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SAM-E Effects on Anxiety

By Tracey Roizman, D.C. ; Updated August 14, 2017

SAMe is a biological compound manufactured from the amino acid methionine reacted with the energy-producing molecule ATP. SAMe has been used to treat a variety of conditions including depression, anxiety, fibromyalgia, arthritis and liver disease.


SAMe has been extensively tested and widely used in Europe since the 1970's. An Italian company has marketed it as a prescription drug and dozens of European studies of the effects of SAMe in humans have found it to be on a par with conventional drugs in the treatment of depression and anxiety, according to the website The U.S. Food and Drug Administration has not conducted sufficient tests on SAMe for drug approval, although it is readily available in the United States as a nutritional supplement.

How it Works

Though the human body produces SAMe, supplemental doses can be helpful at ensuring that the pathways utilizing SAMe for normalizing moods are well-stocked. SAMe is not a hormone or neurotransmitter, but rather is involved in a simple process—known as methylation—that occurs billions of time a day in all living things. Methylation is a chemical reaction whereby a small molecular moiety called a methyl group is swapped from one molecule to another, enabling the methyl-receiving molecule to participate in other reactions. In the case of anxiety, those have to do with balancing hormones and neurotransmitters involved in mood, such as serotonin, melatonin, dopamine and adrenalin.

Dosage and Formulation

For mood disorders the starting level of SAMe is around 400 mg, taken in divided doses. Effective levels vary from person to person and a qualified health practitioner should be consulted to determine the best level that does not cause unpleasant side effects or harm. A study published in the November 2004 issue of BioMed Central Psychiatry treated depression and anxiety in HIV/AIDS patients with dosages starting at 200 mg twice a day, increasing to as much as 1600 mg twice a day over the 8-week course of therapy. The study concluded that SAMe was safe and effective for people living with HIV/AIDS.


When an SAMe molecule donates its methyl group it breaks down into the molecule known as homocysteine, a dangerously toxic compound associated with increased cardiovascular disease, birth defects and depression, according to In order to prevent homocysteine from accumulating, sufficient levels of B vitamins must be present to convert homocysteine into the highly desirable and powerful antioxidant molecule glutathione. Therefore, when taking SAMe supplements, it is advisable to ensure sufficient levels of B vitamins through diet or supplementation.

Side Effects

Side effects are reportedly fewer than with selective serotonin reupake inhibitors and may include nausea, headache, dry mouth, and agitation, according to BMC Psychiatry. Mania has also been noted as an effect in some cases of bipolar disorder.

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