title: From local to global-fifty years of research on Salvia divinorum.
abstract: BACKGROUND
  In 1962 ethnopharmacologists, Hofmann and Wasson, undertook an expedition to Oaxaca, Mexico. These two researchers were the first scientists to collect a flowering specimen of Salvia divinorum allowing the identification of this species. While the species' traditional use is confined to a very small region of Mexico, since Hofmann and Wasson's expedition 50 years ago, Salvia divinorum has become globally recognized for its main active constituent, the diterpene salvinorin A, which has a unique effect on human physiology. Salvinorin A is a kappa-opioid agonist and the first reported psychoactive diterpene.
  
  
  METHODS
  This review concentrates on the investigation of Salvia divinorum over the last 50 years including ethnobotany, ethnopharmacology, taxonomy, systematics, genetics, chemistry and pharmacodynamic and pharmacokinetic research. For the purpose of this review, online search engines were used to find relevant research. Searches were conducted between October 2011 and September 2013 using the search term "Salvia divinorum". Papers were excluded if they described synthetic chemical synthesis of salvinorin A or analogues.
  
  
  RESULTS
  Ethnobotanically there is a comprehensive body of research describing the traditional Mazatec use of the plant, however, the modern ethnobotanical use of this plant is not well documented. There are a limited number of botanical investigations into this plant and there are still several aspects of the botany of Salvia divinorum which need further investigation. One study has investigated the phylogenetic relationship of Salvia divinorum to other species in the genus. To date the main focus of chemistry research on Salvia divinorum has been salvinorin A, the main active compound in Salvia divinorum, and other related diterpenoids. Finally, the effects of salvinorin A, a KOR agonist, have primarily been investigated using animal models.
  
  
  CONCLUSIONS
  As Salvia divinorum use increases worldwide, the emerging cultural use patterns will warrant more research. More botanical information is also needed to better understand this species, including germination, pollination vector and a better understanding of the endemic environment of Salvia divinorum. As well there is a gap in the genetic knowledge of this species and very little is known about its intra-species genetics. The terpenes in Salvia divinorum are very well documented, however, other classes of constituents in this species warrant further investigation and identification. To date, the majority of the pharmacology research on Salvia divinorum has focused on the effects of salvinorin A using animal models. Published human studies have not reported any harmful effects when salvinorin A is administered within the dose range of 0.375-21µg/kg but what are the implications when applied to a larger population? More data on the toxicology and safety of Salvia divinorum are needed before larger scale clinical trials of the potential therapeutic effects of Salvia divinorum and salvinorin A are undertaken.
authors: Southern Cross Plant Science, Southern Cross University, Lismore NSW 2480, Australia. Electronic address: ivan.casselman@scu.edu.au.
authors: Ivan
authors: I
authors: Casselman
authors: Southern Cross Plant Science, Southern Cross University, Lismore NSW 2480, Australia.
authors: Catherine J
authors: CJ
authors: Nock
authors: Southern Cross Plant Science, Southern Cross University, Lismore NSW 2480, Australia.
authors: Hans
authors: H
authors: Wohlmuth
authors: Division of Research, Southern Cross University, Lismore NSW 2480, Australia.
authors: Robert P
authors: RP
authors: Weatherby
authors: Southern Cross Plant Science, Southern Cross University, Lismore NSW 2480, Australia; Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, 29-39 Brunswick Sq. London WC1N 1AX, UK; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Michael
authors: M
authors: Heinrich
mesh_terms: D000818:Animals; D045785:Diterpenes, Clerodane / Q000494:pharmacology; D020834:Ethnopharmacology; D006801:Humans; D008519:Medicine, Traditional; D008800:Mexico; D011619:Psychotropic Drugs / Q000494:pharmacology; D012106:Research; D027544:Salvia / Q000737:chemistry / Q000502:physiology / Q000633:toxicity
chemical_list: D045785:Diterpenes, Clerodane; D011619:Psychotropic Drugs; C090499:salvinorin A
keywords: 2.136: Botany; 2.232: Diterpenoids; 2.312: Hallucinogenic