Brief Primers on the Neuroscience of Psychedelics 2: Salvinorin
Why is Salvia divinorum psychedelic?
Salvinorin is an extremely potent psychedelic molecule isolated exclusively from the Mexican ritual herb Salvia divinorum. The isolation and discovery of its reality shattering properties is quite a story in itself, but we’ll save that for another time.
The classic psychedelics, such as LSD and psilocin, work by activating 5HT2A receptors embedded in neurons deep in the cerebral cortex. This increases the activity of these neurons and allows entirely novel patterns of activity to emerge, experienced as the psychedelic state. Salvinorin, on the other hand, achieves its effects via a completely different and entirely unique mechanism. Rather than activating the 5HT2A serotonin receptors, salvinorin binds and activates a type of opioid receptor known as the kappa receptor, a member of the family of receptors also responsible for the effects of opiates, such as morphine.
Kappa receptors are heavily expressed in the claustrum, a small sheet of highly interconnected neurons sitting beneath the cortex and connected with almost all of its areas. The claustrum’s major function is as a regulator and orchestrator of cortical activity, which it achieves by general inhibition and selective amplification. Strong electrical stimulation of the claustrum causes a swift and powerful inhibition of the cortex and unconsciousness.
In a manner analogous to the conductor of an orchestra, who must control when each set of instruments should sound and when they should again be quiet, the claustrum orchestrates the activity of the cortex by amplifying patterns of cortical activity representing the world model you experience, quieting noisy activity, and guiding the cortex smoothly from state to state.
Kappa receptors are inhibitory, meaning they suppress the activity of neurons in which they’re embedded. As such, by binding to these receptors, salvinorin strongly suppresses the claustrum and thus its control over cortical activity. So, whereas the classic psychedelics excite the cortex, salvinorin employs a kind of release mechanism, disengaging the apparatus that normally keeps cortical activity under control — the cortex is disinhibited, allowing activity that would normally be extinguished to establish itself and propagate through the cortical networks. The cortex loses control over its activity and its flow from state to state.
This might be compared to instructing an orchestra to play a complex symphony faster and faster and then shooting the conductor.
As with the classic psychedelics, neuroimaging studies show an increase in disorganised activity in the brains of subjects given salvinorin. Released from claustral control, entirely novel patterns of activity emerge across the cortex, experienced as a complete shattering of the normal waking world. In a manner similar to DMT, this initial breakdown of the world model is followed, assuming the dosage is sufficient, by the emergence of a new order, albeit an extremely bizarre order. The time course of a typical salvinorin experience, when ingested by vapour inhalation, is also similar to that of the short-acting tryptamines. Almost immediately as the lungs are filled:
“Salvinorin comes on with an irresistibly powerful, spiraling force which is much stronger than that felt on any other psychedelic.” (from D.M. Turner, The Psychedelic Essence of Salvia Divinorum)
Whilst with DMT there is certainly a sense of being thrust into and travelling within the space, there is much more of a physical sensation of bodily and spatial distortion with salvinorin — space, time, and the structure of reality itself are twisted and torn apart, before the tripper is hurled through the fissures wrought by this irresistible process. Often the tripper becomes part of the distorting and reconfiguring manifold of the space. Awareness of the body is usually lost, often with the memory of ever having a body, of ever being human and, in the extreme, of the concept of human existence itself.
This effect is consistent with the sudden loss of claustral control over the large areas of the cortex that maintain not only the structure of the world model, but also the positioning of the body within the world, the sense of self, and their relationship to the environment. All existential points of reference are ripped from their moorings and cast into an unfathomably strange space with no connection to the world lost. When you think about it like that, it’s perhaps not so surprising that Daniel Siebert, the first person to isolate and experiment with pure salvinorin, described it as “tearing apart the fabric of reality”.
For a much more detailed discussion and explanation of the neurological mechanisms behind salvinorin, please refer to my latest book, Reality Switch Technologies: Psychedelics as Tools for the Discovery and Exploration of New Worlds, which covers all the major classes of psychedelics in unprecedented depth and detail. See my website for more details:
https://www.buildingalienworlds.com/books.html
I once inhaled a whiff of Salvinorin, which told me that this was somewhere I did not want to go to.