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The Central Nervous System

Hallucinogenic Therapy

Too bad Alex Shulgin didn’t live to see this article in the New Yorker. It’s on the reviving field of psychiatric treatment using psychedelic drugs. This was an active area in the 1950s and 1960s, as many people know, although some of what people think they know about that era is not true. But it’s been dormant for some time, due to legal, cultural, and funding difficulties. The overselling of the original work didn’t help much, either:

The first wave of research into psychedelics was doomed by an excessive exuberance about their potential. For people working with these remarkable molecules, it was difficult not to conclude that they were suddenly in possession of news with the power to change the world—a psychedelic gospel. They found it hard to justify confining these drugs to the laboratory or using them only for the benefit of the sick. It didn’t take long for once respectable scientists such as Leary to grow impatient with the rigmarole of objective science. He came to see science as just another societal “game,” a conventional box it was time to blow up—along with all the others.

Some of the patients being treated in these new studies are in serious psychological distress – people dealing with major depression or with severe cancer. Other groups are looking at the possibility of addiction treatment. Even normal volunteers, though, rank their experience with (say) psylocibin as extremely signficant and even life-changing.
As a confirmed non-partaker, I’m of two minds about this. I have no doubt that these people are reporting accurately, and that their outlook on life has indeed changed. For people with addiction or depression, this could indeed offer a “reset button” and a way out of their diseased state. At the same time, I don’t actually believe that people taking a hallucinogenic drug are experiencing anything other than the reality of an oddly firing set of synapses – no alternate planes of reality, no encounters with supernatural beings, no removal from the spacetime continuum. I’m perhaps not a good person to ask, though, since I’ve been described by at least one close acquaintance as “annoyingly stable”. (Philosophically, though, it’s true that our only contact with reality is through our mental states and interpretation of our sensory data, which leads – and has led – to a number of interesting and unresolvable arguments).
There are practical issues and difficulties with using such compounds for therapy, but when you think about it, our existing pharmacologic resources mostly depend on altering levels of and response to serotonin, dopamine, and the other neurotransmitters anyway. Psilocybin is merely a more dramatic way of altering those same things. There are uncounted numbers of people out there in psychological misery, sometimes for easily understandable reasons, and sometimes for no reason that anyone can determine. If a hallucinogen can help them, then I think that’s a good thing, and I’m glad that it’s being investigated in a systematic way. From first principles, I don’t see how one can rule in Prozac and rule out psilocybin.

39 comments on “Hallucinogenic Therapy”

  1. anon says:

    “The overselling of the original work didn’t help much, either:”
    Shocking, how unlike every other research field!

  2. dave w says:

    DL: “I don’t actually believe that people taking a hallucinogenic drug are experiencing anything other than the reality of an oddly firing set of synapses”… one could say that about “ordinary” consciousness also!

  3. Rhenium says:

    A very interesting article.
    These are powerful drugs, but so is a great deal of the modern medical arsenal. Useful and not to be treated lightly.
    Ten years ago, legal marijuana was a dream, perhaps this will follow a similar path.

  4. Wavefunction says:

    Psylocibin has a really interesting zwitterionic, amphipathic structure. Is it a membrane disrupter? Does that explain some of its effects?

  5. Squib says:

    “The most compelling insight of that day was that this awesome recall had been brought about by a fraction of a gram of a white solid, but that in no way whatsoever could it be argued that these memories had been contained within the white solid. Everything I had recognized came from the depths of my memory and my psyche. I understood that our entire universe is contained in the mind and the spirit. We may choose not to find access to it, we may even deny its existence, but it is indeed there inside us, and there are chemicals that can catalyze its availability.”- Shulgin

  6. Vilhelm S says:

    While I agree that hallucinogens do not put us into contact with supernatural beings or alternate planes of reality, I don’t think it follows that they do not let us see real things which we otherwise couldn’t.
    Perhaps the best comparison is to Buddhist meditation. There, the theory is that we have a rather crude model of how our mind works; sense perceptions (pain from a stubbed toe, body odor from your boss) immediately leads to emotions, desires, judgments, etc, and in everyday life we do not distinguish between them. In the meditation exercises you examine your thought processes, and (supposedly) adjust them into a more optimal state. What you once thought of as just “you” on more careful examination resolves into many interacting parts.
    I’ve never done drugs, but reports from those that have often talk about becoming aware of this type of thing. E.g., to take one at random: “the concept – that ‘you’ are not actually an integrated whole, the coherency of your sense of self is actually a narrative wrapper around a set of scattered drives and aversions that are only in coincidental proximity if not active tension – well, in addition to bearing some similarities to the Freudian id/ego/superego model, I mean, if you’ve never done psychedelic drugs, well. I’ve tripped out for maybe 50 hours in my life, spent maybe 10 minutes dealing with visual hallucinations, and the rest of it was just grappling with this realization and trying to figure out what to do with it.” (from http://kontextmaschine.tumblr.com/post/83356593464/scientology)
    Huxley outlandishly claimed that “the function of the brain and nervous system and sense organs is in the main eliminative and not productive. Each person is at each moment capable of remembering all that has ever happened to him and of perceiving everything that is happening everywhere in the universe. The function of the brain and nervous system is to protect us from being overwhelmed and confused by this mass of largely useless and irrelevant knowledge, by shutting out most of what we should otherwise perceive or remember at any moment, and leaving only that very small and special selection which is likely to be practically useful.” And this is more or less literally true! We can’t perceive everything that happens in the universe, but there *are* types of brain damage which causes you to perfectly remember everything that happens to you, presumably by disabling the part of the brain that’s responsible for forgetting it. Similarly, autistic people sometimes are able to make realistic drawings that neurotypicals cannot, presumably because they lack what Betty Edwards called the left side of the brain.
    Being aware of what your brain is doing does not have any practical benefit from the perspective of Evolution, but according to the Buddhists it can be very beneficial for *you*. If you buy that, then it seems LSD could be quite helpful.

  7. ed says:

    for me, the effects of lsd were entirely positive. perhaps i am not the type to become dependent or addicted, but I experienced something unique, wonderful and fun and found myself happy not to need to go down that road again. the effects persisted for quite some months – i had regular hypnagogic visions for a long time after (perhaps unrelated).
    perhaps most importantly jimi hendrix, Are you Experienced never sounded better

  8. patentgeek says:

    @wavefunction
    Psilocybin is an agonist of several serotonin structures, most potently at 5-HT2a (as is LSD). The hallucinogenic effects can be abolished in dose-dependent manner by selective 5-HT2a antagonists (e.g., ketanserin). The effects of psilocybin are utterly unlike that classical membrane disrupter, ethanol.
    Derek mentioned Shulgin. Hoffmann’s LSD: My Problem Child has excellent description and discussion of psilocybin effects as well as LSD. Gordon Wasson’s writings are highly recommended also.

  9. Doug Steinman says:

    I am not that familiar with the area of neuroscience. Any thoughts about whether or not such an approach could be useful for patients with dementia?

  10. Anonymous says:

    @4. Wavefunction
    Psilocybin is essentially inactive itself. It is metabolized via dephosphorylation to give the active compound psilocin.

  11. Shaftoe says:

    @wavefunction
    psilocybin is a zwitterionic, amphipathic structure, but it is thought to be a pro-drug of the actual pyschoactive form – psilocin – vial cleavage of the phospate to a phenol. This removes the zwitterionic nature of the molecule.

  12. Shaftoe says:

    @wavefunction
    psilocybin is a zwitterionic, amphipathic structure, but it is thought to be a pro-drug of the actual pyschoactive form – psilocin – via cleavage of the phospate to a phenol. This removes the zwitterionic nature of the molecule.

  13. LeeH says:

    Derek –
    I think you’re kinda missing the point of the treatment, as was hinted by several of the previous posts. It’s not to change reality (i.e. meeting aliens), it’s a way to alter the same reality in a person who was previously in some kind of emotional pain in a way that aleviates that pain and allows them to positively change their behavior.
    A (somewhat extreme) example of how this might work is to use political affiliation as an example. Democrats and Republicans can look at the same everyday realities, but because of perception interpret things differently. Democrats might feel sad and see an overly optimistic solution to a problem that employs a compassionate path to a solution. Republicans might become angry and see a rigid and punishment-centric solution that is disciplinarian in nature. The “truth” of the moment (and therefore the solution) is in the mind of the viewer, based on their genetics, upbringing, experience. This could be altered pharmacologically (I’ve witnessed an example of this very effect, but that’s another story).
    (So beware what might be in those packets of Starbuck’s in your coffee station, lest you become a fan of Elizabeth Warren.)

  14. Anon says:

    “So beware what might be in those packets of Starbuck’s in your coffee station, lest you become a fan of Elizabeth Warren”
    Paranoid much?

  15. johnnyboy says:

    What I remember from my drug-taking youth was that the main attraction from LSD, apart from the fun sensory distortions and the obvious stimulation of pleasure centers, was the sense of being able to reach deep insights into your way of being and thinking. You felt like you were making amazing discoveries about yourself, and the world around you, in a way that felt, well, mind-blowing. The problem was that these insights never really survived the cold light of day; what felt like a major revelation while high looked mundane and banal in a normal state of mind. Also, coming off acid caused pretty severe depression and borderline suicidal ideation, which could certainly be a problem if using this drug for depression therapy.
    By contrast, psilocybin was mostly a good time drug, more about having a laugh and seeing funny stuff rather than having deep thoughts.

  16. Chrispy says:

    I’m surprised there are so many medicinal chemists who have not tried hallucinogens. Where’s your scientific curiosity?!?
    MDMA has my bet for the drug of abuse that will come to be accepted by the medical profession. It has much of the everything-is-connected philosophy of the hallucinogens like LSD without the hallucinations. And, for better or worse, the rave youth of today are engaged in a giant, unclinical trial.

  17. RM says:

    “From first principles, I don’t see how one can rule in Prozac and rule out psilocybin.”
    The biggest argument is one of abuse. Were possession of Prozac to be classed as a Federal felony tomorrow, I highly doubt anyone would seek out underground websites for nondescript packages filled with ‘zac. (Aside, perhaps, for a few poor folks with demonstrable medical conditions for whom Prozac is the only thing bringing them back to “normal”.)
    Heroin works marvelously as a cough suppressant, but no reasonable doctor is going to suggest it in any but the most severe cases. Likewise, new uses for heroin aren’t going to be investigated unless the condition is severely debilitating and it’s specifically heroin that gives the activity.
    Psychedelics may not be as addictive as heroin, but their tendency to be abused for non-medical purposes greatly limits their medical usefulness. (Like medical marijuana, advocates often argue – or are perceived to argue – more from a “foot in the door” perspective than one of genuine medical concern.)
    Chrispy@17 – My scientific curiosity is such that I’m volunteering for the control group.

  18. LeeH says:

    @15 Anon
    You misunderstood the joke. I wanted to imply that someone might want to see if they could turn Derek Democratic, and that they might spike the coffee on his floor. I happen to know that Starbuck’s is provided at his company (one of the things they do very well).

  19. bradpalm1 says:

    I have long argued that legitimate therapeutic indications for ibogaine have long been overlooked in this country. The drug has a fascinating cultural history.
    http://en.wikipedia.org/wiki/Ibogaine

  20. milkshake says:

    I won’t mind the terminal patients getting high, being stoned or hallucinating, (it is not all that different from listening to a voodoo shaman, or befriending a pedophile priest). If the opioid doses could be reduced, this would prolong the patients life, help them to remain more lucid, and suffer fewer opioid bowel complications.

  21. Novae says:

    Chrispy@17 – I actually doubt that MDMA will become that compound. It has too much toxicity. Other phenylethylamine analogues, quite possibly without the N-Me, I think are where we’ll land.

  22. Squib says:

    Strangely enough I actually decided to become a medicinal chemist while under the influence of psilocybin. Although I and many other people I knew in college used these sort of substances quite often back then, I don’t really know of anyone know got “addicted” to them or has really even uses them more than once a year or two 10 years later. Unlike some of the posters here, I got quite a few long lasting insights about myself/life while using. I will say that about 1 in 10 people in my experience has a very bad reaction their first time despite being in a good setting and with experienced people, enough so that they would never try them again.
    IIRC there are some trials in planning/ongoing on using MDMA for PTSD treatment. I’m very excited to see how those turn out. I have some anecdotal evidence from some veterans I know that it can work quite well in a group setting.

  23. Vince Billock says:

    It’s not just oddly firing sets of synapses. Some of the firing has to be incredibly well organized. Moreover, many of the early stage hallucinations experienced with LSD and similar drugs are nearly identical to geometric hallucinations seen with strobe lights, transcranial magnetic stimulation, sensory deprivation, migraine and epilepsy. The exact nature of the early stage hallucinations can be predicted from a combination of nonlinear dynamics and functional neuro-anatomy. The hallucinations provide a window into the ways that self-organized pattern formation interacts with well-understood neural mechanisms in vision. For reviews see Billock & Tsou, PNAS, 2007 or Billock & Tsou, Psychological Bulletin, 2012.

  24. cthulhu says:

    @17 Chrispy: you should read Oliver Sacks’ book about hallucinations; in one chapter he details his experimentation with various mind-altering substances. Gusto to spare (if sometimes lacking in common sense!).

  25. Matthew K says:

    Having just delivered a 2 hour lecture on neurotransmitters I can’t let this pass without comment! Let’s not forget that the “perceptual modulators” such as dopamine, serotonin etc are also powerful modulators of plasticity. So as well as altering perceived reality (perceptual and evaluative processing of stimuli and context, if you prefer) they are also capable of shifting modes of behavioural selection, and also of altering the long term likelihood of behavioural patterns. So although it’s just a different set of synaptic firings driving the hallucinogenic experience, there is also a softening of established connectivity and a re-evaluation of the connections themselves. Moods and emotions are basically evaluations made by the CNS of its current situation, and shape both current and future behaviour – that’s what they are for. We enjoy doing useful things because the enjoyment is part of the process of reinforcing useful behaviour, and so on. So tapping into that communication system is going to have lingering effects driven by the same endogenous processes by which we set our behavioural habits – just bypassing the feedback of behaviour consequences in the external world, by using a direct chemical activation.

  26. Anonymous says:

    It is believed that hallucinogens reduce the activity of a certain brain area which seems to filter all the incoming signals, visuals, sound, smell, and reduce it to a bearable input. (cant find the paper right now, PNAS I think). What you get with hallicinogens might be a input overflow…

  27. daveh says:

    News regarding original research in the field.
    http://dead50.net/
    I’m interpreting the timing of DL’s post as a sign from the universe that I must participate.

  28. Doctor Memory says:

    “I don’t actually believe that people taking a hallucinogenic drug are experiencing anything other than the reality of an oddly firing set of synapses.”
    This is true.
    It is also equally true of every other mental state and interaction with the outside world, including steely-eyed sobriety at 10am after your third cup of coffee.
    (Not to mention the feeling of emotional stability provided by SSRIs and the calm provided to acutely symptomatic schizophrenics by haloperidol.)
    The question is: is that state useful? Can it be used to provide benefits to the user after the active dose has worn off? It’s not by any means a lock that the answer is yes, but some of the results certainly look like they warrant further study.

  29. Anon says:

    #19: Gotcha. Looks like I need some of that Starbucks myself to tune my humormeter!

  30. luysii says:

    You should know that one of the older theories of heavy (not recreational) drug use (alcohol, cigarettes, marihuana, cocaine, heroin, LSD, on and on and on) is that it represented an attempt to treat underlying mental illness. Back in the day, it was almost unheard of to find someone on a psych ward for whatever reason who hadn’t used some of them. Most psych wards smelled like ashtrays.
    Turning this on its logical head, proponents of various forms of drug control argued that the drug use caused the psychiatric problems. It’s the old chicken and the egg problem.
    Naturally as a neurologist, I saw docs who got in trouble with drugs (usually alcohol). One very intelligent doc, who practiced where I did (before he got shut down), told me that the basic problem was that I liked reality and he didn’t.

  31. Doctor Memory says:

    belatedly to @18:
    “The biggest argument is one of abuse. Were possession of Prozac to be classed as a Federal felony tomorrow, I highly doubt anyone would seek out underground websites for nondescript packages filled with ‘zac.”
    Really? Because given the number of friends and family members I have who consider SSRIs to have literally saved their lives, I am quite sure that if it were outlaws for some reason other than gross toxicity (and perhaps even then), a booming black market in the stuff would spring up immediately.

  32. anon says:

    The widely used ‘recreational’ drugs are safe (which as we all know is the hardest thing to design in a molecule) and have at least some benificial effects to users, otherwise they would not take them. To badly quote the film Trainspotting, these people are not stupid. Well done to J&J for cashing in and marketing what is essentially ketamine. Anyone who has ever used it could tell you it could be effective in depression, it’s a shame these people are demonized in our society. No-one who has never taken hallucinogens has ANY IDEA AT ALL what the experience is like, whatever books or papers they’ve read. The first few times on MDMA for example are truly game changing. In their current forms, MDMA, LSD, THC etc etc are blunt tools, they should be the starting point for banishing the pains of the human psych as we have with the pains of the human body.

  33. anonymous says:

    It’s all well and good to give psylocibin to dying people to relieve their anxiety, until somebody has a hell trip. That would be counterproductive.

  34. dave w says:

    Imagine a world in which recreational drug use was considered legitimate, rather than categorically disparaged as “abuse”: suppose ‘Big Pharma’ was allowed to start with something like, e.g., MDMA or LSD, and do the same sort of optimization that is applied to more “conventional” molecules: try to find new hallucinogens with stronger potency, less toxicity, etc. – there’s probably an SAR space here that’s significantly under-explored.
    At present, however, we have this puritanical approach to medication, where everything is Supposed To have an “indication” to relieve a specific “condition”, but not to enhance “normal” functioning. Consider Viagra, for example – one can’t just market it to “improve erectile function” (something the customers have been asking for since the first witch doctor hung out his shingle), but it’s OK to “relieve the Medical Problem of Erectile Dysfunction.” (Similarly with the mood elevation and appetite stimulation associated with marijuana: “euphoria” and “the munchies” are supposed to be Bad Things, but if we describe the same effects as “relief of depression and anorexia” it’s another matter.)

  35. dave w says:

    Imagine a world in which recreational drug use was considered legitimate, rather than categorically disparaged as “abuse”: suppose ‘Big Pharma’ was allowed to start with something like, e.g., MDMA or LSD, and do the same sort of optimization that is applied to more “conventional” molecules: try to find new hallucinogens with stronger potency, less toxicity, etc. – there’s probably an SAR space here that’s significantly under-explored.
    At present, however, we have this puritanical approach to medication, where everything is Supposed To have an “indication” to relieve a specific “condition”, but not to enhance “normal” functioning. Consider Viagra, for example – one can’t just market it to “improve erectile function” (something the customers have been asking for since the first witch doctor hung out his shingle), but it’s OK to “relieve the Medical Problem of Erectile Dysfunction.” (Similarly with the mood elevation and appetite stimulation associated with marijuana: “euphoria” and “the munchies” are supposed to be Bad Things, but if we describe the same effects as “relief of depression and anorexia” it’s another matter.)

  36. tangent says:

    “It’s all well and good to give psylocibin to dying people to relieve their anxiety, until somebody has a hell trip. That would be counterproductive.”
    Might, might not. Fear of dying is a common material for a bad trip, but fear of dying has got to be the prime topic these people are tripping on, right? Unless they are extra-powerful with the denial, I doubt many of these trips are easy fun times. Not relieving their anxiety so much as working past it, because they’ve done dying. A bad trip can be a real education.
    That said, it can also just knock you sideways and be too much to integrate.

  37. NaN mice says:

    “It is believed that hallucinogens reduce the activity of a certain brain area which seems to filter all the incoming signals, visuals, sound, smell, and reduce it to a bearable input.”
    The only time I’ve had actual hallucinations (by accident; I use cyclizine for nausea and I exceeded the recommended daily dose) could very well be described as disabled sensory filters and possibly odd feedback effects. Would explain both the liquid insects (blood flow in retina, add feedback) and strong visual noise. (As it happens, migraine-related hypersensitivity is very different and much more painful.)

  38. Pontiac says:

    Something else important about using psychedelics in psychotherapy is that (afaik) they are used as one-time or few-time doses taken under supervision.
    That’s a different paradigm than most of what is available out there. But, well, if we all accept that people can have psychological problems that have been triggered by acute negative circumstances, as in PTSD, then it doesn’t seem so hard to accept the possibility that acute well structured intervention may be helpful – and so it seems to be.
    This analogy doesn’t hold if the root cause is some more continuously present innate issue.

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