Albert Hofmann's last trip

[C Elegans]

Albert Hofmann, the inventor of lysergic acid diethylamide, LSD, died yesterday aged 102 (so obviously, LSD can't be that bad for your health ).
Obituary: Albert Hofmann, LSD inventor - Telegraph

Seriously, although LSD as a drug of addiction certainly can have harmful effects in some invidivuals, LSD as a neuropharmacological research tool has been of immense value for us working in the field of neuroscience. LSD has contributed to increased understanding of the function and mechanics of the major transmitter substance serotonin, and aided the first steps towards an understanding of the neurobiological basis for human experience. Furthermore, LSD has been highly useful in research about altered states of mind in the healthy and diseased brain. Although LSD has not, as Hoffman himself hoped, proven directly useful as treatment against schizophrenia, it has certainly paved the way for research about psychotic symtoms and other extraordinary experiences that are features of severe neuropsychiatric disorders. It's a fantastic compound.

Judging from the - still limited, mind you - knowledge we have today about the effects of LSD, it is obvious that the dangers of LSD was heavily exaggregated back in the 1960's when the compound was classified as an illegal drug and globally prohibited. Whereas I absolutely do not support Timothy Leary's non-scientific positive support for LSD as a theurapeutic, scientific studies have shown that moderate LSD use in a controlled setting, is not at all associated with the risks that was claimed when it was prohibited. Thus, I was happy to see the ban lifted a few years ago, so LSD and psilocybin (the active hallucinogentic substance in "magic mushrooms", also acting on the serotonin system and also first synthesised by Hoffman) can now be used for research purposes.

RIP dr Hofmann and thanks for this lovely molecule I say that as a researcher. I have never tried if myself. I'd like to, when I get old and don't need to worry about potential aversive effects.

[VonDondu]

I'm not sure what to say about this. Obviously, he was a man who made a contribution to the world, and he seems to have been a swell guy. It's nice that he lived such a long, happy life.

It's too bad that he had to spend so much of his time and energy dealing with the controversy over his invention. To some extent, it was his own fault for promoting and defending his "baby". He couldn't just say, "Take it or leave it." But what else was he supposed to do? The problem with an invention like that is, once you've invented it, nobody seems to hear about the rest of your work. It's like what Jimmy Page said about the success of his song Stairway to Heaven: "How would YOU like to spend the rest of your career trying to top that?"

By the way, if you think LSD is so cool, what about hallucinogenic mushrooms (which are chemically related) and Ecstasy (which was intended to be used as an aid during psychotherapy sessions)? Frankly, I've never had any faith in the potential of mind-altering drugs like the former; but mood-altering drugs like the latter seem more promising. That's just my own uninformed opinion, of course, and it would be nice to hear an informed opinion for a change.

[C Elegans]

Ecstacy, or MDMA, is from my perspective not as all as interesting as LSD, since it is a much "dirtier" molecule, ie it binds acts on several different transmitter systems, not only serotonin but also norepinephrine and dopamine. For research about the function of certain receptors or certain transmitter system, it is better the more selective a molecule is. MDMA is also associated with more adverse effects than LSD, so it will probably never be safe to administer to humans. A pity, since it would be highly interesting to study the putative interaction effects between the serotonin system and the "attachment" hormones oxytocin and vasopressin. Rodent studies have shown that oxytocin and vasopressin are released when MDMA is administered, but the effects on social behaviour would of course be more interesting to evaluate in humans than in rodents.

Magic mushrooms on the other hand, contains psilocybin which is much more closely related to LSD. It's already been used in several studies of attention and memory in humans. Since psilocybin mainly acts on the serotonin 5-HT1A and 5-HT1B receptor, and there are other selective compounds that can block specifically 1A or 1B actions, psilocybin is used as a mechanistic tool to investigate the effects of one receptor subtype at the time. Ie people do a cognitive task without having taken any drugs. Then they do the same task when psilocybin has been administered. Then they do the same task when psilocybin+a 5-HT1A blocker has been administred, which means only the 5-HT1B effects are "in action". Then they do the same task when psilocybin+a 5-HT1B blocker has been administrated. And so on. So psilocybin is also useful, although the pharmacology of LSD has been far more researched.

My interest, and positive views on so called mind-altering drugs, are merely from neuropharmacological research perspective. We can learn more about the biochemistry of human experience in general, and about certain types of experiences that might be related to brain disorders. I am completely unintrested in these drugs as any kind of psychotherapeutics. There have been claims that hallucinogenic drugs facilitate the effects of psychotherapy, but no evidence of this is present since no controlled studies have been performed.
Although Hoffman rejected the extreme ideas proposed by Leary, he still believed LSD would have therapeutic effects in psychiatric disorders. My impression is however that Hofmann believed in the pharmacoterapeutic properties of LSD rather than psychotherapeutic. There is some evidence that LSD and psilocybin may have effect against cluster headache and also some evidence that LSD may be useful in drug addiction treatment. The evidence is weak though, since no randomised, placebo-controlled studies have been performed. Theoretically, it is fully plausible that LSD and/or psilocybin have an effect on cluster headache, since this it's a form of migrain and serotonergic drugs work against migraine. However, I certainly think molecules like LSD and psilocybin should not be used as direct pharmacological treatment due to safely concerns. LSD increases the risk for psychosis, and it is not known if this is true for everyone, or if it just triggers psychosis in individuals who are already prone for this. Currently there is no way to predict who will develop psychosis or not following LSD use, so even if the absolut risk of LSD-induced psychosis is small, it is still an unacceptable risk. Psilocybin use is also associated with certain adverse effects, and MDMA even more so. Thus, my view is that these substances should continue to be used as neuropharmacological research tools, for basic research and for aiding identification of target receptors of interest for development of selective compounds that can be used to treat disease.

[VonDondu]

Very interesting. Thanks for the info.