SAMe and St. John's Wort: Can You Take Them Together?

Use caution — significant interaction

SAMe and St. John's Wort can interact. Additive serotonergic load, and with it a risk of serotonin syndrome. This specific pair has not been studied; St John's wort is a named precipitant of serotonin syndrome in the clinical literature and the same table already grades it critical against every SSRI, SNRI and MAOI. Do not stack them. Two herbal or nutraceutical antidepressants together is not a stronger treatment, it is an untested one — pick one and give it a fair trial. Seek urgent medical help for agitation, shivering, twitching, a racing heart, sweating or fever.

What the evidence says

majorconflict· limited evidence

Both are taken AS antidepressants and both act on monoamine signalling — St John's wort through reuptake inhibition across serotonin, noradrenaline and dopamine, SAMe through methylation-dependent monoamine turnover and 5-HT1A activation.

What to do: Do not stack them. Two herbal or nutraceutical antidepressants together is not a stronger treatment, it is an untested one — pick one and give it a fair trial. Seek urgent medical help for agitation, shivering, twitching, a racing heart, sweating or fever.

SAMe

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St. John's Wort

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Related interactions

SAMe & Trazodone 5-HTP & SAMe St. John's Wort & Trazodone St. John's Wort & Tryptophan 5-HTP & St. John's Wort St. John's Wort & Vitamin D3

Frequently asked questions

Can you take SAMe and St. John's Wort together?: SAMe and St. John's Wort can interact. Additive serotonergic load, and with it a risk of serotonin syndrome. This specific pair has not been studied; St John's wort is a named precipitant of serotonin syndrome in the clinical literature and the same table already grades it critical against every SSRI, SNRI and MAOI. Do not stack them. Two herbal or nutraceutical antidepressants together is not a stronger treatment, it is an untested one — pick one and give it a fair trial. Seek urgent medical help for agitation, shivering, twitching, a racing heart, sweating or fever.
Do SAMe and St. John's Wort interact?: Additive serotonergic load, and with it a risk of serotonin syndrome. This specific pair has not been studied; St John's wort is a named precipitant of serotonin syndrome in the clinical literature and the same table already grades it critical against every SSRI, SNRI and MAOI. Both are taken AS antidepressants and both act on monoamine signalling — St John's wort through reuptake inhibition across serotonin, noradrenaline and dopamine, SAMe through methylation-dependent monoamine turnover and 5-HT1A activation.
Should you separate SAMe and St. John's Wort?: Do not stack them. Two herbal or nutraceutical antidepressants together is not a stronger treatment, it is an untested one — pick one and give it a fair trial. Seek urgent medical help for agitation, shivering, twitching, a racing heart, sweating or fever.

This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.

What the evidence says

majorconflict· limited evidence

Frequently asked questions

Can you take SAMe and St. John's Wort together?

Do SAMe and St. John's Wort interact?

Additive serotonergic load, and with it a risk of serotonin syndrome. This specific pair has not been studied; St John's wort is a named precipitant of serotonin syndrome in the clinical literature and the same table already grades it critical against every SSRI, SNRI and MAOI. Both are taken AS antidepressants and both act on monoamine signalling — St John's wort through reuptake inhibition across serotonin, noradrenaline and dopamine, SAMe through methylation-dependent monoamine turnover and 5-HT1A activation.

Should you separate SAMe and St. John's Wort?

Do not stack them. Two herbal or nutraceutical antidepressants together is not a stronger treatment, it is an untested one — pick one and give it a fair trial. Seek urgent medical help for agitation, shivering, twitching, a racing heart, sweating or fever.