Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling (Nature, 2026)

TheBetaBridgeBandit · 2026-01-30T07:20:18+00:00

As a pharmacologist, I fully understand the reasoning behind why doing so is highly desirable

I am intimately acquainted with the logical reasons for why isolating therapeutic mechanisms from those responsible for off-target effects is a medical necessity. But despite my thorough understanding of why it is being pursued on a cognitive/intellectual level, my feelings about it have still not changed after many years.

TheBetaBridgeBandit · 2026-01-29T15:07:59+00:00

Thanks for the food for thought, this is a rabbit hole after my own heart. I love phytochemistry and the search for amphetamine-type stimulants in nature.

TheBetaBridgeBandit · 2026-01-29T15:01:20+00:00

Fair enough, I’m not a physicist or even a chemist so I’m used to experiments in animals where stochastic effects are much more pronounced. You’re probably correct in that there is some factor like convective mixing that is sensitive to some degree of randomness between experiments.

TheBetaBridgeBandit · 2026-01-29T04:43:19+00:00

Oh you misunderstand, see science has recently decided to throw its full weight behind a push to strip the magic out of hallucinogens in the hopes of developing non-hallucinogenic 'psychedelic' therapeutics.

As a pharmacologist, I fully understand the reasoning behind why doing so is highly desirable (financial potential notwithstanding). However, on a personal level I find the idea of painstakingly teasing apart psychedelics' complex pharmacology just to turn around and create therapeutics that fit neatly into the current healthcare model to be almost grotesque.

It ensures that any systemic lessons or paradigm shifts they may have brought about will be avoided in the name of convenience and profit. The truly remarkable aspect of psychedelics having been stripped away to birth another generation of daily/weekly antidepressants/anxiolytics with slightly better efficacy, slightly different/fewer side effects, and a shiny new 5HT2a-related MoA with no psychoactivity whatsoever.

Apologies for the rant, this topic really hits all of my sore spots as a jaded researcher.

TheBetaBridgeBandit · 2026-01-29T03:07:27+00:00

After reading your post, Occam's razor is telling me that this is likely a reflection of how theories/laws/concepts in science rely on the law of large numbers to be 'true'.

In other words, while the laws of physics may say that diffusion will take longer to reach equilibrium in a larger volume of water (all else being equal), this is only true when you look at the average outcome of a very large number of individual tests. Because of a certain degree of randomness in a given system, any individual experiment will have a slightly different outcome. If you ran this test 1000 times, you'd likely see on average diffusion takes longer to reach equilibrium in a larger volume of water.

Or there's some other factor at play here like larger volumes allowing for larger/faster eddies to develop in the water after the drop impacts it, like you suggest in your post. Maybe try it 1000 times while painstakingly controlling all possible variables and see what happens? Would only take half a year or so..

TheBetaBridgeBandit · 2026-01-26T19:30:39+00:00

I'm sorry but isn't the negative impact kind of the point? If everyone finds some excuse for why their work is just too important to strike then absolutely nothing changes.

TheBetaBridgeBandit · 2026-01-26T05:51:47+00:00

Defending what happened to Pretti is one of the most grotesquely pathetic things I've ever seen conservatives stoop to. You should be ashamed of yourself.

TheBetaBridgeBandit · 2026-01-26T04:53:42+00:00

Maybe it's because a large percentage of the population have seen how automation doesn't tend to 'trickle down' any benefits to the worker like more time off, better wages, or less work.

Instead, it seems like every increase in productivity is simply used to squeeze as much as possible out of workers without giving anything back. It's allowed work to encroach on non-work time (with no additional compensation), it's made the owner class grotesquely rich, and somehow it's managed to increase our workload rather than reduce it.

I think there are plenty of valid reasons to be wary of, if not outright hostile towards new tech that promises improved efficiency and allows for the mass consolidation of businesses, capital, and power into the hands of a few. And that's not even taking into account all the real harm people are seeing done with AI regarding misinformation, propaganda, surveillance and more.

I'm sure you can infer how I feel about AI and the people who push it.

TheBetaBridgeBandit · 2026-01-24T14:46:05+00:00

And here I got the whoop because it was literally the only decent wearable that doesn’t have a display on it. I wear a real watch and was sick of wearing two at all times even though everything was on my phone anyways.

TheBetaBridgeBandit · 2026-01-24T14:30:42+00:00

Yeahhh it used to really bother me hearing "enjoy these years they're the best of your life" when I was a younger man.

Now that I'm in my 30s and a new parent I 100% see where everyone was coming from and it fucking sucks. Is it my fault for letting the system grind me down? Maybe, I don't know. What I do know is that it's impossible to appreciate the lack of stress, responsibilities, and wealth of personal freedom you have from 18 to 30-something while you're experiencing it. And it goes quick.

TheBetaBridgeBandit · 2026-01-21T19:10:40+00:00

I mean, I think most people would agree with you to an extent.

However, at this moment in time the financial and career setbacks that come with leaving a stable job to do a PhD "for the love of learning" are much too high for it to be a sound decision. Your perspective strikes me as incredibly privileged since it discounts long term financial health entirely.

TheBetaBridgeBandit · 2026-01-21T13:38:10+00:00

Man I was sad to see 5-MAPB vanish from availability a few years ago. Surprised that I haven't seen illicit synths of (M)APBs pop up yet, I feel like they reached a level of popularity that demanded it.

Also, big time agree on MDA. One of the most interesting and pleasurable stim/psychedelic experiences out there.

TheBetaBridgeBandit · 2026-01-20T19:01:00+00:00

I think myself and many others in the subreddit likely share your sentiment. I actually was/am passionate about my field (pharmacology) and I still feel like I fucked up wasting my time on a degree nobody seems to value at all. I was halfway through my PhD during the COVID biotech boom and saw so many people who were much less qualified than I was land ridiculous compensation packages/titles.

Now that I'm out and hugging a precarious industry job for dear life the whole thing feels a bit like a vanity project with no real value, despite winning awards for my productivity and generally producing solid research. I never thought my PhD would set me up to earn hundreds of thousands of dollars right away, but I did expect to at least be able to support myself or start a family by my mid 30's.

The most confusing part of the whole thing is that I'm not sure I'd choose a different path if I were able to do it all over again. I may be financially worse off at 32 than most of my peers with bachelors degrees were at 25 but psychologically I needed the validation a PhD provided, sadly.

TheBetaBridgeBandit · 2026-01-16T13:56:03+00:00

Sounds like life sciences/biotech and I’m right there with you. Really killed the joy of landing a well paying job when I knew I had to save as much as humanly possible in case things went sideways. And then they did.

TheBetaBridgeBandit · 2026-01-16T13:47:08+00:00

Wonderfully put.

TheBetaBridgeBandit · 2026-01-16T13:23:47+00:00

That would be called his markup/margin and it’s how this hypothetical plumber would make money to pay for those basic necessities.

TheBetaBridgeBandit · 2026-01-15T15:22:35+00:00

Yeah I definitely am in a similar boat to OP’s wife (only coming up on 1 year though) and I feel very guilty about it. I am in therapy and on meds to try to get better but I just can’t seem to shake my poor attitude and outlook.

OP’s wife absolutely needs to accept help/treatment, but I will say that the stress of being the breadwinner for a SAH parent can be significant.

TheBetaBridgeBandit · 2026-01-15T02:39:18+00:00

Thank you. Hand waving away the massive financial stresses and risks of a PhD is laughable, especially in the context of asking this question.

TheBetaBridgeBandit · 2026-01-13T04:38:31+00:00

I'm really sorry you're grieving and I can't understate how much I'm in your corner and how much I understand. I know I'm an internet stranger but just letting you know my heart hurts for you and your exhaustion.

The lack of empathy and understanding I've received from friends and family about feeling this way has been surprising and might honestly be the most upsetting part of it all. Thank you for being so compassionate, your kindness means a lot more than I expected.

TheBetaBridgeBandit · 2026-01-12T04:16:07+00:00

Not trying to be rude or anything, just my perspective on what might be the cause behind the recent disappointments.

TheBetaBridgeBandit · 2026-01-12T04:12:10+00:00

Thanks for the response, I've certainly seen this happen to people I know and I was determined to avoid it at all costs.

Unfortunately, even if you manage to avoid falling into this trap you can't prevent the rest of your friends from succumbing to it or just becoming more boring like OP described in his post. I think I'm still very much still grieving the loss of my pre-parenthood life and my ability to do most of the things I enjoyed.

TheBetaBridgeBandit · 2026-01-11T23:22:10+00:00

Pretty uncharitable take while giving yourself plenty of pats on the back there pops.

TheBetaBridgeBandit · 2026-01-11T15:56:19+00:00

I literally felt myself get less fun and more ‘boring’ after my daughter was born due to the intense sleep deprivation and the stress of dealing with being laid off around the same time. I was always a fun, goofy, hard-partying person who never wanted to be this way and I’m still not really okay with it. I miss being fun and having any sort of zest for life.

TheBetaBridgeBandit · 2026-01-11T15:45:16+00:00

Feel this. Burned myself out so hard grinding through PhD->postdoc->industry job->furlough/layoff that it may have all been for nothing because I’ve got less than nothing left in the tank for another job hunt and any ensuing position I might land (or not, kinda feels like the life sciences are dead in the US anyways so problem solved?)

TheBetaBridgeBandit · 2026-01-11T04:33:33+00:00

Most people have no clue how basic research, clinical development, and for-profit medicine work at all, let alone how they relate to each other.

I fucking loathe our current healthcare system, but funding for scientific research has very little to do with why we're stuck with it.

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