about time
May 18, 2016 1:23 PM   Subscribe

Magic Mushroom Drug Lifts Depression in Human Trial - "The findings show that more research in this field is now needed. 'This is the first time that psilocybin has been investigated as a potential treatment for major depression', says lead author Dr Robin Carhart-Harris, Imperial College London."
posted by kliuless (51 comments total) 46 users marked this as a favorite
 
This sentence really caught my eye:

All had been clinically depressed for a significant amount of time — on average 17.8 years. None of the patients had responded to standard medications, such as selective serotonin re-uptake inhibitors (SSRIs), or had electroconvulsive therapy.

Christ. How does one even stay alive through eighteen years of treatment-resistant depression? I would love to read the story of one of the people who achieved remission.

The reluctance to permit (careful) experimentation with various psychoactives to see if they can ameliorate depression is going to be looked back on as one of the great cruelties of our puritanical era.
posted by praemunire at 1:27 PM on May 18, 2016 [28 favorites]


Christ. How does one even stay alive through eighteen years of treatment-resistant depression?

Have you ever sat through a really unbearable but finite event, like a four-hour avant-garde theatrical revue? Just take the same attitude towards life itself, at all times. You don't have to do anything drastic; simply take comfort in the certain knowledge that it will, eventually, all be over.
posted by Faint of Butt at 1:39 PM on May 18, 2016 [100 favorites]


Might be THEIR first research but in Ohio in 1968-69 a fair number of tests were ran and I remember very little depression in the effects, jus' sayin'.
posted by Freedomboy at 1:40 PM on May 18, 2016 [7 favorites]


Yeah I did this as self-research in the mid 90s, it was very effective, I should ask my doctor to switch me from Wellbutrin to this.
posted by Hazelsmrf at 1:45 PM on May 18, 2016 [1 favorite]


I wonder to what extent this would apply to other psychedelics (LSD or its analogues, for example), or to substances like MDMA.
posted by acb at 1:50 PM on May 18, 2016


> I wonder to what extent this would apply to other psychedelics (LSD or its analogues, for example), or to substances like MDMA.

And if we lived in a rational world where such questions could be pursued based on their scientific merit without running afoul of short sighted, puritanical restrictions on research, we might already know the answer...
posted by mosk at 2:04 PM on May 18, 2016 [7 favorites]


Indeed. Though even now, there are loopholes.

There are, for example, LSD analogues like 1P-LSD which are legal to sell in various countries (they become illegal to sell, but not possess, in the UK in a week or two, but apparently remain legal in parts of Europe); companies like Lizard Labs which sell them (and have been doing so for a few years) do so as “research chemicals”, which raises hope that at least some of the purchasers were following the scientific method and keeping detailed notes.
posted by acb at 2:13 PM on May 18, 2016 [1 favorite]


'This is the first time* that psilocybin has been investigated as a potential treatment for major depression'

* Other than several thousand years of effective, socially sanctioned use of hallucinogens prior to the onset of civilization.
posted by crazylegs at 2:18 PM on May 18, 2016 [8 favorites]


For anyone interested in quantifying how effective psilocybin was in this trial, the study authors computed an effect size* (Hedge's g) of g = 3.1 after 1 week and g = 2.0 after 3 months.

Hedges g is a slight variation** of a very common measure of effect size, Cohen's d. Both g and d measure the difference between two groups (or the same group at different times, as in this case) in units of standard deviation. A gor d of 1 indicates that two groups/times, in the aggregate, differ by 1 standard deviation. By convention, a gor d of .2 is considered small, .5 is considered medium, and .8 is considered large. Thus, a g of 3 is enormous.

This site allows you to visualize the difference between two (normally distributed) groups for a given value of Cohen's d. Note that it only goes up to 3! Also, the number needed to treat—that is, the number of patients you would have to treat to guarantee that someone significantly improved—for a Cohen's d of 3 is 1.27. For d = 2 it's 1.48. That's astounding—essentially unheard of in psychotherapy research. For comparison, the American Psychological Association tends to quote average effect sizes of psychotherapy (entire courses of treatment of psychotherapy, not just 1 dose!) across theoretical camps in the range of .7 to 1.0.

Given preliminary results indicating an effect size this large, it is nothing short of preposterous to seriously raise the question "is this interesting enough to pursue further as a treatment for depression?" On its face, this is either a fraud/mistake of majestic proportions, or a potential breakthrough treatment for people with depression. Only in a society under the farcical shadow of the drug war could fail to take this result seriously, and only in a viciously industry- and cash-dominated mental health research arena could further research have difficulty being funded.

* Effect size allows you to go beyond the binary determination of "statistically significant" (p < .05) versus "not statistically significant" (p >= .05) to actually quantify how big the magnitude of the effect is. For anyone curious, my ballpark estimates of the 95% confidence interval of the g at 3 months is around the interval of 1.0 to 3.0.

** The difference between g and d is basically a matter of a small bias correction for small sample sizes, but they are on the same scale—namely, units of standard deviation.
posted by mister-o at 2:21 PM on May 18, 2016 [53 favorites]


How does one even stay alive through eighteen years of treatment-resistant depression?

A person can get used to anything. Especially if there isn't hope or any kind of hope of the same shitty situation ending. Your body, mind, and soul adjust to the immovable object.
posted by jenfullmoon at 2:33 PM on May 18, 2016 [12 favorites]


In mental health I've only heard of the amount of sleep deprivation a surgical resident gets through their residency in a meta-analysis on sleep deprivation having that high of cohen's d on depression (going the other way, of course).
posted by hleehowon at 2:42 PM on May 18, 2016 [6 favorites]


How does one even stay alive through eighteen years of treatment-resistant depression?

Well, I read a lot.

I used to play video games, but they make them wrong now.
posted by Ray Walston, Luck Dragon at 3:12 PM on May 18, 2016 [35 favorites]


More intuition on scale: the Cohen's d for the gender difference in height is only about 1.4. This is the only reason why they got away with that small a sample (of course necesitated by drug laws): the power's still good because the effect size is fucking amazing. Here's an astoundingly large list of effect sizes related to student achievement in school. Note that it tops out at 1.6.
posted by hleehowon at 3:25 PM on May 18, 2016 [1 favorite]


I've known people (with depression) who have experimented with microdosing to much success.
Back in my wilder days I found that one MASSIVE (scare the shit out of you, fearing you may never come back) dose could put my depression into remission for months.
posted by aloiv2 at 3:54 PM on May 18, 2016 [1 favorite]


Christ. How does one even stay alive through eighteen years of treatment-resistant depression?

Wanna hear about 50 years?

I am so excited that serious reseach is being done on this sort of treatment. Hopefully, something comes to fruition yet in my lifetime.
posted by Thorzdad at 4:16 PM on May 18, 2016 [5 favorites]


I've known people (with depression) who have experimented with microdosing to much success.
Back in my wilder days I found that one MASSIVE (scare the shit out of you, fearing you may never come back) dose could put my depression into remission for months.


I've had the same experience, and have recently been experimenting with microdosing 4-AcO-DMT, a legal (in the US) "research chemical," with good results.
posted by bradf at 4:23 PM on May 18, 2016 [3 favorites]


It's an open-label trial with n=12. The baseline standard for drug research would be a randomized placebo-controlled trial with a population 10-100x larger than that. If this was any other drug for any other disease I would call this study pretty much useless. The only reason I might give this one a pass is that a larger study isn't feasible, given the legal and cultural environment, and you have to start somewhere. Also because the lead author, David Nutt, is pretty awesome.
posted by dephlogisticated at 5:08 PM on May 18, 2016 [4 favorites]


The stated purpose of this trial seems actually to just be "we're formally establishing that this won't kill people"
posted by showbiz_liz at 5:11 PM on May 18, 2016


The stated purpose of this trial seems actually to just be "we're formally establishing that this won't kill people"

Seriously? Hell, all they had to do was ask.
posted by Thorzdad at 5:55 PM on May 18, 2016 [2 favorites]


I read a similar article a few months ago about the benefits of ketamine.

Christ. How does one even stay alive through eighteen years of treatment-resistant depression?

Well, if you have not known anything else your whole life, then you don't realize the rest of the world doesn't live like this. In some ways that makes the treatment worse, because you start a medication and for a little while the sun breaks through and you realize what you've been missing all these years. Then inevitably it stops working and you go back to where you were, with only the memory of what it could be like left behind.
posted by schroedinger at 5:59 PM on May 18, 2016 [14 favorites]


GIVE ME THE FUCKING MUSHROOMS
posted by mrgroweler at 6:00 PM on May 18, 2016 [4 favorites]


This is very old news. But good to see it making the rounds of modern times.
posted by rmmcclay at 6:03 PM on May 18, 2016 [1 favorite]


It may be old news, but these trials are the hoops we as a society are gonna have to jump through in order to end prohibition, basically. It SHOULDN'T be necessary but I'm glad it's happening. (And, proving 'common knowledge' true is a totally legit use of science!)
posted by showbiz_liz at 6:12 PM on May 18, 2016 [4 favorites]


Like, we in here can say "oh, everyone knows THAT!" But we only had anecdotes. Now there's an actual study that can be pointed to when skeptical people say "well YOU might think it's ok but I heard it makes people psychotic" or whatever.
posted by showbiz_liz at 6:18 PM on May 18, 2016 [2 favorites]


Christ. How does one even stay alive through eighteen years of treatment-resistant depression?

You don't want to know.
posted by teponaztli at 6:28 PM on May 18, 2016 [7 favorites]


Also, I'm one of those skeptical people, and I am because it's pretty heartbreaking to put your faith in yet another medication that's supposed to really work(!). And I'm sure it does! For most people. Why, lots of patients take [insert medication] and say they can't believe they waited so long to try it!

Clinical trials are great, but they're never going to be a guarantee that something is going to help you. Yeah, it can be worth trying, but forgive me if I'm not jumping for joy at [new medication that promises to really make a difference unlike all the others].
posted by teponaztli at 6:37 PM on May 18, 2016 [1 favorite]


The antidepressant effect of psychedelics, including specifically psilocybin, has been demonstrated in research before.

There was a bunch of research conducted on psychedelics in the 60's, including extensively in the field of psychology. It was well established that psilocybin made people happier (including long after the actual dose), helped with therapy, helped with PTSD...

I also recall reading a few years ago about research that found that psilocybin alleviated anxiety and depression in terminally ill cancer patients. Ah, yes, here: http://mobile.nytimes.com/2012/04/22/magazine/how-psychedelic-drugs-can-help-patients-face-death.html?referer=
posted by mysterious_stranger at 6:40 PM on May 18, 2016 [2 favorites]


Christ. How does one even stay alive through eighteen years of treatment-resistant depression?

The immense guilt that comes from potentially abandoning my family keeps me alive.
These articles make me want to cry, though, because I feel like I'll never see the relief they discuss in my lifetime, thanks to our broken social and medical systems. I hope. I do hope. Because that's all I can do.
posted by weeyin at 6:45 PM on May 18, 2016 [13 favorites]


The whole study was with 20 people, taken to get enough power for fMRI. They also did fMRI. This study had statistical power, only because the treatment was that effective. They discuss doing the RCT next, but they also note that it's basically impossible to blind the control, and the possible active placebos are all pretty idiosyncratic.
posted by hleehowon at 6:56 PM on May 18, 2016 [1 favorite]


What caught my eye here is that they gave them tremendous amounts of mushrooms. Normally, when MDMA or LSD or another potent psychedelic drug is administered in a clinical setting, the dosage is way below what would be considered recreational. Normally I repeat that to rain on the parade of fools who think getting right fucking blasted out of your mind is in any way healthy. This is surprisingly different in that the best therapeutic results occur when you get absolutely scrambled by the stuff. Very interesting.

Having had a very, very bad experience on 8 grams (that scarred me for life), I'm curious as to what the researchers did to ensure a positive outcome.
posted by constantinescharity at 6:58 PM on May 18, 2016 [5 favorites]


How does one even stay alive through eighteen years of treatment-resistant depression?

Well, I'm at about that point now. The even more depressing confession of how I stay alive is that I think about not staying alive, basically daily. Reminding myself that I could always quit if it came to that somehow helps me to avoid doing so. I'm not sure how it works, just that killing myself has been a shadow in the corner of my eye for almost two decades now, and saying "I see you there, I'll get to you when the time comes" seems to work better than trying to ignore it.
posted by gloriouslyincandescent at 8:13 PM on May 18, 2016 [14 favorites]


Dammit, this really makes a depressed square even more frustrated to not be connected.
posted by gottabefunky at 8:41 PM on May 18, 2016 [2 favorites]


I recommend acquiring pets. I know that nobody else will take my kitties, so basically when things are really tough I remind myself how much I love my cats and I stick around to make sure they get to stay together and eat the food they like and use their dumb oversized cat trees and receive all the skritches they deserve.
posted by schroedinger at 8:49 PM on May 18, 2016 [16 favorites]


(And, proving 'common knowledge' true is a totally legit use of science!)

Especially since "common knowledge" turns out to be wrong with significant frequency.

The reluctance to permit (careful) experimentation with various psychoactives to see if they can ameliorate depression is going to be looked back on as one of the great cruelties of our puritanical era.

Oh come on. I know that Mefites as a group are completely convinced that doing a ton of drugs is the One True Answer to all problems, but even if it turns out that getting really high really often solves all problems and makes you immortal our social prohibitions on psychoactive use still wouldn't rank in the top 25 cruelties of the era. It might not even make the top 100.
posted by IAmUnaware at 9:34 PM on May 18, 2016


Not even the top 100? Lucky you. You've clearly never had to deal with the hopelessness of feeling a complete lack of interest in life; the physical aches and pains that sap all of your energy; or with the exhaustion of dragging yourself through weeks, months, or even years of your life with thoughts like EVERYONE AROUND YOU WOULD BE HAPPIER IF YOU WERE NEVER BORN THEY ONLY SAY THEY CARE BECAUSE THEY PITY YOU HURRY THE FUCK UP AND DIE DIE MOTHERFUCKER DIE drowning out every other thought in your head. Must be nice.
posted by joedan at 9:51 PM on May 18, 2016 [15 favorites]


Yeah, I'm not looking for a drug to solve all my problems. I know how to solve most of my problems already. I just don't, because hey, couldn't get out of bed a) at all, or b) with enough energy to go a-solvin'. Or maybe I don't care because nothing matters and it doesn't get better.
posted by haapsane at 10:11 PM on May 18, 2016 [3 favorites]


I wonder to what extent this would apply to other psychedelics (LSD or its analogues, for example), or to substances like MDMA.

LSD was a great comfort to me as a (seemingly) seriously depressed young man. I imagine it worked for me much like the ketamine does in the limited clinical trials. I took it about once a year and it was a reset in many ways.

Oddly enough, psilocybin just made me feel sadder. My depression was much more of a serious anxiety, however, perhaps not typical clinical depression. (I still am depressed/very anxious--I self-medicate with marijuana with "OK" results. I wish I had access to LSD these days.)
posted by mrgrimm at 11:00 PM on May 18, 2016 [1 favorite]


IAmUnaware: our social prohibitions on psychoactive use still wouldn't rank in the top 25 cruelties of the era (eponysterical?)

That should be "our legal prohibitions", enforced by a quasi-militaristic strategy, most felt in supplier and some transit countries, and whose direct and indirect effects, aren't visible prominently in most of the urban middle-class US or other developed nations.

Out of curiosity and as a benchmark, which cruelties would you peg to be in the 20-25 ranks?
posted by daksya at 11:19 PM on May 18, 2016


Batman vs. Superman is surely in the top five.

How does one even stay alive through eighteen years of treatment-resistant depression?


Depression impairs one's ability to form and execute plans. When one most wants to die, one is least able to accomplish it.
posted by justsomebodythatyouusedtoknow at 12:17 AM on May 19, 2016 [5 favorites]


Normally, when MDMA or LSD or another potent psychedelic drug is administered in a clinical setting, the dosage is way below what would be considered recreational.

Previous post Therapihkal from a few months ago featured a 3 hour CBC documentary about psychedelic research into its use for treating mental illness. In it, they describe the therapy, and they make it pretty clear that they are administering a much higher dose than what would be taken for a dance or a party.

It's worth a listen, really. All 3 hours. Well written and produced, and I found it quite informative even after many years of reading about this and extensive personal research across decades.
posted by hippybear at 12:47 AM on May 19, 2016 [1 favorite]


I recommend acquiring pets. I know that nobody else will take my kitties, so basically when things are really tough I remind myself how much I love my cats and I stick around to make sure they get to stay together and eat the food they like and use their dumb oversized cat trees and receive all the skritches they deserve.

This. My really low moments have been so much more manageable when Thing 1 and/or Thing 2 do that thing where they intuitively know that something is wrong with Dad and curl up to help it all go away.

By intuition, I mean they're keenly aware if Dad cannot get up off the couch today, he's not going to be able to feed us, so we might as well invest a little time purring on his lap.
posted by scrittore at 4:41 AM on May 19, 2016 [3 favorites]


I'm in the U.S. so I just have to take my Wellbutrin and settle for naming my Shroomish/Breloom "Psilocybin".
posted by charred husk at 6:37 AM on May 19, 2016


Part of me is just cynical about psilocybin and ketamine being non-patentable and therefore not of much interest to drug companies who mostly want hyuuge profits, not reliable return selling products to make people's lives more bearable, and the government's unwillingness to consider drugs that have a recreational component for research on their other usefulness. And my doctor's lack of interest in my chronic anxiety and depression, partly managed by an SSRI that may also be causing other problems. And those of us who started on SSRIs 20 years ago are the long-term study group for the effects.
posted by theora55 at 8:46 AM on May 19, 2016 [1 favorite]


I think that cynicism is warranted, but also - look at the incredible pace of progress on legalizing marijuana. Ten years ago I would have laughed in someone's face if they told me we'd be this far along now. That suggests to me that there's reason for hope on shrooms, as well.
posted by showbiz_liz at 8:58 AM on May 19, 2016


Who didn't know this already?
posted by Liquidwolf at 10:49 AM on May 19, 2016


I don't share the cynicism. Once enough studies establish the usefulness of these drugs, there will be political pressure to get them approved. We aren't talking about some obscure plant extract that no one has heard of, with no bullhorn to get the word out. We're talking about drugs that a large share, maybe most, of the population has already heard of and knows someone who has tried. All that is needed is a shift in public perception, which seems to be happening organically.

Also, drugs can often be more patentable than they appear. For example, esketamine is an enantiomer of ketamine that someone managed to patent, presumably in part because they wanted a way to patent ketamine when its usefulness is established. Similar work could be done with psilocybin. Throw on a methyl group or something, argue it's slightly more effective, patent it, and bam, profit.

Anyway, I for one don't really want this stuff handed out only by clinicians. I want it to be acknowledged as a human right to do what we want with our minds. In the US, this principle can be respectably expressed under the aegis of "freedom of religion" as successfully argued in Gonzales v. O Centro Espirita Beneficente Uniao do Vegetal. It's well and good to seek legitimacy from a clinical angle, but doing that alone kind of misses the point, in my view. To the extent psilocybin helps depressed people, it is probably for the same reasons it helps for those who aren't suffering mental illness. I don't want to have to feign mental illness to take psilocybin, and I don't want the manner in which I do so to be tailored for clinical legitimacy.
posted by andrewpcone at 12:10 PM on May 19, 2016 [5 favorites]


I'm still waiting for the no-adverse-side-effects Ketamine treatment I heard about a few years ago.
posted by Brocktoon at 1:20 PM on May 19, 2016


I wish I had access to LSD these days.

As mentioned upthread - you do.

1P-lsd is not illegal in the U.S. (yet).

A little googling offers some providers, as well as discussions on the merits of same. There is some hoop jumping involved, likely in the form of dealing with bitcoin for payment.

Still - strange days.
posted by not_that_epiphanius at 4:50 PM on May 19, 2016 [2 favorites]


I recommend acquiring pets. I know that nobody else will take my kitties, so basically when things are really tough I remind myself how much I love my cats...

posted by schroedinger


Eponysterical.
posted by acb at 4:47 AM on May 21, 2016




I wish I had access to LSD these days.

As mentioned upthread - you do.

1P-lsd is not illegal in the U.S. (yet).

A little googling offers some providers, as well as discussions on the merits of same. There is some hoop jumping involved, likely in the form of dealing with bitcoin for payment.


Yeah, and a lot of those googled links are defunct or soon will be. Also, I'd be afraid that buying any chemicals (especially in bulk) from a foreign country is going to get me arrested. So no, no real access to LSD.
posted by mrgrimm at 12:05 PM on May 25, 2016


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