Edit: Thanks for sending me down the 5-HT2b rabbit hole. This was the cause of the Phen-Fen appetite suppressant heart issues. All psychedelics do seem to affect 5-HT2b receptors. I assume this is a dose dependent effect—where a daily high dose of Phen-Fen would be much more dangerous than occasional low weight psychedelic doses. But I appreciate the grounded caution and more research is clearly needed, ideally before I’m 70+.
Drugs, prescription or not, can be very bad when used in excess or ignorance. These people know what they're putting in their bodies, and have the knowledge and means to test or even make them, but the majority of drug users don't.
The best way to advance may be to let more smart people try drugs without artificial consequences.
Dose is probably important in all this but it’s hard to say with such a small, probably biased, sample size.
And there is no evidence that McKenna’s drug use did not cause his brain cancer. Absence of evidence is not evidence of absence. The best we can say is that we do not know.
Your ignorance does not indicate lack of research in the real world.
<https://en.wikipedia.org/wiki/David_Nutt>
In 2007 Nutt published a controversial study on the harms of drug use in The Lancet.[17] Eventually, this led to his dismissal from his position in the Advisory Council on the Misuse of Drugs (ACMD); see government positions below. Subsequently, Nutt and a number of his colleagues who had subsequently resigned from the ACMD founded the Independent Scientific Committee on Drugs, which was later re-named Drug Science.[18]
(read: the uk government didn't like what he had to say, that drugs weren't totally appalling meritless things, so they sacked him)
from that wiki page
<https://en.wikipedia.org/wiki/File:HarmCausedByDrugsTable.sv...>
<https://en.wikipedia.org/wiki/File:Development_of_a_rational...>
.svg){kind=link}
But the next time drugs comes up you'll doubtless post the same thing.
there are many studies about these medicines - curious where this statement that there are none is coming from?
here's a tip of the iceberg, a good place to start --
https://www.nature.com/articles/s41591-021-01336-3
https://www.tandfonline.com/doi/abs/10.3109/00952990.2016.11...
https://www.hopkinsmedicine.org/news/newsroom/news-releases/...
https://www.hopkinsmedicine.org/news/media/releases/hallucin...
https://www.hopkinsmedicine.org/news/media/releases/magic_mu...
Also I was interested by your other comment suggesting I think that B6 could increase indogenous production of HT-something in the body... Did I get that right? Could you maybe point me to the direction of more of that type of information?
There are lots of studies on the safety of psychedelics.
Maybe if you don't count frying your brain as a risk to your physical health.
It's maybe less funny today but ridicule remains the appropriate response.
heh. that's mostly fair, though DARE waged a propaganda campaign entirely unmatched by teenage druggies, who are mostly just people trying to get by.
A soda a day rots far more brains than an occasional trip.
https://books.google.nl/books?id=wL5G8s3xpxwC&lpg=PR11&ots=w...
Edit: I'm not a smoker, I'm a toxicnaut.
> MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure.
>MDMA has been administered to approximately 1,700 human subjects with only one serious adverse reaction.
There are currently human studies of MDMA. These would probably not be moving forward if they found "brain frying" although I appreciate your willingness to read abstracts
It does "something" to your cognitive abilities that is not beneficial. I don't know how permanent it is. Probably recoverable in most cases?
Maybe not using 3 time a year (or whatever) but multiple times per week for months on end yes, it makes a person get "funny in the head". I've seen it with more then one person.
I'm not anti drug nor denying therapeutic use (makes sense) but I'm fully convinced from observation MDMA is not risk free or harmless, especially when used to excess. Yes, anecdotal. But just a word of advice for whatever it's worth.
The dangers of riding a horse are immediately apparent and it's easy to link cause and effect. Additionally the damage from a bad horse ride (unless you hit your head) are more likely to be physical trauma, a broken leg etc.
The (possible) negative effects of a drug on cognition are more subtle and harder to attribute.
Again, I'm not anti drug at all (especially legally speaking).
It's just, what I saw and I feel I should relate it as a bit of a cautionary tale. I am convinced overuse of MDMA has a negative effects on the kind of cognition that allows a person to plan, link cause and effect, think abstractly and that kind of thing. It's not a scientific study, just what I believe from observation.
One set might be jacked adrenals due to your propensity for epic soundtracks and caffeine or chocolate consumption.
Another set might be alcohol and social feedback.
If you spend a lot of time in these states, your unbiased function diminishes because you are optimizing for a different chemical bias.
If you are not so far gone, or are exceptionally motivated or introspective, you can integrate those experiences, and it might expand your awareness. If you can’t, or don’t, it might increase your function while using but reduce your sober function. This effect will increase as you spend more and more time ‘high’: you are transitioning function within your own constrained cognitive capacity to a different bias.
That range of regulation is what we drift towards when we start adapting to an exogenous compound (some drug) that is consistently present through repeated dosing.
Considering that information, we do adapt to become "normal functioning" (according to the previously mentioned genetics) and it becomes more difficult again when we suddenly remove the drug (again forcing us out of that range that our genetic regulatory mechanisms would like us in)
During periods that we are using the exogenous compound we can form new habits driven by changes made by the drug which can stick around after removal, as removal of the drug won't suddenly undo many of the synaptic changes that occurred. I think this is what we can call the integration of experiences and I think that long term potentiation is a big factor in those changes (which is a pretty neat topic on its own, I'd recommend reading about LTP if you want to understand some of the mechanisms of learning)
that is not use but abuse, and I'd expect bad consequences.
I was surprised to learn the US Military resurrected MDMA in the 50's and then in the 70's Prof Alex Shulgin got hold of it. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931692/
Other country's handled it differently. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435835/
But it does lend credence to the conspiracy theory that the British security services started flooding the football terraces to reduce the football hooliganism that was blighting the British isles, as "documented" by later films like Football Factory starring Danny Dyer and many more.
Still without it, would the world have what the US call EDM and what others call the Rave culture?
If they experienced serotonin syndrome it was quite easy to just point at the reported seratonergic substance that had been ingested (and which also may not have been present at all, depending on the source).
However, the same is repeated in literature about plain methamphetamine, not just methylene-dioxy-methamphetamine, so I would not entirely trust the current state of science on this.
I trust specific doctors who specialize in psychedelic medicine and psychiatry who have deep understanding of the metabolic pathways and pharmacokinetics of these substances.
https://www.pharmacytimes.com/view/serotonin-syndrome-myths-...
You can't know that. Those are pretty common diseases of advanced age. It might've been the drugs, it might not.
His wife took as many psychedelics as he did, right along with him, and she's fine.
With this kind of super-heavy use of novel psychoactive substances, there really can never be anything but anecdotes. We'll never see double-blind studies of large groups of people taking all the substances that the Shulgins took over their lifetimes, so anecdotes are all we have.
"Drugs don't make you stupid. You already were."
I don't know how much I want to put any faith into that being correct; but the anecdotal evidence definitely seems to agree. From my angle at least.
When taking mystery drugs mixed with other drugs, you really have no idea what that's doing to your brain.
First, he knew exactly what each compound was, as he made them himself. He wasn't trying mystery drugs he was completely clueless about.
Second, he tried the smallest dose he suspected might be safe and active, based on his world-class chemical and pharmacological knowledge.
Third, he didn't (to my knowledge) mix novel compounds, but only tried pure ones.
Fourth, if he got even a hint that they might be toxic, he stopped doing them, and only if there were no hints of toxicity did he slowly, very slowly up the dosage and let his wife/friends try it to see if his experiences were unique due to maybe his own body chemistry or other factors.
This nothing like the majority of people, who often don't have the capacity, desire, patience, or knowledge to test their drugs themselves or go to the effort and expense of having someone else do it for them.
Even if the compounds are tested by, say, groups like DanceSafe at festivals, they can only tell you what in the compound they're testing matches their reference sample.. if it also contains some other novel compound that they don't have a reference sample for then they can't tell you what it is. It's a completely different situation from Shulgin, as he knew exactly what was in the compounds he made himself.
What Shulgin did was still risky... especially in the long-term.. and I personally wouldn't do it myself, just as I wouldn't climb Mt Everest, fly in a wingsuit, go extreme skiing, or risk my life/brain in a million other ways, but I'm grateful to him for doing so in the way he did and publishing the results.
Again, that's completely different from the reckless way most people do mystery drugs.
Read the first part of PiHKAL (ie. the part that's deliberately not published on the website the parent HN post links to).
It's all there. He goes in to great detail about exactly how he did what he did and why.
"EXTENSIONS AND COMMENTARY: This specific compound is probably the first sulfur-containing phenethylamine to have been evaluated as a potentially active CNS stimulant or psychedelic. It was a complete, total, absolute unknown. The first trials were made at the sub-microgram level, specifically at 0.25 micrograms, at 11:30 AM on September 3, 1975. Part of this extreme precaution was due to the uniqueness of a new heteroatom in a phenethylamine system. But part was due to the strange manic excitement that occurred at the time of the isolation and characterizing of the final product in the laboratory. Although it was certainly all placebo response, I was jumpy and unable to stay in the lab for more than a few minutes at a time. Maybe dust in the air? Maybe some skin contact with the free base? Now, I know there was nothing, but the possibility of extraordinary potency was real, and I did indeed wash everything down anyway. In fact, it took a total of 18 trials to work the experimental dosage up to as much as a single milligram. In retrospect, overly cautious. But retrospection, as they say, is cheap."
starting at 1/4 microgram (that's 250 nanograms!), took 18 steps up to a milligram. I approve. And thanks BTW.
However, the entry you quote certainly does illustrate his diligence and commitment to safety. I very much doubt he would have been able to discover and sample something like 400+ psychoactive substances in probably many thousands of trials without being as careful and safety-conscious as he was.
Actually, he avoided animal experimentation. In PiKHAL, I believe he wrote that he hadn't experimented with animals in 20 years. His method was to first try each of the substances he discovered on himself.
To paraphrase him he says something like "inserting thermocouples into that rectums of restrained rabbits is not something that I'm much enthused about and I have a jaundiced view of."
I'll try to find that link and update it heh :)
So for your reference that's exactly what I meant by animal experimentation obviously helped him stay safe by giving him some more data on the compound before he took it himself.
edit: link: last paragraph here https://erowid.org/library/books_online/pihkal/pihkal125.sht...
Then again <https://dirtworship.wordpress.com/2013/04/18/sasha-shulgin-o...>
"This (MME) is one of the very few compounds with which I actually risked (and took) the lives of experimental animals" - worth reading the rest
it wouldn’t make any sense to compare it to an existing sample. not to mention the legality of that, depending on where the festival is happening.
if you are curious, all of their tests are available on their website
1) Sasha generally took low/threshold doses. Drugs are all about the dosage. It might not be so easy for you to replicate that.
2) He was an extraordinarily talented chemist and would make the drugs himself. You would need to either use shrooms/peyote (harder to take low doses( or buy from the darknets (with questionable safety and dosage)
3) He is an anecdote/small sample size, we don't have a large scale study here
4) There is an element of survivorship bias - you've never heard of the chemist who made LSD in their 30s and had a mental breakdown because, well, they didn't write a book
1) It's not that hard to take low doses of psychedelics as regularly or irregularly as you'd like. They are extremely non-compulsive.
2) Testing is not so hard these days in many parts of the world. In my city there are at least a couple mass spectrometry machines available for free testing. Besides that, no need for powders from the internet; growing magic mushrooms at home is a simple project anyone can take on.
3) No we don't have a study, so like a lot of things in life we have to rely on more informal observation and anecdotes. A couple of other notable psychedelic old-timers are Albert Hofmann, Paul Stamets. I've met many "psychedelic seniors" over the years, and they've always been very bright, admirable people.
Personally, I've been using psychedelics for 30y, and while I can see that they aren't completely without risks, on the whole they are of great benefit and I plan on aging into becoming one of these psychedelic seniors myself.
4) Psychedelic use is associated with improved mental health outcomes: - https://journals.plos.org/plosone/article?id=10.1371/journal... - https://journals.sagepub.com/doi/10.1177/0269881114565653 - https://akjournals.com/view/journals/2054/5/2/article-p83.xm...
I haven't heard of the psychedelic chemist who had a mental breakdown, I think that's a myth. The biggest risk to mental health for a psychedelic chemist is ending up in prison.
Anecdotally I do know someone who had a psychotic episode on psychedelics and spent awhile in recovery. They eventually did recover, but that did make me wary.
As for your point about doses - low doses are hard on chemicals because you don't know what you're getting. Using mushrooms, well dosage varies wildly per gram depending on what you've picked. It wasn't a point about addiction.
I have had great experiences on threshold doses of mushrooms (and experimented on much higher doses of acid in my past), but I do think a healthy amount of caution is generally good.
Definitely. These are potent levers, not toys. Knowing your dose is critical and really does need to be emphasized. Thanks.
Re: chemicals - you can know very accurately but you really have to know what you're doing and most people aren't up for the effort.
https://www.nature.com/articles/s41386-022-01301-9
"Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline" (in mice)
Why? If you can take a full dose, you can take a threshold dose. Just divide the full dose up - e.g. dissolve a blotter in a 10ml dropper bottle of vodka. Then 1ml = 10% of a dose (or probably a bit less).
Maybe a bit harder for weird research chems, but if you're getting into those then hopefully you'll do the research to know how to dose correctly.
> use shrooms/peyote (harder to take low doses
Again, why? It's particularly easy to take low doses of shrooms, all you need is a scale that measures down to 0.1g, such as a coffee scale.
> you've never heard of the chemist who made LSD
However, they also didn't die. Because then we would have heard about it.
If you have the means ($100? $200) there are labs (or lab) that will test the chemical for you before you take it.
This is allegedly because the government doesn't want to help illegal drug manufacturers to refine their products. Which, if true, is horrible because it doesn't lead to improved safety but to more dangerous illegal drugs.
Anne was there, too. I talked with her afterwards and she was so kind, sharing stories about their last weekend in Barcelona and the power of a mushroom trip combined with Gaudi’s architectural works and sculptures.
It all made me realize: I still want to be taking psychedelics in my old age. Why not?