1Government Ayurvedic College, Nanded, Maharashtra, India
2Senior Consultant Projects & Operations, Xplora Clinical Research Services Pvt. Ltd., Bangalore, India
3PhD Scholar, Chitkara University, Punjab, India
Stress and anxiety are increasingly prevalent conditions that negatively affect psychological wellbeing and overall quality of life. Although conventional pharmacological treatments are effective, their use may be limited by adverse effects and concerns regarding long term dependency. This has led to growing interest in safe, plant based therapeutic alternatives. Cread AM is an Ayurvedic formulation containing adaptogenic and neuroprotective herbs traditionally used in the management of stress and anxiety. Objective: To evaluate the safety and efficacy of Cread AM in reducing stress and anxiety in adults with mild to moderate symptoms. Methodology: This prospective, non-randomized, single arm clinical study enrolled 24 adults aged 18–60 years with mild to moderate stress and anxiety. Participants received Cread AM capsules (460 mg) orally twice daily for 56 days. Efficacy was assessed using the Perceived Stress Scale (PSS) and the Generalized Anxiety Disorder 7 (GAD 7) questionnaire at baseline and at the end of the study. Serum cortisol levels were evaluated as a physiological stress marker. Safety assessments included vital signs, electrocardiogram (ECG), hematological and biochemical investigations, and monitoring of adverse events. Paired t tests were used for statistical comparisons. Results: All 24 participants completed the study. Mean PSS scores decreased significantly from 23.21 ± 1.44 at baseline to 12.42 ± 3.12 at Day 56 (p < 0.0001). Mean GAD 7 scores also showed a significant reduction from 8.04 ± 0.95 to 2.67 ± 1.05 (p < 0.0001). Serum cortisol levels showed a numerical reduction from 6.10 ± 3.54 to 5.68 ± 3.54; however, this change was not statistically significant (p = 0.572). Vital signs, ECG findings, and laboratory parameters remained within normal limits. Reported adverse events were mild, transient, and unlikely related to the study medication.Conclusion: Treatment with Cread AM was associated with significant reductions in perceived stress and anxiety over an 8week period and demonstrated a favorable safety and tolerability profile. These findings suggest that Cread AM may serve as a safe complementary option for stress and anxiety management.
Stress and anxiety represent a major and growing public health concern because they are highly prevalent and can substantially impair day-to-day functioning. Anxiety disorders are consistently reported among the most common mental disorders worldwide. In addition to distressing emotional symptoms, persistent stress and anxiety are associated with reduced productivity, impaired social relationships, and diminished quality of life, and they often co-occur with sleep disturbance and somatic complaints.The American Heart Association includes stress management among lifestyle strategies to help control high blood pressure—recognizing that chronic stress contributes to physiological responses linked to hypertension and cardiovascular risk. AHA’s public guidance on Managing Stress to Control High Blood Pressure states that stress management is beneficial and can influence risk factors such as blood pressure and unhealthy coping behaviours.
The AHA recommends managing stress as one of the lifestyle behaviours that may help improve or control high blood pressure, alongside diet, exercise, weight, alcohol moderation and smoking cessation. The American Diabetes Association recommends psychosocial assessment in diabetes because psychological distress affects self-management, adherence, and glycaemic outcomes.
From a biological perspective, sustained psychological stress can influence multiple neuroendocrine and neuroimmune pathways. A central mechanism involves dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which orchestrates the hormonal stress response. Altered HPA axis feedback and stress-related changes in glucocorticoid signaling may contribute to chronic cortisol dysregulation and downstream physiological effects. Cortisol, the end product of HPA axis activation, has been widely studied in relation to psychiatric symptoms; both elevated and dysregulated cortisol patterns have been linked to mood and anxiety symptomatology and may affect cognitive function and emotional stability. Although cortisol is only one component of a complex stress response, it is frequently used as an objective biomarker in clinical studies of stress-related conditions.Current evidence-based management strategies for anxiety disorders and stress-related symptoms include psychological interventions (notably cognitive-behavioral approaches), lifestyle modification, and pharmacological therapies such as selective serotonin reuptake inhibitors (SSRIs) and other antidepressants. However, real-world implementation can be limited by access constraints and by medication-related concerns. Guideline discussions emphasize that benzodiazepines should be used cautiously due to risks of tolerance, dependence, and adverse effects in some populations, especially with longer-term use. These practical and safety considerations have increased interest in complementary, non-dependency-forming approaches that may support stress regulation and reduce anxiety symptoms, particularly among individuals with mild to moderate symptom severity or those seeking integrative care options.
Ayurvedic medicine offers a holistic framework for supporting mental well-being through individualized lifestyle measures and botanicals traditionally described as promoting resilience and cognitive balance. Within this context, plant-based adaptogenic and neuroprotective herbs have gained attention as supportive interventions for stress-related symptoms. A growing body of clinical literature has evaluated botanicals commonly used for stress and anxiety, including Withania somnifera (Ashwagandha). While findings across herbal interventions vary depending on formulation quality and study design, available evidence provides a rationale for evaluating standardized botanical combinations using validated clinical endpoints and systematic safety monitoring.To assess symptom change in a standardized manner, validated patient-reported outcome measures are widely used in clinical research. The Perceived Stress Scale (PSS) measures the degree to which individuals appraise their life situations as stressful, while the Generalized Anxiety Disorder-7 (GAD-7) scale is a brief validated measure used to assess generalized anxiety symptom severity over time. Together, these tools capture complementary dimensions of psychological distress and are appropriate for evaluating changes over an intervention period, alongside physiological markers such as serum cortisol and standard clinical safety assessments.Cread-AM is a polyherbal Ayurvedic formulation containing standardized extracts of herbs traditionally used to support cognitive function and emotional balance, including Bacopa monnieri, Withania somnifera, Centella asiatica, Nardostachys jatamansi, and Convolvulus prostratus. Given the prevalence of stress and anxiety symptoms and the need for well-tolerated supportive options, clinical evaluation of such formulations is warranted. Therefore, the present study was conducted to evaluate the safety and clinical effectiveness of Cread-AM in adults experiencing mild to moderate stress and anxiety, using validated symptom scales and physiological/safety assessments over a 56-day intervention period.
Objective
The primary objective of this study was to evaluate the change in stress and anxiety symptom severity following 56 days of treatment with Cread?AM in adults with mild to moderate symptoms.
Primary Objective
Secondary Objectives
Methods
Study design and setting
This was a prospective, open?label, single?arm clinical study designed to evaluate the safety and clinical effectiveness of Cread?AM in adults with stress and anxiety symptoms. Participants received the investigational product for 56 days. Study visits were conducted at baseline (Day 1) and end of study (Day 56 ± 2 days). A telephonic follow?up (Day 28 ± 2 days) was performed to assess treatment adherence, record adverse events, and document any concomitant medication use. The study was conducted at an Ayurvedic clinical center in Bengaluru, India, in accordance with ICH?GCP and applicable national regulatory requirements.
Participants
Adults aged 18–60 years with mild to moderate stress and anxiety symptoms of at least two weeks’ duration were eligible for inclusion. Participants met relevant DSM?5?TR criteria as assessed by the investigator and had a Perceived Stress Scale (PSS) screening score between 10 and 26. Written informed consent was obtained from all participants prior to the initiation of any study procedures.
Participants were excluded if they had clinically significant cardiovascular, hepatic, renal, neurological, or psychiatric disorders, chronic alcoholism, or if they were pregnant or lactating. Additional exclusion criteria included current use of psychotropic or hepatotoxic medications and participation in another clinical study within the prior 90 days.
Intervention
All participants received Cread?AM capsules, an Ayurvedic formulation containing standardized extracts of medicinal herbs traditionally used for stress modulation and cognitive support, including Bacopa monnieri, Withania somnifera, Centella asiatica, Nardostachys jatamansi, Convolvulus prostratus, and others.
Participants were instructed to take one 460 mg capsule orally twice daily after meals for 56 days. Treatment compliance was assessed through participant reporting and product accountability (e.g., returned capsule count and/or dispensing records).
Outcome measures
Primary Endpoints
Secondary Endpoints
Data collection procedures
At baseline and end?of?study visits, participants underwent a physical examination, vital sign assessment, ECG, and laboratory investigations. Psychological outcomes (PSS and GAD?7) were administered at baseline and Day 56. Serum cortisol was measured at the same time points. During the Day 28 telephonic follow?up and throughout the study period, adverse events and concomitant medications were recorded.
Statistical analysis
Descriptive statistics were used to summarize baseline characteristics and outcomes. Continuous variables were summarized as mean ± standard deviation (SD), and categorical variables were summarized as frequencies and percentages. Changes from baseline to Day 56 were analyzed using paired t?tests (two?tailed). A p?value < 0.05 was considered
RESULT
The analysis involved the examination of data sets from a total of 24 subjects who had been completed the study as per the study protocol. The data collected from each of the 24 subjects were incorporated into the analysis of study outcomes.
Perceived Stress (PSS)
A statistically significant reduction in perceived stress was observed following 56 days of treatment with Cread?AM. Mean PSS scores decreased from 23.21 ± 1.44 at baseline to 12.42 ± 3.12 at the end of the study, with a mean difference of 10.79 (95% CI: 9.60 to 11.99, p < 0.0001). This represents a shift from moderate stress levels at baseline to low stress levels at study completion. Figure 1 illustrates the change in PSS scores from baseline to the end of the study. Statistical comparison was performed using a paired t-test (Baseline vs. End of Study), with significance defined as p < 0.001.
Table 1: Change of PSS score from baseline to end of the study
|
PSS Score (Mean ± SD) |
Mean Diff. |
95% CI |
P-value |
|
|
Baseline Visit (Visit 1) |
End of Study (Visit 2) |
|||
|
23.21 ± 1.44 |
12.42 ± 3.12 |
10.79 |
-9.597 to -11.99 |
< 0.0001*** |
Figure 1: Change in PSS score from baseline to end of the study. Statistical comparison was performed by paired t-test: Baseline vs End of Study. ***P < 0.001.
Anxiety (GAD?7)
Anxiety symptoms improved significantly over the treatment period. Mean GAD?7 scores decreased from 8.04 ± 0.95 at baseline to 2.67 ± 1.05 at Day 56, with a mean difference of 5.38 (95% CI: 4.97 to 5.79, p < 0.0001). These findings indicate an improvement from mild anxiety to minimal symptoms in most participants. Figure 2 illustrates the change in GAD-7 scores from baseline to the end of the study. Statistical comparison was performed using a paired t-test (Baseline vs. End of Study), with significance defined as p < 0.001.
Table 2: Change of GAD-7 score from baseline to end of the study
|
GAD-7 Score (Mean ± SD) |
Mean Diff. |
95% CI |
P-value |
|
|
Baseline Visit (Visit 1) |
End of Study (Visit 2) |
|||
|
8.04 ± 0.95 |
2.67 ± 1.05 |
5.38 |
-4.965 to -5.785 |
< 0.0001*** |
Figure 2: Change in GAD-7 score from baseline to end of the study. Statistical comparison was performed by paired t-test: Baseline vs End of Study. ***P < 0.001.
Assessment of Serum Cortisol Levels
Mean serum cortisol levels showed a numerical decrease from 6.10 ± 3.54 at baseline to 5.68 ± 3.54 at the end of the study, with a mean difference of 0.42. This change did not reach statistical significance (95% CI: −1.918 to 1.086; p = 0.572). The findings suggest modest physiological changes despite significant improvements in subjective stress and anxiety measures. Figure 3 illustrates the change in serum cortisol levels from baseline to the end of the study. Statistical comparison was performed using a paired t-test (Baseline vs. End of Study).
Table 3: Mean change in serum cortisol levels from baseline to end of study
|
Serum Cortisol (Mean ± SD) |
Mean Diff. |
95% CI |
P-value |
|
|
Baseline Visit (Visit 1) |
End of Study (Visit 2) |
|||
|
6.10 ± 3.54 |
5.68 ± 3.54 |
0.42 |
1.086 to -1.918 |
0.572 |
Figure 3: Change in serum cortisol levels from baseline to end of the study. Statistical comparison was performed by paired t-test: Baseline vs End of Study.
Safety and Tolerability
Throughout the study, vital signs, ECG findings, and laboratory safety parameters remained within normal reference ranges. No clinically significant changes were observed in hematological, hepatic, renal, or metabolic parameters. Six mild and transient adverse events were reported, including headache, abdominal discomfort, and upper respiratory symptoms. All adverse events were assessed as unlikely related to the study medication and resolved without intervention. No serious adverse events or treatment discontinuations occurred.
Table 4: Mean change in vital signs from baseline to different study visits
|
Vital signs |
Baseline (mean ± SD) |
End of Study (mean ± SD) |
p-value |
|
Body temp. (Range: 36.1-37.5°C) |
36.82 ± 0.41 |
36.90 ± 0.50 |
0.443 |
|
Pulse rate (Range: 60-100 bpm) |
83.58 ± 8.51 |
84.50 ± 7.69 |
0.699 |
|
Respiratory rate (Range: 12-20 bpm) |
15.54 ± 2.30 |
15.63 ± 2.83 |
0.916 |
|
Systolic blood pressure (Range: 90-120 mmHg) |
112.50 ± 10.95 |
111.60 ± 10.72 |
0.802 |
|
Diastolic blood pressure (Range: 60-80 mmHg) |
71.96 ± 7.56 |
71.92 ± 7.56 |
0.986 |
Laboratory safety parameters were evaluated at baseline and at the end of the study to assess the hematological, hepatic, and renal safety of Cread-AM. The mean changes in laboratory values from baseline to end of study are summarized in Table 5. Overall, no clinically significant changes were observed in hematological parameters, including haemoglobin, platelet count, total leukocyte count (TLC), and differential counts (neutrophils, lymphocytes, eosinophils, and basophils). A statistically significant reduction was observed in monocyte percentage (p = 0.014); however, this change was small, remained within normal physiological limits, and was not considered clinically relevant by the investigator.
Liver function, as assessed by serum glutamic-pyruvic transaminase (SGPT), showed a slight numerical decrease from baseline to the end of the study, with no statistically significant difference (p = 0.321). Renal function, evaluated through serum creatinine levels, remained stable throughout the study period (p = 0.152). Random blood sugar (RBS) values showed no statistically or clinically significant change from baseline to end of study.
Overall, the laboratory safety data indicate that Cread-AM was well tolerated, with no clinically meaningful alterations in hematological, hepatic, renal, or metabolic parameters during the 56-day treatment period.
Table 5: Mean change in laboratory safety parameters from baseline to end of the study
|
Baseline (mean ± SD) |
End of Study (mean ± SD) |
p-value |
|
|
Haemoglobin (g/dL) |
13.14 ± 2.29 |
12.83 ± 2.05 |
0.260 |
|
Platelet count (Lakh/cu.mm) |
3.06 ± 0.65 |
3.09 ± 0.63 |
0.819 |
|
TLC (Cells/cu.mm) |
9266.67 ± 2116.12 |
8629.17 ± 2338.80 |
0.209 |
|
Neutrophils (%) |
58.38 ± 8.13 |
59.13 ± 9.81 |
0.617 |
|
Lymphocytes (%) |
30.82 ± 7.21 |
31.14 ± 8.05 |
0.829 |
|
Monocytes (%) |
6.89 ± 1.55 |
6.17 ± 1.51 |
0.014* |
|
Eosinophils (%) |
3.31 ± 1.96 |
2.94 ± 2.30 |
0.405 |
|
Basophils (%) |
0.61 ± 0.25 |
0.63 ± 0.27 |
0.662 |
|
SGPT (U/L) |
21.67 ± 13.66 |
19.33 ± 12.82 |
0.321 |
|
Sr. creatinine (mg/dL) |
0.74 ± 0.18 |
0.78 ± 0.24 |
0.152 |
|
RBS (mg/dL) |
94.41 ± 10.71 |
107.64 ± 51.59 |
0.187 |
DISCUSSION
The present prospective, single?arm study evaluated the effects of Cread?AM (460 mg twice daily for 56 days) in adults with mild to moderate stress and anxiety. Over the 8?week intervention period, participants demonstrated statistically significant and clinically meaningful pre–post improvements in both perceived stress (PSS) and anxiety symptoms (GAD?7), alongside a favorable safety and tolerability profile. A key finding was the marked reduction in PSS and GAD?7 scores from baseline to Day 56. In practical terms, the mean PSS decreased from a level consistent with moderate perceived stress to a level consistent with low perceived stress, while the mean GAD?7 decreased from the mild anxiety range to the minimal symptom range by study completion. Beyond statistical significance, this shift across commonly used severity categories suggests that participants experienced improvement that is likely noticeable in day?to?day functioning (e.g., reduced worry, improved emotional regulation, and better coping with routine stressors). However, because the study did not include a comparison group, these improvements should be interpreted as within?subject change over time rather than definitive evidence of superiority over placebo or standard care. The improvements observed in stress and anxiety are biologically plausible given the multi?component, polyherbal nature of Cread?AM and the traditional use of several included herbs for stress adaptation, cognitive support, and emotional balance. Many Ayurvedic adaptogens are proposed to influence stress responses through modulation of the hypothalamic–pituitary–adrenal (HPA) axis, antioxidant and anti?inflammatory activity, and support of neurotransmitter systems involved in anxiety and mood regulation. In this context, the consistent reductions across both a stress scale (PSS) and an anxiety scale (GAD?7) may reflect a broader normalization of stress reactivity and improved resilience. Importantly, given the formulation contains multiple botanicals, it is not possible in this study to attribute observed effects to any single ingredient; rather, the findings likely reflect a combined or synergistic effect of the formulation as administered. Serum cortisol showed a numerical reduction after treatment but did not reach statistical significance. This pattern—strong improvement in subjective measures with a smaller or non?significant change in a single physiological marker—is not uncommon in stress research. Cortisol is influenced by multiple factors, including circadian rhythm, sleep quality, acute stress exposure, diet, physical activity, and inter?individual variability. If cortisol sampling was not strictly standardized (e.g., time?of?day, fasting state), true treatment?related changes can be difficult to detect, especially in a small sample. Additionally, perceived stress and anxiety questionnaires capture the cognitive appraisal and emotional experience of stress, which may improve even if endocrine markers fluctuate within a normal range. Future studies could strengthen physiological assessment by using multiple time?point sampling (e.g., morning and evening), salivary cortisol with diurnal slope evaluation, or additional objective stress markers such as heart?rate variability or inflammatory biomarkers.
From a safety perspective, Cread?AM was well tolerated in this cohort. Vital signs, ECG findings, and key laboratory parameters remained within normal limits, and no serious adverse events or treatment discontinuations were reported. Mild, transient events (e.g., headache, abdominal discomfort, acidity, cold/cough, fever) resolved without intervention and were assessed as unlikely related to the product. A small statistically significant change was observed in monocyte percentage; however, the magnitude of change was limited and remained within physiologic ranges, suggesting a low likelihood of clinical relevance in this context. High adherence (>95% as recorded in compliance monitoring) further supports acceptability of the regimen and reduces the likelihood that results were driven by inconsistent dosing. Overall, the safety findings are particularly relevant for individuals seeking non?sedating, non?dependency?forming approaches, although broader safety conclusions require larger samples and longer follow?up. Despite encouraging outcomes, several limitations must be considered. First, the single?arm design without placebo or active comparator limits causal interpretation; improvements may reflect placebo effects, regression to the mean, natural symptom fluctuation, increased attention from study participation, or concurrent lifestyle changes. Second, the sample size was small (n=24) and drawn from a single center, which may limit generalizability across different populations and severity profiles. Third, outcomes relied primarily on self?reported symptom scales, and the study did not assess related domains such as sleep quality, depressive symptoms, quality of life, functional impairment, or work productivity, which are often impacted by stress and anxiety. Fourth, the study duration was 56 days with no post?treatment follow?up, so durability of benefit after discontinuation remains unknown. Finally, cortisol was measured as a single biomarker and may not fully represent physiological stress regulation without standardized timing and repeated sampling. Future research should confirm these findings using a randomized, double?blind, placebo?controlled design with adequate power, pre?specified primary endpoints, and rigorous control of confounders. Including intermediate time points (e.g., Day 28) as planned contacts, documenting concomitant behavioral interventions, and measuring broader outcomes (sleep, quality of life, functioning) would help clarify the onset, magnitude, and functional relevance of clinical benefit. In addition, stratification by baseline severity and assessment of dose–response relationships could identify subgroups most likely to benefit. If validated in controlled trials, Cread?AM may be positioned as a supportive option for adults with mild to moderate stress and anxiety symptoms, either as a stand?alone complementary approach or as part of an integrative care model, with appropriate clinical oversight for individuals with severe symptoms or comorbid psychiatric illness.
CONCLUSION
In this prospective 56?day single?arm study, treatment with Cread?AM (460 mg twice daily) was associated with substantial and statistically significant improvements in both perceived stress (PSS) and anxiety symptoms (GAD?7) from baseline to study completion. Safety assessments, including vital signs, ECG, and laboratory parameters, remained within normal limits, and reported adverse events were mild, transient, and not considered treatment?related, indicating good tolerability. Although serum cortisol showed only a numerical (non?significant) reduction, the overall findings suggest that Cread?AM may be a safe and potentially beneficial complementary intervention for adults with mild to moderate stress and anxiety. Given the lack of a control group and the small sample size, these results should be confirmed through larger, randomized, placebo?controlled trials with longer follow?up to establish comparative efficacy and durability of response.
REFERENCES
Dr. Suhasini Deshpande, Manik Chaudhuri, Girisha Maheshwari, Safety and Efficacy of Cread-AM in Managing Stress and Anxiety in Adults: A Single-Arm Study, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 2, 2538-2548. https://doi.org/10.5281/zenodo.18668022
10.5281/zenodo.18668022
