SAMe or SAM-e

Our rating
1 smiley: Evidence for this treatment is promising and it may be useful. It has some evidence to support it, but more evidence is needed to be sure it works. Exclamation mark: However safety or other concerns have been raised for the use of this treatment.


The rating system

  • 3 smiliesThese treatments are very useful. They are strongly supported as effective by scientific evidence.
  • 2 smiliesThese treatments are useful. They are supported by scientific evidence as effective, but the evidence is not as strong.
  • 1 smileyThese treatments are promising and may be useful. They have some evidence to support them, but more evidence is needed to be sure they work.
  • No smiley On the available evidence, these treatments do not seem to be effective.
  • Question markThese treatments have not been properly researched. It is not possible to say whether they are useful or not.
  • Exclamation MarkSafety or other concerns have been raised for the use of these treatments.

What is it?

SAMe (pronounced 'Sammy') is short for S-adenosylmethionine. SAMe is a chemical that is produced naturally by the body.

How does it work?

It is not clear exactly how SAMe might work to help depression. It is thought that SAMe is involved in the production of different chemicals in the body, including neurotransmitters (chemical messengers in the brain). Increasing the levels of certain neurotransmitters, like serotonin, might help reduce symptoms of depression.

SAMe can be taken orally as a supplement and is sometimes given as an injection.

Is it effective?

Some studies have found that SAMe has a positive effect on depressive symptoms. In some cases, SAMe was more effective than a placebo (dummy pill), and about as effective as anti-depressant medication in reducing depression symptoms.

While there have been several studies looking at SAMe for depression, many of these studies are of poor quality. There is very little good-quality scientific evidence on SAMe for the treatment of depression. More research is needed to understand the effectiveness of SAMe, especially for people who have severe depression.

Are there any disadvantages?

Safety concerns have been raised for the use of this supplement. A recent study, conducted with mice, found that SAMe breaks down in the body into molecules which are known to be toxic to humans. This result has not yet been replicated in studies of SAMe with humans.

SAMe may have negative interactions with antidepressant medications and other supplements. People who are taking prescribed anti-depressants or who have Bipolar Disorder should not take SAMe unless they have consulted their doctor first.

Some studies of SAMe have found that it did not cause any more side-effects than placebos or anti-depressant medication. However, it is not clear whether these side-effects were thoroughly investigated. Some participants taking SAMe have reported experiencing anxiety and mania.

Where do you get it?

SAMe is available in health food shops, chemist shops and on the internet.


There is evidence that SAMe appears to be a promising treatment for mild-to-moderate depressive symptoms in the short term. However, SAMe is not recommended for self-help. A recent study suggests SAMe may be toxic and more research is needed to establish that it is safe.

Key references

  • Carpenter DJ. St. John’s Wort and S-Adenosyl methionine as “natural” alternatives to conventional antidepressants in the era of the suicidality boxed warning: What is the evidence for clinically relevant benefit? Alternative Medicine Review. 2011; 16: 17-39.
  • Fukumoto K, Ito K, et al. (2022). Excess S-adenosylmethionine inhibits methylation via catabolism to adenine. Communications Biology 5(1): 313.
  • Galizia I, Oldani L, et al. S‐adenosyl methionine (SAMe) for depression in adults. Cochrane Database of Systematic Reviews; 2016 (10).
  • Sharma A, Gerbarg, P, et al. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. Journal of Clinical Psychiatry. 2017; 78(6), e656.

Last reviewed and updated: 20 April 2022