Herbs and Mental Health

While there have been studies investigating the adaptogenic herb ashwagandha and its use in combating stress, Salve et al. (2019) claim this study to be the first to offer insight into the dose-response of a high concentration root extract. This double-blind study included 60 participants (male and female), with a baseline perceived stress scale (PSS) score greater than 20. The participants were randomly selected to receive capsules of 125 mg of ashwagandha extract, 300 mg of ashwagandha extract, or an identical placebo twice daily for eight weeks in a 1:1:1 ratio. The following measures were taken: stress (using PSS) at baseline, at four weeks and eight weeks; anxiety using the Hamilton-Anxiety (HAM-A) scale; cortisol levels in the blood at baseline and at eight weeks; and sleep quality utilizing a seven-point sleep scale. Fifty eight of the 60 participants completed the study (96.7% completion rate). Both a significant reduction in PSS scores and a drop in cortisol levels were seen in participants who took 250 mg/day or 300 mg/day of ashwagandha extract. Moreover, sleep quality was significantly better in those that received ashwagandha relative to the placebo group. These findings show that the ashwagandha root aqueous extract may have stress and anxiety-relieving properties.

Lopresti et al. (2019) investigated the anxiolytic effect of ashwagandha (withania somnifera) on adults with self-reported high stress and examined potential mechanisms associated with its therapeutic effects in this randomized, double-blind study. Sixty adults were randomly assigned to take either a placebo or 240mg of a standardized ashwagandha once a day. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A); Depression, Anxiety, and Stress Scale -21 (DASS-21); and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. All 60 participants took part for the 60 days and completed the trial. Relative to the placebo, the ashwagandha was associated with statistically significant reductions in anxiety (indicated by HAM-A scores) and morning cortisol levels, and also a drop in depression (shown by the DASS-21). Higher testosterone levels were observed in males (P = 0.038) but not in females over time, although this change was not statistically significant compared with the placebo. Although the consensus following this study was that ashwagandha’s stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis, more research with larger sample sizes, diverse populations, and greater variations in dosages is warranted.

The objective in this study by Chengappa et al. (2018) was to determine if adjunctive therapy with a standardized extract of withania somnifera (WSE) — which has known anti-inflammatory and immunomodulating properties — can improve psychopathology and stress in sufferers of schizophrenia or schizoaffective disorder. In this randomly-assigned, double-blind, placebo-controlled study, 66 patients with exacerbating symptoms were assigned to either 1000mg per day of WSE or a placebo for 12 weeks, in addition to their current antipsychotic medication. Outcomes measured were changes in Positive and Negative Syndrome Scale (PANSS total, positive, negative, and general symptoms) between treatment groups from baseline until the end of treatment, S100 calcium-binding protein B (S100B) and C-reactive protein (CRP) concentrations, and stress and inflammatory indices [using the Perceived Stress Scale (PSS)]. Beginning at four weeks and continuing to the end of treatment, WSE produced significantly greater reductions in PANSS negative, general, and total symptoms (but not positive symptoms) when compared to the placebo. Other changes with WSE treatment included improvements in PSS scores and greater (although not significant) declines in CRP and S100B, as compared to the placebo. Adverse effects observed were mild to moderate and didn’t last long, with somnolence (drowsiness), epigastric discomfort, and loose stools more commonly seen with WSE. Also, no significant between-treatment differences were noted in body weight, vital signs, or laboratory measures, which remained stable. This early study suggests that adjunctive treatment with a standardized extract of withania somnifera provides significant benefits, with minimal side effects, for negative, general, and total symptoms of schizophrenia and stress in patients with recent exacerbations of schizophrenia.

Pratte et al. (2014) provides us with a systematic review of the human-based trials of the herb withania somnifera (WS) as a treatment for anxiety. Of the 62 abstracts that were screened, five were human randomized controlled trials with a treatment arm that included WS as a remedy for anxiety or stress, and were therefore included in this review. Three studies compared several dosage levels of WS extract with placebos using versions of the Hamilton Anxiety Scale, with two demonstrating the significant benefit of WS versus a placebo, and the third demonstrating beneficial effects insufficient to be statistically significant. Another study compared naturopathic care (without the use of drugs) with WS versus psychotherapy, observing greater reductions in Beck Anxiety Inventory (BAI) scores in the WS group (56.5% decrease) than the psychotherapy group (30.5% reduction). The fifth study found larger reductions in Perceived Stress Scale (PSS) scores in the WS group (44%) than the placebo group (5.5%), with the difference being statistically significant. However, Pratte et al. (2014) revealed that all studies exhibited unclear or high risk of bias, and heterogenous design and reporting. This prevented the possibility of meta-analysis. Although all five studies concluded that administration of the herb WS resulted in greater score improvements than placebos in outcomes on anxiety or stress scales, this review recommends considering this evidence with caution, given the aforementioned limitations..

Since “most of the currently available drugs for insomnia exert adverse effects," Langade et al. (2019) set out to test the efficacy and safety of ashwagandha root extract in patients with insomnia and anxiety. The double-blind, randomized study was conducted at Prakruti Hospital in Maharashtra, India. It included 60 patients who were randomly assigned to one of two groups: 40 to the “test” group (given a capsule containing the highest concentration of full-spectrum ashwagandha root extract— 300 mg) and 20 to the “placebo” group (administered an identical capsule containing starch). Both treatments were given twice a day with either milk or water for 10 weeks. The outcomes measured were sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales. The final dataset included 58 subjects (29 in test, 19 in placebo) as one person from each group did not complete the study. At baseline, the parameters were similar in the two groups. Yet over the course of the 12 week intervention, sleep efficiency improved considerably with Ashwagandha (75.62 at baseline to 83.48 after 10 weeks), whereas the SE score seen in the placebo group went from 75.14 at baseline to 79.68 at 10 weeks. Moreover, in the test group, significant improvements were seen in sleep quality, Pittsburgh Sleep Quality Index, anxiety, and sleep onset latency after 10 weeks. Incidentally, the sleep onset latency was enhanced in both test and placebo at five and ten weeks, but at the 10 week mark the sleep onset latency was found to be much shorter in the test group (p = 0.019) than the placebo group. The dose of 300mg of ashwagandha extract twice daily demonstrated not only its sleep-inducing potential but was also reported to be well-tolerated. Large-scale studies are called for to confirm its potential use in improving sleep parameters in insomnia and anxiety sufferers.

Since withania somnifera (WS or “ashwagandha”) is widely used in ayurvedic medicine and is known to potentially have a role in neurodegenerative diseases, this 2019 study investigated the effect of WS on memory impairment due to post traumatic stress disorder (PTSD) in animal models. To induce the animals into PTSD, the single-prolonged rat model was adopted. This involved restraint for 2 hours, forced swimming for 20 minutes, rest for 15 minutes, and diethyl ether exposure for 1-2 minutes. This successfully induced short and long-term memory impairments due to PTSD. The dosing of the WS root powder extract was decided as 500mg/kg/day orally, which was shown to prevent the memory decline induced by PTSD. In addition, WS prevented PTSD-induced changes in oxidative stress biomarkers in the hippocampus. The study concluded that administration of 500mg/kg per day prevented PTSD-induced effects such as memory impairment, probably through preserving changes in antioxidant mechanisms in the hippocampus.

Lopresti et al. (2014) hypothesised that curcumin, the principal curcuminoid derived from the spice turmeric, would be effective in treating depressive symptoms in patients with major depressive disorder (MDD) since it influences several biological mechanisms associated with major depression. Lopresti et al. (2014) treated individuals with MDD with either 500mg of curcumin twice a day, or with a placebo, for eight weeks in this randomized, double-blind study. From baseline to week four, both curcumin and placebo-takers saw improvements in IDS-SR30 (assesses depression severity) and most secondary outcome measures [including Spielberger State-Trait Anxiety Inventory (STAI)]. Curcumin eventually demonstrated more efficacy than the placebo from weeks four to eight, with better IDS-S30 total and mood scores and STAI trait score reported. Interestingly, greater efficacy from curcumin administration was identified in a subgroup of participants with atypical depression. It was concluded that these findings partially supported curcumin’s antidepressant effects in patients with major depressive disorder, but studies with larger sample sizes, longer treatment periods, and greater variation of curcumin dosages are required.

Since docosahexaenoic acid (DHA) is essential for brain development and protection, and its deficiency is linked to the neuropathology of cognitive disorders such as anxiety, Wu et al. (2015) set out to analyze the interaction between DHA and curcumin (believed to complement the actions of DHA in the brain). Curcumin was observed to enhance the synthesis of DHA from its precursor (ALA) and elevate the concentration of enzymes involved in the synthesis of DHA in both liver and brain tissue. An in vivo experiment conducted on rodents reduced anxiety-like behavior, implying that curcumin increases DHA synthesis and thereby causes a rise in DHA levels in the brain. The research team believe these findings have important implications for human health and the prevention of cognitive disease — particularly for populations eating a plant-based diet or for those who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.

Since clinical trials have produced “conflicting” conclusions on the efficacy of the plant polyphenol, curcumin, Ng et al. (2017) conducted this meta-analysis with the purpose of summarizing current evidence and using it to generate hypotheses to assist with future research. A preliminary search on several scientific databases including PubMed yielded 2,081 articles published between 1960 and 2016. A total of 377 patients were reviewed using data from six clinical trials comparing the use of curcumin versus a placebo. Using the Hamilton Depression Rating Scale, curcumin showed significant clinical efficacy in reducing depressive symptoms. Furthermore, three additional studies reported curcumin’s significant anxiolytic effect. This meta-analysis found no adverse effects reported in the trials, and determined that most of the trials had a generally low risk of bias, except for an open trial of curcumin and one single-blind study. There were limitations in this meta-analysis, in that only six trials were available, and duration was not very long — with studies varying from four to eight weeks. Despite this, Ng et al. (2017) report curcumin to be a safe, well-tolerated, and efficacious option for depressed patients.

Hausenblas et al. (2013) sought to provide a comprehensive and statistical review of the randomized controlled trials examining the effects of saffron (crocus sativus L.) for the treatment of major depressive disorder (MDD) following accumulating evidence for the beneficial effects saffron induces in depressive patients. To be selected from the database search results, the randomized controlled trials had to study adults (aged 18 years and older) with symptoms of depression, examine effects of saffron supplementation on depressive signs, and also involve a placebo control or antidepressant comparison group. Five trials, including two placebo-controlled trials and three antidepressant-controlled trials, met the inclusion criteria and were selected for the review. The former trials showed a large effect size for saffron supplementation vs. placebo control in treating depressive symptoms, indicating a significant reduction in symptoms in the saffron intervention group compared to the placebo. When saffron was compared to another antidepressant, a null effect size was revealed, meaning both treatments were similarly effective. Also, the JADAD score of five marked the trials in this meta-analysis were of high quality. To conclude, although long-term follow-ups are needed to affirm these findings, this meta-analysis shows that saffron supplementation can improve symptoms of depression in adults with MDD.

This 2016 trial investigated the effect of lavender on the prevention of stress, anxiety, and postpartum depression in women. Kianpour et al. (2016) point out that during labor, aromatherapy has been shown to reduce anxiety in expecting mothers. This clinical trial involved 140 women admitted to the obstetric and gynecological unit, randomly divided into aromatherapy and non-aromatherapy groups immediately after delivering their babies. The control group (non-aromatherapy) were given routine care after discharge and a follow-up telephone call, while the intervention with aromatherapy entailed three drops of lavender essential oil every eight hours for four weeks. The women in both groups were assessed using the 21-item Depression, Anxiety, and Stress Scale and the Edinburgh Stress, Anxiety, and Depression Scale at two weeks, one month and three months postpartum. The data revealed significantly lower scores for stress, anxiety, and depression in the aromatherapy group at two weeks, one month and three months postpartum, relative to the control group. Therefore the conclusion was that inhaling the scent of lavender for four weeks can prevent stress, anxiety, and depression after childbirth.

Amsterdam et al. (2009) conducted a randomized, double-blind efficacy and tolerability trial of matricaria recutita (chamomile) extract in patients with mild to moderate generalized anxiety disorder (GAD). Their hypothesis was that chamomile would prove superior to a placebo in reducing GAD symptoms with a not too dissimilar safety profile. Out of 57 participants with GAD, 28 were randomly assigned to receive chamomile extract for eight weeks while the other 29 subjects had placebo therapy for eight weeks. The results linked chamomile with a significantly greater reduction in mean total Hamilton Anxiety Rating (HAM-A) score compared to placebo (p = 0.047). Similar trends were observed for the secondary outcomes which included the Beck Anxiety Inventory, Psychological Well-Being score, and Clinical Global Impression Severity score. In terms of tolerability, the incidence of patients experiencing zero to three adverse effects or more was not significantly different between the groups, and only one person in each treatment group discontinued therapy due to adverse events. Amsterdam et al. (2009) claim the data suggests chamomile has modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder (GAD), but note that further studies that replicate these trends are required.

This 2014 review presented the case for curcumin’s potential use as a neuroprotectant and an antidepressant, describing some of its varied mechanisms of action: its possible anti-inflammatory effects and interactions with signal transduction proteins. Tizabi et al. (2014) write that curcumin is believed to be devoid of any side effects and could combat commonly observed co-morbid conditions of neurodegenerative and neuropsychiatric disorders. This review also provides evidence suggesting how this herb’s anti-inflammatory properties have therapeutic potential in treating devastating neurological disorders such as Parkinson’s disease (PD) and neuropsychiatric disorders such as major depressive disorder (MDD). The authors conclude that curcumin or one of its analogs could be of important therapeutic potential in PD and major depression.

Obstacles against the marketing of Curcumin as a drug

Interaction between Gut Microbiota and Curcumin: A new key of understanding for the health effects of Curcumin

Curcumin treatment leads to better cognitive and mood function in a model of Gulf War Illness with enhanced neurogenesis, and alleviation of inflammation and mitochondrial dysfunction in the hippocampus

The potential of treating Gulf War Illness with Curcumin

In this 2019 preclinical study, 129/SvEv mice were administered with 1.5% curcumin while under chronic social defeat stress (CSDS) to determine the extent to which curcumin can promote resilience to stress. This particular strain of mice were used due to their high susceptibility to this type of stress. The social interaction test showed a 4.5-fold increase in resilience, although not all the mice stayed strong under the stress. While 64% were tough and responded to the curcumin, the other 34% of mice remained vulnerable to the CSDS (non-responders). Differences between the responders and the non-responders were that the former released had lower concentrations of IL-6 and released less corticosterone following acute stress exposure, which might provide a novel treatment strategy focusing on the NF-κB pathway. Curcumin also prevented anxiety-like behavior in both responders and non-responders in the elevated-plus maze and open field test. Aubry et al. (2019) may have discovered two roles of curcumin: boosting resilience to CSDS and suppressing anxiety-like characteristics in people under chronic social stress.

While curcumin is known to be a natural polyphenolic compound with antioxidant and anti-inflammatory properties, this 2015 double-blind, cross-over trial investigated its correlation with incidences of anxiety and depressive symptoms among an obese sample. Thirty obese subjects were randomly allocated to receive either curcumin (1 g/day) or placebo for 30 days. A two-week wash-out period followed, before the participants were provided with the alternative regimen for another 30 days. Assessments were made at baseline and at weeks 4, 6 and 10 to determine the severity of the participants’ depression and anxiety. Although Beck Depression Inventory (BDI) scores did not show significant changes, the intake of curcumin was associated with significant reductions in mean Beck Anxiety Inventory (BAI) score of the sample. This trial suggests curcumin may possess anti-anxiety ability among obese individuals.

In this 2016 study, long-term therapy with chamomile (matricaria chamomilla L.) was investigated as a preventer of Generalized Anxiety Disorder (GAD) symptom relapse. The participants were outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD. First, a total of 179 individuals received 500mg of pharmaceutical grade chamomile extract three times per day for 12 weeks. The 93 (51.9%) responders continued in the double-blind randomized controlled trial involving 26 weeks of continuation chamomile therapy or placebo. The outcomes measured were: time to relapse during continuation therapy (analysed using Cox proportional hazards), proportion of the sample that relapsed, adverse effects related to treatment, and changes in vital signs. Relapse was found to be more common at follow-up among the participants that switched to placebo (n = 12/47; 25.5%) than the subgroup that continued on chamomile (n = 7/46; 15.2%). The chamomile-continuation set averaged longer to relapse (11.4 ± 8.4 weeks) compared with placebo (6.3 ± 3.9 weeks), and hazard of relapse was also non-significantly lower for chamomile (hazard ratio, 0.52; P = 0.16). Moreover, at follow-up the group maintained on chamomile experienced significantly fewer GAD symptoms than the placebo group, and significantly dropped in body weight and mean arterial blood pressure. Adverse event rates were low for both chamomile and placebo populations. Although long-term administration with chamomile was safe and significantly reduced moderate-to-severe GAD symptoms, the odds of relapse did not drop significantly (perhaps because of the small sample size and lower rate of relapse in the placebo group). Thus larger studies testing chamomile over placebo in GAD symptom relapse is encouraged.

An open-label study to elucidate the effects of standardized Bacopa Monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children

Neurotransmitter, antioxidant and anti-neuroinflammatory mechanistic potentials of herbal medicines in ameliorating Autism Spectrum Disorder

Phytochemicals in the treatment of Alzheimer's Disease: A systematic review

Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress

Efficacy of curcumin, and a saffron/curcumin combination for the treatment of major depression: A randomised, double-blind, placebo-controlled study