Author Topic: Trip Begins Scientist uncover the molecular origins of an LSD trip  (Read 241 times)

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Offline java

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 Trip Begins Scientist uncover the molecular origins of an LSD trip

https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study


Abstract:
 Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions— both therapeutic and hallucinogenic—are not understood, although activation of the 5-HT2A serotonin receptor (HTR2A) is key. To gain molecular insights into psychedelic actions, we determined the active-state struc- ture of HTR2A bound to 25-CN-NBOH—a prototypical hallucinogen—in complex with an engineered Gaq heterotrimer by cryoelectron microscopy (cryo-EM). We also obtained the X-ray crystal structures of HTR2A complexed with the arrestin-biased ligand LSD or the inverse agonist methiothepin. Comparisons of these structures reveal determinants responsible for HTR2A-Gaq protein interactions as well as the conformational rearrangements involved in active-state transitions. Given the potential therapeutic actions of hallucinogens, these findings could accelerate the discovery of more selective drugs for the treatment of a variety of neuropsychiatric disorders.





https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study
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Offline TryItYoullLikeIt

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Re: Trip Begins Scientist uncover the molecular origins of an LSD trip
« Reply #1 on: September 18, 2020, 03:26:50 PM »
very nice...what's the common name of that 25 structure?
We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita. Vishnu is trying to persuade the Prince that he should do his duty, and, to impress him, takes on his multi-armed form and says, 'Now I am become Death, the destroyer of worlds.

Offline java

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Re: Trip Begins Scientist uncover the molecular origins of an LSD trip
« Reply #2 on: September 18, 2020, 03:37:54 PM »
25CN-NBOH (or NBOH-2C-CN) is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 by a group of researchers at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B.[1][2][3][4] In animal studies, 25CN-NBOH was found to partially substitute for DOI but was considerably weaker at inducing a head-twitch response in mice.[5][6] Another in vivo evaluation of 25CN-NBOH concluded that "Given its distinct in vitro selectivity for 5-HT2A over non 5-HT2 receptors and its behavioral dynamics, 25CN-NBOH appears to be a powerful tool for dissection of receptor-specific cortical circuit dynamics, including 5-HT2A related psychoactivity."[7] Additional in vivo investigations with this ligand is emerging.[8][9] At tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.[10]


....see
  https://en.wikipedia.org/wiki/25CN-NBOH
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Offline TryItYoullLikeIt

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Re: Trip Begins Scientist uncover the molecular origins of an LSD trip
« Reply #3 on: September 19, 2020, 03:16:49 PM »
Interesting
We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita. Vishnu is trying to persuade the Prince that he should do his duty, and, to impress him, takes on his multi-armed form and says, 'Now I am become Death, the destroyer of worlds.

Offline java

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"If you like yourself....then take care of yourself"

Offline TryItYoullLikeIt

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Re: Trip Begins Scientist uncover the molecular origins of an LSD trip
« Reply #5 on: September 21, 2020, 03:42:39 PM »
damn, Tsath writes a tome there haha
We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita. Vishnu is trying to persuade the Prince that he should do his duty, and, to impress him, takes on his multi-armed form and says, 'Now I am become Death, the destroyer of worlds.