S-adenosylmethionine (SAMe) is a naturally occurring compound involved in numerous biochemical processes in the body, including methylation and neurotransmitter synthesis. There is moderate scientific evidence supporting its use in modulating the dopamine system, primarily through its role as a methyl donor in the synthesis of neurotransmitters such as dopamine, serotonin, and norepinephrine. Several studies have demonstrated that SAMe supplementation can influence monoamine neurotransmitter levels in the brain, with some clinical trials indicating antidepressant effects comparable to prescription medications. These antidepressant effects are partly attributed to enhanced dopaminergic and serotonergic activity, suggesting that SAMe may support dopamine-related systems, particularly in mood disorders.

However, while preclinical and clinical studies suggest a mechanistic link between SAMe supplementation and dopamine synthesis, much of the human research focuses on mood and depressive symptoms rather than direct, isolated dopamine system outcomes such as motivation or motor control. The evidence base is moderate (hence a rating of 3), with further research needed to clarify the extent and specificity of SAMe's effects on the dopamine system. Overall, SAMe's use to support the dopamine system is supported by scientific rationale and some clinical evidence, though it is not as robust or direct as for some other agents targeting dopamine.