strongvirtue
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- Joined
- Apr 22, 2021
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Very interesting study, which has found that psychedelic drugs may work by activating receptors that are not accessible to serotonin itself, which explains their therapeutic effects in promoting neuron growth in the brain. This supports the idea that the whole cell is a receptor, as suggested by Ray Peat. Psychedelics are believed to have therapeutic effects due to their ability to promote plasticity in cortical neurons.
www.chemistryworld.com
"Now, researchers in the US have shown that psychedelic drugs promote this neuronal growth by activating intracellular serotonin receptors that are actually inaccessible to serotonin itself. David Olson, the director of the Institute for Psychedelics and Neurotherapeutics at the University of California, Davis, explains that the project stemmed from a problem that had puzzled his group for a long time."
‘We did a lot of mechanistic work that demonstrated that the serotonin 2A receptor is responsible for the plasticity promoting properties of psychedelics in the cortex, and some of their therapeutic behavioural effects,’ says Olson.
‘But what really surprised us was that serotonin itself did not have a lot of these same properties.’
So, Olson’s team set about investigating the structure–activity relationship of compounds that bind to serotonin receptors. By making simple modifications to serotonin and related compounds, these experiments revealed that the molecules’ lipophilicity – their greasiness – seemed to correlate with their ability to promote neuron growth. ‘That suggested to us for the first time that maybe the target was on the inside of the cell,’ says Olson. ‘And so these really greasy compounds that can cross cell membranes can access the target, but very polar molecules like serotonin might not be able to.’
Another question raised by Olson’s team’s project is whether serotonin is really the natural ligand for intracellular serotonin receptors inside cortical neurons. ‘One possibility is that perhaps there are ligands that can cross membranes and activate these receptors,’ says Olson.
Lipophilicity helps explain psychedelic drugs’ therapeutic effects
Understanding why psychedelic drugs that bind to serotonin receptors promote neuron growth, while serotonin itself does not
www.chemistryworld.com
"Now, researchers in the US have shown that psychedelic drugs promote this neuronal growth by activating intracellular serotonin receptors that are actually inaccessible to serotonin itself. David Olson, the director of the Institute for Psychedelics and Neurotherapeutics at the University of California, Davis, explains that the project stemmed from a problem that had puzzled his group for a long time."
‘We did a lot of mechanistic work that demonstrated that the serotonin 2A receptor is responsible for the plasticity promoting properties of psychedelics in the cortex, and some of their therapeutic behavioural effects,’ says Olson.
‘But what really surprised us was that serotonin itself did not have a lot of these same properties.’
So, Olson’s team set about investigating the structure–activity relationship of compounds that bind to serotonin receptors. By making simple modifications to serotonin and related compounds, these experiments revealed that the molecules’ lipophilicity – their greasiness – seemed to correlate with their ability to promote neuron growth. ‘That suggested to us for the first time that maybe the target was on the inside of the cell,’ says Olson. ‘And so these really greasy compounds that can cross cell membranes can access the target, but very polar molecules like serotonin might not be able to.’
Another question raised by Olson’s team’s project is whether serotonin is really the natural ligand for intracellular serotonin receptors inside cortical neurons. ‘One possibility is that perhaps there are ligands that can cross membranes and activate these receptors,’ says Olson.
