The consensus on phenibut is divided among people. Some say that phenibut is a miracle supplement that both energizes and calms you. Other says that phenibut is a dangerous and addictive drug that ought to be controlled by the FDA.
So, what’s the truth? As with most things, the truth lies somewhere in the middle. Taking phenibut supplements can improve cognitive function, especially for those with anxiety. But, users need to be careful. Knowing the risks is essential.
History Of Phenibut
Phenibut is not classed as a pharmaceutical in the United States but is available online as a supplement. You may be wondering how this situation came to be.
Origins
Phenibut was synthesized in the 1960s by Russian researchers trying to make an effective analog for the neurotransmitter GABA.
GABA (Gamma-aminobutyric acid) is the most important inhibitory neurotransmitter of the central nervous system. Adrenaline increases the number of impulses firing between connected neurons, while GABA decreases them. GABA also reduces pain signals, anxiety, and protects against excessive CNS stimulation, including epileptic seizures (1).
The structure of GABA was the starting point. GABA itself is not an ideal medication because drugs given orally must cross the blood-brain barrier to work in the brain. It was thought that by adding chemical groups to GABA, a synthetic analog could be created that better crossed the barrier, increasing its bioavailability and effectiveness (2).
Testing
Phenibut and other synthetic versions of GABA with various modifications were tested for their efficacy in vitro using isolated cat neurons. This test did not involve crossing the blood-brain barrier. While all the synthetic analogs reduced the rate of neuronal firing, none were as effective as GABA. The most potent matched only 70% of GABA’s effect (3).
In vivo tests using rats were performed next. These measured the binding of GABA and its modified analogs at GABA receptors in the brain. All the analogs, including phenibut, bound to these receptors, but less than GABA itself. Even though it was better at crossing the blood-brain barrier, its reduced binding ability at the receptor counteracted this (4).
Phenibut was found to have a similar profile of effects to GABA, but not identical. For example, while GABA acts as an anticonvulsant (seizure preventative), phenibut completely lacks this quality.
Regardless, the results were promising, and Russia approved phenibut for use as a regulated pharmaceutical shortly after its discovery (5).
Status In The United States
Outside of Russia and several neighboring countries, phenibut is not an approved pharmaceutical. In the United States, it is available as a supplement from several online retailers. People report using it to treat social anxiety or improve their cognitive performance. However, others report using it as a recreational drug due to its euphoric effects (6).
In 2019, the FDA issued warning notices to three companies that included phenibut in products labeled as dietary supplements. This was due to evidence suggesting that its neuroactive properties were too strong to be considered as a “dietary” additive. The FDA feared that this label would cause people to assume it was safe and not exercise caution (7).
The Australian government took this concern one step further and designated phenibut as a controlled substance. This means phenibut is unavailable for sale there. The government cited its potential for addiction, withdrawal symptoms and evidence of acute toxicity as reasons for its ruling (8)
For now, phenibut is easily available in the US. Many choose to use it as a nootropic for its cognitive-enhancing abilities. Or, because it reduces anxiety. Others may experience negative side effects, become addicted or feel withdrawals.
Is phenibut safe to use?
It certainly has the potential to benefit and harm the user, depending on how it is used. Having a good understanding of what it is and how it works is a good place to start if you are considering using phenibut supplements.
Effects of Phenibut
Phenibut has a broad spectrum of inhibitory effects on the central nervous system. These include relieving anxiety, treating attention and cognitive disorders, and protecting the brain from damage.
Regulating The GABA System
As a GABA agonist, phenibut mainly works by stimulating GABA-(B) receptors, one of the two classes of GABA receptors. When activated, they start a signal cascade that has downstream effects on certain kinds of brain signaling (9).
This effect is inhibitory. It stops neurons that receive signals from passing them on. This includes anxiogenic signals, those associated with feelings of stress and anxiety. These signals are produced by other neurotransmitters like cortisol. 36/105 user reports from a review of online drug and nootropic forums listed anxiety relief as the desired outcome, with 24 claiming success (10).
GABA activity increases the incidence of alpha brain waves – the kind that promotes a wakeful, attentive and creative state without increasing stress and anxiety (11).
Reducing Anxiety
Studies show phenibut works as an anxiolytic – an anxiety reducer. A Russian study of 62 individuals with anxiety disorders gave subjects either Phenibut or a related compound, Mebicar. Reductions in anxiety were assessed across five standardized testing methods for anxiety symptoms. 79% of the subjects experienced a significant reduction in anxiety, although the trial was not placebo-controlled, as is the standard in the United States (12).
Strikingly similar results were found in another study with the same sample size. 1000 mg/day of phenibut given orally reduced anxiety symptoms for 73.3% of the group. The group also performed better on the Mayer-Salovey-Caruso emotional intelligence test (13).
Emotional intelligence measures a person’s ability to read people, pick up on social cues and form appropriate responses. It is essential in forming and maintaining interpersonal relationships. It is significantly impacted by anxiety disorders, suggesting that phenibut can be specifically helpful for treating social anxiety.
Treating Cognitive Disorders
Several harmful conditions are caused by excessive stimulation of neurons in the brain. As a GABA agonist, phenibut can help to treat these conditions by inhibiting neuronal activity.
One such condition is tension headaches. Also called stress headaches, they are a constant, dull aching in the head or neck, brought on by stress. In a study of 30 volunteers suffering from tension headaches, 15-20 mg/kg of phenibut was given orally, every day for two months. This resulted in a decrease in the “frequency, duration and intensity of the headaches. As a result, the subjects enjoyed reduced anxiety and better sleep (14).
ADHD is another. ADHD is often associated with reported feelings of stress and anxiety. An oral administration of 500mg of phenibut per day improved symptoms in 61.7% of 12-15-year-olds in a study of 34 individuals with the condition (15).
A second study backs up this finding. 50 patients with ADHD participated in a placebo-controlled trial. 500-700mg of phenibut was given daily to half of the patients for one month. The control group was given low doses of multivitamins. Standardized measures of cognitive ability, attention span, memory function, and self-control improved significantly for the treatment group compared to the control group (16).
Boosting Dopamine
GABA inhibits the release of dopamine in the brain. You would expect that phenibut would reduce dopamine too, but at smaller doses, it increases its concentration (17).
As we navigate the world, our brains constantly judge the expected outcomes of potential actions. When we expect there’s a good chance of a positive outcome, we are more strongly motivated towards that goal.
Dopamine plays a significant role in this system of motivation. It is released when our brain judges the reward gained is better than expected, helping us to learn and motivate us further towards similar courses of action (18).
By increasing dopamine as a part of an otherwise inhibitory spectrum of effects, phenibut can provide a feeling of relaxed wakefulness and attention that is desirable for working and socializing. It is this dual mechanism that is probably responsible for the ‘miracle effects’ ascribed to it by some users
Promoting Neurogenesis
Neural pathways in the dopaminergic system directly stimulate the Subventricular Zone (SVZ) of the hippocampus (19). This system is one of two sites in the brain capable of neurogenesis, the creation of new brain cells after infancy.
Adult neurogenesis was not thought to occur before Peter Eriksson and his team of researchers demonstrated its existence in a landmark study in 1998 (20). They used fluorescent DNA labeling techniques to observe new neurons as they were created.
The new neurons play important roles in smell, mood regulation, and memory (21). They are directly implicated in learning, a process that partially functions by the addition of new neurons to existing neural circuitry (22).
GABA is one of the most important regulators of this process at all of its stages. It controls the proliferation of neural stem cells, their differentiation into neurons and their migration and integration into existing circuits (23).
Mice with mutations that impaired GABAergic communication between neurons showed a significantly reduced capacity for neurogenesis when learning or after trauma (24).
Neuroprotection
Neurogenesis is a part of the repair process when the brain suffers damage. Producing new brain cells helps to replace connections that have been lost or broken. So, by boosting dopamine, phenibut can have a neuroprotective effect.
Phenibut enhances neurogenesis in other ways, too. It can increase levels of brain-derived neurotrophic factor (BDNF), in the brain. BDNF is one of the primary neurotrophins, a set of proteins that are the major regulators of neurogenesis (25).
There are also benefits to the brain’s health on a basic level. Phenibut boosts the expression of a gene called VEGF. This gene facilitates healthy blood flow in the brain by creating and maintaining blood vessels (26). Improper circulation causes neurons to die as they are starved of oxygen, so maintaining it is important for neuroprotection.
In a study of rats whose brains were damaged by an electric shock, different GABA analogs were tested for their neuroprotective ability. This was measured by coma period following shock, time to recovery of motor functions, and amnesia after waking up. Phenibut provided the greatest protective effect out of the analogs tested (27).
Limitation Of The Evidence
Most of the evidence supporting phenibut should be taken with a grain of salt. The majority of the studies were done with animal models, so the findings cannot be directly applied to humans.
These studies are mostly from Russia, and while Russian science is not necessarily worse than science from elsewhere, it can be difficult to appraise the validity of these studies due to language barriers and differences in methodology.
Safety
Even though it is an effective treatment for several conditions, public health authorities around the It was mostly unknown outside Russia until 2011, when a large quantity was seized by police in Sweden. In 2012, the United Nations Office of Drugs and Crime designated phenibut as a ‘New Psychoactive Substance’. This designation is given to drugs that are considered to have abuse potential and cause public harm (28).
Phenibut has the potential to cause harm in three major ways: addiction, withdrawal, and intoxication (29).
Addiction
Drugs that interact with the dopaminergic system generally have the potential for addiction. Since dopamine regulates motivation towards rewarding behaviors, drugs that produce instant dopamine hits can become addictive.
Large-scale studies about the addiction potential of phenibut do not exist. There are several case reports of phenibut addiction in several patients.
In one, researchers at an addiction clinic describe a man who used phenibut to self-medicate anxiety, insomnia, and alcohol addiction. After initial success, he became addicted. He turned himself in after experiencing impacts on his personal and professional life (30).
Other case reports describe the abuse of phenibut by people who were already addicted to other drugs. A man with alcohol dependency was found unconscious by his friend after ingesting a large quantity of phenibut and had to be taken to hospital (31).
It is not known whether phenibut has serious addiction potential, but if you struggle or have struggled with addiction to other substances, phenibut may be dangerous for you.
Withdrawal
Serious withdrawal symptoms are described in case reports after patients stopped taking phenibut. These are similar to those experiences when coming of benzodiazepines like Valium. They include insomnia, aggression, physical trembling, and even heart palpitations (32).
One case report describes severe withdrawal symptoms experienced by a university student who took a large amount of phenibut – several grams, at least. These included sweating, prolonged insomnia, and disturbing hallucinations (33).
Addiction clinic staff have reported using drugs similar to phenibut to alleviate these symptoms during withdrawal. One report stated 8-10mg of Baclofen per gram of phenibut normally taken successfully reduced symptoms (34). Using chemically similar drugs to manage withdrawal is a common medical strategy, for example using Methadone to wean addicts off Heroin.
If you are experiencing withdrawal symptoms from phenibut, you should contact an addiction center or hospital for treatment to avoid unpleasant side effects.
Intoxication
Phenibut purchased online usually comes with warnings not to exceed a recommended dosage, typically 2000 mg per day. Still, there is little to stop people from treating themselves with higher doses.
In several case reports of doses exceeding these limits, people entered into states of intoxication. They became aggressive or delirious and generally entered into altered states of consciousness that constituted a danger to themselves or others (35).
A review of phenibut overdose cases presents similar symptoms throughout. Physical symptoms include muscle twitching, tremors, sweating, increased heart rate, and seizures. These were combined with headaches, agitation, aggressiveness, loss of coherence, slurring, and confusion (36).
This long list of symptoms should serve as a fair warning about the dangerous potential of phenibut. But, remember that the dosages in these cases greatly exceeded the recommended dosage.
Therapeutic doses are often between 100-300 mg per day, while overdoses involved up to 15-30 g in one go.
Summary
The danger and promise of phenibut make it a tough question: is phenibut really a safe and effective nootropic?
When taken in a controlled manner, the benefits are maximized and the dangers are mostly negated. It’s exactly the opposite when taking higher doses that exceed the recommended limits.
The best-case scenario is a powerful nootropic that promotes a state of relaxed attentiveness and reduces stress. The worst is an overdose that could land you in the emergency ward.
People with addictive personalities or problems with self-control are most at risk from phenibut. It only takes one lapse of control to cause a potentially harmful overdose or a bad set of withdrawal symptoms.
For others, taking small, regulated doses of phenibut might reduce anxiety in various situations. It can also enhance attention and memory through boosting dopamine.
People with neurological conditions based on overstimulation of neurons – like tension headaches or ADHD – might have the most to gain from phenibut.
A thorough understanding of the risks is essential, and there is no substitute for proper consultation with a doctor before taking any potentially harmful supplements. Phenibut should not be considered a supplement, rather a medication. Always seek a qualified medical opinion before taking it.
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