Phenibut dependence and withdrawals

[Alchemica]

I'd like to share the experiences of a dual diagnosis schizophrenic who had severe issues with phenibut becoming dependent on it. I hope sharing this may help others who fall into the abyss of phenibut dependence.The withdrawals are HELL but here is how he managed to get off it.

The withdrawal is similar to alcohol and benzodiazepine withdrawals and very much akin to baclofen withdrawal

Limited evidence indicates that withdrawal symptoms of phenibut include severe anxiety, nervousness, tremors, agitation, dizziness, irritation, fatigue, loss of appetite, rapid heartbeat, nausea, vomiting, tension, psychosis, hallucinations, and insomnia. These effects may last for up to two weeks. Tolerance may develop rapidly with repeated use.

Phenibut (“PB”) is being used in Russia and Latvia for the treatment of anxiety/alcohol withdrawal symptoms and as a nootropic (140). As a dietary supplement, it is freely available online. When misused, it is typically taken orally in dosages (e.g., 1-3 g) notably superior to the therapeutic ones, thus leading to a risk for overdose. At these dosages, it acts as agonist at GABA-A/B receptors, whilst stimulating dopamine/serotonin neurotransmission as well (141,142).

Its use may rapidly lead to dependence/tolerance (143), with related withdrawal symptoms being managed with baclofen (144). Withdrawal signs/symptoms may include visual and auditory hallucinations, psychomotor agitation, derealization, depersonalization, increased light and sound sensitivity, muscle pain/twitches, tachycardia, nausea, tremor and insomnia (145). Acute intoxication is characterized by tachycardia, visual hallucinations, tremor, nausea and vomiting, with the possible occurrence of the serotonin syndrome (146,147). [link]

After several months of escalating use, tolerance built and he reached 7g/day. His mental state was severely impaired. He managed a slow taper from 3.5grams bd down to 1g bd over 2-3 weeks. Dose reductions of up to 500mg at a time were tolerated but unpleasant¹. Olanzapine (up to 30mg) was prescribed [on top of 20mg/day aripiprazole] to manage psychotic symptoms and sleep deprivation that occurred at the peak. Withdrawal symptoms included increased hallucinations (primarily auditory, slight visual hallucinations), dissociation, insomnia, confusion, disinhibition, strong suicidal ideation, agitation, dysphoria, sweating and intense anxiety.

From 1g bd, the decision to attempt an abrupt withdrawal was made. Diazepam (10mg bd + prn) was used to manage agitation for
8 days (using a slow taper off it) and lower doses of olanzapine (5mg prn) were used as needed for sleep. Pregabalin 150mg nocte was continued (this had initially been 150mg tds several weeks ago). Pulse rate reached 120 bpm. Day 4-5 were the toughest, agitation becoming severe. On day 5, the decision to return to pregabalin 150 tds was made and this dramatically improved his mental state and agitation.

Day 8-9 led to a rebound hypomanic state while agitation was generally managed with the diazepam/pregabalin. By day 12 propranolol prn was considered for residual symptoms on discontinuation of diazepam.

I'd suggest that the best aid for phenibut withdrawals, aside from a slow substitution with baclofen or reinstating a low dose of phenibut acutely, is pregabalin. Phenibut and pregabalin both bind to the α2-δ subunit of voltage-dependent calcium channels (VDCC) [1] while phenibut also has affinity for GABA-B receptors.

[1] Tapers of 500mg every three days have been suggested

Another case of phenibut dependence (8g/day) has been reported:

Phenibut dependence.

Phenibut is a γ-aminobutyric acid (GABA) agonist designed and used as an anxiolytic in Russia. In Western countries, phenibut is not a registered medication but is available through online stores as a supplement. We present a case of a patient who used phenibut to self-medicate anxiety, insomnia and cravings for alcohol. While phenibut was helpful initially, the patient developed dependence including tolerance, significant withdrawal symptoms within 3-4 h of last use and failure to fulfil his roles at work and at home. He finally sought medical assistance in our addictions clinic. We have gradually, over the course of 9 weeks, substituted phenibut with baclofen, which has similar pharmacological properties, and then successfully tapered the patient off baclofen. This required approximately 10 mg of baclofen for each gram of phenibut.

Withdrawal symptoms after Internet purchase of phenibut (β-phenyl-γ-aminobutyric acid HCl) have also been reported.

To the Editors:
Phenibut is a neuropsychiatric drug that is marketed as a dietary supplement in the United States and can be purchased without a prescription. This is a case reportof a young, healthy man who experienced symptoms similar to benzodiazepine withdrawal after abrupt discontinuation of phenibut.

CASE REPORT
Mr L is a 21-year-old man who was referred to the outpatient psychiatric clinic by his primary care physician for evaluation of anxiety. Three weeks before this consultation, the patient started having restlessness in his legs that was increasingly affecting his abilities to study, concentration, and sleep. Two weeks before this appointment, the patient consulted with a sleep specialist and was diagnosed with restless leg syndrome and prescribed pramipexole 1 mg every 8 to 10 hours and zolpidem extended release 12.5 mg at bedtime. He took 2 doses of each medication and discontinued them on his own. These medications provided no relief of his symptoms; hence, he decided to look for alternative treatments. The patient searched for dietary supplements on the Web; he regularly purchases whey protein. He came across a dietary supplement called phenibut and placed an online order. Instead of taking the prescription medications, he took phenibut. The phenibut came in the form of a powder; however, the purity and the strength of the substance were not specified. The patient took phenibut once a day, mixing approximately 1 g of phenibut powder in a glass of water, as recommended on the packaging. The patient took phenibut for the next 10 days and continued to notice relief of his symptoms. Four days before this appointment, the patient stopped taking phenibut altogether and, within 2 to 4 hours, started experiencing the following symptoms: nervousness and shakiness inside, psychomotor agitation, feeling easily annoyed and irritated, fatigue, poor appetite, heart pounding and racing, nausea,insomnia, and feeling tense and keyed up.The patient did not recall experiencing any of the aforementioned symptoms before or while taking phenibut. He only noticed the symptoms when he stopped taking phenibut. To determine whether this was a withdrawal from phenibut, the patient took half the amount of phenibut he usually ingested (1/2 g) and felt almost immediate relief of his symptoms. He continued to wean himself from phenibut by taking half of the recommended amount over a span of 4 days. All in all, the patient took phenibut for 2 weeks. By the time he came for this appointment, he was no longer taking phenibut.

At the time of consultation, the patient appeared mildly anxious (based on data from the MiniYInternational Neuropsychiatric Interview used). Psychiatric history is unremarkable in this patient. He has had no psychiatric hospitalizations, outpatient treatments, suicide attempts, aggressive behaviors, or previous diagnoses. He admitted to drinking alcohol twice a month on average but denied tolerance or withdrawal symptoms. He denied the use of any illicit drugs and tobacco products.Family psychiatric history is positive for depression and anxiety in his biological mother. Aside from the recent diagnosis of restless leg syndrome, the patient has no other known medical conditions. No further laboratory tests were ordered.After careful evaluation of this patient’s symptoms, he meets criteria for a substanceinduced anxiety disorder with onset occurring during the withdrawal of phenibut. The patient was advised to discontinue and discard the phenibut powder. He was then educated regarding the effects of the phenibut he self-prescribed.

DISCUSSION
beta-Phenyl-gamma-aminobutyric acid HCL (phenibut) is a synthetic gamma-aminobutyric acid (GABA) analog that was discovered
and introduced in Russia in the 1960s. It is used to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients. Phenibut has also been used to treat depressive and posttraumatic stress disorders, stuttering, and vestibular disorders. Phenibut acts on GABA receptors and increases release of GABA from presynaptic nerve endings. Phenibut is GABAmimetic at GABAB receptors and at GABAA receptors to some extent. Phenibut can be separated into R- and S-enantiomers. It is easily synthesized in its racemic form, but the biological activity actually resides in R-phenibut. The pharmacological activity of R-phenibut correlates to its binding to GABAB receptors and can be blocked by a GABAB receptor selective antagonist. Studies have compared phenibut with benzodiazepines and diazepam, and common activities to both of these are sedation, affinity to benzodiazepine receptors (by longterm administration), and antiwithdrawal (alcohol and morphine). When benzodiazepines are used or abused for a long time, they may cause adaptive changes in benzodiazepine receptors. Patients may become irritable oranxious or even experience panic attacks if they suddenly stop taking the drugs.When a benzodiazepine is discontinued, the brain experiences the reverse of benzodiazepine intoxication: dysphoria, depression, anxiety, agitation, insomnia, muscle tension, and even seizures. These actions continue until the benzodiazepine is replaced or until the receptors readapt to the sensitivity they had before excessive use of the benzodiazepines. The patient in this case presented with many symptoms similar to a withdrawal from benzodiazepines. These symptoms included depressive symptoms, anxiety, insomnia,and tension. Given the properties of phenibut and its similarities to benzodiazepines,it is evident that the abrupt discontinuation of phenibut, after regular ingestion, can result in withdrawal symptoms similar to those experienced with benzodiazepine withdrawal.This case highlights the importance of taking a detailed history and inquiring about all medications, dietary supplements,vitamins, and the like. Physicians should ask their patients how they acquire these substances and educate them regarding the possible dangers of taking unapproved treatments without consulting a health care professional first.

Edited December 2, 2015 by Alchemica

[stonewolf]

Sounds about right.

Discontinuing Phenibut after several months 1-3g bd was an unpleasant experience. Having said that the agitation was mitigated by diazepam almost entirely.

It was a few weeks of being extraordinarily snappy and sleep being out of the question. The little sleep I did manage to get was fitful. Apart from that, with the aid of 10mg diazepam a day, I was pretty well normal.

IMO Phenibut withdrawal doesn't touch benzo withdrawal in terms of unpleasantness.