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Comment by pmoriarty | Hacker News Reader

First, this study has only been done on rodents.

Second, the reason they call it "non-hallucinogenic" is because the rodents didn't exhibit the so-called "head-twitch response" (or "HTR").

While the HTR in rodents has often (always?) been correlated to substances which have psychedelic (the term "hallucinogenic" is a misnomer) properties in humans, that's no guarantee that the novel compound used in this study won't have psychedelic effects in humans, despite the HTR in rodents.

Finally, since this study was done only on rodents, we still don't know whether it will have any therapeutic effects in humans, or even whether it will be safe.

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Also looks to be a significant MAOI from the data table at the end. MAOIs are known to be antidepressants; I'm not sure if they addressed this in the paper as a confounding factor.

I wouldn't exactly call this an antagonistic behaviour. If it can provide some immediate relief by virtue of being an MAOI antidepressant, and promote the kind of brain plasticity to help people make better pathways, isn't that actually good?

If you meant "it might be that it helped but not because of neuroplasticity effects" you could be right. But assuming they have good basis to think it does, I don't see being an MAOI as a confounding effect in outcome.

MAOIs can be dangerous too, certain combinations with strong MAOIs can be problematic. Foods containing tyramime and many drugs don't play nicely with MAOIs.

There are a number of researchers now who believe that the risk of MAOIs is overblown, for example: https://pubmed.ncbi.nlm.nih.gov/30255284/

That's not what your link says. The claim there is that MAOIs are less dangerous today than in the past because the tyramine content of food has been significantly reduced. In particular cheese, which it says was the only food associated with fatalities due to hypertension, now presents much less of a danger than before.

There are newer classes of of MAOIs called Reversible Selective MAOIs (Moclobemide) that do not have this problem with tyramine containing food.

Also, we don't know yet if the hallucinations are part of the therapeutic value of of the psychedelic compounds.

I was going to say the same. The accounts I've heard of people successfully using ibogaine to overcome life-destroying addictions focused on the critical value - and content - of the visionary effects in helping them change.

That's neat that there is a term (and even a Wikipedia page) for that behavior.

https://youtu.be/ROcQ3AybFks?t=1973

I experience this always when taking LSD - especially during the come up.

I think you're underestimating the support for labelling it "non-hallucinogenic". From the paper:

> Pioneering structure-activity relationship (SAR) studies conducted by Glennon and co-workers demonstrated that, unlike 5-MeO-DMT and other known hallucinogens, 6-MeO-DMT did not substitute for the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) at any dose in rodents trained to discriminate DOM from saline.

Shulgin really makes a good case for testing psychedelics on humans. Ultimately it is the only test if a drug is "good" for therapy or not.

Shulgin hailed from a time before we had all these fancy tests. Binding affinity, mRNA and protein production, physiological changes can all be measured easily in the lab.

There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then.

I think Shulgin was most opposed to animal testing because there wasn't as much to learn from them. Now there is, though admittedly I think we could do with a bit more taste-testing today.

"There's a section in PiHKAL where Shulgin talks about a researcher measuring properties of psychedelics using the twitches of a sheep's stomach. That's because it contains serotonin receptors, and psychedelics induce muscle contraction. This is a common way to measure binding affinity to 5-HT receptors today, but it was quite exotic back then."

Not all psychedelics affect serotonin receptors. For example, muscimol[1], the psychedelic constituent of amanita muscaria mushrooms affects GABA receptors, not serotonin receptors.

So the absence of muscle contractions caused by serotonin activation in sheep stomachs would miss the psychedelic activity of muscimol and other psychedelics which don't affect serotonin receptors.

[1] - https://en.wikipedia.org/wiki/Muscimol

I'd argue that muscimol, salvia, ketamine etc. are hallucinogens, and reserve the label of psychedelic for serotonin agonists. But others argue they deserve the label, so perhaps we could compromise on "classical psychedelic."

The original meaning of psychedelic is "mind manifesting", which has nothing to do with serotonin.

The term "hallucinogen" is a misnomer, because the effects of psychedelic substances (including muscimol, salvia, ketamine, etc..) don't always involve hallucinations.

For example, if you forgive yourself or your parents under their influence (not an uncommon effect), that's not a hallucination.

If you're able to face some traumatic event in your past while under their effects, and are no longer frightened of this traumatic event, that's not a hallucination.

If a suicidal person no longer wants to kill themselves after taking a psychedelic, or a terminally ill person is finally able to achieve peace with the fact that they're going to die, that's not a hallucination.

That's not to mention the quite common feeling while under the effect of psychedelics that what one experiences is "more real" than what one experiences under normal, waking consciousness, etc.

I don't view the term "psychedelic" as perfect, but it's much better than "hallucinogen".

Yes you can learn all about the binding affinity for different receptors, which is great and valuable, it can help you find promising candidates. However you will never know what a drug does and what it's like until human trials.

It’s not like humans haven’t been using ibogaine, and for this very purpose too. If you’re addicted to heroin, the side effects of ibogaine can be worth it.

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