled under the Federal Controlled Substances Act (CSA). Neither Salvia divinorum nor its active constituent salvinorin A has an approved medical use in the U.S.; salvinorin A is a potent and selective kappa opioid receptor agonist(1). According to DEA's National Forensic Laboratory Information System (NFLIS) and System to Retrieve Information From Drug Evidence (STRIDE), federal, state and local law enforcement officials encountered 103 drug exhibits in 2011, 100 drug exhibits in 2012, and 40 exhibits in the first six months of 2013 identified as Salvia divinorum or salvinorin A(1).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.1X10+4(SRC), determined from a structure estimation method(2), indicates that salvinorin A is expected to be immobile in soil(SRC). Volatilization of salvinorin A from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.6X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Salvinorin A is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.9X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.1X10+4(SRC), determined from a structure estimation method(2), indicates that salvinorin A is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.6X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 13(SRC), from an estimated log Kow of 2.2(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2017).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), salvinorin A, which has an estimated vapor pressure of 7.9X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase salvinorin A may be removed from the air by wet and dry deposition(SRC). Salvinorin A does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 3.110-2 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of greater than 1 year and 260 days at pH values of 7 and 8, respectively(1). Salvinorin A contains functional groups that may hydrolyze under environmental conditions (pH 5 to 9); very slow hydrolysis may occur in alkaline soils and waters(1,2). Salvinorin A does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 13 was calculated in fish for salvinorin A(SRC), using an estimated log Kow of 2.2(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of salvinorin A can be estimated to be 3.1X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that salvinorin A is expected to be immobile in soil.

The Henry's Law constant for salvinorin A is estimated as 5.6X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that salvinorin A is expected to be essentially nonvolatile from water surfaces(2). Salvinorin A is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 7.9X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(3).

Water quality data compiled from the Retrieval (STORET) Data Warehouse and the USGS National Water Information System (NWIS) reports surface water and ground water monitoring data for various chemicals but does not include salvinorin A at this time(1).

Occupational exposure to salvinorin A should be low or non-existent since salvinorin A is not produced in the US. Use data indicate that the general population may be exposed to salvinorin A via smoke inhalation and ingestion of the plant Salvia divinorum. Exposure to salvinorin A among the general population is limited to individuals who engage in its illicit use and individuals who are administered the drug in traditional medicine practices. The general public is not likely to be exposed to salvinorin A. (SRC)

The Monitoring the Future survey reports that in 2012, 1.4% of 8th graders, 2.5% of 10th graders, and 4.4% of 12th graders used "Salvia" in the past year(1).

/EXPL THER/ Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases.|/EXPL THER/ The hallucinogenic compound, salvinorin A, is a potent kappa-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1-10 pM) reduced LPS-stimulated nitrite, TNF-alpha and IL-10 (but not IL-1beta) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant. Salvinorin A also prevented KOR and CB1 hyperexpression induced by LPS. In vivo, salvinorin A reduced the LPS- and the carrageenan-induced paw edema and formalin-induced inflammatory pain, in a nor-binaltorphimine and rimonabant-sensitive manner. It is concluded that salvinorin A-via KORs and CB1 receptors-exerts ultrapotent actions on macrophages and also shows moderate antinflammatory effects in vivo.|/EXPL THER/ Salvinorin A (SA), the main active component of Salvia Divinorum, is a non-nitrogenous kappa opioid receptor (KOR) agonist. It has been shown to reduce acute pain and to exert potent antinflammatory effects. This study assesses the effects and the mode of action of SA on formalin-induced persistent pain in mice. Specifically, the SA effects on long-term behavioral dysfunctions and changes in neuronal activity occurring at spinal level, after single peripheral formalin injection, have been investigated. Moreover, the involvement of microglial and glial cells in formalin-induced chronic pain condition and in SA-mediated effects has been evaluated. Formalin induced a significant decrease of mechanical withdrawal threshold at the injected and contralateral paw as well as an increase in the duration and frequency, and a rapid decrease in the onset of evoked activity of the nociceptive neurons 7 days after formalin injection. SA daily treatment significantly reduced mechanical allodynia in KOR and cannabinoid receptor 1 (CB1R) sensitive manner. SA treatment also normalized the spinal evoked activity. SA significantly reduced the formalin-mediated microglia and astrocytes activation and modulated pro and anti-inflammatory mediators in the spinal cord. SA is effective in reducing formalin-induced mechanical allodynia and spinal neuronal hyperactivity. Our findings suggest that SA reduces glial activation and contributes in the establishment of dysfunctions associated with chronic pain with mechanisms involving KOR and CB1R. SA may provide a new lead compound for developing anti-allodynic agents via KOR and CB1R activation.|/EXPL THER/ Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. (See all compounds classified as Hallucinogens.)

Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant. The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels. Sublingual SA doses up to 4 mg were administered in dimethyl sulfoxide/polyethylene glycol 400 solution to eight SD-experienced subjects using a placebo-controlled ascending-dose design. No dose of SA produced significantly greater physiological or subjective effects than placebo. Furthermore, effects did not resemble reported "typical" effects of smoked SD. SA was detectable in plasma and urine, but was, in most cases, below the reliable limit of quantification (0.5 ng/mL). Our results suggest that the sublingual bioavailability of SA is low. Higher doses, alternate formulations, or alternate routes of administration will be necessary to study the effects of SA in humans.|Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 ug/kg; n = 2, 18 ug/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.|The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses of 200-500 ug produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity. Traditionally the herb is consumed either by chewing the fresh leaves or by drinking the juices of freshly crushed leaves. The effects of the herb when consumed this way depend on absorption of salvinorin A through the oral mucosa before the herb is swallowed.

... Salvinorin A /has a/ half-life approximately 8 min in non-human primates ... .

Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. This study represents a systematic examination of this hypothesis. Salvinorin A was isolated from S. divinorum and was evaluated in a battery of in vitro and in vivo procedures designed to detect cannabinoid activity, including CB(1) receptor radioligand and [(35)S]GTPgammaS binding, calcium flux assay, in vivo cannabinoid screening tests, and drug discrimination. Salvinorin A did not bind to nor activate CB(1) receptors. In vivo salvinorin A produced pronounced hypolocomotion and antinociception (and to a lesser extent, hypothermia). These effects were blocked by the selective KOR antagonist, JDTic, but not by the CB(1) receptor antagonist rimonabant. Interestingly, however, rimonabant attenuated KOR activation stimulated by U69,593 in a [(35)S]GTPgammaS assay. Salvinorin A did not substitute for Delta(9)-tetrahydrocannabinol (THC) in mice trained to discriminate THC. These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvinorin A on the endocannabinoid system. Further, the results suggest that rimonabant reversal of salvinorin A effects in previous studies may be explained in part by rimonabant attenuation of KOR activation.|Salvinorin A (SalA), a selective kappa-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP(+) accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP(+)). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the Vmax for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by KOR activation and the KOR-linked extracellular signal regulated kinase-1/2 (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signaling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists.

Treatment. For a patient with a "bad trip" or panic reaction, provide gentle reassurance and relaxation techniques in a quiet environment. 1. Treat agitation or severe anxiety states with diazepam or midazolam. Butyrophenones such as haloperidol are useful despite a small theoretic risk of lowering the seizure threshold. 2. Treat seizures, hyperthermia, rhabdomyolysis, hypertension, and cardiac arrhythmias if they occur. /Lysergic acid diethylamide (LSD) and other hallucinogens/|Specific drugs and antidotes. There is not specific antidote. Sedating doses of diazepam ... may alleviate anxiety, and hypnotic doses ... can induce sleep for the duration of the "trip". /Lysergic acid diethylamide (LSD) and other hallucinogens/|Emergency and supportive measures: 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. 2. Treat coma, seizures, arrhythmias, and hypotension if they occur. 3. Replace fluid losses caused by gastroenteritis with iv crystalloid solutions. /Plants/|Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. Gastric lavage may not be effective in removing larger plant parts. Whole-bowel irrigation may be considered if large amounts of a toxic plant or plant parts were ingested and the patient arrives soon after the ingestion. /Plants/|For more Antidote and Emergency Treatment (Complete) data for Salvinorin A (7 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 ug/kg; n = 2, 18 ug/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.|/HUMAN EXPOSURE STUDIES/ This study examined the overall psychological effects of inebriation facilitated by the naturally-occurring plant hallucinogen Salvia divinorum using a double-blind, randomized, placebo-controlled trial. Thirty healthy individuals self-administered Salvia divinorum via combustion and inhalation in a quiet, comfortable research setting. Experimental sessions, post-session interviews, and 8-week follow-up meetings were audio recorded and transcribed to provide the primary qualitative material analyzed here. Additionally, post-session responses to the Hallucinogen Rating Scale provided a quantitative groundwork for mixed-methods discussion. Qualitative data underwent thematic content analysis, being coded independently by three researchers before being collaboratively integrated to provide the final results. Three main themes and 10 subthemes of acute intoxication emerged, encompassing the qualities of the experience, perceptual alterations, and cognitive-affective shifts. The experience was described as having rapid onset and being intense and unique. Participants reported marked changes in auditory, visual, and interoceptive sensory input; losing normal awareness of themselves and their surroundings; and an assortment of delusional phenomena. Additionally, the abuse potential of Salvia divinorum was examined post hoc. These findings are discussed in light of previous research, and provide an initial framework for greater understanding of the subjective effects of Salvia divinorum, an emerging drug of abuse. /Salvia divinorum/|/HUMAN EXPOSURE STUDIES/ Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. S. divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 ug/kg to 21 ug/kg. Subject-rated drug strength was assessed every 2 min for 60 min after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 min (first time point) and definite subjective effects were no longer present at approximately 20 min after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2(A)) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects.|/HUMAN EXPOSURE STUDIES/Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A. This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use. Eight healthy hallucinogen-using adults inhaled up to 16 doses of salvinorin A (0.375-21 ug/kg) in ascending order. Physiological, behavioral, and subjective effects were assessed every 2 min for 60 min after administration. Qualitative subjective effects were assessed retrospectively via questionnaires at the end of sessions. Persisting effects were assessed 1 month later. Orderly dose-related effects peaked at 2 min and then rapidly dissipated, replicating previous findings. Subjective effects were intense, with maximal drug strength ratings or unresponsiveness frequently observed at high doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale, Pharmacological Class Questionnaire) suggested some overlap with serotonergically mediated classic hallucinogens. Salvinorin A also produced dose-related dissociative effects and impairments in recall/recognition memory. At 1-month follow-up, there was no evidence of persisting adverse effects. Participants reported that salvinorin A effects were qualitatively different from other drugs. Salvinorin A produces a unique profile of subjective and cognitive effects, including strong dissociative effects and memory impairment, which only partially overlap with classic hallucinogen effects. Along with nonhuman studies of salvinorin A, these results are important for understanding the neurobiology of the kappa opioid system and may ultimately have important therapeutic applications.|For more Human Toxicity Excerpts (Complete) data for Salvinorin A (19 total), please visit the HSDB record page.

(-)-salvinorin A

There are no available estimates of Salvia abuse, but a recent increase in Salvia-related media reports and Internet traffic suggest the possibility of an increase in the level of Salvia abuse in the United States and Europe.

Common street names include: Maria Pastora, Sally-D, and Salvia. /Salvia divinorum/

Salvia divinorum is a perennial herb in the mint family that is abused for its hallucinogenic effects. ... Salvia is native to certain areas of the Sierra Mazaleca region of Oaxaca, Mexico. It is one of several plants that are used by Mazatec Indians for ritual divination. /Salvia divinorum/|In the last 10 years, many analogs of narcotic substances have been widely distributed in Japan as easily available psychotropic substances and this has become a serious problem. ... As a countermeasure to prevent the abuse of these substances, the Ministry of Health, Labor and Welfare amended the Pharmaceutical Affairs Law in 2006 so that 31 non-controlled psychotropic substances (11 tryptamines, 11 phenethylamines, 6 alkyl nitrites, 2 piperazines and salvinorin A) and 1 plant (Salvia divinorum) are now controlled as "Designated Substances (Shitei-Yakubutsu)" as of April 2007. Five other compounds (4 phenethylamines and 1 piperazine) were also added to this category in January 2008. /Salvia divinorum/|One of the most potent natural hallucinogens known.

A procedure based on ultra-high-pressure liquid chromatography tandem mass spectrometry has been developed for the determination of mescaline, N,N-dimethyltryptamine, psilocin, psilocybin, salvinorin A in hair of consumers of psychedelic vegetal material such peyote or trichocereus cacti, psilocybe mushrooms, Salvia divinorum or psychedelic beverage ayahuasca. After hair washing with methyl alcohol and diethyl ether and subsequent addition of mescaline-d9 and 3,4-methylenedioxypropylamphetamine as internal standards, hair samples were treated with 250 uL VMA-T M3 reagent for 1 hr at 100 °C. After cooling, 100 uL M3 extract were diluted with 400 uL water and a volume of 10 uL was injected into chromatographic system. Chromatographic separation was achieved at ambient temperature using a reverse-phase column and a linear gradient elution with two solvents: 0.3% formic acid in acetonitrile and 5 mM ammonium formate pH 3. The mass spectrometer was operated in positive ion mode, using multiple reaction monitoring via positive electrospray ionization. The method was linear from the limit of quantification (0.03-0.05 ng/mg depending on analyte under investigation) to 10 ng/mg hair, with an intra- and inter-assay imprecision and inaccuracy always less than 15% and an analytical recovery between 79.6% and 97.4%, depending on the considered analyte. Using the validated method, mescaline was found in concentration range of 0.08-0.13 ng/mg in hair of peyote smokers, 3.2 ng salvinorin A per mg hair were determined in hair from a S. divinorum smoker, 5.6 ng N,N-dimethyltryptamine per mg hair from an ayahuasca user and finally 0.8ng psilocybin per ng hair of a psilocybe consumer.|In recent years, Salvia divinorum has become a major focus by state legislatures throughout the United States looking to prohibit the sale of the psychoactive plant. After researching testing procedures presented in the literature and those employed by crime laboratories throughout the country, it was decided that thin layer chromatography (TLC) and gas chromatography/mass spectrometry (GC/MS) were the methods to use to analyze plant material for salvinorin A. With TLC, salvinorin A was detected from extracted plant material and was easily distinguishable from 13 other Salvia species as well as Cannabis sativa L. (marijuana). When using GC/MS, salvinorin A was best extracted from plant material with chloroform at ambient temperature when using a nonpolar solvent and acetone at ambient temperature when using a polar solvent. By utilizing these techniques, criminalists are now able to confirm the presence of salvinorin A in a submitted plant material suspected to be Salvia divinorum.|To determine the content of the hallucinogen salvinorin A in a variety of Salvia divinorum herbal products and to compare the content with the label claims of potency and purity ... Five herbal products containing Salvia divinorum ... were purchased from the Internet and local drug paraphernalia shops ("head shops"). High performance liquid chromatography and thin-layer chromatography-gas chromatography-mass spectroscopy were used for the analysis. All five samples contained salvinorin A, a psychoactive compound found in Salvia divinorum; however, the salvinorin A concentrations ... measured were much lower than those claimed on the product label. Vitamin E was also found in two samples and caffeine in one sample ...|A simultaneous analytical methodology for substances listed in Japan as non-controlled psychotropic substances is developed. The methods use gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) and present retention times, UV spectra, electron ionization (EI), GC-MS, and electrospray ionization (ESI) LC-MS data. Salvia divinorum is one of these substances. /Salvia divinorum/

The use of vitreous humor and pericardial fluid as alternative matrices to blood and plasma in the field of forensic toxicology is described to quantitate low levels of Salvinorin A using ethion as internal standard. The method was optimized and fully validated using international accepted guidelines. The developed methodology utilizes a solid phase extraction procedure coupled to gas chromatography mass spectrometry operated in the selected ion monitoring mode. The method was linear in the range of 5.0-100 ng/mL with determination coefficients higher than 0.99 in 100 uL of vitreous humor and in 250 uL of each matrix pericardial fluid, whole blood and plasma. The limits of detection and quantitation were experimentally determined as 5.0 ng/mL, intra-day precision, intermediate precision and accuracy were in conformity with the criteria normally accepted in bioanalytical method validation. The sample cleanup step presented mean efficiencies between 80 and 106% in the different biological specimens analyzed. According to the low volumes of samples used, and the low limits achieved using a single quadrupole mass spectrometer, which is available in most laboratories, we can conclude that the validated methodology is sensitive and simple and is suitable for the application in forensic toxicology laboratories for the routine analysis of Salvinorin A in both conventional and unconventional biological samples.|Specific and quantitative analyses of the bioactive components and their metabolites in body fluids are essential to assess the interaction between groups of compounds in dietary supplements and preparations of psychoactives. Reverse-phase LC separations combined with tandem mass spectrometry provide the necessary specificity and sensitivity. In this paper, applications of these methods are described for the analysis of isoflavones, salvinorin A, synephrine isomers and their metabolites in serum, urine and aqueous humor.