title: Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.
abstract: Research in the area of herbal psychopharmacology has revealed a variety of promising medicines that may provide benefit in the treatment of general anxiety and specific anxiety disorders. However, a comprehensive review of plant-based anxiolytics has been absent to date. Thus, our aim was to provide a comprehensive narrative review of plant-based medicines that have clinical and/or preclinical evidence of anxiolytic activity. We present the article in two parts. In part one, we reviewed herbal medicines for which only preclinical investigations for anxiolytic activity have been performed. In this current article (part two), we review herbal medicines for which there have been both preclinical and clinical investigations of anxiolytic activity. A search of MEDLINE (PubMed), CINAHL, Scopus and the Cochrane Library databases was conducted (up to 28 October 2012) for English language papers using the search terms 'anxiety' OR 'anxiety disorder' OR 'generalized anxiety disorder' OR 'social phobia' OR 'post-traumatic stress disorder' OR 'panic disorder' OR 'agoraphobia' OR 'obsessive compulsive disorder' in combination with the search terms 'Herb*' OR 'Medicinal Plants' OR 'Botanical Medicine' OR 'Chinese herb*', in addition to individual herbal medicines. This search of the literature revealed 1,525 papers, of which 53 plants were included in the review (having at least one study using the whole plant extract). Of these plants, 21 had human clinical trial evidence (reviewed here in part two), with the other 32 having solely preclinical evidence (reviewed in part one). Support for efficacy was found for chronic use (i.e. greater than one day) of the following herbs in treating a range of anxiety disorders in human clinical trials: Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis and Echium amoenum. For several of the plants studied, conclusions need to be tempered due to methodological issues such as small sample sizes, brief intervention durations and non-replication. Current evidence does not support Hypericum perforatum or Valeriana spp. for any anxiety disorder. Acute anxiolytic activity was found for Centella asiatica, Salvia spp., Melissa officinalis, Passiflora incarnata and Citrus aurantium. Bacopa monnieri has shown anxiolytic effects in people with cognitive decline. The therapeutic application of psychotropic plant-based treatments for anxiety disorders is also discussed, specifically Psychotria viridis and Banisteriopsis caarti (ayahuasca), Psilocybe spp. and cannabidiol-enriched (low tetrahydrocannabinol (Δ(9)-THC)) Cannabis spp.
authors: Department of Psychiatry and The Melbourne Clinic, Faculty of Medicine, University of Melbourne, 2 Salisbury Street, Richmond, VIC 3121, Australia. jsarris@unimelb.edu.au
authors: Jerome
authors: J
authors: Sarris
authors: Erica
authors: E
authors: McIntyre
authors: David A
authors: DA
authors: Camfield
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D014151:Anti-Anxiety Agents; D010936:Plant Extracts
references: Sci Am. 2010 Dec;303(6):76-9
references: 21141361
references: Planta Med. 2011 Jan;77(2):107-10
references: 20814850
references: Phytomedicine. 2009 May;16(5):485-93
references: 18786819
references: Rev Bras Anestesiol. 2011 Nov-Dec;61(6):702-12
references: 22063371
references: J Nat Prod. 2006 Jan;69(1):59-61
references: 16441069
references: Phytother Res. 2011 Jun;25(6):838-43
references: 21089181
references: Indian J Exp Biol. 2010 Mar;48(3):306-13
references: 21046986
references: Planta Med. 1995 Jun;61(3):213-6
references: 7617761
references: Fitoterapia. 2000 Feb;71(1):19-24
references: 11449465
references: Med J Nutrition Metab. 2011 Dec;4(3):211-218
references: 22207903
references: Phytomedicine. 1998 May;5(3):219-25
references: 23195845
references: Psychosom Med. 2004 Jul-Aug;66(4):607-13
references: 15272110
references: Pharmacol Biochem Behav. 2003 Jun;75(3):547-55
references: 12895672
references: Pharmacol Biochem Behav. 2000 Nov;67(3):489-95
references: 11164077
references: Phytother Res. 2011 Jun;25(6):789-95
references: 21077264
references: Phytomedicine. 2005 Jan;12(1-2):10-6
references: 15693702
references: Psychopharmacology (Berl). 2011 Dec;218(4):649-65
references: 21674151
references: Neuropsychopharmacology. 2011 May;36(6):1219-26
references: 21307846
references: Psychopharmacology (Berl). 2009 Aug;205(3):399-407
references: 19430766
references: Pharmacol Ther. 2004 May;102(2):111-29
references: 15163593
references: Phytomedicine. 2005 Apr;12(4):305-17
references: 15898709
references: J Ethnopharmacol. 2010 Jan 8;127(1):70-6
references: 19799980
references: Biochem Pharmacol. 2002 Nov 1;64(9):1415-24
references: 12392823
references: Psychopharmacology (Berl). 1994 Dec;116(4):469-74
references: 7701051
references: Phytother Res. 2007 May;21(5):481-4
references: 17295387
references: Aust N Z J Psychiatry. 2011 Jan;45(1):27-35
references: 21073405
references: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1458-63
references: 19665511
references: Anesth Analg. 2008 Jun;106(6):1728-32
references: 18499602
references: Pharmacol Biochem Behav. 1997 Dec;58(4):887-91
references: 9408191
references: Phytomedicine. 2002 Jan;9(1):41-7
references: 11924763
references: Prog Neuropsychopharmacol Biol Psychiatry. 1997 May;21(4):697-706
references: 9194150
references: Lancet. 2007 Jul 28;370(9584):319-28
references: 17662880
references: Can J Physiol Pharmacol. 2007 Sep;85(9):933-42
references: 18066140
references: Fitoterapia. 2001 Aug;72(6):698-702
references: 11543974
references: J Psychopharmacol. 2001 Mar;15(1):47-54
references: 11277608
references: Phytother Res. 2011 Jun;25(6):858-62
references: 21105176
references: Planta Med. 1981 Jan;41(1):21-8
references: 7232547
references: Nat Rev Neurosci. 2010 Sep;11(9):642-51
references: 20717121
references: J Clin Psychopharmacol. 2005 Feb;25(1):51-8
references: 15643100
references: Int Clin Psychopharmacol. 2005 Nov;20(6):299-304
references: 16192837
references: J Clin Anesth. 2004 Jun;16(4):305-11
references: 15261327
references: Acta Psychiatr Scand. 1977 Feb;55(2):127-41
references: 842386
references: Neuropharmacology. 2011 Sep;61(3):364-81
references: 21256140
references: J Altern Complement Med. 2012 Jul;18(7):647-52
references: 22747190
references: Nepal Med Coll J. 2010 Mar;12(1):8-11
references: 20677602
references: AANA J. 2007 Oct;75(5):333-7
references: 17966676
references: Psychopharmacology (Berl). 2008 Aug;199(2):223-30
references: 18446323
references: Phytomedicine. 2003 Nov;10(8):640-9
references: 14692724
references: J Ethnopharmacol. 2007 May 4;111(2):308-14
references: 17196350
references: Hum Psychopharmacol. 2012 May;27(3):262-9
references: 22311378
references: Pharmacol Biochem Behav. 1994 Jan;47(1):1-4
references: 7906886
references: J Ethnopharmacol. 2011 Feb 16;133(3):1085-90
references: 21111038
references: Phytomedicine. 2000 Dec;7(6):463-9
references: 11194174
references: J Nerv Ment Dis. 1996 Feb;184(2):86-94
references: 8596116
references: J Ethnopharmacol. 2001 Dec;78(2-3):165-70
references: 11694362
references: Altern Ther Health Med. 2003 Mar-Apr;9(2):74-8
references: 12652886
references: J Anesth. 2012 Feb;26(1):39-44
references: 22048283
references: Biosci Biotechnol Biochem. 2009 Aug;73(8):1866-8
references: 19661714
references: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27
references: 19028540
references: Pharmacol Res. 2009 Jul;60(1):68-73
references: 19427589
references: Biochem Pharmacol. 2000 Jun 1;59(11):1387-94
references: 10751547
references: J Psychopharmacol. 2011 Nov;25(11):1434-52
references: 20855349
references: Phytomedicine. 2010 May;17(6):397-403
references: 20171069
references: Fitoterapia. 2010 Sep;81(6):453-61
references: 20093169
references: Int Pharmacopsychiatry. 1973;8(3):129-44
references: 4140164
references: Phytomedicine. 2010 Jun;17(7):481-93
references: 20378318
references: J Altern Complement Med. 2008 Jul;14(6):707-13
references: 18611150
references: FEBS Lett. 2004 Nov 19;577(3):563-9
references: 15556647
references: Indian J Psychiatry. 2000 Jul;42(3):295-301
references: 21407960
references: Toxicol Sci. 2004 May;79(1):106-11
references: 14737001
references: Eur J Pharmacol. 1994 Aug 1;260(2-3):233-5
references: 7988648
references: Behav Brain Res. 2011 Aug 1;221(1):75-82
references: 21377498
references: Phytomedicine. 2007 Jan;14(1):70-82
references: 17188482
references: Phytomedicine. 2006 Nov;13(9-10):668-76
references: 16488124
references: J Clin Psychopharmacol. 2009 Aug;29(4):378-82
references: 19593179
references: Planta Med. 2007 Jul;73(8):713-7
references: 17562493
references: Neuroreport. 1998 Dec 1;9(17):3897-902
references: 9875725
references: J Ethnopharmacol. 2006 Aug 11;107(1):53-8
references: 16530995
references: J Ethnopharmacol. 2011 Mar 8;134(1):55-61
references: 21129470
references: Pharmazie. 2009 Jan;64(1):63-4
references: 19216234
references: Planta Med. 2008 Dec;74(15):1769-73
references: 19006051
references: J Psychiatr Res. 2007 Sep;41(6):472-80
references: 16808927
references: Phytother Res. 2001 Mar;15(2):162-4
references: 11268119
references: Phytother Res. 2001 Mar;15(2):142-7
references: 11268115
references: J Ethnopharmacol. 1997 Jun;57(1):11-20
references: 9234160
references: J Ethnopharmacol. 2010 Mar 2;128(1):148-53
references: 20051259
references: J Psychopharmacol. 1993 Jan;7(1 Suppl):82-8
references: 22290374
references: J Altern Complement Med. 2002 Jun;8(3):283-91
references: 12165186
references: J Pharm Biomed Anal. 2012 Apr 7;63:120-7
references: 22342658
references: Indian J Psychiatry. 2006 Oct;48(4):238-42
references: 20703343
references: Psychiatry Clin Neurosci. 2002 Dec;56(6):617-20
references: 12485303
references: Am J Chin Med. 2003;31(1):47-59
references: 12723754
references: Psychopharmacology (Berl). 2001 Aug;156(4):481-4
references: 11498727
references: Evid Based Complement Alternat Med. 2012;2012:691258
references: 22028733
references: Behav Brain Res. 2010 Mar 5;207(2):387-93
references: 19857526
references: Phytother Res. 2002 Nov;16(7):650-4
references: 12410546
references: J Ethnopharmacol. 2007 Jul 25;112(3):507-13
references: 17532158
references: Am J Psychiatry. 1997 Jul;154(7):1037-8
references: 9210762
references: J Nat Med. 2009 Jan;63(1):69-74
references: 18663561
references: Planta Med. 2012 Sep;78(14):1529-35
references: 22828921
references: Wien Med Wochenschr. 2007;157(13-14):356-61
references: 17704987
references: Neuroscience. 1997 Nov;81(2):345-51
references: 9300426
references: Phytother Res. 2007 Aug;21(8):703-16
references: 17562566
references: Indian J Med Res. 1991 Aug;94:312-5
references: 1660034
references: Phytomedicine. 1999 Jul;6(3):147-55
references: 10439478
references: Addict Biol. 2002 Oct;7(4):357-64
references: 14578010
references: Planta Med. 1997 Dec;63(6):548-9
references: 9434608
references: J Clin Psychiatry. 2006 Nov;67(11):1735-40
references: 17196053
references: Biol Psychiatry. 2008 Mar 15;63(6):569-76
references: 17884017
references: Recent Pat CNS Drug Discov. 2012 Apr 1;7(1):25-40
references: 22280339
references: J Altern Complement Med. 2009 Aug;15(8):827-36
references: 19614563
references: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004515
references: 17054208
references: J Ethnopharmacol. 2011 Sep 1;137(1):724-9
references: 21742023
references: J Med Food. 2008 Jun;11(2):282-8
references: 18598170
references: Zhong Yao Cai. 2005 Jun;28(6):492-6
references: 16209267
references: Planta Med. 1998 Oct;64(7):603-6
references: 9810264
references: J Clin Psychiatry. 2000 Aug;61(8):575-8
references: 10982200
references: Neurochem Res. 2009 Nov;34(11):1955-61
references: 19760174
references: J Pharmacol Exp Ther. 2003 Jul;306(1):73-83
references: 12660312
references: Nat Prod Commun. 2012 Apr;7(4):471-4
references: 22574444
references: Eur Neuropsychopharmacol. 2011 Dec;21(12):841-60
references: 21601431
references: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1513-6
references: 19737592
references: Pharmacopsychiatry. 1998 Sep;31(5):187-92
references: 9832350
references: Br J Pharmacol. 2010 Feb 1;159(3):659-68
references: 20105177
references: Prog Neuropsychopharmacol Biol Psychiatry. 2010 Mar 17;34(2):362-5
references: 20035818
references: Br J Pharmacol. 2009 Jan;156(1):181-8
references: 19133999
references: Phytother Res. 2013 Jan;27(1):54-61
references: 22451347
references: Planta Med. 2002 Sep;68(9):784-9
references: 12357387
references: J Clin Psychopharmacol. 2000 Dec;20(6):680-4
references: 11106141
references: Phytother Res. 2009 Aug;23(8):1075-81
references: 19165747
references: Nutr J. 2010 Oct 07;9:42
references: 20929532
references: Psychopharmacology (Berl). 1985;85(4):486-7
references: 2862653
references: Phytother Res. 2006 Dec;20(12):1023-35
references: 16909441
references: Life Sci. 2002 Apr 19;70(22):2581-97
references: 12269386
references: J Ethnopharmacol. 2005 Oct 3;101(1-3):100-3
references: 15994042
references: Arch Gen Psychiatry. 2011 Jan;68(1):71-8
references: 20819978
references: J Altern Complement Med. 2008 Mar;14(2):175-80
references: 18307390
references: Cochrane Database Syst Rev. 2003;(1):CD003383
references: 12535473
references: Farmakol Toksikol. 1987 Nov-Dec;50(6):33-7
references: 2893744
references: Nepal Med Coll J. 2007 Mar;9(1):36-9
references: 17593676
references: Phytomedicine. 2006 Jan;13(1-2):23-8
references: 16360929
references: Fitoterapia. 2004 Jul;75(5):457-64
references: 15261383
references: Neuropharmacology. 1995 Sep;34(9):1133-8
references: 8532183
references: J Nat Prod. 2003 Oct;66(10):1333-7
references: 14575433
references: Pharmacol Biochem Behav. 2002 Jul;72(4):953-64
references: 12062586
references: Fitoterapia. 2000 Aug;71 Suppl 1:S117-23
references: 10930722
references: CNS Drugs. 2002;16(11):731-43
references: 12383029
references: Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jun;26(5):855-60
references: 12369257
references: Phytother Res. 2010 Nov;24(11):1605-13
references: 21031616
references: BMJ. 2002 Nov 23;325(7374):1195-8
references: 12446533
references: Prog Neuropsychopharmacol Biol Psychiatry. 1998 Oct;22(7):1105-20
references: 9829291
references: Phytother Res. 2012 Apr;26(4):522-7
references: 21915930
references: J Pharm Pharmacol. 2001 Oct;53(10):1347-56
references: 11697542
references: J Psychopharmacol. 2011 Aug;25(8):1088-100
references: 20937617
references: Psychopharmacology (Berl). 1994 Nov;116(3):385-7
references: 7892432
references: J Clin Pharm Ther. 2001 Oct;26(5):363-7
references: 11679026
references: Neuropsychopharmacology. 2006 Apr;31(4):845-52
references: 16205785
references: CNS Drugs. 2013 Mar;27(3):207-19
references: 23436255
references: Physiol Behav. 2005 Jan 17;83(5):699-709
references: 15639154
references: Life Sci. 2002 Sep 6;71(16):1939-49
references: 12175708
references: Fitoterapia. 2001 Dec;72(8):922-6
references: 11731118
references: Neuropharmacology. 2009 Jan;56(1):174-81
references: 18602406
references: Br J Clin Pharmacol. 2011 Mar;71(3):445-8
references: 21284704
references: Neurochem Res. 2011 Feb;36(2):250-7
references: 21076869
references: Phytother Res. 2007 Jan;21(1):37-43
references: 17072830