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I'm pleased the war on drugs and social stigma gradually stops blocking research on psychedelics but I wish they would also study lesser-known substances and compare. E.g. psilocybin (4-PO-DMT) has an interesting synthetic alternative psilacetin (4-AcO-DMT) - I would love to see it as an extra thing they would compare to in such studies.
The issue is that they’d then have to pay for preclinical studies to determine safety, which would add millions of dollars to the budget. Whereas for psilocybin that work was largely done decades ago.
Nice point. By the way, IMO, some long-known and safe substances should also be given new tries in combination with the researched psychedelics. E.g. I believe piracetam is a great thing to take half an hour before you take MDMA - it may catalyse the effect (in a therapeutic setting especially as speaking boost is among its effects) and prevent hangover. It's not approved by the FDA but widely used in Europe and obviously (given a really huge base of empiric evidence) safe.
5-MeO is also interesting.

https://www.ghres.com/pipeline

Yeah, this one from my own personal experience almost seems like a better candidate. You experience a lot of mental openness/oneness/expansion but there is really no visual component to it. Its helped me quite a bit at times.

For those that don't know it's the chemical present in the glands of the Sonoran desert toad.

It's extremely interesting but it makes less sense to compare it to psilocybin (way too different in experience, dosage and the way you take it) and there in fact is some scientific research activity on it going on. It has already made it to some scientific papers, Forbes and HN.
Distributed anecdotes derisk the lesser known substances before the $ & reputation flow in to study it w/ a hypothesis.

I'm sure it'll happen sooner than later.

4-aco-DMT has been sold on DNMs and used by recreational drug users for a while now as an alternative to psylocibin
We are on the cusp of a new Enlightenment post the nightmare of prohibition. MDMA, Ketamine, Psilocybin, LSD are now all available easily, the middle two in good quality to normal people.

I love it. A couple of my friends take this stuff for the mood uplift. Personally, microdosing has never done the trick for me, but a solid 2.5 mg plus is a solid trip that just pushes me into the motivation zone so hard. I usually avoid it because of the length of the trip but hell is it awesome.

Occasionally I leave the Bay Area and am astounded by the degree to which other people like to have Big Government dictate their personal lives. Texas, for instance, blew my mind. It was like taking three steps back from progress. There are trade offs, I know, but for me, my personal individual freedom is paramount.

I love America’s federal system. I wish more power would be devolved to the states.

As a proud 4th generation Texan, I would like to say going to California in various ways would strike me as being a place that uses state power in backwards ways as well.

Unfortunately for the both of us, not to speak for anything specifically to California, our states have managed to make some bad decisions. I believe I have standing to speak to recent Texas policy in regard to the recent abortion madness, illegalizing delta-8 THC products etc... sad times indeed.

I am very pro federalism myself, and think that competition of polity would be a great unwinding of federal power. But it seems the iterim is going to be the states fighting against the Fed in extreme ways.

Can you elaborate on how Texas has big gov in peoples life that SFBay doesnt?
Under Texas franchise laws, consumers can only buy cars from auto dealers and can’t buy them directly from automakers.

As it stands in the Lone Star State, Tesla’s company-owned outlets can’t legally sell a Tesla in Texas. This is even more hilarious given they are building the Cybertruck in Texas.

Both are authoritarian, just depends on if you like left vs right wing authoritarianism.

Texas more strongly limits the drugs you can put in your body. Limits access to abortions. etc...

California limits guns, has vaccine mandates. Limits smoking in your own condo. etc...

Many people live in mental prison and because they don't know any better, they fear change. They fear that, perhaps they lived majority of their life trapped and only their own ignorance kept them in the cage. They fear to admit that to themselves, they fear the feeling they lost their life to easily preventable pain and misery.
Totally 100% agree, Psilocybin is an incredible medicine.
"Occasionally I leave the Bay Area and am astounded by the degree to which other people like to have Big Government dictate their personal lives. Texas, for instance, blew my mind."

I think it depends on the issues one is using for their perspective. Some people may find CA more oppressive.

>I wish more power would be devolved to the states.

Doesn't everybody!? Why aren't we seeing more of this

We are seeing more of it as the Federal government is more paralyzed due to internal divisions in the country. We've already seen states declare themselves immigration "sanctuary" states where immigration laws will not be enforced, and then others declared themselves gun control "sanctuary" states where gun control laws will not be enforced. States have adopted their own fuel emissions standards. California announced it would ban ICE engines while Texas announced it will tax EV cars.

I'd strongly support more devolution and even a U.S. breakup, TBH. Local government is more accountable and I support localism and local autonomy whenever I can. I'd even support a situation in which states had their own currencies, citizenship rules, etc. I understand this is utopian, but more localism and distribution of power rather than concentration of power is something I generally support.

No. In fact, I think most people want more federal power. They just want that federal power directed in different ways.

For instance, the overwhelming popularity of federal single payer healthcare today signals that people want big government.

Cause it’s prone to failure? America tried the weak federal system where everyone had a different bank and different rules. It was essentially 13 independent smaller “states” than one nation.

Even now people are aghast when Texas limits abortion or tries to outlaw gay marriage or when California’s increased fuel standards affect the entire nation.

Additionally, it makes it impossible for states which would enact stronger gun control measures to enforce them when neighbor states just hand guns out in much less stringent manners.

It also has federal ramifications when gerrymandered districts affect the makeup of our federal law making bodies and increasingly populate them with far more right or left wing representatives than would occur in more balanced districts while disenfranchising voters who’re American systems.

I’m more on the side of California at the end of the day but we’re all Americans here in America, not Texans, Californians, or Iowans. It’s fine to have cultural differences (its what makes the country beautiful in a lot of ways), but the idea we should all just “figure it out with our neighbors” who’re our neighbors cause of relatively arbitrary lines drawn sometimes hundreds of years is a bit crazy and a gift to those who’d see a weak America.

I'm confused, how accessible is this stuff to you? Do you mean black market or prescription?
Right there with you. Last I checked, LSD has been extremely scarce since Hardison got snapped up in 2005. Even if you can get your hands on the stuff (or any of the drugs mentioned for that matter), there's still no guarantee that what you're getting is what the dealer says it is.
You can order a kit and grow them home, in the UK it’s a grey area legally. The grow kits are legal but the mushrooms are not
It’s trivial to get a prescription for ketamine. And I live in the Bay so I just go to my church for psilocybin.
It's crazy that law enforcement actually participates in hounding people who self-medicate rather than going after corrupt medical and political establishment. This completely destroys any trust people have in government, laws and justice. Great that we can see some progress, but I have a feeling that it is only possible because people behind all that corruption finally figured out a way how to monetize it.
It makes perfect sense once you understand that the system is not about truth, justice, etc. It's about forcing conforming to societal expectations and holding on to or expanding the power society has delegated to them.
That’s the definition of evolution, just applied to human societal organisms.
Title should reflect this is in Australia
Are foreign clinical trials meaningless for FDA approval? I only have knowledge from news stories, but I seem to recall oxycontin using sketchy foreign trials to get approval.
Or perhaps you could try working on your Americentric perspective. The internet is international.
HN comes from YC, which was birthed from Silicon Valley. Almost everything on this site has an american centric perspective.
Meh, these treatments are usually limited duration. Even if this is only ever approved in Oz folks could presumably travel abroad to seek treatment. Folks post US-only things here all the time.
Sure but that kind of limits its capacity to make an impact, right?

Pretty much everyone experiences some degree of anxiety. Tons of people here in California, before recreational cannabis was legal, got a medical use permit simply by truthfully telling the teledoc they have anxiety and cannabis might help them with it. Nobody cared whether this anxiety crossed some arbitrary threshold into being a serious medical issue, or if it was just regular old "my life can be stressful, but it sure is nice to relax with a sweet bong hit."

I doubt a single person was turned away because their anxiety wasn't considered "serious" enough, and I'm personally ok with that.

I'd be happy if the same situation happened with psilocybin.

That's a big difference from having to go completely across the world to seek treatment.

The worst anxiety I have ever experienced was from a bad trip that caused intense panic and days of anxiety and paranoia after. Can anybody anecdotally attest to psychedelics helping anxiety?
There are already completed studies that show positive impact from psilocybin on anxiety.

My experience as someone who has mild anxiety (and always feared having a "bad trip") was that, though I had some challenging and uncomfortable (but ultimately rewarding) thoughts during the experience, the "afterglow" was a couple weeks of enhanced mood and little-to-no anxiety.

The afterglow as you put it was quite amazing. I don’t suffer from anxiety myself but my mood and feeling for some time after was incredible. I strongly believe that there is something there worth studying.
These doses are more likely to be sub-"trip" doses. Ones that are enough to influence your mood, emotions, etc, but probably not enough for you to have a full blown trip.
Are there other promising anxiolytics on the horizon? Even more basic, what are the best options available now?
> Are there other promising anxiolytics on the horizon? Even more basic, what are the best options available now?

Well, anxiolytics in general can be grouped in two groups - for acute treatment and for long-term treatment.

For acute treatment, benzodiazepines remain good choice. Therapy with benzodiazepines should not last for more than 6 weeks. Another option is use of 1st generation antihistamines, but tolerance usually develops.

For long term treatment, there are quite many options. Most of antidepressants exhibit anxiolytic effects and they are relatively safe for long-term use. Sympatholytics are also useful - seemingly, slowing heart rate reduces anxiety in mammals. Pregabalin is widely used for anxiety, because it's relatively safe for long-term use.

The gold standard is therapy (first line for anxiety should be CBT). Medication is often warranted but should be used in conjunction with therapy.

Overall, most of mental disorders are complex mixture of psychological and biological factors and best possible treatment usually combines therapy and medication. There is hypothetical logical link - most of antidepressants increase neuroplasticity and neuroplasticity is thought to be necessary for therapy to work.

Phenibut fits the bill and is more widely used and prescribed in Russia. In the US you can buy it in chemical form as its unregulated. Its a quite potent anxiolytic working as a GABA-B Antagonist.

I recommend doing a lot of research though as there are quite a few people that seem to either get hooked on or have a terrible time coming off of this drug/chemical. I personally never had those problems but something to be aware of.

Any guesses about how effective this compound will be and to what percentage of patients?
Just my own one little bit of anecdata, but I credit my handful of youthful psychedelic experiences with having shown me that it was possible to feel anything BUT anxious and depressed and afraid of the world.

As a young dude with a lot of childhood trauma, it was revelatory and profound to feel peace for a day, to feel the world flow around me with a sense of joy and acceptance.

Hard to say how this will all play out in the coming years, but I am excited to see this stuff getting at least a proper chance at being used to help damaged souls in a therapeutic environment.

I highly recommend the documentary "Fantastic Fungi" [1] (2019) to anyone interested in this topic. Can be viewed on Netflix. It will give you a good sense of what's driving the interest in this field.

1. Fantastic Fungi https://g.co/kgs/1UMWga

I think there is a high chance that the short-term results will seem miraculous with significant improvements for issues like anxiety and depression but there will be difficulty with maintaining these improvements long-term without continued sessions and therapy.
Depending on set and setting: anywhere from extremely good to extremely bad. I'm pretty sure they'll be cognizant of creating a positive environment though.
Very high percentage. At least in my experience, the effect is NOT subtle.
100%
Just listened to an interesting podcast on psychiatry and capitalism today that mentioned just how desperate big pharma companies are to get their hands on psychadelics. Podcast essentially argues that psychiatry in large part serves to continue enabling capitalism while papering over the people who are incompatible with capitalism via medication. Very interesting pod for sure.

https://www.madinamerica.com/2021/10/can-critiques-psychiatr...

Psilo + mdma is a more effective way to treat anxiety disorder IME.

Psilo alone can be a little adrenalizing.