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What is it?

SAMe is a chemical that is found naturally in the body. It can also be made in the laboratory.

SAMe has been available as a dietary supplement in the US since 1999, but it has been used as a prescription drug in Italy since 1979, in Spain since 1985, and in Germany since 1989. Researchers discovered the potential usefulness of SAMe for treating osteoarthritis by accident. They were studying SAMe’s effect on depression when the patients they were following reported an unexpected improvement in their osteoarthritis symptoms.

SAMe is used for depression, anxiety, heart disease, fibromyalgia, osteoarthritis, bursitis, tendonitis, chronic lower back pain, dementia, Alzheimer's disease, slowing the aging process, chronic fatigue syndrome (CFS), improving intellectual performance, liver disease, and Parkinson's disease. It is also used for attention deficit-hyperactivity disorder (ADHD), multiple sclerosis, spinal cord injury, seizures, migraine headache, and lead poisoning.

Some women use SAMe for premenstrual syndrome (PMS) and a more severe form of PMS called premenstrual dysphoric disorder (PMDD).

How effective is it?

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

The effectiveness ratings for SAMe are as follows:

Likely effective for...

  • Depression. Taking SAMe by mouth or by injection seems to reduce symptoms of depression. Several studies have shown that SAMe can be beneficial and might be as effective as some prescription medications used for depression (tricyclic antidepressants). Some research also shows that taking SAMe might be helpful for people who do not have a good response to a prescription antidepressant. However, SAMe should not be taken in combination with a prescription antidepressant without the monitoring of a health professional.
  • Osteoarthritis. Taking SAMe by mouth seems to work about as well as aspirin and similar medications, but it can take twice as long to start working. Most people with arthritis need to take SAMe for about a month before they feel better.

Possibly effective for...

  • Symptoms of AIDS-related nerve problems. Taking SAMe intravenously seems to improve some symptoms caused by AIDS related to nerve problems.
  • Fibromyalgia. Some research suggests that taking SAMe by mouth improves symptoms of fibromyalgia. However, evidence on the use of SAMe intravenously for fibromyalgia is inconsistent. Some research suggests it may reduce symptoms, while other research does not.
  • Liver disorder in pregnancy (Intrahepatic cholestasis).. Taking SAMe by mouth or intravenously seems to helpful in treating liver disease during pregnancy.
  • Sexual dysfunction. Research suggests that taking SAMe in addition to antidepressants improves sexual dysfunction in men with depression.

Insufficient evidence to rate effectiveness for...

  • Alcohol-related liver disease.Evidence on the effect of SAMe in alcohol-related liver disease is inconsistent. Some early research shows that taking SAMe by mouth or intravenously reduces some symptoms associated with liver disease, such as jaundice and ankle swelling. However, it does not affect some liver function tests or reduce death or complications.
  • Attention deficit-hyperactivity disorder (ADHD). Research on the effects of SAMe in people with ADHD is not clear. Early research suggests that SAMe might reduce ADHD symptoms in adults. However, some research also suggests it does not improve symptoms.
  • Gilbert’s syndrome. Early research suggests that taking SAMe by mouth or intravenously might help the liver process a substance called bilirubin.
  • Hepatitis. The effects of SAMe in people with hepatitis is unclear. Some early research suggests that taking SAMe by mouth or intravenously improves liver function in people with hepatitis.
  • Liver disease (cirrhosis). Evidence on the effect of SAMe for liver disease is inconsistent. Some early research suggests that taking SAMe by mouth or intravenously improves liver function in people with liver disease.
  • Schizophrenia. Early research suggests that SAMe might reduce aggressive behavior in people with schizophrenia.
  • Blood infection (Sepsis). Some early research shows that taking SAMe in addition to conventional treatment reduces the amount of time needed to recover from a septic infection.
  • Quitting smoking. Early research suggests that SAMe does not help people quit smoking.
  • Heart disease.
  • Anxiety.
  • Bursitis.
  • Tendonitis.
  • Chronic low back pain.
  • Improving intelligence.
  • Premenstrual syndrome (PMS).
  • Premenstrual dysphoric disorder (PMDD).
  • Chronic fatigue syndrome (CFS).
  • Multiple sclerosis.
  • Spinal cord injury.
  • Seizures.
  • Migraine headache.
  • Other conditions.
More evidence is needed to rate SAMe for these uses.

How does it work?

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The body uses SAMe to make certain chemicals in the body that play a role in pain, depression, liver disease, and other conditions. People who don’t make enough SAMe naturally may be helped by taking SAMe as a supplement.

Are there safety concerns?

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SAMe is LIKELY SAFE for most people. It can sometimes cause gas, vomiting, diarrhea, constipation, dry mouth, headache, mild insomnia, anorexia, sweating, dizziness, and nervousness, especially at higher doses. It can make some people with depression feel anxious.

Special precautions & warnings:

Pregnancy and breast-feeding: Not enough is known about the safety of using SAMe during pregnancy and breast-feeding. Stay on the safe side and avoid use.

Children: SAMe is POSSIBLY SAFE when usedtaken by mouth andor used intravenously (by IV) in children in the short-term.

Bipolar disorder: Use of SAMe can cause people with bipolar disorder to convert from depression to mania.

Parkinson’s disease: SAMe might make Parkinson’s symptoms worse.

Surgery: SAMe might affect the central nervous system. This could interfere with surgery. Stop taking SAMe at least 2 weeks before a scheduled surgery.

Are there interactions with medications?

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Do not take this combination.

Dextromethorphan (Robitussin DM, and others)
SAMe can affect a brain chemical called serotonin. Dextromethorphan (Robitussin DM, others) can also affect serotonin. Taking SAMe along with dextromethorphan (Robitussin DM, others) might cause too much serotonin in the brain and serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking dextromethorphan (Robitussin DM, and others).

Medications for depression (Antidepressant drugs)
SAMe increases a brain chemical called serotonin. Some medications for depression also increase the brain chemical serotonin. Taking SAMe along with these medications for depression might increase serotonin too much and cause serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking medications for depression.

Some of these medications for depression include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), and others.

Medications for depression (MAOIs)
SAMe increases a chemical in the brain. This chemical is called serotonin. Some medications used for depression also increase serotonin. Taking SAMe along with these medications used for depression might cause too much serotonin in the body, and serious side effects including heart problems, shivering, and anxiety.

Some of these medications used for depression include phenelzine (Nardil), tranylcypromine (Parnate), and others.


Be cautious with this combination.

Levodopa is used for Parkinson's disease. SAMe can chemically change levodopa in the body and decrease the effectiveness of levodopa. Taking SAMe along with levodopa might make Parkinson's disease symptoms worse. Do not take SAMe if you are taking levodopa.

Meperidine (Demerol)
SAMe increases a chemical in the brain called serotonin. Meperidine (Demerol) can also increase serotonin in the brain. Taking SAMe along with meperidine (Demerol) might cause too much serotonin in the brain and serious side effects including heart problems, shivering, and anxiety.

Pentazocine (Talwin)
SAMe increases a brain chemical called serotonin. Pentazocine (Talwin) also increases serotonin. Taking SAMe along with pentazocine (Talwin) might cause serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking pentazocine (Talwin).

Tramadol (Ultram)
Tramadol (Ultram) can affect a chemical in the brain called serotonin. SAMe can also affect serotonin. Taking SAMe along with tramadol (Ultram) might cause too much serotonin in the brain and side effects including confusion, shivering, stiff muscles, and other side effects.

Are there interactions with herbs and supplements?

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Herbs and supplements with serotonergic properties
SAMe increases a chemical in the brain called serotonin. Taking SAMe along with other herbs and supplements that increase serotonin might lead to too much serotonin and cause serious side effects including heart problems, shivering and anxiety, Herbs and supplements that increase serotonin levels include 5-HTP, Hawaiian baby woodrose, L-tryptophan, and St. John's wort.

Are there interactions with foods?

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There are no known interactions with foods.

What dose is used?

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The following doses have been studied in scientific research:

  • For depression: 400-1600 mg per day.
  • For osteoarthritis: 200 mg three times daily.
  • For fibromyalgia: 800 mg per day.

Other names

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Ademetionine, Adenosylmethionine, Adénosylméthionine, S-Adenosyl Methionine, S-Adénosyl Méthionine, S-Adenosyl-L-Methionine, S-Adénosyl-L-Méthionine, S-Adenosylmethionine, S-Adénosylméthionine, S-Adenosylmethionine Butanedisulfonate, S-Adenosylmethionine Tosylate, S-Adenosylmethionine Tosylate Disulfate, SAM, SAM-e, Sammy.


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To learn more about how this article was written, please see the Natural Medicines Comprehensive Database methodology.methodology (


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To see all references for the SAMe page, please go to

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