From local to global—Fifty years of research on Salvia divinorum, Ivan Casselman et al., 2014

From local to global—Fifty years of research on Salvia divinorum

Ivan Casselman, Catherine J. Nock, Hans Wohlmuth, Robert P. Weatherby, Michael Heinrich

Journal of Ethnopharmacology, 2014, 151, 768–783


a b s t r a c t

Ethnopharmacological relevance : In 1962 ethnopharmacologists, Hofmann and Wasson, undertook an expedition to Oaxaca,Mexico. These two researchers were the first scientists to collecta flowering specimen of Salvia divinorum allowing theidentification ofthisspecies.Whilet he 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 pharmaco-
dynamic and pharmacokinetic research. For the purpose of thisr eview, 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 in to this plant and there are still several aspects ofthe
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 beensalvinorinA,themainactivecompoundin Salvia divinorum, and other related diterpenoids. Finally, the effects of salvinorin A,a KOR agonist, have primarily been investigate dusing animal models.

Conclusions : As Salvia divinorum use increases worldwide, the emerging cultural use patterns will warrant more research. More botanical  information is alson eeded 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 0.375–21 mg/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.