Psychedelics "reopening the brain's critical periods", shifting production of ECM matrix, and resetting the brain to a more "youthful state"?

#1

https://www.nature.com/articles/d41586-023-01920-2?utm_medium=Social&utm_campaign=nature&utm_source=Twitter&error=cookies_not_supported&code=99c9b8a7-1eeb-44f9-bf6b-dc7d6f12e4b9#Echobox=1686908464

https://www.nature.com/articles/s41586-023-06204-3

It seems that “younger” people don’t need psychedelics (they already have enough risks), though I know some who tried them as teens and it permanently changed them (Grimes is on record for trying LSD at 13, and it seems to have been good for her). [I know two others who tried it at 12-14 for who it has been good for too, though **set and setting** applies 5 times over for those who are underage]

But for older people, they can make all the difference… [like weed, which is NOT good for younger people, but beneficial in older people]

Francis Crick was uniquely creative (by the standards of older scientists) later in life [creating TWO entirely new scientific fields at ages at ages when every other scientist would be declining - while his last major breakthroughs in molecular biology were before 1967 - he was still VERY ahead of his time when he studied consciousness] AND the canonical late bloomer, I wonder if his psychedelic use explained it…

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#2

Michael Pollan’s book, How to Change Your Mind, is very interesting.

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#3

Were/are they happy?

#4

I wonder if SSRIs are also helpful in rewiring the brain?

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#5

The conventional serotonergic psychedelics, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and psilocybin, are suggested to have potentially rapid antidepressant effects with a relatively limited side effect profile (Carhart-Harris et al., 2016; Rucker et al., 2016). In the rat PFC, both in vivo and in vitro, LSD, DMT, and the substituted amphetamine psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) promote neuritogenesis, spinogenesis and synaptogenesis (Ly et al., 2018). Furthermore, the synaptic changes induced by psychedelics may be long term. For example, the reported increase in dendritic remodeling detected within 24 h was reported to last for at least 1 month following a single dose of psilocybin (Shao et al., 2021). To date, there are no studies of how these compounds regulate the ECM. Acute administration of DOI produces robust transcriptional responses by recruiting multiple cell types including glia, and significantly increases expression of parvalbumin and somatostatin in activated neuronal ensembles (Martin and Nichols, 2016). In line with this, both psilocybin and ketamine upregulate parvalbumin expression in neurons expressing the immediate early gene cFos (Davoudian et al., 2023). Upregulated somatostatin, a neurotransmitter expressed by a subset of interneurons ensheathed by PNNs (Willis et al., 2022), may potentially alleviate molecular alterations in the case of SUD, as our recent study identified decreased hippocampal somatostatin expression in subjects with SUD (Valeri et al., 2022). Taken together, we speculate that psychedelic drugs may have similar actions on the ECM as psychostimulant drugs, mediating rapid and sustained ECM disassembly upon administration. However, serotonergic psychedelics are not reinforcing, and therefore likely do not carry risk of addiction (Nichols, 2016). Several studies suggest that psychedelics combined with CBT may be promising candidates for improving SUD outcomes and preventing relapse, as they may promote plasticity of brain circuits involved in reward and goal-directed behavior (DiVito and Leger, 2020), potentially in part through ECM remodeling.

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#6

Inactive psychedelic that helps with cluster headaches, although slower pain relief than DMT.