New research shows a link between Salvinorin A and the DMN

The Default Mode Network (DMN) is by now a familiar name in popular psychedelic circles. It’s a collection of brain areas that talk loudly to each other when we’re not doing any focussed tasks – basically when we’re daydreaming, thinking about ourselves, or conceptualising the past or future.

We know two important things about the DMN: it’s overactive in depression, and psychedelics can help to reset it. Studies have shown that classic psychedelics LSD and psilocybin can dramatically reduce the chatter of the DMN during a psychedelic experience, and allow it to re-form itself into a more stable network afterwards – correlating with decreased depressive symptoms.

Salvinorin A, the main psychedelic component of Salvia divinorum, is not at all like these classic psychedelics. While LSD and psilocybin mainly activate 5-HT2A receptors in the brain, and produce highly visual and often introspective psychedelic experiences; Salvinorin A has barely any 5-HT2A activity, instead activating kappa-opioid receptors and sending users on bizarre and often horrifying trips.

I’ve written (and spoken) fairly extensively about the weirdness of Salvia, and what it means for consciousness. Salvia disrupts an area of the brain called the claustrum, and this is correlated with an almost complete dismantling of typical conscious experience. Our usually coherent and coordinated stream of sensory perceptions, understanding of selfhood, and grasp of the concept of time, dissolves into a barely comprehensible array of pure sensation. Existence is literally ripped apart, in a very fundamental and powerful way, which is not seen as often in classic psychedelics.

Now, new research has shown that Salvinorin A is also connected to the DMN. Twelve experienced psychonauts were given doses of Salvinorin A while in an MRI machine, which showed that the unique psychedelic reduced the connectivity of the DMN in a very similar way to LSD and psilocybin.

This is very preliminary data and there are a number of potential issues with the sample of participants. But it’s the first time we’ve seen brain scans of people under the influence of Salvinorin A, and it shows us that the dampening-down of the DMN may be a pretty universal feature of psychedelic substances.

With this interesting finding comes the usual neuromemery we’ve come to expect from physicalist scientists: The authors of the research paper subtly suggest that reductions in DMN connectivity are causing antidepressant effects, rather than simply being correlated with them.

The importance of this distinction becomes especially clear with Salvia. We know, from decades of research and countless testimonies, that the Salvia experience is profoundly different in quality from typical psychedelics. While Salvinorin A may well be associated with a similar reduction in DMN activity as LSD, it would be a mistake to think the two psychedelics could be approached in the same way by a psychedelic therapist.

We need to avoid a future where psychedelic therapists work through an MRI machine, spewing keywords at a patient while watching the DMN parameters creep towards acceptable levels of disconnection. Instead, psychedelic therapy needs to take the subjective experience of the patient as the primary source of information.

Thanks to this research, we have more evidence that there is a very basic and quite consistent neural correlate with ego dissolution and the mystical experience. But the activity of the DMN doesn’t tell us anything about the quality of psychedelic experiences, or which therapeutic approaches are most likely to bring about healing in an individual patient with a unique substance.

Full paper: Doss, M.K., May, D.G., Johnson, M.W. et al. The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain. Sci Rep 10, 16392 (2020). https://doi.org/10.1038/s41598-020-73216-8

12 thoughts on “New research shows a link between Salvinorin A and the DMN

  1. This is interesting but the DMN always seems to me to be too vaguely defined. It may mean something precise to neuroscientists but whenever I read about it seems lie a catch-all of stuff going on at various times in the brain. For example, Wikipedia says this:

    ” It can also be active during detailed thoughts related to external task performance. Other times that the DMN is active include when the individual is thinking about others, thinking about themselves, remembering the past, and planning for the future”.

    “Though the DMN was originally noticed to be deactivated in certain goal-oriented tasks and is sometimes referred to as the task-negative network, it can be active in other goal-oriented tasks such as social working memory or autobiographical tasks. The DMN has been shown to be negatively correlated with other networks in the brain such as attention networks”.

    So it lumps together “thinking about others, thinking about themselves, remembering the past, and planning for the future”. Sometimes is negatively correlated with goal-oriented tasks, sometimes it isn’t.

    So maybe the dampening down of the DMN with psychedelics really doesn’t tell us much at all except under their influence we become intensely focused on the experience the psychedelic is producing.

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  2. The real problem with psychedlics is that they do not provide a cure. Whatever relief they provide in the short term soons wears off. Often within a couple of days. It is true that a psychedelic experience can be profound while it lasts. I very much doubt that it will significantly help permanently change the neural pathways of somebody who has suffered long term chronic depression.

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  3. I just met a woman today who suffers from severe depression and panic disorders, and has been diagnosed with schizophrenia. She claims that this did not happen until she took psychedelics to treat what was before just a mild depression with mild anxiety.

    In her experience, taking psychedelics exacerbated and aggravated the problem. Under the watchful eye of therapists who have been using these substances for at least 20 years.

    Though as a counselor I will investigate how various psychedelic substances might indeed be used to help my clients, I am extremely doubtful that The Nuro chemistry really has anything to do with particular mood states.

    And this really has to do with the fundamental problem of consciousness itself. Because, there is no reason why any chemical state should equal any sort of sensation, or understanding about anything at all. There is a huge epistemological gap between the function of neurons and Nuro chemistry and the fact that we have a conscious experience about it.

    Has anyone who is taking psychedelics without previous knowledge about what kind of trip you’re supposed to have involves, such an experience is beyond comprehension. And actually, given particular cultural manifestations, each experience will be accommodated and appear in different fashions. And further, that’s such cultural constructions cannot be reduced it to some “common human “spirit. By the simple fact that in order to do that we have to assume that there is a fundamental human cultural norm. Which, if we understand any sort of critical theory at all, the only thing that requires even an inkling of a common human experience is utterly contained by domination and oppression.

    And so that also draws my skepticism into this kind of research. I am wondering if the people who are doing this kind of psychedelic research are not convincing themselves, seeing things in the research them selves, either because they take psychedelics themselves, or because they don’t.

    I’m not entirely sure of someone who takes psychedelics involved in a scientific research program as a researcher, is really coming up on actual “facts”. Due to the nature of the problem of consciousness, with which psychedelics are so invested.

    I am concerned that the people who are so excited about research into psychedelics are not controlling for this phenomenon.
    Nor am I sure how they would. But I’m pretty positive that in order for us to control for this random occurrence of biased confirmation exacerbated by the discrepancies which occur between the experience and the supposed sober intelligence, We would first have to be honest about what kind of experience we’re actually having. And I’m not sure that people who are so excited about the psychedelic experience are being able to understand what is actually occurring in their experience, so excited that they are about it.

    But I appreciate your blog and a peach ate your reports. 👍🏾

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    • ….That having been said, I also know a young woman who had an extremely problematic childhood and adolescence. Plagued by anxiety and suicidal thoughts, institutionalism, eating disorder. And by the time she was 20, shit about had enough of all the various types of conventional medicines and therapists and institutions. And she started researching about psilocybin. This was about 10 years ago. And then one evening, After a long period of investigating all the various aspects of psilocybin, she got a quarter ounce. And went home into her bedroom and ate the whole thing at once. And she had an incredible experience she said and since that day her anxiety has been minimal and her depression manageable. And she doesn’t have suicidal thoughts nor any sort of eating problem.

      Personally, I Think very little of these two situations will be found in any sort of neuroscience. I think it ultimately has to do with conceptualization of reality. It doesn’t have to do with cognition, or chemicals necessarily. Because still we have no, zero, nothing, no idea whatsoever, no hypothesis nor any viable notion whatsoever why Nuro chemistry should have anything to do with developing a consciousness in the way that we actually experience reality.

      At best, we can only describe smidge it, small tiny portions of reality that we have to find into particular phrases and clauses, again, each of those meetings which have nothing to do, have no conceivable relationship to me having an experience of those cognitions at all, nor what they mean nor how they relate to any sort of reality that I’m in countering whatsoever.

      So, while all the chemistry is really interesting. I think what will tend to happen is a religion will develop around a particular kind of science, which will lead us down a rabbit hole and cause certain outcomes that will lead to even more aggravating problems as we continue to try and enforce this conceptual synthetical a priority relationship between the thought and the body (world).

      Nevertheless, I think we’re always wins out is a bunch of people who want to get high and get together in a group and then decide upon certain things. That is the nature of reality. It doesn’t matter what it is, as long as we have enough people earth supporting the particular ideology, then they can make money from it, they can support themselves and feed themselves. And I’m just wondering what kind of weird world war we’re going to have with a bunch of people are high and shit but they know nothing about, invested as they are in just the pure experience that they’ve created out of their own imaginations . 🤣

      Sorry, I’m just being a total dork and a total devils advocate right here. 🍄

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      • Psychedelics have been researched for around 70 years, most of which has been under the most strict and draconian regulation and scrutiny imaginable. For this alone, I would say that your skepticism is a little misplaced.

        No scientific research occurs without hypotheses, which basically means that you only find what you are looking for. Psychedelic research is no more guilty of this than any other area of research, and for at least 40 years has been rigorously subjected to hypotheses seeking to prove that they either cause, or greatly exacerbate mental illnesses, and not only has no evidence been found to show that, the opposite has been found to be true — that psychedelics, under the correct conditions, actually do improve mental health, and reduce mental illness.

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      • Perhaps it is misplaced. But not from lack of investigation. Probably more than most.
        And exactly my point you notice and make: Under what conditions are hypothesis about psychedelic experiences based?

        By the researchers who have never experienced such a state? Or the ones that have?

        For the ones that haven’t, sure we can make some arbitrary designation about what “improve mental health” means. And sure, I am open to using whatever vehicles are available to me to help someone with their difficulties. Yet, having thoroughly explored the wide space of psychedelic experience, I am skeptical that modern science is really using them affectively. By virtue of the fact that I’m not sure what mental health really is. And, by virtue of the fact that I think modern science, so far as the psychedelic experience goes, can only view may be a small portion, of what psychedelics are really involved with so far as an individual experience. I’m not sure if research and psychedelics is not a non sequitur. Lol.

        And for those that have, how much are they forming their “objective researched opinions, on their own version of what is supposed to happen as a “spiritual experience”. And how are we to “guide” a person to a psychedelic experience when most people’s version of a spiritual experience which improves mental health is a truncated form of the actual psychedelic experience?

        And “under the correct conditions”. ??

        Yes, the usual rhetoric about “attitude and place“. So basically we want to take the full potential of the human experience and fit it into a box that we called mental health.

        I guess my issue has to do with what are we really trying to do here. And are we able to be honest with what we are trying to do.

        I’m generally skeptical that people that are researching psychedelics are doing so in full honesty of what they are trying to accomplish, Simply because I’m skeptical that those people are even capable of understanding what they’re trying to do.

        I’m not necessarily saying that they cannot. But I am skeptical, yes.

        And yes, as a counselor I will be open to these possibilities for helping people. But again, I am skeptical of the “research community“, simply because it sounds like someone is going to sell everyone a bill of goods for mental health.

        And, I would not say that psychedelics way to either side of either deteriorating mental health or contribute a good mental health. I would say that psychedelics are ultimately neutral. And given whatever condition of use, cannot be fully controlled, and the person will ultimately go wherever they’re going to go. And “psychedelic research science” I am afraid he’s going to use statistics in order to skew towards what they want to see people get from it. Rather than seeing what is actually occurring and reporting it unbiased.

        For, everyone knows the only reason that marijuana is legal is because people when I get home. And so I yes again, I am very skeptical about this “psychedelic research”, because ultimately people just want to get high. A bunch of people have been getting high on this shit for so long, they have these great spiritual experiences, and then they figure that the reason why people have a bad experience is because the nature of the psychedelic experience is good. And so they see something of a bad trip as inherently wrong and something to be avoided. This alone can disqualifies the “research” . Because again, what are we really trying to do here?

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      • …I mean, think about all those silicon valley teckkies that are going down to South America and taking Psychedelics trying to “get inspired“ by a profound spiritual experience of some sort of shamanistic whatever whatever.

        On one hand, yeah maybe it’s good if these silicon valley people blow their minds and have an experience that changes their life such that they can never work in Silicon Valley again; maybe that’s a good thing, because they have some insight into humanity. But maybe it’s a bad thing because I care about them as human beings. Kind of an irony there.

        But if they’re going down there for the sole purpose of getting inspiration to create new technology, I’m not sure if that’s such a great thing. I’m not sure that such a great thing if people do a bunch of cocaine so they can get inspired and be productive, or do speed.

        Any sort of these modern capitalistic modes of using substances, yes I approach from a very skeptical standpoint .

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  4. Nice blog and post! We should be cautious about the connection between hallucinogens and the DMN. It is thought that stimulants also facilitate a deactivation of the DMN during tasks requiring attention. This is not exactly a ‘trippy’ state. Instead, it seems like most things that are strange, interesting, or anything that captivates our attention to the present situation will help deactivate the DMN. I Linked this at the bottom.

    Something interesting is almost every mental health problem involves increased activation of the kappa opioid receptor system. This is essentially a major focus of my writing. PTSD, depression, anxiety, the subjective experience of dysphoria, hallucination, schizophrenia all have been connected to increased kappa opioid receptor activity. Many of the healing effects of psychedelics can be traced to this mechanism as well. LSD seems to attenuate the effects of kappa opioid receptor stimulation. Also the endogenous kappa agonist is anti-neuroplastic.

    You can read an essay where I’ve explored this:
    https://mad.science.blog/2020/07/03/chemical-exorcism/

    Here is the dopamine DMN study:
    Tomasi, D., Volkow, N. D., Wang, R., Telang, F., Wang, G. J., Chang, L., … & Fowler, J. S. (2009). Dopamine transporters in striatum correlate with deactivation in the default mode network during visuospatial attention. PloS one, 4(6), e6102.
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006102

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