Table 1.
Effects of Ashwagandha (Withania somnifera, WS) on stress, insomnia, anxiety, and depression in human trials.
| WS Material Given | Standardization/ Chemical Composition | Dosage | Control | Subjects | Behavioral Outcomes | Biological Outcomes | Authors’ Conclusions | Refs. | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| KSM-66; Batch#: KSM/19/S013; Ixoreal Biomed Inc) Capsules of aqueous root extract | >5% withanolide content | 300 mg twice daily with milk or water 8 weeks |
Starch | 80 adults (18-50 yrs) (two-armed trial: 40 healthy and 40 insomnia, male to female ratio NR) | ▼SOL, ▼WASO, ▲TST, ▲TIB, ▲SE, ▼PSQI, ▼HAM-A (insomnia only), ▼MARS rating, ▲sleep quality | Safety: physical exam and lab tests (blood pressure, body weight, routine blood test) | Improved sleep and anxiety | [63] | ||||
| KSM-66 Ashwagandha Root extract (Ixoreal Biomed Inc.) Capsules of aqueous root extract |
NR | 300 mg twice daily with water 12 weeks |
Starch | 50 healthy older adults (60-85 yrs, male to female ratio NR) | ▲WHOQOL-Bref score, ▼sleepiness scale score, ▼MARS rating, ▼sleep quality rating High PGAET rating, high PGATT rating |
Not assessed | ▲QoL, ▲sleep quality, ▲mental alertness | [64] | ||||
| KSM-66 Ashwagandha root extract, (Ixoreal Biomed Inc.) Capsules of aqueous root extract, Batch#: KSM/VG/18/1085 |
NR | 125 mg twice daily OR 300 mg twice daily 8 weeks |
125 mg starch | 60 adults (18-55 yrs, male to female ratio NR) with PSS score ≥20 and no other psychiatric conditions | ▼PSS score, ▼HAM-A score (600 mg dose only), ▼sleep quality rating | ▼serum cortisol | ▼stress, ▼anxiety | [60] | ||||
| KSM-66, (Ixoreal Biomed Inc.) Capsules of aqueous root extract, Batch#: KSM/14/270 |
>5% withanolides | 300 mg twice daily with milk or water 10 weeks |
Starch powder | 60 adults (18-60 yrs; 31:9 male to female for WS group, 16:4 for placebo group) with insomnia | ▼SOL, ▼WASO, ▲TST, ▲TIB, ▲SE, ▼MARS rating, ▲sleep quality rating, ▼PSQI score, ▼HAM-A score | Not assessed | ▼insomnia, ▼anxiety | [65] | ||||
| KSM-66 Ashwagandha; (Ixoreal Biomed) Capsules of root extract | 5% withanolides | 300 mg twice daily with water 8 weeks |
“Inert filler” | 52 overweight to obese adults (18-60 yrs; 38 males, 14 females) with chronic, routine work stress (PSS score ≥20, BMI 25 - 39.9 kg/m2) | ▼PSS score, ▲OHQ score, ▼TFEQ score ▼FCQ-T score |
▼serum cortisol, ▼body weight, ▼BMI | ▼stress, ▲well-being, ▼food cravings | [58] | ||||
| KSM-66 Ashwagandha extract (Ixoreal Biomed) Capsules of root extract prepared “without using alcohol or synthetic solvents” | ≥5% withanolide content | 300 mg twice daily after food with water 8.5 weeks (60 days) |
“Neutral substance” | 64 stressed adults (18-54 yrs; 41 males, 23 females; WHO-5 well-being score <5; PSS score of at least 14) | ▼PSS score, ▼GHQ score, ▼DASS score | ▼serum cortisol | ▼stress | [57] | ||||
| Sensoril®, (Natreon Inc.) Capsules of aqueous extract |
≥8% Withanolide glycosides (withanosides and sitoindosides), ≥32% carrier oligosaccharides, ≤2%Withaferin A | 250 mg twice daily for 1 week, then 500 mg twice daily for 11 weeks 12 weeks |
“Inactive ingredients” | 66 adults (18-75 yrs, 21:13 male to female for WS group, 14:20 for placebo group) with schizophrenia or schizoaffective disorder (MINI and PANSS score ≥60) and recent symptom exacerbation. On stable antipsychotic dose. | ▼PANSS score, ▼PSS score, ▼PANSS single item depression and anxious/depression scores |
▼hsCRP, S100B (nsd), no significant difference in serum IL-6 | ▼stress, depression, and anxiety symptoms in schizophrenia | [66] [59] |
||||
| WS Material Given | Standardization/ Chemical Composition | Dosage | Control | Subjects | Behavioral Outcomes | Biological Outcomes | Authors’ Conclusions | Refs. | ||||
| Sensoril®; (Natreon Inc., New Jersey) Capsules of aqueous extract |
“Minimum concentration of the critical bioactive withanolide glycosides and carrier oligosaccharides, but only traces of Withaferin A” | 250 mg twice daily for 1 week, then 500 mg twice daily for 11 weeks 12 weeks |
“Inactive ingredients” | 66 adults (18-75 yrs, 21:13 male to female for WS group, 14:20 for placebo group) with schizophrenia or schizoaffective disorder (MINI and PANSS score ≥60) | ▼PANSS score, ▼PSS score |
▼hsCRP, S100B (nsd), no significant difference in serum IL-6 | ▼stress in schizophrenia | [59] | ||||
| Sensoril® (Natreon Inc.) or Essentra®; (NutraGenesis) Capsules of aqueous root and leaf extract of a withaferin A and corresponding withanolide glycoside-predominant genetically uniform chemotype |
11.90% withanolide glycosides, 1.05% withaferin A, 40.25% oligosaccharides, 0.05% alkaloids, 3.44% polysaccharides | 125 mg daily OR 125 mg twice daily OR 250 mg twice daily taken before lunch and dinner 8.5 weeks (60 days) |
Excipient placebo | 130 adults (18-60 yrs; 95 males, 38 females) with moderate to severe anxiety (mHAM-A score of 24-42) | ▼mHAM-A score | ▼serum cortisol, ▼CRP, ▼FBG, ▼TC, ▼TG, ▼LDL-C, ▼VLDL-C, ▲HDL-C, ▲Hemoglobin, ▼pulse rate, ▼systolic and diastolic blood pressure | ▼stress, ▼anxiety | [62] | ||||
| Shoden; (Arjuna Natural private Ltd.) Capsules of leaf and root extract |
21 mg withanolide glycosides | 120 mg daily with water in the evening 2 hrs before meal 6 weeks |
Rice powder | 150 adults (18-65 yrs; 72 males, 78 females) with non-restorative sleep (RSQ-W score ≤50) | ▲RSQ-W total score, ▲WHOQOL-Bref score, ▼SOL, ▲SE, ▲TST, ▼WASO, ▼average awakening time | Hematologic safety markers (nsd) | improved sleep quality | [67] | ||||
| Shoden; (Arjuna Natural Ltd.) Capsules of ethanol:water (70:30) extract |
35% withanolide glycosides | 240 mg once daily after dinner with 250 mL of water 8.5 weeks (60 days) |
Roasted rice powder | 60 healthy adults (18-65 yrs; 37 males, 23 females) with HAM-A scores 6-17 | ▼HAM-A score, ▼DASS-21 (near significant) | ▼serum cortisol, ▼serum DHEA-S, ▲serum testosterone (males only) | ▼anxiety, ▼stress | [61] | ||||
| Tablets of ethanolic plant extract | NR / NR | 250 mg twice daily 6 weeks |
Placebo | 39 adults (41.3 + 13.8 yrs; 61.5% male) with GAD, mixed anxiety and depression, panic disorder and adjustment disorder with anxiety | Global Rating Scale score (nsd), ▼HAS score | Not assessed | “Anxiolytic potential”; Safe and well tolerated | [68] | ||||
| Granules of dried root | NR | 4 g thrice daily with milk 8.5 weeks (60 days) |
Granules of wheat flour | 86 participants (16-60 yrs, male to female ratio NR) with GAD | HARS score (▼ anxious mood; other anxiety scores nsd between groups) | Not assessed | ▼anxiety; potential placebo effect | [69] | ||||
| Iranian WS (70% ethanol) Capsules of ethanolic root extract with lactose as excipient |
Not assessed | 1 g daily 6 weeks |
Lactose | 40 adults (39.29 +10.10 yrs; 11:7 male:female for WS group; 40.50 + 7.76; 11:11 male:female for placebo group) with GAD on SSRIs | ▼HAM-A score | Not assessed | ▼anxiety in GAD in combination with SSRIs | [70] | ||||
▼= significant decrease compared to placebo; ▲= significant increase compared to placebo; BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; BD-NOS = Bipolar disorder, not otherwise specified; BMI = Body Mass Index; CGI = Clinical Global Impressions scale; CRP = C-reactive protein; DASS = Depression Anxiety Stress Scale; DASS-21 = Depression Anxiety Stress Scale-21; DHEA-S = Dehydroepiandrosterone sulfate; FBG = Fasting Blood Glucose; FCQ-T = Food Cravings Questionnaire – Trait; FQ = Fatigue Questionnaire; GAD = General Anxiety Disorder; GHQ = General Health Questionnaire; HAM-A/HARS = Hamilton Anxiety Rating Scale; HDL-C = High density lipoprotein cholesterol; IL-6 = Interleukin 6; LDL-C = Low density lipoprotein cholesterol; MADRS = Montgomery-Asberg Depression Rating Scale; MARS = Mental Alertness on Rising; mHAM-A = modified Hamilton Anxiety Rating Scale; MINI = Mini-International Neuropsychiatric Interview; MYMOP = Measure Yourself Medical Outcomes Profile; NR = Not reported; NOS = Not otherwise specified; OHQ = Oxford Happiness Questionnaire; nsd = Non-significant decrease; PANSS = Positive and Negative Syndrome Scale; PGAET = Physician’s Global Assessment of Efficacy to Therapy; PGATT = Patient’s Global Assessment of Tolerability to Treatment; PSS = Perceived Stress Scale; PSQI = Pittsburgh Sleep Quality Index; RSQ-W = Restorative Sleep Questionnaire-Weekly; S100B = S100 Calcium-binding protein B; SE = Sleep efficiency; SF-36 = Short Form-36; SOL = Sleep Onset Latency; SSRI = Selective serotonin reuptake inhibitor; SST = Set Shifting Test; STDT = Strategic Target Detection Test; TBT = Total Bed Time; TC = Total Cholesterol; TG = Triglycerides; TIB = Total Time in Bed; TFEQ = Three-Factor Eating Questionnaire; TST = Total Sleep Time; VLDL-C = Very low density lipoprotein cholesterol; WASO = Wake After Sleep Onset; WHOQOL-Bref = WHO Quality of Life-BREF; YMRS = Young Mania Rating Scale; QoL = Quality of Life