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'''S-Adenosyl methionine''' ('''SAMe''', '''Ademethionine''') is a methyl donating compound that circulates in the blood and provides methyl groups to maintain metabolic reactions.<ref>Homocysteine. | https://www.ncbi.nlm.nih.gov/pubmed/10762063</ref> SAMe is an amino acid methionine bound to an ATP molecule; this molecule 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'.
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%. <ref>Bioavailability of S-adenosyl methionine and impact on response in a randomized, double-blind, placebo-controlled trial in major depressive disorder. | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156851/</ref>
'''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.<ref>{{cite journal | vauthors=((Finkelstein, J. D.)), ((Martin, J. J.)) | journal=The International Journal of Biochemistry & Cell Biology | title=Homocysteine | volume=32 | issue=4 | pages=385–389 | date= April 2000 | issn=1357-2725 | doi=10.1016/s1357-2725(99)00138-7}}</ref> 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%.<ref>{{cite journal | vauthors=((Mischoulon, D.)), ((Alpert, J. E.)), ((Arning, E.)), ((Bottiglieri, T.)), ((Fava, M.)), ((Papakostas, G. I.)) | journal=The Journal of clinical psychiatry | title=Bioavailability of S-Adenosyl Methionine and Impact on Response in a Randomized Controlled Trial in Major Depressive Disorder | volume=73 | issue=6 | pages=843–848 | date= June 2012 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156851/ | issn=0160-6689 | doi=10.4088/JCP.11m07139}}</ref>
A review of trials assessing oral doses of SAMe between 200mg and 1600mg notes that they appear to have similar efficacy to Tricyclic Antidepressants and more effective than placebo.<ref>A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia. | http://www.ncbi.nlm.nih.gov/pubmed/20191258</ref>
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.<ref>{{cite journal | vauthors=((Chan, A.)), ((Remington, R.)), ((Kotyla, E.)), ((Lepore, A.)), ((Zemianek, J.)), ((Shea, T. B.)) | journal=The Journal of Nutrition, Health & Aging | title=A vitamin/nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia | volume=14 | issue=3 | pages=224–230 | date= March 2010 | issn=1760-4788 | doi=10.1007/s12603-010-0054-5}}</ref>
==Chemistry==
==Chemistry==
S-adenosyl methionine is a molecule, found endogenously 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 R<sub>2</sub> with an amino group and at R<sub>4</sub> with a methylthio (carbon-sulphur) group. S-adenosyl methionine is an essential methyl donator in metabolic reactions.
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 R<sub>2</sub> with an amino group and at R<sub>4</sub> with a methylthio (carbon-sulphur) group. It is an essential methyl donator in metabolic reactions.{{citation needed}}
==Pharmacology==
==Pharmacology==
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.<ref>Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. | http://www.ncbi.nlm.nih.gov/pubmed/12420702/</ref>
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.<ref name="Mischoulon">{{cite journal | vauthors=((Mischoulon, D.)), ((Fava, M.)) | journal=The American Journal of Clinical Nutrition | title=Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence | volume=76 | issue=5 | pages=1158S–61S | date= November 2002 | issn=0002-9165 | doi=10.1093/ajcn/76/5.1158S}}</ref>
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.<ref>Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases. | http://www.ncbi.nlm.nih.gov/pubmed/15922112</ref>
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.<ref>{{cite journal | vauthors=((Williams, A. C.)), ((Ramsden, D. B.)) | journal=Medical Hypotheses | title=Nicotinamide homeostasis: a xenobiotic pathway that is key to development and degenerative diseases | volume=65 | issue=2 | pages=353–362 | date= 2005 | issn=0306-9877 | doi=10.1016/j.mehy.2005.01.042}}</ref> 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==
==Subjective effects==
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
In comparison to the effects of other nootropics such as [[noopept]], this compound can be described as conferring both physical stimulation and cognitive stimulation.
In comparison to the effects of other nootropics such as [[noopept]], this compound is reported to produce more physical and cognitive stimulation.
{{effects/base
{{effects/base
|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Stimulation]]''' - The stimulation which SAM-e presents can be considered as subtle, yet persistent and energetic comparable to that of [[caffeine]], although less forced.
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Bodily control enhancement]]''' - In addition to raising energy levels, SAM-e shows efficacy in improving joint mobility in those with osteoarthritis.<ref>[Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis]. | http://www.ncbi.nlm.nih.gov/pubmed/12436324</ref>
*'''[[Effect::Bodily control enhancement]]''' - In addition to raising energy levels, SAM-e shows efficacy in improving joint mobility in those with osteoarthritis.<ref>{{cite journal | vauthors=((Witte, S.)), ((Lasek, R.)), ((Victor, N.)) | journal=Der Orthopade | title=[Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis] | volume=31 | issue=11 | pages=1058–1065 | date= November 2002 | issn=0085-4530 | doi=10.1007/s00132-002-0366-1}}</ref>
*'''[[Effect::Dehydration]]'''
*'''[[Effect::Dehydration]]'''
*'''[[Effect::Diarrhea]]'''
*'''[[Effect::Diarrhea]]'''
*'''[[Effect::Headaches]]'''
*'''[[Effect::Headaches]]'''
*'''[[Effect::Muscle spasms]]'''
*'''[[Effect::Muscle spasms]]'''
*'''[[Effect::Pain relief]]''' - This appears to be about as effective as NSAIDS such as [[ibuprofen]] for joint inflammation and pain.<ref> Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. | http://www.ncbi.nlm.nih.gov/pubmed/3318442</ref>
*'''[[Effect::Pain relief]]''' - This appears to be about as effective as NSAIDS such as [[ibuprofen]] for joint inflammation and pain.<ref>{{cite journal | vauthors=((Caruso, I.)), ((Pietrogrande, V.)) | journal=The American Journal of Medicine | title=Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease | volume=83 | issue=5A | pages=66–71 | date=20 November 1987 | issn=0002-9343 | doi=10.1016/0002-9343(87)90854-0}}</ref>
*'''[[Effect::Stamina enhancement]]'''
*'''[[Effect::Stamina enhancement]]'''
*'''[[Effect::Stimulation]]''' - The stimulation which Sam-e presents can be considered as subtle, yet persistent and energetic comparable to that of [[caffeine]], yet even less forced in nature.
*'''[[Effect::Stomach cramps]]'''
*'''[[Effect::Stomach cramps]]'''
*'''[[Effect::Tactile enhancement]]'''
*'''[[Effect::Tactile enhancement]]'''
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*'''[[Effect::Focus enhancement]]'''
*'''[[Effect::Focus enhancement]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Mania]]'''<ref>A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC315487/</ref>
*'''[[Effect::Mania]]'''<ref>{{cite journal | vauthors=((Berigan, T. R.)) | journal=Primary Care Companion to The Journal of Clinical Psychiatry | title=A Case Report of a Manic Episode Triggered by S-Adenosylmethionine (SAMe) | volume=4 | issue=4 | pages=159 | date= 2002 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC315487/ | issn=1523-5998}}</ref>
*'''[[Effect::Memory enhancement]]'''
*'''[[Effect::Memory enhancement]]'''
*'''[[Effect::Mindfulness]]'''
*'''[[Effect::Mindfulness]]'''
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}}
}}
===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:
There are no clinically significant side-effects of Sam-e supplementation acutely. Although side-effects are not commonly reported with SAMe, numerous studies note a small set of participants who experience [[mania]] after supplementing SAMe. It is not common, but it does appear 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.<ref> S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC535560/</ref><ref> Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. | http://www.ncbi.nlm.nih.gov/pubmed/12420702</ref>
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.<ref>{{cite journal | vauthors=((Shippy, R. A.)), ((Mendez, D.)), ((Jones, K.)), ((Cergnul, I.)), ((Karpiak, S. E.)) | journal=BMC Psychiatry | title=S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS | volume=4 | pages=38 | date=11 November 2004 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535560/ | issn=1471-244X | doi=10.1186/1471-244X-4-38}}</ref><ref name="Mischoulon"/>
Sam-e is also hypothesized to raise homocystine to harmful levels, but this has yet to be proven in a laboratory environment. <ref>Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. | http://www.ncbi.nlm.nih.gov/pubmed/9262350</ref> Still, it is advised to take Sam-e along with folate and B12.
SAM-e is also hypothesized to raise homocystine to harmful levels, but this has yet to be proven in a laboratory environment. <ref>{{cite journal | vauthors=((Loehrer, F. M.)), ((Schwab, R.)), ((Angst, C. P.)), ((Haefeli, W. E.)), ((Fowler, B.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans | volume=282 | issue=2 | pages=845–850 | date= August 1997 | issn=0022-3565}}</ref> Still, it is advised to take Sam-e along with folate and B12.
Regardless, it is strongly recommended that one be familiar with [[responsible drug use|harm reduction practices]] when using Sam-e.
Regardless, it is strongly recommended that one be familiar with [[responsible drug use|harm reduction practices]] when using this substance.
===Tolerance and addiction potential===
===Tolerance and addiction potential===
S-Adenosyl methionine is [[Addiction potential::not habit-forming with a low potential for abuse]]. It does not seem to be capable of causing psychological or physiological dependence among users.
SAM-e is [[Addiction potential::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).
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 issues==
==Legal status==
*'''United States''' - Sam-e is approved and legal over the counter for purchase.
*'''Russia''' - Sam-e is available by prescription.
*'''United States''' - SAM-e is approved and legal over the counter for purchase.
*'''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.<ref>Psychoactive Substances Act 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted</ref>
*'''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.<ref>{{Citation | title=Psychoactive Substances Act 2016 | url=https://www.legislation.gov.uk/ukpga/2016/2/contents/enacted}}</ref>
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.
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]
Pharmacology
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 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 ☠.
In comparison to the effects of other nootropics such as noopept, this compound is reported to produce more physical and cognitive stimulation.
Physical effects
Stimulation - The stimulation which SAM-e presents can be considered as subtle, yet persistent and energetic comparable to that of caffeine, although less forced.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
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]
↑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. ISSN1357-2725.
↑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. ISSN1760-4788.
↑ 4.04.1Mischoulon, 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. ISSN0002-9165.
↑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. ISSN0306-9877.
↑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. ISSN0085-4530.
↑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. ISSN0002-9343.
↑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. ISSN0022-3565.
