Editor’s note: With Mark Crislip away on yet another vacation, we present an inaugural guest post from Abby Campbell, a practicing MD, Ph.D and contributor at HealthyButSmart.com. Welcome Abby!
Ball-and-stick diagram of the phenibut molecule
On average for the past year, phenibut has been typed into google 49,500 times a month. Phenibut is a supposed wonder drug that claims to promote sociability and lessen anxiety.
When people run that search in Google, they find stores that sell phenibut, as well as blogs and forums where people discuss and make recommendations for the use of phenibut. The main qualification of these people is that they themselves have taken the drug.
What a searcher doesn’t find is any reference to any credible research. Yet another supplement market has been born driven by anecdotal social marketing, and no one seems to care about the evidence.
What is phenibut?
Phenibut is a designer drug which was synthesized by a group of Russian scientists in the 1960s. Perekalin and his colleagues in St. Petersburg added a phenyl ring to butyric acid to make what we now call phenibut. The addition of the phenyl group to the butyric acid enables the compound to cross the blood-brain barrier and enter the brain.
This basic chemical structure of the compound explains the origins of the name ‘phenibut’. Phenibut is also known as fenibut and is sold under the brand names of Noofen and Citrocard.
Phenibut is structurally similar to the neurotransmitter GABA (gamma amino butyric acid). GABA occurs naturally in the human nervous system and has a calming effect on the brain.
GABA itself does not cross the blood brain barrier and so is not viable as a drug or supplement to reduce anxiety. The addition of the phenyl ring by the Russian scientists overcame the problem of penetration into the brain. However this means that phenibut is not totally identical to human GABA which means that we can’t just extrapolate information on GABA to phenibut, as some websites have done.
What is phenibut used for?
Phenibut is a licensed medication in Russia and is used for a variety of conditions including anxiety, insomnia, post- traumatic stress disorders, depression, stuttering, tics, attention deficit disorders, and vestibular disorders.
Unlike most other anxiolytic drugs, phenibut is also promoted as a nootropic drug, which implies that it can improve motivation, attention, and concentration.
Phenibut is not licensed as a prescription medication by the FDA in the USA but is available as a nutritional supplement.
It is interesting to look at the process behind the licensing of nutritional supplements to understand why phenibut is positioned as a nutritional supplement and not a drug.
Individual countries review the data on any agent and make a decision as to whether or not to allow the sale of that substance. As an example, St John’s Wort and gingko are approved for sale in the USA but it is illegal to sell them in Ireland.
Substances which are approved for sale can then be licensed as either a medicinal product or as a dietary supplement. The Dietary Supplement Health and Education Act of 1994 (DSHEA) defines and oversees dietary supplements in the USA. Phenibut fits under the remit of the DHSEA as a synthetic amino acid derivative. The FDA has guidelines on the regulations for labelling any dietary supplement – specifically if any dietary supplement such as phenibut claim to affect well-being or the structure or function of the body then there must be a disclaimer stating that the claim has not been evaluated by the FDA and that the product is not intended to treat to prevent any disease.
However there is a technical loophole in the labelling guidelines for dietary supplements. The FDA tries to make a distinction between ‘disease’ claims and ‘health maintenance’ claims when it comes to dietary supplements. The FDA tightly regulates ‘disease claims’ but there is much less regulation when it comes to ‘health maintenance’ claims. As an example, it is perfectly acceptable to say that calcium helps build strong bones but not OK to say it cures osteoporosis. So technically this means that a manufacturer of phenibut can decide to say that their product ‘helps keep you calm’ which is a ‘health maintenance’ claim. However they cannot say that phenibut ‘reduces anxiety’ (a disease claim) without getting FDA approval.
Another advantage of fitting under the ‘health maintenance’ umbrella is that the FDA does not require the manufacturer to obtain pre-marketing authorisation, as is the case with supplements making disease claims.
So phenibut has dodged that hurdle for the time being, but the real question is, “Do their claims have any scientific validity?”
Let’s take a look.
So Russian cosmonauts used it…
There is an “interesting” story about the use of phenibut in the Russian space program. In 1975, a US-Russian joint space mission known as Apollo-Soyuz ran into technical problems on the Russian side. No solution could be found to fix the docking mechanism of the Soviet Soyuz spacecraft.
When all seemed lost, the Russian astronauts were instructed to take phenibut and rest. According to the story, the restorative powers of the rest and phenibut helped the astronauts stay calm find a really creative solution to the problem which saved the day.
This popular story speaks to the combined anxiolytic and nootropic effects of phenibut which is sometimes called ‘the Russian wonder drug’.
Story telling has been described as ‘data with a soul’ and this is, to some, a great story. Sometimes it is easy to be carried away with a story which romanticizes a difficult situation.
It is great that things worked out for the Russian team but it is worth noting that phenibut was used as a last ditch effort when all else had failed and there was nothing to lose. The Russians certainly did not use phenibut as an early performance enhancer, as some websites have claimed.
What is the actual evidence for phenibut in the medical literature?
There are over 300 published papers on phenibut. This is actually relatively little information on a drug that has been around for over fifty years.
Many of these publications are in the Russian language and/or are based on studies in cats, rats or mice. Straight away this raises issues. Our four legged friends are great but can hardly tell us much about a prosocial wonder drug (and may fail to reveal problems in humans).
One online medical platform summarized things simply by saying “phenibut has not been studied in people and so no-one can say if it might work as a medicine.”
But if someone was trying to be overly fair to phenibut, they could say that the lack of information on it can be explained by the fact that it is not a licensed medication in the USA.
So let’s look in more detail at the available research to see what support there is for the many claims about it.
Does phenibut relieve anxiety?
I was able to find just 37 studies relating ‘phenibut’ and ‘anxiety’. The majority of these studies are in the Russian language which makes it difficult to assess the quality of the information. From just looking at the title of the Russian studies we can tell that quite a few of these studies are based on rat, mice or cat models.
The human studies are largely confined to observational studies in children and all come from one research group in Russia.
The same group did a study in adults and gave phenibut at a dose of 1,000mg/day to 62 adults with protracted anxiety-phobic disorders and concluded that the findings “may lead to the conclusion that phenibut is highly effective in the treatment of patients with protracted anxiety phobic disorders.”
For one, this is a tiny sample, it’s only ever been looked at by one group of researchers, and in a study not subject to peer review.
For two, this study used phenibut in people with protracted anxiety, not like the people you read about on internet forums trying phenibut for a “little social worry”.
Oh, and the risks?
Two studies described phenibut-related dependence and withdrawal symptoms. One of the case reports in The BMJ described a patient who self-medicated with phenibut for anxiety. The patient reported that the phenibut was beneficial at the beginning but that he subsequently developed tolerance and withdrawal symptoms. The withdrawal symptoms were severe and the patient needed a nine-week detoxification program under medical supervision to come off phenibut. It would be pretty hard to justify any initial anxiety relief given the fact that the patient needed a nine week detox.
Bottom Line: There is no solid evidence to support the efficacy of phenibut in anxiety and there are reports of significant side effects.
Does phenibut help with sleep?
I found five published papers relating to sleep and phenibut. Only one of these studies related to humans, and it looked at phenibut in patients with alcoholic abstinence syndrome. Again this is nothing that would be of any use to someone who was just looking for a nutritional supplement that promotes a good night’s sleep.
Bottom Line: There is no convincing direct evidence that phenibut helps with sleep.
Does phenibut help in body building and weight training?
Again there are no great studies on phenibut for body building or weight training. There are some studies on the use of other GABA-like drugs on growth hormone which have been extrapolated to mean that phenibut may benefit be of benefit in body building. However there is no direct evidence that phenibut itself helps with body building and we cannot just extrapolate from GABA-based drugs to phenibut.
Bottom Line: We can’t say either way if phenibut helps in body building and weight training.
Does phenibut enhance sexual performance?
There are no published studies or case reports on the role of phenibut in enhancing sexual performance. Even the original studies which looked at the relationship between the structure of phenibut and its activity makes no mention of a role for phenibut relating to sex.
Bottom Line: We can’t say either way if phenibut enhances sexual performance.
What are the side effects of phenibut?
Side effects of phenibut include headache and depression. An overdose of phenibut can result in lowered body temperature, muscle relaxation and sleepiness.
There is an editorial which describes phenibut as a potentially dangerous product. There is also a case report of two patients who purchased phenibut online and who presented to urgent care with serious phenibut related toxicity. Both patients had measurable levels of phenibut in their blood.
One of these patients used phenibut with THC and alcohol and had to be admitted to the intensive care unit for airway protection. He needed airway protection because of his ‘behavioural state’. This is really worrying and should be the end of the line for anyone doing their best to be “open minded” about phenibut.
Even the original research on phenibut says that its effects depended on the emotional state of the animal. Anxious but passive cats had reduced anxiety but developed aggression (and phenibut did not affect the aggression of already-aggressive cats)!
But this of course is beside the point.
Bottom line: To put it mildly, Phenibut does not have a good safety profile.
Conclusion: Clever marketing, little evidence
Phenibut is a cleverly-designed drug with an even cleverer marketing campaign. There is no legitimate evidence to support the fact that it works for any of the stated purposes, but there are worrying reports of significant toxicity. Efforts should be made to balance the informational scales, and lessen enthusiasm for yet another untested marketing-driven supplement.