Drug Interactions

Kratom & Trazodone: Are They Safe to Use Together?

Trazodone is an antidepressant drug belonging to a class of drugs known as serotonin antagonists and reuptake inhibitors (SARI). It is used for the treatment of depression, anxiety, and insomnia. This drug works by maintaining a healthy level of serotonin, which regulates mood, appetite, and sleep.

 When trazodone and kratom are consumed together, an agonistic reaction can occur. Trazodone exerts a sedative effect, and kratom in high doses also causes sedation. Combining both drugs can result in severe drowsiness and respiratory depression. Both drugs also affect serotonin receptors in the body, which can cause a severe reaction known as serotonin syndrome.

Last updated 3 months ago by Dr. Devin Carlson

Kratom & Trazodone: Are They Safe to Use Together?

Does Kratom Interact With Trazodone?

Trazodone can interact with kratom agonistically and metabolically. This can cause an increased risk of side effects, including sedation, headaches, nausea, and serotonin syndrome. The interaction is considered moderate to high.

It’s always best to talk to your doctor before combining kratom and trazodone.

1. Increased Effect (Agonistic Interaction)

There is an agonistic interaction between kratom and trazodone.

Agonistic interaction occurs when two substances having the same effect are used together. These substances produce a similar effect by acting on the same receptors or acting on different receptors that cause similar responses.

Kratom acts as a stimulant in lower doses, but it can cause sedation in higher doses. It primarily works on mu-opioid receptors, resulting in pain relief [1]. Kratom also affects D2 dopamine and serotonin (5-HT2c and 5-HT7) receptors, with potential antipsychotic and antidepressant effects [2].

Trazodone acts via antagonism of serotonin receptors and inhibition of serotonin transporters. The drug has an antidepressant effect and sleep-inducing properties [3].

Due to their similar effects, kratom and trazodone can cause marked sedation and even respiratory depression. As both drugs affect serotonin, using them together can lead to a severe side effect known as serotonin syndrome [4]. Serotonin syndrome is characterized by restlessness, confusion, and loss of muscle coordination.

2. Slowed Elimination (Metabolic Competition)

All oral drugs need to be metabolized once consumed. The liver produces enzymes that mediate drug metabolism. Using two drugs metabolized by common enzymes results in a slower breakdown of both drugs.

Trazodone is mainly metabolized by the liver enzyme CYP3A4 [5]. Kratom is also metabolized by CYP3A4. The two drugs may compete for metabolism, resulting in an increased duration of effect of both substances.

Trazodone is an antidepressant and, when consumed daily, can accumulate in the blood up to toxic levels, mainly when used with kratom.

Kratom & SARI Interactions

Trazodone is a serotonin receptor and reuptake inhibitor. This class of drugs treats major depressive disorders. In addition, these drugs are used in post-traumatic stress disorder and sleep disorders.

Other SARIs and kratom have a similar level of risk.

Other serotonin receptor agonists and reuptake inhibitors that kratom will interact with include:

  • Etoperidone (Axiomin, Etonin)
  • Lorpiparazole (Normarex)
  • Mepiprzole (Psigodal)
  • Nefazodone (Serzone, Nefadar)

Is it Safe to Take Kratom With Trazodone?

No. It is not safe to take kratom with trazodone.

Kratom and trazodone’s interaction is considered moderate to severe.

Kratom in high dosage can increase the sleep-inducing effect of trazodone. This can lead to severe drowsiness even after the intended duration of action of the drugs. In addition, serotonin syndrome is a dangerous side effect of both drugs.

Consult your prescribing physician before the use of these drugs. If you notice any side effects, seek help from a medical professional.

What is Trazodone?

Trazodone is a serotonin receptor antagonist and reuptake inhibitor. It is a triazolopyridine derivative.

Trazodone inhibits serotonin transporter and blocks the reuptake of serotonin, which results in improved mood. The drug also shows antagonism in 5-HT2A and 5-HT2c serotonin receptors. The drug also blocks histamine and alpha-1-adrenergic receptors.

The drug helps manage major depressive disorder. It is also valuable for generalized anxiety disorder, post-traumatic stress disorder, and insomnia.

Trazodone Details & Specifications:

Drug NameTrazodone
Trade nameAzona, Cirzodone, Codipzona, Deprax, Depryl, Desyrel, Diapresan, Donaren, Mesyrel, Molipaxin, Nestrolan, Reslin, Sideril, Tazodac, Torlex, Trarett, Trazalon, Trazo, Trazodona, Trazolan, Trazone, Trazonil, Triticum, Tronsalan
ClassificationSerotonin antagonists and reuptake inhibitors, Antidepressant 
CYP MetabolismCYP3A4
Interaction With KratomAgonistic
Risk of InteractionModerate to high

What Is Trazodone Used For?

Trazodone is primarily used for the treatment of depression. The uses of trazodone are:

For the Treatment of Major Depressive Disorders

Trazodone is used for the treatment of depression with or without anxiety. It is used due to its minimal anticholinergic activity but can also augment the antidepressant effect of other antidepressants. Due to its sedative effect,  it is very effective in geriatric patients who have depression with insomnia.

For the Treatment of Anxiety Disorders

Trazodone helps with post-traumatic stress disorder, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder. The sleep-inducing property helps reduce sleep disturbances and nightmares in post-traumatic stress disorder.

For Use in Treatment of Insomnia

Treatment of insomnia is one of the off-label uses of trazodone. It is used in low doses as a sleeping aid.

What’s the Dose of Trazodone?

The recommended initial dose of trazodone is 75 to 150 mg orally per day. Doctors adjust the amount according to the needs of the patient. 

Generic & Brand Name Versions

  • Azona
  • Cirzodone
  • Codipzona
  • Deprax
  •  Depryl
  •  Desyrel
  •  Diapresan
  • Donaren
  •  Mesyrel
  •  Molipaxin
  •  Nestrolan
  •  Reslin
  •  Sideril
  • Tazodac
  • Torlex
  •  Trarett
  •  Trazalon
  •  Trazo
  •  Trazodona
  •  Trazolan
  •  Trazone
  •  Trazonil
  •  Triticum
  • Tronsalan

What Are the Side Effects of Trazodone

  • Agitation
  • Blurred vision
  • Confusion
  • Dizziness
  • Dry mouth
  • Edema
  • Fatigue
  • Headache
  • In coordination
  • Nausea
  • Tremor
  • Vomiting

What is Kratom?

Kratom comes from Mitragyna speciosa, a tree of the coffee family found in Southeast Asia. The plant exhibits properties similar to opioids, though it interacts with other systems.

Because of its wide array of effects, some governments have banned it. However, the World Health Organization studied kratom and determined it is safe. This backs up hundreds of years of use and anecdotal reports — as does the available research.

What’s Kratom Used For?

Those native to Southeast Asia, where kratom grows plentifully, have used this plant as traditional medicine for a long time. The rest of the world is now catching on to its vast uses. Here are the top reasons people use kratom — sometimes even replacing their prescriptions.

What is the Dose of Kratom?

The dose depends on the effects you’re looking for. Start with a low amount to see how it affects you.

  • Pain, anxiety, and sleep: Larger doses, usually 6-12 g
  • Energy, focus, and mood: Smaller doses, usually 2-5 g

Kratom doesn’t affect everyone the same way, and many factors come into play. The kratom dosage guide can help narrow down the right dose for the job.

What Are the Side Effects of Kratom?

Kratom gets its fair share of negative press, but that’s about all it amounts to. The reality is there’s little risk to using kratom as long as it’s used responsibly. That means not combining it with other substances, using it only when necessary, and taking breaks from it.

There are some side effects to be aware of — including addiction — though they tend to be mild and short-lived.

What Are the Different Types of Kratom?

Kratom’s effects also depend on the strain. When buying kratom, pay attention to the strain so you aren’t surprised. Here’s a look at each strain color and their common effects.

White Vein Kratom

This form of kratom comes from immature, white-veined leaves. It provides euphoria and a sense of well-being, boosts energy, and improves cognitive functioning.

Red Vein Kratom

The red vein kratom comes from mature leaves and is used often for pain management. It helps in relaxation, reduces anxiety, and provides sedation.

Green Vein Kratom

The green vein kratom falls in the middle of the red and white strains. These offer a pleasant balance; they’re neither too stimulating nor too relaxing — although the effects are prominent depending on the dose.

Yellow Vein Kratom

The yellow kratom strains are from fermented leaves and are similar to green strains, except they tend to last longer and have a pronounced relaxing property.

Key Takeaways: Is it Safe to Mix Kratom & Trazodone?

Kratom and trazodone can have a moderate to high level of interaction. Their interaction is agonistic, though they are also metabolic competitors. Both trazodone and high doses of kratom induce sleep, so taking them together can cause dangerous levels of sedation.

Furthermore, serotonin syndrome is another adverse effect of both drugs, leading to agitation, dilated pupils, loss of muscle coordination, rapid heart rate, and even death if left untreated.

Do not take these medications without consulting your doctor.


  1. Todd, D. A., Kellogg, J. J., Wallace, E. D., Khin, M., Flores-Bocanegra, L., Tanna, R. S., McIntosh, S., Raja, H. A., Graf, T. N., Hemby, S. E., Paine, M. F., Oberlies, N. H., & Cech, N. B. (2020). Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions. Scientific reports, 10(1), 19158.
  2. Johnson, L. E., Balyan, L., Magdalany, A., Saeed, F., Salinas, R., Wallace, S., Veltri, C. A., Swogger, M. T., Walsh, Z., & Grundmann, O. (2020). The Potential for Kratom as an Antidepressant and Antipsychotic. The Yale journal of biology and medicine, 93(2), 283–289.
  3. Fagiolini, A., Comandini, A., Catena Dell’Osso, M., & Kasper, S. (2012). Rediscovering trazodone for the treatment of major depressive disorder. CNS drugs, 26(12), 1033–1049.
  4. Brogdon, H. D., McPhee, M. M., Paine, M. F., Cox, E. J., & Burns, A. G. (2022). A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and Subsequent Treatment of Kratom Use Disorder With Buprenorphine/Naloxone. Journal of addiction medicine, 10.1097/ADM.0000000000000968. Advance online publication.
  5. Rotzinger, S., Fang, J., & Baker, G. B. (1998). Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug metabolism and disposition: the biological fate of chemicals, 26(6), 572–575.

Learn More About Kratom-Drug Interactions