Charles_Voynich
Greenlighter
- Joined
- Apr 13, 2017
- Messages
- 32
DMT is absolutely the primary endogenous ligand of the Sigma1R:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/
Considering what we're starting to know about the psychedelic's unilateral ability to induce neural plasticity, increase dendritic branching, dendritic spines, stimulate production of neurotrophic factors, and modulate synaptic homeostasis, I see absolutely no reason why DMT would not be an endogenous regulator of neuroplasticity. Of course there are some theories that DMT is preferentially produced during REM sleep as a means to maintain synaptic homeostasis, which is fine and good and all but as of yet unproven. Interestingly enough, the enzyme that is responsible for producing DMT (indolethylamine N-methyl transferase, INMT) is absolutely not expressed in the human brain, with expression highest in lung tissue:
https://www.ncbi.nlm.nih.gov/pubmed/10552930
There is also some evidence to suggest that DMT is actively transported across the BBB by means of an unknown transporter, although those studies are rather old and may be dubious. Taken together with DMT's incredibly short half-life, this seems to suggest there's a system designed to move DMT into the brain, and the inactivate it, with phenomenal efficiency and speed. Also, the Sigma1R has been shown to respond to DMT in two unique, dose-dependent modes; at low doses, the Sigma1 ligands facilitate assembly of Sigma1R trimers, disassociate BiP, cause mitochondrial Ca2+ influx and IP3R activation (not to mention BDNF secretion), whereas at high doses, the Sigma1R gets trafficked to the plasmalemmal membrane where it inactivates voltage-dependent sodium and potassium channels. I think this bi-directional, dose-dependent Sigma1R activity serves as a "volume knob" for neuroplasticity.
In short, hell yeah DMT has a "purpose". I'd like to see an INMT knockout animal and test them for learning and memory deficits!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/
Considering what we're starting to know about the psychedelic's unilateral ability to induce neural plasticity, increase dendritic branching, dendritic spines, stimulate production of neurotrophic factors, and modulate synaptic homeostasis, I see absolutely no reason why DMT would not be an endogenous regulator of neuroplasticity. Of course there are some theories that DMT is preferentially produced during REM sleep as a means to maintain synaptic homeostasis, which is fine and good and all but as of yet unproven. Interestingly enough, the enzyme that is responsible for producing DMT (indolethylamine N-methyl transferase, INMT) is absolutely not expressed in the human brain, with expression highest in lung tissue:
https://www.ncbi.nlm.nih.gov/pubmed/10552930
There is also some evidence to suggest that DMT is actively transported across the BBB by means of an unknown transporter, although those studies are rather old and may be dubious. Taken together with DMT's incredibly short half-life, this seems to suggest there's a system designed to move DMT into the brain, and the inactivate it, with phenomenal efficiency and speed. Also, the Sigma1R has been shown to respond to DMT in two unique, dose-dependent modes; at low doses, the Sigma1 ligands facilitate assembly of Sigma1R trimers, disassociate BiP, cause mitochondrial Ca2+ influx and IP3R activation (not to mention BDNF secretion), whereas at high doses, the Sigma1R gets trafficked to the plasmalemmal membrane where it inactivates voltage-dependent sodium and potassium channels. I think this bi-directional, dose-dependent Sigma1R activity serves as a "volume knob" for neuroplasticity.
In short, hell yeah DMT has a "purpose". I'd like to see an INMT knockout animal and test them for learning and memory deficits!