Classical psychedelics and benzodiazepines - does inhibition of subjective effects negate potential neurological/psychological benefits?

[Vastness]

Something I've been wondering for a while - obviously it is well know that benzodiazepines primarily, but to a less extent even gabapentinoids sometimes have a somewhat muting effect on some of the actual deeper headspace of psychedelics (the latter group being perhaps a bit more up to debate, I don't have much experience with the combination myself, but it seems likely there would be a muting of sorts of the deeper mind expanding effects - benzos, however I have a fair bit of recent experience combining with psychedelics, for better or worse - specifically diazepam).

Anyway I wonder if this translates to a blockage of the measured effects of significant increase of "crosstalk" within the brain, and by extension, or separately, most or all of the longer term proposed neurological and psychological benefits (assuming for the moment, that this is a given within this hypothesis, no matter your own thoughts on the current science and the exact definition of a "benefit").

My own perception is that there probably is some muting effect to the therapeutic potential, but not a complete negation, as I still feel I learn lessons and new perspectives on life even within the messier benzo-clouded escapades... although the "purer" ones, undiluted by such chemicals are unquestionable more profound and I would venture to say clearly more "useful" over, the alternative which admittedly, can become a largely heonistic pursuit.

Interested both in scientific interactions at the neurochemical level, and interpretations of the likelihood of changes at the more ethereal psychological level as a result of this. Either proven data or pure speculation is welcome!

 

[Skorpio]

I feel like this question can be boiled down to these three points.

1) Do sedatives cloud the experiential aspect of psychadelics?

2) Are the beneficial effects of psychadelics divorcable from the experiential effects? (How much of the beneficial effects are biochemical a la BDNF and how much are from the radical change in perspective?)

3) Do sedatives inhibit the biochemical processes of psychs?

I do think an argument could be made that this view is too dualistic, but I dont think its cut and dry either way.

Studies show beneficial effects (increase of BDNF) of psychadelics in both rodents and cultured cells, which leads credence to some degree of a biochemical effect that can reduce depressive and addictive behaviors (in rodents, not cultured cells). The cultured cell experiments are interesting to me because they are unable to experience crosstalk and increased entropy, so

But psychadelics do have stronger benefits in therapeutic settings, and people have the best results typically when they have strong mystical experiences.

So, there is probably some contribution of both aspects here. I personally think sedatives will dose dependently blunt the psychological effects, although a low dose that takes away fear may facilitate introspection. High doses will cause amnesia, which will void the psychological effects.

I am not sure to what degree sedatives will inhibit the biochemical effects of psychadelics. This is an interesting question to me and I will scan the literature. (Also it would honestly be a pretty cut and dry experiment to do it in cell culture or mice and have a nice western blot of BDNF/trkb phosphorylation as your reporter.

I guess I didnt really answer the question, but those are key factors in it. Maybe somebody else could add something pertinent.

Here are my refs
Cell culture increases bdnf/nerve growth phenotypes

Psychedelics Promote Structural and Functional Neural Plasticity

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote …

www.sciencedirect.com

Psychs are anti addictive in mice

A single administration of the hallucinogen, 4-acetoxy-dimethyltryptamine, prevents the shift to a drug-dependent state and the expression of withdrawal aversions in rodents - PubMed

Despite several studies suggesting the therapeutic use of 5-hydroxytryptamine receptors type 2A (5-HT_2A ) agonists in the treatment of substance use disorders, the neurobiological basis accounting for such effects are still unknown. It has been observed that chronic exposure to drugs...

www.ncbi.nlm.nih.gov

A good primer on the high level effects on psychs and cognition

REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical...

pharmrev.aspetjournals.org