Psilocybin-assisted psychotherapy vs. placebo in treatment of alcohol disorder
jamanetwork.com
jamanetwork.com
>Participants correctly guessed their treatment assignment in 93.6% of the first sessions, reporting a mean (SD) certainty of 88.5% (23.2%). In the second session, 94.7% guessed correctly, and mean (SD) certainty was 90.6% (21.5%). Study therapists correctly guessed treatment 92.4% of the time for first sessions and 97.4% for second sessions, and their mean (SD) certainties were 92.8% (16.3%) and 95.4% (2.9%), respectively.
This is not a criticism, as these trials are very hard to blind, but as you can see in hindsight they could as well have not bothered with blinding at all. So we need to interpret this as a randomized but unblinded trial.
The researchers are well aware of this, and I suspect it will inform the next steps of their research.
>Several limitations of the study warrant discussion. First, diphenhydramine was ineffective in maintaining the blind after drug administration, so biased expectancies could have influenced results. Control medications such as methylphenidate,42 niacin,2 and low-dose psilocybin1 likewise did not adequately maintain blinding in past psilocybin trials, so this issue remains a challenge for clinical research on psychedelics.
1. With a high dose of shrooms, you're definitely going to know whether you were tripping or not.
2. If they can find another agent that mimics the effect of tripping, well then it's not really a placebo anymore.
I was really confused about the entire concept of blinding a study like this until I read your comment... Now I realize they are indeed proceeding from the assumption that the phenomenological experience is somehow distinct from the mechanism of action.
That seems really unlikely to me- these drugs are unique because of the phenomenological experience! It seems self evident that this experience is the reason for therapeutic effects.
Imagine the absurdity of trying to design a study blinding the effects of meditation for example. Meditation has measurable benefits, but what are the chances those aren't caused by the psychological effects of experiencing meditation?
You might be right, maybe you're even probably right, but it's not self evident to me.
Psychedelics have an impact at the microgram range, with a single dose. They could be hundreds of thousands of times more potent, or, it could be the experience.
They have a good point. The whole “chemical imbalance” thing has come under significant scrutiny as of late.
In this design, I have to imagine both groups' sessions were very much affected by thoughts of "am I about to trip or is this just allergy relief?" To be honest, I am uncomfortable with the thought of a participant being unsure if they had been given a psychedelic.
Consider that a non-trivial number got it wrong! To me that signals some of the control group participants may have been quite agitated.
I wouldn't mind seeing a self-controlled design where participants are randomized to receive either psilocybin with therapy or non-psilocybin therapy first, but ultimately end up receiving both. As others have noted it's not just the drug, it's the drug and the experience of therapy so I think the two ought to be packaged.
Ultimately though, what I am most curious about is the long term sustenance (and/or repeatability) of any effects and also whether any negative effects appear later.
The first wave of psychedelic research also showed some promise, but their utility faded. Have we gotten any better? Six months of alcohol use disorder or depression relief is great and useful, but the goal ultimately is long term relief.
There are probably rules demanding blinding for these studies. Let's hope they don't hold back the research for too long.
So focused they are, it seems, on the therapeutic development angle (receptors, agonists, drugs, etc), that they've forgotten that the brain/mind is a processing network of neurones that can exhibit phenomena of multiple levels of complexity. Sure, a particular neurotransmitter or receptor may be involved in a particular pathway, but that's just signalling, not the process itself, let alone its totality.
The issues at hand are complex, it’s worth trying to control just to find out what the mechanisms are.
Also apologies for all of the air quotes in this ‘comment’
Popular with ravers because they’re easier to handle on the dance floor.
It would be interesting to identify drugs that behave in this way and use them as comparators.
The doses of benadryl they were giving them as an "active placebo" are approaching levels where you do start to get some... Interesting (and often extremely distressing) deliriant effects.
0/10 would not recommend tripping on benadryl,
> I will not be the least but surprised if some slow news day in Congress is filled by a Rand Paul type complaining that people are becoming alcoholics to trick doctors into giving them party drugs.
Rand Paul is a doctor by trade, I'd find it strange if doctors didn't have something to say about that, or if doctors that became politicians had nothing to say about it. Should doctors not care that people are abusing the system and lying to them in order to get prescriptions?
This is Paul's position on cannabis[0]:
> you ought to be able to pretty much do what you want to do as long as you don't hurt somebody else
and "has supported efforts to legalize in Kentucky"[0].
All in all, I don't follow your point there.
And in addition to that, anigbrowl believes Paul isn't sincere when he professes to believe that "you ought to be able to pretty much do what you want to do as long as you don't hurt somebody else", which is why they chose him as an example, but that wasn't the important part.
Maybe you'll tell me more about your belief that Paul is insincere but I don't count mind reading among my beliefs, so we'll just have to agree to disagree and - hopefully - agree that wilfully ignorant offhand remarks add nothing to HN. Perhaps take the time to find a non-libertarian, non-doctor from the Republicans to use in future and the tribalism will at least be less blatant and egregious.
The rushed rollout and forced mandates of these products across the country invited much criticism. If that's a tough pill to swallow, maybe you'd be happier in Canada or Australia, or China, for that matter - their COVID policies are basically the same in abnegating personal choice and freedom for bodily autonomy.
It's been shocking to observe how quickly society descended into "trust the science", when time and again the public has been betrayed for trusting these institutions, the pharmaceutical companies, the politicians and even scientists.
I'm not saying I agree with one side or the other completely, but it's a relief to see the tide of public opinion turning toward critical thinking. (Maybe not though, the manufacture of consent is as powerful as ever.)
Exactly.
Look to a man's actions. Ignore his words.
Plenty more than most politicians it would seem?
Possibly. But until you can control for it, you'll never know if it's real or just a placebo effect.
You can't do double-blind psychedelics trials. Researchers should stop wasting their time trying.
That's basic science.
Doing science that answers just that question would be valuable on its own. Knowing why/how it helps would be nice, but if it definitely helps…
I guess saying “this is just a sugar pill but it might help” and “this is a psychoactive substance that might make you trip a bit but also seems to measurably help some people though we’re not sure if it’s just a placebo” might have different placebo effects. Or maybe it actually works and it’s just hard to know.
The point is if it measurably works better than other substances, including definite placebos, why not use it?
We should want the outcome with sufficiently high probability and within whatever risk tolerance we define. Not the outcome in a way that satisfies a specific group of scientists. That’s not to criticise the scientists or their science, it’s important to do it, and knowing is better than not, but not knowing everything shouldn’t necessarily stop us if the risk/reward is there.
And "prove"? What does that mean? (Big epistemology rabbit hole).
I'll make the same point I did in my other comment more literally. I have a hypothesis that giving a 5k jog, three times a week to sedentary but otherwise healthy individuals will lower resting heart rate. I get my study population and randomize between treatment and control. Treatment does the running program for six weeks. Control does nothing.
Treatment has a mean reduction in resting heart rate of 4 bpm. p = 0.01. n = 200.
Have I proven anything? Do you think this was placebo? If it was debated if jogging reduced resting heart rate, was this study useful?
Possibly not practical, would need a lead in phase where people practice breathwork, then selection of people able to have an experience, then actually running the trial.
It’s hard to convey why that would be or even what a ‘mystical’ experience is, but speaking as someone who has been profoundly helped by this modality in my own journey, that finding tracks pretty well with my experience.
Obviously take studies of new findings with a grain of salt, and n=1 anecdotes even more hesitantly, but before psychedelic medicine, I was stuck in a deep depression that no psychological, psychiatric, or medical treatment could budge.
I wanted desperately for anything to help, begging for even a placebo effect I could hang my hat on!
After beginning treatment utilizing psychedelic medicine, I have been given a life I could have never imagined before. I’m not cured by any means and it’s not all sunshine and roses, but I went from virtually being a shut-in, sometimes incapable of showering even once a week, to enjoying being around people, hanging out with old friends and making new ones, and easily handling a 40-hour work week at a retail job, within 6 months. After being stuck for four and a half years before that, unemployed and numb inside.
And that’s only the quantitative, objective measures. I’ve also gained a richness in my emotional being that I was shut off from before that I’m so incredibly grateful to have received.
To be clear, this has been the most difficult thing I’ve ever done in my life, but without a doubt it has also been the most rewarding.
One more earnest warning, I’m not advocating you or anyone else pursue this treatment. While I do believe it represents a major step forward in the treatment of many forms of mental illness, it is not a magic pill or a quick fix.
It should be regarded with the same seriousness as any surgery or other major medical intervention. This stuff can be very disruptive to your life in the short and medium term and there are very real risks involved that you can’t simply hand-wave away. There are a lot of advocates in the field who I feel are too overzealous and push people towards it hard and bill it as a panacea. Do your research and be cautious, and don’t take lightly the decision to pursue this form of treatment. You are the one who must make these decisions for yourself, in your life.
If you are interested in learning about psychedelic medicine, one very helpful resource I’ve come across for beginners is “The Beginner’s Guide to Psychedelic Medicine” [1] by Tucker Max.
Best of luck to you in your journeys, all of you. And no matter what’s happened to you or what you’ve done, or what you’re going through right now, I want you to know that you matter! You deserve to have a wonderful life, and I hope that every day brings you a little closer to that lovely place, and with it a little more hope! “Remember, I’m pulling for ya! We’re all in this together!” [2]
[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707356/
[1] https://www.tuckermax.com/beginners-guide-to-psychedelics/
Please please please remember this point. If you are going to start a psychedelic journey, do some prep work first!
It seems reckless to presume the difference (between blinded and unblinded) is small. The numbers you cite (94.7% and 90% confidence) have nothing to do with the question you're trying to answer.
For example, an important difference may be with respect to expectations. If you're told you're receiving a psychedelic treatment, you may go into the experience with different expectations than if you were unsure about what treatment you were getting.
One wonders why even tried this approach, other than satisfying funding and review bureaucrats that prefer not to think.
I would imagine that everyone who got psilocybin guessed correctly.
If you stay up for 48 hours, go to sleep, get a random injection after an hour or two, wake up ~10 hours later. I would think you'd probably cut that ~90% down significantly
https://www.theguardian.com/science/2012/aug/23/lsd-help-alc...
Desperate.
It's searchable (tho not well) and you can apparently set up email alerts for new trials. Hope it helps!
https://www.australianclinicaltrials.gov.au/anzctr_feed/form
Some people, for whatever reason, are just unable to separate themselves from the experience or accept what is happening without extreme stress. It's almost like classic psychedelics act more like disassociatives for them.
manic symptoms vs. depressive symptoms can definitely be linked to strain, and the balance of constituent psychoactives...of which there are plenty. ask a reputable bud tender for sleepy weed and i wager your experience might be more pleasant.
If we’re works for you, great. If it doesn’t, something else will.
I ate 4.5g and laid on my couch with a notebook and relaxing music on. I had a list of issues that I needed to work through (obtained through the therapy), and I just sat there and ruminated on it for 6-7 hrs. It was difficult, but cathartic.
I noted my thoughts/conclusions and discussed the whole thing with my therapist afterwards, and while I can't say my depression is cured, it's much much MUCH better.
Maybe there's someone who does psilocybin research in your area? Or, remote to another area? While I'm sure literally having your therapist right there is very effective, I'm of the opinion that therapy + shrooms in general is really effective too.
Astonishingly enough, quite a huge part of the population don't seem to think this as important. This honestly shocks me.
What about ill-informed, irresponsible adults? 30% of Americans believe in astrology [1]. A growing number are anti-vaxers.
The number of people that believe some amount of utterly batshit things is not small!
Let's list them:
1. Cocoa beans 2. Coffee beans 3. Cola Beans 4. Macca 5. Ginkgo
and the list keeps going and growing every decade.
To illustrate this, I started drawing recently starting from scratch. It’s distressing to realize how much my own brain intercepts and modify what my actual eyes see, to show me a picture that isn’t reality (proportions are changed for instance, we tend to naturally draw faces without forehead when the forehead is actually half the face).
The point I’m trying to make is that the brain is very weird and biased already to make all kinds of mistakes or overlook things without adding magical thinking on top. Believing things like “it’s gods will” or “it can be prayed away” would seriously bias and interfere with treatment or available evidence, I feel.
Without the time of birth one can say very little, because the time of birth configures all of the 12 houses of the chart. The houses reflect ones experience in material reality. The sun in the 1st house in Libra is vastly different than the sun in the 12th house in Libra, to use a simplistic example.
But yes, a careful analysis of a natal chart that includes an accurate birth time and place of birth would very precisely determine someones personality. It could also determine the personalities of the parents, indicate the nature of partners and friends, health, the home and work environment and just about anything else you can think of. Not in precise specific detail (though one _can_ get specific), but thematically. And further, one can project this chart forward through time to determine future events involving said themes, also with great accuracy.
Unfortunately however, the weakest link in astrology is the astrologer, as has been said time and again. It requires extraordinary skill and learning gained through years of study, like any technical craft.
If they're not hurting anyone else, people can believe whatever they want. It's by having people try out large amounts of disparate beliefs that we can best figure out what works and what doesn't. Homogeneity is death.
[0] And see below with good comment re double blind part.
Similarly, the moral panic about psychedelics was because it threatened vested business and corporate interests (and the economic war with communism), especially when slogans such as "Turn on, tune in, drop out" because associated with them.
If he is correct then you could argue that drugs have not been seen as witchcraft since the beginning of Christianity. But I wasn't really trying to argue historical fact, simply that it's a long held mainstream belief within Christianity.
So yes it is easy to fault the Church of Rome and others like it, but also there is benefit in gentler means of enlightenment.. is that not the higher evolutionary goal? Having more powerful black-metal shows or whatever, is not fertile and not productive over time.. Whereas the focus of the Church of Rome now is the family, stability and arguably forming the social strength to make strong military. There are other groups to pick on that way, not exclusive to the Church of Rome.
I go out of my way to explain this because I also have Catholic-or-not conflicts in my own family tree.. so it is a real issue, for sure. I will also add that schizophrenia is a real and serious condition, and could be ignorantly connected to some strong drugs. Sadly, marijuana is now linked to schizophrenia in a small percentage of the population that is prone to that.. So .. more research needed.
Taking nightshades and "speaking with the devil" seems entirely plausible to what people of that cultural mindset would have experienced. Erowid's Datura experience vault has a collection of first hand accounts of the experience, and they sound quite terrifying: being in a dream-like state for days at a time with heavy amnesia, hallucinations of people who aren't really there, dark ominous imagery and out of body experiences. Much more realistic hallucinations than are reported from psilocybes. See also "flying ointment" for some interesting (nsfw) context to 'witches riding brooms".
“You understand what I’m saying? We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin. And then criminalizing both heavily, we could disrupt those communities,” Ehrlichman said. “We could arrest their leaders. raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did.”
- Nixon domestic policy chief John Ehrlichman
> Propaganda - The systematic propagation of a doctrine or cause or of information reflecting the views and interests of those advocating such a doctrine or cause.
It pays to collect a breadth of news / information from all sides and dive deep into any subject you want to know well (can't do everything).
In terms of identifying it, typically you'll see general discussion without diving into facts and / or name calling. Alternatively, you'll see downplaying of particular events, specifically of ones own "side" so to speak.
Here's a few articles that are clearly propaganda:
- "Fiery but mostly peaceful protests ..." - https://a57.foxnews.com/static.foxnews.com/foxnews.com/conte...
- "Larry Elder is the Black face of white supremacy. You’ve been warned " - https://www.latimes.com/california/story/2021-08-20/recall-c...
There's two tactics I've seen:
1. Omission - A group of similarly aligned pundits, reports, etc will not report on a topic. This is when the topic is likely partially true, but they have no response. Think "Hunter Biden Laptop" - which was reported pre-2020 election; but only reported on by the left wing news in 2022 (https://nypost.com/2022/03/17/hunter-bidens-infamous-laptop-...)
2. Propaganda - The more common thing you'll see is spin or dismissive name calling. Things like...
- "Why inflation can actually be good for everyday Americans and bad for rich people" - https://www.cnn.com/2021/12/01/economy/inflation-good-bad-wi...
I personally think the above is damage control and effectively paid propaganda. Clearly inflation is bad for everyone, no one likes paying more.
- "Climate change: How to talk to a denier" - https://www.bbc.com/news/blogs-trending-61844299
You'll see the name calling "denier" or "anti" a lot in the spins (think: "climate change denier", "election denier", "anti-vaxx", "anti-science", etc). Most of the time, if you actually read articles about said "denier", they really take a more nuanced view. The article itself is titled to attract a particular kind of reader. Often you have to read between the lines or go to a transcript to get a clear understanding of the persons views.
If you can't tell, I take particular beef with CNN. But most news on all sides of the spectrum are effectively doing the same. My particular beef with CNN started when they said (paraphrased): "It's illegal to read documents from wikileaks, you must get your news / interpretations from us" - https://streamable.com/6g5v
What I was wondering aloud is, do some people have ideas about a way to discern what's more or less propagandized? IE, even being propagandized, it is relatively less so and safer for mental health (since being scooped up into a culture war can be pretty taxing). I was asking hoping someone might chime in with different perspectives/strategies. Something I might glean insight from.
https://www.thecrimson.com/article/1973/1/24/the-crimson-tak...
Just because something grows in nature does not mean it is safe or must be tolerated.
Or possibly we are all just being blown around by the best propagandists.
You can also jump off a (naturally occurring) cliff and that’s not illegal (as long as no one pushed you I guess).
My perhaps misinformed impression of Leary was that he held the view psychedelics were best used by the intelligentsia who should then pass on what they learned to the general public. Maybe it just shifted after Leary was ostracized by academia and pushed into the same camp as Kesey in the fullness of time.
It's not something I've spent much time researching.
Speaking of tests on the unsuspecting public...
See https://en.wikipedia.org/wiki/MKUltra#Experiments_on_America...
Presuming the psychological magnitude of their experiences I can find my way into the psychology of someone being propelled into some decade long mania of propheticism and hubris (not to justify or sugarcoat the consequences).
>Interventions Study medications were psilocybin, 25 mg/70 kg, vs diphenhydramine, 50 mg (first session), and psilocybin, 25-40 mg/70 kg, vs diphenhydramine, 50-100 mg (second session). Psychotherapy included motivational enhancement therapy and cognitive behavioral therapy.
25mg is an extremely small dose! Much smaller than most micro-dose regiments at 0.5g
From another article I read:
> Common varieties such as Psilocybe cubensis and Psilocybe semilanceata contain around 6 -10mg of psilocybin per gram of dried mushrooms
So a 25mg dose of psilocybin is on the order of 2.5 - 4 grams of dried mushrooms, which is a hefty amount.
https://www.leafly.com/learn/psychedelics/how-to-dose-mushro...
Obviously the benefits is a fleeting and difficult to pin down thing. Outside of a clinical setting, experiences with psychedelics range from life-changing to life-destroying, with most people seemingly in the middle with "it's just fun". It certainly does not seem reliable.
I had actual HPPD for about a year after my trip, e.g. I could reproduce certain visual effects by looking in a certain way. I think it also caused my tendency to experience pretty strong open-eye hallucinations while meditating, which are called "makyo" in Japanese.
Of course, maybe none of this is due to the LSD usage, but I think some of it probably is.
After my 2 LSD trips with 100ug and very good setting (and I thought at the time good enough set) I slowly became very depressed and suicidal and had a total crisis. I actually had to seek out religion (which I always hated as a life long atheist) to be able to cope and not kill myself. It got close at some point and basically every since suicide has been lingering over my head. It made it a possibility: before LSD if I had stress I would lament at the world being unfair or something, after LSD if I have stress (even just minor work stress) I just can't stop thinking about killing myself. I'm on a waiting list for therapy but it is very long.
The absurd part about the LSD community is that even after telling other psych users all that, the response of about 50% of people is that I should take more at a higher dose...
(And, off-topic, but the scrollbar on the left here is interesting. Looks like it's a LTR block overflowing a RTL block. I don't think I like it, but, interesting!)