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| Chemical Nomenclature | |||||||||||||||||||||||||||||||||||||||||
| Common names | Semax | ||||||||||||||||||||||||||||||||||||||||
| Substitutive name | L-Methionyl-L-α-glutamylhistidyl-L-phenylalanyl-L-prolylglycyl-L-proline | ||||||||||||||||||||||||||||||||||||||||
| Systematic name | (2S)-1-[2-{[(2S)-1-[(2S)-2-{[2-{[(2S)-2-{[(2S)-2-amino-4-methylsulfanylbutanoyl]amino}-4-carboxybutanoyl]amino}-3-(1H-imidazol-5-yl)propanoyl]amino}-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino}acetyl]pyrrolidine-2-carboxylic acid | ||||||||||||||||||||||||||||||||||||||||
| Class Membership | |||||||||||||||||||||||||||||||||||||||||
| Psychoactive class | Stimulant / Nootropic | ||||||||||||||||||||||||||||||||||||||||
| Chemical class | Peptide | ||||||||||||||||||||||||||||||||||||||||
| Routes of Administration | |||||||||||||||||||||||||||||||||||||||||
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Semax (natively labeled Семакс) is a Russian pharmaceutical neuropeptide developed in the 1980s and approved for clinical use in 1996 after a 14-year-long testing period[2]. While commonly prescribed in Russia, Ukraine, and other CIS nations for a wide range of conditions including stroke/ischemic brain injury, Alzheimer's, depression, generalized anxiety, peptic ulcer disease, and weakened immune system, it has gained limited recognition elsewhere as a nootropic due to its mildly stimulating and anxiolytic effects, neuroprotective properties, and limited side effect profile.
Though domestic vendors outside of the CIS frequently do not carry it, Semax is otherwise fairly accessible and proportionally inexpensive in larger markets. Semax is most usually found as nasal spray due to its very low oral bioavailability as a peptide, though it may also be administered subcutaneously for somewhat higher potency.
While Semax generally has noticeable effects within minutes of administration[3], many therapeutic effects frequently only manifest at maximum efficacy after use in a longer-term regimen[4], owed in large part to upregulation of its signaling receptor site ("reverse tolerance") after consistent usage[5]. Some effects are usually noted after administration of a 100µg dose, though frequent users often find doses as high as 1.2mg to be optimal for therapeutic effects. It is strongly advised that users start at a low dose and gradually increase to an acceptable level rather than begin at even a relatively standard dose.
Semax is noted for being generally well-tolerated, with only a small percentage of subjects noting presence of any side effects[6].
Chemistry
Semax is a synthetic analogue of the short fragment of adrenocorticotropic hormone (ACTH)[7], a peptide released by the pituitary gland released by biological stress. Semax's amino acid sequence is written as Met-Glu-His-Phe-Pro-Gly-Pro. Initially, research found that administration of ACTH profoundly improved learning in animals, though the short duration of the base peptide in the body (1-2 minutes) made it infeasible as medication; addition of the Pro-Gly-Pro to the synthetic analogue of ACTH was shown to considerably boost both duration and efficacy of the desirable effect.
Pharmacology
Semax's neuroprotective and neuroregenerative effects are commonly attributed to its elevation and expression of brain-derived neurotrophic factor (BDNF)— a protein which supports synaptic and dendritic growth/maintenance, as well as the promotion of protective pathways, enhancing cell survival— and its signaling receptor, TrkB[8].
Additionally, Semax rapidly stimulates dopaminergic and serotonergic systems, which has been shown to greatly potentiate the effects of more conventional psychostimulants like dextroamphetamine[9] as well as posing anxiolytic, antidepressant, and anti-stress (biological and psychological) properties as a result[10][11].
Subjective effects
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 PsychonautWiki contributors. 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 
-
- Stimulation - While noticeable, Semax's stimulation is generally mild and unlikely to overstimulate on its own, though it noticeably potentiates the effects of more conventional stimulants.
- Stamina enhancement
- Decreased libido - This effect is frequently only noted after medium-to-long-term use.
- Headache - Though uncommon, mild tension headaches can present at high doses.
- Pain relief - This effect is generally only noted during physical stress or exercise.
Visual effects 
Cognitive effects 
-
- Anxiety suppression - Though not as strong as its relative chemical Selank, Semax's anxiolytic effects are sometimes strong enough to largely mitigate the anxiogenic properties of commonly-paired stimulants like amphetamine.
- Emotion enhancement or emotion suppression - Both are reported to a pronounced degree only after medium-to-long-term use, though emotion suppression may be more immediately pronounced depending on subject's propensity to emotional dysregulation.
- Focus enhancement
- Thought acceleration
- Analysis enhancement
- Memory enhancement - Semax's pronounced enhancement of both short and long-term memory encoding and recall are commonly attributed to its glutamatergic effects[12].
- Motivation enhancement
- Cognitive euphoria
- Wakefulness
- Increased music appreciation
- Mania - This effect only rarely presents at excessive doses (either an overly high dose, or a medium-high dose taken without prior low-dose usage).
Toxicity and harm potential
Though not unsafe, excessively high doses are occasionally capable of producing highly uncomfortable or undesirable effects, such as mania or headache. Anecdotal reports additionally indicate that Semax's elevation of brain-derived neurotrophic factor (BDNF) can precipitate hair loss, though this generally ceases within 1-3 months of the subject's final dose.
Lethal dosage
A lethal dosage for Semax has not been established, though specific testing on the matter has established that even an increase of 200 times the effective dosage (about 10mg/kg) was unable to produce a fatal outcome[13], likely attributable to the speed that the body eliminates peptides— Semax's half-life, the amount of time it takes for total concentration to fall to 50% of the original dose, is 4 minutes[7].
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As opposed to other stimulants, Semax does not appear to have any significant physical or psychological dependence liability, and does not produce symptoms of withdrawal upon discontinuation. Anecdotal reports, however, indicate that tolerance to its simulating effects may develop after sustained use, though other desirable effects (i.e. its nootropic properties) seem to have the opposite effect, building with sustained use due to upregulation of its signaling site.
Dangerous interactions
- Stimulants: Due to its significant potentiation of other dopaminergic stimulants, combining Semax with a considerable dose of substances like caffeine may produce highly unpleasant or undesirable effects like overstimulation
Legal status
- Russia, Ukraine, and other CIS nations: Semax is a legally-regulated prescription medication in the CIS and, as such, may only legally be obtained via medical prescription. Semax entered the Russian List of Vital & Essential Drugs in 2011[14].
- Australia: No laws or reports indicate possession or consumption of Semax to be illegal in Australia.
- China: No laws or reports indicate possession or consumption of Semax to be illegal in China, and numerous vendors ship from/within the Chinese mainland.
- France: No laws or reports indicate possession or consumption of Semax to be illegal in France.
- Germany: Though not legally recognized nor regulated, anecdotal reports indicate that shipments of Semax from American vendors are subject to seizure by German customs due to lack of FDA approval[15]. No known reports indicate domestic shipping issues.
- United Kingdom: While Semax may technically fall under the provisions of the Psychoactive Substances Act of 2016, numerous vendors appear to legally sell to British customers.
- United States: Semax is not legally recognized nor regulated in the United States. Its lack of recognition by the FDA has led some vendors to mark Semax as "not for human consumption".
See also
Further reading
References
- ↑ http://www.semaxint.com/pharmacology.htm
- ↑ http://www.semaxint.com/history.htm
- ↑ https://pubmed.ncbi.nlm.nih.gov/30225715/
- ↑ https://pubmed.ncbi.nlm.nih.gov/29798983/
- ↑ https://www.researchgate.net/publication/6798584_Semax_an_analog_of_ACTH4-10_with_cognitive_effects_regulates_BDNF_and_trkB_expression_in_the_rat_hippocampus
- ↑ https://pubmed.ncbi.nlm.nih.gov/15792140/
- ↑ 7.0 7.1 http://www.semaxint.com/pharmacology.htm
- ↑ https://pubmed.ncbi.nlm.nih.gov/16996037
- ↑ https://pubmed.ncbi.nlm.nih.gov/16362768/
- ↑ https://pubmed.ncbi.nlm.nih.gov/17850024/
- ↑ https://link.springer.com/article/10.1134%2FS0012496613060161
- ↑ https://pubmed.ncbi.nlm.nih.gov/21476267/
- ↑ https://patents.google.com/patent/RU2045958C1/en
- ↑ http://apps.who.int/medicinedocs/en/d/Js19766ru/
- ↑ https://www.reddit.com/r/Nootropics/comments/47ql5f/german_customs_seized_and_destroyed_my/