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S-Adenosyl-L-Methionine (SAMe)


Laura Shane-McWhorter

, PharmD, University of Utah College of Pharmacy

Reviewed/Revised Jan 2022 | Modified Sep 2022

What is SAMe?

S-adenosyl-L-methionine (SAMe) is a naturally occurring chemical in the human body, produced largely by the liver. It is also manufactured synthetically as a supplement.

What claims are made about SAMe?

Does SAMe work?

Scientific studies so far do not clearly confirm that SAMe has most of its claimed benefits and more research is needed.

However, in 2 studies reviewed in a 2002 analysis SAMe was shown to be as effective as nonsteroidal anti-inflammatory drugs (NSAIDs) in treating people with osteoarthritis, but without the side effects common with NSAID use.

In some studies, SAMe used in combination with an antidepressant was useful for people who had depression that did not abate with treatment using a selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) Several types of medications can be used to treat depression: Selective serotonin reuptake inhibitors (SSRIs) Norepinephrine-dopamine reuptake inhibitors, serotonin modulators, and serotonin-norepinephrine... read more (SSRI), but this benefit was not confirmed in later studies.

What are the possible side effects of SAMe?

No serious side effects have been reported. People with a bipolar disorder should not use SAMe, because it can cause manic episodes.

Some less serious side effects that have been reported include digestive problems, as well as dry mouth, headache, dizziness, and skin rashes.

What drug interactions occur with SAMe?

Combining certain antidepressant drugs, such as clomipramine, with SAMe may increase serotonin levels, which may cause serotonin syndrome Serotonin Syndrome Serotonin syndrome is a potentially life-threatening drug reaction that tends to cause high body temperature, muscle spasms, and anxiety or delirium. Serotonin is a chemical that transmits impulses... read more , a serious disorder characterized by fever, confusion, rapid heart rate, anxiety, tremors, and other symptoms. SAMe may also decrease levodopa levels (deficient in people who have Parkinson disease Parkinson Disease (PD) Parkinson disease is a slowly progressive degenerative disorder of specific areas of the brain. It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone... read more ) and thus decrease the effectiveness of drugs that aim to treat Parkinson disease by increasing levodopa levels.


SAMe seems to be a useful treatment for osteoarthritis and may help relieve depression. The American Psychiatric Association states that SAMe is an option in people who prefer natural treatments. The Canadian Network for Mood and Anxiety Treatments states that SAMe may be considered a first- or second-line treatment for mild to moderate depression. Other claimed benefits require more evidence for confirmation.

People who plan to take SAMe with certain antidepressants such as clomipramine should talk to their doctor about the risks, because serotonin levels may increase and result in serotonin syndrome. People with Parkinson disease should avoid SAMe because it may decrease the benefit of certain drugs used to treat Parkinson disease. Overall, SAMe appears to be safe for most people.

Drugs Mentioned In This Article

Generic Name Select Brand Names
INBRIJA, Larodopa
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