Drug info - Sam-E Thread: Potentiation and Recovery?

[nleksan]

SWIM has searched the forum and read everything available on the nootropic Sam-E, but does not feel that there is enough information available here on this wonderful drug. SWIM would like to preface this thread by saying that he has diagnosed depression, ADD, and anxiety disorder, and was prescribed Sertraline (Zoloft) for three months, after which he discontinued taking the medication. SWIM felt that Sertraline caused far too many side effects and interfered with far too many of his regular activities to be worth the minor relief from his depression and panic attacks. SWIM began searching for another solution, one that wouldn't make him feel like he was losing touch with who he really was, and one that also didn't interfere with usage of psychedelics. After a bit of research, SWIM discovered Sam-E. He began the first month taking 400mg daily, and is now taking 200mg a day. He also takes 400mg of Acetyl L-Carnitine and 200mg of Alpha Lipoic Acid, along with 10mg Dextroamphetamine and 200mg Ginseng. He has noticed significant relief from depression, feeling much more like himself than he thought he ever would again. It has not done much to help with panic attacks, but he did not really expect it to provide much relief with those anyway.

Well, that was a much longer introduction than SWIM expected to write, so now he would like to provide some information for those looking at this wonderful nootropic, as well as some personal insight and questions. Let SWIM also note that he is a pharmacology student specializing in neuropharmacology. (Note: Much of the sources SWIM will be quoting will be Wikipedia, as he feels that on this specific topic it provides the most concise, detailed information he can find on the internet. Also, it will allow some of the much more experienced and intelligent members on the board to express their opinion while having all of the relevant information in one thread)

S-adenosyl methionine (SAM) is a cofactor involved in methyl group transfers. SAM was first discovered in 1952.[1] It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase EC 2.5.1.6. Transmethylation, transsulfuration and aminopropylation are the metabolic pathways that use SAM. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver.[1]
The methyl group (CH3) attached to the methionine sulfur atom in SAM is chemically reactive. This allows donation of this group to an acceptor substrate in transmethylation reactions. More than 40 metabolic reactions involve the transfer of a methyl group from SAM to various substrates such as nucleic acids, proteins and lipids.

- Wikipedia

Basically, what SWIM gets from this text, is that Sam-E allows other substances to more readily pass the blood-brain barrier due to its ability to attach a methyl group to the substance (CH3). Although Sam-E is known for it's ability to regulate and perhaps repair neurotransmitters, perhaps its involvement with methyl group transfers is actually allowing more "ingredients" of neurotransmitters to actually make their way into the brain? SWIM has not performed any extensive research, but he has found that taking 5-HTP seems to have much more of an effect since he has been using Sam-E than it did before.

SAM cycle

The reactions that produce, consume and regenerate SAM are called the SAM cycle. In the first step of this cycle, the SAM-dependent methylases (EC 2.1.1) that use SAM as a substrate produce S-adenosyl homocysteine as a product.[2] This is hydrolysed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase EC 3.3.1.1 and the homocysteine recycled back to methionine through transfer of a methyl group from 5-methyltetrahydrofolate, by one of the two classes of methionine synthases EC 2.1.1.13 or EC 2.1.1.14. This methionine can then be converted back to SAM, completing the cycle.[3]

[edit] Polyamine biosynthesis

Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by Adenosylmethionine decarboxylase EC 4.1.1.50 to form S-adenosyl-5'-3-methylpropylamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.[4]
SAM is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as dopamine and serotonin. Methyltransferases are also responsible for the addition of methyl groups to the 2' hydroxyls of the first and second nucleotides next to the 5' cap in messenger RNA.[5][6]

- Wikipedia

SWIM finds the SAM cycle to be rather fascinating, but due to his limited knowledge thus far of neurochemistry, does not fully understand what is going on. SWIM is wondering if someone with a better understanding would be able to enlighten him. Basically, what SWIM understands from this is that Sam-E should be of use to those who have used psychedelics, MDMA, or amphetamines due to its involvement with the biosynthesis of serotonin and dopamine. Perhaps this is why SWIM felt that he was more affected by 5-HTP while taking Sam-E than he was without it? SWIM is also curious about the effects this might have concurrently with L-Tyrosine, a precursor to Dopamine and Norepinepherine.

Possible side effects

SAM-e & Homocysteine: Once SAM-e donates its methyl group to choline, creatine, carnitine, DNA, tRNA, norepinephrine, and other compounds, it is transformed into S-adenosyl-homocysteine, (SAH). Normally, homocysteine in the presence of Vitamin B6, B12, and folic acid (SAM-e's main co-factors), will eventually be converted back into methionine, SAM-e, or cysteine, glutathione and other useful substances. However if adequate amounts of these vitamins are not present, SAM-e will not break down properly, consequently the full benefits of SAM-e will not be obtained, and homocysteine may increase to unsafe levels.
High levels of homocysteine, have been associated with atherosclerosis (hardening and narrowing of the arteries), as well as an increased risk of heart attacks, strokes, liver damage, and possibly Alzheimer's disease. Therefore Vitamin B supplements are often taken along with SAM-e. These vitamins help metabolize the homocysteine into other useful compounds. [1][20]
Another reported side effect of SAMe is insomnia, therefore the supplement is often taken in the morning.[19]
Therapeutic doses range from 800 mg/day to 1600 mg/day, although lower and higher doses are used.[14][21] Consult with your physician before and during use.

- Wikipedia

SWIM is wondering what the noticeable side effects of an increase in homocysteine would be, as he has a history of heart disease in his family and would like to take any precautions necessary to avoid the same terrible fate. SWIM also realizes that the dose he is taking is below the noted therapeutic dose, but still feels that it does not need to be increased, which is somewhat perplexing. Perhaps SWIM's biology is just a little different than other's.

SWIM is also curious about the possibility of serotonin syndrome with this drug. SWIM has taken LSD, mushrooms, 2C-E, 5-MeO-AMT (and my God will he never do that again. Sold fake blotter), amphetamines (daily per prescription), and is a daily cannabis user. SWIM has found that it increased the potency of LSD and mushrooms, and it only took one day before his tolerance was completely back down again. This interested SWIM, as on the sertraline his response was greatly diminished to both psychedelics. He had to take twice the dose of mushrooms he usually does to trip, resulting in him eating 7 grams. With Sam-E, however, he found that 2 grams gave him a very, very strong trip. With LSD, on sertraline he found that even eating 6 or 7 blotters would just make him feel dissociated and spaced out, but lacking the typical inner dialogue that he loves LSD so much for. With Sam-E, he took 2 doses from the same batch and has never had such intense visuals. It did not noticeable affect 2C-E (granted the only time he's taken it without Sam-E was the first time, accidentally consuming 35mg) so there is not much of a reference point. Although he did trip very hard on 15mg concurrent with 200mg Sam-E. It has no noticeable effect on cannabis usage.

With the 5-MeO-AMT, however, SWIM just felt horrible the next day; depressed, lazy, lifeless. Taking Sam-E along with 5-HTP reduced the symptoms noticeably, and SWIM was back to normal in a day or two. SWIM feels that Sam-E might be more useful for recovery from psychedelic or MDMA usage than the more popular 5-HTP because of its ability to repair neurotrasmitters, rather than just elevate their precursors in hopes that it will in turn elevate the chemicals.

Well, that is all he wrote. Hopefully this will provide some information on this interesting and potentially very useful nootropic. And thanks in advance for anything that can be contributed to the thread.

[Beta]

According to my cat, Sam-e is very effective alone or with lsd and mdma. Alone, it just puts you in a good mood (like a very light mdma). With lsd and mdma, it makes the experience stronger in a very positive way...

[senorsalvia]

Might Swim suggest that the usage of dextroamphetamine with your Sam-E is reason in, and of itself to suspect you are not merely feeling the relif from the Sam-E............... Adding an upper really clouds your honest appraisal of the benefits of the nootropic on its own.............

[nleksan]

Originally Posted by senorsalvia

Might Swim suggest that the usage of dextroamphetamine with your Sam-E is reason in, and of itself to suspect you are not merely feeling the relif from the Sam-E............... Adding an upper really clouds your honest appraisal of the benefits of the nootropic on its own.............

SWIM is aware of this, but has been prescribed various amphetamines for over 6 years now, so he feels that he can pretty accurately judge the effects of other substances on top of his medication.

[senorsalvia]

Thanks for the clarification.... Senor SWIM can understand, as there was a time yrs ago, where he was taking prescribed Zoloft... At first, SWIMr had somewhat unusual interaction with his other drugs of choice, after a few weeks, SWIM was also able to accurately judge any interaction effects/ or lack thereof......Not trying to be picky/just precise--------------

[Alfa]

How about larger amount like 1500 mg? Did anyone try that as a recreational dose?

[JTC3889]

for that kind of experiment, it may be wise to supplement folic acid b6 and b12 to prevent harmful levels of homocystine.

[nleksan]

Originally Posted by JTC3889

for that kind of experiment, it may be wise to supplement folic acid b6 and b12 to prevent harmful levels of homocystine.

SWIM was aware of this and was doing so, but he is glad you brought it up as he forgot to mention it in his original post.

Note: SWIM is no longer taking SAM-e, as he found it did not work well with his new medication (desoxyn).

[Jasim]

Swim just learned of this medication and was instantly interested. Swim was unable to find much of interest on EBSChost, but is curious about SAMs usefulness in recreational drug use, either alone or in combination to enhance another drug.

Has anyone had a first-hand experience with S-Adenosyl Methionine in a recreational fashion?

Does anyone have any published scientific sources with more info on SAM? Swim is curious as to what exactly SAM does in the brain.


Swim has also become aware of the idea that SAM can replenish glutathione. Glutathione is an important chemical in phase II metabolism and can prevent toxic accumulations of some substances. Glutathione depletion is of particular concern with respect to acetominophen toxicity. Swim is curious if SAM could be used to offset acetominophen toxicity when acetominophen containing drugs are abused.

Jasim added 1 Minutes and 22 Seconds later...

Originally Posted by nleksan

Note: SWIM is no longer taking SAM-e, as he found it did not work well with his new medication (desoxyn).

Could swiy elaborate on this? What exactly happened?

[Barksdale]

SWIM has just ordered now. Wondering what it's best to mix it with though?