Benzodiazepines (drug interactions)

DEFINITION: Central nervous system depressant medications used as muscle relaxants, sedatives, and anticonvulsants in treating insomnia, anxiety, epilepsy, muscle spasms, alcohol withdrawal, and some symptoms experienced by individuals with cancer

INTERACTIONS: Grapefruit juice, hops, kava, melatonin, passionflower, pregnenolone, valerian

DRUGS IN THIS FAMILY: Alprazolam (Xanax), chlordiazepoxide hydrochloride (Libritabs, Librium, Limbitrol, Lipoxide, Mitran, Reposans-10, Sereen), clonazepam (Klonopin), clorazepate dipotassium (Gen-XENE, Tranxene-T, T-Tab), diazepam (Diastat, Valium, Valrelease, Vazepam), estazolam (ProSom), flurazepam hydrochloride (Dalmane, Durapam), halazepam (Paxipam), lorazepam (Ativan), oxazepam (Serax), quazepam (Doral), temazepam (Razepam, Restoril, Temaz), triazolam (Halcion), midazolam (Nayzilam, Seizalam)

Grapefruit Juice

Effect: Possible Harmful Interaction

Grapefruit juice slows the body’s normal breakdown of several drugs, including some benzodiazepines, allowing them to build up to potentially dangerous levels in the blood. Research indicates that this effect can last for three days or more following the last glass of juice. Because of this risk, if one takes benzodiazepines, the safest approach is to avoid grapefruit juice altogether.

Hops, Kava, Passionflower, Valerian

Effect: Possible Harmful Interaction

The herb kava (Piper methysticum) has a sedative effect and is used for anxiety and insomnia. Combining kava with drugs in the benzodiazepine family, which possess similar effects, could result in “add-on” or excessive physical depression, sedation, and impairment. In one case report of a fifty-four-year-old man hospitalized for lethargy and disorientation, these side effects were attributed to his having taken the combination of kava and alprazolam for three days.

Experimental studies suggest that kava, similarly to benzodiazepines, exerts its sedative effects at binding sites in the brain called GABA receptors.

Other herbs with a sedative effect that might cause problems when combined with benzodiazepines include ashwagandha (Withania somnifera), calendula (Calendula officinalis), catnip (Nepeta cataria), hops (Humulus lupulus), lady’s slipper (Cypripedium), lemon balm (Melissa officinalis), purple passionflower (Passiflora incarnata), sassafras (Sassafras officinale), skullcap (Scutellaria lateriflora), valerian (Valeriana officinalis), and yerba mansa (Anemopsis californica). Because of the potentially serious consequences, one should avoid combining these herbs with benzodiazepines or other drugs that also have sedative or depressant effects unless advised by one’s physician.

Melatonin

Effect: Supplementation Possibly Helpful

Melatonin is a natural hormone that regulates sleep. Many people who take conventional sleeping pills (most of which are in the benzodiazepine family) find it difficult to quit. The reason is that when one tries to stop the medication, one may experience severe insomnia or interrupted sleep. A double-blind, placebo-controlled study of thirty-four people who regularly used such medications found that melatonin at a dose of 2 milligrams (mg) nightly (in a controlled-release formulation) could help them discontinue the use of the drugs. However, further research found conflicting results.

Other research found a reciprocal relationship between benzodiazepines and melatonin, in which long-term benzodiazepine use causes a disruption in the normal secretion of melatonin. Adding a melatonin supplement may help restabilize this, but only with the advice of a medical professional.

Warning: It can be dangerous to stop using benzodiazepines if one has taken them for a while. Consult a physician before trying melatonin to help handle benzodiazepine withdrawal or before trying to stop benzodiazepine medication under any conditions.

Pregnenolone

Effect: Supplementation May Decrease Effectiveness

The adrenal glands naturally produce the hormone pregnenolone, but when marketed as a dietary supplement, it is claimed to improve cognitive function, stress, and depression, although scientific evidence supporting these uses is limited. It is widely sold as a kind of “fountain of youth.” However, the only direct evidence that pregnenolone supplements have any effect relates to a potential interaction between the hormone and benzodiazepine drugs. In a carefully designed clinical trial, regular use of pregnenolone was found to greatly decrease the sedative effects of diazepam (Valium). The reasons for this interaction are not known. However, people who rely upon benzodiazepine drugs may find them less effective if pregnenolone is added into the mix.

Kava

Effect: Possibly Helpful for Medication Cessation

Although they are highly effective for anxiety, benzodiazepine drugs can cause unpleasant and dangerous withdrawal symptoms when they are discontinued.

A six-week, double-blind, placebo-controlled trial of forty people who had been taking benzodiazepines found that the use of kava significantly reduced withdrawal symptoms and helped maintain control of anxiety. This trial involved close medical supervision and a very gradual tapering of benzodiazepine dosages. Persons should not discontinue anti-anxiety medications except on the advice of a physician, as withdrawal symptoms can be life-threatening.

However, when taken with benzodiazepines, Kava can prevent the breakdown of the drug, causing increased sedative effects for a longer period. Kava should not be taken with benzodiazepines except under close medical supervision.

Bibliography

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Takanaga, H., et al. “Relationship between Time after Intake of Grapefruit Juice and the Effect on Pharmacokinetics and Pharmacodynamics of Nisoldipine in Healthy Subjects.” Clinical Pharmacology and Therapeutics, vol. 67, 2000, pp. 201-14, doi:10.1067/mcp.2000.104215. Accessed 10 Dec. 2025.