SAM-e – A Nootropic for Improving Cognition & Fighting Depression

Many people take supplements in the hope that they can improve aspects of their lives without incurring major side-effects or having to rely on prescriptions.  As many as there are available, only a select few of them rise to the status of “life-changing” or “incredibly powerful”.  One of those rare substances is S-Adenosyl Methionine (abbr. SAM-e), which has been hailed as an effective treatment for many problems and is a favorite among many users of nootropics.

What is SAM-e?

same not sammySAM-e is an important cosubstrate in the human body, which means it facilitates enzymatic reactions to produce chemicals that we need to function. Specifically, SAM-e is involved withmethyl group transfers or methylation to produce proteins, neurotransmitters, and other biochemicals.

Since methylation in humans is not always at optimal levels (due to genetics and other factors), SAM-e can have widespread benefits by allowing such reactions to occur at a steady rate.

The mental effects associated with this supplement are derived from its influence in bolstering the production of common monoamines such as dopamine, serotonin, and norepinephrine.

Usage and Treatment


Perhaps the most common reason SAM-e is sought after is for its utility as an antidepressant.  A few studies have concluded that compared to placebo, SAM-e had a significant positive effect on treating mild to moderate depressive symptoms.  What makes it better than a typical antidepressant is its lack of unpleasant side effects like headaches and sexual dysfunction.

However, you don’t need to be diagnosed with a disorder to truly feel its brilliant effects on mood.  SAM-e can be taken by almost anyone and it can be mood-lifting, thanks to the role of methylation in increasing and maintaining dopamine and serotonin levels.  Those who do not benefit from SAM-e might already be methylating at a high level, or even too much.  Overall, it seems to be gathering steam as a potential treatment for depression, one that we could see in the very near future.

Other Medical Treatments

There is promise for using SAM-e as a treatment for osteoarthritis, due to its ability to assist the regrowth of cartilage in joints.  It can also generally help the regulation of inflammation and pain throughout the body, assisting with conditions such as fibromyalgia.

Besides all of this, SAM-e could be useful in treating liver disease due to its ability to process and recycle chemicals (many of them being harmful) through methylation.  SAM-e is metabolized to several different substance including cysteine and glutathione – both of which are critical to liver function.

As a Nootropic

SAM-e can be a very effective nootropic, especially when used in combination with other ones.  The primary reason being, of course, an increase in neurotransmitter production.  Increased neurotransmitters levels such as with acetylcholine, norepinephrine, and dopamine are associated with speed, fluidity, and enhanced focus.

The Perceptiv nutraceutical stack we covered a few months ago combined SAM-e with other supplements such as ALCAR, N-Acetylcysteine, and specific B-vitamins.  The magic of Perceptiv was that every ingredient was extremely synergistic with one another, stopping free radicals and helping to pave healthy neural pathways in the brain.  SAM-e is described as the “pivot”, or the most important member of the stack, according to its creator.


Even though it shows promise in treating a variety of conditions, SAM-e is typically only available as a supplement.  It is usually taken orally via an enteric-coated tablet, but an injectable form with a high bioavailability exists.  Prescriptions for SAM-e can be found in Italy, which is also where most (if not all) SAM-e in the world is produced via a special fermentation process.

Tablets of SAM-e are available in 200mg and 400mg quantities, measuring in terms of pure S-Adenosyl Methionine.  The salt form usually taken is SAM-e Tosylate Disulfate, which is sometimes labelled as the SAM-e itself and can cause confusion on the dosage.  Therefore when you choose a product, look for the number regarding the pure form of SAM-e.  Due to the unstable nature of the molecule (it degrades when exposed to air), tablets are best kept in a foil blister-pack

SAM-e is best taken in the morning on an empty stomach, to ensure maximum absorption.  Another reason to take it earlier in the day is that some people experience wakefulness or insomnia if taken towards nighttime.  The effective dose is anywhere from 200 to 800 milligrams, under normal circumstances.  Some people take more or less, and with higher dosages it is usually split into two separate doses in the day.

Side Effects