Valerian

Valerian/Drug Interactions:

  • GeneralGeneral: In review research, herb-drug interactions with valerian have reportedly been of limited clinical significance and minor risk to patients under conventional pharmacotherapy (113). Regardless, vigilant monitoring for potential interactions was nonetheless suggested by investigators.
  • AcetaminophenAcetaminophen: In an in vitro study of human liver microsomes, methanolic extracts of valerian, as well as valerian-hops extracts, caused reductions in the rate of formation of acetaminophen glucuronides (114).
  • AlcoholAlcohol: Concomitant use of valerian and ethanol should be avoided due to a theoretical risk of potentiation of central nervous system (CNS) depressant effects, and a report of mental status changes in an individual using both (115). However, there is controversy in this area (60; 116; 117).
  • AnalgesicsAnalgesics: In human research, valerian demonstrated self-reported analgesic effects, including reduced pain severity and duration, decreased occurrence of menstruation-related syncope, and diminished use of concomitant pain relievers (1).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on a review, valerian should be discontinued up to two weeks before elective surgery, due to a risk for increased bleeding (62).
  • AnticonvulsantsAnticonvulsants: It has been suggested anecdotally that valerian products may interact with antiseizure medications. However, human data are lacking.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Based on animal and human research, valerian may increase the amount of the effects and side effects, such as drowsiness, caused by antidepressants, although this is an area of controversy (57).
  • Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs)Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs): Based on animal and human research, valerian may increase the amount of the effects and side effects, such as drowsiness, caused by antidepressants, although this is an area of controversy (57). According to electroencephalography (EEG) assessment in healthy humans, a mixed-ingredient commercial product (Neurapas? balance) containing valerian, passionflower, and St. John's wort, reduced selective brain frequencies (alpha1, alpha2, beta1) in areas similar to those typically seen with conventional antidepressant medications, such as fluoxetine (59).
  • AntidiarrhealsAntidiarrheals: A brief episode of confusion was reported in one patient using valerian with loperamide (Imodium?) and St. John's wort (Hypericum perforatum L.) (118).
  • AntihistaminesAntihistamines: In theory, valerian may increase the side effects, including the amount of drowsiness, caused by antihistamines such as diphenhydramine (Benadryl?).
  • AntihypertensivesAntihypertensives: In clinical research, valerian caused a significant decrease in systolic blood pressure responsivity; however, a significant reduction in diastolic blood pressure was lacking (24). The heart rate reaction to laboratory-induced mental stress also declined in the valerian treatment group. In animal research, orally administered Valeriana officinalis L. root ethanolic and aqueous extracts demonstrated significant anticoronaryspastic and antihypertensive effects against pitressin-induced coronary spasm and pressor response, similar to those exhibited by nifedipine (5).
  • AntineoplasticsAntineoplastics: In cellular research, valerian root-derived acylated iridoids weakly inhibited the growth of various procarcinogenic human cell lines (119). Valepotriates (including those from Valeriana jatamansi) have been found to exert cytotoxic effects on hepatoma cell lines and inhibit DNA and protein synthesis; didrovaltrate prolonged survival in mice bearing ascitic tumors (14; 15; 120). In a review, valerian was identified as an agent that may potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors (22).
  • AntispasmodicsAntispasmodics: Based on secondary sources, valerian may possess antispasmodic properties.
  • AnxiolyticsAnxiolytics: In clinical research, valerian reduced symptoms of anxiety (8; 57; 50; 66; 65). Theoretically, valerian may have additive effects when taken with other anxiolytics
  • Aromatase inhibitorsAromatase inhibitors: Valepotriates have been found to exert cytotoxic effects on hepatoma cell lines and inhibit DNA and protein synthesis; didrovaltrate prolonged survival in mice bearing ascitic tumors (14; 15). In a review, valerian was identified as an agent that may potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors (22).
  • BarbituratesBarbiturates: In animal and human research, valerian increased the amount of drowsiness caused by barbiturates such as phenobarbital, although this is an area of controversy. Caution is advised while driving or operating machinery.
  • BenzodiazepinesBenzodiazepines: In animal and human research, valerian increased the amount of drowsiness caused by benzodiazepines such as lorazepam (Ativan?) or diazepam (Valium?), although this is an area of controversy (50). Caution is advised while driving or operating machinery.
  • Beta-blockersBeta-blockers: In a randomized trial, a combination of 100mg of valerian extract and 20mg of propranolol was found to impair performance on a written concentration test more than valerian alone (which was reported to slightly improve performance) (69). However, comparison to propranolol alone was lacking, so it is unclear if the effects were due to the beta-blocker only, or to the combination with valerian. The study itself was methodologically weak, raising questions about the validity of the results.
  • BronchodilatorsBronchodilators: In anesthetized guinea pigs, orally administered Valeriana officinalis L. root ethanolic and aqueous extracts (50, 100, and 200mg/kg) demonstrated significant antibronchospastic properties against histamine-induced and Oleaceae antigen challenge-induced bronchospasm (5).
  • CaffeineCaffeine: In clinical research, a fixed valerian-hops extract combination (Ze 91019) was found to antagonize caffeine (121).
  • Cardiovascular agentsCardiovascular agents: Although extensive study is lacking, valerian may cause adverse effects on the heart, especially if high doses are used for long periods of time. Tachycardia and high output cardiac failure were reported following withdrawal of valerian in one patient with a history of coronary artery disease who had been self-medicating with high doses "for many years" (23). Large doses have reportedly caused bradycardia (anecdotally). In human research, valerian acupressure demonstrated an immediate relaxation response in severely ill intensive care unit (ICU) patients, as per heart rate variability data (122).
  • CodeineCodeine: In animal and human research, valerian increased the amount of drowsiness caused by codeine, although this is an area of controversy. Caution is advised while driving or operating machinery.
  • Cytochrome P450- modifying agentsCytochrome P450- modifying agents: In in vitro research, valerian exhibited effects on CYP450 enzymes (28; 29; 30). However, in human research, mixed results were reported. In one study, valerian lacked statistically significant evidence of cytochrome P450 activity modulation, specifically for CYP1A2, CYP2D6, CYP 2E1, or CYP3A4/5 (32). In another clinical study, multiple nighttime doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and a lack of effect on CYP2D6 activity in healthy volunteers (31).
  • Dermatologic agentsDermatologic agents: In a well-conducted clinical trial, one incident of valerian-related rash was reported (27).
  • Diphenhydramine (Benadryl?)Diphenhydramine (Benadryl?): In theory, valerian may increase the side effects, including the amount of drowsiness, caused by antihistamines such as diphenhydramine (Benadryl?).
  • Disulfiram (Antabuse?)Disulfiram (Antabuse?): Valerian tinctures often contain high alcohol content (15-90%), and may theoretically elicit a disulfiram reaction.
  • FlunitrazepamFlunitrazepam: In laboratory research, some commercial valerian extracts demonstrated interactions with [3H]flunitrazepam and [3H]MK-801 binding to rat synaptic membranes (6). There was considerable fluctuation among the different valerian extracts.
  • Gastrointestinal agentsGastrointestinal agents: In human research, incidences of stomach upset or pain, nausea, vomiting, diarrhea, epigastralgia, and pyrosis have been reported (25; 26). A brief episode of confusion was reported in one patient using valerian with loperamide (Imodium?) and St. John's wort (Hypericum perforatum L.) (118).
  • HepatotoxinsHepatotoxins: Because valerian poses a theoretical risk of hepatotoxicity based on human reports (16), it may increase the risk of liver damage when taken with hepatotoxic agents.
  • Hormonal agentsHormonal agents: In in vitro research, methanolic extracts of valerian, as well as valerian-hops extracts caused reductions in the rate of formation of testosterone and estradiol glucuronides (114).
  • Immunomodulatory agentsImmunomodulatory agents: According to a review by the U.S. National Toxicology Program, ethyl acetate extracts of Valeriana officinalis reportedly inhibited NF-?B activity in HeLa cells (21).
  • Loperamide (Imodium?)Loperamide (Imodium?): A brief episode of acute delirium was reported in one patient during concomitant use of loperamide and valerian (118). However, causality could not be established, as the patient was also taking St. John's wort (Hypericum perforatum). The condition resolved rapidly with discontinuation of treatment.
  • LorazepamLorazepam: In a case report, combined intake of valerian (Valeriana officinalis L.) and passionflower (Passiflora incarnata L.) reportedly caused shaking of the hands, throbbing, muscular fatigue, and dizziness when taken concomitantly with lorazepam (50). An additive or synergistic effect among active ingredients has been purported.
  • LoreclezoleLoreclezole: In in vitro research, Khom et al. noted that valerenic acid may potentiate and inhibit gamma-aminobutyric-acid A (GABA[A]) receptors (54). The authors reported that valerenic acid was identified as a subunit specific allosteric modulator of GABA(A) receptors that is likely to interact with the loreclezole-binding pocket.
  • Metronidazole (Flagyl?)Metronidazole (Flagyl?): A disulfiram reaction may occur when metronidazole and alcohol are used concomitantly. Due to the high alcohol content in some valerian tinctures, this combination may theoretically cause such a reaction.
  • Mood stabilizersMood stabilizers: Based on secondary sources, valerian may interact with mood stabilizers.
  • MorphineMorphine: In an in vitro study of human liver microsomes, methanolic extracts of valerian, as well as valerian-hops extracts caused reductions in the rate of formation of morphine glucuronides (114).
  • Neurologic agentsNeurologic agents: Animal and human research has shown potential CNS actions of valerian (33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 27; 51; 52; 25; 53). According to in vitro research, valerenic acid may potentiate and inhibit GABA(A) receptors (54; 55; 56). In human dopaminergic neuroblastoma SH-SY5Y cells, Valeriana jatamansi-derived iridoids demonstrated a moderate neuroprotective effect against 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity (123; 124)
  • PentobarbitalPentobarbital: In an animal study examining the effects of odorant inhalation on the sleep-wake states in rats, valerian inhalation significantly prolonged pentobarbital-induced sleeping time and total sleep time and caused a significant shortening in sleep latency (55).
  • SedativesSedatives: Based on animal and human research, valerian, either alone or in combination with other herbs such as hops or kava, may theoretically potentiate the effects of CNS depressant drugs (125; 87; 7; 126; 127; 128; 55; 129; 130; 102; 45; 47; 84; 25; 131; 132; 79; 122), although studies in humans taking CNS-active medications concurrently with valerian have lacked demonstration of an increased rate of adverse effects (117; 94; 95). Short-term impairments in vigilance and concentration, as well as mild fatigue, have been reported in trials; residual sedative effects appear to be less pronounced than those associated with benzodiazepines (95; 69; 94; 70).
  • TamoxifenTamoxifen: In a review, valerian was identified as an agent that may potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors (22).
  • VasodilatorsVasodilators: In clinical research, valerian caused a significant decrease in systolic blood pressure responsivity; however, a significant reduction in diastolic blood pressure was lacking (24). In animal research, valerian demonstrated significant anticoronaryspastic and antihypertensive effects against pitressin-induced coronary spasm and pressor response, similar to those exhibited by nifedipine (5).
  • VasopressinVasopressin: In rabbits given vasopressin, valepotriates reduced the incidence of cardiac arrhythmias (133). The clinical relevance in humans is unclear.

    • Valerian/Herb/Supplement Interactions:

  • AnalgesicsAnalgesics: In human research, valerian demonstrated self-reported analgesic effects, including reduced pain severity and duration, decrease occurrence of menstruation-related syncope, and diminished used of concomitant pain relievers (1).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Based on a review, valerian should be discontinued up to two weeks before elective surgery, due to a risk for increased bleeding (62).
  • AnticonvulsantsAnticonvulsants: It has been suggested anecdotally that valerian products may interact with antiseizure medications. However, human data are lacking.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Based on animal and human research, valerian may increase the effects and side effects, such as drowsiness, caused by antidepressants, although this is an area of controversy (57). Valerian may have additive effects when taken with SSRIs.
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Based on animal and human research, valerian may increase the amount of drowsiness caused by antidepressants, although this is an area of controversy (57). Valerian may have additive effects when taken with SSRIs. According to EEG assessment in healthy humans, a mixed-ingredient commercial product (Neurapas? balance) containing valerian, passionflower, and St. John's wort reduced selective brain frequencies (alpha1, alpha2, beta1) in areas similar to those typically seen with conventional antidepressant medications, such as fluoxetine (59).
  • AntidiarrhealsAntidiarrheals: A brief episode of confusion was reported in one patient using valerian with loperamide (Imodium?) and St. John's wort (Hypericum perforatum L.) (118).
  • AntihistaminesAntihistamines: In theory, valerian may increase the side effects, including the amount of drowsiness, caused by antihistamines such as diphenhydramine (Benadryl?).
  • AntineoplasticsAntineoplastics: In cellular research, valerian root-derived acylated iridoids weakly inhibited the growth of various procarcinogenic human cell lines (119). Valepotriates (including those from Valeriana jatamansi) have been found to exert cytotoxic effects on hepatoma cell lines and inhibit DNA and protein synthesis; didrovaltrate prolonged survival in mice bearing ascitic tumors (14; 15; 120). In a review, valerian was identified as an agent that may potentially increase the risk of breast cancer or interact with tamoxifen or aromatase inhibitors (22).
  • AntispasmodicsAntispasmodics: Based on secondary sources, valerian may possess antispasmodic properties.
  • AnxiolyticsAnxiolytics: Based on human research, valerian may have additive effects when taken with other anxiolytics (8; 57; 50).
  • BronchodilatorsBronchodilators: In anesthetized guinea pigs, orally administered Valeriana officinalis L. root ethanolic and aqueous extracts (50, 100, and 200mg/kg) demonstrated significant antibronchospastic properties against histamine-induced and Oleaceae antigen challenge-induced bronchospasm (5).
  • CaffeineCaffeine: In clinical research, a fixed valerian-hops extract combination (Ze 91019) was found to antagonize caffeine (121).
  • Cardiovascular agentsCardiovascular agents: Although extensive study is lacking, valerian may cause adverse effects on the heart, especially if high doses are used for long periods of time. Tachycardia and high output cardiac failure were reported following withdrawal of valerian in one patient with a history of coronary artery disease who had been self-medicating with high doses "for many years" (23). Large doses have reportedly caused bradycardia (anecdotally). In human research, valerian acupressure demonstrated an immediate relaxation response in severely ICU patients, as per heart rate variability data (122).
  • Cytochrome P450-modifying agentsCytochrome P450-modifying agents: In in vitro research, valerian has exhibited effects on CYP450 enzymes (28; 29; 30). However, in human research, mixed results have been reported. In one study, valerian lacked statistically significant evidence of cytochrome P450 activity modulation, specifically for CYP1A2, CYP2D6, CYP 2E1, or CYP3A4/5 (32). In another clinical study, multiple nighttime doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and a lack of effect on CYP2D6 activity in healthy volunteers (31).
  • Dermatologic agentsDermatologic agents: In a well-conducted clinical trial, one incident of valerian-related rash was reported (27).
  • Gastrointestinal agentsGastrointestinal agents: In human research, incidences of stomach upset or pain, nausea, vomiting, diarrhea, epigastralgia, and pyrosis have been reported (25; 26). A brief episode of confusion was reported in one patient using valerian with loperamide (Imodium?) and St. John's wort (Hypericum perforatum L.) (118).
  • HepatotoxinsHepatotoxins: Because valerian poses a theoretical risk of hepatotoxicity, it may increase the risk of liver damage when taken with hepatotoxic agents.
  • Hops (Humulus lupulus)Hops (Humulus lupulus): In in vitro research, valerian and hops combination preparations have shown effects on human liver microsomes (114). In human research, combination valerian and hops has demonstrated sleep-inducing effects (126; 87; 7; 131; 132).
  • Hormonal agentsHormonal agents: In an in vitro study of human liver microsomes, methanolic extracts of valerian, as well as valerian-hops extracts caused reductions in the rate of formation of testosterone and estradiol glucuronides (114). In a pilot study, a morning-evening menopause formula combination formula, containing valerian and other herbs (the morning capsule contained Panax ginseng, black cohosh, soy, and green tea extracts; the evening capsule contained black cohosh, soy, kava, hops, and valerian extracts) significantly reduced menopausal symptoms, including the number of hot flashes (134).
  • HypotensivesHypotensives: In clinical research, valerian caused a significant decrease in systolic blood pressure responsivity; however, a significant reduction in diastolic blood pressure was lacking (24). In animal research, valerian demonstrated significant anticoronaryspastic and antihypertensive effects against pitressin-induced coronary spasm and pressor response, similar to those exhibited by nifedipine (5).
  • Immunomodulatory agentsImmunomodulatory agents: According to a review by the U.S. National Toxicology Program, ethyl acetate extracts of V. officinalis reportedly inhibited NF-?B activity in HeLa cells (21).
  • Kava (Piper methysticum)Kava (Piper methysticum): In a telephone survey, one woman reported nausea, diaphoresis, muscle cramping, weakness, and elevated pulse and blood pressure after a single dose of a combination of St. John's wort, kava, and valerian (135). In human research, the coadministration of valerian (LI-156) and kava (LI-15) improved various domains of stress-induced insomnia, including time to sleep, hours of sleep, and mood upon waking (79),
  • Lemon balmLemon balm: Lemon balm (Melissa officinalis) and valerian (Valeriana officinalis) combination formulations have been used as mild sedatives, anxiolytics, and hypnotics (8). Therefore, valerian may have additive effects when taken concomitantly with lemon balm.
  • MelatoninMelatonin: Based on in vitro research, valerian may have interactions with melatonin (56). Theoretically, valerian may increase the side effects or the amount of drowsiness caused by melatonin. Caution is advised while driving or operating machinery.
  • Mood stabilizersMood stabilizers: Based on secondary sources, valerian may interact with mood stabilizers.
  • Motherwort (Leonurus cardiaca)Motherwort (Leonurus cardiaca): In a mouse model, maximum prolongation of barbiturate-induced sleep was achieved when "no-effect" doses of Leonurus cardiaca and powdered valerian root suspensions were administered concurrently (136; 21). The authors noted that this demonstrates mutual potentiation of specific activity of these extract powders and excellent bioavailability of their active constituents.
  • Neurologic agentsNeurologic agents: Animal and human research has shown potential CNS actions of valerian (33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 27; 51; 52; 25; 53). In human dopaminergic neuroblastoma SH-SY5Y cells, Valeriana jatamansi-derived iridoids demonstrated a moderate neuroprotective effect against 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity (123; 124).
  • Passionflower (Passiflora incarnata L.)Passionflower (Passiflora incarnata L.): An additive or synergistic effect among active ingredients in valerian (Valeriana officinalis L.), passionflower (Passiflora incarnata L.), and lorazepam has been purported, based on findings from a human case report (50). Also in humans, combination valerian, passionflower, and St. John's wort (Neurapas? balance) has been shown to alter brain wave activity similarly to conventional antidepressant medications (59). The potentiation of benzodiazepine-mediated GABA receptor inhibition has been proposed as a possible mechanism of action (50).
  • SedativesSedatives: Based on animal and human research, valerian, either alone or in combination with other herbs such as hops or kava, may theoretically potentiate the effects of CNS depressant drugs (125; 87; 7; 126; 127; 128; 55; 129; 130; 102; 45; 47; 84; 25; 131; 132; 79; 122), although studies in humans taking CNS-active medications concurrently with valerian have lacked demonstration of an increased rate of adverse effects (117; 94; 95). Short-term impairments in vigilance and concentration, as well as mild fatigue, have been reported in trials; residual sedative effects appear to be less pronounced than those associated with benzodiazepines (95; 69; 94; 70).
  • St. John's wort (Hypericum perforatum)St. John's wort (Hypericum perforatum): In human research, combination valerian, passionflower, and St. John's wort (Neurapas? balance) has been shown to alter brain wave activity similarly to conventional antidepressant medications (59). Delirium and agitation were reported in one patient taking valerian, St. John's wort, and loperamide (Imodium?) (118). The condition resolved rapidly with discontinuation of treatment. In a telephone survey, one woman reported nausea, diaphoresis, muscle cramping, weakness, and elevated pulse and blood pressure after a single dose of combination St. John's wort, kava, and valerian (135).
  • VasodilatorsVasodilators: In clinical research, valerian caused a significant decrease in systolic blood pressure responsivity; however, a significant reduction in diastolic blood pressure was lacking (24). In animal research, valerian demonstrated significant anticoronaryspastic and antihypertensive effects against pitressin-induced coronary spasm and pressor response, similar to those exhibited by nifedipine (5).

    • Valerian/Food Interactions:

  • CaffeineCaffeine: In clinical research, a fixed valerian-hops extract combination (Ze 91019) was found to antagonize caffeine (121).

    • Valerian/Lab Interactions:

  • Blood pressureBlood pressure: In clinical research, valerian caused a significant decrease in systolic blood pressure responsivity; however, a significant reduction in diastolic blood pressure was lacking (24).
  • Electroconvulsive therapyElectroconvulsive therapy: Based on a review, valerian may have interactions with electroconvulsive therapy (137).
  • Electroencephalography (EEG)Electroencephalography (EEG): Animal research has shown potential CNS actions of valerian (33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49). According to EEG assessment in healthy humans, a mixed-ingredient commercial product (Neurapas? balance) containing valerian, passionflower, and St. John's wort reduced selective brain frequencies (alpha1, alpha2, beta1) in areas similar to those typically seen with conventional antidepressant medications, such as fluoxetine (59).
  • Heart rateHeart rate: The heart rate reaction to laboratory-induced mental stress declined in the valerian treatment group (24). In severely ill ICU patients, valerian acupressure induced an immediate relaxation response, as demonstrated by heart rate variability data (122).
  • Hormone panelHormone panel: In an in vitro study of human liver microsomes, methanolic extracts of valerian, as well as valerian-hops extracts, caused reductions in the rate of formation of testosterone and estradiol glucuronides (114).
  • Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), lactate dehydrogenase (LDH), alkaline phosphatase, bilirubin)Transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), lactate dehydrogenase (LDH), alkaline phosphatase, bilirubin): Hepatotoxicity has been associated with some multiherb preparations that include valerian (16). The contribution of valerian itself cannot be determined from these reports, due to the potential hepatotoxicity of other ingredients (e.g., skullcap), as well as the possibility of adulteration with unlisted herbs (such as the known hepatotoxic herb germander, which is often mistakenly harvested as skullcap). Furthermore, reports on 50 cases of overdose with a combination preparation containing hyoscine, cyproheptadine, and valerian indicated the expected symptoms of cyproheptadine and hyoscine toxicity, but signs of hepatotoxicity were lacking in the short or long term (17; 18). In a case study, three-times-weekly consumption of a valerian-containing tea (5cc of valerian root extract) for three weeks with concomitant intake of 10 vaimane tablets (containing 125mg of dry valerian extract each) resulted in the apparent manifestation of acute hepatitis (100). Laboratory evidence revealed elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in spite of normal physical examination. Moreover, mild fibrosis and liver inflammation were also seen upon liver biopsy.