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The Mechanism of Action for Valerian (Valeriana officinalis) In the Treatment of Insomnia

Summary:

  • Valerian (Valeriana officinalis) is most commonly used for the treatment of insomnia and anxiety disorders.        
  • Valerian has a mechanism of action similar to benzodiazepines; however, instead of binding to the gamma subunit like a benzodiazepine, it appears to bind to the beta subunit on the GABA-A receptor instead.  Regardless, it has the same effect on chloride movement into the neuron when the major inhibitory neurotransmitter, GABA, binds to the GABA-A receptor, thereby causing a hyperpolarized state.
  • In addition, valerian has also been shown to decrease the removal or metabolism of GABA, thereby allowing GABA to stay around longer.
  • Overall, the clinical trial evidence suggests that valerian may be useful for treating insomnia; however, there is a lack of well designed clinical trials that support this claim or provide evidence of its long-term efficacy and safety (i.e., beyond 4 to 6 weeks).

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Reviewers: 
Donald S. Nuzum, PharmD, BCACP, CDE
Last Reviewed:
October 2015

Explanation

  • Valerian (Valeriana officinalis) extract comes from a flowering plant native to Europe and Asia, but is also found in North America.1-3  It is most commonly used for the treatment of insomnia and anxiety disorders and its use dates back to the times of ancient Greece and Rome.1,2,4-7  It is also permitted or considered an acceptable option for sleep related disorders in the U.K. (Medicines Control Agency), Canada (Health Canada), Australia (Therapeutic Goods Administration), Germany (Commission E) and France.3,8,9  Valerian comes in a number of dosage forms (dried root, tincture, and fluid extract) and contains bornyl acetate, sesquiterpenoids (valerenic acid, acetoxyvalerenolic acid) and some lipophilic iridoids called valepotriates.10  While the specific ingredient responsible for the activity of valerian has not been identified, it is thought that a combination of sesquiterpenoids and valepotriates may be involved in its mechanism of action.8,10  According to the National Sleep Foundation, over 50% of American adults experience one or more symptoms of insomnia at least a few nights a week.11  In addition, self-treatment of various problems by patients (especially with the use of natural or herbal medicines) is on the rise across the world.12-14  Therefore, there is a good chance patients will consider the use of valerian to treat their sleep related problems. 

    How does valerian work to improve sleep problems or insomnia?   
    One of the oldest and most commonly prescribed treatments for insomnia are the benzodiazepines (e.g., diazepam, alprazolam).15  Simply stated, the mechanism of action of valerian is similar to that of  benzodiazepines.16,17  As it relates to insomnia, benzodiazepines are known to hasten sleep onset, decrease nocturnal awakenings, and increase total sleep time.15  Benzodiazepines do this by increasing, or potentiating, the binding of the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) to the GABA-A receptor.18  GABA-A receptors, found in the CNS, are most commonly made up of a combination of 5 protein subunits (2-alpha, 2-beta, and 1-gamma).18 In the absence of a benzodiazepine, GABA will weakly bind to the alpha subunit on the GABA-A receptor and allow the negatively charged chloride to diffuse into the neuron.  However, in the presence of a benzodiazepine, the benzodiazepine will allosterically bind to the gamma subunit on the GABA-A receptor, which causes GABA to bind to the alpha subunit more effectively than before.18  This causes a greater movement of chloride into the neuron, thereby causing the neuron to be hyperpolarized (more negatively charged inside the cell as compared to outside the neuron; from -70 mV to about -80 mV).  This now makes the neuron less responsive to stimulation by excitatory postsynaptic potentials (EPSPs), thus suppressing the CNS.  As stated before, the mechanism of action of valerian is similar to that of a benzodiazepine; however, instead of binding to the gamma subunit like a benzodiazepine, it appears to bind to the beta subunit on the GABA-A receptor.17  Regardless, it has the same effect on chloride movement into the neuron resulting in a hyperpolarized state.  In addition, valerian has also been shown to decrease the removal or metabolism of GABA thereby increasing the likelihood that GABA will bind to its receptor and elicit the effects described above.19 

                     

    Overall, the clinical trial evidence suggests that valerian may be useful for treating insomnia; however, there is a lack of well designed clinical trials that support this claim or provide evidence of its long-term efficacy and safety (i.e., beyond 4 to 6 weeks).1,2,4-7  Regardless, the side effect profile of valerian seems to be tolerable with headaches, dizziness, and GI disturbances being the most common complaints, though not significant.1-7  There is insufficient data to accurately determine if the physical dependency commonly seen with benzodiazepines or the effects of alcohol are potentiated with valerian use.  However, due to its known mechanism of action and the lack of long-term data, caution is warranted until proven otherwise.  Common doses of 300 to 400 mg of standardized extract (containing at least 0.5% essential oil) at bedtime may be seen for the treatment of insomnia.20

    References:

    1. National Center for Complementary and Alternative Medicine: National Institutes of Health.  Herbs at a glance: Valerian.  Last accessed on 2-14-2009.
    2. National Institutes of Health: Office of Dietary Supplements.   Valerian.  Bethesda, Maryland.  Version: 1/16/2008.  Last accessed on 2/14/09.
    3. Health Canada.  Natural Health Products.  Valerian.  March 30, 2007.  Last accessed on 2-14-2009.
    4. Donath F, Quispe S, Diefenbach K et al.  Critical evaluation of the effect of valerian extract on sleep structure and sleep quality.  Pharmacopsychiatry  2000;33:47-50.
    5. Stevinson C, Ernst E.  Valerian for insomnia: a systematic review of randomized clinical trials.  Sleep Med  2000;1:91-9.
    6. Ziegler G, Ploch M, Miettinen-Baumann A et al.  Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia - a randomized, double-blind, comparative clinical study.  Eur J Med Res  2002;7:480-6.
    7. Miyasaka LS, Atallah AN, Soares BG.  Valerian for anxiety disorders.  Cochrane Database Syst Rev  2006;18:CD004515.
    8. Ebadi M.  Valerian.  In:  Pharmacodynamic basis of herbal medicine. 2nd Ed.  Taylor & Francis Group. Boca Raton, FL. 2007:599-609.
    9. Therapeutic Goods Administration. Department of Health and Ageing: Australian Government.  Substances that may be used in listed medicines in Australia.  Version 12/2007.  Last accessed on 2/14/2009.
    10. Goppel M, Franz G.  Stability control of valerian ground material and extracts: a new HPLC-method for the routine quantification of valerenic acids and lignans.  Pharmazie  2004;59(6):446-52.
    11. National Sleep Foundation.  Sleep-related problems: Insomnia and sleep.  Last accessed on 2/14/2009.
    12. World Health Organization.  Traditional medicine fact sheet.  Revised last on December 2008.  Last accessed on 2/14/2009.
    13. National Center for Complementary and Alternative Medicine: National Institutes of Health.  The Use of complementary and alternative medicine in the United States: 2007 National Health Interview Survey Report.  Last accessed on 2/14/2009.
    14. Health Canada.  Natural Health Products.  Baseline natural health products survey among consumers, March 2005.  Last accessed on 2-14-2009.
    15. Hirst A, Sloan R.  Benzodiazepines and related drugs for insomnia in palliative care.  Cochrane Database Syst Rev  2002;4:CD003346.
    16. Mennini T, Bernasconi P, Bombardelli E et al.  In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzodiazepine and barbiturate receptors.  Fitoterapia  1993;64:291.
    17. Benke D, Barberis A, Kopp S et al.  GABA(A) receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts.  Neuropharmacology  2009;56:174-81.
    18. Raffa RB, Rawls SM, Beyzarov EP.  Chapter 3: Drugs Used in Disorders of the Central Nervous System and Treatment of Pain.  In: Netter's Illustrated Pharmacology.  Elsevier Inc.  Philadelphia, PA.  2005:57-67.
    19. Gabel TG.  Chapter 11: Herbal Medications, Neutraceuticals, and Anxiety and Depression.  In: Herbal Medicinals: A Clinicians Guide. Miller LG, Murray WJ eds.  Pharmaceutical Products Press. New York, NY.  1998:209-10.
    20. Inhibition of gamma-aminobutyric acid catabolism by valerenic acid derivatives.  Planta Med  1982;46:219-20.

MESH Terms & Keywords

  • Insomnia, Valerian Root, Valerian Root Herbal Supplement, Valeriana officinalis