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Comment by GenerocUsername | Hacker News Reader

Doubt.

It's maybe possible that LSD (and per the article, LSD-like chemicals) has a chemical effect on depression, but based on the fact that MANY different psycadelics exhibit similar anti depression abilities, it seems more likely that it is the actual experience of the trip that confers most of the benefit.

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“It’s possible that consuming glucose (and other forms of sugar) has an effect on weight gain, but based on the fact that MANY different foods exhibit similar weight-related effects, it seems more likely that it is the actual experience of flavor that makes the body convert calories to fat.”

I heard an interesting counterploint the other day. I think the statement is completely unfounded but figured I'd share because it sounds reasonable...

"Memories are formed by neural pathways, and it is these memories / correlations that form a basis for (some) mental illness. Taking psychedelics can help take another perspective on these memories and rewrite these these pathways / correlations."

This is specifically true for some phobias:

https://ec.europa.eu/research-and-innovation/en/horizon-maga...

Wow this sheds some new light on an anecdotal experience if mine:

I once watched a climber free climb a moderate 30 meter route me and my friends had just completed with ropes, and he mentioned his LSD hallucination was peaking as he saw us at the top.

I considered that maybe climbers like him have exceptionally higher risk tolerance or a habituated comfort with psychedelics and climbing. However, as someone with a reasonable amount of exposure to both of those (separately), it still baffled me. This feels like a more palatable explanation in tandem with higher risk tolerances and habituation.

Great read. Thanks for sharing!

Wasn't there something about artificial sweeteners causing the brain to release hormones that lead to insulin resistance? So the brain is reacting to the "flavor" rather than the actual sugar (or more precisely, the neurological pathway that consciousness experiences as sweet taste is also linked to this sugar-related physiological chain reaction).

I think this might've been a myth.

I wore a constant glucose monitor for a while (Veri), and drinking soft drinks filled with all kinds of artificial sweeteners caused no glucose changes. If sweeteners caused a spike in insuline, I would see glucose levels fall.

I tried finding research on the subject once, and couldn't find anything legit.

> I wore a constant glucose monitor for a while (Veri), and drinking soft drinks filled with all kinds of artificial sweeteners caused no glucose changes.

It doesn't cause immediate changes, it causes long-term changes to glucose response by altering the gut microbiome. Here's a recent double-blind randomized controlled trial showing these effects that was discussed on HN a few weeks back:

https://www.cell.com/cell/fulltext/S0092-8674(22)00919-9

This is the first study that I think showed this pretty conclusively.

Yes, it was on the frontpage of HN a few weeks ago. Off the top of my head the results were that certain artificial sweeteners spike insulin and some don't.

This doesn’t pass the smell test for an in vivo result. If they spiked insulin in a physiological meaningful way without actual glucose you’d expect hypoglycemia. It’s not like insulin resistance is an acute process.

You should read the study: https://www.cell.com/cell/fulltext/S0092-8674(22)00919-9

Did you? It doesn’t contradict anything I stated.

I don’t think the GPs informal synopsis characterizes the gist of that paper in any meaningful way.

I thought it was that the reduce insulin sensitivity, so you’re affected when you DO have sugar on the future?

Not really a fair comparison. How can you compare weight gain to a mental illness?

Precisely. That's why the placebo effect is so effective.

While this is a completely fair counterpoint, the part that GP didn’t mention is that a patient’s subjective experience is usually ignored or minimized in psychological research, which prefers to focus on behavior and biological phenomena (because they are easier to measure).

It seems to me like the “trip” aspect is at least worth some investigation.

...except sweetness isn't what all those foods have in common?

Maybe it's part of the "actual experience" that you don't feel depressed any more. The hallucinations, who needs those. Therapeutically what matters is the increased feeling of well-being that lasts for weeks if not longer.

The hallucinations do really help. Its very difficult to be depressed when all the trees are dancing and shining. LSD and the likes also avoids congnitive hallucinations in most people so you're perfectly aware that it's just the wind.

set and setting. 2C-E showed me how I was a tiny spec, on a tiny speck of a planet, in an infinitely large universe, cold and unfeeling and uncaring, loved only in a tiny way by only a couple of other tiny specs, all of whom would die in a brief instant, cosmically speaking. it was like Carl Sagan showed up to tell me how meaningless my existence was.

also, unbearable sensory overload as the panic attack worsened, seconds took minutes to pass, and my kidneys felt like they were failing (they were fine though.)

the ego death was more or less permanent. my "self" never recovered, I had to build a new one. uncanny experiences of feeling like I wasn't my parents' real daughter, that my phone was a dead person's. I wasn't the same person. but this person is better than she was.

so.. worth it in the (years-)long run, but hardly sunshine and roses! bad trips are scary. 2C-E is known for being cold and analytical, but I'm sure you can have similar experiences on acid.

What is a “cognitive hallucination”? LSD can absolutely change your thought patterns

Unless the thing that makes the trees dance and shine rather than loom and glow ominously is the same thing that has the anti depressant effect.

I personally think pearl clutching about the idea someone might have fun whilst benefiting from medicine is stupid and there's no reason psychedelics should not be available to anyone who is screened for potential contraindications, but there's no reason to assert that all of the different effects are inexorably linked.

I'm thinking that "having fun" is what cures us from depression. Fun and "goodness". Love and happiness. Spirituality. Hallucinations can be fun, which is a good thing. But I think these scientists are onto something trying to extract the "good thing" that is good even without hallucinations.

> Therapeutically what matters is the increased feeling of well-being that lasts for weeks if not longer.

But what if that is a consequence of the 'hallucinations' changing your perspective on things? What if the psychedelic break with baseline reality for a few hours is the trigger that changes things?

It's definitely interesting to try and understand. I also just react poorly to people trying to create 'useful' versions of a drug without the 'fun' parts. I don't dabble any more but the experience of compounds like these was well worth the time invested.

(I put hallucinations in quotes above because I think there's a difference between the psychedelic experience and something all-out hallucinatory, read erowid reports on belladonna, datura and brugmansia for the latter)

It is "fun" to get out of depression. Things start feeling fun again. But depression is a mind-set, how you see things. I'm not saying hallucinations couldn't change your mindset, for the better.

A trip is more than a series of visual disturbances. It's an emotional rollercoaster. Your perception of yourself and your surroundings changes drastically and you have many insights that you perceive as very significant. This can help take your attention away from irrelevant things and direct it to more meaningful things in your normal life.

And even the hallucinations can show you that we construct our realities in every instant of our lives. You know this already of course but knowing and experiencing are two different things.

I agree with this. There are novel tryptamines that exist that bind to 5HT2A but don't cause a trip. I've tried a couple of them. They do have effects upon mood, generally positive, but they are distinctly different than the effects on mood from an actual trip.

I think the difference comes from the meaning and significance that come from the experience of the trip itself. The meaning is logically and emotionally interwoven with your perspective, effectively changing it. I believe experience is required for that profound perspective shift, and non-psychedelic 5HT2A agonists don't provide that experience.

I am also doubtful, but the new molecules look quite a bit different to both LSD-like and tryptamine psychedelics, so it will be interesting to see what will the test subjects say, if it gets that far.

There are also primarily dopaminergic psychedelics like ibogaine that have even more potent therapeutic benefits. This suggests it is not sertonergic effects that are the primary therapy.

Maybe the only reason you associate positively with the trip is that it's paired with anti depressant effects.

[citation needed]

There is significant evidence that MDMA, LSD and psilocybin, which are all psychedelic drugs but wildly different chemically, have a significant impact on depression.

https://en.wikipedia.org/wiki/Psychedelic_therapy

Every single one of these has an effect on serotonin receptors, there are a lot of clinical antidepressants that don’t make you trip but affect serotonin.

So I don’t think this is actually proof of the trip being needed

There’s also some evidence that those serotonergic antidepressants actually worsen depression and make it chronic.

The difference is that antidepressants have a temporary effect on serotonin levels and thus need to be taken continuously, while a "trip" on psychedelics appears to actually be able to rewire your brain, so a single dose can have permanent or at least much more long-lasting effects.

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