S-adenosyl-L-methionine (SAMe) is a compound found naturally in the body. SAMe helps produce and regulate hormones and maintain cell membranes.

A synthetic version of SAMe is available as a dietary supplement in the U.S. In some countries in Europe, SAMe is a prescription drug.

SAMe can be taken orally, through a muscular injection or by IV. People generally use SAMe to treat depression, osteoarthritis and liver disease. However, SAMe can also interact with antidepressant medications.


Research on SAMe use for specific conditions shows:

  • Depression. While research has shown that SAMe has a positive effect in treating depression, most studies weren’t well designed and included a small number of people.
  • Liver disease. More studies are needed to determine whether SAMe is beneficial for people who have liver disease.
  • Osteoarthritis. Many studies comparing the use of SAMe with nonsteroidal anti-inflammatory drugs showed that each provided similar pain relief and improvement in joint function, but SAMe produced fewer side effects. A smaller number of studies haven’t shown the same results.

Our take

Green light: Generally safe

Generally safe

SAMe appears to be safe and might be effective in treating depression and osteoarthritis. However, SAMe might interact with antidepressants. Don’t use SAMe and prescription antidepressants together.

Safety and side effects

Side effects from SAMe are usually mild.

SAMe can cause:

  • Digestive problems, such as nausea, diarrhea or constipation
  • Mild insomnia
  • Dizziness
  • Irritability
  • Anxiety
  • Sweating

If you have bipolar disorder, don’t take SAMe without talking to your doctor first. The supplement might increase anxiety and mania.

If you have a compromised immune system, talk to your doctor before taking SAMe. People who have a weakened immune system may be at increased risk of an infection caused by bacteria known as pneumocystis. SAMe may boost this microorganism’s growth.


Possible interactions include:

  • Antidepressants and other drugs and supplements that increase levels of serotonin. Don’t take SAMe with antidepressants. The combination could cause effects similar to a condition caused by high levels of the chemical serotonin to accumulate in your body (serotonin syndrome).
  • Antipsychotics. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
  • Amphetamines. Be cautious when taking these drugs with SAMe. The combination could increase the risk of serotonin syndrome.
  • Dextromethorphan. Taking SAMe with this cough suppressant could increase the risk of serotonin syndrome.
  • Levodopa. SAMe might reduce the effectiveness of levodopa (Inbrija), a medication used to treat Parkinson’s disease.
  • Narcotics. Taking SAMe with meperidine (Demerol) or tramadol (Ultram, ConZip) could increase the risk of serotonin syndrome.
  • St. John’s wort. Be cautious when taking this supplement with SAMe. The combination could cause serotonin syndrome.

Nov. 18, 2020