This is your brain. This is your brain on drugs.
April 12, 2016 4:46 AM   Subscribe

The profound impact of LSD on the brain has been laid bare by the first modern scans of people high on the drug. The images, taken from volunteers who agreed to take a trip in the name of science, have given researchers an unprecedented insight into the neural basis for effects produced by one of the most powerful drugs ever created. [Guardian link]

Link to original paper, which contains more images and detailed information. (Of note -- brain scans of the same people on both placebo and active agent 2 weeks apart are compared for the study.)
posted by hippybear (66 comments total) 43 users marked this as a favorite
 
Not the first study by David Nutt, Robin Carhart-Harris and the rest of this research group at Imperial College London; they have previously done similar neuroimaging work on the effects of psilocybin. Because I'm sure it will come up, another study of theirs addresses the possible psychotherapeutic effects of psilocybin, stemming from the fact that it enhances autobiographical recall. They've also published on the "paradoxical" benefits of LSD, with the paradox being that it generates psychosis-like effects in the short term followed by heightened emotional lability which (they conjecture) can lead to longer-term well-being.

Also, notice that Amanda Feilding is among their co-authors. In addition to her work on public policy relating to hallucinogens, you may know her as the artist who once trepanned herself.
posted by informavore at 5:14 AM on April 12, 2016 [7 favorites]


I had no idea it makes your brain so cheerful-looking.
posted by ostranenie at 5:49 AM on April 12, 2016 [5 favorites]


Scientist finds that LSD use enhances optimism, announces it could improve the mental health and well-being of normal people, could turn out to be the Higgs Boson of neuropsychology.
posted by Segundus at 5:53 AM on April 12, 2016 [2 favorites]


After an epic mushroom experience while alone in the forest for a week or so, I returned to my job in the real world with an utterly different attitude. Co-workers all said things like "Wow, you must have had an amazing vacation! You're so HAPPY!" And "Gee, you seem so much more relaxed and open now than before you went away, what happened?" The euphoria went on and on, long after I'd metabolized the last of the psilocybin.

I daresay the experience changed me permanently--I became a much more accepting and grounded a person as the result of a few hours spent whooping for joy in the trees. It was a major turning point and altered my priorities forever. Sadly, I later learned that not everyone can handle an experience as intense as mine turned out to be. You have to have a good idea of who you really are and possess some discipline over your own thoughts or things can get dicey. It's not for everyone but it surely did help me.

The last psychedelic experience I had involved some very clean windowpane and a long day in the museums of D.C. I enjoyed boundless energy and curiosity and every exhibit, every artwork was fascinating. I was peaking as we entered the entertainment section of the American Museum and my sister--who was not tripping and in fact did not know I was--commented that she knew nothing of the items in the case before us, which traced the history of American entertainment. I found that every single thing I'd ever read about what we were seeing was instantly accessible, and additionally I had new insight. I was able to discuss 19th century dialect comedians and their context within a country of immigrants as we viewed Harry Lauder's cane, the role of vaudeville and the rise of film and radio and television as we studied Charlie McCarthy, the ruby slippers, etc. It was like an informational orgasm--everything was fascinating and meaningful. In the midst of this I looked up to discover that perhaps a dozen museum goers had drifted over and were raptly following my analyses. When I reddened and explained that I was not in fact a museum tourguide, someone quickly said "that's okay, can we listen anyway? What you're saying is very interesting." Later that day I broke down a Helen Frankenthaler painting at the Hirschorn such that a guard stopped us to say that it was a favorite and that he'd loved my interpretation. It was one of the most enjoyable days of my life.

Powerful medicine indeed.
posted by kinnakeet at 6:05 AM on April 12, 2016 [117 favorites]


I really hope all this recent research on psychedelics has an effect on its demonization and criminalization in the US. I look forward to, fifteen or twenty years from now, living in a world with relatively easy access to psychedelics for both therapy and recreation, without all the stigma of being a dirty hippy weirdo.
posted by dis_integration at 6:08 AM on April 12, 2016 [3 favorites]


Heartily concur with kinnakeet's report, and have had analogous experiences which I won't bore eveyrone with (except being asked to explain the Dobbshead T shirt while tripping far too hard for comfort in the Tate. That was... a thing).

LSD and psilocybin are doing and thinking drugs just as much as they are introspective and deconstructive. There really is a lot to explore - oh, if only we had the frameworks and protocols and support to do so safely and legally. It makes me so sad that we've wasted half a century (at the same time, hey, it's not been entirely wasted).

Coincidentally, Radio 4 ran a drama yesterday, The Liberty Cap, about the experimental use of psilocybin in depression. From the description:

The Liberty Cap is written by Hattie Naylor (award winning playwright whose many plays include Ivan and the Dogs and The Diary of Samuel Pepys) and made in consultation with Dr Robin Carhart-Harris, a psycho-pharmacologist at Imperial College London, who is conducting research into psychedelic drugs and their potential therapeutic uses.

Scientific research into psychedelic drugs has been effectively shut down for decades but is now becoming more widespread. The action of this drama is inspired by clinical trials that are currently taking place and the ethical questions they raise, although all characters portrayed are entirely fictional.


It's pretty good, and makes good use of sound to illustrate the psychedelic experience. Should be available worldwide at that link for a month.
posted by Devonian at 6:32 AM on April 12, 2016 [2 favorites]


It was like an informational orgasm--everything was fascinating and meaningful.

Once while I was tripping balls I lectured a business student on Lew Welch, Joseph Campbell, and the redemptive power of myth.
posted by octobersurprise at 6:33 AM on April 12, 2016 [5 favorites]


All you guys had profound intellectual experiences on acid. I just fell down a deep fucking hole and shattered into a million pieces, then spent the next twelve hours curled in a ball on some stranger's bed trying to pull the fragments of me back together enough so that I could take a few steps without screaming.

I did everything you're supposed to do (dropped with friends, in a safe place, with fun and interesting things to do). It sucked. A lot.
posted by xthlc at 6:43 AM on April 12, 2016 [16 favorites]


Once upon at time, in a land now far away, I sailed into a supermarket in Crouch End (London)... to be brought short by the neon day-glo pulsating colours of a long rack of tins of Heinz Baked Beans. I retreated post-haste.
posted by Mister Bijou at 6:45 AM on April 12, 2016 [4 favorites]


Oh God do not ever go in a supermarket
posted by thelonius at 6:47 AM on April 12, 2016 [31 favorites]


One of my most memorable experiences involving dropping acid was realizing that I was pretty sure the Lion King was only 30 minutes long.

I actually really liked taking acid when I was young, but I wouldn't do it now, mostly because my brain got scarier as I got older. (The nascent anxiety and depression from my youth has blossomed into a place I would not want to visit as a high adult.)
posted by Kitteh at 6:47 AM on April 12, 2016 [10 favorites]


One of my most memorable experiences involving dropping acid was realizing that I was pretty sure the Lion King was only 30 minutes long.

What on earth was your most forgettable one? That time you became convinced the train left at 8.35 instead of 8.42?
posted by Segundus at 6:49 AM on April 12, 2016 [19 favorites]


Your eyes collect raw visual data, but what you "see" is meaning derived from that data. The visual cortex has pattern detection circuits that are designed to identify certain components of visual data--simple things like edges and symmetry--and those feed into higher-level circuits that detect things like shapes, and those in turn feed into higher-level circuits that identify objects, faces, words, etc. (processing can also be "top-down"--being primed to identify an object makes it easier to do so). Turning up the sensitivity of those circuits increases their ability to identify patterns, but also increases the likelihood that they will detect patterns in random noise. By disinhibiting the visual cortex and enhancing resting-state connectivity with other areas, LSD and other hallucinogens greatly increase your tendency to "see" patterns that aren't there.

There's a theory that something similar happens when your visual cortex is starved of information, which is why sensory deprivation or vision loss can produce visual hallucinations. It may also be relevant to dreaming.

The fact that the hallucinations that LSD produces are simple and geometric in nature, and generally able to be distinguished from reality, suggests that it acts primarily on lower-level circuits, at least in terms of visual processing. Anticholinergics, in contrast, can produce complex delusions, acting more on the level of comprehension than on visual mechanics.
posted by dephlogisticated at 6:50 AM on April 12, 2016 [15 favorites]


The fact that the hallucinations that LSD produces are simple and geometric in nature, and generally able to be distinguished from reality...

Someone has not heard about "heroic dosing."
posted by StickyCarpet at 6:56 AM on April 12, 2016 [5 favorites]


Yeah, at high doses anything goes, but that's basically true of any centrally-acting agent, including drugs that aren't classified as hallucinogens. Benadryl, for instance, is psychomimetic at high doses.
posted by dephlogisticated at 7:15 AM on April 12, 2016 [3 favorites]


I did everything you're supposed to do (dropped with friends, in a safe place, with fun and interesting things to do). It sucked. A lot.

To be fair, you did all the things you're supposed to do and that's why it ended safely. I'm sorry it sucked for you but good on you for taking proper precautions.
posted by VTX at 7:28 AM on April 12, 2016 [8 favorites]


I both enjoyed and found therapeutic my past experiences with LSD and psilocybin, but I'm with Kitteh in that I'm not sure if I'd repeat those experiences more. My last time with LSD was when I was in a bad place mentally, and it really did not help, to say the least. I absolutely think the bans on exploring their therapeutic potential is ridiculous, but I also realize that they are powerful substances that work best when you are working best.
posted by Panjandrum at 7:30 AM on April 12, 2016




I got pissed off at a shirt, walked 1/4 mile towards a giant glowing can of Pepsi and then, using money, bought a tiny Pepsi machine from it, had a semi-religious experience listening to Ozzy Osborne, and spent half a shift at Burger King watching cheese slices melt in the fryolator. Among other things.

I suspect my brain was mighty colorful those days.

I was young and invincible then. I would never in a million years do it now.
posted by bondcliff at 7:31 AM on April 12, 2016 [3 favorites]


i am in exactly kitteh's space. i had fun when i was younger (although it did take me years to enjoy kissing again after one trip) but i don't think i'm wired for that sort of experience any more.
posted by nadawi at 7:32 AM on April 12, 2016 [2 favorites]


Acid and mushrooms are not for everyone. To say the least.

One friend begged me to trip with her even though my instincts told me she was a bad candidate, freighted with difficult issues that tripping was unlikely to resolve. I tried to lock down a safe, peaceful weekend space for her, got everything I could in line (music that she loved and responded well to, some good wine, some pleasant visuals) but when the time came she basically went into the same mode exthlc described above. I did what I could to talk her into a more positive space, but she was overtaken by her demons.

I recognize that there are phases of a trip that are transitional and difficult. Mushrooms have a stage where there's nausea, dysphagia and other unpleasantness. Experience has taught me that, for me at least, this can be gotten through, and the results are worth the effort. In my friend's case, however, the drug led her in a bad direction from which she was unable to disengage.

Now that a number of years have passed since my last experience I'm not sure I want or need to pass through that particular portal again. Psychedelics tend to make one hyperaware of one's physical being, and now that my frame has more wear on it I'm not sure I want to go there. If someone handed me a clean blotter as I stood inside the MOMA, I might reconsider.
posted by kinnakeet at 7:57 AM on April 12, 2016 [4 favorites]


Reminds me of the revival of the use of psilocybin for terminal cancer patients.
posted by clawsoon at 7:57 AM on April 12, 2016 [2 favorites]


The visual cortex has pattern detection circuits that are designed to identify certain components of visual data--simple things like edges and symmetry--and those feed into higher-level circuits that detect things like shapes, and those in turn feed into higher-level circuits that identify objects, faces, words, etc. (processing can also be "top-down"--being primed to identify an object makes it easier to do so).

Is the mind a machine or a comptuer? I don't think so. No circuits up here in my brain. Unless you're a cyborg. You can be a materialist without falling prey to the idea that the brain is a computer, or that thought is calculation. Reason has capacities broader than mere reckoning, like consciousness, apperception, artistic insight, and the capacity to perceive the good.
posted by dis_integration at 8:05 AM on April 12, 2016 [1 favorite]


I actually really liked taking acid when I was young, but I wouldn't do it now, mostly because my brain got scarier as I got older. (The nascent anxiety and depression from my youth has blossomed into a place I would not want to visit as a high adult.)

Sigh, yes, this. The last time I tripped I had a bad trip for a bit (presaging future problems with crowd-claustrophobia), which then resolved. I watched trees dance on the beach for a couple hours.

No circuits up here in my brain. Unless you're a cyborg. You can be a materialist without falling prey to the idea that the brain is a computer, or that thought is calculation. Reason has capacities broader than mere reckoning, like consciousness, apperception, artistic insight, and the capacity to perceive the good.

All of which are caused by different parts--circuits, if you will--of your brain processing information in different ways.
posted by feckless fecal fear mongering at 8:08 AM on April 12, 2016 [5 favorites]


I dropped the last tab of yellow sunshine as we crossed the Currituck bridge. Avalon Pier was silhouetted in the glare of the rising sun. By the time I got to Jeanette's Pier, I was fully peaking. The water was cold and a light NW breeze raised a pattern of small ripples on the face of the water, each green edge reflecting the yellow orange sun. Schools of menhaden outside were dark spots being harried by diving birds. Sharps edges of color streaked from every ripple.

Robbie whistled and I looked out to see a set peaking over near the pier. Paddle, paddle paddle, focused on the sheer muscular feedback of moving through the water, the tail of my board being lifted up, then standing. Cold spray in my eyes, closing them, and turning at the bottom blind. The wall was a perfect set up I see even today. Trim, tuck, the lip coming over and - smack - right in the face. Bounced off the bottom and coming up as the second wave in the set is pitching over right on my head. A quick breath then back to the washing machine. Kick to the surface again but now I've washed in enough to be out of the impact zone. I body surf in and get my board - totally sober except for the trails.

The pictures in the linked article are pretty but not too informative. Consider the locus ceruleus. Activation of this small group of neurons inhibits muscular activity in the sleeping animal. Ablation of this nucleus causes cats to get up and act out their dreams, not the occasional twitch. The observation of widespread increased metabolic rate in neurons does not mean that the drug acts on all those neurons directly. Stimulation or inhibition of a small area can have widespread effects on the entire cerebrum. Data from mapping of receptor types using labelled ligands is necessary to interpret these findings.

What is interesting is that repeated stimulation and release of neurotransmitters is also trophic and creates new synapses. Repeated use can actually change personalities long term, which we already knew.
posted by sudogeek at 8:09 AM on April 12, 2016 [1 favorite]


@sudogeek - speaking from personal experience as well, Outer Banks trip = best trip...
posted by kuanes at 8:12 AM on April 12, 2016


I have also traversed the Hallways of Always. Saw some freaky stuff there. Saw Big Sky Mind, too. Later, I was lucky enough to attend a Buddhist university and study psychology in a master's program whose curriculum was designed by a "crazy wisdom lineage" Tibetan monk and heavily informed by the experiential knowledge of psychedelics. A very humane and nuanced clinical framework for dealing with all kinds of mental states grew out of it. Also, if this kind of thing is your bag, I recommend the brilliant Storming Heaven: LSD and the American Dream, by Jay Stevens.
posted by Bob Regular at 8:17 AM on April 12, 2016 [3 favorites]


I'm sold. Meetup?
posted by naju at 8:29 AM on April 12, 2016 [6 favorites]


Don't wanna blow anyone's cover, but one of the authors is MeFi's own :-)
posted by busted_crayons at 8:31 AM on April 12, 2016


Yo, @sudogeek, your OBX experience brought back a memory.

I grew up going to Nags Head annually beginning in 1960, stopping in the late 70s when development overtook the islands. I returned in the late 80s and was tempted to try a little mushrooming there. The memory of what the area had been vs what it had become was so overwhelming it resulted in one of the very few truly bad trips I ever experienced.

Still can't get over Jeanette's being made of concrete, BTW.
posted by kinnakeet at 8:31 AM on April 12, 2016


All of which are caused by different parts--circuits, if you will--of your brain processing information in different ways.

I don't want to derail this into a debate over the computational theory of mind. Suffice it to say that I disagree, and have good philosophical reasons for doing so. In the context of psychedelic experiences, my intuition that the brain is not computational in any traditional sense comes from my tripping days, which gave me the insight that we have to leave room for the capacity for radical, uncalculated moral insight, the kind we get in a rapturous or mystical experience like tripping, and that reducing the human being to a calculating machine is dangerous. We are more than calculating machines, we are material spirits. (It is no coincidence that we have a tendency to describe the human being using the metaphor of the most advanced technology we know. In the 17th & 18th century we were a pneumatic-mechanical system of pulleys and levers, today we're a computer. Whatever comes next, we'll start thinking of ourselves in those terms as well. Humanity exceeds whatever mechanistic metaphor we attempt to subsume it under, because of its spiritual nature).
posted by dis_integration at 8:31 AM on April 12, 2016 [6 favorites]


Yeah, no. Assumes facts not in evidence. Everything we think, do, say, comes from the interactions of however umpty-many grey cells in the old noggin. There's nothing else.
posted by feckless fecal fear mongering at 8:33 AM on April 12, 2016 [1 favorite]


Mushrooms have a stage where there's nausea, dysphagia and other unpleasantness.

This reminds me of a question I had when I read that New Yorker article linked above, about the use of psilocybin for terminal cancer patients. I had always heard that mushrooms first made you vomit (or maybe I'm conflating them with peyote), but I haven't heard nausea mentioned in these new articles about research into its effects. I wondered, does the nasuea only happen if you actually ingest the mushrooms vs. somehow taking only the psilocybin drug? Like, is there some way of taking the drug that doesn't make you nauseous first?
posted by dnash at 8:39 AM on April 12, 2016


I've been tripping many times but the last one was a wild one. Over a sequence of trips I'd had periods of unease where it felt like something big was getting ready to come up but not quite. I have a dark past, a family history of trauma and abuse, and my own share of demons, and I had been working through a lot of this.

In the final trip, my most recent, it finally broke and it was like some kind of psychic storm. Lying on the bed the room started to spin and I felt the wind pick up and start to whip and blow things away. The parts of me that I defined through my relation to others; the mythology of my family and my country; the parts of my partner's personality that I had borrowed and used as my own; the certainty that things would always work out; all not rooted, all gone. I felt a real risk of being blown away completely and if that had happened I would have been gone altogether and I don't know what happens then. Probably something like being curled up in a ball for hours. But because I had tripped many times and worked through enough I felt a few parts of me anchored to the ground, like strong beams in a barn that held as the tornado blew the roof and walls away. I am alive, this much I know, and this is enough to build on.

In this moment I found an opportunity to define myself, free at last of all the things other people had burdened me with. I defined a moral code and a purpose that flowed from it. No longer plagued with indecision or tortured by expectations, I live with a settled calmness and steadiness now. But I can't live in the world the same way. All around me I just see layers and layers of indescribable pain and suffering. It drips from the walls, everywhere.

I'm fairly convinced that The Matrix is about LSD. The experience of taking a pill and having your reality ripped away and finding that the whole world is some kind of collective fiction and that really we are all living in a slavery that we were born into. Waking up and finding reality being indescribably dark and yet knowing that it is true and you can never go back, though perhaps part of you wishes you could. Why do my eyes hurt? You've never used them.
posted by anybodys at 8:40 AM on April 12, 2016 [6 favorites]


"Today, a young man on acid realized that all matter is merely energy condensed to a slow vibration, that we are all one consciousness experiencing itself subjectively, there is no such thing as death, life is only a dream, and we are the imagination of ourselves. Here's Tom with the Weather." -- Bill Hicks.
posted by DirtyOldTown at 8:59 AM on April 12, 2016 [16 favorites]


I found the experience of acid pretty "meh" back in my 20s. Not negative, just not my bag. I'm generally more inclined toward either speedy things or alcohol. But now that I'm in my 40s, dealing with some stubbornly intractable low-level depression and ennui, having now seen at least four articles on the therapeutic potential of psychedelics, I have to say that my interest in tripping has been piqued.
posted by desuetude at 9:03 AM on April 12, 2016 [5 favorites]


Ketamine also seems to have effects on depression (both from studies and anecdata from myself) without the potential pitfalls of full-on acid/shrooms tripping.
posted by feckless fecal fear mongering at 9:04 AM on April 12, 2016 [2 favorites]


I first heard that quote as part of some album track. It has since struck me that it aligns pretty well with my understanding of string theory. I know it's supposed to sound like a deep, drug inspired, hippy-dippy sort of observation but when I hear it I just think, "Wait, isn't that just string theory?"

It would be like me tripping balls and saying something, "Duuuude, you what people need? They like, need a place to have a real, elemental fire INSIDE their house! That way people could live in their modern homes and still feel connected to the caveman lifestyle."

"Um yeah, we have that. It's called a fire-place and you've been staring at ours for the last two hours."
posted by VTX at 9:13 AM on April 12, 2016 [3 favorites]


Is the mind a machine or a comptuer? I don't think so. No circuits up here in my brain.

Visual processing is one of the areas of neurobiology most amenable to reductionary analysis, and hence one of the things we understand best about the brain. It's a so-called "easy problem": not because it's simple, but because it's explicable. We don't know why red looks so red (a "hard problem" of consciousness, concerning subjective experience), but we do know how the mapping of neuronal connections distinguishes a line. In fact some of the preliminary processing is done by the neurons in your retina. You can literally map them out like a circuit diagram and it makes sense.

Whether the whole brain can be understood in this fashion is a different question--one that differs in terms of scale and complexity if nothing else.
posted by dephlogisticated at 9:21 AM on April 12, 2016 [7 favorites]



Yeah, at high doses anything goes, but that's basically true of any centrally-acting agent, including drugs that aren't classified as hallucinogens. Benadryl, for instance, is psychomimetic at high doses.


Diphenhydramine has anticholinergic action, which means at high doses it acts similarly to scopolamine, atropine, and the other delieriants you were just talking about. It should be "classified as a hallucinogen" if they are.
posted by atoxyl at 9:34 AM on April 12, 2016 [1 favorite]


Is there inherently something wrong with just agreeing that, whether the brain actually functions like a circuit or not, it's a useful metaphor in this context?

Then we can maybe move past this derail.
posted by VTX at 9:38 AM on April 12, 2016


Doing mushrooms was like having an entire happy childhood in one afternoon, and I only did a sixteenth of an ounce. The effects stayed with me for months if not years.

Meanwhile, legally prescribed antidepressants deleted my sex drive, added 25 pounds to my frame, and were less effective at the whole "making me not depressed" thing.

I'm excited we're probably close to being able to really study the medical potential of marijuana, but I think it may pale in comparison to what we might be able to accomplish with mushrooms and other drugs of that kind. If only they'd LET people.
posted by showbiz_liz at 9:57 AM on April 12, 2016 [8 favorites]


I don't know. The data suggesting long term therapeutic results for psychedelics actually kind of makes me nervous. Because if it makes permanent positive changes to the brain, that suggests it can also make permanent negative changes. I had generally classed the various "she jumped out of a window because she had taken acid in the past and had a flashback" type stories from the 60s and 70s as the usual drug war stuff, but maybe that's not entirely so.

That's not to say that they shouldn't be used, especially since chronic depression is one of the most deadly and intractable kinds of mental illness. But I would be extremely wary of them.
posted by tavella at 9:57 AM on April 12, 2016 [4 favorites]


I have to say that this whole thread is a mini-trip in and of itself. I love it.
posted by blucevalo at 9:58 AM on April 12, 2016 [1 favorite]


Diphenhydramine has anticholinergic action, which means at high doses it acts similarly to scopolamine, atropine, and the other delieriants you were just talking about. It should be "classified as a hallucinogen" if they are.

Drugs rarely hit only one target and activity at a target is a function of concentration (in pharmacology this is quantified as the dissociation constant). A great many drugs have some degree of action at cholinergic receptors (this is a big problem in geriatric pharmacy because the elderly are particularly sensitive to these effects). It wouldn't make sense to classify all of those drugs as hallucinogens. Instead, by convention, you generally classify drugs based on their most common uses or most prominent effects. So diphenhydramine would be an antihistamine in most contexts. Scopolamine and atropine would be anticholinergics because that's their primary use.
posted by dephlogisticated at 10:02 AM on April 12, 2016


Benadryl, for instance, is psychomimetic at high doses.

Yeah is it! I mean... so I've been told...

Voice of Glenda the Good Witch emanating from the kitchen sink: "Your car keys fell behind the dresser and your self is a collection of incidental interactions reflecting a cosmic light of consciousness."

Thanks, I've been looking for those.
posted by cmoj at 10:19 AM on April 12, 2016 [5 favorites]


I know we’ve had this discussion before, but my experiences were less than fantastic. Many years ago I did acid once (?) and mushrooms several times (even though I never liked it, that was the way I rolled back then). I was always sick, weird, wired and uncomfortable. The closest thing I can relate it to is staying up for days drinking coffee. Much like that it seemed to go on forever. The best part was when it was finally over and I fell asleep the next day.

It’s amazing to read how different other people’s experiences were.
posted by bongo_x at 10:22 AM on April 12, 2016


I found that every single thing I'd ever read about what we were seeing was instantly accessible, and additionally I had new insight. [...] It was like an informational orgasm--everything was fascinating and meaningful.

this rather aptly describes the first few hours of the most harrowing psychedelic experience I ever had. I was intellectually firing on all cylinders, and communicating it all effortlessly. Until something happened ...

I just fell down a deep fucking hole and shattered into a million pieces,

and I rather went the other way. The metaphor that I eventually arrived at was that of a viewpoint, there being a great valley below and the closer you got to the edge the better the view got, but the actual edge was unclear, unmarked. the only way to find the very best view was to go one step too far, and then off you went ....

Not to your death, but a hell of a fall regardless. One hopes that as we do a better job of allowing psychedelics into our culture, we get better at noting the edges and how to assist those who've gone and found them.
posted by philip-random at 10:34 AM on April 12, 2016 [2 favorites]


Drugs rarely hit only one target and activity at a target is a function of concentration (in pharmacology this is quantified as the dissociation constant). A great many drugs have some degree of action at cholinergic receptors (this is a big problem in geriatric pharmacy because the elderly are particularly sensitive to these effects). It wouldn't make sense to classify all of those drugs as hallucinogens. Instead, by convention, you generally classify drugs based on their most common uses or most prominent effects. So diphenhydramine would be an antihistamine in most contexts. Scopolamine and atropine would be anticholinergics because that's their primary use.

Sure I guess it's just when you said "at high doses anything goes, but that's basically true of any centrally-acting agent" and then brought up Benadryl as if it were a big surprise I was thinking, not really, it has a very anticholinergic side-effect profile and has occasionally been used for related indications.
posted by atoxyl at 11:12 AM on April 12, 2016 [1 favorite]


... at high doses anything goes...
Looking forward to Maureen Dowd's column.
posted by MtDewd at 11:12 AM on April 12, 2016 [6 favorites]


And as far as I know scopolamine isn't generally prescribed for the purpose of inducing hallucination so attempting to strongly enforce the boundaries of that category just seemed a little strange.
posted by atoxyl at 11:26 AM on April 12, 2016 [1 favorite]




thelonius: "Oh God do not ever go in a supermarket"

Hey! Have some other not great places!
Disneyland
A record fair*

*Though I did only spend $20 and walked out with more me holding a stack of 30+ dusty records like some sort of cartoon character.
posted by wcfields at 11:39 AM on April 12, 2016


Oh, man, tripping at Disneyland has been some of the most fun I have ever had in my life. Take a 5 minute walk and you're in a completely new engineered environment with a lot new to explore! I'd do that again tomorrow if I lived close enough and could afford admission.
posted by hippybear at 11:43 AM on April 12, 2016 [1 favorite]


the best place to go when you've had some mushroom tea:

a crystal fair
(the kind where they have trays of crystals in shallow water, especially)
posted by burgerrr at 11:46 AM on April 12, 2016


I think I started off on the wrong foot a little though I hadn't intended simply to be pedantic about it I just wanted to fill in a little more "5-HT2A agonists tend to do this, muscarinic antagonists tend to do this, dopamine D2 agonists tend to do this" (some of these are not recommended and not psychedelic) beyond whether things are traditionally classified as psychoactive or not. As dephlog said most drugs are really hitting different targets to different degrees.

Some young or desperate users looking to try diphenhydramine might pick up a product (such as Benadryl Cold) that contains a combination of medicines, including acetaminophen. Products containing acetaminophen should NEVER be used recreationally, even once. The dosages of products necessary for recreational use will deliver a potentially liver-damaging amount of acetaminophen. Especially in combination with alcohol, with repeated doses, in combination with other drugs, or in sensitive people, acetaminophen can lead to permanent liver damage, liver disease, or even death.

Fair warning but:

a.) pure diphenydramine is not hard to find
b.) it's a pretty bad idea in iteself
posted by atoxyl at 11:58 AM on April 12, 2016




traditionally classified as psychoactive

psychoactive in an interesting/recreational way I mean - we all know DPH will put you to sleep
posted by atoxyl at 1:25 PM on April 12, 2016


The psychedelics (meaning the tryptamines and phenethylamines) have a pretty unique profile in terms of the type of hallucinations they produce. Delirium, though, is a much more common and nonspecific effect. Just about any CNS-acting drug has the potential to produce delirium in the context of overdose. Certainly the anticholinergics, but you also see delirium with benzos (a significant problem in the ICU setting), opioids (especially those with kappa receptor activity, like pentazocine), antidepressants (serotonin syndrome), stimulants (acute psychosis), the dissociative anesthetics, cannabinoids, etc. Hit the gas hard enough on any of the major neurotransmitter systems and shit hits the fan.

Anticholinergic effects can be therapeutic or harmful, depending on the context. Delirium is one potential effect (not a desired one obviously), but there are a bunch. In the case of diphenhydramine, the anticholinergic effects are largely incidental to its use, though the drying can be useful with seasonal allergies. It does carry an indication for EPS, but in practice the default is benzatropine because it's less sedating (no significant H1 activity). Scopolamine, like benzatropine, is pretty selective so the anticholinergic effects are the whole reason for using it.
posted by dephlogisticated at 2:38 PM on April 12, 2016 [2 favorites]


opioids (especially those with kappa receptor activity, like pentazocine)

The active ingredient of Salvia divinorum is also a κ-opioid receptor agonist.

you also see delirium with benzos

A number of drugs that mess with GABA can do interesting things too - e.g. Muscimol from psychoactive Amanita mushrooms or Ambien and the other Z-drugs as has become fairly infamous.

again sorry if it came off like I was picking a fight with you my intended point was pretty compatible what you're saying I think - there are multiple pathways that can induce profound alterations of consciousness in ways that are sorta-psychedelic-like but subjectively distinct and not fully captured by categories like "hallucinogen" or "deliriant" or even "psychedelic" (which I also think is best reserved for the classic 5-HT2A drugs).
posted by atoxyl at 4:02 PM on April 12, 2016


No worries, I'll take any excuse to geek out on psychopharmacology. If you're interested in kappa receptors and the neural correlates of consciousness, check out Stiefel et al. It's mostly just conjecture but it's damn interesting conjecture.
posted by dephlogisticated at 5:03 PM on April 12, 2016 [1 favorite]


Benadryl, for instance, is psychomimetic at high doses.

Hey so as someone who has often taken large doses of Benadryl to sleep, how high are we talking? I'd always assumed that the occasional hallucinations I had then were due to the sleep deprivation that had motivated me to take so much in the first plae, but maybe it was the Benadryl itself?

(These days I try to stay under 100mg/night because beyond that I risk entering that awful "I really have to pee but I can't pee" stage of Benadryl overdose.)
posted by Jacqueline at 6:57 PM on April 12, 2016




My, oh my, where to begin... The Capitol Theater in Port Chester or the Philly Spectrum...
posted by mikelieman at 11:20 PM on April 12, 2016 [1 favorite]


bad acid trip :P
David Shapiro wanders around the beach for a few days in a newspaper suit. A cartoon odyssey.
posted by kliuless at 5:32 PM on April 13, 2016


Psychedelics tend to make one hyperaware of one's physical being, and now that my frame has more wear on it I'm not sure I want to go there.

Yup. One of my most distinct memories as a teenager was urinating and thinking "I am an animal who is going to die, full of smooshy gushy tubes of liquid."

It also made me more aware of how deadly smoking is, but it took another decade for that to really kick in enough to quit.
posted by aydeejones at 12:07 PM on April 26, 2016


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