The effect of Salvia divinorum and Mitragyna speciosa extracts, fraction and major constituents on place aversion and place preference in rats

J Ethnopharmacol. 2014;151(1):361-4. doi: 10.1016/j.jep.2013.10.059. Epub 2013 Nov 7.


Ethnopharmacological relevance: Consumer use of botanicals has increased despite, in many instances, the paucity of research demonstrating efficacy or identifying liabilities. This research employed the place preference/aversion paradigm to characterize the psychoactive properties of Salvia divinorum extract (10, 30, 100mg/kg), salvinorin A (0.1, 0.3, 1.0mg/kg), Mitragyna speciosa MeOH extract (50, 100, 300 mg/kg), Mitragyna speciosa alkaloid-enriched fraction (12.5, 25, 75 mg/kg) and mitragynine (5, 10, 30 mg/kg) in rats.

Material and methods: Following apparatus habituation and baseline preference scores, male Sprague-Dawley rats were given eight counter-balanced drug versus vehicle conditioning trials followed by a preference test conducted under drug-free states. S(+)-amphetamine (1mg/kg) served as the positive control (in Exp. 2) and haloperidol (0.8, 1.0mg/kg) served as the negative control in both studies.

Results: Rats displayed place aversion to both Salvia divinorum and salvinorin A that exceeded that of haloperidol. Rats showed place preference to mitragynine that was similar to that of S(+)-amphetamine. This CPP effect was much less pronounced with the Mitragyna speciosa extract and its fraction.

Conclusions: These findings suggest that both botanicals possess liabilities, albeit somewhat different, that warrant caution in their use.

Keywords: Mitragyna speciosa; Mitragynine; Place preference/aversion; Salvia divinorum; Salvinorin A.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Dose-Response Relationship, Drug
  • Hypnotics and Sedatives / chemistry
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Mitragyna / chemistry*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Salvia / chemistry*


  • Hypnotics and Sedatives
  • Plant Extracts