The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea-pig ileum

Neurogastroenterol Motil. 2006 Jan;18(1):69-75. doi: 10.1111/j.1365-2982.2005.00725.x.


Salvia divinorum is a widespread hallucinogenic herb traditionally employed for divination, as well as a medicament for several disorders including disturbances of gastrointestinal motility. In the present study we evaluated the effect of a standardized extract from the leaves of S. divinorum (SDE) on enteric cholinergic transmission in the guinea-pig ileum. SDE reduced electrically evoked contractions without modifying the contractions elicited by exogenous acetylcholine, thus suggesting a prejunctional site of action. The inhibitory effect of SDE on twitch response was abolished by the opioid receptor antagonist naloxone and by the kappa-opioid antagonist nor-binaltorphimine, but not by naltrindole (a delta-opioid receptor antagonist), CTOP (a mu-opioid receptor antagonist), thioperamide (a H(3) receptor antagonist), yohimbine (an alpha(2)-receptor antagonist), methysergide (a 5-hydroxytryptamine receptor antagonist), N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) or apamin (a blocker of Ca(2+)-activated K(+) channels). Salvinorin A, the main active ingredient of S. divinorum, inhibited in a nor-binaltorphimine- and naloxone-sensitive manner electrically induced contractions. It is concluded that SDE depressed enteric cholinergic transmission likely through activation of kappa-opioid receptors and this may provide the pharmacological basis underlying its traditional antidiarrhoeal use. Salvinorin A might be the chemical ingredient responsible for this activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Diterpenes / antagonists & inhibitors
  • Diterpenes / pharmacology*
  • Diterpenes, Clerodane
  • Drug Interactions
  • Electric Stimulation
  • Enteric Nervous System / drug effects*
  • Enteric Nervous System / physiology
  • Guinea Pigs
  • Hallucinogens / pharmacology*
  • Ileum / drug effects*
  • Ileum / innervation*
  • Ileum / physiology
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Myenteric Plexus / drug effects
  • Parasympathetic Nervous System / drug effects*
  • Parasympathetic Nervous System / physiology
  • Plant Extracts / pharmacology
  • Salvia / chemistry*
  • Stimulation, Chemical
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology


  • Diterpenes
  • Diterpenes, Clerodane
  • Hallucinogens
  • Plant Extracts
  • Acetylcholine
  • salvinorin A