Welcome to

Phenibut Use Disorder:

today’s
What is it and how can we help?
webinar!
Dr. Andriy V. Samokhvalov, MD, PhD

CAMH, April 5th, 2018

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 Dr. Andriy V. Samokhvalov, MD, PhD
Centre for Addiction and Mental Health
University of Toronto
Phenibut Use Disorder:
What is it and how can we help?
Dr. Andriy V. Samokhvalov, MD, PhD

CAMH, April 5th, 2018

Conflict of Interest

• Nothing to disclose

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Objectives
• Outline the history of Phenibut and describe its clinical
effects

• Describe Phenibut withdrawal and present case studies

• Propose a treatment model for Phenibut use disorder.

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Phenibut… Pheni… What?

© Tamar Meyer, our amazing knowledge

translation expert

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A Bit of History
• Phenibut (Russian: Фенибут), was synthesized and studied in
Saint Petersburg (Leningrad then) in 1960s
• For a while Phenibut was a part of the Russian astronaut
(cosmonaut) med kit!
• From Russian online pharmacopeia:
• Tranquilizer:
• reduces tension, anxiety, improves sleep, potentiates
sedatives
• Has nootropic properties:
• Improves brain circulation and perfusion
• Indicated for:
• Neuroses (anxiety disorders)
• Insomnia
• Tics and stuttering
• Vertigo

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Recommended Usage
• From Russian online pharmacopeia:
• Recommended doses:
• Used in 2-3 weeks long courses
• Adults:
• 250-500 mg PO TID
• Max daily dose: 2500 mg
• Children
• 250 mg PO TID for children 8-14 y.o.
• 50-100 mg PO TID for children <8 y.o.
• Alcohol withdrawal management:
• 250-500 mg PO TID + 750 mg PO qHS
• Still less than 2500 m/day
• Side effects:
• Irritability, agitation, anxiety, vertigo, headache,
hypersomnolence
• Overdose:
• Vomiting, somnolence, hypotension, kidney failure
• Fatty liver at doses higher than 7,000 mg per day

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Available Online as a Supplement
• Apparently it’s easily available online as a supplement
• Moreover, it’s effectively promoted as a nootropic drug that
helps with mood and anxiety symptoms
• Not approved by either FDA or Health Canada

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 A Bit of Pharmacology
• Structurally Phenibut is very similar to GABA
• It works on GABAB receptors
• GABA is one of the major inhibitory
neurotransmitters
• Two classes of receptors:
• GABAA: an ionotropic receptor, effectively
a chlorine channel
• GABAB: a metabotropic receptor, G-protein
linked

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 GABAA vs GABAB Receptors
• GABA effects are essentially the same – hyperpolarization of the
cell membrane and accordingly – inhibition of the affected
neuron(es)
• GABAA are ion channels, they are fast and result in stronger
inhibition
• Located primarily in the brain and have anxiolytic, sedating and
hypnotic effects
• Ligands: Alcohol, Benzodiazepines and Z-drugs,
Barbiturates
• GABAB are G-proteins, they are slower and result
in weaker inhibition
• Located both in the brain and in the spinal cord –
have muscle relaxant effects
• Ligands: Baclofen, Phenibut

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Clinical Effects of Phenibut
• GABAB-mediated effects
• Brain: Mild anxiolytic effect
• Spinal cord: Muscle relaxant
• Based on the product monograph:
• Nootropic properties
• Improved circulations
• Mitigation of alcohol withdrawal
• Effectively used there
• Similar substance, baclofen, is used for alcohol use disorder in
Europe esp. France
• Potential for cross-tolerance with other GABA-ergic compounds such as
alcohol, GHB, benzodiazepines, barbiturates, baclofen
• Potential for physiological dependence
• Potential for positive reinforcing effects

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 User Experience
(taken from YouTube)
• “For over a decade and a half I assaulted my GABA receptors with Xanax. By all accounts
Phenibut withdrawal should have been worse for me than the average person... but it wasn't
bad at all and I'd venture to say it was actually extremely tolerable. I am now comfortable in
my life taking it occasionally (I'm taking it 1-2 days per week), no longer suicidal, and have a
solution to my anxiety problems sitting in my cabinet next to my daily multivitamins.
Personally I think the medical community should look at it as a potential life-changing
medicine and not a nootropic dietary supplement (I found no significant cognitive
improvements through Phenibut).”

• “For the first few hours I have a distinctly 'benzo feeling': slowed reactions, direct muscle
relaxation, slight dizziness and a general feeling of 'who gives a damn?' I feel very un-
confident & lazy (yet good...) during this initial phase. ”

• “I just recently started experimenting w Kratom and it changed my life! I also suffer from
G.A.D anxiety disorder so this Phenibut seems like it would be a great social tool. my only
problem is I don’t know where to order it. can anyone tell me or point me in the right way?”

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Online Phenibut Themes
• There are quite a few YouTube videos on how to get it, how to use
it, how to go off it etc.
• The main themes are:
• It’s a “Smart” drug
• Anxiolytic / antidepressant
• Remedy for hangover / alcohol withdrawal
• Often used with Kratom for this purpose
• Useful for bodybuilders (similar to GHB)
• Causes dependence and withdrawal
• Gabapentin /pregabalin do not help much

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Some E-mails That I Have Received
• After publishing a case report on Phenibut detoxification, I’ve
received a series of e-mails from Phenibut users from Germany
and USA) who:
• Used several grams of Phenibut per day
• Could not stop using it because of the fear of withdrawal
• Withdrawal would be described as:
• Anxiety and depressive symptoms (“waves of extreme
depression/anxiety”)
• Emotional lability, lack of energy (“I couldn't leave bed or stop
crying for 2 to 3 days”)
• Agitation and irritability
• Lack of concentration
• Lack of motivation
• Insomnia
• Spasticity, muscle twitches
• Fear of seizures

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A Bit of Epidemiology (or lack of)
• We have virtually no data on the Phenibut use
• No information in Eastern-European sources
• The data from Eastern Europe cannot be applied to North America as
it’s legal and non-prescription medication there and it’s not
approved, but available as a supplement here
• Some indicators that what we see is just a tip of the iceberg:
• I have reviewed several manuscripts submitted to various
journals on Phenibut in the past 2 years, cannot disclose the
content, but there is clearly some interest and some cases and
case series of Phenibut use / abuse / use disorder
• The individual feedback / e-mails I receive
• Some colleagues reported seeing patients who use Phenibut
• Tens of thousands of views of YouTube videos on Phenibut

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 The Case

An actual clinical case that was published in

BMJ Case Reports

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Clinical Case: History
• The patient was a 35-year-old married man with two children,
employed full-time as an IT specialist
• Long history of alcohol use
• Consumed alcohol since the age of 12
• Daily drinking since the age of 17
• Family history of alcohol abuse on both maternal and paternal sides
• Diagnosed with gout at the age of 32 and stopped drinking then
• History of parental neglect, emotional and physical abuse
• He reported being very stressed, having anger issues
• He also reported having used multiple substances to cope with
ongoing stress, depression, anxiety and insomnia.
• He used opioids (various preparations of codeine, poppies,
Kratom) and benzodiazepines (phenazepam and diazepam). These
were obtained from friends’ prescriptions, purchased over the
counter or online.
• The patient had never received specialised addiction treatment
before.

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Clinical Case: Phenibut
• At the time of the assessment, he has been abstinent from alcohol and actively
using the ‘supplements’ Phenibut (for 10 months) and Kratom (for 2 years).
• He stated that he had been purchasing Phenibut as an online supplement to self-
medicate his anxiety, dysphoria and cravings for alcohol.
• At that time he has been taking 8 g of Phenibut and 18 g of Kratom per day.
• The patient found these two ‘supplements’ very helpful for coping with withdrawal
symptoms from alcohol, benzodiazepines and poppies.
• At the same time he was unable to stop using them.
• He made several attempts to decrease his use of Phenibut, but experienced
heightened anxiety, anger and irritability.
• He felt very hostile towards his work colleagues and family members. He was
isolating himself at home to keep from losing his temper.
• Discontinuation of Kratom precipitated mild-to-moderate opioid withdrawal
symptoms.
• The patient sought medical advice on how to stop taking these two ‘supplements’,
primarily Phenibut.
• He also wanted help with underlying anxiety and depression that he had
experienced for the past 18 years during the periods of abstinence from alcohol
and other substances.

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 Phenibut Use Disorder Diagnosis
• Neither Phenibut nor Kratom are mentioned in DSM-5
• Would be classified as Other Specified Substance Use Disorder
Diagnostic Criteria:
• A problematic pattern of use of a substance leading to clinically
significant impairment or distress, as manifested by at least two of the
following, occurring within a 12-month period:
1. The substance is often taken in larger amounts or over a longer period than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control use of the substance.
3. A great deal of time is spent in activities necessary to obtain the substance, use the substance,
or recover from its effects.
4. Craving, or a strong desire or urge to use the substance.
5. Recurrent use of the substance resulting in a failure to fulfill major role obligations at work,
school, or home.
6. Continued use of the substance despite having persistent or recurrent social or interpersonal
problems caused or exacerbated by the effects of its use.
7. Important social, occupational, or recreational activities are given up or reduced because of use
of the substance.

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Phenibut Use Disorder Diagnosis
Diagnostic Criteria:
8. Recurrent use of the substance in situations in which it is physically hazardous.
9. Use of the substance is continued despite knowledge of having a persistent or recurrent physical
or psychological problem that is likely to have been caused or exacerbated by the substance.
10. Tolerance, as defined by either of the following:
• A need for markedly increased amounts of the substance to achieve intoxication or desired
effect.
• A markedly diminished effect with continued use of the same amount of the substance.
11. Withdrawal, as manifested by either of the following:
• The characteristic withdrawal syndrome
• The substance (or a closely related substance) is taken to relieve or avoid withdrawal
symptoms.
Severity, based on the number of symptoms (Mild, Moderate, Severe) and remission status.

Full Diagnosis:
Alcohol Use Disorder, In Full Sustained Remission
Phenibut Use Disorder, Severe
Kratom Use Disorder, Severe
• NB: Also, concurrent mood and anxiety disorders must have been ruled out / in

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Clinical Case: Treatment Strategy
Treatment strategy:
• substitute prescription medications with less abuse potential and better-
known pharmacological profiles for the ‘supplements’ Phenibut and
Kratom and then to taper off
• Buprenorphine/naloxone was considered as a substitution agent for
Kratom
• Baclofen was selected for treatment of Phenibut dependence:
• Similar in structure and pharmacological
profile to Phenibut.
• Baclofen would be more appropriate
than using benzodiazepines as it has
almost identical structure and
mechanism of action
• Also, history of alcohol and
benzodiazepine use disorder precluded
the use of benzodiazepines (or GABAA
agents)
• Baclofen can also be used for the
treatment of alcohol use disorder

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Clinical Case: Treatment Outcome
• We gradually cross-tapered the patient from Phenibut to baclofen
• Started with 8 mg of Phenibut per day
• Gradually substituted each gram of Phenibut with 5-10 mg of
Baclofen over the course of 9 weeks
• Tapered the patient off baclofen over the course of 15 weeks
• Full schedule is available at:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604470/pdf/b
cr-2012-008381.pdf
• The patient was able to successfully stop using Kratom and reported
only mild withdrawal symptoms (self-limiting diarrhoea, diaphoresis
and restlessness lasting for several days).
• Patient was prescribed citalopram for management of anxiety and
depressive symptoms
• Supportive counselling was provided

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Treatment

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Principles
“The good physician treats the disease; the great physician
treats the patient who has the disease.”

Treatment Principles:
• As with any addiction and with any patient we must understand
and address the following:
• Current substance use patterns
• Factors affecting the use of these
substances
• Trauma, Ego deficits, Insight
• Motivation to change
• Previous substance use patterns
• Underlying mental disorder(s)
• Cognitive distortions
• Concurrent medical and psychiatric issues

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Treatment Setting
• In our case scenario we chose the outpatient setting
• As with benzodiazepines withdrawal symptoms might last long
enough, sometimes weeks, thus the outpatient treatment seems
to be the most appropriate.
• Inpatient treatment would be recommended in case a patient
wants to stop taking Phenibut completely and/or there is a risk of
severe and complicated withdrawal:
• Abrupt discontinuation (i.e. the “supplement” is
unavailable or on a backorder)
• Polysubstance use
• Risk of life-threatening symptoms such as seizures
• Medical conditions predisposing to seizures (epilepsy,
withdrawing from alcohol or benzodiazepines)
• Compromised medical status (hypertension, recent
cardio- or cerebrovascular event etc.)

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Biological Treatments
• Substitution treatment
• The main substitution agent would be baclofen
• Withdrawal management (if chosen)
• Baclofen
• Alpha 2 Delta (α2δ) Ligands:
• Gabapentin
• Pregabalin
• Symptomatic treatment:
• Mirtazapine for insomnia / depressive Sx / anxiety
• Benzodiazepines / Z-drugs for anxiety / insomnia
• Buspirone for anxiety
• SSRI / SNRI for anxiety / depressive Sx / irritability

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 Psychosocial Tx: What can we offer?
• Supportive psychotherapy
• Prochaska and DiClemente model
• Precontemplation / Contemplation
• Brief Interventions / MI to help
patient to move to the more
advanced stages
• Preparation / Action / Maintenance /
Relapse
• CBT / Structured Relapse Prevention
• Treatment of underlying conditions:
• CBT for Anxiety / Depression / Insomnia
• IPT / BA for depression
• Trauma-Informed CBT for trauma-
related conditions

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Supportive Psychotherapy
• Most basic and effective techniques:
• Foster and protect therapeutic alliance
• Formulate the case
• Educate the patient and family
• Focus on here and now
• Manipulate the environment
• Be a good “parent” / role model
• Hold and contain the patient / Lend “Ego”
• Manage transference
• Maximize adaptive coping mechanisms
• Encourage patient activity
• Decrease alexithymia
• Make connections
• Raise self-esteem

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SBIRT
• Screening per se is likely not very helpful as we don’t know the
prevalence and it doesn’t seem to be alarmingly high
• If your patient uses Phenibut
• Assess the situation
• Amounts used, duration of use, withdrawal symptoms
• Explore the motivation to use
• What does Phenibut do for the patient?
• Anxiety? Depression? Another substance? Weight loss? Insomnia?
Memory?
• Provide a Brief Intervention
• If you feel that you cannot provide help at this point – Refer to
Treatment

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Brief Interventions
• Based on principles of Motivational Interviewing
• Use the FRAMES approach:
• Feedback: Give feedback on the risks and negative consequences of
substance use. Seek the client's reaction and listen.
• Responsibility: Emphasize that the individual is responsible for making his
or her own decision about his/her drug use.
• Advice: Give straightforward advice on modifying drug use.
• Menu of options: Give menus of options to choose from, fostering the
client’s involvement in decision-making.
• Empathy: Be empathic, respectful, and non-judgmental.
• Self-efficacy: Express optimism that the individual can modify his or her
substance use if they choose. Self-efficacy is one's ability to produce a
desired result or effect.

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Structured Relapse Prevention
• Based on CBT and incorporates MI
• Developed at CAMH (ARF then)
• Five phases:
• Assessment
• Motivational interviewing
• Individualized treatment planning
• Initiation of change
• Maintenance of change
• 12 sessions, individual or group format
• Available both for substance use disorders and for concurrent disorders
• Amazing source of information provided with references

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Other Psychosocial Treatments
• Bibliotherapy
• Trauma-informed CBT for patients with traumatic experiences
• Concurrent Insomnia:
• Sleep Hygiene / Pharmacotherapy
• CBT for Insomnia
• Concurrent Anxiety:
• CBT for anxiety
• Concurrent Depression:
• CBT / IPT / BA
• Brief psychodynamic psychotherapies

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References:
1. Samokhvalov AV, Paton-Gay L, Balchand K, Rehm J. Phenibut dependence. BMJ Case Rep
2013; 2013: bcr2012008381.
2. Misch DA. Basic Strategies of Dynamic Supportive Therapy. J Psychother Pract Res. 2000;
9(4): 173–189.
3. Lapin I. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug
Rev 2001;7:471–81
4. Babu KM, McCurdy CR, Boyer E. Opioid receptors and legal highs: salvia divinorum and
Kratom. Clin Toxicol 2008;46:146–52
5. Schmidt MM, Sharma A, Schiifano F, et al. “Legal highs” on the net—evaluation of UK-based
websites, products and product information. Forensic Sci Int 2011;206:92–7
6. Watson R. EU drug monitoring agency voices concerns over “legal
highs”. BMJ 2010;341:c6491.
7. Magsalin RM, Khan AY. Withdrawal symptoms after internet purchase of Phenibut (β-phenyl-
γ-aminobutyric acid HCl). J Clin Psychopharmacol 2010;30:648–9
8. Ashton H. Benzodiazepine withdrawal: an unfinished story. BMJ 1984;288:1135–40
9. CAMH Manual for Structured Relapse Prevention:
http://www.camh.ca/en/hospital/Documents/Forms/AllItems.aspx?RootFolder=%2fen%2fho
spital%2fDocuments%2fwww%2ecamh%2enet%2fPublications%2fResources_for_Profession
als%2fSRP&FolderCTID=0x01200069AE48F34861CF41ADC42D75F796BA9E

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 Thank You!

• Any questions are welcome!

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