The Efficacy and Safety of Add-on Ginko TD (Ginkgo Biloba) Treatment for PTSD: Results of a 12-Week Double-Blind Placebo-Controlled Study


Objective: Exposure to traumatic stressors lead to activation of arousal responses mediated by serotonergic and noradrenergic systems and it may cause a change in numerous neurotransmitters and neuroendocrine systems. There is ample experimental and clinical evidence to suggest that Ginkgo biloba extract is neuroprotective and has antioxidant properties and can restore stress-induced elevation in brain levels of catecholamines, 5-HT and plasma corticosterone to normal level.
Method: In a 12-week, double-blind, placebo-controlled study, the efficacy and safety of adding-on a fixed-dose (200mg) of Ginkgo TD to the previous treatment regime of adults with PTSD were examined. Subjects were forty male and female outpatients from a public-owned psychiatric clinic who met criteria for PTSD seven month after a 6.3 Richter earthquake in Bam city on December 26, 2003. The changes in five symptom domains including posttraumatic stress, anxiety and affective symptoms, general health and subjective stress after trauma were ssessed at weeks 0, 12 and 16 to examine effectiveness of the added-on Ginkgo TD and stability of its effects.
Results: Ginkgo TD was associated with a significantly greater improvement than placebo in PTSD patients as measured by five symptom domain scales including: GHQ-28; Watson PTSD Scale; HAM-D; HAM-A and IES (p= 0.02, 0.01, 0.001, 0.01, 0.02 respectively) Four weeks after the discontinuation of intervention, no significant difference was determined between the two groups in the five outcome measures (p= 0.005, 0.01, 0.004, 0.005, 0.01 respectively). No significant difference was observed between the two groups in terms of side effects.
Conclusions: We found Ginkgo TD to be superior to placebo as an adding-on in the treatment of PTSD. Although we did not examine the comparative efficacy of Ginkgo TD on the three main elements of PTSD, beneficial effects both on specific PTSD symptomatology and general conditions including anxiety, depression, general health and perceived stress were indicated.

Norris FH. Epidemiology of trauma: frequency and impact of different potentially traumatic events on different demographic groups. J Consult Clin Psychol 1992; 60: 409-418.

Norris FH, Friedman MJ, Watson PJ, Byrne CM, Diaz E, Kaniasty K. 60,000 disaster victims speak: Part I. An empirical review of the empirical literature, 1981-2001. Psychiatry 2002; 65: 207- 239.

Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995; 52: 1048-1060.

Breslau N, Davis GC, Andreski P, Peterson E. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 1991; 48: 216-222.

Breslau N, Davis GC, Andreski P, Peterson EL, Schultz LR. Sex differences in posttraumatic stress disorder. Arch Gen Psychiatry 1997; 54: 1044-1048.

Creamer M, Burgess P, McFarlane AC. Post- traumatic stress disorder: findings from the Australian National Survey of Mental Health and Well-being. Psychol Med 2001; 31: 1237.

Narrow WE, Rae DS, Robins LN, Regier DA. Revised Prevalence Estimates of Mental Disorders in the United States: Using a Clinical Significance Criterion to Reconcile 2 Surveys' Estimates. Arch Gen Psychiatry 2002; 59: 115.

Andrews G, Slade T, Peters L. Classification in psychiatry: ICD-10 versus DSM-IV. Br J Psychiatry 1999; 174: 3.

Schnurr PP, Green BL. Trauma and health: physical health consequences of exposure to extreme stress. Washington, DC: American Psychological Association; 2004.

Ouimette P, Cronkite R, Henson BR, Prins A, Gima K, Moos RH. Posttraumatic Stress Disorder and Health Status Among Female and Male Medical Patients. J Trauma Stress 2004; 17: 1-9.

McCrone P, Knapp M, Cawkill P. Posttraumatic stress disorder (PTSD) in the Armed Forces: health economic considerations. J Trauma Stress 2003; 16: 519-522.

Van Der Kolk BA, Burbridge JA, Suzuki J. The psychobiology of traumatic memory. Clinical implications of neuroimaging studies. Ann N Y Acad Sci 1997; 821: 99-113.

McEwen BS. The neurobiology of stress: from serendipity to clinical relevance. Brain Res 2000; 886: 172-189.

Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM, et al. Elevated CSF corticotropin-releasing factor concentrations in posttraumatic stress disorder. Am J Psychiatry 1997; 154: 624-629.

Yehuda R, Giller E, Levengood RA, Southwick SM, Siever LJ. Hypothalamic-pituitary-adrenal functioning in post-traumatic stress disorder: expanding the concept of the stress response spectrum. In: Friedman MJ CD, Deutch AY. Eds. , ed. Neurobiological and Clinical Consequences of Stress: From Normal Adaptation to PTSD. Philadelphia PA: Lippincott-Raven; 1995. p. 351- 365.

McEwen BS, de Kloet ER, Rostene W. Adrenal steroid receptors and actions in the central nervous system. Physiol Rev 1986; 66: 1121- 1189.

Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 1995; 152: 973-981.

Gurvits TV, Shenton ME, Hokama H, Ohta H, Lasko NB, Gilbertson MW, et al. Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder. Biol Psychiatry 1996; 40: 1091-1099.

Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP, et al. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci 2002; 5: 1242- 1247.

Charney DS, Deutch AY, Krystal JH, Southwick SM, Davis M. Psychobiologic mechanisms of posttraumatic stress disorder. Arch Gen Psychiatry 1993; 50: 295-305.

Charney DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 2004; 161: 195-216.

Hashimoto S, Inoue T, Koyama T. Effects of conditioned fear stress on serotonin neurotransmission and freezing behavior in rats. Eur J Pharmacol 1999; 378: 23-30.

Inoue T, Koyama T, Yamashita I. Effect of conditioned fear stress on serotonin metabolism in the rat brain. Pharmacol Biochem Behav 1993; 44: 371-374.

DeFeudis FV. Ginkgo biloba Extract (EGb 761): Pharmacological Activities and Clinical Applications. Paris: Elsevir 1991; 9.

Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992; 340: 1136-1139.

Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Hum Psychopharmacol 1994; 9: 215–222.

Kanowski S, Herrmann WM, Stephan K, Wierich W, Hrr R. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry 1996; 29: 47-56.

Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF. A placebo- controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997; 278: 1327-1332.

Christen Y, Maixent JM. What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine. Cell Mol Biol (Noisy- le-grand) 2002; 48: 601-611.

Maclennan KM, Darlington CL, Smith PF. The CNS effects of Ginkgo biloba extracts and ginkgolide B. Prog Neurobiol 2002; 67: 235-257.

Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieu K, Fiskum G. Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brain Res 2001; 922: 282-292.

Klein J, Chatterjee SS, Lffelholz K. Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba. Brain Res 1997; 755: 347-350.

Prehn JH, Krieglstein J. Platelet-activating factor antagonists reduce excitotoxic damage in cultured neurons from embryonic chick telencephalon and protect the rat hippocampus and neocortex from ischemic injury in vivo. J Neurosci Res 1993; 34: 17.

Shah ZA, Sharma P, Vohora SB. Ginkgo biloba normalises stress-elevated alterations in brain catecholamines, serotonin and plasma corticosterone levels. Eur Neuropsychopharmacol 2003; 13: 321-325.

Pacak K, Palkovits M, Kopin IJ, Goldstein DS. Stress-Induced Norepinephrine Release in the Hypothalamic Paraventricular Nucleus and Pituitary-Adrenocortical and Sympathoadrenal Activity: In Vivo Microdialysis Studies. Front Neuroendocrinol 1995; 16: 89-150.

Sur TK, Bhattacharyya D. The effect of panax ginseng and diazepam on brain and hypothalamic 5- hydroxytryptamine during stress. Indian J Pharmacol 1997; 29: 318-321.

Jones MT, Gillham B, Campbell EA, Al-Taher AR, Chuang TT, Di Sciullo A. Pharmacology of neural pathways affecting CRH secretion. Ann N Y Acad Sci 1987; 512: 162-175.

Plotsky PM, Cunningham ET Jr, Widmaier EP. Catecholaminergic modulation of corticotropin- releasing factor and adrenocorticotropin secretion. Endocr Rev 1989; 10: 437-458.

Marcilhac A, Dakine N, Bourhim N, Guillaume V, Grino M, Drieu K, et al. Effect of chronic administration of Ginkgo biloba extract or Ginkgolide on the hypothalamic-pituitary-adrenal axis in the rat. Life Sci 1998; 62: 2329-2340.

Bolanos-Jimenez F, Manhaes de Castro R, Sarhan H, Prudhomme N, Drieu K, Fillion G. Stress-induced 5-HT1A receptor desensitization: protective effects of Ginkgo biloba extract (EGb 761). Fundam Clin Pharmacol 1995; 9: 169-174.

Huguet F, Drieu K, Piriou A. Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761). J Pharm Pharmacol 1994; 46: 316-318.

Bastianetto S, Zheng WH, Quirion R. The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C. J Neurochem 2000; 74: 2268-2277.

Curtis-Prior P, Vere D, Fray P. Therapeutic value of Ginkgo biloba in reducing symptoms of decline in mental function. J Pharm Pharmacol 1999; 51: 535-541.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text revision. Washington, DC: American Psychiatric Association; 2000.

Sharifi V, Assadi SM, Mohammadi MR, Amini H, Kaviani H, Semnani Y, et al. [Reliability and feasibility of the Persian version of the structured diagnostic interview for DSM-IV (SCID)]. Advances in Cognitive Science 2004; 6: 10-22.

Watson CG, Juba MP, Manifold V, Kucala T, Anderson PE. The PTSD interview: rationale, description, reliability, and concurrent validity of a DSM-III-based technique. J Clin Psychol 1991; 47: 179-188.

Toozandeh Jani H. Comparative efficacy of anxiety control, psychopharmacotheraoy and their combination in treatment of anxiety disorders. Tehran: Iran university of medical science; 1993.

Gharayi B. Assessment of cognitive patterns among comorbid depression and anxiety patients. Tehran: Tehran Institute of Psychiatry; 1993.

Fataa L. Comparative efficacy of clomipiramine, exposure and response prevention and their combination in treatment of obsessive compulsive disorder. Tehran: Tehran Institute of Psychiatry; 1991.

Noorbala AA MK, Bagheri-Yazdi A, Yasami MT. Profile of mental health in I.R Iran. Tehran: Ministry of Health Publications; 2001.

Panaghi L, Hakim shooshtari M, Atari Mogadam J. [Persian version validation in impact of event Scale-Revised]. Tehran University Medical Journal 2006; 64: 52-60.

Ward W. Psychiatric morbidity in Australian veterans of the United Nations peacekeeping force in Somalia. Aust N Z J Psychiatry 1997; 31: 184- 193.

Woelk H, Arnoldt KH, Kieser M, Hoerr R. Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial. J Psychiatr Res 2007; 41: 472-480.

Stein MB, Kline NA, Matloff JL. Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study. Am J Psychiatry 2002; 159: 1777-1779.

Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2007: CD003120.

Hoerr R. Behavioural and psychological symptoms of dementia (BPSD): effects of EGb 761. Pharmacopsychiatry 2003; 36 Suppl 1: S56-61.

Mix JA, Crews WD, Jr. A double-blind, placebo- controlled, randomized trial of Ginkgo biloba extract EGb 761 in a sample of cognitively intact older adults: neuropsychological findings. Hum Psychopharmacol 2002; 17: 267-277.

Stein DJ, Zungu-Dirwayi N, Van der Linden GJH, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD)(Cochrane Review). Cochrane Library 2004.

IssueVol 2 No 2 (2007) QRcode
Controlled clinical trial Ginkgo biloba Post traumatic stress disorder

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Habibi LK, Ghorbani B, Norouzi AR, Gudarzi SS, Shams J, Yasami M-T. The Efficacy and Safety of Add-on Ginko TD (Ginkgo Biloba) Treatment for PTSD: Results of a 12-Week Double-Blind Placebo-Controlled Study. Iran J Psychiatry. 2(2):58-64.