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1/ Ever heard of the “brain supplement” PHENIBUT? It’s available online and reports of toxicity and withdrawal have popping up over the last decade. Here’s a #tweetorial to help inform our colleagues. @AdamRodmanMD @medpedshosp @ToxAndHound
2/ First, a poll. Which of the following medications does phenibut’s chemical structure most resemble?
3/ Phenibut and baclofen are nearly identical structurally, except one additional chlorine. There are also structural similarities to our primary inhibitory neurotransmitter, GABA, and to gabapentinoids. Understanding this can help us understand what to expect from phenibut use 
4/ Phenibut was synthesized in the early 1960s by Russian scientists, and was reported to have GABA-B agonist activity, as well lesser GABA-A and dopamine agonist effects. (PMID: 11830761) Baclofen also exerts its effects as a GABA-B receptor agonist.
5/ Phenibut’s anxiolytic and “mind focusing” effects were thought to be beneficial in high stress situations. As such, Russian cosmonaut first aid packs reportedly carried phenibut. PMID: 661205 theconversation.com/weekly-dose-ph…
6/ Phenibut has been marketed online in recent years as a dietary nootropic (aka “smart drug” or “cognitive enhancing”) supplement. Here are some photos of product I found online.
7/ In the early 2010s, reports began arising of phenibut withdrawal manifesting w/ agitation & hallucinations, and insomnia. Then reports of phenibut toxicity manifesting as CNS depression, or CNS excitation with delirium. PMID: 26114346
8/ Why would overdose produce CNS depression and/or excitation? Shouldn’t it be one or the other? That’s interesting because a similar spectrum of effects of toxicity is noted with phenibut’s close cousin, baclofen. PMID: 16454779
9/ The thought is that pre-synaptic GABA-B receptors get flooded by baclofen (or phenibut), which then “inhibits the inhibitor” (ie inhibits the release of GABA by inhibitory neurons) thereby potentially causing CNS excitation and seizures.
10/ Following regular phenibut use, a withdrawal syndrome similar to ETOH or benzo WD can occur. Tx with benzos is a start, but baclofen may be needed to obtain control. Baclofen doses ranged 10-30mg 3x/day. (PMID: 28614159; PMID: 30878413)
11/ Another paper (PMID: 23391959) used a slow phenibut taper and a 20 week (😮) baclofen taper for outpatient management of phenibut dependence. The authors estimated 10mg of baclofen was needed to substitute for 1 gram of phenibut.
12/ Phenibut use may be used with another nootropic, tianeptine (TNPT). TNPT is also purchased online, and may be used for its antidepressant or mu opioid agonist effect. TNPT looks like a TCA, but doesn’t seem to have the extreme CV- & Neuro-toxicity of a TCA. (PMID: 30070980)
13/ I’ve not been able to locate any statement that phenibut is illegal in the US. However, the FDA issued a warning letter to some companies earlier this year, stating that phenibut does not meet the definition of a “dietary ingredient.” It's still readily procured online.
14/ A final poll to review. Phenibut can/is:
15/ Thx @ToxTalks @jonbcole2 @jmmarraffa for their prior reports in this area. Here’s a link to my PubMed search string if you’d like to learn more. //END// tinyurl.com/y4evuujp
