June 26, 2026
Spencer W. Wheeler, Jonathan Dinsmore, Natalie L. Dyer
preprint
Salvia divinorum is a unique psychedelic whose active compound, salvinorin A, acts on kappa opioid receptors. In an online survey of 321 participants about their most recent salvia experience, the average number of items endorsed on the Salvia Experience Checklist (SEC) was 16.5 out of 58, and the average Hallucinogen Rating Scale (HRS) score was 186.36. Scores on all HRS subscales correlated significantly with SEC scores. Exploratory factor analysis of the SEC yielded 10 factors, and content analysis identified 16 major themes. Higher SEC scores were associated with stronger extract potency and with smoking as the administration method. The findings help characterize salvia's phenomenology and support further development of the SEC.
SSP Modern Pharmacy and Medicine
May 25, 2026
Nadiia Kutsenko
Salvia divinorum and its active compound Salvinorin A pose high toxicological risk, rapid psychotropic action, and legal control difficulties. Their availability online and in informal markets, combined with a perception as natural products, challenges public health, forensic practice, and regulators. The rapid onset of effects, unpredictable behavioral reactions, and difficulty detecting use via routine toxicology increase their relevance for medico-pharmaceutical law and forensic pharmacy. Italy's experience and the new EUDA mandate show that effective counteraction requires legislative control, forensic pharmaceuticals, digital market monitoring, prevention, early-warning systems, public education, and health system preparedness. Cross-border distribution, internet promotion, and misleading marketing as harmless herbal products need attention. An integrated approach can reduce misuse, improve detection, and strengthen cooperation among healthcare, law enforcement, forensic experts, and regulators.
Biomedicines
February 21, 2026
Maximiliano Ganado, Carmen Rubio, Javier Pérez-villavicencio et al.
Psychedelic effects are not solely driven by serotonin receptors. The compound salvinorin A, from Salvia divinorum, produces altered consciousness by directly activating kappa opioid receptors (KORs), bypassing serotonin entirely. This review synthesizes evidence from lab studies, animal models, and human brain imaging. Salvinorin A triggers a specific signaling pathway (β-arrestin bias) that causes rapid receptor desensitization, disrupts thalamocortical communication, suppresses dopamine activity in reward circuits, and fragments large-scale brain networks. Despite being a potent opioid agonist, it has low abuse potential because its aversive effects and dopamine suppression prevent positive reinforcement. Understanding opioid receptor mechanisms expands psychedelic neuroscience beyond serotonin-focused models and may guide development of treatments for depression, addiction, and chronic pain.
Universität Zürich, ZORA
October 10, 2025
Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena Aicher et al.
Salvinorin A, the main psychoactive compound in Salvia divinorum and a potent kappa opioid receptor agonist, has been tested in animal models of pain, stroke, addiction, and depression. It shows anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects. However, findings on depression are inconsistent, with both antidepressant and depressogenic outcomes reported. Toxicity data indicate anxiogenic effects and motor and cognitive impairment, with minimal impact on vital parameters. Pharmacokinetic data show rapid onset, fast peak, and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles.
Translational psychiatry
October 10, 2025
Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena D Aicher et al.
3 citations
Salvinorin A, the main psychoactive compound in Salvia divinorum, shows therapeutic potential for pain, addiction, and stroke in animal models, but its side effects—including anxiety, motor and cognitive impairment—may limit clinical use. A systematic review and meta-analysis of 82 studies found anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, though depression results were inconsistent. Doses ranged from 0.1 to 10 mg/kg, with rapid onset and a half-life of about one hour. Sixteen structurally distinct analogues were identified with potentially improved safety and pharmacokinetic profiles. Findings support further development of analogues to overcome the side effect profile.
Int J Mol Sci
June 11, 2025
4 citations
Salvia divinorum is a psychoactive plant with a complex pharmacological profile that has attracted scientific interest for both its potential therapeutic applications and associated health risks. This review analyzes the toxic and therapeutic effects of S. divinorum, evaluating its possible medical uses while highlighting consumption risks. It also examines the plant's recreational use, global consumption trends, and legal status. The article synthesizes current research to clarify the implications of S. divinorum use and inform future studies on its pharmacological potential and regulatory considerations.
Indian Internet Journal of Forensic Medicine and Toxicology
October 30, 2024
Aravind Ajid, Boban Babu, Abhijith G Jayachandran
Salvia divinorum, a psychoactive plant that induces intense hallucinations, is increasingly abused as a recreational drug, partly due to easy online availability and limited legal restrictions in many countries. Traditionally used by the Mazatec Indians in spiritual healing, its use has also been reported in India.
BMC plant biology
October 1, 2024
Scott A Ford, Rob W Ness, Moonhyuk Kwon et al.
9 citations
Diviner's sage (Salvia divinorum) produces salvinorin A (SalA), a hallucinogen that activates the human κ-opioid receptor and may help treat chronic pain, addiction, and PTSD. Only two of the roughly twelve steps in SalA's biosynthesis were known. A high-quality chromosome-level genome assembly was produced, with an N50 of 41.4 Mb and 98.4% BUSCO completeness. The diploid genome is about 541 Mb. Two diterpene biosynthetic gene clusters were found, rich in new cytochrome P450s and crotonolide G synthase, which forms an early dihydrofuran ring. Other enzyme classes for later steps were scattered across the genome. Most candidate genes were not induced by methyl jasmonate. This genome enables discovery of the remaining SalA pathway steps.
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
August 14, 2024
Frederick A. Bagdasarian, Hanne D. Hansen, Chi‐hyeon Yoo et al.
Psilocybin, a serotonergic agonist, and Salvinorin-A, a kappa-opioid receptor agonist, both alter functional connectivity in the brains of non-human primates, but their effects overlap and differ in specific regions. Using fMRI, the study examined how these psychedelics influence connections within the default mode network and the claustrum. The findings suggest that each substance targets distinct receptor systems, leading to both shared and unique patterns of brain network activity, which may help explain their different mechanisms of action.
ACS Chemical Neuroscience
June 25, 2024
Jingyuan Chen, Frederick A. Bagdasarian, Hanne D. Hansen et al.
11 citations
Using fMRI in nonhuman primates, this work compared how two different hallucinogens—psilocybin, a serotonergic psychedelic, and salvinorin-A, a kappa-opioid receptor agonist—alter resting-state functional connectivity. Both drugs acutely desynchronized the default mode network and affected a network involving the claustrum, prefrontal cortex, anterior cingulate cortices, and angular gyrus, supporting a cortico-claustro-cortical model for probing hallucinogen effects regardless of serotonergic activity. Thalamo-cortical changes appeared dependent on 5-HT2AR activation. The findings offer a framework for understanding mechanisms common across hallucinogenic drug classes.
Therapeutic advances in psychopharmacology
February 1, 2015
Hannah Steeds, Robin L Carhart-Harris, James M Stone
132 citations
Schizophrenia involves positive, negative, and cognitive symptoms, and about one-third of patients do not respond to existing medications. This review evaluates how drugs acting on dopaminergic, glutamatergic, serotonergic, cannabinoid, GABA, cholinergic, and kappa opioid systems model aspects of schizophrenia in animals and humans. Understanding interactions between these neurotransmitter systems and their links to symptoms is crucial for forming a coherent hypothesis of schizophrenia's pathogenesis and developing new therapies.
Psychopharmacology
March 1, 2013
Katherine A Maclean, Matthew W Johnson, Chad J Reissig et al.
134 citations
Inhaled salvinorin A, the active compound in Salvia divinorum, produces intense, dose-related subjective and cognitive effects that peak within 2 minutes and rapidly dissipate. In eight healthy adults with hallucinogen experience, high doses frequently caused maximal drug strength ratings or unresponsiveness. The compound induced dissociative effects and impaired recall and recognition memory, with some overlap with classic hallucinogens but a qualitatively distinct profile. No persisting adverse effects were observed at one-month follow-up. These findings contribute to understanding the kappa opioid system and may inform future therapeutic applications.
Journal of medical toxicology : official journal of the American College of Medical Toxicology
March 1, 2012
Christopher D Rosenbaum, Stephanie P Carreiro, Kavita M Babu
356 citations
Many new drugs of abuse available online remain unfamiliar to healthcare providers. Herbal marijuana alternatives like K2 or Spice contain synthetic cannabinoids mixed with plant matter. Synthetic cathinones ("bath salts") have caused nationwide emergency visits for severe agitation, sympathomimetic toxicity, and death. Kratom, from Mitragyna speciosa, has opioid-like effects and is used for chronic pain and opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with therapeutic potential but banned in many states due to psychiatric concerns. Methoxetamine is marketed as "legal ketamine." Piperazine derivatives (e.g., BZP, TMFPP) reemerge as "legal Ecstasy." These drugs are often perceived as safe but can cause life-threatening adverse effects. The paper covers background, pharmacology, clinical effects, detection, and management of these exposures.
Drug and alcohol dependence
May 1, 2011
Matthew W Johnson, Katherine A Maclean, Chad J Reissig et al.
134 citations
Salvinorin A, the psychoactive compound in Salvia divinorum, produces rapid, dose-dependent subjective effects that peak at 2 minutes and subside within 20 minutes after inhalation. In a double-blind, placebo-controlled study with 4 healthy hallucinogen-using adults, doses from 0.375 to 21 μg/kg increased ratings of mystical-type experiences and effects similar to classic hallucinogens. Salvinorin A did not significantly raise heart rate or blood pressure. Participants reported intense experiences involving altered spatial orientation, pressure on the body, childhood memories, cartoon-like imagery, and contact with entities. The findings suggest salvinorin A has a unique profile that includes mystical-type effects.
British Journal of Pharmacology
May 5, 2009
Daniela Braida, Valeria Capurro, Alessia Zani et al.
145 citations
Salvinorin A, the active ingredient in Salvia divinorum, produced both anxiety-reducing and antidepressant-like effects in rats and mice. These effects were prevented by blocking either kappa-opioid or CB1 cannabinoid receptors. Salvinorin A reduced fatty acid amide hydrolase activity in the amygdala but showed very weak binding to CB1 receptors. The findings suggest that both kappa-opioid and endocannabinoid systems mediate these mood-altering effects, which may help explain subjective experiences reported by recreational users.
Clinical Toxicology
January 1, 2008
Kavita M. Babu, Christopher R. McCurdy, Edward W. Boyer
221 citations
Salvia divinorum and Kratom are unscheduled dietary supplements that activate opioid receptors and produce distinct psychoactive effects. Salvinorin A, from Salvia divinorum, is a highly selective kappa-opioid receptor agonist that causes visual hallucinations and synesthesia. Kratom's main alkaloid, mitragynine, acts as a partial opioid agonist with morphine-like effects, while its minor alkaloid 7-hydroxymitragynine is more potent than morphine. Both Kratom alkaloids activate supraspinal mu- and delta-opioid receptors, which explains their use by chronic narcotics users to ease opioid withdrawal. Despite widespread Internet availability, these substances elude traditional toxicologic monitoring, and the article aims to inform toxicologists and poison control specialists about them.
Drug and alcohol dependence
November 8, 2006
Débora González, Jordi Riba, José Carlos Bouso et al.
163 citations
Salvia divinorum, a plant containing the potent kappa-opioid receptor agonist salvinorin-A, is increasingly used recreationally outside its traditional Mazatec context. Among 32 recreational users surveyed, smoking the extract was the preferred method. Effects were intense but short-lived, appearing within one minute and lasting 15 minutes or less. Users reported psychedelic-like changes in visual perception, mood, and bodily sensations, along with a marked alteration in the perception of external reality and self, resulting in impaired ability to interact. While some effects resembled those of classical psychedelics, the intense derealization and impairment appear unique to salvia. High scores on both LSD and PCAG subscales of the ARCI support kappa-opioid receptor activation as the underlying mechanism.
Life sciences
December 22, 2005
Thomas E Prisinzano
128 citations
The Mexican mint Salvia divinorum is currently an unregulated hallucinogen, leading online botanical companies to market it as a legal alternative to other controlled plant hallucinogens, and its misuse is predicted to increase rapidly. The active ingredient, salvinorin A, acts as a kappa opioid receptor agonist in both laboratory and animal studies. This review covers the current state of research into the psychopharmacology of S. divinorum.
Psychopharmacology
May 1, 2005
Yong Zhang, Eduardo R Butelman, Stefan D Schlussman et al.
198 citations
Salvinorin A, a hallucinogen from Salvia divinorum, is a potent kappa opioid receptor agonist. In mice, higher doses (1.0 and 3.2 mg/kg) significantly decreased dopamine levels in the caudate putamen but not in the nucleus accumbens, an effect blocked by a kappa opioid receptor antagonist. These same doses caused conditioned place aversion and reduced locomotor activity. The findings suggest that salvinorin A's reduction of striatal dopamine may contribute to its aversive and motor-suppressing effects, consistent with its in vitro characterization as a kappa opioid receptor agonist.
The Journal of pharmacology and experimental therapeutics
March 1, 2004
Charles Chavkin, Sumit Sud, Wenzhen Jin et al.
212 citations
Salvinorin A, a diterpene from Salvia divinorum, is a high-affinity and selective full agonist at human kappa-opioid receptors. In human embryonic kidney-293 cells, salvinorin A fully inhibited forskolin-stimulated cAMP production, while derivatives like 2-propionate and 2-heptanoate were partial agonists. Further tests using chimeric G proteins confirmed its potency and efficacy. In Xenopus oocytes with minimal receptor reserve, salvinorin A acted as a full agonist, more efficacious than standard agonists U50488 and U69593, and similar to dynorphin A. The 2-position substituent is critical for receptor binding and activation. Salvinorin A is the first known naturally occurring non-nitrogenous full agonist at kappa-opioid receptors.
Trends in pharmacological sciences
March 1, 2003
Douglas J Sheffler, Bryan L Roth
151 citations
Salvinorin A, a naturally occurring hallucinogen as potent as LSD, works by selectively activating the kappa opioid receptor (KOR). It is unique among KOR agonists because it contains no nitrogen. This selectivity suggests the KOR could be a target for developing drugs to treat perception-related disorders such as schizophrenia, Alzheimer's disease, and bipolar disorder.
Proceedings of the National Academy of Sciences of the United States of America
September 3, 2002
Bryan L Roth, Karen Baner, Richard Westkaemper et al.
782 citations
Salvinorin A, the active compound in the hallucinogenic plant Salvia divinorum, potently and selectively activates kappa opioid receptors while having no effect on the serotonin 5-HT(2A) receptor targeted by classical hallucinogens like LSD. This makes it the first known naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A produces perceptual distortions, the findings suggest that kappa opioid receptors play a key role in modulating human perception and that kappa opioid-selective antagonists could be developed as novel treatments for disorders involving perceptual distortions, such as schizophrenia, dementia, and bipolar disorders.
Journal of psychoactive drugs
January 1, 1994
L J Valdés
147 citations
Salvia divinorum, a vision-inducing mint used by the Mazatec people of Mexico, is grown in the United States as a legal hallucinogen. Contrary to traditional belief that it has mild psychotropic activity, the plant is quite powerful when ingested correctly—by chewing fresh leaves as a quid, eating them raw, preparing an aqueous infusion, or smoking dried leaves. Its major active ingredient is the neoclerodane diterpene salvinorin A, demonstrated in animals and humans. Inactive orally, the compound is effective in doses of 200 to 500 mcg when smoked, making it the first documented diterpene hallucinogen and the most potent naturally occurring hallucinogen isolated. This article reviews the plant's use, chemistry, effects in animals and humans, and abuse potential.
The Journal of Organic Chemistry
November 1, 1984
Leander J. Valdés, William M. Butler, George M. Hatfield et al.
174 citations
The hallucinogenic Mexican mint Salvia divinorum contains two terpenoid compounds, divinorin A and divinorin B. Divinorin A is a psychotropic terpenoid, while divinorin B is also present. The work describes the isolation and characterization of these compounds from the plant.