Can You Mix Kratom & Hydroxyzine (Vistaril)?

Does Kratom Interact With Hydroxyzine (Vistaril)?

Kratom has an agonistic interaction with hydroxyzine, causing an increased risk of side effects, including sedation. It can also cause metabolic inhibition, where both substances use the same enzymes for metabolization, causing the drugs to remain in the body longer than they should be.

The interaction between the two is considered moderate.

Even if the interaction is moderate, it may differ from person to person, especially if the two drugs are taken long-term and in large quantities.

Always take advice from your doctor before taking kratom with hydroxyzine.

Kratom’s interaction with hydroxyzine can occur in two ways:

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

When two drugs with similar effects are taken together, pharmacologic agonism occurs. This can enhance their impact and cause an increase in potency, which is not always beneficial.

The mechanism of action of kratom and hydroxyzine are very different. The active ingredient of kratom acts by stimulating opioid receptors, whereas hydroxyzine acts as an antihistamine. But both can cause sleepiness and lethargy.

Thus, if taken together, they may cause severe lethargy, somnolence, and depression of vital centers in the brain.

This interaction can have serious adverse effects like brain fog (confusion), morbid drowsiness, and sedation.

B. Kratom May Slow Down Hydroxyzine’s Metabolism (Metabolic Competition)

Metabolic competition can occur when similar enzymes metabolize two or more compounds, which slows down their metabolization and prolongs the duration of their effects.

Kratom and hydroxyzine are both metabolized by similar enzymes in the liver, namely CYP3A4 and CYP2D6 [1].

Therefore, when consumed simultaneously, they can compete for these enzymes, which slows their metabolism and elimination and leads to overaccumulation of both drugs within the body.

Such metabolic competition can increase the risk of adverse effects and toxicity. This may be prevented or controlled by taking the two drugs at different times or lowering the dosage.

Kratom & Hydroxyzine Interactions

Hydroxyzine is an antihistamine. Other antihistamines combined with kratom can cause similar interactions.

Other antihistamines that kratom may interact with are:   

Is It Safe To Take Kratom With Hydroxyzine (Vistaril)?

Kratom and hydroxyzine can interact with each other moderately. Taking them together for long durations or in high doses is not recommended.

Taking high doses of these drugs together can be lethal. This is because they can result in excessive sedation and depress vital centers in the brain. Also, several unwanted adverse effects may occur due to slowed elimination of both drugs.

If you must take them together, do so only after consulting your doctor. Never start them on your own.

What Is Hydroxyzine (Vistaril)?

Hydroxyzine is a piperazine derivative and classified as a first-generation antihistamine. It was first patented in 1956 and was approved for sale by Pfizer later in the same year.

Histamine causes inflammation and allergy. It also has other vital roles like neuroregulation of the sleep-wake cycle [2].

This is why antihistamines often cause sedation. It works on multiple targets in the body and is used to treat anxiety, sleeping difficulties, allergies, nausea, and vomiting.

Hydroxyzine Specifications

Drug NameHydroxyzine
Trade NameVistaril, Atarax, NOVO-Hydroxyzin, PMS-Hydroxyzine HCL, PMS-Hydroxyzin    
ClassificationFirst-generation antihistamine
CYP MetabolismCYP3A4
Interaction With KratomAgonistic and metabolic competition
Risk of InteractionModerate

What Is Hydroxyzine Used for?

Hydroxyzine, a first-generation antihistamine, has several clinical uses. Some of them are:

Relief From Anxiety

Hydroxyzine is known to cause symptomatic relief of anxiety [3]. The dose used for anxiety is 50 to 100 mg every 4 to 6 hours.

Pain Management After Delivery

It is used as an adjunct to reduce the dose of opioids for pain management after delivery [4]. The amount used for pain management is 50 to 100 mg every 4 to 6 hours.

Managing Allergy Symptoms

It also manages allergy symptoms [5]. It prevents mast cells in the skin from releasing histamine. Histamine is a mediator of allergic reactions such as hives. The recommended dose of hydroxyzine is 25 mg every 6 to 8 hours to treat allergies.

For Sedation Before Major Surgery

Histamine is one of the major factors that regulate the waking phase of the sleep-wake cycle. Thus, antihistamines like hydroxyzine can help sedate the patient before surgery.

Nausea & Vomiting

Hydroxyzine can help manage nausea and vomiting by suppressing the vomiting center in the brain. The drug dose for nausea and vomiting is 25 mg given intramuscularly.

Difficulty Sleeping

Hydroxyzine has some effect on serotonin, a neurotransmitter thought to regulate sleep. So, it may help people with sleeping difficulties.

What Are the Side Effects of Hydroxyzine?

With clinical doses of hydroxyzine, serious side effects are rare.

Some side effects that may occur with hydroxyzine are:

  • Dry mouth
  • Drowsiness
  • Sedation
  • Tremors
  • Convulsions (seizures)
  • Headache

What is Kratom?

Kratom, or Mitragyna speciosa, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties [6]. It is a member of the coffee family. The active alkaloids of kratom are mitragynine and 7-hydroxymitragynine.

7-hydroxymitragynine is more potent than mitragynine, though it’s not as abundant [7]. Kratom is commonly consumed by preparing the leaves into tea or grinding them into a powder.

Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria [8]. It has scores of health benefits depending on strain and dose. It has been used to prevent burnout among Asian laborers since the early 19th century.

Kratom is a stimulant in low doses but a sedative in high doses.

What Is Kratom Used For?

Kratom has many uses, but these are the most common.

What is the Proper Dose of Kratom?

To figure out the right dose, you need to consider a few things. What are you using kratom for? What’s your tolerance level?

Kratom doses vary a lot, but here are the general guidelines.

  • Small doses: 2-5 g
  • Medium doses: 5-8 g
  • Larger doses: 8-12 g

Remember, smaller amounts are more energizing while more significant amounts are better for sleep and pain relief. For a more detailed guide, use a dose calculator.

What Are the Side Effects of Kratom?

Kratom is well-tolerated as long as it’s used responsibly. While there are some side effects, these are most common with large amounts and long-term use. In general, kratom is low-risk, and its side effects go away quickly.

Nausea & Vomiting

Nausea is almost always a sign that you have taken more kratom than your body can handle [9]. Making kratom tea with ginger is a great way to soothe nausea.


Constipation may occur due to the stimulation of opioid receptors [9]. Staying hydrated can help you avoid constipation. Also, you can take food rich in fibers to avoid this unwanted effect.

Lethargy & Sedation

Kratom is generally stimulating at first. This stimulation tends to fade off into a gentle relaxation later on. Once you continue to use kratom daily, these effects will start to change. The initial energetic rush will become shorter and less pronounced.

If you continue to use kratom after its beneficial effects wane, you may develop chronic fatigue as your dopamine and adrenaline systems burn out [9]. To avoid lethargy, you should reduce the dose and frequency of taking kratom.

Lightheadedness & Dizziness

Lightheadedness and dizziness can result in high doses. Dizziness occurs due to a drop in blood pressure or dehydration [10]. To avoid dizziness, you should lie down and avoid sudden movements.


Brain fog or confusion may result from inappropriately high doses. To avoid confusion, you must stay hydrated, have a balanced diet, and stick to smaller doses of kratom.


Kratom is used to treat anxiety, but if you use a lot of it every day, kratom may cause anxiety. To avoid this, make sure you take a small dose and reduce the frequency of intake.

What Are the Different Types of Kratom?

Depending on the color of the vein of the kratom leaf, it has been classified into four types:

White Vein Kratom

White strains are best for those seeking heightened energy, focus, and concentration as it possesses energy-boosting properties.

Red Vein Kratom

Red strains of kratom are best for sleep and pain. They are powerful and fast-acting with numbing and relaxing effects.

Green Vein Kratom

Green vein kratom is a balance between white and red types of kratom. It has both stimulant and sedative effects which depend on the dose taken.

Yellow Vein Kratom

Yellow vein kratom can come from fermented green vein kratom and is smoother with more relaxing properties.

Key Takeaways

Kratom and hydroxyzine work via different mechanisms, but both can cause sedation. When taken together, there is a moderate interaction between the two drugs which can cause an increased risk of side effects, including a dangerous slowing of brain activity.

It is best not to take them together as it may result in life-threatening events such as depression of vital brain centers.

If you are taking hydroxyzine and would like to take kratom, or vice versa, consult a doctor first.


  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). Xenobiotica, 49(11), 1279-1288.
  2. Barbier, A. J., & Bradbury, M. J. (2007). Histaminergic control of sleep-wake cycles: recent therapeutic advances for sleep and wake disorders. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 6(1), 31-43.
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  5. Estelle, F., Simons, R., & Simons, K. J. (2002). Clinical pharmacology of H1-antihistamines. Histamine and H1-Antihistamines in Allergic Disease: Second Edition Revised and Expanded, 141–178.
  6. Ismail, I., Wahab, S., Sidi, H., Das, S., Lin, L. J., & Razali, R. (2019). Kratom and Future Treatment for the Opioid Addiction and Chronic Pain: Periculo Beneficium? Current Drug Targets, 20(2), 166–172.
  7. Kruegel, A. C., Uprety, R., Grinnell, S. G., Langreck, C., Pekarskaya, E. A., le Rouzic, V., Ansonoff, M., Gassaway, M. M., Pintar, J. E., Pasternak, G. W., Javitch, J. A., Majumdar, S., & Sames, D. (2019). 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Central Science, 5(6), 992–1001.
  8. Swogger, M. T., & Walsh, Z. (2018). Kratom use and mental health: A systematic review. Drug and Alcohol Dependence, 183, 134–140.
  9. Warner, M. L., Kaufman, N. C., & Grundmann, O. (2015). The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. International Journal of Legal Medicine 2015 130:1, 130(1), 127–138.
  10. Wahbeh, A., Nasralah, T., El-Gayar, O., Al-Ramahi, M., & Noshokaty, A. el. (2021). Adverse Health Effects of Kratom: An Analysis of Social Media Data. Computer Information Systems Faculty Publications.

Further Reading