LSD-Like Molecules Counter Depression Without the Trip (ucsf.edu) 40
"Scientists have designed compounds that hit the same key receptor that LSD activates without causing hallucinations. A single dose produced powerful antidepressant and antianxiety effects in mice that lasted up to two weeks. The study was recently published in the journal Nature. UC San Francisco reports: The compounds were designed to fit into the 5HT2a receptor, which is the main target of psychedelics like LSD and psilocybin mushrooms. The receptor is also activated by serotonin, a naturally occurring hormone that regulates mood, cognition and many other functions in the body. The 5HT2a receptor is thought to play a role in schizophrenia and other psychotic disorders, as well as anxiety and depression, and a host of antipsychotic and antidepressant drugs block its activity. The new molecules activate it, but in a very different way than psychedelics.
[...] Although it's been known for several decades that 5HT2a receptors activate different signaling pathways in cells, until now there were no compounds selective enough to see what each pathway did. The scientific team discovered the receptors could set off two different pathways, a hallucinatory pathway and an antidepressant/antianxiety one. LSD activates the first one more, while the new compounds activate the second one more. "The receptors are like antennae," said Brian Shoichet, PhD, professor of pharmaceutical chemistry in the UCSF School of Pharmacy. "They pick up a chemical signal, and downstream a bunch of things get activated in a cell."
The compounds had been selected from a computational library of 75 million candidates. Jonathan Ellman, PhD, the Eugene Higgins Professor of Chemistry, and professor of pharmacology at Yale, synthesized them. And the UCSF, UNC, Yale team worked for more than a year to optimize them. "The final molecules were 100 times more potent than what we started with," Shoichet said, although they were still not nearly as strong as LSD. "In the animals they are very potent, much more potent than Prozac." The team expanded to test the designer molecules in mice, adding William Wetsel, PhD, who directs the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke. His lab looked for head twitch responses that are the tell-tale signs of psychedelic activity in mice. But the mice hardly twitched. Wetsel's lab ran the mice through a battery of tests to see if the molecules could ameliorate symptoms analogous to human anxiety and depression. And they were highly effective. After many years, what had begun as a science experiment arrived at a discovery with great clinical promise. "The team's next project will be optimizing the compounds, making them selective enough to be used in clinical trials," adds the report.
"A key issue will be making molecules that have no affinity for 5HT2b. Drugs that hit this receptor, like the banned diet drug fen-phen, can cause valvular heart disease when taken chronically. That receptor is also hit by psychedelics, particularly LSD."
[...] Although it's been known for several decades that 5HT2a receptors activate different signaling pathways in cells, until now there were no compounds selective enough to see what each pathway did. The scientific team discovered the receptors could set off two different pathways, a hallucinatory pathway and an antidepressant/antianxiety one. LSD activates the first one more, while the new compounds activate the second one more. "The receptors are like antennae," said Brian Shoichet, PhD, professor of pharmaceutical chemistry in the UCSF School of Pharmacy. "They pick up a chemical signal, and downstream a bunch of things get activated in a cell."
The compounds had been selected from a computational library of 75 million candidates. Jonathan Ellman, PhD, the Eugene Higgins Professor of Chemistry, and professor of pharmacology at Yale, synthesized them. And the UCSF, UNC, Yale team worked for more than a year to optimize them. "The final molecules were 100 times more potent than what we started with," Shoichet said, although they were still not nearly as strong as LSD. "In the animals they are very potent, much more potent than Prozac." The team expanded to test the designer molecules in mice, adding William Wetsel, PhD, who directs the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke. His lab looked for head twitch responses that are the tell-tale signs of psychedelic activity in mice. But the mice hardly twitched. Wetsel's lab ran the mice through a battery of tests to see if the molecules could ameliorate symptoms analogous to human anxiety and depression. And they were highly effective. After many years, what had begun as a science experiment arrived at a discovery with great clinical promise. "The team's next project will be optimizing the compounds, making them selective enough to be used in clinical trials," adds the report.
"A key issue will be making molecules that have no affinity for 5HT2b. Drugs that hit this receptor, like the banned diet drug fen-phen, can cause valvular heart disease when taken chronically. That receptor is also hit by psychedelics, particularly LSD."
For LSD this is a good thing (Score:5, Interesting)
If it were mushrooms I would argue the benefit is in the trip... but LSD lasts way too bloody long and in my experience was too abstract for real soul searching. Plus, this is just symptom management by the sounds of it.
Not that I'm an LSD aficionado... it's been 25 years since that time. 5 times. Last time I did an atrocious amount and had the kind of complete ego stripping trip people dream of. I mean "orbiting the singularity", and reconstructing my self during the come down. Realized that that was it... it was never going to be that good again. Never went back.
Ah, I miss the indestructibility of youth...
Re:For LSD this is a good thing (Score:5, Interesting)
Unless we settle for managing the symptoms while at the same time giving up on looking for the root cause, there's nothing wrong with treating acute symptoms. And there's especially nothing wrong if the treatment has far milder side effects than conventional treatment.
Hypothetical: Take a broken leg for example, which say was caused by stepping into air while walking on stairs causing one to fall down and break a leg. Now you could try to remove all stairs to prevent such an incident in the future and maybe you'd be successful. But that won't heal the legs that are already broken.
Now of course depression doesn't exactly work like a broken leg. Though from what I know from my psychologist and psychiatrist colleagues (in software development), you can't fix acute depression by just treating the root cause. In that regard it very much acts like an acute wound that requires treatment which often comes with significant side effects that must be weighed, while of course you should be looking for the root cause to prevent it from happening again.
Re: For LSD this is a good thing (Score:2)
You're right, and I shouldn't have sounded dismissive of the value of symptom management here.
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from what I know from my psychologist and psychiatrist colleagues (in software development), you can't fix acute depression by just treating the root cause
Hard to do when you don't know what the root cause is. Nobody has ever proven a biological basis for depression. There are some drugs that kinda work, but all of them have severe side effects (often including causing depression, or even making users suicidal... like Prozac did to one of my good friends when we were teenagers.)
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Though in some cases it can be brought down to an external stressors, which when removed lead to improvement.
Take "Adjustment disorder" as an example (part of even professional people believe it's not even a proper thing because of its vagueness), which has overlapping symptoms with PTSD, anxiety, and depression (requires some differential diagnosis that rules those three out).
Among those that see it as a valid condition (which w
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My concern is as usual that people are anxious or depressed because of real shit happening but will be pathologized and medicated because that's profitable, and fixing the real problems causing the anxiety isn't. Those problems are provably the problem, and biology is not provably the problem, but they will go where the money is anyway.
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It's usually used as a generalized term that's not as stigmatizing as a diagnosis of a more "permanent" disorder that a professional can put on the bill for the health care provider, for example signalling to the health care insurance that the therapy costs may be just temporary and if its fixed now it will prevent further cost down the line, while of course in truth the diagnosis will be refined over time as more information comes in.
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Conflating my real and legitimate concern with conspiracy theorist bullshit is a cheap tactic. There is a cure, and it's unfucking society instead of medicating everyone who realizes it is unsustainable.
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If it came across as an accusation, let me apologize. I'm sorry.
As far as "unfucking society" being the cure, the efficacy of that approach would have to be proven first, and we'd also need to figure out how to feasibly "unfuck society" in that particular regard at least.
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Every measure of society is always in hindsight
Nonsense.
by the time there's any common concept of society it's already obsolete
So? There are uncommon concepts of society which are accurate.
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So, leave society to the historians, and work on yourself and your own life.
Absolutely not. That has always been a recipe for oppression. The tree of liberty, remember?
Society isn't a thing .it's a perspective
Society is what we collectively make it.
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You seem have a religious view of society.
I have a realistic view of existence. Things don't just happen, unless people make them happen. They don't just work out for the best.
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Well, one will never be done, the other can be done quickly and cheaply.
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Well, one will never be done, the other can be done quickly and cheaply.
Cheaply for who? There are real drawbacks to overmedicating the population, it causes actual problems. The military created the cocaine drug epidemic by giving soldiers cocaine in WWI, and the methamphetamine epidemic by giving them speed in WWII (and every conflict since.) The government created the opioid epidemic by not reining in Purdue. All of these drug problems are creating real problems which negatively affect even people with money here in the USA.
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Yes, but compared to trying to fix everything in society. it's still quick and cheap.
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I feel like you could fix "everything" (or at least enough to where most people could relax properly once in a while) in society relatively rapidly, but it sure wouldn't be cheap.
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Like a lot of other people I sure can agree with the general sentiment, but a absolutely must acknowledge the vagueness, where different people may have very different takes on what's "wrong" or "needs fixing" in society and how to do so.
For example if you asked a Taliban, they'd likely to have a pretty concise opinion on the matter. If you asked a Trumpster, they'd also very likely have some pretty strong o
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The people know are suffering form anxiety and depression need help now, not later, when you fix all problems of society. Especially when we don't seem to be even going in the direction of achieving that.
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Managing the symptoms is often what provides the greatest benefit for an acute (urgent) issue.
Nah, they just aren't tracking the long-term effects of dependency even though they're everywhere. Treating symptoms instead of causes results in a dependency 100% of the time (some things like aspirin or ibuprofen are small enough that it's irrelevant,) treating causes results in cures. Pharmaceutical companies and shrinks focus on treating symptoms because a) it's what produces long-term clients and b) they can get away with it because people tend to prefer "make it go away" to "there's some deep work w
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If it were mushrooms I would argue the benefit is in the trip... but LSD lasts way too bloody long and in my experience was too abstract for real soul searching. Plus, this is just symptom management by the sounds of it.
Not that I'm an LSD aficionado... it's been 25 years since that time. 5 times. Last time I did an atrocious amount and had the kind of complete ego stripping trip people dream of. I mean "orbiting the singularity", and reconstructing my self during the come down. Realized that that was it... it was never going to be that good again. Never went back.
Ah, I miss the indestructibility of youth...
I hear ya.
It's about 25 years since I last took LSD, I recall (most of it), to this day.
I was at a local club - the worst place to trip - took a taxi to "the drug zone" (where I could purchase things) and somehow "lucked" out on some smiley micro's - I got a bunch, for about 10 other people at that club.
It was intense - turned that club upside down and back to front for those people - including the DJ - total freakout.
The trip lasted 36 hours, during which I somehow managed to get home, sleep and then head
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If it were mushrooms I would argue the benefit is in the trip... but LSD lasts way too bloody long and in my experience was too abstract for real soul searching. Plus, this is just symptom management by the sounds of it.
Not that I'm an LSD aficionado... it's been 25 years since that time. 5 times. Last time I did an atrocious amount and had the kind of complete ego stripping trip people dream of. I mean "orbiting the singularity", and reconstructing my self during the come down. Realized that that was it... it was never going to be that good again. Never went back.
Ah, I miss the indestructibility of youth...
Of course the whole point of LSD is the trip. And the supposed "antidepressant" or whatever effects (yeah, sure) is just a pretext druggies use while lobbying to increase its availability.
*in mice* (Score:3)
I swear humans are the real lab rats, running an entire medical testing industry for a species of super intelligent space mice.
Re: *in mice* (Score:4, Funny)
Re:*in mice* (Score:5, Funny)
Well, the main cause of cancer in mice is research labs...
Always Taking the Fun from Everything (Score:4, Funny)
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Just sayin'...
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This actually exists, FYI. [punchedibles.com]
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That mushrooms were made illegal is a crime against humanity. It's good to see that we're finally starting to waking up, though I fear we have a very long way to go...
Side effects may include (Score:3, Funny)
Bullshit (Score:2)
Next there will be weed that fight cancer without getting you high.
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I feel like over-the-counter CBD being used as a panacea already has brought us to that point.
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Sometimes that is a good thing
Ibogaine is a compound found in the root of the Iboga plant and is used in African shamanistic religions to heal a person's soul [time.com]
Beyond that, it is the most effective known treatment for opioid addiction with a lower recidivism rate than NA, Methadone, therapy, suboxone, etc...
It literally alters the brain to no longer be addicted in the course of a 10 hour trip
Oh yeah, it has DMT [erowid.org] in it and in rare cases results in cardiac arrest
This is a BIG DEAL in America where it is consider