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Advances in understanding how psychedelics work in the brain

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Human
[YOUTUBE]

HD :

This talk presented a brief overview of what psychedelics are, and several significant events in this field in the past four decades. A comparison will be made between molecular structures, and how they were related to the structure of the neurotransmitter serotonin. The receptors that have been identified as targets for psychedelics were discussed, and their brain localization noted, followed by a brief description of where the receptors are located, and what happens inside the cell after the receptor is activated by a psychedelic. Comments included about the different intracellular signaling pathways that can be activated, and which one(s) may be important for altering consciousness. A diagram of connectivity between key brain regions was discussed, which will show how some of the effects of psychedelics may be induced. Particular note will be made of the difficulty in identifying psychedelic molecules in the absence of human experimentation, which is illegal. There will then be a discussion of the use of drug discrimination to identify “LSD-like” molecules, and an example from the author’s laboratory of the use of rigid analogues to identify important structural features of molecules such as LSD. Finally, a discussion was presented of the unique psychopharmacology of LSD, which occurs in two time-dependent phases, and the hypothesis that LSD may be converted in the body into an active metabolite that may be responsible for this time-dependent activity.


Psychedelic Science in the 21st Century, a conference in San Jose, California, April 15-18 2010, organized by MAPS - the Multidisciplinary Association for Psychedelic Studies in collaboration with: the Heffter Research Institute, The Council on Spiritual Practices, & the Beckley Foundation
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A very nice talk! Gotta love this man :]
 
Thanks for posting this, it answers some questions I've had for a long time. The anti inflammatory and immune regulating action of psychadelics is particularly interesting.
 
Thank you for that! Fascinating stuff. And the breakdown of the studies throughout the years is great for reference.
 
i very much enjoyed this elucidatory lecture, but found it curious how Nichols was dismissive of Salvia. i mean, characterizing it as "much ado about nothing" seems a little... mistaken?!
 
blue lunar night said:
... but found it curious how Nichols was dismissive of Salvia. i mean, characterizing it as "much ado about nothing" seems a little... mistaken?!
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I enjoyed this lecture as well. He is a kind and brilliant fellow. I would imagine he has never smoked Salvia Divinorum himself? So much of his assessment is based on his scientific understanding of specific brain functions and the neuroreceptors which fit into his hypothesis and so, respond accordingly. Lady Salvia does not fit into his hypothesis, as a genuine psychedelic. Despite this assessment... it is in fact, most psychedelic in it's effects. But I can also see his vantage point and his educated perspective, as well.

He does mention that he believes that Salvia lacks the "Mind manifesting" quality of other psychedelics. Also, of "no particular illumination" and as lacking "brain activation type effects". Not particularly a complimentary opinion. In addition, he sites the high frequency of the induction of dissociation and dysphoria. And yet, has he smoked any leaf or extract? Or done any quidding? I personally do find it quite mind expanding and dreamlike.

Maybe we need to extend our definition of hallucinogens to include substances that effect other receptors than the serotonin 2A receptors and/or dopamine D2 receptors? Or are these the defining factors? I have a hard time accepting that Salvia only triggers the cap opioid receptors. Anyone know in more detail about where, in terms of receptors, Salvinorin A targets? Or just the cap opioid receptors?
 
I don't know whether this is really relevant here but @ Erowid Online Books : "TIHKAL" - #26 LSD-25

Sasha Shulgin said:
BOL-148. 2-Bromo-N,N-diethyllysergamide. This synthetic ergot derivative, along with its 1-methyl homologue MBL-61 (mentioned below) should be used as powerful tools for studying the mechanism of action of LSD in the human animal. It does not have LSD-like effects in man. At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days, and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD. How can serotonin be argued as a neurotransmitter that is a major player in explaining the action of psychedelic drugs, when this compound is nearly without activity?
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cellux said:
I don't know whether this is really relevant here but @ Erowid Online Books : "TIHKAL" - #26 LSD-25

Sasha Shulgin said:
BOL-148. 2-Bromo-N,N-diethyllysergamide. This synthetic ergot derivative, along with its 1-methyl homologue MBL-61 (mentioned below) should be used as powerful tools for studying the mechanism of action of LSD in the human animal. It does not have LSD-like effects in man. At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days, and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD. How can serotonin be argued as a neurotransmitter that is a major player in explaining the action of psychedelic drugs, when this compound is nearly without activity?
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It can still be argued all right in full force; diferent metabolism, different processing, sequestration and different end-targets of either molecule.
 
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