Known interactions

Adapin, Amber Touch-and-Heal, Amitriptyline, Amitriptyline Injection, Amoxapine, Anafranil, Aquatab C Tablets, Aquatab DM, Asendin, Aventyl, Aventyl Oral Solution, Benylin, Benylin Expectorant Liquid, Budeprion SR, Buproban, Bupropion, Bupropion Extended-Release, Bupropion SR, Bupropion Sustained-Release (Zyban), Carbex, Celexa, Celexa Solution, Cheracol D Cough Liquid, Children's Formula Cough Syrup, Citalopram, Citalopram Oral Solution, Citalopram orally-disintegrating tablets, Clear Tussin 30 Liquid, Clomipramine, Cold & Cough Tussin Softgels, citalopram orally-disintegrating tablets, Delsym, Demerol Injection, Demerol Oral, Demerol Syrup, Desipramine, Desyrel, Dextromethorphan, Dextromethorphan, Guaifenesin, and Potassium Guaiacolsulfonate, Diabetic Tussin DM Liquid, Doxepin, Doxepin Oral Solution, Doxepin Topical, Effexor, Elavil, Elavil Injection, Eldepryl, Endep, Etrafon, Extra Action Cough Syrup, Fenesin DM Tablets, Fluoxetine and Olanzapine, Fluoxetine capsules (Sarafem), Fluoxetine Oral Solution, Fluoxetine tablets or capsules, Fluvoxamine, fluoxetine delayed-release capsules, Genatuss DM Syrup, Guaifenesin and Dextromethorphan, Guaifenesin and Dextromethorphan Oral Solution, Guaifenex DM Tablets, Guiatuss CF Syrup, Guiatuss DM Syrup, Guiatussin with Dextromethorphan Liquid, Halotussin DM Sugar Free Syrup, Halotussin DM Syrup, Hardhay, Humibid DM, Humibid DM Sprinkle Capsules, Humibid DM Tablets, Hypericum, Hypericum perforatum, Imipramine, Imipramine HCl, Imipramine Pamoate, Iobid DM Tablets, Isocarboxazid, Klamath Weed, Kolephrin GG/DM Liquid, L-tryptophan, Ludiomil, Luvox, Maprotiline, Marplan, Maxifed DM Tablets, Medent-DM Tablets, Meperidine and Promethazine Oral, Meperidine Hydrochloride Injection, Meperidine Oral, Meperidine Syrup, Meprozine, Millepertuis, Muco-Fen-DMT Tablets, Mytussin DM Liquid, Naldecon Senior DX Liquid, Nardil, Nefazodone, Norpramin, Nortriptyline, Nortriptyline Oral Solution, Pamelor, PanMist-DM Tablets, Panmist-DM Syrup, Parnate, Paroxetine, Paroxetine Oral Suspension, Paxil, Paxil CR, Paxil Suspension, Perphenazine and Amitriptyline, Pertussin, Phanatuss DM Syrup, Phenadex Senior Liquid, Phenelzine, Phenergan DM, Profen Forte DM Tablets, Profen II DM Liquid, Profen II DM Tablets, Prometh with Dextromethorphan, Promethazine and Dextromethorphan, Promethazine DM, Protriptyline, Protuss DM Tablets, Prozac, Prozac Oral Solution, Prozac Weekly, Pseudoephedrine, Guaifenesin and Dextromethorphan, Pseudoephedrine, Guaifenesin, Dextromethhorphan Liquid, Pseudovent DM, Respa-DM Tablets, Rhinosyn-DMX Syrup, Robafen CF Syrup, Robafen DM Syrup, Robitussin CF Syrup, Robitussin Cough, Robitussin DM Syrup, Rosin Rose, Safe Tussin 30 Liquid, Sarafem, Scot-Tussin Senior Clear Liquid, Selegiline, Sertraline, Sertraline Oral Solution, Serzone, Silexin, Siltussin DM Syrup, Sinequan, Sinequan Oral Solution, SJW, St. John's Wort, Sudal-DM, Surmontil, Symbyax, Tipton Weed, Tofranil, Tofranil PM, Tolu-Sed DM Syrup, Touro CC Tablets, Touro DM, Tramadol, Tramadol and Acetaminophen, Tranylcypromine, Trazodone, Triavil, Trimipramine, Tryptophan, Tuss-DM, Ultracet, Ultram, Vanatrip, Vanatrip Injection, Venlafaxine, Vicks 44E Liquid, Vicks Pediatric Forumula 44E Liquid, Vivactil, Wellbutrin, Wellbutrin SR, Wellbutrin XL, Z-Cof DM Syrup, Zoloft, Zoloft Oral Solution, Zonalon Cream, Zyban.

Quick guide to SAM

Scientific Name: S-adenosyl methionine (SAM-e)

Other Names: Ademetionine, AldoMet, S-adenosyl-L-methionine, SAM, Sammy

Who is this for?

Neurotransmitters are chemicals that carry messages from nerve cells to other cells. Low levels of the neurotransmitters, dopamine, norepinephrine, and serotonin are associated with depression. SAM-e is known to raise levels of dopamine and norepinephrine in the brain, and it may also accelerate the production, uptake, and re-release of serotonin. Although possible additional antidepressant actions of SAM-e have not been confirmed, results of some studies suggest that SAM-e may increase the sensitivity of receptors that react to these neurotransmitters or improve the ability of neurotransmitters to attach to active receptors. All of these effects are thought to help relieve depression.

SAM-e may also be useful in treating other conditions of the central nervous system. It has been studied for treating dementia, which is a progressive failure in thought processes caused by brain damage or disease. Alzheimer's disease is a leading cause of dementia. Frequently, dementia is associated with low levels of SAM-e in the brain and spinal cord and the fluid surrounding them. SAM-e deficiencies have also been identified in individuals who have nerve damage from HIV/AIDS, multiple sclerosis, or spinal cord degeneration. Recent study results show that SAM-e may help to relieve the symptoms of adult attention deficit hyperactivity disorder (ADHD). Additionally, it may relieve symptoms of fibromyalgia, a condition that causes generalized pain in the muscles and joints. SAM-e is being studied for treating all these conditions, but more research is needed to verify its effectiveness for them.

SAM-e is also used widely to treat arthritis. It accumulates in synovial fluid, the thick gel that lubricates and cushions the joints. Chemicals resulting from the body's breakdown of SAM-e are known to relieve pain and fight inflammation, which is one of the body's reactions to irritation, injury, or infection. Inflammation involves pain, redness, and swelling in the area of the damage and it can occur within body structures, such as joints, as well as on the surface of the skin. Additionally, SAM-e may not only prevent the erosion of cartilage by blocking destructive enzymes, it may even stimulate new cartilage to grow.

Individuals with liver conditions — including cirrhosis — often have low levels of methionine in their blood. Furthermore, the ability to convert methionine into SAM-e declines in individuals with liver diseases because the damaged liver cannot produce adequate amounts of the enzymes needed to break down methionine. As a result, the levels of antioxidants that also depend on SAM-e to be produced, decrease. Antioxidants are thought to protect body cells from damage caused by a chemical process called oxidation. Oxidation produces oxygen free radicals, natural chemicals that may suppress immune function and cause tissue damage.Glutathione, one of the antioxidants derived from SAM-e, inactivates potentially toxic chemicals such as alcohol, thereby protecting the liver from injury. In animal studies, the lack of SAM-e hampered liver cell growth and repair. SAM-e may also help to relieve a condition known as intrahepatic cholestasis, which may be associated with pregnancy, some forms of hepatitis, and other short-or long-term liver diseases. Intrahepatic cholestasis involves the inability to release bile normally from the liver. Bile builds up and results in symptoms such as intense itching and a yellow-colored skin. In at least two small studies, women who were given SAM-e to control intrahepatic cholestasis in the last third of their pregnancies achieved relief from symptoms while showing no apparent side effects.

SAM-e has been studied for use in a number of other conditions that may be related to methionine or SAM-e deficiencies. For example, many people living with AIDS have low levels of both methionine and SAM-e. It is believed that supplemental SAM-e may delay or prevent the spinal cord deterioration (myelopathy) that often accompanies infection with HIV as well as helping to relieve the depression often associated with the condition. Other studies have found that methionine/SAM-e deficiency during pregnancy may be a factor in abnormal formation of the central nervous system in developing infants. The resulting “neural tube defects” may lead to extremely serious birth defects such as spina bifida (incomplete closure of the spinal column) or anencephaly (the absence of brain parts). Separate studies in animals show that SAM-e may be an antidote for lead poisoning and for the potentially fatal liver damage that may follow overdoses of acetaminophen. All these possible uses of SAM-e appear promising, but they need further study before SAM-e can be recommended for any of them.

When should I be careful taking it?

Because some study evidence suggests that SAM-e may worsen the symptoms of Parkinson's disease, individuals who have Parkinson's disease should not take SAM-e.

Cases of mania (extreme euphoria, excitability, and hyperactivity) have been attributed to the use of SAM-e by individuals who have bipolar disorder or major depression. Therefore, individuals who have these conditions are advised to take SAM-e only when its use is supervised by a healthcare professional.


Although SAM-e has been studied in pregnant women, its routine use is not recommended during pregnancy.

Not enough is known about how SAM-e might affect an infant to recommend its use while breast-feeding. Small children should also avoid taking SAM-e because its possible long-term effects on growth are not known.

What side effects should I watch for?

Serotonin syndrome, a rare but potentially dangerous oversupply of serotonin in the body, may be caused by SAM-e. Uncontrolled serotonin syndrome may result in coma, seizures, and death. Symptoms of serotonin syndrome include:

  • Confusion
  • Excitement
  • Fever
  • Hallucinations
  • Inability to coordinate muscles
  • Restlessness
  • Shakiness
  • Vomiting

Less Severe Side Effects

Generally, most side effects associated with taking or injecting SAM-e have been mild and temporary. They include:

  • Anxiety
  • Constipation or diarrhea
  • Dizziness
  • Dry mouth
  • Frequent urination
  • Headache
  • Insomnia
  • Nausea
  • Sweating
  • Thirst

What interactions should I watch for?

Prescription Drugs

If SAM-e is taken with prescription antidepressants that belong to the classes known as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs), serotonin levels may become excessive. Serotonin syndrome is possible.

  • SSRIs include fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
  • TCAs include amitriptyline, amoxapine, doxepin and nortriptyline

The risk of side effects from a third type of prescription antidepressants known as monoamine oxidase inhibitors (MAOIs) may be increased if SAM-e is taken at the same time. MAOI therapy should be stopped a minimum of 2 weeks before SAM-e starts. MAOIs include Marplan, Nardil, and Parnate. Potential side effects may be:

  • Aggressive behavior
  • Coma
  • Confusion
  • High blood pressure
  • High body temperature

Certain drugs, such as meperidine and tramadol (Ultram) that are usually given to reduce pain may also raise serotonin levels in the body. If one of these pain-fighting drugs is used at the same time as SAM-e, the risk of serotonin syndrome may increase.

Non-prescription Drugs

Dextromethorphan (DM) is an anti-coughing ingredient in many non-prescription cough and cold products such as Nyquil and Robitussin DM. Because it may have an increasing effect on serotonin levels, taking dextromethorphan with SAM-e may result in a higher risk of side effects.

Herbal Products

Potentially, if SAM-e is taken with St John's wort, which also may increase serotonin levels, the risk of serotonin syndrome may also increase.

Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals.

Should I take it?

SAM-e is a chemical that is produced in the body from the metabolism of methionine, one of the essential amino acids. Amino acids are used by the body primarily to make proteins. Essential amino acids are necessary for body functions, but the body cannot make them — they must be obtained from the diet in foods such as dairy products, fish, meat, and whole grains. Once methionine has been absorbed, enzymes change it into SAM-e, which is found in all cells of the body. In turn, SAM-e breaks down into several chemicals that are involved in a number of basic processes. Some of them maintain the stability and flexibility of cell walls. Others are necessary for the production of essential body components such as hormones and neurotransmitters. Chemicals from SAM-e assist with the processing of dietary fats in the liver and they also act as anti-inflammatory, antioxidant, and pain-controlling agents.

Much of the research on SAM-e has been done in Europe, particularly in Italy, where SAM-e was discovered in the 1950s. Approved as a prescription drug in Italy since 1976 and subsequently in other European countries, SAM-e was not introduced in the United States until the late 1990s. It is a non-prescription dietary supplement in this country. Although an ordinary diet usually supplies more than enough methionine to produce adequate amounts of SAM-e, certain groups of individuals, including strict vegetarians and individuals whose immune function has been weakened by chemotherapy or disease, may not produce sufficient amounts. Natural production of SAM-e decreases as individuals age, as well. Commercially available supplemental SAM-e is manufactured from fermented yeasts.

Dosage and Administration

The body's use of SAM-e depends on the availability of other dietary supplements including folic acid, vitamin B6, and vitamin B12. These three ingredients are often included into a single tablet with SAM-e to make dosing easier and to assure adequate supplies of all four components. Most of the SAM-e available in the United States comes in enteric-coated tablets because SAM-e is not well absorbed when taken orally. Enteric-coated tablets are designed to resist stomach acid and dissolve in the small intestines, where more of the SAM-e may be absorbed. For the same reason, SAM-e is best taken on an empty stomach, at least one hour before a meal.

Although higher doses have been used in studies, the maximum daily dose of SAM-e is generally considered to be 1,600 mg (1.6 grams). Different doses of SAM-e have been used to treat different conditions. Some common recommendations are:

ConditionOral Dose Range (Daily)Injected Dose Range (Daily)
AIDS myelopathyNo recommendation800 mg
Cirrhosis1200 mg to 1600 mgNo recommendation
Depression400 mg to 1,600 mg200 mg to 400 mg
Fibromyalgia 800 mgNo recommendation
Intrahepatic Cholestasis1600 mg800 mg
Osteoarthritis600 mg400 mg

Note: While some individuals have experienced a lessening of depression as soon as 3 days after beginning to take SAM-e, its full effects may take several weeks to develop.


A substance that results from the breakdown of the dietary amino acid, methionine by the body, SAM-e has shown effectiveness for relieving depression, treating arthritis, and preventing liver damage. It may also be useful in delaying or preventing the deterioration of mental functioning caused by dementia.


Individuals with Parkinson's disease should avoid using SAM-e because it may worsen symptoms. Small children and women who are pregnant or breast-feeding are advised not to take supplemental SAM-e, and individuals with bipolar disorder or major depression should use SAM-e only with the advice and supervision of a healthcare professional.

Side Effects

A slightly increased risk of serotonin syndrome - a dangerously high level of serotonin in the blood - may be associated with using SAM-e. Its more common and less serious side effects may include:

  • Anxiety
  • Constipation or diarrhea
  • Dizziness
  • Headache
  • Insomnia
  • Nausea
  • Sweating


SAM-e may increase the chance of developing serotonin syndrome if it is taken with prescription drugs such as SSRI or TCA antidepressants or certain pain-relieving drugs, the non-prescription cough and cold product dextromethorphan, or St. John's wort. The risk of developing side effects including confusion and high blood pressure may be higher if SAM-e is taken within 2 weeks of antidepressants known as MAOIs.


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(Note: The above information is not intended to replace the advice of your physician, pharmacist, or other healthcare professional. It is not meant to indicate that the use of the product is safe, appropriate, or effective for you.)

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