Salvia: a one-of-a-kind psychoactive plant

Salvia divinorum is a really unique psychedelic drug. Like many interesting psychoactive plants, Salvia has been used culturally for centuries. The Salvia plant was grown in secretive groves by the Mazatec tribe in Oaxaca, Mexico. The tribe chewed Salvia leaves in religious rituals, revering the healing and psychoactive properties of the plant. In the 1960s, anthropologists visited the tribe and took cuttings of Salvia to the western world. Salvia contains the most potent naturally occurring hallucinogen we know of. See here for more information about Salvia divinorum.

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Flowering Salvia divinorum

Along with the classical psychedelic effects such as visual distortions, Salvia also induces feelings of strange movement, shifting realities and a loss of control. Scientists often call Salvia’s effects ‘psychotomimetic’, meaning Salvia mimics the delusions experienced in disorders such as Schizophrenia.

What makes Salvia so unique? For one thing Salvia’s main psychotropic compound, Salvinorin A, has a unique structure that is quite different from the classical psychedelics. More importantly, Salvinorin A activates an unusual receptor, the kappa-opioid receptor (KOR). Drugs that activate the KOR have been known to induce psychotomimetic effects like depersonalisation and a disruption of reality. That means it’s likely that the activation of this receptor is Salvia’s main mode of action.


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Salvinorin A has a unique structure compared to the classical psychedelics LSD and psilocybin.


In a ground-breaking 2002 paper, Bryan Roth and his colleagues set out to investigate the receptor targets of Salvinorin A, including the three families of opioid receptors (mu, delta and kappa), and families of receptors activated by the classical psychedelics such as 5-HT and dopamine receptors. They carry out ‘radioligand-binding assays’, where Salvinorin A is labelled with a radioactive marker that they can track. This means the researchers can ‘see’ Salvinorin A binding to the KOR while measuring how strong the binding is. The authors carry out this experiment in vitro (in a petri dish).

The authors found that Salvinorin A bound very strongly to KORs, and did not bind to the other opioid receptors, mu and delta. They also found that Salvinorin A did not bind at all to 5-HT receptors, which are important targets of LSD and psilocybin. Salvinorin A seems to be a very unique psychedelic, activating targets that no other psychedelic drug had previously been found to activate.


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Binding strength of Salvinorin A and LSD to various neurotransmitter receptors. 5-HTR = serotonin receptors, DAR = dopamine receptors, MOR = mu-opioid receptors, DOR = delta-opioid receptors, KOR = kappa-opioid receptors. Adapted from Roth et al (2002).


So in addition to Salvia being the world’s most potent natural psychedelic, it’s also unique in the way it works in our brains. Salvinorin A belongs to a rare class of molecules that activate KORs very selectively, and it’s very likely this is the main mode of action through which Salvia achieves its ‘psychotomimetic’ effects.

The fact that KOR activation causes disorientation, loss of touch with reality and loss of self-awareness tells us something; KORs are probably involved in systems in the brain that regulate perception and cognition. Understanding Salvia’s mechanisms could lead to the development of new treatments for psychiatric disorders, or even help us understand the basic mechanisms of consciousness itself.

Originally posted on Coffeesh0p.com, on 15th May 2014

References

Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P & Rothman RB (2002) Salvinorin A: a potent naturally occurring nonnitrogenous kappa-opioid selective agonist. PNAS 99(18):11934-11939

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