Herbs and Mental Health

This 2019 paper is focused on curcumin, a component of the spice turmeric and a widely used ingredient in food recipes. Curcumin is well recognized for its strong anti-inflammatory, antioxidant, anti-cancer, and antimicrobial characteristics. In addition, curcumin is used in diabetes, arthritis, and several hepatic, renal, and cardiovascular diseases. In this review, curcumin is examined on its potential use in neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent studies have suggested that curcumin can perhaps prevent or delay the onset of neurodegenerative diseases. This article also discusses the recent progress that has been made to improve the therapeutic efficacy of the curcumin/curcuma formulation, and to ensure safe and effective drug delivery despite low bioavailability and toxicity reports. As well as summarizing the ongoing clinical trials on curcumin for various neurodegenerative diseases, this review showcases the patent details of curcuma/curcumin in India. [NPID: India, Indian, turmeric, curcumin, herb, spice, inflammation, antioxidant, Alzheimer’s, Parkinson’s, MS, multiple sclerosis, Huntington’s, Prions, Down’s, autism, anxiety, depression, aging]

This 2019 study used a specific attention deficit hyperactivity disorder (ADHD) model in rats to test the therapeutic potential of baicalin (an herbal extract). This rat model (using spontaneously hypertensive rats) depended on the dopamine deficit theory. Firstly, 50 rats were randomly chosen to be treated with either methylphenidate (MPH), baicalin, or saline. The group receiving baicalin were administered with one of three strengths (50 mg/kg, 100 mg/kg, or 150 mg/kg). All rats were treated for 4 weeks, even the rats used in the control experiment (10 Wistar Kyoto rats). Hyperactivity decreased and spatial learning memory deficit improved in the ADHD-model rats that received baicalin (100mg/kg and 150mg/kg) and in those administered with methylphenidate, compared with the saline treatment. Moreover, methylphenidate considerably increased dopamine levels in two areas of the brain (the prefrontal cortex and the striatum). Dopamine levels were also found to be significantly higher after treatment with baicalin but only in the striatum. It may be that baicalin targets the striatum. These results demonstrated the effectiveness of baicalin in controlling the core symptoms of ADHD. There were connections between the pharmacological impact of baicalin with the synthesis and release of dopamine, suggesting that baicalin may be effective at treating ADHD. [NPID: ADHD, baicalin, herbs, herbal extract, dopamine, hyperactivity, methylphenidate]

This 2020 study examines Scutellaria baicalensis (S. baicalensis/Chinese Skullcap), Hericium erinaceus (H. erinaceus/Mushroom) and Rhodiola rosea (R. rosea), three herbs with favorable risk-benefit profiles that appear to effectively alleviate anxiety or depression. These traditional folk medicinal herbs target the principal biochemical events that are implicated in mental disorders. Additionally, these herbal treatments to some extent mimic the mechanisms of actions of conventional antidepressants and mood stabilizers but are said to be better tolerated. To elaborate, these alternative treatment options influence neurotransmitter and neuro-endocrine systems, stimulate the growth and development of nervous tissue and neurotrophic factors, and counteract oxidative stress, mitochondrial dysfunction, and inflammation. Although some experimental and clinical studies have released promising results, further analysis is required to better understand the antidepressant-like effects of these herbs. [NPID: depression, antidepressant, herbs, herbal, alternative, medicines, Scutellaria baicalensis, Hericium erinaceus, Rhodiola rosea, anxiety, mood]

Since curcumin has been hypothesized to effectively treat symptoms of various neuropsychiatric disorders, this 2020 systematic review was focused on finding articles that tested curcumin on participants affected by mental disorders. Curcumin, a constituent of turmeric (a spice frequently used in Asian countries), in fact has demonstrated anti-inflammatory and antioxidant properties. Seven articles were found to involve individuals affected by major depressive disorder, while two other studies had subjects who suffered from depression secondary to a medical condition. This review discovered that curcumin had an overall significant effect on depressive and anxiety symptoms (with large effect size) while causing limited adverse effects. The findings suggest that curcumin might improve depressive and anxiety symptoms in those affected with depression, but this data should be cautiously interpreted given its small sample size. Additional testing is recommended, particularly in Western countries where curcumin does not form a part of the usual dietary regimens. [NPID: curcumin, turmeric, spices, herbs, herbal, alternative, medicines, depression, anxiety, review, Asia, Asian, major depressive disorder, MDD]

The objective of this 2019 study was to confirm the antidepressant-like effects of baicalin on mice induced with chronic unpredictable mild stress (CUMS). Another aim was to determine the pharmacological mechanisms involved. After mice underwent chronic unpredictable mild stress to induced depression, several behavioral tests were performed. Certain cells (PC12) were pretreated with baicalin for 2 hours, before being stimulated with corticosterone for 24 hours. Following CUMS treatment, the mice demonstrated depressive-like symptoms such as decreased sucrose consumption, and increased immobility time in the tail suspension test (TST) and forced swim test (FST). The baicalin significantly reduced these changes. Moreover, the herbal treatment inhibited inflammatory cytokine levels in the blood, hippocampus homogenate and cell culture medium. This present study backed up the evidence on biacalin’s antidepressant effects on depression and may have identified a possible pathway involved (the HMGB1/TLR4/NF-κB pathways). [NPID: mice, animal, rodent, baicalin, Scutellaria radix, stress, depression, antidepressant, herbal, herbs, alternative, medicine]

This 2021 review examined a selection of studies concerning the antidepressant effects of ginsenosides on major depressive disorder animal models. The systematic review looked at trials that tested the impact of ginsenoside on whole, living organisms or cells (in vivo models). A meta-analysis was then conducted to assess behavioral changes induced by ginsenoside Rg1 since this was the most commonly studied ginsenoside. Of the twenty-three studies included in the final analysis, twelve of these analyzed ginsenoside Rg1. The majority of these 12 studies reported significant differences in 2 of the measures when compared with the vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity (variation) across studies. The results nonetheless suggest that ginsenosides represent promising antidepressants. Ginsenosides, and the Rg1 subtype in particular, seemed to reduce symptoms of depression in animal models. [NPID: ginsenosides, herbs, herbal, alternative, medicines, depression, major depressive disorder, MDD, animal, antidepressants]

Although Crocus sativus (commonly known as saffron) has demonstrated its antidepressant properties, this 2020 study explored the impact of consuming saffron capsules on food craving, body weight, and depression in overweight women with mild to moderate depression. The seventy-three women who participated all had a BMI of 25 or above. They were randomized to either receive 30 mg of Crocus sativus capsules or 30mg of placebo capsules daily in this 12-week clinical trial. The results showed that the average depression scores were significantly lower in the saffron group, compared to the placebo group. But there was no evidence of saffron influencing food cravings in the women. Moreover, the treatment group experienced fewer side effects than the placebo group. This trial indicated that saffron capsules did not effectively reduce food cravings in overweight patients with mild/moderate depression but can potentially help reduce their depressive symptoms. [NPID: saffron, depression, women, overweight, depressed, antidepressants, crocus, cravings, alternative, herbs, herbal]

Since depression and sexual problems are commonly seen in patients with coronary artery disease (and affecting their quality of life), this 2017 study was conducted to determine the efficacy of saffron and crocin (one of its main constituents) on improving mental health and quality of life in people with coronary artery disease. The patients (aged between 40-65 years) were divided into 3 groups: one placebo and 2 intervention groups. One of these intervention groups received 30 milligrams of saffron aqueous extract, while the other group was given 30 milligrams of crocin for 8 weeks. The study design was randomized and double-blind, meaning that neither the participants nor the researcher knew which treatment or intervention the subjects were receiving until the clinical trial was over. Compared to pre-treatment, both the saffron and crocin intervention groups saw significant reductions in depression scores in one of the measures (Beck’s Depression Inventory). There was no apparent difference in total depression score between the saffron and crocin groups. Both groups markedly enhanced patients’ quality of life, although they had no major effect on sexual desire. Ultimately, both saffron and crocin improved depression and quality of life in patients with coronary heart disease. [NPID: saffron, crocin, herbs, mental health, alternative, medicine, Iran, Iranian, depression, sexual desire, sexuality, coronary artery disease]

Since there has been a recent growth in long-term use of alternative medicine, Borgonetti et al. (2020) inspected Helichrysum stoechas (L.) Moench methanolic extract (HSE) as a potential treatment for anxiety- and depression-related symptoms. HSE has shown its ability to inhibit monoamine oxidases (MAOs), which is how a class of existing antidepressants (called MAO Inhibitors) act. A selection of tests indicated that HSE reduces anxiety-like (but not depressive-like symptoms) in a dose-dependent manner. In addition, HSE did not affect pain modulation in the mice, demonstrating its selectivity for reducing anxiety-like behavior. Moreover, sedation, impaired motor coordination or memory was not detected after taking active doses of HSE. Furthermore, other effects of anxiety (reduction in the phosphorylation of ERK44/42, disruption of brain-derived neurotrophic factor (BDNF) expression and cyclic AMP response element binding) were reversed by HSE. This suggests that HSE may protect against anxiety-like behavior. To conclude, the intake of HSE through the oral route may be a potentially effective therapy for the management of anxiety disorders. [NPID: BDNF, herbs, helichrysum, anxiety, herbal, hippocampus, medicinal, noradrenergic neurons]

While the medicinal plants Rhodiola rosea L. (rhodiola, golden root) and Crocus sativus L. (saffron) have both shown significant antidepressant effects, this 2018 study aimed to assess the effectiveness of a rhodiola-saffron combination in treating mild to moderate depression. With the help of general practitioners (GPs), 45 adults with mild or moderate depression were given a combination of rhodiola and saffron extracts (one tablet, 154 mg of rhodiola and 15 mg of saffron; recommended dose two tablets per day for 6 weeks). After 6 weeks of daily ingestion, the patients’ depressive assessment scores (Hamilton Rating Scale for Depression) noticeably decreased by 58%. In fact, 85.4% of the patients’ scores improved. Looking at the other measures for anxiety and depression (Hospital Anxiety and Depression Scale anxiety and depression), there were marked reductions again at 6 weeks. From 2 weeks post-intake, the decreases in scores were significant. Both the GP and the patient agreed that their depression had improved by the end of the study. Moreover, no severe adverse effects were reported. This observational study supports the use of a rhodiola and saffron combination in the management of mild to moderate depression. These compounds may also provide anxiolytic benefits, but a double-blind placebo-controlled study is warranted to provide further evidence. [NPID: major, herbs, depressive, anxiety, rhodiola, crocus]

This 2019 paper examines the Japanese local citrus plant, Citrus tumida, since one of its components (hesperidin) has anti-inflammatory properties. Sato et al. believe that anti-inflammatory reagents may have roles in interventions designed to prevent and alleviate risk of depression. Studies have shown enhanced stress resilience in mice facing sub-chronic and mild social defeat following consumption of immature Citrus tumida fruit peels. Moreover, taking 0.1% hesperidin significantly increased stress resilience and modified kynurenine (KYN) levels in various areas of the brain (KYN is believed to be involved in chronic inflammation). These findings suggest that dietary hesperidin elevates resilience to stress through prevention of KYN signaling. [NPID: herbs, animal depression, hesperidin, kynurenine, social, defeat]

This 2020 study examines Melissa officinalis L and Lavandula angustifolia Mill (Lavender) since they have been used to treat depression in Asia and have even been referred to as treatments for depression in traditional Persian literature. Araj-Khodaei et al. set out to compare the efficacy of these herbs to fluoxetine in the treatment of mild to moderate depression. The participants were 45 adult outpatients with major depression. The subjects were randomized to receive either 2g of M. officinalis, 2g of L. angustifolia, or 20mg of fluoxetine, before being examined for depressive symptoms at weeks 0, 2, 4 and 8. The results indicated that both M. officinalis and L. angustifolia had similar effects to fluoxetine in mild to moderate depression. Having said that, the absence of a placebo group was one of the limitations of this trial. Additional support from large-scale trials assessing the anti-depressant effect of these two herbs is needed. [NPID: herbs, depression, Fluoxetine, herbal, lavandula angustifolia, melissa, persian]

With interest in the potential therapeutic use of some Cannabis sativa plant compounds rising, García-Gutiérrez et al. (2020) focus on one of the main phytocannabinoids, cannabidiol (CBD) since it has no potential for becoming a drug of abuse (unlike THC). This review presents a variety of animal and human studies to portray the anxiolytic, antidepressant, and antipsychotic effects of CBD. For example, preliminary clinical trials back up CBD’s efficacy as an anxiolytic, antipsychotic, and antidepressant. More importantly, these trials demonstrate the positive benefit-risk in favor of using CBDs. The results from the rodent studies suggest that CBD’s impact depends on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. Moreover, the pharmacological activity of CBDs have been associated with cannabinoid receptors, the 5-HT1A receptor, and neurogenesis factors. Overall, these results are promising and encourage further research (on a large scale) to analyze CBD as a potential new drug for the treatment of these psychiatric disorders. [NPIDs: herbs, cannabis, sativa, phytocannabinoids, CBD, animal, depression, psychosis]

This 2020 article is centered on the essential oils extracted from the fresh fruit of Citrus bergamia Risso et Poiteau, and its potential use in managing anxiety. This oil is currently being utilized in aromatherapy to reduce pain, help induce sleep, and/or minimize the impacts of stress-induced anxiety. Preclinical research has indicated that bermagot essential oils (BEOs) alter certain neurotransmissions and produce an effect similar to anxiolytic but not consistent with that of the benzodiazepine diazepam. Neurotransmissions other than GABAergic may therefore play a part in this mechanism. One of these is serotonergic (5-HT) neurotransmission, which is believed to have a function in anxiety. The 5-HT1A subtype of serotonergic receptors appear to play a particularly important role in anxiety. Rombolà et al. say that adjusting this 5-HT1A receptor may influence some of the anxiolytic-relaxant effects of bergamot essential oils. [NPID: anxiety, herbs, motor, aromatherapy, Bergamot, serotonin, neurotransmission]

Fuladi et al. (2020) investigated W. somnifera root extract on its therapeutic potential in reducing standard generalized anxiety disorder (GAD) symptoms (Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect). The sample group included 40 patients who were diagnosed with GAD and were taking Selective Serotonin Reuptake Inhibitors (SSRIs, a class of antidepressants). The participants were then randomized to either receive one capsule of the extract or placebo per day for six weeks. Although the GAD symptom severity of the control group decreased during the course of the trial, there were greater reductions in Hamilton anxiety rating scale (HAM-A) in the treatment group versus the control group (14 vs 8 units reduction, respectively). Moreover, there was a particularly significant difference in symptom severity between the second and sixth week in the treatment group. No adverse effect was reported during this trial. This study concludes that W. somnifera extract may be a safe and effective form of adjunctive therapy to SSRIs in generalized anxiety disorder. [NPID: Generalized, herbs, anxiety, herbal, disorder, Withania Somnifera]

Bitencourt & Takahashi (2018) examine cannabidiol (CBD), a constituent of Cannabis sativa without the psychoactive effects of Δ9-tetrahydrocannabinol since they have been reported to help remove undesirable memories and block their reconsideration. Since the endocannabinoid (eCB) system is thought to be involved, CBD may be a potentially therapeutic drug for post-traumatic stress disorder (PTSD). While PTSD affects around 10% of people at some point in life, the current pharmacological therapies are lacking in efficacy and cause substantial side effects. Recent studies have confirmed that CBD can modify important aspects of unpleasant memories in humans and significantly improve the symptomatology of PTSD. The aim of this review was to demonstrate CBD’s therapeutic potential by presenting preclinical and human experimental studies. Hopefully this raises awareness of CBD’s use cases in treating these disorders related to inappropriate retention of unpleasant memories. [NPID: herbs, memories, endocannabinoid, fear, PTSD]

Since chamomile had shown its efficacy vs. placebo in people with Generalized Anxiety Disorder (GAD) in a previous study, Keefe et al. (2016) conducted this randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. The patients with moderate to severe generalized anxiety disorder were randomly chosen to take 1500mg of chamomile extract daily for up to 8 weeks. Of the 179 subjects, 58.1% showed clinical response while 15.6% prematurely discontinued treatment. Symptom severity was also reported to have decreased over time (indicated by GAD-7 rating). Moreover, the secondary outcomes (that marked anxiety and well-being) improved in a statistically significant and clinically meaningful way. Adverse events occurred in 11.7% of the sample, although there was no serious side effect. To summarize, chamomile extract reduced the generalized anxiety disorder symptoms over 8 weeks at a rate comparable to those observed during conventional anxiolytic drug therapy and demonstrated a better safety profile. [NPID: herbs, alternative, complementary, anxiolytic, botanical, Chamomile, GAD, herbal]

Cai et al. (2020) report their findings on the antidepressant-like effects of penta-acetyl geniposide ((Ac)5GP, a derivative of geniposide (a major active component of Gardenia jasminoides Ellis). While the rats were under chronic unpredictable mild stress (CUMS), (Ac)5GP treatment seemed to alleviate the depression-like behaviors induced by CUMS. Moreover, the elevations in interleukins (IL-1β, IL-6) and tumor necrosis factor (TNF-α) mRNA normally observed in chronic unpredictable mild stress were reversed by the (Ac)5GP. It was therefore thought that (Ac)5GP treatment improved the depression-like behaviors in rats possibly by inhibiting neuroinflammation in certain areas of the brain (prefrontal cortex) and blocking activations of proteins (NF-κB and NLRP3). [NPID: antidepressant, herbs, stress, HPA, NF-κB, neuroinflammation]

In this 2018 study, Wang et al. examined honokiol (the main component of Magnolia officinalis) and its ability to reduce depressive-like symptoms in rats with chronic unpredictable mild stress (CUMS). This investigation comes after honokiol demonstrating a variety of pharmacological activities. The potentially antidepressant effects of honokiol were tested in the rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Additionally, blood samples were taken to monitor the concentrations of hormones, proteins and receptors (hippocampal brain-derived neurotrophic factor [BDNF] and glucocorticoid receptor α [GRα] levels) to assess possible mechanisms. Finally, the honokiol (given at 2, 4, and 8 mg/kg) was found to reduce behavioral dysfunctions induced by the chronic unpredictable mild stress. The treatment also normalized the hyperactivity of the limbic hypothalamic-pituitary-adrenal (HPA) axis associated with chronic unpredictable mild stress. These data confirm that honokiol possesses antidepressant-like properties. [NPID: antidepressant, brain-derived neurotrophic factor, BDNF, stress, herbs, Honokiol; Hypothalamic–pituitary–adrenal HPA.]

This 2014 study investigates the effect of an extract of maca, a Peruvian medical food with anxiolytic and antidepressant properties eaten for thousands of years. Ai et al. aimed to determine the behavioral, anatomical, and biochemical impact of the petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three doses of maca extract were used (125, 250, and 500 mg/kg) for 6 weeks, while the positive control drug investigated was fluoxetine at 10 mg/kg. The extracts at 250 and 500 mg/kg significantly reduced the duration of immobility time in the tail suspension test (an assessment that suspends the mice by their tails and records their behavior). At these doses, the granule cell layer in the dentate gyrus appeared thicker (dentate gyrus = part of the hippocampus thought to contribute to the formation of new episodic memories). The cortisol concentrations of the mice significantly dropped also after administration of the extract at 250mg/kg and 500mg/kg. After six weeks of treatment, noradrenaline and dopamine levels were raised by maca extract, and the activity of reactive oxygen species was significantly inhibited. This study associates the petroleum ether extract of maca with the lowering of oxidative stress in the mouse brain, and with the activation of the noradrenergic and dopaminergic systems. In addition, the results provide evidence that the extract exhibits antidepressant-like effects. [NPID: maca, herbs, peruvian, depression, stress, fluoxetine, hippocampus, memory, cortisol, noradrenaline, dopamine, oxidative]

Due to the emerging evidence that plant-based biologically active compounds may slow down the onset and progression of Alzheimer's disease (AD), D'Onofrio et al. (2017) conducted a systematic review examining the current literature on phytochemicals’ potential use in the management of Alzheimer’s disease. The review included articles that assessed cognitive, functional and clinical status using the suitable measures, and had participants aged 60 and above, with AD diagnosed according to the criteria of National Institute on Aging-Alzheimer's Association (NIAAA). In total, ninety-seven articles were included. It appeared that numerous phytochemicals slow down the onset of AD, delay disease progression, and lead to recovery. Despite these positive signs, it is highlighted that more data is required on these phytochemicals and its molecular targets in order to ensure safety if these compounds are to be used to treat Alzheimer’s. [NPID: Alzheimer’s, cognition, herbs]

Dave et al. (2014) point out how poor the average response rates are (70%) of children with attention-deficit hyperactivity disorder (ADHD) taking psychostimulant medications. The children may not respond to the medication or in some cases suffer from adverse effects such as nausea, insomnia, and weight loss. This study therefore tries to find an effective treatment of ADHD using the standardized Bacopa monnieri extract (SBME). Conducted in Mumbai, India, this open-label trial recruited thirty-one children between the ages of 6 and 12. The onset of ADHD was before the kids were 7 years old. The SBME was given at 225mg per day for a period of 6 months. To assess ADHD symptom scores at baseline and at post-treatment, the Parent Rating Scale was used. The scores were significantly reduced after treatment with SBME, with the exception of social problems. There was a 93% reduction in score for restlessness, as well as improvement in self-control seen in 89% of the participants. Similarly, scores for learning problems, impulsivity, and psychiatric problems were reduced in 78%, 67%, and 52% of the kids, respectively. Total subtest scores reduced by at least 20% in the majority of the subjects (74%), while 26% of the children also scored between 21-50% less in the total subtests. It was concluded that the standardized extract of B monnieri was effective in ameliorating the children’s ADHD symptoms while also being well tolerated. [NPID: ADHD, attention, herbs, self-control, restlessness, impulsivity, Bacopa, SBME]

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. [NPID: curcumin, turmeric, antioxidants, anti-inflammatory, anxiety, depression, obesity, herbs]

Kodali et al. (2018) investigated the efficacy of curcumin in protecting rats’ cognitive and mood function since it has been reported to possess neurogenic, anti-inflammatory, antioxidant, and memory and mood enhancing properties. On a daily basis, for 28 days, the male rats were exposed to low doses of chemicals that have been associated with the Gulf War Illness (GWI). The rodents were then randomly selected to either receive curcumin daily or a vehicle treatment for 30 days. The rats given daily curcumin showed better cognitive and mood function sixty days after treatment, indicated by behavioral assessments such as object location, novel object recognition and novelty suppressed feeding tests. Moreover, these animals demonstrated improved neurogenesis (formation of new neurons in the brain) and reduced inflammation. Furthermore, in this Gulf War Illness (GWI) rat model, curcumin appeared to increase expression of antioxidant genes and normalize expression of multiple genes related to mitochondrial respiration. The researchers conclude that curcumin is efficacious in the maintenance of memory and mood function among GWI rats. It was suggested that the enhanced neurogenesis, protection from inflammation and oxidative stress, and the normalized mitochondrial respiration may underlie curcumin’s beneficial effects on rats’ memory and mood. [NPID: herbs, cognition, mood, anti-inflammatory, memory, curcumin, turmeric, neurogenesis]

This 2020 review article explores the scientific research conducted so far on curcumin, an active compound of the perennial herb Curcuma longa. While scientists have examined the therapeutic effects of countless natural compounds on chronic human diseases such as cancer, cardiovascular disease, and neurodegenerative disease, curcumin is of particular interest because of its diversity of molecular targets. However, the clinical effectiveness of curcumin is weak due to its low bioavailability (proportion that enters the bloodstream) and rapid metabolism. When given orally, animal-based studies and phase 1 clinical studies have discovered that little curcumin is absorbed by the intestine, and that it is metabolized by the intestine as well as the liver. Researchers have tried to improve the bioavailability of curcumin through various methods over the last decade. Thus, there are several enhanced curcumin-based formulations ranging in terms of bioavailability. Finally, this review discusses the pharmacokinetics of curcumin (data concerning the movement of drugs around the body) and the problems that exist for marketing curcumin as a drug. [NPID: herbs, curcumin, Curcuma, cancer, cardiovascular, neurodegenerative, pharmacokinetics]

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. [NPID: herbs, curcumin, depression, anti-inflammatory, neurological disorders, Parkinson’s disease, Parkinson’s, major depressive disorder, MDD]

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. [NPID: matricaria recutita, herbs, chamomile, generalized anxiety disorder, anxiety, GAD]

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. [NPID: saffron, depressive, MDD, depression, herbs]

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. [NPID: DHA, herbs, development, cognition, anxiety, curcumin, anxiety, vegan, plant-based, neurological]

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. [NPID: withania somnifera, WS, WSE, ashwagandha, anxiety, herbs, ayurvedic, neurodegenerative, PTSD, memory, hippocampus]

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. [NPID: withania somnifera, WSE, anxiety, stress, herbs]

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. [NPID: withania somnifera, WSE, anti-inflammatory, schizophrenia, stress, herbs]

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.[NPID: ashwagandha, herbs, stress, cortisol, anxiety, depression, HPA axis]