Does Kratom Interact With Tianeptine?
Kratom has a high chance of interacting negatively with tianeptine.
Kratom’s alkaloids and tianeptine stimulate opioid receptors [1, 2]. Taking both compounds simultaneously could cause strong sedation, increasing the risk of severe side effects and overdose.
Tianeptine and kratom are also metabolic competitors —meaning they require the same enzymes in the liver for their proper breakdown. When taken together, the metabolism rate of both substances could be slowed down.
Tianeptine is metabolized by CYP3A4, as well as other enzymes such as CYP2C19 and CYP3A5 [3]. Several kratom alkaloids also require CYP3A4 [4], so there’s a good chance these substances will compete to bind with such enzymes.
If the metabolism rate slows down, both substances will remain in the body longer. For kratom, this means longer-lasting effects, but for tianeptine, this implies the risk of toxicity and serious side effects.
The dosing schedule for tianeptine is strict. This medication needs to be titrated effectively — which means the amount of the drug being metabolized matches the amount of the drug that’s consumed.
Pushing tianeptine’s titration out of balance by taking kratom could lead to a gradual increase in serum levels of the drug — eventually leading to toxicity.
Toxicity from tianeptine can be severe — leading to seizures, nausea, fever, and more.
Always consult your doctor before taking any medications and combining them with other substances, including kratom.
Kratom & Tricyclic Antidepressant Interactions
Tianeptine is classified as a tricyclic antidepressant. Mixing kratom and tricyclic antidepressants can lead to a long list of side effects and should be avoided.
Although tianeptine fits into this drug class, it has different pharmacological properties than other class members.
Other related tricyclic antidepressants kratom may interact with include:
- Amitriptyline
- Amoxapine
- Desipramine (Norpramin)
- Doxepin
- Imipramine (Tofranil)
- Nortriptyline (Pamelor)
- Protriptyline
- Trimipramine
Is It Safe to Take Kratom With Tianeptine?
It’s not safe to mix tianeptine with kratom.
While not everyone will experience side effects from this combination, the severity of these effects is reason enough to avoid this combination for any reason.
If you’re dead set on taking kratom with your tianeptine, speak to your doctor first — they may advise you to reduce your dose of the medication or separate the dose of kratom and tianeptine by at least 2 hours to minimize risk.
What is Tianeptine?
Tianeptine is an atypical antidepressant sold under the brand names Stablon and Coaxil. It was first discovered in France during the 1960s [5].
Tianeptine has been used to treat Major Depressive Disorder (MDD) in 66 countries, but the FDA has not approved its use in the U.S.
This medication is technically considered a tricyclic antidepressant, which makes it similar to medications such as amitriptyline, desipramine, nortriptyline, and others — but it works through mechanisms not shared by other members of this class, which is why it’s considered an “atypical” antidepressant.
Tianeptine Specs
| Name | Tianeptine |
| Trade Name | Stablon, Coaxial |
| Classification | Tricyclic antidepressants |
| CYP Metabolism | None. Tianeptine is metabolized by β-Oxidation. |
| Interaction with Kratom | Agonistic interaction |
| Risk of Interaction | Moderate to high |
What is Tianeptine Used For?
Tianeptine is prescribed in 66 countries for major depressive disorder. It has also been used to treat various conditions, including irritable bowel syndrome, asthma, and anxiety.
When used for recreational purposes, it can be very dangerous.
People have reported 50-60 mg causing sedation and an impaired ability to drive. Those who take tianeptine at 85 mg or more have experienced nodding off and vivid dreams.
What Are the Side Effects of Tianeptine?
Tianeptine produces fewer cardiovascular side effects than most tricyclic antidepressants. However, it can still cause severe side effects.
Common side effects of tianeptine may include:
- Abdominal pain
- Agitation
- Anxiety
- Constipation
- Dizziness
- Drowsiness
- Dry mouth
- Headache
- Insomnia
- Irritability
- Nausea
- Nightmares
- Weight gain
Serious side effects of tianeptine may include:
- Bitter taste
- Blurred vision
- ECG changes
- Euphoria
- Fatigue
- Flatulence
- Gastralgia
- Hepatitis
- Hot flushes
- Hypomania
- Micturition disturbances
- Orthostatic hypotension
- Palpitations
- Premature ventricular contractions
- Protracted muscle aches
- Pruritis
- Tremor
What is Kratom?
Kratom (Mitragyna speciosa) is a species of tree from Southeast Asia. It’s a member of the coffee family and is found in Papua New Guinea, Myanmar, Malaysia, Indonesia, and Thailand.
The leaves of the kratom tree contain about a dozen alkaloids — each with unique pharmacological effects. Some of these alkaloids act like opiates, blocking the transmission of pain and activating the reward pathway in the brain — others regulate immune function or muscle contraction [6].
What’s Kratom Used For?
Kratom is used for many medicinal and recreational purposes. It isn’t prescribed in most areas, but evidence suggests it may be helpful for several different issues.
Some of the most common and modern uses of kratom include:
- ADHD (Attention Deficit & Hyperactivity Disorder)
- Anxiety
- Arthritis pain
- Benzodiazepine withdrawal syndrome
- Chemotherapy-related pain
- Chronic back pain
- Depression
- Energy & focus
- Fibromyalgia
- Insomnia
- Migraines
- Mood
- Opiate withdrawal symptoms
- Nerve pain
- Pain
- Psoriatic arthritis
- Weight loss
What’s The Dose of Kratom?
If you’re new to kratom, starting with a very low dose of kratom first (2 grams or less) is a wise idea. A low dose of kratom will give you energy, whereas a higher dose (6-12 grams) tends to be sedating.
General dosage guidelines for kratom include the following:
- Low-Dose (2–6 grams of dried powder)
- High-Dose (6–12 grams of dried powder)
The more you take, the more likely you can experience side effects. Therefore, don’t take more than 12 grams.
Suggested: Can You Overdose on Kratom?
What Are the Side Effects of Kratom?
Kratom is generally well-tolerated. It doesn’t tend to cause a lot of side effects. However, you have a heightened risk when taking more than the suggested dose.
Common side effects of kratom include:
- Addiction & dependence
- Anxiety or restlessness
- Constipation
- Diarrhea
- Dizziness
- Depression
- Frequent urination
- Headaches
- Heart palpitations
- High blood pressure
- Liver damage (with long-term use)
- Low libido
- Nausea and vomiting
- Numbness
- Sedation and prolonged sleepiness
- Withdrawal symptoms
Related: What Are the Kratom Wobbles?
What are the Different Types of Kratom?
Kratom comes in many different strains, separated into four main classes — white, red, green, and yellow.
There are dozens of individual strains within each class. Each has its own set of effects, benefits, and side effects.
Here’s a quick run-down of the different kratom strain classes:
- White Vein Kratom — Best for energy, focus, and concentration. The effects are euphoric and energizing.
- Red Vein Kratom — Best for sleep and pain, powerful and fast-acting. The effects are numbing and relaxing.
- Green Vein Kratom — Balanced between white and red (sedating and stimulating).
- Yellow Vein Kratom — Made from a combination of white kratom and other strains. Effects cover all ranges of the spectrum (sedating or stimulating).
Key Takeaways: Is it Safe to Mix Kratom & Tianeptine
Tianeptine and kratom should never be used together. This combination has a high chance of side effects — many of which are severe and potentially life-threatening.
If you’re taking tianeptine and want to try kratom, speak with your doctor first.
Some users take kratom to deal with withdrawal symptoms from tianeptine. Doing this may help reduce or eliminate withdrawal symptoms, but you should still speak with your doctor before trying this method.
References
- Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., & Watanabe, K. (2004). Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life sciences, 74(17), 2143-2155.
- Gassaway, M. M., Rives, M. L., Kruegel, A. C., Javitch, J. A., & Sames, D. (2014). The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist. Translational psychiatry, 4(7), e411-e411.
- Kirchheiner, J., Nickchen, K., Bauer, M., Wong, M. L., Licinio, J., Roots, I., & Brockmöller, J. (2004). Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Molecular psychiatry, 9(5), 442-473.
- Kamble, S. H., Sharma, A., King, T. I., León, F., McCurdy, C. R., & Avery, B. A. (2019). Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom). Xenobiotica, 49(11), 1279-1288.
- Alamo, C., Garcia-Garcia, P., Lopez-Munoz, F., & Zaragozá, C. (2019). Tianeptine, an atypical pharmacological approach to depression. Revista de Psiquiatría y Salud Mental (English Edition), 12(3), 170-186.
- Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., & Watanabe, K. (2004). Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life sciences, 74(17), 2143-2155.
