How Hallucinogens Play Their Mind-Bending Games

complexPHILOSOPHY

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Zeroing in on a group of cells in a high layer of the cortex, a team of researchers from Mount Sinai School of Medicine, Columbia University and the New York State Psychiatric Institute may finally have found the cause of the swirling textures, blurry visions and signal-crossing synesthesia brought on by hallucinogenic drugs like LSD, peyote and "'shrooms." The group, which published its findings in this week's issue of Neuron, may have settled a long-simmering debate over how psychedelic drugs distort human perception.
"There's this huge body of literature about these compounds, and I think this paper begins to nail down how the heck they're working in the brain," says Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill. "It's not the end of the story, but I'd say it's the end of the beginning of the story."

Since the 1980s researchers in this field have agreed that LSD, which was first synthesized by Swiss scientists in 1938, likely affects serotonin 2A receptors in the brain (serotonin is a neurotransmitter suspected to play a role in the communication of mood and consciousness). These receptors show up in many places in the brain, including several areas in the cortex (known for sensory perception), and the thalamus (an interior region known for relaying messages to the cortex as well as regulating arousal and awareness).

The current research was performed by creating a mouse model that enabled scientists to observe behavioral and cell-signaling responses to hallucinogenic drugs by comparing them with those triggered by lisuride, an anti-Parkinson's disease drug chemically similar to LSD that does not have hallucinogenic effects. After determining that mice given psychedelic drugs consistently experience head twitching, the team bred mice with the serotonin 2A receptor knocked out to determine whether the hallucinogens still caused head twitching.

After testing many candidate regions, the researchers localized the effects of hallucinogens to the pyramidal neurons in layer V of the somatosensory cortex, a relatively high-level region known to modulate the activity of other sections in the cortex and subcortical areas. Using what he calls an "imperfect but usual analogy," Stuart Sealfon, a neurologist at Mount Sinai Hospital in New York City likens the receptors to a lock into which both hallucinogenic and nonhallucinogenic keys fit. While LSD may turn this lock to the right, kicking off one set of responses, lisuride turns the tumbler to the left, an action that only causes a subset of those responses. "Both the hallucinogens and the nonhallucinogens activate what we would call the classical signaling cascade downstream of this receptor in these cells," Sealfon says. "But, the hallucinogens, we show, are activating an additional signaling cascade and we believe the sum of both of them together is probably what causes the effect we see."

U.N.C., Chapel Hill's Roth says that the new study's localization of LSD's effect on the pyramidal neurons in level V makes sense. "We know that LSD profoundly affects human consciousness and awareness & so this tells us that the receptor on those neurons is an important locus for modulating consciousness," he explains. "If you muck up the actions of those neurons, it wouldn't be so surprising that you would affect consciousness."

Still, the finding does not appear to have silenced the debate.

While Roth concedes that cortical serotonin 2A receptors are likely part of the mechanism of hallucinogenic drugs, Dave Nichols, a molecular pharmacologist at Purdue University, believes the thalamus must be involved in some manner. "The thalamus is the major relay station for sensory information that is sent to the cortex, and there are serotonin 2A receptors localized in the thalamus and the reticular nucleus of the thalamus, which controls the flow of information through the thalamus," he argues. "For the authors to say that a unique mechanism has been identified that does not involve the thalamus, I therefore think cannot be correct."

While consensus on the exact way hallucinogens work may be a ways off, Sealfon says the research goes far in demystifying the effects of drug abuse. Also, he notes, drugs similar to LSD are routinely prescribed to patients suffering from mental illnesses, often without doctors' full understanding their effects. "If you could understand what makes a drug like LSD or mescaline have such a dramatic effect, then the principles behind that and the approaches developed for [gaining that understanding] can be applied to drugs that are used to treat neurological and psychiatric conditions," he says, adding that doctors can then "identify what drugs will have less side-effects and more specific effects".

How Hallucinogens Play Their Mind-Bending Games
Researchers isolate cells affected by LSD and mescaline, potentially leading to more treatments for neurological and psychiatric disorders
By Nikhil Swaminathan


The article can be found here [ Link ]
 
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what psych drugs are similiar to LSD? ive been on lots of different classes of psychiatric meds and have never experienced anything remotely similar to acid. SSRIs affect serotonin and can cause tracers and feelings of the " serotonin yawns" if you know what i mean by that, but is nothing like acid. who would gice LSD to a psychotic anyway, any tests of hallucinogens given to psych patients ive read about, like at lexington state facility, produce a dysphoric reponse opposite to that when a normal person takes it and acieves an euphoric state of mind. so what meds are close to LSD? anyone know because i want to get prescribed acid for my bipolar, id like to talk to god for a while
 
visualvalium said:
what psych drugs are similiar to LSD? ive been on lots of different classes of psychiatric meds and have never experienced anything remotely similar to acid. SSRIs affect serotonin and can cause tracers and feelings of the " serotonin yawns" if you know what i mean by that, but is nothing like acid. who would gice LSD to a psychotic anyway, any tests of hallucinogens given to psych patients ive read about, like at lexington state facility, produce a dysphoric reponse opposite to that when a normal person takes it and acieves an euphoric state of mind. so what meds are close to LSD? anyone know because i want to get prescribed acid for my bipolar, id like to talk to god for a while

Caffergot's about the closest you're going to get there buddy.

Understanding how hallucinogens are able to temporarily induce mental states similar to those found in psychiatric illnesses gives us a better idea of what might be going wrong in a schizophrenic brain, for instance, that isn't going wrong in a normal brain until LSD is brought into the picture.

The point is that psychedelics play a huge role in the development of psychopharms, but that role is sort of like "Ok now we see precisely what we DONT want to happen in the brain, lets design a pharmaceutical that can stop it."

Antipsychotics are designed to block the very mechanisms you're seeking in LSD, not mimick them.

(PS Dr. Roth is my hero, I love that his name is everywhere and Roth labs isn't a mile from my house)
 
great article. it conveys the information concisely without dumbing it down to much. thanks for posting :)
 
Mehm said:
great article. it conveys the information concisely without dumbing it down to much. thanks for posting :)

I hate reading second-hand information so I hunted down the source...

Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior

Which I'm hosting here: http://www.unc.edu/~dlinz/Hallucino...ted Signaling Pathways to Affect Behavior.pdf


And is also old news over in this thread: http://www.bluelight.ru/vb/showthread.php?t=290726

My friend was telling me I had to read this paper the other day, and it turns out the one I hunted down was the one he was talking about. Go figure.
 
psychedelicious said:
They mean chemically similar, not similar in effects, visualvalium.


Awesome article, thanks for post.


SSRI's are more closesly related to anti-histamines (prozac was synthesised from dipenhydramine for example) and most anti-psychotics had their birth within the benzodiazepine classs- so what psychiatric drugs could they be referring to that are related to hallucinogens, besides some MAOI's which are not evenly commonly used? The article actually refers to their effects, not chemistry.
 
lisuride is an anti-parkinson's drug chemically similar to LSD with a different set of effects. that was what he was talking about, i think
 
complexPHILOSOPHY said:
............................... psychedelic drugs distort human perception ....... "If you muck up the actions of those neurons......"QUOTE]

I know they are ostensibly trying to find supportive treatment for people with difficult and unfortunate conditions - which is undoubtedly excellent.

But it seems they can't miss a trick when it comes to reinforcing the "drugs are bad" propaganda.

E
 
Progressive research, yet the view of LSD and psychedelics remains the same: they induce hallucinations and are psychomimetic.
 
EntheoDjinn said:
complexPHILOSOPHY said:
............................... psychedelic drugs distort human perception ....... "If you muck up the actions of those neurons......"QUOTE]

I know they are ostensibly trying to find supportive treatment for people with difficult and unfortunate conditions - which is undoubtedly excellent.

But it seems they can't miss a trick when it comes to reinforcing the "drugs are bad" propaganda.

E

Not sure why you quoted me, considering it was an article I posted. I didn't make those claims, homie!
 
Whoa, I was not aware that Bryan Roth moved to UNC from Case Western. If I had known, I probably would have applied to their neuroscience PhD program.
 
Aidan of TCC said:
Understanding how hallucinogens are able to temporarily induce mental states similar to those found in psychiatric illnesses gives us a better idea of what might be going wrong in a schizophrenic brain, for instance, that isn't going wrong in a normal brain until LSD is brought into the picture.

LSD and similar tryptamines/phenethylamines (lets just say, lsd-like serotonergic hallucinogens) do not cause psychomimetic states. this was thought to be the case decades ago, but it has been proven that the effects of LSD on the brain are nothing like psychosis.

on the other hand, this doesnt come from research, but something i myself have noticed: ive seen dxm make people seem like they were genuinely psychotic. i dont wanna say its true with all dissociates, as ive never felt "crazy" on k, but then again i myself never felt "crazy" on dex.. but i believe dissociates are much more likely to induce psychotic states, especially dxm.. and i know fuck all about pcp. i only have experience with dxm and ketamine as far as dissociatives go.
 
Well I'm perplexed. Drugs similar to LSD or other psychedelics are not prescribed for mental illness such as schizophrenia or bipolar disorder. I would also note that a major distinction between Axis I psychotic disorders and the effects of psychedelics is that individuals under the influence of psychedelics usually maintain an understanding that their disturbed state is a result of a drug. Individuals who are psychotic due to mental illness often loose such a distinction and feel quite certain that their beliefs and perceptions are accurate understandings of reality. Sure at peak moments, normal consciousness is abandoned but not for long if one's "psychosis" is drug induced.
 
Interesting article, but far from unanimous. I don't believe they'll ever unlock all the secrets. They just weren't meant to be found, at least i like to think so :)
 
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