Last Updated: October 28, 2022

Gabapentin is a central nervous system depressant that slows down activity in the brain and body. The drug can be helpful for treating many different conditions, including various types of nerve pain. However, gabapentin also has some side effects, especially when mixed with other medications. If you or someone you love is taking gabapentin, being aware of the substances that interact with it can help keep you and your loved ones safe.

Gabapentin and OTC Medications

Most over-the-counter (OTC) medications do not have a drug interaction with gabapentin. However, the OTC pain reliever naproxen (Aleve) is an exception. Naproxen can increase the amount of gabapentin that your body is exposed to, leading to higher-than-expected gabapentin levels. Although doctors aren’t sure how significant this interaction is, it is best for people who take gabapentin to double-check with a doctor or pharmacist before taking naproxen.

Some over-the-counter antihistamines can also interact with gabapentin. This is generally limited to antihistamines that can make you drowsy, like diphenhydramine (Benadryl). Because both gabapentin and Benadryl can be sedating, mixing them can cause additive side effects that can be dangerous in severe cases.

Gabapentin and Antacids

Some antacids can cause an up to 20% reduction in gabapentin’s ability to absorb into your body. This can cause gabapentin to be less effective than expected. In particular, antacids that contain magnesium or aluminum have this drug interaction with gabapentin. These include:

• Gaviscon
• Maalox
• Mylanta
• Phillips’ Milk of Magnesia

If you take an antacid that contains magnesium or aluminum and are prescribed gabapentin, you should take gabapentin no sooner than two hours after the antacid to minimize the interaction. 

Gabapentin and Alcohol

Because gabapentin and alcohol are both central nervous system depressants, you should avoid mixing them. Taking them together can increase the risk of additive side effects from both substances, including sedation and dizziness. In addition, if you take gabapentin enacarbil (Horizant), the long-acting form of gabapentin, drinking can cause the medication to be released too quickly into your bloodstream. This increases the risk of side effects.

Gabapentin and Stimulants

Gabapentin and stimulants work on different areas of the central nervous system. While gabapentin works by slowing down the central nervous system and causing side effects like sedation, stimulants speed it up. As a result, stimulant side effects can include wakefulness. 

When used as prescribed, gabapentin and stimulants can be safely taken together. However, some people who take illicit stimulants may attempt to use gabapentin to soften the “crash” that comes after a stimulant high. Mixing drugs that have not been prescribed to you can be dangerous. 

Stimulants can include illicit methamphetamine and cocaine, as well as legal stimulants like:

• Adderall
• Vyvanse
• Ritalin
• Concerta
• Focalin

Gabapentin and Benzodiazepines

Gabapentin and benzodiazepines are both central nervous system depressants that slow down brain activity. For this reason, mixing them can be dangerous, especially if you don’t take them exactly as prescribed. A major risk of mixing the drugs is slowed breathing, which can be fatal in some cases. Experts recommend taking the lowest effective dose of gabapentin if you must take both gabapentin and a benzodiazepine.

Benzodiazepines include:

• Ativan
• Xanax
• Valium
• Klonopin 

Gabapentin and Opioids

Mixing gabapentin and opioids can be very dangerous, especially if you take opioids that have not been prescribed to you. Gabapentin and opioids have an additive effect that slows down the central nervous system, so taking them together can increase your risk of overdose. Sometimes, gabapentin can even make the opioid less effective, as is the case with hydrocodone.

Gabapentin was a factor in 2,975 overdose deaths between 2019 and 2020. Around 90% of these overdose deaths also involved opioids. Opioids include:

• Fentanyl
• Oxycodone
• Morphine
• Methadone
• Hydrocodone
• Hydromorphone

Gabapentin and Antidepressants

Gabapentin is often taken together with antidepressants, especially when treating conditions like nerve pain. However, because some antidepressants are sedating and slow down the central nervous system, they should be used cautiously with gabapentin. This includes tricyclic antidepressants (TCAs); however, TCAs can be prescribed alongside gabapentin and used safely if you follow your doctor’s instructions. 

Taking too much gabapentin or higher doses of TCAs than prescribed can be dangerous. This is because they can have an additive sedative effect on your brain, putting you at risk of slowed breathing. TCAs include:

• Amitriptyline 
• Doxepin
• Imipramine 
• Nortriptyline

Gabapentin and Antipsychotic Medications

Gabapentin does not have major interactions with antipsychotic medications. However, it is important to remember that some antipsychotic medications, such as quetiapine (Seroquel), can be sedating. Because gabapentin is a central nervous system depressant that has sedative effects, mixing these medications can lead to increased sedation. This can be dangerous in some cases, especially if you take higher gabapentin or antipsychotic doses than prescribed. 

Antipsychotics include:

• Aripiprazole (Abilify)
• Clozapine (Clozaril)
• Olanzapine (Zyprexa)
• Risperidone (Risperdal)
• Paliperidone (Invega)
• Quetiapine (Seroquel)
• Ziprasidone (Zeldox)

Gabapentin and Marijuana

Gabapentin and marijuana can both have sedative effects on the brain. If you take gabapentin and cannabis together, these effects can be additive and may be dangerous in some cases. This includes the potential for slowed breathing, which can be fatal. The risk is compounded if the cannabis you take is illicit and not provided by a registered marijuana dispensary. This is because additives can vary, and illicit marijuana may be laced with other substances that further interact with gabapentin, such as fentanyl.