Salvia divinorum
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'''Salvia divinorum''' (Lamiaceae) — '''ska María pastora''' — is a perennial herb native to cloud forests in Oaxaca, Mexico. Its primary psychoactive compound, [[substance:salvinorin-a]], is unique among [[substance_class:psychoactive/hallucinogen|hallucinogens]] — it contains no nitrogen atom{{cite|pubmed=12192085|anchor=743be708}}. Salvinorin A activates [[glossary:kappa-opioid-receptor|kappa-opioid receptors]], suppressing [[glossary:dopamine]] and disrupting the [[glossary:circuit|circuits]] that sustain a coherent sense of reality{{cite|pubmed=12192085|anchor=c3b747dd}}{{cite|pubmed=16223871|anchor=fa05fd3f}}{{cite|doi=10.3390/biomedicines14020476|anchor=afa2f992}}.
The Mazatec people of Oaxaca have used ''Salvia divinorum'' in healing ceremonies for centuries, ingesting fresh leaves to enter visionary states{{cite|doi=10.1002/hup.2304|anchor=ac476bab}}{{cite|pubmed=23627785|anchor=12889e83}}. Western scientists described the plant in 1962; in 2002, salvinorin A was identified as a kappa-opioid [[glossary:agonist]] — a hallucinogenic mechanism independent of [[glossary:serotonin]]{{cite|pubmed=12192085|anchor=7a8594a1}}{{cite|doi=10.1016/j.jep.2013.11.032|anchor=85414dfe}}. Internet sales during the 2000s spread salvia globally as a legal hallucinogen, prompting bans across dozens of US states and several countries{{cite|doi=10.1002/hup.2304|anchor=d94a4864}}.
[[index:effects|Subjective effects]] include complete loss of environmental [[glossary:awareness]], vivid [[effect:internal-hallucinations]], deep [[glossary:disorientation]] in space and time, and distorted body sense{{cite|doi=10.1007/s00213-012-2912-9|anchor=1b3bc1f4}}. Smoked preparations produce a sudden, overwhelming immersion lasting under 20 minutes; traditional leaf quids yield a gentler shift over 30–90 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=d161551a}}{{cite|pubmed=23627785|anchor=435a4c46}}. [[effect:dysphoria]], intense fear, and brief [[effect:amnesia]] are common at smoked doses — characteristic features of the kappa-opioid mechanism, not rare [[glossary:adverse-effects|side effects]]{{cite|doi=10.1007/s00213-012-2912-9|anchor=00d9ee79}}.
No fatalities have been directly attributed to salvinorin A, and no [[glossary:dependence]] syndrome has been described{{cite|doi=10.3390/ph14020116|anchor=0e5f7313}}{{cite|doi=10.3390/biomedicines14020476|anchor=150950f7}}. The primary risks are psychological — the kappa-opioid mechanism makes dysphoric, frightening experiences common, and [[glossary:case-report|case reports]] link use to lasting [[glossary:psychosis]] in psychiatrically vulnerable individuals{{cite|doi=10.1080/02791072.2015.1073815|anchor=ea1bd3d8}}. No human pharmacokinetic data have been published, commercial extract [[glossary:potency]] labels are often inaccurate{{cite|doi=10.1021/acsomega.2c06106|anchor=7a719dd7}}, and several areas of risk remain formally unstudied.
'''Salvia divinorum''' ('''Salvia''', '''ska María pastora''', '''seer's sage''') is a perennial herb in the family Lamiaceae (mint family), endemic to the cloud forests of the Sierra Mazateca in Oaxaca, Mexico. Its pharmacology is driven by [[substance:salvinorin-a]], a neoclerodane diterpenoid and the first known [[glossary:naturally-occurring|naturally occurring]] non-nitrogenous [[glossary:kappa-opioid-receptor]] (KOR) [[glossary:agonist]]{{cite|pubmed=12192085|anchor=c02f3eec}}. When smoked or vaporized, effects onset within approximately 2 minutes and resolve within 15–20 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=5364443b}}; traditional buccal quid preparations produce a more gradual experience lasting 30–90 minutes{{cite|pubmed=23627785|anchor=10995910}}.
First formally described by Epling and Játiva in 1962 from specimens collected during R. Gordon Wasson and [[article:hofmann|Albert Hofmann]]'s expedition to the Sierra Mazateca{{cite|doi=10.1016/j.jep.2013.11.032|anchor=4449460e}}, ''S. divinorum'' has been used in Mazatec divinatory healing ceremonies for centuries. The identification of salvinorin A as a selective KOR agonist in 2002 established a unique pharmacological mechanism — hallucinogenic [[glossary:potency]] without [[glossary:serotonin]] [[glossary:5-ht2a]] [[glossary:receptor]] involvement{{cite|pubmed=12192085|anchor=51131142}}. Controlled human studies at Johns Hopkins, Yale, and UC San Diego between 2009 and 2016 characterised the dose-response pharmacology{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=c3d05dfd}}{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=ee760fa4}}, but no therapeutic applications have advanced to late-stage clinical trials. The plant is not federally scheduled in the United States but is banned or restricted in approximately 27 US states, Canada ([[glossary:schedule-iv]]), the United Kingdom, Australia (Schedule 9), Germany, and several other jurisdictions{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=cd0694e8}}.
Salvinorin A acts as a highly selective [[glossary:full-agonist]] at KOR with no clinically significant activity at the serotonin 5-HT₂A receptor or at over 50 other screened molecular targets{{cite|pubmed=12192085|anchor=9e84ecf1}}. KOR [[glossary:activation]] suppresses mesolimbic dopaminergic [[glossary:transmission]] in the [[glossary:nucleus-accumbens]] and disrupts thalamocortical signalling{{cite|pubmed=16223871|anchor=f5da5393}}{{cite|doi=10.3390/biomedicines14020476|anchor=021f0df2}}, producing the substance's characteristic [[substance_class:psychoactive/dissociative]] and hallucinogenic effects without the [[effect:euphoria]] or positive [[glossary:reinforcement]] associated with [[glossary:serotonergic-psychedelics|classical psychedelics]] or [[glossary:mu-opioid-receptor]] agonists.
The experiential profile is dominated by intense dissociation, spatial and [[effect:temporal-disorientation]], [[effect:depersonalization|depersonalisation]], [[effect:proprioceptive-distortion]], and vivid [[effect:internal-hallucinations]] — including [[effect:entity-contact]] and immersive scenario experiences{{cite|doi=10.1007/s00213-012-2912-9|anchor=ee142caf}}. [[effect:dysphoria]] is more frequently reported than euphoria, particularly with traditional buccal preparations{{cite|pubmed=23627785|anchor=6a96176e}}. Effects and duration vary substantially by preparation method: smoked preparations produce a rapid, intense, short-duration experience, whereas traditional fresh-leaf quid preparations produce milder, more gradual effects.
No human fatalities have been directly attributed to salvinorin A{{cite|doi=10.3390/ph14020116|anchor=198635ee}}{{cite|doi=10.3390/ijms26125588|anchor=56e8e21e}}, and controlled human studies documented no significant cardiovascular effects at psychoactive doses{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=f73b67a2}}. Salvinorin A displays low [[glossary:abuse-potential]] due to KOR-mediated dopaminergic suppression and aversive [[glossary:phenomenology]]; no formal [[glossary:dependence]] syndrome or [[glossary:withdrawal]] has been described{{cite|doi=10.3390/biomedicines14020476|anchor=2eb1b42f}}{{cite|doi=10.3389/fphar.2015.00190|anchor=17615599}}. The primary risks are acute psychological — intense fear, panic, [[glossary:disorientation]], and transient [[effect:amnesia]] are common at typical smoked doses{{cite|doi=10.1007/s00213-012-2912-9|anchor=9156386e}} — with [[glossary:case-report|case reports]] linking use to persistent [[glossary:psychotic-episodes]] in individuals with possible pre-existing psychiatric [[glossary:vulnerability]]{{cite|doi=10.1080/02791072.2015.1073815|anchor=ece68a05}}. No formal human pharmacokinetic study with [[glossary:plasma-concentration]]–time data has been published, no controlled dose-response data exist for the traditional quid preparation, and no systematic [[glossary:contamination|contaminant]] [[glossary:surveillance]] of commercial products has been conducted.
'''Salvia divinorum''' (Lamiaceae) — '''ska María pastora''', '''seer's sage''' — is a perennial herb endemic to the cloud forests of Oaxaca, Mexico. Its principal psychoactive constituent, [[substance:salvinorin-a]], is the first known non-nitrogenous [[substance_class:pharmacological/kappa-opioid-receptor-agonist]]{{cite|pubmed=12192085|anchor=8a14ef43}}. Salvinorin A acts by activating [[glossary:kappa-opioid-receptor|kappa-opioid receptors]], suppressing [[glossary:mesolimbic-pathway|mesolimbic dopamine]] [[glossary:transmission]] and disrupting thalamocortical signalling{{cite|pubmed=16223871|anchor=b6bbe036}}{{cite|doi=10.3390/biomedicines14020476|anchor=f7c1582e}}.
Formally described in 1962 from specimens collected during Wasson and [[article:hofmann|Hofmann]]'s Sierra Mazateca expedition{{cite|doi=10.1016/j.jep.2013.11.032|anchor=cd9b5ca7}}, the plant has been used in Mazatec divinatory healing ceremonies for centuries. Salvinorin A's 2002 identification as a selective KOR [[glossary:agonist]] revealed a hallucinogenic mechanism entirely independent of [[glossary:serotonin]] [[glossary:5-ht2a]] [[glossary:receptor|receptors]]{{cite|pubmed=12192085|anchor=3f2b2ee5}}. Not federally scheduled in the United States, the plant is nonetheless banned or restricted in approximately 27 US states, Canada, the United Kingdom, Australia, and other jurisdictions{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=cea49cdf}}.
[[index:effects|Subjective effects]] include intense dissociation, [[effect:depersonalization|depersonalisation]], [[effect:spatial-disorientation]], [[effect:proprioceptive-distortion]], and vivid [[effect:internal-hallucinations]]{{cite|doi=10.1007/s00213-012-2912-9|anchor=f9617fc1}}. Smoked preparations produce rapid, overwhelming immersion lasting under 20 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=9a719b07}}; traditional buccal quids yield subtler effects over 30–90 minutes{{cite|pubmed=23627785|anchor=fd1d94ae}}. [[effect:dysphoria]], intense fear, and transient [[effect:amnesia]] are commonly reported at typical smoked doses{{cite|doi=10.1007/s00213-012-2912-9|anchor=4f5889ab}}.
No human fatalities have been directly attributed to salvinorin A{{cite|doi=10.3390/ph14020116|anchor=75f0ae97}}{{cite|doi=10.3390/ijms26125588|anchor=364ef3f3}}, and no [[glossary:dependence]] syndrome has been described{{cite|doi=10.3390/biomedicines14020476|anchor=6790aa46}}{{cite|doi=10.3389/fphar.2015.00190|anchor=d925aa5b}}. The primary risks are psychological — KOR-mediated dysphoria makes distressing experiences common, and [[glossary:case-report|case reports]] link use to persistent [[glossary:psychosis]] in psychiatrically vulnerable individuals{{cite|doi=10.1080/02791072.2015.1073815|anchor=ec2fd0d3}}. No formal human pharmacokinetic study has been published, and no systematic [[glossary:contamination|contaminant]] [[glossary:surveillance]] of commercial products exists.
===Traditional and historical use===
The Mazatec people of the Sierra Mazateca in Oaxaca, Mexico, have used ''Salvia divinorum'' in divinatory healing ceremonies (''veladas'') for centuries, where the plant is known as ''ska María pastora'' ("leaves of Mary the Shepherdess"){{cite|doi=10.1002/hup.2304|anchor=c23dd213}}{{cite|pubmed=23627785|anchor=9dc665fb}}. A ''curandera'' (healer) administers the plant to enter a visionary state for diagnostic or therapeutic purposes{{cite|doi=10.1016/j.jep.2013.11.032|anchor=bafd08f9}}{{cite|pubmed=23627785|anchor=f3e60fe8}}. Field researcher Diaz documented three traditional preparations between 1973 and 1983: a fresh-leaf quid held in the mouth for buccal [[glossary:absorption]], a cold-water infusion of crushed leaves, and direct chewing with juice retained [[glossary:sublingual|sublingually]]{{cite|pubmed=23627785|anchor=6c0071aa}}.
The exact antiquity of Mazatec use remains uncertain — while centuries of practice are commonly cited, the earliest documented ethnographic accounts date to the mid-20th century, and no pre-colonial archaeological or documentary evidence has been identified.{{flag|citation-needed}}
===Western discovery and research===
The plant was first brought to Western attention through R. Gordon Wasson's ethnomycological expeditions to the Sierra Mazateca beginning in the late 1930s. In 1962, Wasson and [[article:hofmann|Albert Hofmann]] collected the first flowering specimen, enabling Epling and Játiva to publish the formal botanical description{{cite|doi=10.1016/j.jep.2013.11.032|anchor=401c6a4a}}{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=efc18a0a}}. The active compound was isolated independently by Ortega et al. in 1982 (as "[[substance_class:chemical/salvinorin]]") and Valdes et al. in 1984 (as "divinorin A"); these were later confirmed identical{{cite|doi=10.1016/j.jep.2013.11.032|anchor=477dba26}}.
The landmark discovery came in 2002, when Roth et al. identified [[substance:salvinorin-a]] as a potent, selective [[substance_class:pharmacological/kappa-opioid-receptor-agonist]] — the first non-nitrogenous compound found to produce hallucinogenic effects through this mechanism{{cite|pubmed=12192085|anchor=77e1de73}}. Controlled human studies at Johns Hopkins{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=e89f40f3}}{{cite|doi=10.1007/s00213-012-2912-9|anchor=3ea1631f}}, Yale{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=87be2c8e}}, and California Pacific Medical Center{{cite|doi=10.1007/s00213-010-2103-5|anchor=9cf7ebde}} subsequently characterised dose-response pharmacology between 2009 and 2016, with [[glossary:antagonist]] challenge confirming the [[glossary:kappa-opioid-receptor]] mechanism in humans{{cite|doi=10.1093/ijnp/pyw016|anchor=731e9308}}.
===Modern era===
During the 1990s and 2000s, ''S. divinorum'' gained popularity as a legal [[substance_class:psychoactive/hallucinogen]] alternative, with internet sales driving international [[glossary:awareness]]{{cite|doi=10.1002/hup.2304|anchor=c6d53651}}{{cite|doi=10.1016/j.addbeh.2011.06.004|anchor=fed0a8b8}}. A wave of US state-level bans followed in the mid-2000s{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=47666007}}. The [[glossary:drug-enforcement-administration|DEA]] listed the plant as a "Drug and Chemical of Concern" in 2009 but has not pursued federal scheduling{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=4fda1093}}.
The United Kingdom banned ''S. divinorum'' under the Psychoactive Substances Act 2016{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=dbd0723a}}, Canada added it to [[glossary:schedule-iv]] in 2017{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=2153591c}}, and the plant remains absent from UN [[glossary:drug-control|international drug control]] conventions{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=3b6753fc}}. Research interest has shifted in the 2020s toward salvinorin A analogues as potential therapeutics for pain, [[glossary:addiction]], and gastrointestinal disease{{cite|doi=10.1039/d0np00028k|anchor=9676c066}}{{cite|doi=10.1002/ibd.21873|anchor=cf39f1c8}}, though none have entered clinical trials.
===Traditional and historical use===
The Mazatec people of the Sierra Mazateca in Oaxaca use ''Salvia divinorum'' — known as ''ska María pastora'' — in healing ceremonies (''veladas''), where a ''curandera'' administers fresh leaves to enter a visionary diagnostic state{{cite|doi=10.1002/hup.2304|anchor=95ae2884}}{{cite|pubmed=23627785|anchor=63c51d19}}{{cite|doi=10.1016/j.jep.2013.11.032|anchor=06f72b0a}}. Centuries of practice are commonly cited, but the earliest documented Western accounts date to the mid-20th century.{{flag|citation-needed}}
===Western discovery and research===
R. Gordon Wasson's expeditions first brought the plant to Western attention in the late 1930s. Botanists Epling and Játiva formally described the species in 1962 from Wasson and [[article:hofmann|Hofmann]]'s first flowering specimen{{cite|doi=10.1016/j.jep.2013.11.032|anchor=81e38324}}{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=8acd7080}}. In 2002, [[substance:salvinorin-a]] was identified as a selective [[glossary:kappa-opioid-receptor]] [[glossary:agonist]] — the first non-nitrogenous [[substance_class:psychoactive/hallucinogen]]{{cite|pubmed=12192085|anchor=b3ea8ba5}}.
===Modern era===
Internet sales during the 1990s–2000s made ''S. divinorum'' globally available as a legal hallucinogen{{cite|doi=10.1002/hup.2304|anchor=44e7aad0}}, prompting US state bans{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=e5c34c2c}} and a [[glossary:drug-enforcement-administration|DEA]] "Drug and Chemical of Concern" listing in 2009{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=a37faef7}}. The plant remains absent from UN drug conventions{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=1ed85554}}, and recent research focuses on salvinorin A analogues as potential treatments for pain and [[glossary:addiction]]{{cite|doi=10.1039/d0np00028k|anchor=2914866a}}{{cite|doi=10.1002/ibd.21873|anchor=b803b5a3}}.
===Discovery and early record===
The Mazatec people of the Sierra Mazateca in Oaxaca, Mexico, have used ''Salvia divinorum'' in divinatory healing ceremonies (''veladas'') for centuries, where it is known as ''ska María pastora'' ("leaves of Mary the Shepherdess"), ''yerba de la pastora'', and ''hojas de María Pastora''{{cite|doi=10.1002/hup.2304|anchor=c7c9fe06}}{{cite|pubmed=23627785|anchor=5fc30330}}. The plant was first brought to Western scientific attention through R. Gordon Wasson's ethnomycological expeditions to the Sierra Mazateca beginning in the late 1930s. In 1962, Wasson and [[article:hofmann|Albert Hofmann]] collected the first flowering specimen of ''S. divinorum'', enabling formal botanical identification{{cite|doi=10.1016/j.jep.2013.11.032|anchor=8fbbddc1}}.
===Traditional use===
Traditional Mazatec use centres on divinatory healing ceremonies conducted by a ''curandera'' (healer), in which the plant is consumed to enter a visionary state for diagnostic or therapeutic purposes{{cite|doi=10.1016/j.jep.2013.11.032|anchor=645fedca}}{{cite|pubmed=23627785|anchor=d42f51a7}}. Field research conducted by Diaz between 1973 and 1983 documented three principal preparation methods: a fresh-leaf quid (crushed or rolled leaves held in the mouth for buccal [[glossary:absorption]]), a water infusion (crushed fresh leaves mixed with cold water), and direct chewing of fresh leaves with juice retained [[glossary:sublingual|sublingually]]{{cite|pubmed=23627785|anchor=1850c3e9}}. The traditional water preparation produced short-lasting light-headedness, [[effect:dysphoria]], tactile and proprioceptive sensations, [[effect:depersonalization|depersonalisation]], amplified sound [[glossary:perception]], and increased visual and auditory imagery — but generally not full [[glossary:hallucination|hallucinations]]{{cite|pubmed=23627785|anchor=4c1699dc}}. These effects were considerably milder than those subsequently observed with the smoked preparation.
The exact antiquity of Mazatec ''S. divinorum'' use remains uncertain. While centuries of use are commonly cited, the earliest documented ethnographic accounts date to the mid-20th century; no pre-colonial archaeological or documentary evidence has been identified.{{flag|citation-needed}}
===Western encounter and research===
Epling and Játiva published the formal botanical description in ''Botanical Museum Leaflets'' in 1962{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=8e004905}}. The active compound was first isolated as "[[substance_class:chemical/salvinorin]]" by Ortega et al. in 1982, and independently as "divinorin A" by Valdes et al. in 1984; these were later confirmed to be identical{{cite|doi=10.1016/j.jep.2013.11.032|anchor=388b18de}}. Siebert published the first systematic pharmacological investigation documenting psychoactive effects from inhalation in 1994{{cite|doi=10.1016/j.jep.2013.11.032|anchor=16ec45b7}}{{cite|doi=10.1002/hup.2304|anchor=051e80a0}}.
The landmark mechanistic discovery came in 2002, when Roth et al. identified [[substance:salvinorin-a]] as a potent, selective [[substance_class:pharmacological/kappa-opioid-receptor-agonist]] with no activity at the [[glossary:serotonin]] [[glossary:5-ht2a]] [[glossary:receptor]]{{cite|pubmed=12192085|anchor=a56992b9}}. Chavkin et al. confirmed [[glossary:full-agonist]] [[glossary:efficacy]] at the cloned human [[glossary:kappa-opioid-receptor]] in 2004{{cite|pubmed=14718611|anchor=ddbbbe3b}}. Between 2009 and 2016, controlled human studies at Johns Hopkins{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=8a6a0a37}}{{cite|doi=10.1007/s00213-012-2912-9|anchor=e9316501}}, Yale{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=5c4cf3ca}}, and California Pacific Medical Center{{cite|doi=10.1007/s00213-010-2103-5|anchor=3cbc1d7d}} characterised the dose-response pharmacology and confirmed the KOR mechanism in humans via [[glossary:antagonist]] challenge{{cite|doi=10.1093/ijnp/pyw016|anchor=fae275a8}}.
===Regulatory history===
During the 1990s and 2000s, ''S. divinorum'' gained popularity as a legal alternative to classical [[substance_class:psychoactive/hallucinogen|hallucinogens]], with internet sales driving international [[glossary:awareness]]{{cite|doi=10.1002/hup.2304|anchor=c02c555d}}{{cite|doi=10.1016/j.addbeh.2011.06.004|anchor=67f99a19}}. A wave of US state-level bans followed in the mid-2000s{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=cc802403}}. The US [[glossary:drug-enforcement-administration]] listed ''S. divinorum'' as a "Drug and Chemical of Concern" in 2009 but has not initiated formal federal scheduling{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=c251cdb8}}. Internationally, the United Kingdom banned the substance under the Psychoactive Substances Act 2016{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=44057141}}, Canada added it to [[glossary:schedule-iv]] of the [[glossary:controlled-drugs-and-substances-act]] in 2017{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=03c4389e}}, and multiple other jurisdictions enacted domestic restrictions. ''S. divinorum'' remains absent from the three UN [[glossary:drug-control|international drug control]] conventions{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=df494a41}}.
In the 2020s, research interest has shifted toward salvinorin A analogues as potential therapeutics for pain, [[glossary:addiction]], and gastrointestinal disease{{cite|doi=10.1039/d0np00028k|anchor=2ed6002c}}{{cite|doi=10.1002/ibd.21873|anchor=3be99bcc}}, though no analogue has entered clinical trials.
===Taxonomy and family===
''Salvia divinorum'' Epling & Játiva belongs to the genus ''Salvia'', the largest genus in the mint family (Lamiaceae){{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=9e83d1d5}}. It is one of the very few ''Salvia'' species with documented psychoactive properties. The species was formally described in 1962 from the first flowering specimen collected during Wasson and [[article:hofmann|Hofmann]]'s expedition{{cite|doi=10.1016/j.jep.2013.11.032|anchor=2d8a1c65}}.
===Native range and habitat===
The plant is endemic to cloud forests of the Sierra Mazateca in Oaxaca, Mexico, growing in humid, shaded ravines at roughly 300–1,800 metres [[glossary:elevation]].{{flag|citation-needed}} It requires moist conditions and does not tolerate frost or direct sun. Wild populations are rare; the plant reproduces almost entirely through stem cuttings.{{flag|citation-needed}}
===Identification===
''S. divinorum'' reaches 1–1.5 metres tall with hollow, square stems — characteristic of the mint family — and large (10–30 cm), serrated leaves. Flowers appear rarely in cultivation: white with purple calyces.{{flag|citation-needed}} Large leaf size, hollow square stems, and sprawling growth distinguish it from other salvias.
===Taxonomy and family===
''Salvia divinorum'' Epling & Játiva is a perennial herb in the genus ''Salvia'', the largest genus in the family Lamiaceae (mint family){{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=f8fee9ac}}. It is among the very few ''Salvia'' species with documented psychoactive properties. The species was formally described in 1962 from the first flowering specimen collected during Wasson and [[article:hofmann|Hofmann]]'s expedition to the Sierra Mazateca{{cite|doi=10.1016/j.jep.2013.11.032|anchor=207900d8}}. No subspecies or chemotype variants are recognised in the botanical literature.
===Native range and habitat===
The plant is endemic to the cloud forests of the Sierra Mazateca in Oaxaca, Mexico, where it grows in humid, shaded ravines at [[glossary:elevation|elevations]] between approximately 300 and 1,800 metres.{{flag|citation-needed}} It favours dark, moist conditions under forest canopy and does not tolerate direct sunlight or frost. Wild populations are considered rare; the plant is primarily propagated vegetatively through stem cuttings, as seed production is extremely limited.{{flag|citation-needed}}
===Identification===
''S. divinorum'' is a sprawling herb that can reach 1–1.5 metres in height. Its stems are square in cross-section — characteristic of the mint family — hollow, and brittle. Leaves are large (10–30 cm), ovate, green, with serrated margins. Flowers appear rarely in cultivation; when present, they are white with purple calyces, arranged in racemes.{{flag|citation-needed}} The plant is most readily distinguished from other ''Salvia'' species by its unusually large leaf size, hollow square stems, and sprawling growth habit.
===Harvesting and processing===
Traditional Mazatec harvesting involves picking fresh leaves immediately before preparation{{cite|pubmed=23627785|anchor=f538db05}}. In modern commercial contexts, leaf material is dried and sold as plain leaf or processed into concentrated extracts via solvent extraction. Drying and [[glossary:storage-conditions]] affect [[substance:salvinorin-a]] content variably, and commercial extract [[glossary:potency]] labelling does not reliably correspond to measured concentration{{cite|doi=10.1021/acsomega.2c06106|anchor=a90ea0c5}}.
| Family | Lamiaceae (mint family) |
| Genus | ''Salvia'' L. |
| Species | ''Salvia divinorum'' Epling & Játiva |
| Native range | Sierra Mazateca, Oaxaca, Mexico |
| Cultivation status | Both wild-harvested and cultivated (vegetative propagation) |
| POWO accepted name | ''Salvia divinorum'' Epling & Játiva{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:456121-1|anchor=3c0ea7d9}} |
===Dominant compound===
The principal — and essentially sole — psychoactive constituent of ''Salvia divinorum'' is [[substance:salvinorin-a]] (salvinorin A), a neoclerodane diterpenoid. Unlike virtually all other known [[glossary:naturally-occurring|naturally occurring]] [[substance_class:psychoactive/hallucinogen|hallucinogens]], salvinorin A contains no nitrogen atom, placing it outside conventional alkaloid classification{{cite|pubmed=12192085|anchor=93534943}}. It is nonetheless discussed alongside plant alkaloids due to its psychoactive [[glossary:potency]]. Salvinorin A is a highly selective [[glossary:full-agonist]] at the [[glossary:kappa-opioid-receptor]] (KOR) with no significant activity at [[glossary:serotonin]] [[glossary:5-ht2a]] [[glossary:receptor|receptors]] or over 50 other screened molecular targets{{cite|pubmed=12192085|anchor=8bc1efd2}}.
===Binding characteristics===
Salvinorin A engages KOR through an unconventional binding mode — interacting with residues in transmembrane domains II and VII rather than the transmembrane III aspartate used by classical [[substance_class:psychoactive/opioid]] ligands{{cite|doi=10.1039/d0np00028k|anchor=6af12f2f}}. It displays pronounced β-arrestin-biased signalling, which produces rapid [[glossary:receptor-desensitization|receptor desensitisation]] and distinguishes its pharmacological profile from that of [[glossary:endogenous]] dynorphins and classical KOR [[glossary:agonist|agonists]]{{cite|doi=10.3390/biomedicines14020476|anchor=ff49dcab}}. Full agonist [[glossary:efficacy]] at the cloned human KOR was confirmed by Chavkin et al. in 2004{{cite|pubmed=14718611|anchor=51a49eeb}}.
===Minor diterpenoids===
Several structurally related diterpenoids — including [[substance_class:chemical/salvinorin|salvinorins]] B, C, D, E, and F — have been isolated from ''S. divinorum'', but none have demonstrated significant pharmacological activity at psychoactive-relevant targets. Salvinorin A accounts for the entirety of the plant's known psychoactive effects.
===Variability===
Salvinorin A concentration varies across individual plants, cultivation conditions, and preparation methods. Commercial products show substantial deviation between labelled and measured salvinorin A content{{cite|doi=10.1021/acsomega.2c06106|anchor=8c4aace4}}. Extract products are labelled with strength multipliers (5×, 10×, 20×) that do not reliably correspond to measured concentration, making dose calibration from product labelling unreliable.
The active constituents of ''Salvia divinorum'' are neoclerodane diterpenoids — not alkaloids. [[substance:salvinorin-a]] contains '''no nitrogen atom''', making it structurally unique among potent [[substance_class:psychoactive/opioid]] [[glossary:receptor]] ligands, which typically require a basic nitrogen for [[glossary:receptor-binding|receptor engagement]]{{cite|pubmed=12192085|anchor=4051a187}}.
===Primary constituent: salvinorin A===
Salvinorin A (C₂₃H₂₈O₈; molecular weight 432.5 g/mol) is the principal psychoactive compound in ''S. divinorum'' and the first reported [[glossary:naturally-occurring|naturally occurring]] non-nitrogenous [[substance_class:pharmacological/kappa-opioid-receptor-agonist]]{{cite|pubmed=12192085|anchor=3f8011bb}}. The compound was first isolated as "[[substance_class:chemical/salvinorin]]" by Ortega et al. in 1982 and independently as "divinorin A" by Valdes et al. in 1984; these were confirmed to be identical{{cite|doi=10.1016/j.jep.2013.11.032|anchor=f841337f}}.
====Concentration in plant material====
Chambers et al. (2023) quantified salvinorin A in commercial products using DART-HRMS (direct analysis in real time–high resolution [[glossary:mass-spectrometry]]){{cite|doi=10.1021/acsomega.2c06106|anchor=cc534acc}}:
Labeled [[glossary:potency]] multipliers (e.g., "5×," "20×," "50×") do '''not''' reliably correspond to actual salvinorin A concentrations. This discrepancy has been documented across products sold in Japan, the United States, Portugal, and Mexico{{cite|doi=10.1021/acsomega.2c06106|anchor=037ebed2}}. No published HPLC quantification study comparing salvinorin A concentrations across different cultivars or clonal [[glossary:lineage|lineages]] was identified; the 0.89–7.8 mg/g range in dried leaf reflects inter-study variability rather than controlled cultivar comparison.
====Preparation-dependent bioavailability====
Salvinorin A is sufficiently heat-stable to survive combustion and vaporisation, enabling delivery to the respiratory mucosa when leaves or extracts are smoked{{cite|doi=10.3390/ph14020116|anchor=1028df30}}. When swallowed, salvinorin A is rapidly hydrolysed by gastrointestinal esterases to '''salvinorin B''', the primary [[glossary:metabolite]], which is pharmacologically inactive at [[glossary:kappa-opioid-receptor]]{{cite|doi=10.3390/ph14020116|anchor=b0727688}}. This [[glossary:hydrolysis]] explains the oral route's lack of psychoactivity and the importance of buccal mucosal [[glossary:absorption]] in traditional quid preparations.
===Minor constituents===
''S. divinorum'' contains additional minor neoclerodane diterpenoids including salvinorins B through J and divinatorins A through F{{cite|doi=10.1055/s-2007-981566|anchor=e1f12423}}. These occur at trace concentrations and do not contribute meaningfully to the plant's psychoactive profile. Salvinorin B, the primary metabolite of salvinorin A produced by ester hydrolysis, is inactive at KOR{{cite|doi=10.3390/ph14020116|anchor=ec4139ff}}.
| Material | Salvinorin A concentration |
|---|---|
| Raw/dried leaf | Average 1.54 mg/g (published range across studies: 0.89–7.8 mg/g) |
| Enhanced extract ("5×") | 13.0 mg/g |
| Enhanced extract ("50×") | 53.2 mg/g |
| Enhanced extract ("60×") | 29.3 mg/g |
===Dominant compound===
[[substance:salvinorin-a]] is the principal — and essentially only — psychoactive compound in ''Salvia divinorum''. It is a neoclerodane diterpenoid, not a true alkaloid: it contains no nitrogen atom{{cite|pubmed=12192085|anchor=a3dadb15}}. At [[glossary:kappa-opioid-receptor|kappa-opioid receptors]], salvinorin A acts as a potent [[glossary:full-agonist]] with no activity at [[glossary:serotonin]] [[glossary:receptor|receptors]] or over 50 other molecular targets tested{{cite|pubmed=12192085|anchor=7211b622}}.
===Binding and signalling===
Salvinorin A engages kappa-opioid receptors through an unusual molecular interaction — it binds differently from conventional [[substance_class:psychoactive/opioid]] drugs{{cite|doi=10.1039/d0np00028k|anchor=521be7fa}}. It also produces rapid [[glossary:receptor-desensitization|receptor desensitisation]], meaning the effect diminishes quickly with repeated dosing in a single session{{cite|doi=10.3390/biomedicines14020476|anchor=f941ca84}}. Full agonist activity at the human kappa-opioid receptor was confirmed in 2004{{cite|pubmed=14718611|anchor=f3bb03c3}}.
===Minor diterpenoids and variability===
Several related compounds — [[substance_class:chemical/salvinorin|salvinorins]] B through F — are present in the plant but show no meaningful psychoactive activity. Salvinorin A concentration varies across plants and growing conditions. Commercial extracts show substantial inaccuracy in [[glossary:potency]] labelling — measured salvinorin A content frequently deviates from what is stated on the product{{cite|doi=10.1021/acsomega.2c06106|anchor=827e9fbf}}.
===Where it acts===
[[substance:salvinorin-a]] is a selective [[glossary:full-agonist]] at the [[glossary:kappa-opioid-receptor]] with no activity at [[glossary:serotonin]] [[glossary:5-ht2a]] — the primary target of [[glossary:serotonergic-psychedelics|classical psychedelics]]{{cite|pubmed=12192085|anchor=9070de0d}}. This was confirmed in a human [[glossary:antagonist]]-challenge study: naltrexone fully blocked salvinorin A's subjective and neuroendocrine effects, while the 5-HT₂A antagonist ketanserin did not{{cite|doi=10.1093/ijnp/pyw016|anchor=ebfe31f6}}. KOR [[glossary:activation]] suppresses [[glossary:dopamine]] release in the [[glossary:nucleus-accumbens]]{{cite|pubmed=16223871|anchor=878993ac}} and disrupts thalamocortical [[glossary:circuit|circuits]]{{cite|doi=10.3390/biomedicines14020476|anchor=c188becf}}, producing dissociation and [[glossary:hallucination]] without [[effect:euphoria]] or positive [[glossary:reinforcement]].
===What it changes===
KOR activation engages the brain's [[glossary:endogenous]] stress-response system — the same dynorphin circuits that counter-modulate [[glossary:reward]]{{cite|doi=10.3389/fphar.2015.00190|anchor=1a4d22ea}}{{cite|doi=10.3390/biomedicines14020476|anchor=91332329}}. Dopaminergic suppression in [[glossary:mesolimbic-pathway|mesolimbic pathways]] explains the characteristically aversive quality and low [[glossary:abuse-potential]]. [[glossary:disruption]] of large-scale cortical network connectivity has been proposed as the [[glossary:substrate]] for dissolution of [[glossary:self-referential-thought|self-referential processing]] during the experience{{cite|doi=10.3390/biomedicines14020476|anchor=dce37277}}. Dose-related increases in [[glossary:plasma]] prolactin and cortisol have been documented in humans{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=f7e71487}}.
{{DiscoverMore|Open Questions}}
* No human pharmacokinetic data with plasma sampling exist for any [[glossary:route-of-administration]].
* The mechanism by which the traditional quid produces effects via buccal [[glossary:absorption]] — while a controlled [[glossary:sublingual]] liquid formulation did not{{cite|doi=10.1007/s00213-010-2103-5|anchor=d55962b7}} — remains unresolved.
* No neuroimaging studies of salvinorin A in humans have been published.
{{/DiscoverMore}}
===Where it acts===
[[substance:salvinorin-a]] selectively activates [[glossary:kappa-opioid-receptor|kappa-opioid receptors]] with no activity at [[glossary:serotonin]] [[glossary:receptor|receptors]]{{cite|pubmed=12192085|anchor=cc2ca66a}}. A human study confirmed this: naltrexone fully blocked salvinorin A's effects while serotonin-receptor [[glossary:blockade]] did not{{cite|doi=10.1093/ijnp/pyw016|anchor=6aef687e}}. This suppresses [[glossary:dopamine]] in [[glossary:mesolimbic-pathway|reward circuits]]{{cite|pubmed=16223871|anchor=bc777ebc}} and disrupts cortical networks sustaining a [[glossary:sense-of-self]]{{cite|doi=10.3390/biomedicines14020476|anchor=86e4c9d2}} — producing [[glossary:hallucination]] and dissociation without [[effect:euphoria]].
===What it changes===
Activating kappa-opioid receptors engages the brain's stress-response system, explaining the characteristically aversive quality of the experience{{cite|doi=10.3389/fphar.2015.00190|anchor=44bd82e4}}{{cite|doi=10.3390/biomedicines14020476|anchor=fc446871}}. Dopamine suppression in reward circuits removes the pull toward repeated use. Measurable stress-hormone rises — cortisol and prolactin — are documented in humans at psychoactive doses{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=14ee4beb}}.
{{DiscoverMore|Open Questions}}
* No human pharmacokinetic data with [[glossary:plasma]] sampling exist for any [[glossary:route-of-administration]].
* The mechanism by which the traditional quid produces effects via buccal [[glossary:absorption]] — while a controlled [[glossary:sublingual]] liquid formulation did not{{cite|doi=10.1007/s00213-010-2103-5|anchor=262bfe7e}} — remains unresolved.
* No neuroimaging studies of salvinorin A in humans have been published.
{{/DiscoverMore}}
The ''Salvia divinorum'' experience resists classification within established [[substance_class:psychoactive/psychedelic]], [[substance_class:psychoactive/dissociative]], or [[substance_class:psychoactive/opioid]] frameworks. Smoked preparations produce a sudden, total immersion — complete loss of [[glossary:awareness]] of the physical environment, vivid [[effect:internal-hallucinations]] including [[effect:entity-contact]] and immersive scenario experiences, and profound spatial and [[effect:temporal-disorientation]]{{cite|doi=10.1007/s00213-012-2912-9|anchor=fe64e948}}. The traditional fresh-leaf quid yields a subtler perceptual shift: light-headedness, altered proprioception, amplified auditory [[glossary:perception]], and [[effect:depersonalization|depersonalisation]] without full hallucinatory breakthrough{{cite|pubmed=23627785|anchor=86f63069}}. [[glossary:set-and-setting]] strongly modulate experience quality, with unfamiliar or chaotic environments consistently associated with distressing outcomes{{cite|doi=10.1080/02791072.2016.1179376|anchor=a93bf4bf}}.
Pharmacologically, ''S. divinorum'' occupies a unique niche — [[glossary:kappa-opioid-receptor]] agonism produces perceptual [[glossary:disruption]] without the euphoric [[glossary:valence]] of [[glossary:serotonergic-psychedelics]] or the anaesthetic dissociation of [[glossary:nmda-receptor]] [[glossary:antagonist|antagonists]] like [[substance:ketamine]]{{cite|pubmed=12192085|anchor=81b71b6c}}{{cite|doi=10.3390/biomedicines14020476|anchor=e6757dcb}}. [[effect:dysphoria]] is the modal affective tone, not a side effect — a direct consequence of the kappa-opioid mechanism that distinguishes it from virtually every other hallucinogenic substance.
The ''Salvia divinorum'' experience is unlike any other [[substance_class:psychoactive/hallucinogen]]. Smoked preparations produce sudden total immersion — loss of environmental [[glossary:awareness]], vivid [[effect:internal-hallucinations]], and profound [[glossary:disorientation]] in space and time{{cite|doi=10.1007/s00213-012-2912-9|anchor=689ae2a4}}. The traditional leaf quid yields something milder: light-headedness, altered body sense, and detachment from self without full hallucinatory breakthrough{{cite|pubmed=23627785|anchor=356e935e}}.
Pharmacologically, the experience sits in its own category — neither the warm connectivity of [[glossary:serotonergic-psychedelics]] nor the anaesthetic numbness of [[substance:ketamine]]{{cite|pubmed=12192085|anchor=979ea91b}}{{cite|doi=10.3390/biomedicines14020476|anchor=0eb5d6c9}}. [[effect:dysphoria]] is the default emotional tone. [[glossary:set-and-setting]] exert unusually strong influence on whether an experience moves toward fear or tolerable strangeness{{cite|doi=10.1080/02791072.2016.1179376|anchor=d4885f00}}.
This section describes the major preparation methods for ''S. divinorum'', their pharmacokinetic profiles, and preparation-specific effect character. Dose data are presented per preparation; see the Dose by preparation card for the structured reference.
===Dried leaf (smoked)===
The most common modern preparation. Dried leaf material ([[substance:salvinorin-a]] concentration averaging 1.54 mg/g, range 0.89–7.8 mg/g{{cite|doi=10.1021/acsomega.2c06106|anchor=66c6fc8f}}) is smoked in a pipe or water pipe. Salvinorin A is heat-stable and rapidly absorbed through the respiratory mucosa{{cite|doi=10.3390/ph14020116|anchor=f5b0ba37}}.
* '''Dose range studied:''' 0.375–21 μg/kg inhaled salvinorin A in controlled human studies{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=b8376b0b}}. The European Union Drugs Agency reports 200–500 μg as typical doses for vivid effects{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=a0852dd7}}.
* '''Onset:''' Approximately 2 minutes (peak effects coincide with onset at the first measured time point){{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=a15da4bc}}
* '''Duration:''' Approximately 15–20 minutes (definite [[index:effects|subjective effects]] absent by approximately 20 minutes){{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=93243051}}
* '''Effect character:''' Dose-related increases on the [[substance_class:psychoactive/hallucinogen]] Rating Scale and Mysticism Scale{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=825ef34a}}. Internal and [[effect:external-hallucinations]], [[effect:spatial-disorientation]], [[effect:depersonalization|depersonalisation]] and [[effect:derealization|derealisation]], [[effect:proprioceptive-distortion]], [[effect:entity-contact]], revisiting of childhood memories, cartoon-like visual imagery, [[effect:temporal-disorientation]], and [[effect:amnesia]] for portions of the experience{{cite|doi=10.1007/s00213-012-2912-9|anchor=8275d423}}{{cite|doi=10.1007/s00213-011-2470-6|anchor=eafa9799}}. Post-acute residual [[glossary:fatigue]] and mild cognitive fog lasting hours{{cite|doi=10.1007/s00213-011-2470-6|anchor=c4232967}}.
* '''Cardiovascular effects:''' No significant increase in [[glossary:heart-rate]] or [[glossary:blood-pressure]] across doses up to 21 μg/kg{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=07e19e20}}.
===Enhanced extract (smoked)===
Commercial products labeled "5×," "10×," "20×," "50×" etc. are dried leaf material enriched with additional salvinorin A. Measured salvinorin A content ranges from 13.0 to 53.2 mg/g — an 8- to 35-fold increase over plain leaf{{cite|doi=10.1021/acsomega.2c06106|anchor=e33c4be4}}. [[glossary:pharmacokinetics]] are identical to smoked dried leaf, but the dose of salvinorin A per gram of material is substantially higher.
{{Warning}}Labeled [[glossary:potency]] multipliers do '''not''' reliably predict actual salvinorin A content. A product labeled "60×" was measured at 29.3 mg/g — lower than a "50×" product at 53.2 mg/g{{cite|doi=10.1021/acsomega.2c06106|anchor=8954a914}}. Users cannot determine true potency from label claims. No [[glossary:controlled-study|controlled human study]] using commercial enhanced extracts has been published.{{/Warning}}
===Fresh-leaf quid (buccal)===
The traditional Mazatec preparation. Fresh leaves are crushed, rolled, or chewed and held in the mouth, with juice retained against the buccal and [[glossary:sublingual]] mucosa for 15–30 minutes{{cite|pubmed=23627785|anchor=58e7940e}}{{cite|doi=10.1016/j.jep.2013.11.032|anchor=43709983}}. Buccal [[glossary:absorption]] partially bypasses the gastrointestinal [[glossary:hydrolysis]] that inactivates swallowed salvinorin A.
* '''Dose:''' Typically 8–28 fresh leaves (ethnographic reports){{cite|pubmed=23627785|anchor=74537e04}}
* '''Onset:''' Approximately 15–30 minutes
* '''Duration:''' 30–90 minutes{{cite|pubmed=23627785|anchor=7b6e23b6}}
* '''Effect character:''' Based on field observations, effects include light-headedness, [[effect:dysphoria]], tactile and proprioceptive sensations, depersonalisation, amplified sound [[glossary:perception]], and increased visual and auditory imagery — generally '''not''' full visual [[glossary:hallucination|hallucinations]] at traditional doses{{cite|pubmed=23627785|anchor=6cf49f86}}.
{{Info}}No controlled pharmacokinetic or dose-response study of the fresh-leaf quid preparation has been published. All onset, duration, and effect characterisation data derive from ethnographic field observations.{{/Info}}
===Water infusion===
Fresh leaves crushed and mixed with cold water, consumed as a drink. Used traditionally but presumed less potent than the quid due to shorter buccal contact time and potential gastrointestinal [[glossary:degradation]] of salvinorin A{{cite|pubmed=23627785|anchor=95075f1c}}. No controlled study data exist for this preparation.
===Sublingual (liquid formulation)===
A [[glossary:placebo-controlled-trial]] of sublingual salvinorin A in a liquid formulation produced '''no psychoactive effects'''{{cite|doi=10.1007/s00213-010-2103-5|anchor=901292ee}}. The discrepancy between this null result and the reported activity of the traditional quid may reflect differences in mucosal contact dynamics — mechanical chewing stimulates mucosal [[glossary:blood-flow]] and provides prolonged contact time with plant matrix — but this [[glossary:hypothesis]] has not been formally tested.
===Oral (swallowed)===
Inactive. Salvinorin A is rapidly hydrolysed to pharmacologically inactive [[substance_class:chemical/salvinorin]] B by gastrointestinal esterases{{cite|doi=10.3390/ph14020116|anchor=758e0d68}}. No controlled human data exist for oral administration.
====Fresh-leaf quid (buccal)====
'''Fresh-leaf quid''' is the traditional Mazatec preparation. Fresh leaves are held in the mouth, with juice absorbed through the cheek and under the tongue{{cite|pubmed=23627785|anchor=4be4ed42}}. Onset: 10–20 minutes to full effect. Duration: 30–90 minutes{{cite|pubmed=23627785|anchor=97eac1cd}}. The experience is milder than smoked preparations — light-headedness, altered body sense, and mild imagery without full hallucinatory breakthrough. Requires fresh [[glossary:plant-material]].
====Dried leaf (smoked)====
'''Dried leaf''' — plain, non-enhanced — is smoked in a pipe or water pipe. Onset within approximately 2 minutes; effects resolve within 15–20 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=f8f2708f}}. Even without concentration, plain leaf at higher amounts can produce complete dissociation from the physical environment. [[glossary:potency]] varies by plant source, drying method, and storage.
====Concentrated extract (smoked or vaporised)====
'''Concentrated extracts''' are sold with strength multipliers (5×, 10×, 20×, 60×+). These are most associated with overwhelming experiences and adverse psychological reactions. Labelled potency frequently does not reflect actual [[substance:salvinorin-a]] content{{cite|doi=10.1021/acsomega.2c06106|anchor=cf45b64a}}. Onset and duration mirror plain leaf — roughly 2 minutes onset, 15–20 minutes duration — but [[glossary:intensity]] at equivalent mass is dramatically higher.
====Water infusion (oral)====
'''Water infusion''' — crushed fresh leaves mixed with cold water — is a documented traditional preparation{{cite|pubmed=23627785|anchor=2e326a59}}. Effects are mild and brief. Rarely encountered outside traditional Mazatec contexts.
Per-preparation dose tiers, timelines, and [[glossary:bioavailability]] data are in the Dose · by preparation card on this page.
====Toxicity====
No human fatalities have been directly attributed to [[substance:salvinorin-a]]{{cite|doi=10.3390/ph14020116|anchor=f88312af}}{{cite|doi=10.3390/ijms26125588|anchor=9da4b92e}}. Controlled human studies found no significant changes in [[glossary:heart-rate]] or [[glossary:blood-pressure]] at doses of 0.375–21 μg/kg inhaled{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=8ad67b72}}.
[[glossary:animal-model|Animal studies]] indicate salvinorin A impairs long-term memory at high doses — an effect blocked by [[substance_class:pharmacological/kappa-opioid-receptor-antagonist|kappa-opioid receptor antagonists]], confirming the mechanism{{cite|doi=10.1177/1091581811418538|anchor=33385c66}}. Brief [[effect:amnesia]] during the acute experience is reported in human studies{{cite|doi=10.1007/s00213-012-2912-9|anchor=7dc6341d}}.
Commercial ''S. divinorum'' products carry labelling accuracy concerns — measured salvinorin A content deviates substantially from labelled [[glossary:potency]]{{cite|doi=10.1021/acsomega.2c06106|anchor=9c343dc5}}. No published [[glossary:surveillance]] of pesticide residues, heavy metals, or microbial [[glossary:contamination]] in commercial products exists.
{{flag|safety-citation-needed}} The absence of contaminant surveillance data does not indicate absence of contamination — it reflects a gap in the published [[glossary:evidence-base]].
====Psychological Risks====
Intense fear, panic, and extreme [[glossary:disorientation]] are common at typical smoked doses, particularly with concentrated extracts or in uncontrolled settings{{cite|doi=10.1080/02791072.2016.1179376|anchor=415752e5}}. [[effect:dysphoria]] is more frequently reported than [[effect:euphoria]]{{cite|pubmed=23627785|anchor=e9b6c274}}. Complete loss of environmental [[glossary:awareness]] is the primary [[glossary:acute-risk]] — individuals may fall, contact hazards, or injure themselves without recognising danger.
[[glossary:case-report|Case reports]] have linked ''S. divinorum'' use to persistent [[glossary:psychotic-episodes]] in individuals with possible pre-existing psychiatric [[glossary:vulnerability]]{{cite|doi=10.1080/02791072.2015.1073815|anchor=a2d98fdc}}. One case involved a psychotic episode resistant to two [[glossary:medication|medications]] before resolving with a third{{cite|doi=10.1701/3888.38708|anchor=31222705}}. Multiple reviews flag elevated psychiatric risk in adolescents and those with underlying psychotic conditions{{cite|doi=10.1002/hup.2304|anchor=38d8a95e}}{{cite|doi=10.1111/appy.12225|anchor=11889a01}}.
The causal relationship between ''S. divinorum'' and persisting [[glossary:psychosis]] is '''not''' established — all published cases involve individuals with potential pre-existing vulnerability, and no prospective psychiatric outcome data exist.
====Tolerance and Dependence====
Rapid loss of effect with repeated dosing within a single session ([[glossary:tachyphylaxis]]) is commonly reported{{cite|doi=10.1080/02791072.2016.1179376|anchor=6df1e6a7}}. No [[glossary:dependence]] syndrome has been described in the clinical literature{{cite|doi=10.1111/appy.12225|anchor=4836c3a2}}. The aversive experience and [[glossary:dopamine]] suppression in [[glossary:mesolimbic-pathway|reward circuits]] explain the substance's low [[glossary:abuse-potential]]{{cite|doi=10.3390/biomedicines14020476|anchor=3ff21ea9}}{{cite|pubmed=16223871|anchor=ef71bed6}}.
Over 52% of surveyed users reduced or stopped use within 12 months, most citing dislike of effects or loss of interest{{cite|doi=10.1002/hup.2304|anchor=90a1e8a9}}. No [[glossary:withdrawal]] has been described. Multiple reviews conclude salvinorin A has '''low abuse potential'''{{cite|doi=10.3390/biomedicines14020476|anchor=9ebadbf9}}{{cite|doi=10.3389/fphar.2015.00190|anchor=0b046a62}}.
====Drug Interactions====
{{Warning}}All herb–[[glossary:drug-interaction]] assessments for ''S. divinorum'' are based on [[glossary:in-vitro|in vitro]] metabolic data and theoretical pharmacodynamic mechanisms. '''No clinical pharmacokinetic interaction study''' has been conducted in humans for salvinorin A. The interaction severities below are inferred, not empirically established.{{/Warning}}
Salvinorin A is processed by [[glossary:liver-enzymes]] [[glossary:cyp2d6]], CYP1A1, CYP2E1, and CYP2C18, with an additional processing pathway (UGT2B7); it is also a P-glycoprotein [[glossary:substrate]]{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=3a54f25f}}. [[glossary:inhibitor|Inhibitors]] of CYP2D6 (fluoxetine, paroxetine, quinidine) or CYP2E1 (disulfiram) could raise salvinorin A levels and prolong effects.
* '''CNS depressants''' ([[substance_class:psychoactive/opioid|opioids]], [[substance_class:chemical/benzodiazepine|benzodiazepines]], [[substance:alcohol]], [[substance:cannabis]]): Additive [[glossary:central-nervous-system|CNS]] [[effect:depression]], disorientation, and impaired motor control are theoretically possible.{{flag|safety-citation-needed}}
* '''Lithium:''' [[glossary:seizure]] risk has been reported anecdotally with [[substance:lithium]] in combination with [[substance_class:psychoactive/psychedelic|psychedelics]]. No specific case report with salvinorin A exists.{{flag|safety-citation-needed}}
* '''MAOIs and SSRIs:''' Theoretical pharmacodynamic concern given [[glossary:kappa-opioid-receptor]] and [[glossary:serotonin-transporter]] interactions. No clinical case reports.{{flag|safety-citation-needed}}
====Contraindications====
'''Absolute:'''
* '''Personal or family history of psychotic disorders''' (schizophrenia, schizoaffective [[glossary:disorder]], bipolar disorder with psychotic features) — case reports document persistent psychotic episodes in individuals with possible pre-existing vulnerability{{cite|doi=10.1080/02791072.2015.1073815|anchor=13277b6f}}{{cite|doi=10.1701/3888.38708|anchor=785d9fb7}}
'''Relative:'''
* '''Adolescence''' — elevated risk flagged in multiple reviews; the developing brain may be especially sensitive to kappa-opioid-mediated dopamine suppression{{cite|doi=10.1002/hup.2304|anchor=2c1b8360}}{{cite|doi=10.1111/appy.12225|anchor=25730c1b}}
* '''Pregnancy and breastfeeding''' — no published safety data exist{{flag|safety-citation-needed}}
* '''Hepatic impairment''' — [[glossary:enzyme]] involvement in salvinorin A [[glossary:metabolism]] suggests possible altered [[glossary:clearance]] in liver disease{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=dabd2741}}
* '''Concurrent use of CYP2D6 or CYP2E1 inhibitors''' — theoretical risk of increased salvinorin A exposure
* '''Unsupervised settings or environments with fall risk''' — [[effect:motor-control-impairment]] and complete environmental unawareness at typical smoked doses create physical injury risk{{cite|doi=10.1080/02791072.2016.1179376|anchor=50b88757}}
Standard urine drug screens do '''not''' detect salvinorin A. [[glossary:detection]] requires a specialised laboratory test (LC-MS/MS){{cite|pubmed=18652747|anchor=6556b214}}.
====Toxicity====
No human fatalities have been directly attributed to [[substance:salvinorin-a]]{{cite|doi=10.3390/ph14020116|anchor=e798cdef}}{{cite|doi=10.3390/ijms26125588|anchor=7f2e05f0}}. No formal [[glossary:lethal-dose|LD50]] has been established. The most recent [[glossary:systematic-review]] of preclinical data found no evidence of significant physiological [[glossary:toxicity]] at psychoactive doses{{cite|doi=10.1038/s41398-025-03638-3|anchor=8d26e04b}}.
Controlled human studies found no significant increase in [[glossary:heart-rate]] or [[glossary:blood-pressure]] across inhaled doses from 0.375 to 21 μg/kg{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=dc165e73}}. This distinguishes salvinorin A from [[glossary:serotonergic-psychedelics|classical psychedelics]], which reliably elevate heart rate.
Salvinorin A (160–640 μg/kg, s.c.) impaired spatial long-term memory, episodic memory, and aversive memory in rats while sparing short-term memory; these effects were blocked by the selective κ-opioid [[glossary:antagonist]] nor-BNI, confirming KOR mediation{{cite|doi=10.1177/1091581811418538|anchor=24fd7f75}}. [[effect:amnesia]] for portions of the acute experience is also documented in human studies{{cite|doi=10.1007/s00213-012-2912-9|anchor=f74eddf7}}.
Commercial ''S. divinorum'' products carry labelling accuracy concerns — measured salvinorin A content deviates substantially from labelled [[glossary:potency]]{{cite|doi=10.1021/acsomega.2c06106|anchor=965e7b42}}. No published systematic [[glossary:surveillance]] of pesticide residues, heavy metals (lead, cadmium, arsenic, mercury), mycotoxins, or microbial [[glossary:contamination]] in commercial products was identified. No ISO/IEC-accredited testing programmes or Certificate of Analysis requirements specific to ''S. divinorum'' products exist in any jurisdiction.
{{flag|safety-citation-needed}} The absence of contaminant surveillance data does not indicate absence of contamination — it reflects a gap in the published [[glossary:evidence-base]].
====Psychological Risks====
Intense fear, panic, and extreme [[glossary:disorientation]] are common at typical smoked doses, particularly with concentrated extracts or in uncontrolled settings{{cite|doi=10.1080/02791072.2016.1179376|anchor=ec46de59}}. [[effect:dysphoria]] is more frequently reported than [[effect:euphoria]]{{cite|pubmed=23627785|anchor=e93880c6}}. Complete loss of [[glossary:awareness]] of the physical environment constitutes the primary [[glossary:acute-risk]] — users may fall, walk into hazards, or injure themselves without recognising danger.
[[glossary:case-report|Case reports]] have linked ''S. divinorum'' use to persistent [[glossary:psychotic-episodes]] in individuals with possible pre-existing psychiatric [[glossary:vulnerability]]{{cite|doi=10.1080/02791072.2015.1073815|anchor=969f646d}}. One report described a psychotic episode following unintentional consumption, resistant to two pharmacological treatments before resolving with brexiprazole{{cite|doi=10.1701/3888.38708|anchor=505305e0}}. Multiple reviews flag elevated psychiatric risk in adolescents, users of other substances, and individuals with underlying psychotic [[glossary:disturbance|disturbances]]{{cite|doi=10.1002/hup.2304|anchor=d07f605a}}{{cite|doi=10.1111/appy.12225|anchor=e4e204c2}}.
The causal relationship between ''S. divinorum'' and persisting [[glossary:psychosis]] is '''not''' established — all published cases involve individuals with potential pre-existing vulnerability, and no prospective psychiatric outcome data exist.
====Tolerance & Dependence====
[[glossary:tachyphylaxis]] — rapid loss of effect with repeated dosing within a single session — is commonly reported{{cite|doi=10.1080/02791072.2016.1179376|anchor=12763b28}}. No formal [[glossary:tolerance]] study exists in humans.
No [[glossary:dependence]] syndrome has been described in the clinical literature{{cite|doi=10.1111/appy.12225|anchor=589af6d8}}. The aversive [[glossary:phenomenology]] and KOR-mediated dopaminergic suppression underlie the substance's low [[glossary:abuse-potential]]{{cite|doi=10.3390/biomedicines14020476|anchor=520b94a8}}{{cite|pubmed=16223871|anchor=7c0e377d}}. Survey data indicate over 52% of users reduced or ceased use within 12 months, citing dislike of effects (33%) and loss of interest (29%){{cite|doi=10.1002/hup.2304|anchor=ed48115e}}.
No [[glossary:withdrawal]] has been characterised. Multiple reviews conclude that salvinorin A has '''low abuse potential''' based on aversive phenomenology, dopaminergic suppression, and absence of positive [[glossary:reinforcement]] in animal [[glossary:self-administration]] paradigms{{cite|doi=10.3390/biomedicines14020476|anchor=d04f79d0}}{{cite|doi=10.3389/fphar.2015.00190|anchor=276e875a}}.
====Drug Interactions====
{{Warning}}All herb–[[glossary:drug-interaction]] assessments for ''S. divinorum'' are based on [[glossary:in-vitro|in vitro]] metabolic data and theoretical pharmacodynamic mechanisms. '''No clinical pharmacokinetic interaction study''' has been conducted in humans for salvinorin A. The interaction severities below are inferred, not empirically established.{{/Warning}}
Salvinorin A is metabolised by [[glossary:cyp2d6]], CYP1A1, CYP2E1, and CYP2C18, with additional [[glossary:glucuronidation]] via UGT2B7, and is a P-glycoprotein [[glossary:substrate]]{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=9bdadae3}}. Drugs that inhibit CYP2D6 (fluoxetine, paroxetine, quinidine) or CYP2E1 (disulfiram) could theoretically increase salvinorin A [[glossary:plasma-concentration|plasma levels]] and prolong effects. P-glycoprotein [[glossary:inhibitor|inhibitors]] (verapamil, cyclosporine) could alter [[glossary:central-nervous-system|CNS]] distribution.
* '''CNS depressants''' ([[substance_class:psychoactive/opioid|opioids]], [[substance_class:chemical/benzodiazepine|benzodiazepines]], [[substance:alcohol]], [[substance:cannabis]]): Additive CNS [[effect:depression]], disorientation, and impaired motor control are theoretically possible.{{flag|safety-citation-needed}}
* '''Lithium:''' [[glossary:seizure]] risk has been reported anecdotally with [[substance:lithium]] in combination with [[substance_class:psychoactive/psychedelic|psychedelics]]. No specific case report with salvinorin A exists.{{flag|safety-citation-needed}}
* '''MAOIs and SSRIs:''' Theoretical pharmacodynamic concern given KOR–[[glossary:serotonin-transporter]] interactions. No clinical case reports.{{flag|safety-citation-needed}}
====Contraindications====
'''Absolute:'''
* '''Personal or family history of psychotic disorders''' (schizophrenia, schizoaffective [[glossary:disorder]], bipolar disorder with psychotic features) — case reports document persistent psychotic episodes in individuals with possible pre-existing vulnerability{{cite|doi=10.1080/02791072.2015.1073815|anchor=b5117195}}{{cite|doi=10.1701/3888.38708|anchor=224fe22b}}
'''Relative:'''
* '''Adolescence''' — elevated risk flagged in multiple reviews; developing brain vulnerability to KOR-mediated dopaminergic suppression is a mechanistic concern{{cite|doi=10.1002/hup.2304|anchor=62558113}}{{cite|doi=10.1111/appy.12225|anchor=830a8b82}}
* '''Pregnancy and breastfeeding''' — no published safety data exist{{flag|safety-citation-needed}}
* '''Hepatic impairment''' — [[glossary:cytochrome-p450|CYP enzyme]] involvement in salvinorin A [[glossary:metabolism]] suggests possible altered metabolism in liver disease{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=b0be268f}}
* '''Concurrent use of CYP2D6 or CYP2E1 inhibitors''' — theoretical risk of increased salvinorin A exposure
* '''Unsupervised settings or environments with fall risk''' — [[effect:motor-control-impairment]] and complete loss of environmental awareness at typical smoked doses create physical injury risk{{cite|doi=10.1080/02791072.2016.1179376|anchor=e297e389}}
Standard immunoassay drug screens do '''not''' detect salvinorin A. [[glossary:detection]] requires specific LC-MS/MS methodology{{cite|pubmed=18652747|anchor=76dc67d1}}.
====Fresh-leaf quid (buccal)====
'''Fresh-leaf quid''' is the traditional Mazatec preparation. Freshly picked leaves are rolled or crushed into a bolus and held in the mouth, with juice retained for buccal and [[glossary:sublingual]] [[glossary:absorption]]{{cite|pubmed=23627785|anchor=c136a33a}}. Onset is gradual (10–20 minutes), with effects lasting 30–90 minutes{{cite|pubmed=23627785|anchor=c4c26048}}. The experience is markedly milder than smoked preparations — light-headedness, altered proprioception, [[effect:depersonalization|depersonalisation]], and enhanced imagery without full hallucinatory breakthrough. This preparation requires fresh [[glossary:plant-material]], limiting availability outside cultivation regions.
====Dried leaf (smoked)====
'''Dried leaf''' (plain, non-enhanced) is smoked in a pipe or water pipe. Onset occurs within approximately 2 minutes, with effects resolving within 15–20 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=63c64d03}}. The experience is considerably more intense than the quid — complete dissociation from the physical environment is possible even with plain leaf at higher amounts. [[glossary:potency]] varies by plant source, drying method, and [[glossary:storage-conditions]].
====Concentrated extract (smoked/vaporised)====
'''Concentrated extracts''' are produced by solvent extraction of dried leaf material and sold with strength multipliers (5×, 10×, 20×, 60×+). These preparations are most commonly associated with intense, overwhelming experiences and adverse psychological reactions. Labelled potency frequently does not reflect measured [[substance:salvinorin-a]] content{{cite|doi=10.1021/acsomega.2c06106|anchor=8226eb0c}}. Onset and duration mirror dried leaf (approximately 2 minutes onset, 15–20 minutes duration), but [[glossary:intensity]] at equivalent mass is dramatically higher. The unpredictability of extract potency makes dose calibration from product labelling unreliable.
====Water infusion (oral)====
'''Water infusion''' — crushed fresh leaves mixed with cold water — is a documented traditional preparation{{cite|pubmed=23627785|anchor=81b2e507}}. Effects were described as mild and short-lasting in ethnographic field research. This preparation is rarely encountered outside traditional Mazatec contexts.
Per-preparation dose tiers, timelines, and [[glossary:bioavailability]] data are in the Dose · by preparation card on this page.
===Forms and Identification===
''Salvia divinorum'' products range from plain dried leaf to highly concentrated extracts (5×, 10×, 20×, and higher). Labelled [[glossary:potency]] does not reliably correspond to measured [[substance:salvinorin-a]] content{{cite|doi=10.1021/acsomega.2c06106|anchor=d9f3109f}}. No standard testing programme or Certificate of Analysis requirement exists for these products.
Lower-strength preparations (plain leaf or 5×) offer more predictable dosing than high-concentration extracts. No [[glossary:reagent-kit|reagent testing]] kit reliably quantifies salvinorin A in home settings.
===Set and Setting===
[[glossary:set-and-setting]] exert unusually strong influence on the ''S. divinorum'' experience{{cite|doi=10.1080/02791072.2016.1179376|anchor=384d4ed6}}. The substance's capacity to obliterate environmental [[glossary:awareness]] makes the physical setting critical.
A quiet, dimly lit indoor space with soft surfaces and no sharp edges or hazards is essential. A sober, trusted [[glossary:sitter]] is not optional at any dose above threshold. The sitter's role is physical safety — preventing falls, contact with flame, and wandering into dangerous areas.
The sitter should not attempt to interact with or redirect the experience unless physical safety is at risk.
===Guidelines===
{{Guideline}}
====Practical Guidance====
* Begin with plain dried leaf before attempting any concentrated extract
* Use the smallest amount possible for a first experience — salvinorin A is active at microgram doses
* Ensure a sober sitter is present throughout the experience and for at least 15 minutes after apparent offset
* Sit or lie down before administration — never stand during onset
* Remove all fire sources, sharp objects, and fall hazards from the immediate environment
* Do not drive or operate machinery for at least one hour after effects resolve
* Do not [[glossary:redose]] within the same session — [[glossary:tachyphylaxis]] makes repeated dosing unpredictable
* Avoid use in unfamiliar environments, at social gatherings, or in any setting where uncontrolled movement poses a risk
* Avoid combining with [[glossary:cns-depressants]], [[substance:alcohol]], or other psychoactive substances
{{/Guideline}}
===Emergency Response===
{{Emergency}}
====Recognising an emergency====
* Complete unresponsiveness lasting more than 5 minutes after smoking
* Attempts to stand, walk, or run while unaware of physical surroundings
* Severe panic with [[glossary:agitation]] that does not begin to resolve within 10–15 minutes
* [[glossary:self-harm]] attempts or violent behaviour
* [[glossary:psychosis|Psychotic symptoms]] ([[effect:paranoia]], [[effect:delusions]], disorganised speech) persisting beyond 30 minutes after smoking
====Immediate steps====
* Ensure the person is in a safe position (seated or lying on their side) and cannot fall or contact hazards
* Speak calmly and reassuringly — do not physically restrain unless they are in immediate danger
* If panic is present, reassure them the effects are temporary and will pass within minutes
* Call emergency services if psychotic symptoms persist beyond 30 minutes, if there is any injury, or if the person remains unresponsive
====What to tell the dispatcher====
State the substance (Salvia divinorum or salvinorin A), the approximate amount and preparation used, time of administration, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] exist in many jurisdictions and provide legal protection for reporting drug-related emergencies.
No pharmacological reversal agent for salvinorin A is available outside clinical settings. Naltrexone blocks [[glossary:kappa-opioid-receptor]] effects but is not carried by first responders and is not indicated for acute field management.
{{/Emergency}}
===Aftercare and Integration===
{{Aftercare}}
====Post-Experience Processing====
The [[glossary:intensity]] of the ''S. divinorum'' experience frequently leaves individuals shaken or emotionally unsettled even after acute effects resolve. Allow 30–60 minutes of quiet recovery before returning to normal activities.
[[effect:amnesia]] for portions of the experience is common{{cite|doi=10.1007/s00213-012-2912-9|anchor=ae521db1}}. Writing or recording impressions shortly after can help with processing. Persistent [[effect:dysphoria]], [[effect:anxiety]], or a sense of unreality lasting more than 24 hours warrants professional consultation.
[[glossary:hydration]] and a light meal after the experience may ease physical discomfort. Avoid further psychoactive [[glossary:substance-use]] for the remainder of the day.
{{/Aftercare}}
===Recovery and Support===
{{Recovery}}
====Cessation and Support Resources====
Compulsive ''S. divinorum'' use is rare due to the substance's aversive character and low [[glossary:reinforcement]] potential{{cite|doi=10.3390/biomedicines14020476|anchor=20a814c1}}. Any pattern of use that causes [[glossary:distress]] or [[glossary:impairment]] warrants professional attention.
If ''S. divinorum'' use has triggered or worsened psychiatric symptoms — particularly psychosis, persistent anxiety, or [[effect:depersonalization|depersonalisation]] — seek evaluation from a mental health professional experienced with substance-related presentations.
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7)
* '''Crisis Text Line:''' Text HOME to 741741
* '''Emergency services:''' Call 911 (US) or local emergency number for acute psychiatric crisis
{{/Recovery}}
===Forms & Identification===
''Salvia divinorum'' products range from plain dried leaf to highly concentrated extracts labelled with strength multipliers (5×, 10×, 20×, and higher). Labelled [[glossary:potency]] does not reliably correspond to measured [[substance:salvinorin-a]] content{{cite|doi=10.1021/acsomega.2c06106|anchor=f9c91764}}, and no ISO/IEC-accredited testing programme or Certificate of Analysis standard exists for these products.
When purchasing commercial products, lower-strength preparations (plain leaf or 5×) offer more predictable dosing than high-concentration extracts. Starting with plain dried leaf before attempting extracts allows calibration of individual [[glossary:sensitivity]]. No [[glossary:reagent-kit|reagent testing]] kit reliably quantifies salvinorin A content in home settings.
===Set & Setting===
[[glossary:set-and-setting]] exert unusually strong influence on the ''S. divinorum'' experience{{cite|doi=10.1080/02791072.2016.1179376|anchor=7d8a588f}}. The substance's capacity to obliterate [[glossary:awareness]] of the physical environment makes controlled, familiar settings essential.
A quiet, dimly lit indoor space with soft surfaces and no sharp edges or hazards is strongly recommended. A sober, trusted [[glossary:sitter]] is considered essential — not optional — at any dose above threshold. The sitter's role is physical safety: preventing falls, contact with flame, and wandering into dangerous areas. The sitter should not attempt to interact with or redirect the user's experience unless physical safety is at risk.
===Guidelines===
{{Guideline}}
====Practical Guidance====
* Begin with plain dried leaf before attempting any concentrated extract
* Use the smallest amount possible for a first experience — salvinorin A is active at microgram doses
* Ensure a sober sitter is present throughout the experience and for at least 15 minutes after apparent offset
* Sit or lie down before administration — never stand during onset
* Remove all fire sources, sharp objects, and fall hazards from the immediate environment
* Do not drive or operate machinery for at least one hour after effects resolve
* Do not [[glossary:redose]] within the same session — [[glossary:tachyphylaxis]] makes repeated dosing unpredictable
* Avoid use in unfamiliar environments, at social gatherings, or in any setting where uncontrolled movement poses a risk
* Avoid combining with [[glossary:cns-depressants]], [[substance:alcohol]], or other psychoactive substances
{{/Guideline}}
===Emergency Response===
{{Emergency}}
====Recognising an emergency====
* Complete unresponsiveness lasting more than 5 minutes after smoking
* Attempts to stand, walk, or run while unaware of physical surroundings
* Severe panic with [[glossary:agitation]] that does not begin to resolve within 10–15 minutes
* [[glossary:self-harm]] attempts or violent behaviour
* [[glossary:psychosis|Psychotic symptoms]] ([[effect:paranoia]], [[effect:delusions]], disorganised speech) persisting beyond 30 minutes after smoking
====Immediate steps====
* Ensure the person is in a safe position (seated or lying on their side) and cannot fall or contact hazards
* Speak calmly and reassuringly — do not physically restrain unless they are in immediate danger
* If panic is present, reassure them the effects are temporary and will pass within minutes
* Call emergency services if psychotic symptoms persist beyond 30 minutes, if there is any injury, or if the person remains unresponsive
====What to tell the dispatcher====
State the substance (Salvia divinorum or salvinorin A), the approximate amount and preparation used, time of administration, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] exist in many jurisdictions and provide legal protection for reporting drug-related emergencies.
No pharmacological reversal agent for salvinorin A is available outside clinical settings. Naltrexone blocks [[glossary:kappa-opioid-receptor]] effects but is not carried by first responders and is not indicated for acute field management.
{{/Emergency}}
===Aftercare & Integration===
{{Aftercare}}
====Post-Experience Processing====
The [[glossary:intensity]] and alien quality of the ''S. divinorum'' experience frequently leaves users shaken, confused, or emotionally unsettled even after acute effects resolve. Allow 30–60 minutes of quiet recovery before returning to normal activities.
[[effect:amnesia]] for portions of the experience is common{{cite|doi=10.1007/s00213-012-2912-9|anchor=28655e8c}}. Writing or recording impressions shortly after can help with processing. Persistent [[effect:dysphoria]], [[effect:anxiety]], or [[effect:derealization]] lasting more than 24 hours warrants professional consultation.
[[glossary:hydration]] and a light meal after the experience may ease physical discomfort. Avoid further psychoactive [[glossary:substance-use]] for the remainder of the day.
{{/Aftercare}}
===Recovery & Support===
{{Recovery}}
====Cessation and Support Resources====
Compulsive ''S. divinorum'' use is rare due to the substance's aversive [[glossary:phenomenology]] and low [[glossary:reinforcement]] potential{{cite|doi=10.3390/biomedicines14020476|anchor=09584cf5}}. However, any pattern of use that causes [[glossary:distress]] or [[glossary:impairment]] warrants professional attention.
If ''S. divinorum'' use has triggered or worsened psychiatric symptoms — particularly psychotic features, persistent anxiety, or [[effect:depersonalization|depersonalisation]] — seek evaluation from a mental health professional experienced with substance-related presentations.
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7)
* '''Crisis Text Line:''' Text HOME to 741741
* '''Emergency services:''' Call 911 (US) or local emergency number for acute psychiatric crisis
{{/Recovery}}
''Salvia divinorum'' and [[substance:salvinorin-a]] are '''not listed''' under any of the three UN [[glossary:drug-control|international drug control]] conventions{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=a2372954}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=9f664eb4}}. This absence from international scheduling has produced a fragmented global legal landscape, with control measures implemented piecemeal at national and sub-national levels. In the United States, ''S. divinorum'' is not federally scheduled but is banned or restricted in approximately 27 states; internationally, it is controlled in Canada, the United Kingdom, Australia, Germany, Japan, and several other jurisdictions.
{{flag|citation-needed}} US state-level legal status is subject to frequent change. The classifications above are based on 2024 [[glossary:secondary-source|secondary sources]] and require verification against current state statutes.
Because salvinorin A is a diterpenoid with no nitrogen atom, it does not fall within the structural definitions used by many [[glossary:structural-analog]] acts or blanket scheduling frameworks designed around nitrogenous psychoactive compounds. Jurisdictions that control ''S. divinorum'' have done so by specifically naming the plant, the compound, or by applying broad psychoactive-substance legislation (as in the United Kingdom's Psychoactive Substances Act 2016).
| Jurisdiction | Status | Notes |
|---|---|---|
| United States (federal) | Not scheduled | DEA lists ''S. divinorum'' as a "Drug and Chemical of Concern" but has not initiated formal scheduling{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=80ecbe73}} |
| United States (states — banned) | Controlled substance (~27 states) | Outright bans in Delaware, Florida, Illinois, Kansas, Kentucky, Louisiana, Mississippi, Missouri, Nebraska, North Dakota, Ohio, Oklahoma, Pennsylvania, South Dakota, Tennessee, Texas, Virginia, and others{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=977a5a5f}} |
| United States (states — age-restricted) | Age restriction only | California (18+), Maine{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=aa661aba}} |
| United States (states — unrestricted) | No state-level restriction | ~22 states including Alaska, Arizona, Idaho, Massachusetts, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, Oregon, South Carolina, Utah, Washington, West Virginia, and DC{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=9e25ca8a}} |
| Canada | Schedule IV | Controlled since 2017 under the Controlled Drugs and Substances Act{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=0acc4918}} |
| United Kingdom | Banned | Prohibited since 26 May 2016 under the Psychoactive Substances Act 2016; salvinorin A is not individually named{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=09cc1a4e}} |
| Australia | Schedule 9 — Prohibited | Most restrictive schedule under the Therapeutic Goods Act; live plants also prohibited{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=5a1ed3d9}} |
| Germany | Controlled | Controlled since approximately 2015 under narcotics law{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=44413ced}} |
| EU member states (selected) | Domestic restrictions vary | Belgium, Denmark, Estonia, Finland, Iceland (EEA), Ireland, Italy, Romania, Slovakia, Spain, and Sweden have enacted domestic restrictions{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=6adc1985}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=a82e4dd8}} |
| Japan | Controlled | Controlled since 2007{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=9a9a38db}} |
| Brazil, South Korea, Norway, Poland | Domestic restrictions | Various domestic controls in effect{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=7213b1b9}} |
''Salvia divinorum'' and [[substance:salvinorin-a]] are '''not listed''' under any UN [[glossary:drug-control|international drug control]] convention{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=84f89334}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=1a97f07a}}. This has produced a fragmented global legal landscape. In the United States, the plant is not federally scheduled — the [[glossary:drug-enforcement-administration|DEA]] lists it as a "Drug and Chemical of Concern" but has not pursued scheduling{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=98a8d1ad}} — but approximately 27 states have banned or restricted it. Canada added it to [[glossary:schedule-iv]] in 2017{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=ab498e0a}}. The United Kingdom banned it under the Psychoactive Substances Act 2016{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=5d30a6c1}}. Australia places it on Schedule 9 — the most restrictive category — including live plants{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=bb0d9a52}}. Germany, Japan, and numerous [[glossary:member-state|EU member states]] have enacted domestic controls{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=c9870d7b}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=e1a07fb3}}. Because salvinorin A contains no nitrogen atom, it falls outside the structural definitions used by many drug [[glossary:structural-analog]] laws — jurisdictions that control it have done so by specifically naming the plant or compound.
{{Warning}}
Legal status changes frequently. This overview reflects the status as of the article's last update and is not legal advice. Verify current law in the relevant jurisdiction before acting on this information.
{{/Warning}}
===Primary receptor target===
[[substance:salvinorin-a]] is a '''selective full agonist at the kappa-opioid receptor''' ([[glossary:kappa-opioid-receptor]]) with no clinically significant activity at the [[glossary:serotonin]] [[glossary:5-ht2a]] [[glossary:receptor]] — the canonical target of [[glossary:serotonergic-psychedelics|classical psychedelics]]{{cite|pubmed=12192085|anchor=034efb23}}{{cite|doi=10.1093/ijnp/pyw016|anchor=9ec33a6c}}. This [[glossary:selectivity]] was confirmed in a human [[glossary:antagonist]]-challenge study: naltrexone ([[substance_class:psychoactive/opioid]] receptor antagonist) fully blocked the subjective, cardiovascular, and neuroendocrine effects of inhaled salvinorin A, whereas ketanserin (5-HT₂A antagonist) did not{{cite|doi=10.1093/ijnp/pyw016|anchor=ee9899e7}}. Screening against a battery of over 50 receptors, [[glossary:transporter|transporters]], and [[glossary:channel|ion channels]] identified no other significant targets{{cite|pubmed=12192085|anchor=466e57aa}}. Salvinorin A displays pronounced β-arrestin-biased signalling that distinguishes it from [[glossary:endogenous]] dynorphins and classical KOR [[glossary:agonist|agonists]], producing rapid [[glossary:receptor-desensitization|receptor desensitisation]]{{cite|doi=10.3390/biomedicines14020476|anchor=a36b4f5a}}. Its non-nitrogenous [[glossary:scaffold]] enables a distinct binding epitope — engaging residues in transmembrane domains II and VII of KOR rather than the transmembrane III aspartate typical of classical opioid ligands{{cite|doi=10.1039/d0np00028k|anchor=62dd010d}}.
===CNS mechanism===
KOR [[glossary:activation]] by salvinorin A engages several interconnected neural systems{{cite|doi=10.3389/fphar.2015.00190|anchor=efbb2761}}{{cite|doi=10.3390/biomedicines14020476|anchor=4d90d7dc}}:
* '''Thalamocortical disruption:''' KOR activation in thalamocortical [[glossary:circuit|circuits]] is the primary mechanism underlying the profound perceptual alterations — dissociation, [[glossary:hallucination|hallucinations]], and [[effect:spatial-disorientation]]{{cite|doi=10.3390/biomedicines14020476|anchor=874907eb}}.
* '''Mesolimbic dopaminergic suppression:''' Salvinorin A decreases extracellular [[glossary:dopamine]] in the [[glossary:nucleus-accumbens]] without affecting serotonin{{cite|pubmed=16223871|anchor=ee65fc13}}. This suppression explains the characteristically aversive or dysphoric quality and the substance's low [[glossary:abuse-potential]].
* '''Large-scale network fragmentation:''' Functional connectivity [[glossary:disruption]] across cortical networks has been proposed as a [[glossary:substrate]] for the dissolution of [[glossary:self-referential-thought|self-referential processing]] during the experience{{cite|doi=10.3390/biomedicines14020476|anchor=eab70b11}}.
* '''Neuroendocrine effects:''' Dose-related increases in [[glossary:plasma]] prolactin and cortisol have been documented in humans{{cite|doi=10.1016/j.biopsych.2012.06.012|anchor=74e5a8c0}}.
The endogenous KOR ligands, the dynorphins, are core components of the stress-response system and counter-modulate [[glossary:mesolimbic-pathway|dopaminergic reward]]. Salvinorin A's engagement of this system explains its unique pharmacological profile: intense hallucinogenic and [[substance_class:psychoactive/dissociative]] effects '''without''' the [[effect:euphoria]] and positive [[glossary:reinforcement]] characteristic of serotonergic psychedelics or [[glossary:mu-opioid-receptor]] agonists{{cite|doi=10.3389/fphar.2015.00190|anchor=2f3e8001}}{{cite|doi=10.3390/biomedicines14020476|anchor=08161ae4}}.
===Pharmacokinetics===
No formal human pharmacokinetic study with [[glossary:plasma-concentration]]–time curves has been published. Preclinical data from rats ([[glossary:intraperitoneal]] administration) provide the available quantitative parameters{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=36859205}}:
Salvinorin A is a confirmed P-glycoprotein substrate{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=fa6f523a}}. Human CYP isoforms metabolising salvinorin A [[glossary:in-vitro|in vitro]] include [[glossary:cyp2d6]], CYP1A1, CYP2E1 (greatest effect — 31.1% decrease in concentration), and CYP2C18, with additional [[glossary:glucuronidation]] via UGT2B7{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=a98e1f6e}}. The rapid time course of human effects when smoked — onset at approximately 2 minutes, offset by approximately 20 minutes{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=6ae4975e}} — is consistent with rapid [[glossary:brain-penetration|CNS penetration]] and [[glossary:elimination]].
===Open questions===
* No human pharmacokinetic data with plasma sampling exist for any [[glossary:route-of-administration]].
* The mechanism by which the traditional quid preparation produces effects via buccal [[glossary:absorption]] while a controlled [[glossary:sublingual]] liquid formulation did not{{cite|doi=10.1007/s00213-010-2103-5|anchor=ab26a096}} remains unresolved — mechanical chewing may enhance mucosal [[glossary:blood-flow]] and prolong contact time, but this [[glossary:hypothesis]] has not been formally tested.
* No neuroimaging studies (fMRI, PET, EEG) of ''S. divinorum'' as administered to humans have been published.
| Parameter | Value (rat, i.p.) |
|---|---|
| Plasma half-life | 75 min |
| Brain half-life | 36 min |
| Volume of distribution (Vd) | 47.1 L/kg |
| Clearance (Cl/F) | 26 L/h/kg |
| Brain-to-plasma ratio | 0.050 |
The ''Salvia divinorum'' experience defies simple categorisation within established [[substance_class:psychoactive/psychedelic]], [[substance_class:psychoactive/dissociative]], or [[substance_class:psychoactive/opioid]] frameworks. Preparation is the primary modifier: smoked or vaporised administration produces a rapid, overwhelming immersion that frequently obliterates [[glossary:awareness]] of the physical environment, whereas the traditional fresh-leaf quid produces a subtler perceptual shift without full hallucinatory breakthrough{{cite|pubmed=23627785|anchor=63944455}}. [[glossary:set-and-setting]] exert pronounced influence on experience quality, with unfamiliar or chaotic environments consistently associated with distressing outcomes{{cite|doi=10.1080/02791072.2016.1179376|anchor=a391921e}}. The aversive or dysphoric character reported by many users is a pharmacological feature of [[glossary:kappa-opioid-receptor]] agonism, not a dosing error.
''S. divinorum'' occupies a pharmacological niche distinct from [[glossary:serotonergic-psychedelics|classical serotonergic psychedelics]] (psilocybin, [[substance:lsd]]) and from other dissociatives ([[substance:ketamine]], [[substance:pcp]]). The KOR [[glossary:agonist]] mechanism produces perceptual [[glossary:disruption]] and dissociation without the euphoric [[glossary:valence]] or serotonergic [[effect:geometry|visual geometry]] characteristic of [[substance_class:pharmacological/serotonin-2a-receptor-agonist|serotonin 2A receptor agonists]], and without the [[glossary:nmda-receptor]]-[[glossary:antagonist]] [[glossary:anesthesia|anaesthesia]] of [[substance_class:chemical/arylcyclohexylamine|arylcyclohexylamines]]{{cite|pubmed=12192085|anchor=8f3c73d4}}{{cite|doi=10.3390/biomedicines14020476|anchor=1eadb3c2}}.
===Toxicity===
No human fatalities have been directly attributed to [[substance:salvinorin-a]] alone in the published literature{{cite|doi=10.3390/ph14020116|anchor=479d9bf5}}{{cite|doi=10.3390/ijms26125588|anchor=1409c6dd}}. No formal [[glossary:lethal-dose|LD50]] has been established in humans or in published preclinical models. The most recent [[glossary:systematic-review]] and meta-analysis of preclinical data found no evidence of significant physiological [[glossary:toxicity]] at psychoactive doses{{cite|doi=10.1038/s41398-025-03638-3|anchor=f98cbeb2}}.
====Cardiovascular====
Controlled human studies found '''no significant increase''' in [[glossary:heart-rate]] or [[glossary:blood-pressure]] across inhaled doses from 0.375 to 21 μg/kg{{cite|doi=10.1016/j.drugalcdep.2010.11.005|anchor=ea0b1c6a}}{{flag|additional-citations-needed}}. This distinguishes salvinorin A from [[glossary:serotonergic-psychedelics|classical serotonergic psychedelics]], which reliably increase heart rate.
====Cognitive====
Salvinorin A (160–640 μg/kg, s.c.) impaired spatial long-term memory, episodic memory, and aversive memory in rats while sparing short-term memory; effects were blocked by the selective κ-opioid [[glossary:antagonist]] nor-BNI, confirming KOR mediation{{cite|doi=10.1177/1091581811418538|anchor=e40fe920}}. [[effect:amnesia]] for portions of the acute experience has been documented in human studies{{cite|doi=10.1007/s00213-012-2912-9|anchor=a9e59223}}.
====Contaminant and adulterant risk====
Commercial ''S. divinorum'' products carry labeling accuracy concerns: measured salvinorin A content deviates substantially from labeled [[glossary:potency]] claims{{cite|doi=10.1021/acsomega.2c06106|anchor=845a3c27}}{{flag|additional-citations-needed}}. No published systematic surveillance of pesticide residues, heavy metals (lead, cadmium, arsenic, mercury), mycotoxins, or microbial [[glossary:contamination]] in commercial ''S. divinorum'' products was identified in this literature search. No reports of [[glossary:synthetic]] salvinorin A [[glossary:adulterant|adulteration]] appear in the published record. No ISO/IEC-accredited testing programmes or Certificate of Analysis requirements specific to ''S. divinorum'' products have been established in any jurisdiction.
{{flag|safety-citation-needed}} The absence of contaminant surveillance data does not indicate absence of contamination — it reflects a gap in the published evidence base.
===Psychological risks===
====Acute====
Intense fear, panic, and extreme disorientation are common at typical smoked doses, particularly with concentrated extract preparations or in uncontrolled settings{{cite|doi=10.1080/02791072.2016.1179376|anchor=487c262c}}. [[effect:dysphoria]] is more frequently reported than [[effect:euphoria]]{{cite|pubmed=23627785|anchor=39046bd2}}. The unpredictable [[glossary:intensity]] and disorienting character of the experience — including complete loss of awareness of the physical environment — constitute the primary [[glossary:acute-risk]].
====Chronic and psychiatric====
El-Khoury and Sahakian (2015) reviewed the literature and presented two [[glossary:case-report|case reports]] linking ''S. divinorum'' use to persistent psychotic [[glossary:disorder|disorders]] in individuals with possible pre-existing vulnerabilities{{cite|doi=10.1080/02791072.2015.1073815|anchor=2586b865}}. Dedomenici et al. (2022) reported a psychotic episode following unintentional consumption, resistant to two pharmacological treatments before resolving with brexiprazole{{cite|doi=10.1701/3888.38708|anchor=131142bc}}. Multiple reviews flag elevated psychiatric risk in adolescents, users of other substances of abuse, and individuals with underlying psychotic [[glossary:disturbance|disturbances]]{{cite|doi=10.1002/hup.2304|anchor=d7fa8378}}{{cite|doi=10.1111/appy.12225|anchor=4a027c82}}.
The causal relationship between ''S. divinorum'' and persisting [[glossary:psychosis]] is '''not''' established. All published case reports involve individuals with potential pre-existing psychiatric [[glossary:vulnerability]], and no prospective psychiatric outcome data exist.
===Tolerance & dependence===
====Tolerance====
[[glossary:tachyphylaxis]] — rapid loss of effect with repeated dosing within a single session — is commonly reported by recreational users{{cite|doi=10.1080/02791072.2016.1179376|anchor=7af5e235}}{{flag|additional-citations-needed}}. No formal published [[glossary:tolerance]] dose-escalation study exists in humans.
====Dependence====
No formal [[glossary:dependence]] syndrome has been described in the published clinical literature{{cite|doi=10.1111/appy.12225|anchor=89114ff3}}. The aversive [[glossary:phenomenology]] and KOR-mediated dopaminergic suppression — rather than enhancement — are thought to underlie the substance's low [[glossary:abuse-potential]]{{cite|doi=10.3390/biomedicines14020476|anchor=8d0a634c}}{{cite|pubmed=16223871|anchor=37fcc9d2}}. Internet survey data indicate that over 52% of users reported reducing or ceasing use within the prior 12 months, with the most common reasons being dislike of the [[index:effects|subjective effects]] (33%) and loss of interest (29%){{cite|doi=10.1002/hup.2304|anchor=59d95915}}.
====Withdrawal====
No published [[glossary:withdrawal]] has been characterised for ''S. divinorum'' or salvinorin A.
====Abuse potential====
Multiple reviews conclude that salvinorin A has '''low abuse potential''' based on aversive phenomenology, dopaminergic suppression, and absence of positive [[glossary:reinforcement]] in animal [[glossary:self-administration]] paradigms{{cite|doi=10.3390/biomedicines14020476|anchor=8f299043}}{{cite|doi=10.3389/fphar.2015.00190|anchor=7c5a0f8f}}.
===Drug interactions===
{{Warning}}All herb–[[glossary:drug-interaction]] assessments for ''S. divinorum'' are based on [[glossary:in-vitro|in vitro]] metabolic data and theoretical pharmacodynamic mechanisms. '''No clinical pharmacokinetic interaction study''' has been conducted in humans for salvinorin A. The interaction severities below are inferred, not empirically established.{{/Warning}}
====Pharmacokinetic interactions (CYP-mediated)====
Salvinorin A is metabolised by [[glossary:cyp2d6]], CYP1A1, CYP2E1, and CYP2C18, with additional [[glossary:glucuronidation]] via UGT2B7, and is a P-glycoprotein [[glossary:substrate]]{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=0bbe3c36}}{{flag|additional-citations-needed}}. Drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine, quinidine) or CYP2E1 (e.g., disulfiram) could theoretically increase salvinorin A [[glossary:plasma-concentration|plasma levels]] and prolong effects. P-glycoprotein [[glossary:inhibitor|inhibitors]] (e.g., verapamil, cyclosporine) could alter [[glossary:central-nervous-system|CNS]] distribution.
====Pharmacodynamic interactions (mechanism-based)====
* '''CNS depressants''' ([[substance_class:psychoactive/opioid|opioids]], [[substance_class:chemical/benzodiazepine|benzodiazepines]], [[substance:alcohol]], [[substance:cannabis]]): Additive CNS [[effect:depression]], disorientation, and impaired motor control are theoretically possible. No specific case reports exist.{{flag|safety-citation-needed}}
* '''Lithium:''' [[glossary:seizure]] risk has been reported anecdotally with [[substance:lithium]] in combination with [[substance_class:psychoactive/psychedelic|psychedelics]]. No specific case report with salvinorin A has been published.{{flag|safety-citation-needed}}
* '''MAOIs and SSRIs:''' Theoretical pharmacodynamic concern given KOR–[[glossary:serotonin-transporter]] interactions. No clinical case reports.{{flag|safety-citation-needed}}
===Contraindications===
====Absolute====
* '''Personal or family history of psychotic disorders''' (schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features): Case reports document persistent [[glossary:psychotic-episodes]] in individuals with possible pre-existing vulnerability{{cite|doi=10.1080/02791072.2015.1073815|anchor=a6012378}}{{cite|doi=10.1701/3888.38708|anchor=302467ed}}.
====Relative====
* '''Adolescence:''' Elevated risk flagged in multiple reviews{{cite|doi=10.1002/hup.2304|anchor=c8367e0b}}{{cite|doi=10.1111/appy.12225|anchor=9ac05eaf}}. Developing brain vulnerability to KOR-mediated dopaminergic suppression is a mechanistic concern.
* '''Pregnancy and breastfeeding:''' No published safety data exist. No data means no established safety.{{flag|safety-citation-needed}}
* '''Hepatic impairment:''' [[glossary:cytochrome-p450|CYP enzyme]] involvement in salvinorin A [[glossary:metabolism]] suggests possible altered metabolism in liver disease{{cite|doi=10.1016/j.ejpb.2009.01.002|anchor=546fd7cc}}. No published clinical data exist.
* '''Concurrent use of CYP2D6 or CYP2E1 inhibitors:''' Theoretical risk of increased salvinorin A exposure (see Drug interactions above).
* '''Unsupervised settings or environments with fall risk:''' [[effect:motor-control-impairment]] and complete loss of environmental awareness at typical smoked doses create risk of physical injury{{cite|doi=10.1080/02791072.2016.1179376|anchor=0a117c79}}.
====Detection====
Standard immunoassay panels (SAMHSA urine drug screens) do '''not''' detect salvinorin A. [[glossary:detection]] requires specific LC-MS/MS methodology{{cite|pubmed=18652747|anchor=9ffb1f77}}{{flag|additional-citations-needed}}.
''Salvia divinorum'' and [[substance:salvinorin-a]] are '''not listed''' under any of the three UN [[glossary:drug-control|international drug control]] conventions — the 1961 Single Convention on Narcotic Drugs, the 1971 [[glossary:convention-on-psychotropic-substances]], and the 1988 Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=53bbb68d}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=c8df3778}}. This absence from international scheduling has resulted in a highly fragmented global legal landscape, with control measures implemented piecemeal at the national and sub-national level.
{{flag|citation-needed}} US state-level legal status is subject to frequent change. The classification of individual states listed above is based on 2024 [[glossary:secondary-source|secondary sources]] and requires verification against current state statutes before publication.
Because salvinorin A is a diterpenoid with no nitrogen atom, it does not fall within the structural definitions used by many [[glossary:structural-analog]] acts or blanket scheduling frameworks designed around nitrogenous psychoactive compounds. Jurisdictions that control ''S. divinorum'' have done so by specifically naming the plant, the compound, or by applying broad psychoactive-substance legislation (as in the United Kingdom's Psychoactive Substances Act 2016).
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States (federal) | Not scheduled (Controlled Substances Act) | DEA lists ''S. divinorum'' as a "Drug and Chemical of Concern" but has not initiated formal scheduling. A 2002 Congressional bill to ban the substance failed.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=7bc27bcf}} |
| United States (states — banned) | Controlled substance (approximately 27 states) | Outright bans in Delaware, Florida, Illinois, Kansas, Kentucky, Louisiana, Mississippi, Missouri, Nebraska, North Dakota, Ohio, Oklahoma, Pennsylvania, South Dakota, Tennessee, Texas, Virginia, and others.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=fc906c16}} |
| United States (states — age-restricted) | Age restriction only | California (18+), Maine.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=acfc82cf}} |
| United States (states — unrestricted) | No state-level restriction | Approximately 22 states including Alaska, Arizona, Idaho, Massachusetts, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, Oregon, South Carolina, Utah, Washington, West Virginia, and the District of Columbia.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum_in_the_United_States|anchor=391460b8}} |
| Canada | Schedule IV (Controlled Drugs and Substances Act) | Controlled since 2017.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=e09508fa}} |
| United Kingdom | Banned (Psychoactive Substances Act 2016) | Prohibited since 26 May 2016 under blanket psychoactive substances ban. Salvinorin A is not individually named; the act applies category-wide.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=038521a6}} |
| Australia | Schedule 9 — Prohibited Substance | Most restrictive schedule under the Therapeutic Goods Act. Live plants also prohibited.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=5019a9a6}} |
| Germany | Controlled (narcotics law) | Controlled since approximately 2015.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=36488837}} |
| EU member states (selected) | Domestic restrictions vary | Belgium, Denmark, Estonia, Finland, Iceland (EEA), Ireland, Italy, Romania, Slovakia, Spain, and Sweden have enacted domestic restrictions. Not all EU member states restrict ''S. divinorum''.{{cite|url=https://www.euda.europa.eu/publications/drug-profiles/salvia_en|anchor=dd9e46f8}}{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=b1f05c9f}} |
| Japan | Controlled | Controlled since 2007.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=ff528ebf}} |
| Brazil, South Korea, Norway, Poland | Domestic restrictions | Various domestic controls in effect.{{cite|url=https://en.wikipedia.org/wiki/Legal_status_of_Salvia_divinorum|anchor=27498d32}} |
Evidence Changes34 added
+Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB 2002— Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.
+Carlezon WA, Beguin C, DiNieri JA, Baumann MH, Richards MR, Todtenkopf MS, Rothman RB, Ma Z, Lee DY, Cohen BM 2006— Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats
+Ganado M, Rubio C, Pérez-Villavicencio J, Serrano N, Romo-Parra H, Lee Á, Rubio-Osornio M 2026— Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A.
+Casselman I, Nock CJ, Wohlmuth H, Weatherby RP, Heinrich M 2014— From local to global-fifty years of research on Salvia divinorum.
+MacLean KA, Johnson MW, Reissig CJ, Prisinzano TE, Griffiths RR 2013— Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects.
+Johnson MW, MacLean KA, Reissig CJ, Prisinzano TE, Griffiths RR 2011— Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum
+Diaz JL 2013— Salvia divinorum: a psychopharmacological riddle and a mind-body prospect.
+Brito-da-Costa AM, Dias da Silva D, Gomes NGM, Dinis-Oliveira RJ, Madureira-Carvalho Á 2021— Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects
+Calado S, Pires B, Rosendo LM, Rosado T, Gallardo E, Duarte AP 2025— Salvinorin A and Salvia divinorum: Toxicology, Pharmacological Profile, and Therapeutic Potential
+Butelman ER, Kreek MJ 2015— Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders
+El-Khoury J, Sahakian N 2015— The Association of Salvia divinorum and Psychotic Disorders: A Review of the Literature and Case Series.
+Zawilska JB, Wojcieszak J 2013— Salvia divinorum: from Mazatec medicinal and hallucinogenic plant to emerging recreational drug
+Chambers MI, Giffen-Lemieux JE, Musah RA 2023— Rapid Detection and Quantification of Hallucinogenic Salvinorin A in Commercial Salvia divinorum Products by DART-HRMS
+Ranganathan M, Schnakenberg A, Skosnik PD, Cohen BM, Pittman B, Sewell RA, D'Souza DC 2012— Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the kappa opioid agonist Salvinorin A in humans.
+Chavkin C, Sud S, Jin W, Stewart J, Zjawiony JK, Siebert DJ, Toth BA, Hufeisen SJ, Roth BL 2004— Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations.
+Mendelson JE, Coyle JR, Lopez JC, Baggott MJ, Flower K, Everhart ET, Munro TA, Galloway GP, Cohen BM 2011— Lack of effect of sublingual salvinorin A, a naturally occurring kappa opioid, in humans: a placebo-controlled trial.
+Maqueda AE, Valle M, Addy PH, Antonijoan RM, Puntes M, Coimbra J, Ballester MR, Garrido M, González M, Claramunt J, Barker S, Lomnicka I, Waguespack M, Johnson MW, Griffiths RR, Riba J 2016— Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans.
+Ford JA, Watkins WC, Blumenstein L 2011— Correlates of Salvia divinorum use in a national sample: findings from the 2009 National Survey on Drug Use and Health
+Fichna J, Dicay M, Lewellyn K, Janecka A, Zjawiony JK, MacNaughton WK, Storr MA 2012— Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors.
+Jenks AA, Walker JB, Kim SC 2011— Evolution and origins of the Mazatec hallucinogenic sage, Salvia divinorum (Lamiaceae): a molecular phylogenetic approach
+Grundmann O, Phipps SM, Zadezensky I, Butterweck V 2007— Salvia divinorum and Salvinorin A: An Update on Pharmacology and Analytical Methodology
+Hutton F, Kivell B, Boyle O 2016— Quite a Profoundly Strange Experience: An Analysis of the Experiences of Salvia divinorum Users.
+Zürrer WE, Wettstein L, Aicher HD, Scheidegger M, Ineichen BV 2025— The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies.
+Braida D, Donzelli A, Martucci R, Capurro V, Sala M 2011— Learning and memory impairment induced by salvinorin A, the principal ingredient of Salvia divinorum, in wistar rats
+Dedomenici M, Arienti V, Mazzoni F, Politi P, Migliarese G 2022— Case report: the psychotic-mystical effects related to an unaware use of Salvia divinorum
+Mahendran R, Lim HA, Tan JY, Chua SM, Winslow M 2016— Salvia divinorum: An overview of the usage, misuse, and addiction processes
+Teksin ZS, Lee IJ, Nemieboka NN, Othman AA, Upreti VV, Hassan HE, Syed SS, Prisinzano TE, Eddington ND 2009— Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen
+McDonough PC, Holler JM, Vorce SP, Bosy TZ, Magluilo J, Past MR 2008— The detection and quantitative analysis of the psychoactive component of Salvia divinorum, salvinorin A, in human biological fluids using liquid chromatography-mass spectrometry
Data Field Changes1 changed · 15 unchanged
| Field | r1 | r2 | |
|---|---|---|---|
| Summary | (empty) | → | Salvia divinorum is a hallucinogenic plant of the Lamiaceae family, endemic to Oaxaca, Mexico, containing the kappa-opioid receptor agonist salvinorin A. First described in 1962, it has been used in Mazatec divinatory ceremonies for centuries. |
Effects Profile Changes101 added
Added (101)
Auditory distortionperception
0.400.40
Auditory hallucinationsperception
0.300.30
Auditory suppressionperception
0.500.50
Brightness alterationperception
0.500.50
Color alterationperception
0.600.60
Depth perception distortionperception
0.800.80
Environmental patterningperception
0.500.40
External hallucinationsperception
0.900.80
Geometryperception
0.600.60
Holotropic stateperception
0.800.70
Internal hallucinationsperception
0.900.90
Object activationperception
0.700.60
Object transformationsperception
0.800.70
Perspective distortionperception
0.900.90
Perspective hallucinationsperception
0.700.70
Proprioceptive distortionperception
0.900.90
Sensory deprivationperception
0.600.50
Spatial disorientationperception
0.900.90
Synesthesiaperception
0.500.40
Vestibular distortionperception
0.800.80
Visual acuity suppressionperception
0.600.60
Visual breathingperception
0.500.40
Visual driftingperception
0.700.70
Visual flippingperception
0.600.50
Visual haze / noiseperception
0.500.50
Visual magnificationperception
0.500.40
Visual meltingperception
0.700.60
Visual morphingperception
0.900.80
Visual processing suppressionperception
0.700.70
Visual scenery slicingperception
0.700.60
Bodily dissociationbody
0.900.90
Bodily heavinessbody
0.600.50
Body schema distortionbody
0.900.90
Dizzinessbody
0.800.80
Involuntary body movementsbody
0.700.70
Laughter fitsbody
0.500.50
Motor control impairmentbody
0.900.90
Muscle relaxationbody
0.500.50
Nauseabody
0.300.30
Nystagmus (eye wobbles)body
0.500.50
Physical fatiguebody
0.500.60
Pupil constrictionbody
0.600.70
Sedationbody
0.800.80
Spontaneous body sensationsbody
0.600.60
Tactile hallucinationbody
0.500.40
Tingling / electric sensationsbody
0.500.50
Tremblingbody
0.500.50
Vibrations / buzzingbody
0.500.50
Vomitingbody
0.300.20
Amnesiathinking
0.900.90
Analysis suppressionthinking
0.700.70
Cognitive dysphoriathinking
0.700.70
Cognitive fatiguethinking
0.500.60
Cognitive impairmentthinking
0.900.90
Confusionthinking
0.900.90
Decision impairmentthinking
0.800.80
Deliriumthinking
0.700.60
Delusionsthinking
0.600.50
Focus suppressionthinking
0.800.80
Information processing suppressionthinking
0.800.80
Language suppressionthinking
0.700.70
Memory fragmentationthinking
0.900.90
Memory suppressionthinking
0.800.80
Motivation suppressionthinking
0.600.60
Novelty enhancementthinking
0.800.80
Thought disorganizationthinking
0.900.90
Thought loopsthinking
0.500.50
Anxietyfeeling
0.800.70
Depressionfeeling
0.400.30
Dysphoriafeeling
0.800.70
Emotional labilityfeeling
0.600.60
Euphoriafeeling
0.300.30
Paranoiafeeling
0.600.50
Automaticityself
0.700.70
Boundary dissolutionself
0.900.80
Cognitive disconnectionself
0.900.90
Communication suppressionself
0.800.80
Depersonalizationself
0.900.90
Derealizationself
0.900.90
Ego dissolutionself
0.900.80
Identity alterationself
0.900.80
Self-control suppressionself
0.900.80
Sociability suppressionself
0.700.70
Social disconnectionself
0.900.90
Jamais vutime
0.500.50
Present-moment absorptiontime
0.700.70
Temporal disorientationtime
0.900.90
Time alterationtime
0.900.90
Time cessationtime
0.700.60
Cessationtranspersonal
0.700.50
Death-rebirth sequencetranspersonal
0.700.40
Entity contacttranspersonal
0.700.50
Existential realizationtranspersonal
0.600.50
Near-death experiencetranspersonal
0.700.30
Noetic insighttranspersonal
0.600.50
Non-dual awarenesstranspersonal
0.700.60
Transpersonal feelingstranspersonal
0.600.50
Transpersonal visionstranspersonal
0.800.70
Unity and interconnectednesstranspersonal
0.700.60
Voidnesstranspersonal
0.700.50
Reality testing impairmentawareness
0.900.90