SAMe (S-Adenosyl-L-Methionine)
SAMe is a methyl donor involved in neurotransmitter synthesis, with strong evidence supporting its use for depression treatment, osteoarthritis pain relief, and liver health. It is often used as an adjunct to SSRIs.
Evidence last reviewed: 20 Apr 2026
The evidence for SAMe is strong for osteoarthritis pain relief and moderate for depression treatment. However, its effectiveness for other neuropsychiatric disorders is less established, indicating a need for further research.
Osteoarthritis pain reliefAdults with osteoarthritis · Systematic reviewHigh
SAMe is effective in reducing pain associated with osteoarthritis, comparable to non-steroidal anti-inflammatory drugs.
Neuropsychiatric disorder managementAdults with various neuropsychiatric disorders · Systematic reviewLow
SAMe holds promise for treating multiple neuropsychiatric conditions, though evidence is limited and further study is needed.
Depression treatmentAdults with major depressive disorder · Systematic reviewModerate
SAMe shows promising evidence for efficacy and safety in treating major depressive disorder, both as monotherapy and as an augmentation to other antidepressants.
Hormonal Balance and Mood Enhancement
Combining Pregnenolone with SAMe can support hormonal balance and enhance mood. Pregnenolone is a precursor to various hormones, supporting hormonal balance, while SAMe is known for its mood-enhancing and joint-supporting properties.
Forms & usage▾
Take 400–1600 mg daily, preferably on an empty stomach.