Grapefruit Juice —Possible Harmful Interaction | Hops, Kava, Passionflower, Valerian —Possible Harmful Interaction | Melatonin —Supplementation Possibly Helpful | Pregnenolone —May Decrease Activity of Drug | Kava —Possibly Helpful
Medications in the benzodiazepine family exert calming and sedative effects and are used to treat anxiety and insomnia. Benzodiazepines are also used as muscle relaxants and anticonvulsants. They work by increasing the effects of the neurotransmitter (a chemical messenger) GABA. Benzodiazepine drugs include:
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.1 A recent study indicates that this effect can last for 3 days or more following the last glass of juice.2
Because of this risk, if you take benzodiazepines, the safest approach is to avoid grapefruit juice altogether.
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 54-year-old man hospitalized for lethargy and disorientation, these side effects were attributed to his having taken the combination of kava and alprazolam for 3 days.3
Experimental studies suggest that kava, similarly to benzodiazepines, exerts its sedative effects at binding sites in the brain called GABA receptors.4,5,6
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), passionflower ( Passiflora incarnata), sassafras ( Sassafras officinale), skullcap ( Scutellaria lateriflora) , valerian ( Valeriana officinalis), and yerba mansa ( Anemopsis californica).
Because of the potentially serious consequences, you should avoid combining these herbs with benzodiazepines or other drugs that also have sedative or depressant effects unless advised by your physician.
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 you try to stop the medication, you may experience severe insomnia or interrupted sleep. A double-blind, placebo-controlled study of 34 individuals who regularly used such medications found that melatonin at a dose of 2 mg nightly (in a controlled-release formulation) could help them discontinue the use of the drugs.7
Warning: It can be dangerous to stop using benzodiazepines if you have taken them for a while. Consult your physician before trying melatonin to help handle benzodiazepine withdrawal or before trying to stop benzodiazepine medication under any conditions.
Supplementation May Decrease Effectiveness of the Drug
The hormone pregnenolone is widely sold as a kind of "fountain of youth." However, the only direct evidence that pregnenolone supplements have any effect at all 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).9 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.
Although they are highly effective for anxiety, benzodiazepine drugs can cause unpleasant and dangerous withdrawal symptoms when they are discontinued.
A 6-week, double-blind, placebo-controlled trial of 40 people who had been taking benzodiazepines found that use of kava significantly reduced withdrawal symptoms and helped maintain control of anxiety.8
Note: This trial involved close medical supervision and very gradual tapering of benzodiazepine dosages. Do not discontinue anti-anxiety medications except on the advice of a physician, as withdrawal symptoms can be life threatening.
1. A to Z Drug Facts [book on CD-ROM]. 2nd ed. St. Louis, MO: Facts and Comparisons; 2000.
2. Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther. 2000;67:201-214.
3. Almeida JC, Grimsley EW. Coma from the health food store: interaction between kava and alprazolam. Ann Intern Med. 1996;125:940-941.
4. Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl). 1994;116:469-474.
5. Boonen G, Haberlein H. Influence of genuine kavapyrone enantiomers of the GABA-A binding site. Planta Med. 1998;64:504-506.
6. Boonen G, Ferger B, Kuschinsky K, et al. In vivo effects of the kavapyrones (+)-dihydromethysticin and (+/-)-kavain on dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid levels in striatal and cortical brain regions. Planta Med. 1998;64:507-510.
7. Garfinkel D, Zisapel N, Wainstein J, et al. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159:2456-2460.
8. Malsch U, Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology (Berl). 2001;157:277-283.
9. Meieran SE, Reus VI, Webster R, et al. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004;29:486-500.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015