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Summary sheet: SAM-e
S-Adenosyl methionine.svg
Chemical Nomenclature
Common names S-Adenosyl Methionine, SAM-e, Methylguanidoacetic Acid
Systematic name (2S)-2-Amino-4-(((2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl)methyl-methylsulfonio)butanoate
Class Membership
Psychoactive class Nootropic
Chemical class Nitrogenous organic acid
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.

Bioavailability 2-10%
Threshold 200 mg
Light 400 - 800 mg
Common 800 - 1200 mg
Strong 1200 - 1600 mg
Heavy 1600 mg +
Total 8 - 12 hours
Onset 100 - 180 minutes

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.


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.[1] 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'.[citation needed]

SAM-e is available over the counter and by prescription in the treatment of depression and osteoarthritis. It is generally distributed in enteric-coated tablets, which allows the supplement to pass through the low pH environment of the stomach to the gastrointestinal tract, raising the bioavaliability by 600%.[2]

Enteric coated SAM-e tablets.

A review of trials assessing oral doses of SAM-e between 200mg and 1600mg notes that they appear to have similar efficacy to tricyclic antidepressants as well as being more effective than placebo.[3]


S-adenosyl methionine is an endogenous molecule, found as a substrate synthesized by the sub-groups adenosine and methionine through an the enzyme methionine adenosyltransferase. The adenosine subcomponent is comprised of an adedine nucleobase bonded to a ribose chain. This ribose chain is attached to the terminal carbon of the methionine group. Methionine is a butyl carboxylic acid substituted at R2 with an amino group and at R4 with a methylthio (carbon-sulphur) group. It is an essential methyl donator in metabolic reactions.[citation needed]


SAM-e is an endogenous molecule that has numerous roles including methyl donation in neurotransmitter synthesis, antioxidative effects (radical scavenging, glutathione precursor), anti-inflammatory effects, and neuroprotective effects.[4]

SAM-e, in addition to providing ATP to the cell, also can convert nicotinamine into N-methyl-nicotinamide (NMNA) via nicotinamide N-methyltransferase, NMNA which can prevent choline efflux from the brain and neuron, a process which may account for some of SAM-e's nootropic effects.[5] The involvement of SAM-e in the process of synthesizing serotonin, creatine and dopamine likely play a role in nootropic effects as well.

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 ☠.

In comparison to the effects of other nootropics such as noopept, this compound is reported to produce more physical and cognitive stimulation.

Physical effects

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Toxicity and harm potential


This toxicity and harm potential section is a stub.

As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

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.[9][4]

SAM-e is also hypothesized to raise homocystine to harmful levels, but this has yet to be proven in a laboratory environment. [10] Still, it is advised to take Sam-e along with folate and B12.

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

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.

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).

Legal status

  • United States - SAM-e is approved and legal over the counter for purchase.
  • Germany - SAM-e is sold as a dietary supplement.
  • Russia - SAM-e is available by prescription.
  • United Kingdom - It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[11]

See also

External links


  1. Finkelstein, J. D., Martin, J. J. (April 2000). "Homocysteine". The International Journal of Biochemistry & Cell Biology. 32 (4): 385–389. doi:10.1016/s1357-2725(99)00138-7. ISSN 1357-2725. 
  2. Mischoulon, D., Alpert, J. E., Arning, E., Bottiglieri, T., Fava, M., Papakostas, G. I. (June 2012). "Bioavailability of S-Adenosyl Methionine and Impact on Response in a Randomized Controlled Trial in Major Depressive Disorder". The Journal of clinical psychiatry. 73 (6): 843–848. doi:10.4088/JCP.11m07139. ISSN 0160-6689. 
  3. Chan, A., Remington, R., Kotyla, E., Lepore, A., Zemianek, J., Shea, T. B. (March 2010). "A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia". The Journal of Nutrition, Health & Aging. 14 (3): 224–230. doi:10.1007/s12603-010-0054-5. ISSN 1760-4788. 
  4. 4.0 4.1 Mischoulon, D., Fava, M. (November 2002). "Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence". The American Journal of Clinical Nutrition. 76 (5): 1158S–61S. doi:10.1093/ajcn/76/5.1158S. ISSN 0002-9165. 
  5. Williams, A. C., Ramsden, D. B. (2005). "Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases". Medical Hypotheses. 65 (2): 353–362. doi:10.1016/j.mehy.2005.01.042. ISSN 0306-9877. 
  6. Witte, S., Lasek, R., Victor, N. (November 2002). "[Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis]". Der Orthopade. 31 (11): 1058–1065. doi:10.1007/s00132-002-0366-1. ISSN 0085-4530. 
  7. Caruso, I., Pietrogrande, V. (20 November 1987). "Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease". The American Journal of Medicine. 83 (5A): 66–71. doi:10.1016/0002-9343(87)90854-0. ISSN 0002-9343. 
  8. Berigan, T. R. (2002). "A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe)". Primary Care Companion to The Journal of Clinical Psychiatry. 4 (4): 159. ISSN 1523-5998. 
  9. Shippy, R. A., Mendez, D., Jones, K., Cergnul, I., Karpiak, S. E. (11 November 2004). "S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS". BMC Psychiatry. 4: 38. doi:10.1186/1471-244X-4-38. ISSN 1471-244X. 
  10. Loehrer, F. M., Schwab, R., Angst, C. P., Haefeli, W. E., Fowler, B. (August 1997). "Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans". The Journal of Pharmacology and Experimental Therapeutics. 282 (2): 845–850. ISSN 0022-3565. 
  11. Psychoactive Substances Act 2016