Major Depression Serotonin Precursors: SAMe

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SAMe (pronounced "Sammy") stands for S-adenosyl-L-methionine. SAMe is a compound produced by the liver and used throughout the body in a chemical process called methylation. Methylation, essential to many chemical reactions in the body, is one of the last steps in the production of serotonin, dopamine and norepinephrine.

Because there are no foods that have high SAMe levels, our bodies must make this substance. Our liver usually creates SAMe from the amino acid (protein) methionine, which is found in many foods. Interestingly, supplementing with methionine does not work as well as supplementing with SAMe, because creating SAMe takes multiple steps and requires many co-factors (other nutrients, such as vitamin B12, folate and others) to ensure that the process is successful.


While the use of SAMe in your body is diverse (it participates in over 35 biochemical processes), the process of interest in depression is the creation of the neurotransmitters dopamine, serotonin and norepinephrine. SAMe affects these neurotransmitters in different ways. First, SAMe slows the breakdown of these brain chemicals, allowing them to work longer. In addition, SAMe speeds production of the receptors which receive these neurotransmitters. The presence of additional receptors allows the neurotransmitters that are present to work more effectively. Some research suggests that SAMe may also make the existing receptors more responsive (better able to receive messages from neurotransmitters). All of these functions combine to create increased levels of neurotransmitters, which decreases depressive symptoms. Research confirms that both depressed and non-depressed people who supplement with SAMe have higher overall levels of serotonin, dopamine, and norepinephrine. In research on treating depression, the positive effects of SAMe have been impressive. These studies, however, have been small, so it is difficult to determine which groups of people will benefit most from this supplement.

It appears that SAMe works well for people with mild depressive symptoms (who have no real risk for or indication of suicidal behavior), and not so well for people with more severe MDD. SAMe may also benefit people who cannot take standard antidepressant medications due to their side effects. SAMe could also be used in conjunction with other (standard) anti-depressants, but only as prescribed by a qualified practitioner. Scientists need additional research on SAMe to determine its effectiveness, interactions with other medications, and place within the family of depression therapies.

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Safety and Dosing

Dosing for SAMe is typically between 800mg/day and 1600mg/day. SAMe is very safe at recommended dosages. Because it is essentially a protein, it has no real side effects other than gastrointestinal upset and the possibility of triggering mania in people with bipolar disorder.

SAMe increases the risk of developing a rare condition called serotonin syndrome (or serotonin toxicity) that produces mental confusion, agitation, headache, shivering, sweating, hypertension, tachycardia (fast heart rate), and other symptoms. Check with your health care provider before incorporating SAMe into your therapy.

WARNING: SAMe has been suspected of causing manic episodes in people with Bipolar Disorder (manic depression). While the number of these cases is low, it is best to avoid SAMe if you suffer from Bipolar Disorder, or if you aren't sure if you have Bipolar Disorder vs. Major Depression. If you use SAMe, begin treatment only with the support of a licensed health care professional.

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