#22

I’m simply citing standard medical sites and the vast majority of published discussions. For example:
https://med.virginia.edu/toxicology/wp-content/uploads/sites/268/2021/07/July21-Phenibut.pdf
Pretty reasonable write up from medical toxicologists.

Even ChatGPT (that famous medical site!) apparently has it wrong, and is agreeing with the medical toxicologist as it states:
Phenibut primarily acts on two types of receptors in the brain:

  1. GABA-B Receptors: Phenibut is a GABA analog, meaning it mimics the neurotransmitter gamma-aminobutyric acid (GABA). It primarily binds to and activates GABA-B receptors. Activation of these receptors typically leads to a calming or sedative effect.
  2. Dopamine Receptors: Phenibut also affects dopamine receptors, particularly D2 receptors. Dopamine is a neurotransmitter involved in pleasure, motivation, and reward pathways in the brain. By modulating dopamine receptors, phenibut can influence mood and motivation.

These dual actions contribute to its anxiolytic (anti-anxiety), sedative, and mood-enhancing effects. However, due to its potential for tolerance, dependence, and withdrawal symptoms, phenibut should be used cautiously and under medical supervision.

Anyway, don’t have a horse in this race - the question was phenibut being similar to kratom … the answer was no.

I have a rare patient on this, and I don’t see a reason to advise on its use. With Kratom - much more common, and I do feel the need to have expertise (which I have) and be able to advise on it.

I’m pretty happy taking the write-up from the medical toxicologists at University of Virginia. But again, I don’t really care as it isn’t something I’ll advise patients on the use of.

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#23

Unfortunately most of the research on phenibut has come out of Russia, and (aside from being written in Russian) their pharmacology papers are often so poor qualtiy as to be almost worthless.

The best guess as to phenibut’s MoA comes from pregabalin and gabapentin research, and I can tell you from personal experience that pregabalin and phenibut (and also 4-methylpregabalin) would be subjectively indistinguishable for most people. If one is splitting hairs then phenibut is slightly more sedating (which I attribute to the mild GABA-B agonism). Baclofen is a more selective GABA-B agonist and it feels nothing like the pregabalin and phenibut, it’s just a dull sedative.

In an anxiolytic model, the Vogel conflict test, pregabalin produced robust effects in all parental
strains and R217A wildtype mice but was inactive in R217A mutant mice, producing a
small non-significant effect. Furthermore, the anticonvulsant effects of pregabalin in the
maximal electroshock test were seen only at higher dosages of pregabalin than in wild
type mice. These results are consistent with a significant contribution of binding at the
alpha2delta type 1 protein for both anxiolytic and anticonvulsant action of pregabalin in mouse models. [ref]

The D2 claim is just wtf, because I don’t believe you’ll find a single piece of primary literature showing phenibut directly activates D2 receptors (same with GABA-A), much less even binds to them.

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#24

I just meant it is a drug.

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#25

I agree – I guess among the reasons why I stay away from these and won’t Rx Gabapentin or Pregabalin long term is the significant evidence that agents in this area of pharmacology - regardless of exactly what mechanism there is some GABA activity seem to increase risk of dementia. Not nearly as bad as anticholingergics - but it is a risk. Short term/intermittent is something I don’t get excited about.
However, I’d see these agents as likely to increase aging, so I stay away from them. Alcohol gets to fall into the same boat.
On the original question on the post - I’d say Kratom + Rapamycin – just be careful about inhibiting Rapa’s metabolism and boosting levels … and Marijuana — think is going to age individuals prematurely, especially if smoked …

#26

With an edible and EDM @ 180 bpm, I can run forever.

#27

At one point I took phenibut for a few months straight because it was the only thing that touched my gastritis pain. I’ll say that when using consistently there’s some cognitive impairment, mainly issues with semantic memory encoding and abstract and quantitative reasoning.

Preclinical research suggest that alpha2delta is a factor mediating the cell-cell interactions necessary for synaptogenesis, and gabapentin was shown to antagonize this process. That’s been my assumption for what causes the cognitive sides.

While it certainly doesn’t qualify as a nootropic, I think phenibut is a useful tool for acute stress and increasing sociability, or even as a day enhancer. It also combines brilliantly with psychedelics, blocking anxiety while mostly leaving the depth of the experience unaffected. That said, your clinical approach is certainly one that I agree with. Much of my experimetatiom is out of curiosity and psychological optimization, physical longevity isn’t the only factor in my equation.

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