Does Phenibut Deserve Its Bad Rap? Undervalued Nootropic Effects of Phenibut

Phenibut gets a lot of flack in the nootropics community. It’s tagged as “high risk” on r/nootropics. But this label has justification. Phenibut is a central nervous system depressant with benzodiazepine-like effects. Another reason for Phenibut’s stigmatization is its association with dependence and withdrawal.

I used to avoid Phenibut for these reasons. Given Phenibut’s pharmacodynamic profile, it’s possible that it could increase the risk of cognitive decline, as is observed with benzodiazepines.

I’ve since revised my opinion. Phenibut definitely has a place in the nootropic enthusiast’s armamentarium. I think Phenibut is particularly valuable for enhancing sleep quality. Optimizing sleep quality and cognitive function go hand-in-hand. A great Nature paper discusses how features of sleep spindles correlate with fluid intelligence.

Like Gabapentin, there’s reason to think that Phenibut enhances slow wave sleep. And using drugs to improve slow wave sleep is a solid nootropic strategy, especially if your sleep quality is impaired.

Gabapentin vs Phenibut

Back in 2012, I was doing some research on the effects of anticonvulsants (used to treat epilepsy) on sleep architecture. At the time, I was working in a circadian neurobiology lab.

Most anticonvulsants seem to suppress slow wave sleep (SWS). SWS is the stage of sleep that’s most restorative. It’s when growth hormone is released and is required for the memory-consolidating effects of sleep. Even Lamictal, which is a relatively “clean” drug with a more tolerable side effect profile suppresses deep sleep.

But there’s a notable exception. The anticonvulsant Gabapentin has the opposite effect: it increases slow wave sleep. Although the study was under-powered, 10 healthy subjects treated with Gabapentin realized an increase in slow wave sleep.

Gabapentin is structurally very similar to Phenibut. They’re both GABA analogues. Gabapentin has a cyclohexane ring at the delta carbon of GABA. At this same position, Phenibut has an aryl (phenyl)  group. The molecular geometry of Gabapentin and Phenibut is very similar.

This similar geometry may explain why Gabapentin and Phenibut both block α2δ subunit-containing calcium channels. It’s also this antagonism that mediates Gabapentin’s ability to enhance deep sleep. For a long time, Phenibut was thought to primarily affect GABA-B receptors, but now α2δ subunit-containing calcium channels have emerged as the main target.

It’s not hard to imagine that Phenibut would enhance slow wave sleep as well.  Anecdotally, users have reported that Phenibut improves their sleep quality.

Similar Molecular Geometry of Gabapentin and Phenibut

Gabapentin structure

Gabapentin has a cyclohexane ring at the delta position of GABA.

Phenibut has an aryl group (benzene ring), also at the delta position.

Phenibut has an aryl group (benzene ring), also at the delta position.

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