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Phenibut
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Revision as of 21:02, 28 March 2018 by >Bzshd(Add potential reverse-tolerance effects for nootropic effects)
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Phenibut is a closely related in structure to gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. The addition of a phenyl ring to the GABA molecule allows it to cross the blood-brain barrier and produce psychoactive effects.[4]
It is structurally related to baclofen, pregabalin, and gabapentin.[4]
Phenibut was developed in the Soviet Union in the 1960s, where it has been used as a pharmaceutical drug to treat a wide range of ailments, including post-traumatic stress disorder, anxiety, depression, asthenia, insomnia, alcoholism, stuttering, and vestibular disorders, and other conditions.[5][6][4] In the rest of the world, phenibut is not approved for clinical use and is instead sold as a nutritional supplement.
Although it is commonly marketed as a nootropic by retailers, evidence that it enhances cognition is limited. It is generally accepted that phenibut has anxiolytic effects in both animal and in humans.[4] Due to its habit-forming properties, it is highly advised to use harm reduction practices if using this substance.
Phenibut is a derivative of GABA with a phenyl group in the β-position. It has a near identical structure as baclofen, lacking only a chlorine atom in the para-position of the phenyl group[7] and contains phenethylamine in its structure.[8]Pregabalin also has a near identical structure as phenibut, except it has an isobutyl group instead of a phenyl group.
Phenibut is a chiral molecule and thus has two potential configurations, as (R)- and (S)-enantiomers.[9]
Most commercial phenibut is in the form of the hydrochloride salt (HCl). In this form, the phenibut is reacted with hydrochloric acid to form a stable, easily dissolvable, acidic, crystalline salt.
Alternatively, phenibut can exist as a free amino acid (FAA). In this form, phenibut is close to pH neutral, non-crystalline, slow to dissolve and mildly bitter. The FAA form has about 20% more phenibut molecules on an equal mass basis compared to phenibut HCl. Phenibut FAA has the advantage of being suitable for sublingual, rectal, or intranasal use, which can be more efficient, faster acting, and predictable for some. Phenibut FAA is converted to phenibut HCl in the stomach. Equal masses of the two forms will have roughly equivalent effects when taken the same way (FAA may be slightly stronger).
Pharmacology
Phenibut is substantially more complex in its pharmacological profile than most other depressants. Unlike most depressants such as benzodiazepines, phenibut acts as a full agonist of the GABABreceptor, similar to baclofen and high doses of GHB.[10] At higher doses, phenibut loses its selectivity of GABAB, and gains additional activity as a GABAAagonist.[11] Phenibut's effects at the GABAB receptor are responsible for its sedating effects.
Recent research has shown that phenibut binds to and blocks α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids such as gabapentin
and pregabalin.[12] Both enantiomers of phenibut show this action with similar efficacy. The R-enantiomer possesses five-fold greater affinity for
α2δ subunit-containing voltage-gated calcium channels relative to the GABAB receptor, whereas the S-entantiomer does not have any efficacy at the GABAB receptor.[12]
The analgesic effects of phenibut in rodents are not mediated by the GABAB receptor but by the blockage of α2δ subunit-containing voltage-gated calcium channels.[12]
Additionally, phenibut has been found to increase dopamine levels within the brain. It is not known how this contributes to its effects.[4]
Subjective effects
In comparison to other commonly used GABAergic depressants such as alcohol or benzodiazepines, phenibut is reported to be longer lasting, more euphoric and more recreational at higher doses.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
Sedation - At lower doses, phenibut has a mild physical and mental stimulation effect, encouraging movement, wakefulness, and productivity. At common doses and higher, it becomes physically sedating, encouraging sleep and lethargy. Sleeping after dosing a small amount results in a deep, restful sleep which can leave the user feeling refreshed and alert upon waking.
Orgasm suppression - At higher doses, rather than reducing sensitivity, phenibut has a propensity to cause spontaneous motor control loss when nearing orgasm.
Respiratory depression - This effect is generally mild compared to that experienced on many other depressants. However, it may become dangerously amplified if phenibut is combined with other substances that depress breathing.
Nausea - Phenibut can induce mild to extreme nausea depending greatly on dose and tolerance. When it occurs, it usually manifests roughly 5 hours after the initial dose and generally involves waves of nausea accompanied by vomiting and excessive sweating.
Internal hallucinations - One may experience a state of semi-consciousness and hypnagogia during heavy dosage nodding which results in dream-like states and up to level 3 imagery. This is often accompanied by ill-defined geometry.
Empathy, affection, and sociability enhancement - Phenibut has been reported to produce prosocial and mild entactogenic effects which, although much weaker than that of traditional entactogens such as MDMA, are prominent and well-defined even at common doses.
Rebound anxiety - Rebound anxiety is a commonly observed effect with anxiolytic substances like phenibut. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction.
Residual sleepiness - While phenibut can be used as an effective sleep-inducing aid, their effects may persist into the morning afterward, which may lead users to feel "groggy" or "dull" for up to a few hours if not longer.
Depression - A low mood can be experienced as an after-effect of high or frequent dosing.
Depersonalization - Feelings of mild to strong depersonalization may present themselves after phenibut usage, particularly when it is taken frequently at higher doses.
Phenibut hydrochloride is highly caustic and in many sensitive users can cause intestinal discomfort and diarrhea with some lower digestive tract bleeding.[citation needed]
Due to the extremely long come up period relative to other substances, some users may experience an urge to redose out of the belief that it is weak or not working. This should be avoided to prevent overdose.
Phenibut is moderately physically and psychologically addictive, although this usually only occurs with heavy abuse of the substance.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. In mice, some evidence suggests that the nootropic effects may increase over several days of chronic administration.[4]
After cessation, the tolerance returns to baseline in 7 - 14 days.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction.
Phenibut presents cross-tolerance with [[Cross-tolerance::all GABAgenic depressants]], meaning that after its consumption, most depressants will have a reduced effect.
Dangerous interactions
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and dying from the resulting suffocation. If a sudden loss of consciousness occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - It is dangerous to combine phenibut with stimulants due to the risk of excessive intoxication. Stimulants mask the sedative effect of phenibut, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of phenibut will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of phenibut per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
As such, it may contain incomplete or wrong information. You can help by expanding it.
Australia: Phenibut is a schedule 9 substance in Australia as of February 1st 2018, meaning it is illegal to possess, import, supply or manufacture.[citation needed]
United Kingdom: Phenibut is uncontrolled and is legal to possess. It may be illegal to produce, supply, or import this drug under the Psychoactive Substance Act 2016, which blanketly applies the aforementioned restrictions on all "psychoactive substances" with exemptions for alcohol, nicotine and "medicinal products".[14]
United States: Phenibut is uncontrolled, meaning it is legal to possess without any sort of license or prescription.[15]
↑Shulgina, G. I. (1986). "On neurotransmitter mechanisms of reinforcement and internal inhibition". The Pavlovian journal of biological science (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/2431377
↑Shulgina, G. I. (1986). On neurotransmitter mechanisms of reinforcement and internal inhibition. Integrative Physiological and Behavioral Science, 21(4), 129-140.
↑Dambrova, M., Zvejniece, L., Liepinsh, E., Cirule, H., Zharkova, O., Veinberg, G., & Kalvinsh, I. (2008). Comparative pharmacological activity of optical isomers of phenibut. European Journal of Pharmacology, 583(1), 128-134.
↑Zyablitseva, E. A.; Pavlova, I. V. (2010). "Effects of the GABA Receptor Agonist Phenibut on Spike Activity and Interactions between Neocortex and Hippocampus Neurons in Emotionally Negative Situations". Neuroscience and Behavioral Physiology. 40 (9): 1003–1011. doi:10.1007/s11055-010-9360-y. ISSN0097-0549.
↑ 12.012.112.2Dambrova, M.; Zvejniece, L.; Liepinsh, E.; Cirule, H.; Zharkova, O.; Veinberg, G.; Kalvinsh, I. (2008). "Comparative pharmacological activity of optical isomers of phenibut". European Journal of Pharmacology (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/18275958
↑Koski, A., Ojanperä, I., & Vuori, E. (2002). Alcohol and benzodiazepines in fatal poisonings. Alcoholism: Clinical and Experimental Research, 26(7), 956-959.
