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Nootropic

SAM-e

Also called S-Adenosyl Methionine, Methylguanidoacetic Acid, Adohcy

Original Wikipedia articleen.wikipedia.org/wiki/S-Adenosyl_methionine revision used (24 October 2026)

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Common dose · Oral800–1200 mg PW
Onset100–180 minutes PW
Total8–12 hours PW

Dosage

Oral

SourceThresholdLightCommonStrongHeavy
PsychonautWiki200 mg PW400–800 mg PW800–1200 mg PW1200–1600 mg PW1600 mg+ PW

Bioavailability: 2–10% PW

What dose are you on? (self-reported, unverified)
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Duration

Route · sourceOnsetCome-upPeakOffsetTotalAfter-effects
Oral · PsychonautWiki100–180 minutes PW–––8–12 hours PW–

Mixing

Acute combinations: what happens when these are taken close together. Entries backed by a medical journal or agency are listed first.

Backed by medical journals

Awaiting sourcePeer-reviewed reports on acute combinations, from PubMed and the journals the harm reduction sites cite.

Risks and toxicity

There are no clinically significant side-effects of acute SAM-e supplementation. Although side-effects are not commonly reported with SAMe, numerous studies note a small set of participants who experience mania after supplementing SAM-e. While not common, it appears to be related to SAMe supplementation for unknown reasons; it has been reported in some persons without history of mania as well and does not appear to be related to any pathological condition per se.[6][7] PW

SAM-e is also hypothesized to raise homocystine to harmful levels, but this has yet to be proven in a laboratory environment. Still, it is advised to take Sam-e along with folate and B12.[8] PW

Regardless, it is strongly recommended that one be familiar with harm reduction practices when using this substance. PW

Tolerance and addiction potential

SAM-e is not habit-forming with a low potential for abuse. It does not seem to be capable of causing psychological or physiological dependence among users. PW

Tolerance to many of the effects of S-adenosyl methionine develops over several weeks of prolonged and repeated use. This results in users having to administer increasingly larger doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). PW

Testing

Awaiting sourceReagent reactions and test kit guidance from a harm reduction testing service.

Effects

Awaiting sourceSubjective and physical effects from PsychonautWiki or TripSit.

Overview

S-Adenosyl-L-methionine (also called S-Adenosyl methionine, Ademethionine and commonly as SAMe and SAM-e) is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation in biological organisms. SAMe is an amino acid methionine bound to an ATP molecule that circulates in the blood naturally and acts as a 'methyl donor'. A methyl group in chemistry is simply a carbon molecule (bound to some hydrogens), and donating a methyl group to other molecules can accelerate or preserve reactions in the body as a form of metabolic 'maintenance'.[1] PW⚠ PsychonautWiki itself has flagged this text: citation needed.

S-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or Adonat, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver. More than 40 methyl transfers from SAM are known, to various substrates such as nucleic acids, proteins, lipids and secondary metabolites. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase. SAM was first discovered by Giulio Cantoni in 1952.[2] WP

In bacteria, SAM is bound by the SAM riboswitch, which regulates genes involved in methionine or cysteine biosynthesis. In eukaryotic cells, SAM serves as a regulator of a variety of processes including DNA, tRNA, and rRNA methylation; immune response; amino acid metabolism; transsulfuration; and more. In plants, SAM is crucial to the biosynthesis of ethylene, an important plant hormone and signaling molecule.[3][4] WP

SAM has been studied for depression, osteoarthritis, and liver diseases with inconclusive results, and while generally considered safe short-term, its long-term safety, use during pregnancy, and risks for people with bipolar disorder or compromised immune systems remain unclear.[5] WP

History

Awaiting sourceHistory and culture from Wikipedia or PsychonautWiki, with their citations.

Pharmacology

Pharmacokinetics

Oral SAM achieves peak plasma concentrations three to five hours after ingestion of an enteric-coated tablet (400–1000 mg). The half-life is about 100 minutes.[10] WP

Chemistry

Formula
C15H23N6O5S+ PC
Formula (Wikipedia infobox)
C15H22N6O5S WP⚠ Wikipedia and PubChem give different formulas. Both are shown as each source has it.
Note
⚠ The PubChem record carries a charge, so it may describe an ion or salt of this substance rather than the substance itself.
Molar mass (g/mol)
399.4 PC
IUPAC name (computed by PubChem)
(3-amino-3-carboxypropyl)-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]-methylsulfanium PC
SMILES
C[S+](CCC(C(=O)O)N)C[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=NC3=C(N=CN=C32)N)O)O PC
InChIKey
MEFKEPWMEQBLKI-YDBXVIPQSA-O PC
PubChem CID
9865604

User reports

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Listings
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Top stories
Awaiting sourceShort summaries of the most-read reports, each linked, saying only what the report says.

Bluelight bluelight.org

Listings
Awaiting sourceTrip report threads and this substance's discussion forum.
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Reddit reddit.com

Listings
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Top stories
Awaiting sourceShort summaries of the most-read reports, each linked, saying only what the report says.

Pop culture

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References

  1. Journal / agency Finkelstein, J. D., Martin, J. J. Homocysteine. The International Journal of Biochemistry & Cell Biology. April 2000. doi:10.1016/s1357-2725(99)00138-7
  2. Journal / agency Cantoni, GL. The Nature of the Active Methyl Donor Formed Enzymatically from L-Methionine and Adenosinetriphosphate. J Am Chem Soc. 1952. doi:10.1021/ja01131a519
  3. Journal / agency Ding, Wei; Smulan, Lorissa J.; Hou, Nicole S.; Taubert, Stefan; Watts, Jennifer L.; Walker, Amy K. S-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. Cell Metabolism. 2015-10-06. doi:10.1016/j.cmet.2015.07.013 · PMID 26321661 · PMC4598287
  4. Journal / agency Wang, X.; Oh, M. W.; Komatsu, S. Characterization of S-adenosylmethionine synthetases in soybean under flooding and drought stresses. Biologia Plantarum. 2016-06-01. doi:10.1007/s10535-016-0586-6
  5. Journal / agency S-Adenosyl-L-Methionine (SAMe): In Depth. January 11, 2017
  6. Journal / agency Shippy, R. A., Mendez, D., Jones, K., Cergnul, I., Karpiak, S. E. S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS. BMC Psychiatry. 11 November 2004. doi:10.1186/1471-244X-4-38
  7. Journal / agency Mischoulon, D., Fava, M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. The American Journal of Clinical Nutrition. November 2002. doi:10.1093/ajcn/76/5.1158S
  8. Journal / agency Loehrer, F. M., Schwab, R., Angst, C. P., Haefeli, W. E., Fowler, B. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. The Journal of Pharmacology and Experimental Therapeutics. August 1997
  9. Other Psychoactive Substances Act 2016
  10. Journal / agency Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW. S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. ISRCTN36233495. BMC Musculoskelet Disord. February 2004. doi:10.1186/1471-2474-5-6 · PMID 15102339 · PMC387830

Text and values on this page are quoted from PsychonautWiki (CC BY-SA 4.0), Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.