DXM & Weed, Kratom, LSD: Dextromethorphan Interactions

Last Updated: June 3, 2020

It is easier to buy dextromethorphan over the counter than illicit drugs. People often use it in higher doses to get DXM high feeling. Dextromethorphan alone is intoxicating, but interactions with other drugs or medicines can enhance its effects. The most common side effects of dextromethorphan drug interactions occur when DXM is taken together with antidepressants, stimulants, opioids, opiates, alcohol, and weed.

Dextromethorphan Interaction With Antidepressants

Mixing DXM with antidepressants could lead to serotonin syndrome. This happens when the brain gets flooded with too much serotonin. The most common side effects of taking DXM and antidepressants together are:

  • Dry mouth
  • Agitation or restlessness
  • Excessive sweating and high fever
  • Loss of muscle coordination, seizures
  • Nausea
  • Diarrhea or constipation
  • Headache
  • Shivering, goosebumps and muscle spasms
  • Irregular heartbeat
  • Confusion, delirium, and hallucinations
  • Unconsciousness
  • Libido changes

DXM And Xanax

There is clinically significant interaction between dextromethorphan and Xanax, which requires using it only under special circumstances.

Dizziness with poor motor coordination are commonly associated with dextromethorphan and Xanax interaction, and there is currently no scientific study that sanctions a safe DXM amount that can be combined with Xanax. Other side effects of combining the two are:

  • Anxiety and paranoia
  • Violence
  • Lethargy
  • Concentration difficulties
  • Increased blood pressure
  • Difficulty in speaking

Some people, especially the elderly, can experience impairment in judgment, thinking, and motor coordination.

Zoloft And Dextromethorphan

When mixing Zoloft and dextromethorphan, a clinically significant interaction occurs. So, it is recommended to avoid this combination, as the risk of the interaction outweighs the benefit. The sedating effects of Zoloft can significantly increase when taken together with dextromethorphan. As a result, Dextromethorphan and Zoloft interaction could lead to a feeling of uneasiness, headaches, and drowsiness. Other side effects of mixing the two are:

  • Extreme mood changes
  • Shaking and shivering
  • Drastic changes in blood pressure
  • Blurred vision
  • Tremor, muscle stiffness and incoordination
  • Stomach cramp

Dextromethorphan And Prozac (Fluoxetine)

When taken together, a significant interaction occurs, and it is also recommended to avoid this combination. Prozac could make the body process DXM at a slower rate. Dextromethorphan and Prozac interaction could also lead to sedation hence inducing dizziness, nausea, and headache. Adverse effects of a DXM and Prozac interaction are:

  • Changes in blood pressure
  • Extreme changes in body temperature
  •  Inconsistency in muscle movements
  • Mood imbalance

what if take dxm with prozac?

Dextromethorphan And Lexapro (Escitalopram)

The interaction between dextromethorphan and Escitalopram could cause clinically significant interactions, so these medicines must be taken under special conditions. This combination is likely to cause heart racing, and an uncomfortable, twitchy feeling for a while. In severe cases, mixing the two could lead to a coma or death. Other side effects include:

  • Incoordination, shaking and shivering
  • Blurred vision
  • Stomach cramp
  • Severe cases could lead to a coma or even death.

DXM Interaction With Stimulants

As in the case of antidepressants, the interactions between DXM and amphetamine containing medicines can also suddenly heighten the serotonin level in the body. Therefore, such an interaction is likely to increase blood pressure levels and heartbeat rates and induce an uncomfortable feeling, agitation, and restlessness. Using stimulants together with DXM could cause:

  • Changes in blood pressure
  •  Hallucinations and confusion
  • Excessive sweating, shaking or shivering
  • Nausea
  • Diarrhea, stomach cramps, and vomiting
  • Incoordination
  • Blurred vision

DXM And Adderall

A DXM Adderall interaction is not safe, even when dextromethorphan is used to offset Adderall tolerance, as a clinically significant interaction may appear. In a DXM and Adderall combo, DXM acts as an NMDA receptor antagonist, and this could reduce the onset of amphetamine tolerance. Effects of mixing Dextromethorphan and Adderall are seizures, muscle spasms, and confusion.

Phenibut And DXM

The combination of dextromethorphan and Phenibut could cause a significant interaction, which requires using it under the supervision of a doctor. DXM and Phenibut give a euphoric feeling when used together. Phenibut increases the dextromethorphan adverse effects when mixed together, leading to sedation, anxiety, agitation and irritability, allergic reactions, and high blood pressure.

DXM And Pseudoephedrine

There is no available information about the interaction between dextromethorphan and pseudoephedrine. Using dextromethorphan and pseudoephedrine together could cause adverse reactions. It is not advised to take dextromethorphan and pseudoephedrine together recreationally. The most common pseudoephedrine and DXM recreational dose effects include:

  • Vomiting
  • Drowsiness
  • Constipation
  • Restlessness and nervousness
  • Dizziness and headache
  • Fear and anxiety
  • Loss of appetite

what if take dxm with Pseudoephedrine?

DXM And Caffeine

The combination of dextromethorphan and caffeine can be taken simultaneously to determine acetylation phenotypes and oxidation. A report by the US National Library of Medicine National Institutes of Health shows that the two can be mixed to offer an innocuous and non-invasive method for assessing polymorphic drug metabolism in different pediatric populations.

Mixing Dextromethorphan With Opioids

The interaction between dextromethorphan and opioids could cause severe and harmful effects by increasing the amount of serotonin in the body. Thus, the two types of medication should not be taken together.

The interactions between opioids and dextromethorphan are severe, and the results of this could be:

  • Changes in body temperature and blood pressure
  • Heart palpitations
  • Confusion and agitation
  • Restlessness and seizures
  • Heavy sweating and shivering
  • Fever
  • Nausea and vomiting
  • Dizziness
  • Hallucinations
  • Blurred visions
  • Stomach upsets

DXM And Kratom

A significant interaction occurs while using dextromethorphan and Kratom together. So, this combination must be avoided.

When used with a potentiator, kratom side effects last longer. A DXM Kratom combo can have serious side effects like:

  • Lack of coordination
  • Eye wobbles
  • Constipation
  •  Liver damage
  • Tachycardia.

DXM And Hydrocodone

Mixing dextromethorphan and hydrocodone may cause a significant interaction. It is recommended to avoid this combination, as taking dextromethorphan and hydrocodone together may cause:

  • Confusion
  • Extreme blood pressure changes
  • Increased heart rate
  • Spasms

Severe cases may lead to coma or death. Used together in high doses, DXM and hydrocodone could impair someone’s ability to operate hazardous machinery or a vehicle due to their sedative effects.

death after dxm and hydrocodone interaction

DXM And Oxycodone

Both dextromethorphan and oxycodone have better efficacy in the treatment of neuropathic pain. However, taking DXM and oxycodone together could lead to severe side effects, which calls using it under the supervision of the healthcare provider, like:

  • Constipation
  • Lightheadedness
  • Confusion
  • Disassociation
  •  Increased heart rate
  • Drowsiness

Dextromethorphan And Opiates Interactions

The use of DXM with opiates helps in lowering the dose of opiates while maintaining its analgesic effect. Though opiates can have additive or synergistic interactions with dextromethorphan. Common side effects that one could experience after taking the two include:

  • Respiratory depression
  • Sedation
  • Nausea
  • Dizziness
  • Constipation
  • Vomiting
  • Tolerance
  •  Physical dependence

Dextromethorphan And Codeine

Taking dextromethorphan and codeine together can cause a significant interaction. The body converts codeine into morphine. The use of dextromethorphan and codeine may prevent the body from converting codeine into morphine, thus reducing the body’s ability to relieve pain. Taking codeine and dextromethorphan could also lead to seizures, blood pressure changes, fever, incoordination, and tremors.

DXM And Morphine

The DXM potentiation effect increases the analgesic action of morphine and decreases its dose. However, mixing together may cause a significant interaction, which can create social and health problems. Dextromethorphan doesn’t alter physical dependence, euphorigenic, or respiratory depressant capacities of morphine.

Mixing DXM With Other Medications

The use of DXM with other medication, like Gabapentin, Benadryl, Prednisone, and Warfarin may have benefit when taken under the supervision of the healthcare provider. However, the misuse of these medications and dextromethorphan may potentiate the risk of dangerous adverse reactions, such as:

  • Nausea and vomiting
  • Confusion and dizziness
  • Nervousness and fever
  • Sedation
  • Coma
  • Some extremities could lead to death.

Gabapentin And DXM

A significant interaction between dextromethorphan and gabapentin occurs when used together. However. This mixing can be useful for alleviating pain problems. Taking dextromethorphan and gabapentin could enhance some side effects, such as dissociation and difficulty in concentrating.

It is advisable to avoid handling dangerous machinery or vehicles after using DXM and gabapentin, due to their mind-altering side effects when used together.

DXM And Benadryl (DPH, Diphenhydramine)

Using diphenhydramine and DXM for cough treatment in some OTC cough and cold medicine is common. When mixing DXM and Benadryl, a significant interaction could occur. Though, Taking together, enhancing dextromethorphan sleep effects. But dangerous side effects, in elderly persons, such as impairment in judgment, thinking, and motor coordination may appear after taking dextromethorphan and Benadryl together for a long period of time.

Since mix dextromethorphan and Benadryl could lead to lethargy and lesser attentiveness, it’s advisable to avoid operating a vehicle or dangerous machinery after use.

mixing dxm with benadryl

Mixing DXM With Tessalon Perles (Benzonatate)

Can one take Tessalon Perles with dextromethorphan? There is no available information about interaction between Tessalon and dextromethorphan. Using benzonatate alone may cause drowsiness, upset stomach, and many other side effects. Dextromethorphan and benzonatate could lead to more adverse reactions, like breathing and heartbeat problems, and hallucinations.

Prednisone And Dextromethorphan

There are no interactions found between dextromethorphan and prednisone. Some healthcare providers advise using prednisone and dextromethorphan together for the relief of cough. However, the mixing of both may cause mild side effects. Severe allergic reactions after using dextromethorphan and prednisone are rare, but the prolonged use of DXM and prednisolone may lead to dependence or tolerance.

Dextromethorphan And Warfarin

It is not recommended to use dextromethorphan with warfarin, as a significant interaction may occur. Dextromethorphan slows down the warfarin’s metabolism.

So, in this case, it is advised to monitor warfarin dose by a doctor.

Dextromethorphan And Ibuprofen

There is not enough evidence of drug interaction between Ibuprofen and DXM. However, mixing dextromethorphan and ibuprofen should be done cautiously, so it’s better to consult a therapist before using them together. While there is no enough proof, a few reports indicate that the two medications cause heart attacks when used together.

DXM And Doxylamine Succinate

A significant interaction occurs between dextromethorphan and Doxylamine Succinate when used together. Both medications are used to treat cough in many OTC cold medicines. In very rare cases the next side effects may appear:

  • allergic reactions (rash; itching; peeling skin)
  • mouth or lips swelling
  • chest or throat tightness

Doxylamine and DXM should not be used by someone who has taken an MAO inhibitor, as dangerous side effects may occur, like trouble breathing, swallowing.

Dextromethorphan And Acetaminophen

This combination is common in most OTC cold medicines. However, using dextromethorphan and acetaminophen together leads to a synergistic effect that could be tragic. Some ingredients of DXM syrup and acetaminophen have hazardous effects when taken in high doses and could cause heart rate problems, pressure changes, nervousness, fever, heart attacks, stroke, and death.

Dextromethorphan And Chlorpheniramine

Using dextromethorphan with chlorpheniramine may cause a minor interaction. Most non prescribed cold medicines for relieving cough contain chlorpheniramine as an antihistamine and dextromethorphan antitussive class.

DXM And Ambien (Zolpidem)

Mixing dextromethorphan with ambien could cause a significant interaction. The misuse of DXM, together with zolpidem, can lead to impairment in motor coordination, judgment, and thinking to some people, especially the elderly. Taking DXM and Zolpidem can increase the chances of mild side effects. However, it would be dangerous to operate a vehicle or hazardous machinery after taking the two.

DXM Interactions With Other Substances

DXM is commonly used with hard drugs and narcotics for recreational purposes. While the dextromethorphan half-life is about 6 hours, the effects after the combination of DXM could be more severe and long-lasting. Common side effects of DXM abuse with other substances include:

  • Hallucinations
  • Blackouts
  • Restlessness
  •  Nervousness
  • Blood pressure changes
  •  Heart attacks
  • Death

DXM And Weed

Some adolescents resort to extracting DXM from capsules or tablets and then mix this powder of DXM and weed to get high, but a significant interaction may occur. The combination of DXM and weed has such effects as delusions, agitation, mood changes. Taking weed and DXM may increase the risk of many dangerous side effects:

  • hallucinations
  • impaired thinking
  • profound loss of coordination
  • increased heart rate
  • liver damage

After taking DXM and cannabis, the concentration may diminish, thus making it hazardous to drive or operate heavy machinery.


Some adolescents mix dextromethorphan and LSD to get more intense hallucinations, but this mixing could cause a significant interaction, which must be avoided. Taking LSD and DXM causes dangerous adverse reactions, such as, high blood pressure, increased heart rate, and dilated pupils. Additionally, drug-specific side effects could also occur, leading to appetite loss, fevers, numbness, tremors, and weakness. It’s no surprise that combining DXM with LSD could alter brain function, and lead to hallucinations and “trippy” effects.

DXM And Nicotine

Some people are reported to use DXM as a way of combating nicotine withdrawal symptoms and cravings. However, persistent use could worsen the situation and lead to drowsiness, vomiting, constipation, dizziness, diarrhea, nervousness, and restlessness. Taken together, nicotine seems to potentiate DXM effects vastly to the extent that one cigarette can floor the user on a second plateau trip.

mixing dxm with nicotine

DXM Interaction With Food

While some food and drug combinations work well together, there is no interaction while using DXM on a full stomach or not. However, administration of dextromethorphan with some foods may cause a significant interaction. Grapefruit and lime slow down body enzymes from breaking down the drug, hence prolonging the effects and half-life of DXM.

DXM And Grapefruit

A significant interaction occurs when taking dextromethorphan with grapefruit.

This is because grapefruit contains enzymes that extend the effect of dextromethorphan by making it hard for the body to dismantle DMX further. Hallucinations and somnolence could occur while using dextromethorphan with grapefruit.

DXM And Limes

The effects of using DXM with limes are quite similar to those from DXM and grapefruit interaction. Using lime with dextromethorphan causes a significant interaction and also must be avoided. Limes may block enzymes responsible for breaking down dextromethorphan. As a result, the medication builds up in the bloodstream, hence enhancing its side effects. One would suffer:

  • Nausea
  • Drowsiness
  • Vomiting
  • Constipation
  • Diarrhea
  • Restlessness
  • Nervousness
  • Increased heart rate

Severe Dextromethorphan Interactions

Severe and toxic reactions could occur when dextromethorphan is clinically administered to someone being treated with MAO inhibitors. Possible adverse results include extreme hyperpyrexia, tremors, and even death.

Using DXM together with any of the following medicines is not recommended:

  • Clorgyline
  •  Iproniazid
  • Isocarboxazid
  • Moclobemide
  • Nialamide
  • Pargyline
  • Phenelzine
  • Procarbazine
  • Rasagiline
  • Safinamide
  • Selegiline
  • Toloxatone
  • Tranylcypromine
  • Methylene blue

risking to take severe dxm interactions

cough suppressant without dextromethorphan may be prescribed to persons who have been taking the drugs above. Tremors, shivering, fever, stiffness, heavy sweating, restlessness, palpitations, agitation, confusion, coordination problems, or diarrhea after taking dextromethorphan should be reported to a physician.

Avoid Dangerous Interactions With Dextromethorphan

Combination of DXM and other substances, drugs or food doesn’t influence dextromethorphan half-life time, but it affects its MOA in the body and common health. Combining dextromethorphan with other drugs for euphoric effects can cause significant interactions in most cases. Avoid these combinations, as the risks outweigh the benefits, especially when DXM containing products are taken, in which dextromethorphan is only the small part of the composition. Also, minor interactions can occur, but it is advised to take these medications under the supervision of a doctor. The minor interactions can be avoided by taking steps to get through this interaction risk and considering alternative drugs.

Finding rehab centers as quickly as possible will improve the process of recovery. Also, the proper treating the addiction may help with managing the gradual withdrawal of dextromethorphan as well as remove the negative effects of bad interactions.

Page Sources

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  2. Kim Vo, Patricia J Neafsey, and Carolyn A Lin. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students. 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309786/
  3. Damaj MI, Flood P, Ho KK, May EL, Martin BR. Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. 2005. https://www.ncbi.nlm.nih.gov/pubmed/15356218
  4. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. 2002. https://www.ncbi.nlm.nih.gov/pubmed/12095536
  5. Ai-Leng Foong, Kelly A. Grindrod, Tejal Patel, Jamie Kellar. Demystifying serotonin syndrome (or serotonin toxicity). 2018.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6184959/

Published on: August 6th, 2019

Updated on: June 3rd, 2020

About Author

Peter J. Grinspoon, MD

Dr. Peter Grinspoon is an experienced physician with long-term clinical practice experience. As a former analgesic addict, Dr. Grinspoon knows precisely how important it is to provide patients with effective treatment and support. Medical writing for him is the way to communicate with people and inform them about their health.


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