Phenibut is a structurally similar synthetic derivative of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that acts as a central nervous system (CNS) depressant. Originally developed by Russian scientists in the 1960s, it was used as an auxiliary treatment for youth undergoing psychiatric treatment. (17) It was later used by Russian cosmonauts to induce relaxation and enhance cognitive function during space travel. (23) Since then, it has received global recognition for its performance and cognition-enhancing CNS effects.
Start using supplements in clinical practice
In several countries, phenibut is considered a controlled substance requiring a prescription. (21) In the United States, however, it has been mired in controversy due to the unclear nature of its classification as a supplement ingredient. Whereas it is not a controlled substance, the Food and Drug Administration (FDA) also states “Phenibut is a substance that does not meet the statutory definition of a dietary ingredient,” deeming it inappropriate for use in dietary supplements.
Recently, the FDA issued three warning letters to U.S. companies manufacturing and selling dietary supplement products containing phenibut, indicating the FDA will continue to impose more stringent oversight of phenibut going forward. (27)
What is phenibut used for?
The effects of phenibut are primarily linked to its agonistic behavior on GABAB receptors, whereas the form of GABA used in supplements acts as an agonist of GABAA receptors. Both receptors induce an inhibitory or depressant effect, creating a sense of calm or relaxation.
Phenibut is also shown to stimulate dopamine receptors in the brain, creating a simultaneously relaxing and euphoric effect. Its sedative effects are considered an effective treatment for insomnia, anxiety, fear-based pathologies, and attention deficit hyperactivity disorder. It is also shown to increase mood, focus, cognitive function, and energy, and is, therefore, widely considered a nootropic, or agent that improves cognition and memory. (17)
What are the concerns with phenibut?
Unlike GABA, phenibut is considered a psychoactive substance due to its ability to cross the blood-brain barrier. It also demonstrates conditioning effects, requiring increasing doses to elicit similar effects experienced at lower initial doses. These two factors contribute to its addictive properties, leading many international health authorities to ban or control its use. (2)
Furthermore, phenibut withdrawal symptoms can include psychological and physical symptoms, including anxiety, depression, tremors, insomnia, dizziness, and feelings of dissociation. (1) Combined with other psychoactive compounds like alcohol, benzodiazepines, and opioids, phenibut can also lead to harmful effects, including death. (11)(25)
7 Phenibut alternatives
Phenibut’s primary effects are thought to be a result of its ability to agonize GABAB receptors and stimulate dopamine receptors, thereby creating a relaxing effect coupled with increased energy, focus, and attention. (17)
Although there is no natural substance that induces all of these effects, several are able to create similar or synergistic effects. The following is a sampling of the various nutraceutical or botanical ingredients that could be used in isolation or combination as an alternative to phenibut.
1. γ-aminobutyric acid (GABA)
The primary alternative to phenibut is its natural cousin and fellow GABA-receptor agonist, γ-aminobutyric acid (GABA). Although its effects are still not well understood and it is generally accepted that GABA does not cross the blood-brain barrier, (3) GABA has been shown to induce a calming, anxiolytic effect that can be used for hyperstimulation conditions like anxiety, insomnia, and hyperactivity. (19)
It is also believed that it may induce effects on the brain by affecting the enteric nervous system and subsequent gut-brain axis. (16) Combined with Theanine, GABA has also shown to decrease sleep latency and improves NREM sleep. (15)
2. L-γ-glutamylethylamide (L-theanine)
L-theanine, an amino acid found primarily in green tea leaves, can help promote relaxation and sleep. A study of individuals with major depressive disorder (MDD) found that L-theanine administered daily over eight weeks decreased anxiety, depressive symptoms, and sleep disturbances. (10) Another double-blind, placebo-controlled trial examined the effects of L-theanine supplementation on healthy adults when confronted with a stressor. L-theanine reduced both the subjective stress response and salivary cortisol response to the stressor, supporting the anti-stress effects of L-theanine. (28)
3. 5-Hydroxytryptophan (5-HTP)
5-Hydroxytryptophan (5-HTP) is an intermediary compound produced by the body as it converts the amino acid tryptophan to melatonin or serotonin. Due to its ability to increase serotonin levels, 5-HTP is commonly used to treat serotonin deficiency-related symptoms, including depression, anxiety, insomnia, premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and attention deficit hyperactivity disorder (ADHD). (8)
Although 5-HTP is known to cross the blood-brain barrier and is one of the more widely used supplement ingredients, the research around its effects remains limited. However, it is currently accepted that 5-HTP can increase satiety and be effectively used to treat disordered eating pathologies. (4)(5)
Melatonin, a neurotransmitter-like compound (often considered a hormone) produced by the pineal gland, is synthesized from tryptophan through a series of reactions. These reactions are stimulated by darkness and suppressed by light, which suggests that melatonin is involved in the regulation of the body’s sleep cycle, the circadian rhythm, and other body functions. (20)
Research has shown that melatonin improves sleep quality, increases total sleep time, and decreases sleep onset latency (SOL). (20) A meta-analysis found that melatonin supplementation of 5 mg administered at 10 p.m. shortened time to sleep and increased sleep duration, indicating improved sleep quality. (22)
Further, a systematic review examining the effectiveness of melatonin supplementation on sleep found that the administered dose of melatonin ranged from 0.3 to 10 mg per day, (7) indicating that effective dosing for individuals may vary.
Made recently more popular with the widespread adoption of bone broth and organ meats, glycine is an amino acid and neurotransmitter that is shown to induce a calming effect in patients. It has both stimulatory and inhibitory effects on the brain. Although research is limited, studies show that glycine can have a positive effect on sleep quality, (12) cognition, and fatigue. (30)
6. Calming herbs
Melissa officinalis (lemon balm) is an herb native to North America used most commonly for its sedating and relaxing effects. It is shown to induce calmness or decrease alertness, (14) and improve mild-moderate anxiety disorders. (6)
Myo-inositol, the most common supplemental form of inositol, is a small compound structurally similar to glucose. Although previously classified as a B vitamin, it is now considered a pseudovitamin and is found primarily in whole grains and citrus fruits. (13) It is commonly used for blood sugar regulation and treating polycystic ovarian syndrome (PCOS), but it may also be effective in treating anxiety and panic attacks, (24) depression, (18) and PMDD. (9)
The bottom line
Phenibut is a synthetic version of GABA that crosses the blood-brain barrier and can elicit psychoactive effects on the brain. Although historically mired in controversy due to not being classified as a drug nor a supplement ingredient, the FDA has recently started to enforce that U.S. supplement manufacturers should not use phenibut in their products. As a result, the availability of phenibut-containing products is likely to decline.
Instead, practitioners have the option of using multiple alternative ingredients that would elicit similar but non-psychoactive and, therefore, non-addictive properties.
Quality supplement plans in less than a minuteTry Fullscript
- Ahuja, T., Mgbako, O., Katzman, C., & Grossman, A. (2018). Phenibut (β-Phenyl-γ-aminobutyric Acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Reports in Psychiatry, 2018, 1-3.
- American Addictions Centre. (2018). What is phenibut? How does addiction start? Retrieved from https://americanaddictioncenters.org/phenibut
- Boonstra, E., de Kleijn, R., Colzato, L.S., Alkemade, A., Forstmann, B.U., & Nieuwenhuis, S. (2015). Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Frontiers in Psychology, 6,1520.
- Cangiano, C., Ceci, F., Cascino, A., Del Ben, M., Laviano, A., Muscaritoli, M., … Rossi-Fanelli, F. (1992). Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. American Journal of Clinical Nutrition, 56(5), 863-7.
- Cangiano, C., Laviano, A., Del Ben, M., Preziosa, I., Angelico, F., Cascino, A., & Rossi-Fanelli, F. (1998). Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. International Journal of Obesity and Related Metabolic Disorders, 22(7), 648-54.
- Cases, J., Ibarra, A. Feuillère, N., Roller, M., & Sukkar, S.G. (2011). Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Journal of Nutrition and Metabolism, 4(3), 211–218.
- Costello, R.B., Lentino, C. V., Boyd, C.C., O’Connell, M.L., Crawford, C.C., Sprengel, M.L., & Deuster, P.A. (2014). The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutrition Journal, 13, 106.
- Eriksson, O., Wall, A, Olsson, U., Marteinsdottir, I., Holstad, M., Ågren, H., … Naessén, T. (2016). Women with premenstrual dysphoria lack the seemingly normal premenstrual right-sided relative dominance of 5-HTP-derived serotonergic activity in the dorsolateral prefrontal cortices: A possible cause of disabling mood symptoms. PLoS One, 11(9), e0159538.
- Gianfranco, C., Vittorio, U., Silvia, B., & Francesco, D. (2011). Myo-inositol in the treatment of premenstrual dysphoric disorder. Human Psychopharmacology, 26(7), 526-30.
- Hidese, S., Ota, M., Wakabayashi, C., Noda, T., Ozawa, H., Okubo, T., & Kunugi, H. (2016). Effects of chronic l-theanine administration in patients with major depressive disorder: An open-label study. Acta Neuropsychiatrica, 29(2), 72-79.
- Högberg, L., Szabó, I., & Ruusa, J. (2012). Psychotic symptoms during phenibut (beta-phenyl-gamma-aminobutyric acid) withdrawal. Journal of Substance Use, 18(4), 335-338.
- Inagawa, K., Hiraoka, T., Kohda, T., Yamadera, W., & Takahashi, M. (2006). Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms, 4(1), 75-77.
- Indyk, H. (2006). Nonvitamin micronutrients. Journal of AOAC International, 89(1), 288-9.
- Kennedy, D.O., Scholey, A.B., Tildesley, N.T.J, Perry E.K., & Wesnes, K.A. (2002). Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacology Biochemistry and Behavior, 72(4), 953-964.
- Kim, S., Jo, K., Hong, K.B., Han, S.H., & Suh, H.J. (2019). GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharmaceutical Biology, 57(1), 65-73.
- Krantis, A. (2000). GABA in the mammalian enteric nervous system. American Physiological Society, 15(6).
- Lapin, I. (2001). Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug. CNS Drug Reviews, 7(4), 471-81.
- Levine, J., Barak, Y., Gonzalves, M., Szor, H., Elizur, A., Kofman, O., & Belmaker, R.H. (1995). Double-blind, controlled trial of inositol treatment of depression. American Journal of Psychiatry, 152(5), 792-4.
- Lydiard, R.B. (2003). The role of GABA in anxiety disorders. Journal of Clinical Psychiatry, 64(Suppl 3), 21-7.
- Malhotra, S., Sawhney, G., & Pandhi, P. (2004). The therapeutic potential of melatonin: A review of the science. Medscape General Medicine, 6(2), 46.
- Medsafe. (2018). Classification of phenibut: Submission to the medicines classification committee. Retrieved from https://www.medsafe.govt.nz/profs/class/Agendas/Agen60/5.5.1-Phenibut-submission.pdf
- Nagendra, R. P., Maruthai, N., & Kutty, B. M. (2012). Meditation and its regulatory role on sleep. Frontiers in Neurology, 3.
- Neumyvakin, I.P., Krupina, T.N., Polevoĭ, L.G., & Semeĭkina, L.A. (1978). Principles for making up pharmaceutical kits to supply cosmonauts with drug packs. Kosm Biol Aviakosm Med, 12(3), 27-31.
- Palatnik, A., Frolov, K., Fux, M., & Benjamin, J. (2001). Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. Journal of Clinical Psychopharmacology, 21(3), 335-9.
- Samokhvalov, A.V., Paton-Gay, L., Balchand, K., & Rehm, J. (2013). Phenibut dependence. BMJ Case Reports, 2013.
- Sayorwan, W., Siripornpanich, V., Piriyapunyaporn, T., Hongratanaworakit, T., Kotchabhakdi, N., & Ruangrungsi, N. (2012). The effects of lavender oil inhalation on emotional states, autonomic nervous system, and brain electrical activity. Journal of the Medical Association of Thailand, 95(4), 598-606.
- U.S. Food and Drug Administration. (n.d.). Phenibut in dietary supplements. Retrieved from https://www.fda.gov/food/dietary-supplement-products-ingredients/phenibut-dietary-supplements
- White, D., Klerk, S. D., Woods, W., Gondalia, S., Noonan, C., & Scholey, A. (2016). Anti-stress, behavioural and magnetoencephalography effects of an l-Theanine-based nutrient drink: A randomised, double-blind, placebo-controlled, crossover trial. Nutrients, 8(1), 53.
- Woelk, H., & Schläfke, S. (2010). A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine, 17(2), 94-9.
- Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., & Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126-131.