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Salvia divinorum

A psychoactive mint used in Mazatec practice whose active compound, salvinorin A, is a kappa-opioid agonist rather than a serotonergic psychedelic, producing a short and markedly dissociative state.

State of the evidence

Synthesized

Synthesized from 25 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for Salvia divinorum, salvinorin, salvinorin a, diviner's sage, ska maria pastora, ska pastora, then ranked by relevance.

Salvia divinorum and its active compound salvinorin A produce intense, short-lived dissociative and hallucinogenic effects through selective kappa opioid receptor agonism, distinct from classic serotonergic psychedelics. Preclinical studies show potential therapeutic effects (anti-nociceptive, anti-inflammatory, neuroprotective, anti-addictive) but also adverse effects (anxiogenic, motor/cognitive impairment). Human studies are limited to small samples, and while subjective effects are well-characterized, evidence for therapeutic efficacy in humans is lacking.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.

Salvinorin A is a potent and selective kappa opioid receptor agonist with no activity at the 5-HT2A serotonin receptor.

experimental study

Salvia divinorum has unique pharmacology and therapeutic potential but has been banned due to psychiatric effects.

review

Salvia divinorum contains the selective kappa opioid agonist salvinorin A, producing visual hallucinations and synesthesia.

review

Salvinorin A is a full agonist at kappa-opioid receptors, more efficacious than partial agonists.

experimental study

Higher doses of salvinorin A decreased dopamine levels in the caudate putamen, caused conditioned place aversion, and reduced locomotor activity.

experimental study

Divinorin A is a psychotropic terpenoid and divinorin B is also present in Salvia divinorum.

research article

Salvia divinorum produces psychotropic effects comparable to other Mazatec hallucinogens and is used in traditional healing.

ethnographic and pharmacological review

Salvia divinorum produces intense, short-lived psychedelic-like effects with marked derealization, supporting kappa-opioid receptor activation.

cross-sectional survey Sample size: 32

Salvinorin A is a selective, non-nitrogenous agonist of the kappa opioid receptor, a potential target for treating perceptual disorders.

review

Salvinorin A is the first documented diterpene hallucinogen and the most potent naturally occurring hallucinogen, effective at 200-500 mcg when smoked.

review

Salvinorin A exhibited anxiolytic- and antidepressant-like effects mediated by kappa-opioid and endocannabinoid systems.

experimental study

Inhaled salvinorin A produces dose-related dissociative effects and memory impairment that peak at 2 minutes and rapidly dissipate.

double-blind, placebo-controlled study Sample size: 8

Salvinorin A produced dose-related increases in mystical-type experiences and subjective effects similar to classic hallucinogens without affecting heart rate or blood pressure.

double-blind, placebo controlled study Sample size: 4

Kappa opioid pharmacological drug models, including salvinorin A, may model aspects of schizophrenia.

review

Salvinorin A is a kappa opioid receptor agonist, and the plant's unregulated status is leading to increased online marketing and predicted misuse.

review

The Salvia Experience Checklist scores correlated with the Hallucinogen Rating Scale and with extract potency and smoking method.

cross-sectional survey Sample size: 321

Effective counteraction to Salvia divinorum requires an integrated approach combining legislative control, monitoring, and public education.

review

Salvinorin A induces psychedelic effects through selective kappa opioid receptor agonism with β-arrestin-biased signaling, distinct from serotonergic mechanisms.

review

Salvinorin A exhibits anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, but also anxiogenic effects and motor/cognitive impairment.

systematic review and meta-analysis

Salvinorin A exhibits anti-nociceptive, anti-inflammatory, neuroprotective, and anti-addictive effects, but side effects may limit clinical application.

systematic review and meta-analysis

Salvia divinorum presents both potential therapeutic applications and health risks, warranting further research.

review

Salvia divinorum is increasingly abused as a recreational drug, facilitated by internet availability and lack of restrictions.

review

A chromosome-level genome assembly identified diterpene biosynthetic gene clusters and candidate genes for salvinorin A biosynthesis.

genome assembly and analysis

Psilocybin and Salvinorin-A produce overlapping and differing effects on functional connectivity within the default mode network and claustrum.

observational cohort

Both psilocybin and salvinorin-A acutely desynchronized the default mode network and affected a cortico-claustro-cortical network.

within-subject fMRI study

Points of agreement

  • Salvinorin A is a potent and selective kappa opioid receptor agonist, distinct from serotonergic psychedelics.
  • Subjective effects are intense, short-lived (minutes), and include dissociative and hallucinogenic experiences.
  • Preclinical studies show potential therapeutic effects (pain, inflammation, neuroprotection, addiction) but also adverse effects (anxiety, motor/cognitive impairment).
  • The plant is increasingly used recreationally, facilitated by internet availability and legal loopholes.

Conflicts

  • Findings on depression are inconsistent: some studies show antidepressant-like effects, others depressogenic outcomes.
  • Human studies report both overlap with classic hallucinogens and unique dissociative effects, with some participants noting qualitative differences.
  • Therapeutic potential is highlighted in some reviews, while others emphasize risks and lack of human data.

Gaps

  • No large-scale human clinical trials on therapeutic efficacy.
  • Long-term effects and abuse potential in humans are not well studied.
  • Durability of effects and optimal dosing for therapeutic applications are unclear.
  • Most studies are preclinical; human data are limited to small samples and retrospective surveys.
  • Blinding in human studies is challenging due to intense subjective effects.
Browse these studies in the library
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is Salvia divinorum, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when Salvia divinorum or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

311 articles · 27 from the last two years · 1,134,277 participants across 69 studies reporting sample size

Common study designs

review 74 case study 10 preclinical study 12 experimental study 52 theoretical or philosophical paper 13

Subjective Effects and Characteristics of Salvia Divinorum Use from a Retrospective Largescale Survey

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.

Clinical and Pharmacological, Forensic and Pharmaceutical Profile of Hallucinogenic Sage Salvia Divinorum: Regulatory Restrictions, Internet Accessibility to Consumers, Risks to Public Health in Italy

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.

Opioid Receptors in Psychedelia: Indirect Serotonergic Modulation of Direct KOR Activation by Salvinorin A

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.

The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies.

Translational Psychiatry October 10, 2025 Wolfgang Emanuel Zürrer, Lionel Wettstein, Helena 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.

The translational potential of salvinorin A: systematic review and meta-analysis of preclinical studies

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.

Salvinorin A and Salvia divinorum: Toxicology, Pharmacological Profile, and Therapeutic Potential.

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.

Diviner's Sage (Salvia divinorum Epling & Játiva Lamiaceae)

January 23, 2025 Mai M. Younis, Ahmed M. Elissawy, Samir M. Osman et al.

Salvia divinorum, a hallucinogenic plant from the mint family endemic to Oaxaca, Mexico, has been traditionally used by the Mazatec people for medicinal purposes including treating arthritis, inflammation, gastrointestinal problems, and headaches, as well as in ceremonies for its psychoactive properties. Its main psychoactive component, salvinorin A, is a neoclerodane diterpene that acts as a potent and selective agonist on κ opioid receptors, causing hallucinations and loss of physical control. The chapter summarizes the plant's botany, habitat, ecology, ethnobotany, pharmacology, and medicinal effects.

The original caretakers of salvinorin A and recognizing Indigenous contributions to science.

Nat Chem November 1, 2024

This work argues that Indigenous communities, particularly the Mazatec people of Oaxaca, Mexico, are the original caretakers of salvinorin A, the psychoactive compound in Salvia divinorum. It calls for recognizing their historical and ongoing contributions to the scientific understanding of this substance, challenging the erasure of Indigenous knowledge in Western scientific narratives. The text emphasizes the ethical importance of acknowledging Indigenous stewardship and intellectual contributions to research on psychoactive plants.

Salvia divinorum – A New Entity in the Psychedelic Scene in India

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.

A chromosome level reference genome of Diviner's sage (Salvia divinorum) provides insight into salvinorin A biosynthesis.

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.

Clinical trials

All Salvia divinorum trials →