By now there isn’t serious doubt anymore about the fact that psychedelics of the 5ht2a agonist type have a huge therapeutic potential. The classical psychedelics, particularly Psilocybe mushrooms, are increasingly used to treat otherwise treatment resistant depression. Study after study shows that even outside of therapeutic settings, risk of suicide and depression is dramatically reduced in those who have taken the mushrooms. In addition, evidence strongly suggests that people’s personality changes after taking Psilocybe mushrooms.
It’s important however to understand that the classical psychedelics, like mescaline cactuses, DMT containing plants, MAO inhibitors like Syrian Rue and Psilocybe mushrooms are not the only kind of psychedelics found in nature that have a huge unappreciated therapeutic potential. There are also atypical psychedelics, that have effects significantly different from the effects observed with classical psychedelics. The most prominent atypical psychedelic is Salvia Divinorum, which targets the Kappa opioid receptor in our brain. Another atypical psychedelic is Iboga, which targets the Kappa opioid receptor, the NMDA receptor and a number of other receptors. However, there’s reason to believe that the psychedelic potential of many plants has not been discovered by humans so far. Recently, two species of Salvia were discovered in Turkey that contain the same psychoactive substance as Salvia Divinorum, though at around 10% of the amount normally found in S. Divinorum.
In addition, there has been an extract produced from a tree in South America that functioned as a Kappa opioid agonist, although I can’t find the study anymore unfortunately. More interestingly perhaps, is the discovery of a Kappa opioid agonist in a mushroom. Collybia maculata is a widespread fungus, commonly known as the Spotted Toughshank. Although the Kappa opioid agonist was discovered to work in mice, it’s still not known to this day whether or not the mushroom itself is hallucinogenic in humans. Whereas the Aztecs and other Mesoamerican civilizations regularly used Psilocybe mushrooms in ritualistic settings, European civilization was completely unaware until around the 19th century of the psychedelic potential of Psilocybe mushrooms that are highly widespread throughout Europe. In a similar manner, it’s likely that our planet is covered with plants, mushrooms and even animals, the psychedelic potential of which has remained unknown up until this day.
Chronic exposure to stress taxes your Kappa opioid receptors, causing them to retract into the neurons and become inactive, thereby causing the symptoms of excessive stress. The native ligand for the Kappa opioid receptor is known as Dynorphin. It’s released in response to excessive dopamine in the brain, as excessive dopamine can be damaging (it’s linked to psychosis, among other issues). When dynorphin binds to the Kappa opioid receptor, it’s generally an unpleasant experience. The kappa opioid receptor is involved in experiencing social pain. As we age, we’re exposed to a lot of stress, thereby causing more of our kappa opioid receptors to retract into our neurons. In response to this, Dynorphin struggles to bind to the kappa opioid receptor. The effect this has is to increase the circulation of dynorphin in our body. This in turn, contributes to some of the effects we tend to notice in people as they age: Older people become more pessimistic, more anxious and more depressed.
Anxiety and depression tend to co-exist in the same person. In addition, both of these issues are linked to anhedonia: The inability to experience pleasure. It’s thought that “given the high comorbidity of depressive and anxiety disorders, KOR signalling and control of DA function may underlie the pathogenesis of both“. These problems are also what we notice in young people exposed to a lot of stress. In response to acute social stress, the young animals produce a lot of dynorphin. In response to chronic stress, the animals adapt to the stress and dynorphin production is reduced. The animals take on a subordinate role and become anxious, depressed and anhedonic. The Kappa-dynorphin system has been overtaxed.
The peculiar thing is that although activating the Kappa opioid receptor is generally seen as an unpleasant experience for animals, not all animals experience it as unpleasant. Female mice exposed to social defeat enjoy sticking around in places where they’re exposed to a synthetic kappa opioid agonist. Female mice that were never exposed to social defeat, don’t enjoy sticking around in such places. Even more interesting is that a subset of mice exposed to social stress, respond by becoming more social, in response to exposure to small doses of synthetic kappa opioid aognists.
Salvinorin A, the active ingredient in Salvia, is a very potent Kappa opioid agonist. Could it be that Salvinorin A “resets” the brain’s Kappa opioid receptors in people who have suffered chronic stress, allowing them to enjoy their lives again? No? Too far fetched? Well, that’s exactly what we see in rats. Another example is seen here. There is a subset of people out there, who genuinely seem to enjoy repeatedly exposing themselves to high doses of salvia, whereas most people find it to be a rather unpleasant experience. It seems to me that this subset of people is unwittingly resetting the Dynorphin-Kappa opioid system in their brain. Some accounts of individuals who have taken Salvia Divinorum back up this hypothesis.
There has also been a study of 500 people who took Salvia Divinorum regularly. It found that Salvia improved people’s mood for more than 24 hours in a substantive group of people:
Baggottet al. (2010) analyzed a sample of 500 S. divinorum and salvinorin A users. The findings of this study on the effects of salvinorin A are similar to studies conducted on humans in a laboratory setting (Johnson et al. 2011; Addy 2012; MacLean et al. 2013), principally presenting positive after-effects. After-effects occurring in the first 24 hours after administration of the drug include increased insight (for 47% of the sample), improved mood (44.8%), calmness (42.2%), increased connection with universe or nature (39.8%), but also weird thoughts (36.4%) and things seeming unreal (32.4%). Adverse effects were reported by a smaller number of subjects, like difficulty concentrating (12.0%), anxiety (9.4%), and/or worsened mood (4.0%). Interestingly, 25.8% of participants also reported positive effects lasting 24 hours or more after use, the majority of which reported an improved mood and “antidepressant-like effects” (46.5%). It was calculated that people who expressed high possibility of using S. divinorum again and people who had used the plant for auto-psychotherapy were more likely to report positive after-effects lasting more than 24 hours. Adverse effects were rare, only 4.4% of the 500 subjects sample reported negative effects (usually anxiety) lasting 24 hours or more after use of S. divinorum.
Perhaps most interesting of all, are the studies suggesting links between Kappa opioid receptor availability and social status, or the link between the Kappa opioid receptor and child abuse. The earlier mentioned survey of 500 S. Divinorum users reported increased self-confidence in 21.6% of users, compared to decreased self-confidence in 2.4% of users. It would thus seem that Salvia Divinorum may have the potential to override the long-term effects of negative childhood events.
There are many more things worth discussing about Salvia. Terence McKenna mentions some of them in the above video. Salvia Divinorum doesn’t have a clear history. People figured out in the 60’s that the Mazatec of Mexico use the plant, but the Mazatec have no native name for the plant. The plant is poorly fertile and seems to have been cultivated for a long time, but nobody has any clear record of how it was used or who cultivated it, though there are suspicions one of the numerous mysterious plants used by the Aztecs may have been Salvia and it somehow ended up being used by the Mazatec. Its closest relative is now thought to be Salvia Venulosa, which grows on a different continent. There are numerous species of Salvia in Mexico, but Salvia Divinorum is most closely related to a species found in Colombia.
Perhaps most mysterious is the name used by the Mazatec: “Eyes of the Shepherdess.” Who is this shepherdess? Christian traditions don’t mention a shepherdess. There are shepherds found in the Bible, but no shepherdess. Native American religious mythology does not appear to refer to a shepherdess either. And yet, Salvia Divinorum is associated with the figure of a shepherdess. Those who take Salvia Divinorum report meeting a shepherdess. Sometimes she is said to be surprised or afraid to meet them. Other times, she leads a parade in a carnival and the subject partakes in this parade.
A number of Salvia archetypes that people commonly experience are mentioned in the above video. Ending up on conveyor belts, transforming into objects, revisiting of childhood places and memories, these are other experiences subjects often report. In high doses, some subjects report being exposed to a realm where every individual human life is visible. Different people’s lives are witnessed in the form of bubbles. The subject has to return to find his own bubble, lest he ends up experiencing the life of an entirely different person. In my own experience while chewing Salvia, I experienced a moment where I closed my eyes and imagined myself sitting in a hut at night, with a fire nearby, chewing the salvia. It felt as if I were in America, centuries ago. The experience began feeling increasingly real, until it made me worired, as I could imagine it eventually feeling more “real” than my own life. I thus opened my eyes to abandon this vision.
Other experiences commonly reported include people witnessing a book full of their experiences in life, or witnessing a giant wheel, or witnessing reality being unzipped. Most noteworthy however, may be the circus that many people claim to visit after taking Salvia. Why do these peculiar events happen to people? The world we live in is ultimately composed of certain archetypes, at least in the sense that the human brain interprets its observations through archetypes. Some of these archetypes that are witnessed, may be connected to the brain trying to make sense of what is happening to it through memories it has of the world it has experienced. The brain feels as if it is being moved against its will, so the image is summoned of a conveyor belt. The brain feels as if the experience is surreal and the ego has been split up, so the person feels as if they were participating in a strange parade in a circus. If the Salvia realm appears cartoonish, it may be because not all the details of these archetypes are filled in by our mind, just as cartoons appeal to children because they can not be distracted by details that are irrelevant to what is genunely happening.
To say that Salvia is an atypical psychedelic distracts from the more interesting consideration, that Salvia is a surreal psychedelic. I tend to refer to Salvia Divinorum as the younger surreal Goth sister of the Psilocybe mushroom. It seems to me that to genuinely enjoy Salvia Divinorum requires a certain personality orientation: Gloomy, dark and surreal. For most people, Salvia Divinorum is a frightening experience they don’t want to repeat. For others, it is the greatest gift of nature.
Interesting article. I was always intrigued by the alkaloid that Salvia produces and how it affects an opioid receptor.
You may also find interesting is that Dynorphin, the natural kappa opioid ligand, is released when you are in short term heat stressors too. Heat stressors like being in a sauna for 15 minutes or during a very strenuous workout. It’s what makes you feel very uncomfortable in heat or vigorous exercise. This pathway of Dynorphin to the KOR also triggers another mechanism. Your body creates more Mu Opioid Receptors and also the MORs become more sensitive to endorphin. The happy feel good chemical.
I also just read that the opioid agonist in Salvia is just a efficacious as Dynorphin while not having a similar structure to Dynorphin or other KOR agonists, which is that they all contain nitrogen whereas Salvia does not. Maybe the agonist in Salvia is tricking your body to thinking you are receiving Dynorphin. But in that maybe it also makes your MORs more sensitive to endorphin just like short term released Dynorphin does.