Drug Interactions, Kratom Guides

Is It Safe to Mix Kratom & Coffee (Caffeine)? What Are The Risks?

Mitragynine is the major alkaloid present in kratom. When used in lower doses, it acts as a partial agonist at μ-opioid receptors and exerts various clinical effects, including euphoria and anxiolysis. But, higher doses of kratom may lead to excessive sedation.

On the other hand, coffee has caffeine as its main active ingredient and is a stimulant. But, when taken improperly, headache, nausea, anxiety, racing heart, and, eventually, tiredness may ensue.

The final effect may be agonistic or antagonistic depending on the kratom taken. Therefore, it is best to have a strategy for taking these drugs together.

Medically reviewed by Dr. Devin Carlson

Last updated 1 month ago by Wade Paul

Is It Safe to Mix Kratom & Coffee (Caffeine)? What Are The Risks?

Does Kratom Interact With Coffee?

As mentioned in the previous paragraphs, kratom and coffee may have similar or opposite effects. Thus, the combination may be additive or subtractive, which depends on a number of factors like dose, strain, and method of intake of these drugs. These drugs interact with each other in the following manner.

A. Coffee Enhances the Effects of Kratom (Agonistic Interaction)

When two drugs acting on the same or different receptors produce similar effects, pharmacologic agonism occurs.

Coffee blocks adenosine receptors in the central nervous system [3], promoting alertness and wakefulness. Kratom acts on the noradrenaline system (fight or flight), causing increased concentration and energy when taken in lower doses. Thus, the effect of kratom and coffee may overlap, leading to an agonistic interaction and an increased risk of side effects.

Coffee blocks adenosine receptors in the part of the brain preparing for sleep, but it does not decrease the production of adenosine itself. The body makes more since the current amount isn’t working.

Once the effect of coffee wears off, an increased amount of adenosine will bind to the adenosine receptors, which may induce tiredness. In this way, an unusually high dose of coffee may cause sedation as the caffeine fades.

Thus combining low doses of the two drugs can have an overall stimulatory effect that may not be optimal and can cause agitation, heart palpitations, and distractibility. Combining high amounts of these drugs will have severe sedative effects.

B. Coffee Diminishes the Effects of Kratom (Antagonistic Interaction).

When two drugs acting on the same or different receptors produce opposite effects, pharmacologic antagonism occurs.

Let us take an example of the combination of high-dose kratom (more than 8 grams) and coffee. In this situation, the high dose of kratom behaves as a sedative, and the coffee is a stimulant. This will cancel out or greatly diminish the effects of one of them, called an antagonistic interaction. Antagonism holds even if a low dose kratom (less than 5 grams) and a high dose of coffee (more than 400 mg) are combined, though not until the caffeine wears off. For a while, this would still be an antagonistic interaction.

The metabolism pathways of these drugs are different. Kratom is mainly metabolized by CYP3A4, CYP3A5, and CYP2D6 [1]. Coffee is metabolized by CYP1A2 [2]. So, there is no metabolic competition.

Kratom & Coffee Interactions

Caffeine belongs to the methylxanthine class of central nervous system stimulants [4].

Other compounds that belong to this group and interact with kratom are as follows:

  • Aminophylline
  • Diphylline
  • Theobromine
  • Theophylline

Is It Safe To Take Kratom With Coffee?

These two drugs act on different receptors and have different metabolic pathways, but they can have similar effects. Small doses of these drugs in combination are unlikely to be lethal or cause anything more than uncomfortable side effects but check with your doctor to be sure.

Taking them together will either enhance or decrease the effect of these drugs, as described in the above paragraphs. It’s best to take these drugs at different times.

The half-life of coffee is about 3 hours, and kratom is 20 hours. So, it would be best to take kratom at least 3 hours after drinking coffee. This will decrease the potential chances of agitation and distractibility.

Taking coffee at a different time has a significant advantage for kratom users. Taking low-dose coffee can help reduce the dependence on kratom and prevent the development of kratom tolerance.

What Is Coffee?

Coffee is a plant belonging to the genus Coffea. Within the genus, there are around 500 genera and 6000 species. There are approximately 25 to 100 species of coffee plants. The size of the plant can range from small shrubs to large trees. There are two important coffee species in the commercial coffee industry: Arabica and Robusta.

Arabica trees are costly to cultivate because the ideal terrain for their production is steep (2000 to 6000 feet above sea level). Also, these trees are more disease prone and require more care and attention. Robusta trees are grown in central and western Africa and Southeast Asia. Robusta is cheaper to cultivate, is less disease-prone, and can withstand high temperatures of up to 85℉ [5].

When we encounter the term coffee, we understand the brewed drink prepared from roasted beans obtained from the coffee plant.

Caffeine action is thought to be mediated by several mechanisms: [6]

  • Blockade of adenosine receptors
  • Inhibition of phosphodiesterase
  • Release of calcium from various intracellular stores
  • Antagonism of benzodiazepine receptors

Caffeine Specs:

Drug Name Coffee/ Caffeine
Trade Name N/A
Classification Methylxanthine class of CNS stimulants
CYP Metabolism CYP1A2
Interaction With Kratom Agonistic or antagonistic
Risk Of Interaction Mild to moderate

What Is Coffee Used For?

Coffee is mainly used to boost attention and concentration and improve productivity. 

Several other off-label uses have been described in studies, including [7]:

Lowers Mortality in Cardiovascular Disease

Coffee consumption is associated with decreased mortality due to all the causes of cardiovascular diseases, e.g., coronary heart disease, stroke, etc.

Liver & Gastrointestinal Outcomes

Any versus no coffee consumption is associated with approximately 29% less risk of non-alcoholic fatty liver disease.

Prevents Metabolic Disorders

Coffee intake is consistently related to a lower risk of type 2 diabetes mellitus.

Prevents Neurological Diseases

Intake of coffee might delay the onset of symptoms of Parkinson’s disease.

Prevention of Various Forms of Cancer

Coffee has effectively prevented various forms of cancer, including liver cancer, oral cancer, prostate cancer, leukemia, melanoma, etc.

What Is the Appropriate Dose of Coffee?

A dose less than 400 mg per day is considered safe and effective for adults. The amount should not go beyond 200 mg per day in pregnant women, breastfeeding mothers, and children.

What Are the Side Effects of Coffee?

Side effects are extremely rare when the dose is below 400 mg per day in adults. However, at high doses, it is possibly unsafe.

Some side effects are as follows:

  • Insomnia
  • Nervousness
  • Restlessness
  • Increased heart rate
  • Increased breathing rate

Also see: Are Caffeine Pills Safe?

What Is Kratom?

Kratom is a tree indigenous to Southeast Asia. Kratom contains more than 50 alkaloids, but the most abundant is mitragynine. Kratom has been used since ancient times in Southeast Asia and is still popular among heavy workers to prevent exhaustion and improve mood.

Mitragynine is converted to 7-hydroxymitragynine in vivo. Mitragynine and 7-hydroxymitragynine act as partial agonists at mu-opioid receptors [8]. This leads to various effects similar to opioids, e.g., anxiolysis, euphoria, and sedation. Despite this, kratom is not an opioid. It works on many other systems and is nowhere near as dangerous or addictive.

Kratom is unique because it has stimulating and sedating effects, depending on the dose. A smaller amount is generally stimulatory, and a larger dose causes significant sedation.

What Is Kratom Used For?

Kratom is used for several clinical purposes:

What Is the Proper Dose of Kratom?

The dose of kratom depends on several factors, such as weight, strain, and desired effect. Lower doses are considered stimulatory, and higher doses are essentially sedative. Novices should start with a low dose. As the body adapts to a certain dose, the amount can slowly increase. However, you should avoid any dose above 12 grams.

What Are the Side Effects of Kratom?

Severe side effects following an average dose of kratom are highly unlikely. However, higher doses can cause many adverse reactions, such as:

Fortunately, most side effects are easy to avoid. Take breaks, avoid combining kratom with other medications, and use as little as possible. Doing this will keep you comfortable and will help you avoid addiction.

Know the signs of kratom addiction and back off if you feel it’s getting out of control. Most people don’t have much of a problem since this addiction is not as strong or dangerous as an addiction to opiates.

What Are the Different Types of Kratom?

There are several types of kratom. The classification is done based on the color of the mid-vein of the leaves. On this basis, kratom strains fall into the following types:

White Vein Kratom

White vein kratom boosts energy, improves concentration and performance, and uplifts mood. The effects are due to a high concentration of mitragynine.

Red Vein Kratom

Red vein kratom is used for its pain relief and calming effects and is the most popular form of kratom. The effects are due to a high concentration of 7-hydroxymitragynine.

Green Vein Kratom

Green strains are the middle option between white and red strains. They produce stimulating and nootropic effects or sedation, but to a lesser degree and depending on the dose.

Yellow Vein Kratom

Yellow strains usually possess the qualities of green vein kratom, but the effects are longer-lasting and often mellower.


Key Takeaways: Kratom & Coffee

Kratom and coffee have a lot in common. Combining them is like combining two drugs that perform either the same or opposite task, depending on the dose of these drugs.

Either they’ll cancel each other out, or you’ll end up far too stimulated, increasing the risk for heart palpitations, anxiety, nausea, and others.

The additive or subtractive effect of the drugs is not always desirable, so it is best to take these drugs at different times. However, consult your doctor first.

References

  1. 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). Https://Doi.Org/10.1080/00498254.2018.155281949(11), 1279–1288.
  2. Perera, V., S Gross, A., & J McLachlan, A. (2012). Measurement of CYP1A2 activity: a focus on caffeine as a probe. Current drug metabolism13(5), 667-678.
  3. Fredholm, B. B. (1995). Adenosine, Adenosine Receptors and the Actions of Caffeine *. Pharmacology & Toxicology76(2), 93–101.
  4. Spiller, G. A. (Ed.). (1998). Caffeine (pp. 225-231). Boca Raton, FL, USA:: CRC Press.
  5. What is Coffee? (n.d.). Retrieved April 30, 2022, from https://www.ncausa.org/About-Coffee/What-is-Coffee
  6. Pharmacology of Caffeine – Caffeine for the Sustainment of Mental Task Performance – NCBI Bookshelf. (n.d.). Retrieved April 30, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK223808/
  7. Poole, R., Kennedy, O. J., Roderick, P., Fallowfield, J. A., Hayes, P. C., & Parkes, J. (2017). Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. The BMJ359, j5024.
  8. Obeng, S., Wilkerson, J. L., León, F., Reeves, M. E., Restrepo, L. F., Gamez-Jimenez, L. R., Patel, A., Pennington, A. E., Taylor, V. A., Ho, N. P., Braun, T., Fortner, J. D., Crowley, M. L., Williamson, M. R., Pallares, V. L. C., Mottinelli, M., Lopera-Londoño, C., McCurdy, C. R., McMahon, L. R., & Hiranita, T. (2021). Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats. Journal of Pharmacology and Experimental Therapeutics376(3), 410–427.

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