Fuladi S, Emami SA, Mohammadpour AH, Karimani A, Manteghi AA, Sahebkar A. Assessment of Withania somnifera root extract efficacy in patients with generalized anxiety disorder: a randomized double-blind placebo-controlled trial. Curr Clin Pharmacol. Published online April 13, 2020. doi: 10.2174/1574884715666200413120413.
To assess the effect of an extract of Withania somnifera on symptoms of generalized anxiety
Randomized, double-blind, placebo-controlled trial
Forty patients who were undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) participated in this trial. They met the criteria for generalized anxiety disorder (GAD) diagnosis as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). They were randomly selected for the treatment group (W somnifera root extract, 1 g/day; n=22) or the placebo group (n=18). Patients received either the extract or placebo daily for 6 weeks.
Study Parameters Assessed
To assess the severity of GAD symptoms at baseline as well as at week 2 and week 6 of the trial, researchers used the Hamilton Anxiety Rating Scale (HAM-A). The HAM-A scale contains 14 questions rating the severity of common GAD symptoms, from 0 to 4.
Primary Outcome Measures
HAM-A scores during the course of the trial revealed a significant amelioration of GAD symptoms in the treatment group versus placebo (P<0.05). There was also a significant difference in the reduction of GAD score between the 2nd (P=0.04) and 6th week (P=0.02) in the treatment group. The extract was safe, and researchers observed no adverse effect during the trial.
Withania somnifera (ashwagandha) root extract is statistically efficacious at 1 gram per day after 2 weeks and even more so after 6 weeks of treatment. It has also been found to be safe to use while on SSRIs.
In alternative medical care, many patients seek treatment for anxiety and its related conditions such as insomnia, chronic stress, and muscle tension. Many of the pharmaceuticals available have adverse effects. For example, the commonly prescribed lorazepam, a benzodiazepine, can cause dizziness, weakness, drowsiness, and tiredness. It can also be habit-forming.1 Studies reveal that Withania somnifera reduces stress, reduces serum cortisol levels, and enhances GABA signaling in the central nervous system.2-5
Withania somnifera has a long history of use in Ayurveda. One randomized, double-blind, placebo-controlled study conducted in India with a total of 60 patients for 10 weeks used a high-potency, full-spectrum root extract of 300 mg twice daily.2 The study monitored sleep-onset latency, sleep efficiency, sleep quality, total sleep time, and anxiety. In all parameters, there was significant improvement. Sleep efficacy was observed to increase further after 10 weeks, from the baseline, indicating long-term treatment is best. Larger studies are needed to confirm these findings. Another similarly structured study in 2019 revealed significant improvement in sleep, reduction of perceived stress (P<0.05 and P<0.001), lowered cortisol levels (P<0.05 and P<0.0001) with, respectively, 125 mg and 300 mg Withania somnifera twice daily.3
Withania somnifera was safely used in combination with SSRIs, a class of drugs that often precludes the use of many other natural agents.
Another study with 64 participants evaluated the safety and efficacy of high-concentration, full-spectrum extract of Withania somnifera as an adaptogen. The randomized, double-blind, placebo-controlled study focused on those affected by chronic stress and included serum cortisol as a marker. After 60 days, serum cortisol levels were substantially reduced (P=0.0006) in the Withania somnifera group relative to the placebo group. No adverse events were reported. The authors concluded that Withania somnifera is safe and effective in improving one’s stress resistance and, therefore, may improve quality of life.4
Gamma aminobutyric acid (GABA) signaling dysfunction is associated with generalized anxiety disorder, insomnia, muscle spasms, and seizures.6-9 One study used microtransplanted oocytes to study the GABA receptors and their sensitivity in relation to Withania somnifera.5 The study demonstrated for the first time that an aqueous extract of Withania somnifera is a potent agonist of GABAp1 receptors, and this activation was not significantly different than those produced by exogenous GABA.
In keeping with the traditional Ayurvedic use of Withania somnifera, clinical trials have revealed that it may be useful for patients with GAD, sleep-onset and sleep-quality issues, elevated cortisol levels, and other stress-related conditions such as muscle tension. An essential take-home finding of the current study under review is that Withania somnifera was safely used in combination with SSRIs, a class of drugs that often precludes the use of many other natural agents.
- Lorazepam. Medline Plus. https://medlineplus.gov/druginfo/meds/a682053.html#side-effects. Accessed July 20, 2020.
- Langade D, Kanchi S, Salve J, Debnath K, Ambegaokar D. Efficacy and safety of ashwagandha (Withania somnifera) root extract in insomnia and anxiety: a double-blind, randomized, placebo-controlled study. Cureus. 2019;11(9):e5797.
- Salve J, Pate S, Debnath K, Langade D. Adaptogenic and anxiolytic effects of ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study. Cureus. 2019;11(12):e6466.
- Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 2012;34(3):255-262.
- Candelario M, Cuellar E, Reyes-Ruiz JM, et al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol. 2015;171:264-272.
- Loscher W. Relationship between GABA concentrations in cerebrospinal fluid and seizure excitability. J Neurochem. 1982;38(1):293-295.
- Brambilla P, Perez J, Barale F, et al. GABAergic dysfunction in mood disorders. Mol Psychiatry. 2003;8(8):721-737.
- Plante DT, Jensen JE, Winkelman JW. The role of GABA in primary insomnia. Sleep. 2012;35(6):741-742.
- Mathews GC. The dual roles of GABA in seizures and epilepsy generate more excitement. Epilepsy Curr. 2007;7(1):28-30.