Medical Research Psychedelics Science

Salvia, Sage of the Diviners

The leaves of Salvia divinorum, aka sage of the diviners, exemplify another example of our Earth’s flora used for ceremonial or ritualistic purposes by indigenous, shamanic peoples like the Mazatecs of Oaxaca, Mexico. [1] Salvia has been suggested to be the tangible form of the mythical pipiltzintzintli used by the Aztecs, but others suggest that the Aztec word relates Cannabis sativa. [2]

While the leaves once were mostly eaten, it’s more modern to vaporize or combust them to liberate the plant’s powerful, hallucinogenic effects. The experience is rather short-lived compared to other journeys like a trip from lysergic acid diethylamide, lasting a mere 15 minutes or so, compared to hours. The amount of time that elapses does not foreshadow a negligible experience, however, as the effects of the plant have been likened to near-death experiences, a loss of “body ownership,” and corresponding out-of-body experiences. [3] More on that coming soon.

The active ingredient in salvia is a diterpenoid called salvinorin A. This molecule is a κ-opioid receptor agonist (activator), and κ-opioid receptors provide potential pathways for therapeutic options aimed at treating addiction and depression. [4] In fact, hallucinogenic κ-opioid receptor agonists like ibogaine [5] and salvinorin A [6] have already revealed how they might help combat opioid and cocaine addiction.

A 2020 study out of Johns Hopkins University School of Medicine sought to understand salvinorin A’s effects on measures of functional connectivity, which essentially relates the strength of connections between different parts of the brain that are working during certain activities and reinforced with use. [7] The researchers hypothesized that salvinorin A would modulate default mode network connectivity, as has been shown with other psychedelics.

Our default mode network basically turns on when we’ve tuned out the outside world. This system activates during daydreaming, thinking about the past, etc., and as our own Loren DeVito, Ph.D. put it, “Most psychedelics are believed to affect the default mode network aka the pathways that have been strengthened over time that enable the auto-pilot, driving-to-work behavior that you snap into even though your commute has changed. Psychedelics supposedly work to disrupt these long-entrenched roads and help create new pathways.”

The study evaluated the experiences of 12 male participants. [7] Study requirements included having had more than ten lifetime hallucinogen uses, one of which had to be an inhaled hallucinogen use, one a past year hallucinogen use, and one a past year inhaled psychoactive drug. Participants also could not have a diagnosis of a mental condition like schizophrenia, bipolar disorder, depression, or substance abuse.

The participants inhaled vapor from a flask containing 15 µg per kilogram of their body weight. So, a 200-lb person would receive approximately 1.4 mg of salvinorin A. The participants wore eyeshades and refrained from moving about or talking to others for 30 minutes after their salvia session. Their brain activity was measured using functional magnetic resonance imaging.

The peak drug strength rating (an 8 on a scale of 0-10) occurred near the two-minute mark post-inhalation. At 15 minutes, the rating dropped to a 3, and after 45 minutes, had tapered off to a 1. The researchers found that salvinorin A tended to decrease static functional connectivity within resting state networks like the default mode network, whereas the diterpenoid increased static functional connectivity between these networks. Put more simply, salvinorin A may affect the brain in a similar way to other psychedelics. [7]


  1. Wasson R. A new Mexican psychotropic drug from the mint family. Botanical Museum Leaflets, Harvard University. 1962;20(3):77-84. [journal impact factor = N/A; times cited = 77 (Semantic Scholar)]
  2. Valdés LJ 3rd, Díaz JL, Paul AG. Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). J Ethnopharmacol. 1983;7(3):287-312. [journal impact factor = 3.690; times cited = 153 (Semantic Scholar)]
  3. Maqueda AE, Valle M, Addy PH, et al. Salvinorin-A induces intense dissociative effects, blocking external sensory perception and modulating interoception and sense of body ownership in humans. Int J Neuropsychopharmacol. 2015;18(12):pyv065. [journal impact factor = 4.333; times cited = 39 (Semantic Scholar)]
  4. Lalanne L, Ayranci G, Kieffer BL, Lutz PE. The kappa opioid receptor: from addiction to depression, and back. Front Psychiatry. 2014;5:170. [journal impact factor = 2.849; times cited = 113 (Semantic Scholar)]
  5. Mash DC, Duque L, Page B, Allen-Ferdinand K. Ibogaine detoxification transitions opioid and cocaine abusers between dependence and abstinence: clinical observations and treatment outcomes. Front Pharmacol. 2018;9:529. [journal impact factor = 4.225; times cited = 13 (Semantic Scholar)]
  6. Kivell BM, Ewald AW, Prisinzano TE. Salvinorin A analogs and other κ-opioid receptor compounds as treatments for cocaine abuse. Adv Pharmacol. 2014;69:481-511. [journal impact factor = N/A; times cited = 34 (Semantic Scholar)]
  7. Doss MK, et al. The acute effects of the atypical dissociative hallucinogen salvinorin A on functional connectivity in the human brain. Scientific Reports. 2020;10(16392). [journal impact factor = 3.998; times cited = 2 (Semantic Scholar)]

Image Credit: 三猎, CC BY-SA 4.0, via Wikimedia Commons

About the author

Jason S. Lupoi, Ph.D.

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