December 7, 2010
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My last post talked about the depressing lack of progress in treatments for depression and other common psychological disorders. Talking cures and antidepressants alike are subject to the "dodo effect," which decrees that all therapies are roughly as effective—or ineffective—as one another. The dodo effect implies that treatments harness the placebo effect, the patient’s expectation of improvement. Claims that one therapy beats all the others often reflect researchers’ favoritism, called the "allegiance effect".
After reading the post one of my smart-ass students asked, "What about psychedelic therapies? Are those subject to the dodo and allegiance effects, too?" Good questions. He knew that, although bashing conventional psycho-treatments, I’ve written positively about psychedelics’ therapeutic potential. Does my reporting reflect countercultural allegiance to psychedelics and distrust of clinical psychology, psychiatry and Big Pharma? Maybe a little. But I’ve also pointed out the risks of drugs such as DMT and LSD as well as the role of suggestion in shaping psychedelic trips.
Psychedelics clearly exploit the placebo effect, but in complicated ways. To make clinical trials of a drug more rigorous, researchers sometimes give subjects in the control group an "active placebo," which unlike a sugar pill has discernable physiological or mental effects, so subjects can’t easily tell whether they are in the control group. If psychedelics are placebos, they should perhaps be called hyperactive placebos, because their psychotropic effects are so dramatic.
In the early 1960s Harvard University psychologist Timothy Leary, who later morphed into a counterculture guru, proposed that psychedelic trips are shaped by "set and setting." Set is mind-set, your overall psychic makeup as well as your expectations, hopes, fears. Setting is, well, setting—meaning the trip’s locale as well as cultural context. If you think your trip will help you overcome alcoholism, obsessive-compulsive disorder, melancholy or fear of death, there is a chance it will, especially if you are tended by a caring therapist in a safe, clinical setting. Given the right set and setting, you might even have a religious experience.
The legendary Good Friday experiment, carried out in a Boston chapel on Good Friday 1962, shows the importance of set and setting—and the potential upside and downside of hyperactive placebos. Walter Pahnke, a psychiatrist studying under Leary, gave 10 divinity students psilocybin and 10 students an active placebo, nicotinic acid, which produces face-flushing and other effects. Most of those who received psilocybin had spiritual and even mystical experiences, which deepened their religious faith and improved their relations with others long after the trip ended, Pahnke reported in a 1966 write-up of the experiment.
What Pahnke neglected to mention was that most of the psilocybin-takers feared at times that they were "going crazy" or "dying," according to a follow-up study carried out by Rick Doblin, founder and head of the Multidisciplinary Association for Psychedelic Studies. Moreover, one extremely agitated participant, called L. R., veered between paranoia and mania. Suddenly convinced that he was the messiah, he burst out of the chapel and ran screaming through the streets of Boston. Only with difficulty did Pahnke and others chase L. R. down and persuade him to return to the church, where Pahnke injected him with Thorazine.
Pahnke’s failure to report these tribulations reveals the allegiance effect at its worst; his omission resembles that of pharmaceutical companies that bury evidence when a drug doesn’t work. Researchers at Johns Hopkins University carried out an experiment like Pahnke’s in 2006 and reported in Psychopharmacology (pdf) that psilocybin "can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance." Subjects endured anxiety but no L. R.–scale freak-outs.
I witnessed the healing power of psychedelics firsthand in 2002 when I traveled to a Navajo reservation to participate in a peyote ceremony with 20 members of the Native American Church. My companion was John Halpern, a psychiatrist at Harvard Medical School studying peyote’s effects. The focus of the all-night ceremony was a Navajo family—a husband and wife and their young son and daughter—afflicted, like many on the reservation, with medical and financial problems. The evening was in many respects agonizing, but the confessions, sobbing, moaning and vomiting seemed to have a cathartic effect. By morning, the husband and wife were beaming; their troubles seemed to have dissipated, at least temporarily.
Did this apparent therapeutic effect result from mescaline—the hyperactive ingredient of peyote? Or was it from the beautiful rituals of the ceremony that poetically evoked the Navajos’ spiritual bond to nature? The outpouring of compassion from the family’s friends and neighbors? The hypnotic chants of the medicine man who led the ceremony? The husband and wife’s expectations? Who knows? Maybe peyote is just a hyperactive placebo, but there was no doubt in my mind that for that family on that night, it worked.
Photo of flowering peyote cactus courtesy of Wikimedia Commons
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Wow, I guess it is getting harder and harder deny that psychedelic drugs have some therapeutic qualities. There is a reason why so many cultures, like the Native Americans, have been using them for hundreds of years. If it ends up becoming an every day thing, however, and gets added to the therapists arsenal, the whole game is going to change.
Link to thisAs someone studying to become a chemical engineer, this particularly interests me. Could it be possible that pharmaceutical companies are going to start churning out prescription psychedelics. Could we, some day, be getting over the counter Acid? Seems kinda crazy, but if a pharmaceutical company could come up with something that could be easily controlled and had minimal chance for bad trips, this whole thing could get spring boarded into the mainstream.
Final thought, in class you have talked about Brave New World several times. One of the major themes of that book is how people are encouraged to use drugs in order to forget their everyday concerns. Is there any possibility that using psychedelics could be the beginning of that? If so, how do we prevent that from happening?
See you in class tomorrow
your Smart-ass Student
While I strongly support the study of medicinal benefits of psychedelics, this article doesn’t really say anything. It doesn’t go beyond the question it asks in the title. There is no scientific thoughts in this article, just a small piece of history and a big ‘what if’. There is serious study to be done in this field, and I don’t see why science ignores ‘set and setting’ aspect of the trip. From first hand experience, this is the biggest and most important variable in a good trip (good trip meaning medicinal, beneficial, not just getting high). Science is having a hard time getting the facts out of their experiments, inconsistency is rampant in their studies. This isn’t due to poor scientists, this is due to the nature of what they are studying, people react differently. This is where ‘set and setting’ is so important. There isn’t one correct set or setting, but is personal to experimentee. This, IMO, is where you start studying the drug. We all know where ACID came from and how it was used, now we need to use it properly before studying it and putting final thoughts to paper.
I know people that have used psychedelics before and don’t understand the ‘set and setting’ part. These people were usually lucky when doing it, and abuse it in the future and have bad trips. And that is 99.9% of the critisism against the drug.
Link to thisAlso, to put a little scientific though on my own comment; Scientists are dealing with more than 1 variable here. The first is the drug, and the 2nd is the mindset of the person doing the drug. You will have variable outcomes with the same person, the same drug, and different settings (and often the same person, same drug, and same setting). These variables have to be eliminated before doing any research. Mind set and setting are the best way to remove the variables. That is why it is so hard to test a large sample of people. I think that science should be studying people that know how to use the drugs and how to eliminate thier own variables. Studying Joe Shmoe next door isn’t going to tell you anything, but studying people like Leary and Kesey can potentially unlock some mysteries that can lead to further and mroe efficient studies.
Link to thisIt is true psychedelics are not well understood. It is equally true that each one is different from the others. As Nichols has identified, each psychedelic has a different range of receptors that it occupies.
This article is rather lightweight, as it does not make use of what psychedelic bibliography is available now. It fails to mention that there are records of thousands of sessions without any serious problems.
Considering the extreme range of circumstances, the millions of doses taken and the range of human frailty, from the frightened to the diabolical, the record of these compounds is remarkable. If it were an industrial process it would be six-sigma, or close to it, even for the rather idiotic stunts pulled taking LSD in public.
Link to thisI cant see how you can distinguish between psychaedelic drugs (natures psychotropic) and pharmaceutical drugs (man’s attempt at replicating natures psychotropic)as
Link to thisthey both work on the principle of manipulating neurotransmitters and their receptors.
The results are not surprising either. The setting and stimuli that you provide will have a resultant effect in the mind of the subject. Thoughts being patterns in the brain.
Of course it’s a placebo effect. Psychedelics dramatically enhance the placebo effect. That’s how they work, at least in terms of a cure. Good article. But they don’t work on me anymore, as I know too much about how they work. Last time taking mushrooms in Amsterdam was disappointing, even though I took a fairly large dose. Hardly any effect at all, while people around me were totally tripping out.
Link to thisThe idea of using a dissociative substance , which a hallucinogenic drug is to re-associate the conflict one can have with one’s own perception of self, should not be surprising. Freud talked about the unconsciousness conscience having conflicts with the perception of self being one the major causes of neurosis. The idea of cogitative therapy which is a real life tool to train self to recognize reality is another long recognized way to approach the problem. The idea of combining the two with a dissociative or hallucinogenic substance puts the mind in neutral and a calibration should be possible. One would have to be careful not to have outside cognitive clues or the real risk of creating deeper chasms if the truth is not in reality true. It would seem that if false truth is put forth to try and "improve" no benefit or possibly a worsening of the size of the conflict can occur.. The idea of using dissociation to make the mind have the chance to realign itself under the correct circumstances is undeniably sound, in fact it may be the only way to cure. please note in nature and the natural world if it can be broken it can be repaired if one understands the true process involved which takes direct observation not running simulations on computers. Computers are great but they can only quickly tell you what is already known. my favorite tool both as a business manager and a scientist is the starting place of ; THROUGH DIRECT OBSERVATION DETERMINE THE EXACT…. NATURE OF THE PROBLEM OR QUESTION. If you are looking for a needle in a haystack you would be bettered served to look for a needle in a needle factory or needle store. The way to know for sure what would happen is to put it to the test.
Link to thisThe second argument for the merit of this path is the fact that most substances that n-methy d-aspartate inhibitors or modifiers are also dissociative substances. All you have to do is google scholar nmda and ptsd, TBI, or Parkinson’s, and Huntington’s, to know you are on the right track chemically. there is much research that actually shows brain plasticity and neural-protective qualities of N-methy D-aspartate inhibitors. Quite a bit of the mental health and stress response happens on the break down of glutamate and it is the substances like quinolinic acid and others that keep the brain from healing itself in some cases.
Though I am a scientist, I have somehow magically retained the part of me that longs to heal another and I say…PLACEBO EFFECT? SO WHAT! I recognize the need to distinguish between placebo and physiology; in fact, it’s pretty important and all we currently have when studying effects of novel drugs. But I can guarantee you that the family that were healed by the mescaline didn’t give a damn about the placebo effect. All they cared about was that it worked. And though it is important to distinguish between the two….keep it in perspective….the goal of most research is to somehow improve upon the human condition. If the placebo effect does that? Why not? That’s not to say go out and give every clinically depressed patient mescaline, but maybe we are asking the wrong questions…..maybe we should be studying the placebo effect in itself. How can we harness the power of the placebo effect to cure? The power of anticipating positive outcome?
Link to this"Use new drugs quickly, while they still work."
Link to this- attributed to Armand Trousseau, 19th century French internist.
What a fascinating blog post! Psychedelics continue to intrigue, and with good reason: they are the most powerful psychiatric medicine – or religious sacrament – ever known to humanity.
I would quibble with the phrase "hyperactive placebo" as applied to psychedelics. The experience certainly can be quite active, especially mentally, but can also be extraordinarily calm. More importantly, "hyper-" indicates something pathological or over done, but the intense psychedelic experience is medically effective and given the purpose and context, appropriate and normative.
I view psychedelics as increasing "suggestibility," rather than as placebos. That’s why mind set and the setting have so much influence on the phenomenology of the psychedelic experience. If a good "active placebo" should have a noticeable effect, but one that is not related to the action of the drug being evaluated, psychedelics have a noticeable effect alright, but one that due to the influence of set and setting is generally intimately related to the variable being studied (e.g., end-of-live anxiety, or alcoholism). This explicitly excludes psychedelics from being used as a placebo in any study of any variable: due to their suggestibility effect, the psychedelics engender too much identity with the object of focus for them to ever be unrelated to the variable of interest.
You say "Who knows?" what is causing the positive clinical outcomes being seen in all the current psychedelic research projects – sadly, you are so right – and this is exactly why new psychedelics research is so crucially important. This most-powerful class of drugs needs to be studied intensively, fully understood, and when appropriate, actively applied to ease suffering. The government needs to not just approve, but also fund, psychedelic research.
Thank you, John, for your excellent post and for exploring the issue of psychedelics that is so important for the future of society.
– Neal M. Goldsmith, Ph.D.
Author, Psychedelic Healing: The Promise of Entheogens for Psychotherapy and Spiritual Development
http://www.nealgoldsmith.com/psychedelics
I couldn’t agree more! We need a well-funded "Institute for the Scientific Study of Placebo, Psychosomatics, Spontaneous Remission, and Stigmata."
Link to thisFar from problematic, the suggestibility generated by psychedelics is one of the foundations upon which successful psychedelic therapy must be built.