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. [NPID: adaptogens, herbs, ashwagandha, stress, anxiety, cortisol]

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, stress, cortisol, anxiety, depression, HPA axis]

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]

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]

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. [NPID: insomnia, ashwagandha, anxiety, herbs]

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]

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.[NPID: curcumin, turmeric, depression, depressive, MDD, anxiety, mood]

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, development, cognition, anxiety, curcumin, anxiety, vegan, plant-based, neurological]

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. [NPID: curcumin, depression, herbs, mood]

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]

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. [NPID: herbs, lavender, stress, anxiety, postpartum, aromatherapy, motherhood, pregnancy, 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. [NPID: matricaria recutita, herbs, chamomile, generalized anxiety disorder, anxiety, GAD]

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]

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 2020 review outlines the most recent studies conducted on curcumin, a polyphenol compound derived from Curcuma longa (turmeric), including its strong links with the microbiota that live in the human gut. Curcumin, which has been used for centuries in traditional Asian medicine as well as for cooking purposes as a spice all over the world, has also attracted the attention of the healthcare sector. Known for its anti-inflammatory and antioxidant mechanisms, curcumin has been proposed to manage diabetes, gastrointestinal and neurological diseases, as well as several types of cancer. However, scientists are still working on fully understanding its pharmacology, and there remains inconsistencies in findings with regards to curcumin’s activity in vivo (within a living organism) and in vitro (outside a living organism). Since high concentrations of this compound have been found in the gastrointestinal tract, it has been recently proposed that the impact of curcumin is directly controlled mainly in this part of the body. This hypothesis would clear up the paradox between curcumin’s wide range of pharmacological activity and its low bioavailability. Additionally, curcumin and its metabolites have been seen to have influence on the microbiota. It is believed that curcumin regulates intestinal microflora, while gut microbiota may biotransform curcumin, suggesting the importance of microbial inhabitants of the human body for curcumin activity. The microbiota have several key roles in human physiology, and its depletion in the gut can have great consequences with regards to human disease development. [NPID: herbs, curcumin, turmeric, asian, anti-inflammatory, gastrointestinal, microbiota]

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]

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

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. [NPID: chamomile, anxiety, generalized anxiety disorder, GAD, 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]

Kardani et al. (2019) review the medicinal herbs that hold the most potential in preserving neuronal structure and function (neuroprotective effects). Autism spectrum disorder (ASD) is an example of a neurodevelopmental problem that affects all aspects of the sufferer’s social development. Currently, pharmacological treatments are being used to lessen some of the symptoms such as self-mutilation, aggression, repetitive and stereotyped behaviors, inattention, hyperactivity, and sleep disorders. But there is not yet an effective medication for autism. The underlying origin of the disorder is not well understood. But oxidative stress is believed to be involved, while the serotonergic, adrenergic and dopaminergic systems have also been implicated. This review finds that the medicinal herbs Zingiber officinale, Astragalus membranaceu, Ginkgo biloba, Centella asiatica and Acorus calamus, have antioxidant activity, and may be neuroprotective. The writers suggest that these herbs may be suitable, at least in theory, in terms of a management strategy for autism. [NPID: neuroprotective, Autism, social, oxidative, herbs]

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]

This 2019 study investigated thymoquinone, a natural antioxidant found in abundance in the curative plant Nigella sativa seed's oil. Since the amyloid beta (Aβ) peptide contributes the most to the advancement of Alzheimer's disease (AD), Alhibshi et al. tested thymoquinone on its neuroprotective potential in Aβ1-42 -induced neurotoxicity. The cholinergic neurons used in this study were derived from cultured human induced pluripotent stem cells (hiPSC). The thymoquinone diminished the amount of cell death and apoptosis caused by Aβ1-42, inhibited the production of reactive oxygen species induced, and replenished the level of intracellular antioxidant enzyme glutathione. Furthermore, thymoquinone was shown to reduce synaptic toxicity caused by Aβ1-42. These findings suggest that thymoquinone may be a promising therapeutic agent to reduce the risk of developing Alzheimer’s disease and other disorders of the central nervous system. [NPID: thymoquinone, herbs, Alzheimer’s, CNS]

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, peruvian, depression, stress, fluoxetine, hippocampus, memory, cortisol, noradrenaline, dopamine, oxidative]

Lopresti & Drummond (2017) highlight the potential of curcumin (derived from the spice turmeric) and saffron as antidepressants that have been indicated by several studies already. In this randomized, double-blind trial, 123 participants with major depressive disorder were randomly selected to receive either: placebo control; low-dose curcumin, high-dose curcumin, or a combination of low-dose curcumin with saffron (15mg b.i.d.) for 12 weeks. The measure Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used to assess depression severity, while the Spielberger State-Trait Anxiety Inventory (STAI) examined the subjects’ state and trait anxiety. The combined curcumin plus saffron treatment was associated with significantly bigger improvements in depressive symptoms compared to placebo, as well as better STAI-state and STAI-trait scores. The treatments with active drugs were the most effective when given to people with atypical depression, in comparison to the other patients. However, there were no marked differences in response between the low and high doses of curcumin or the curcumin/saffron combination. To summarize the results, the active drug treatments (including the different doses of curcumin and combination with saffron) were found to be effective in reducing depressive and anxiolytic symptoms in people with major depressive disorder. [NPID: curcumin, turmeric, saffron, depression, MDD]

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, Honokiol; Hypothalamic–pituitary–adrenal HPA.]

The main objective of this 2021 study was to determine the effects of taking saffron (30mg standardized extract daily for 8 weeks) on emotional well-being in healthy adults with feelings of low mood and anxiety and/or stress (but not to the clinical levels). Jackson et al. also assessed the short-term impact of taking saffron in response to a lab-based psychosocial stressor. This was a double-blind, randomized design where the participants were randomly assigned to receive either saffron extract or placebo for 8 weeks, with neither the subjects nor the experimenter aware of which treatment was being administered. At the end of the study, it was revealed that the saffron treatment group reported lower depression scores and better social relationships than before the experiment. In addition, saffron consumption mitigated the typical stress-induced reduction in heart rate variability (HRV) observed during exposure to the lab-based psychosocial stressor. It was deduced that saffron extract may positively influence subclinical depressive symptoms in healthy individuals and may help raise resilience against the development of stress-related psychiatric disorders. [NPID: anxiety, crocetin, depression, heart, variability, saffron]

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, stress, HPA, NF-κB, neuroinflammation]

Shinjyo et al. (2020) decided to further examine Valerian (Valeriana officinalis L.), a popular herbal medicine used as a sleep aid, to comprehend why they have previously featured in clinical studies without consistent results. Sleep problems are also commonly related to various comorbidities such as anxiety. This review aims to provide a broader view of valerian’s use in various associated disorders. Sixty studies were highlighted for its relevance to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A meta-analysis suggested that the inconsistent outcomes are due to the variable quality of herbal extracts (the whole root/rhizome may be more likely to provide reliable effects). Furthermore, its therapeutic effects may be greater when combined with other herbal compounds. Importantly, the intake of valerian did not cause any severe adverse effects in the participants (aged between 7 and 80 years). In summary, Valerian may be a safe and effective herb for inducing sleep and preventing associated disorders. But it appears that revision of the quality control processes is needed. [NPID: anxiety; herbal, insomnia, sleep, systematic review, valerian]

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: alternative, complementary, anxiolytic, botanical, Chamomile, GAD, herbal]

In this 2018 study, 80 healthy adults were randomized to drink either 250 mL of rosemary water or plain mineral water, before completing a series of cognitive tasks and being examined on alertness and fatigue. Hemoglobin levels (total, oxygenated and deoxygenated) were also taken at baseline and throughout the cognitive testing procedure. The results indicated that rosemary water had several small but statistically significant benefits, compared with mineral water. While cognition was found to be better after consuming the rosemary water, the level of deoxygenated hemoglobin was markedly higher when the rosemary water treatment group performed the cognitive tasks, compared with the mineral water group. This is of particular interest since it suggests that oxygen extraction may be triggered when there is cognitive demand. Overall, this study points out the various beneficial properties of rosemary water. [NPID: rosemary, water, cognitive, oxygenated, hemoglobin]

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: memories, cannabidiol, endocannabinoid, fear, PTSD]

The purpose of this 2021 study was to analyze the use of complementary alternative medicine (CAM) in depression among a sample of depressed patients in Iran. It was revealed that of the 300 participants, 37.6% used complementary alternative medicines. There was a significant difference in duration of disease and body mass index between the CAM users and non-users. Specifically, CAM use was heavily linked with the female sex, disease duration, overweight, obesity, and self-employment. Among complementary alternative medicines, herbal medicine was most frequently used (97.35%), followed by pray therapy (23.89%). The most widely used herbs included borage (77%), chamomile (46.9%), and lavender (21.2%). Furthermore, the study found that 62.8% of the patients were using CAM therapies for their effectiveness. But most of the patients did not consult with the physicians before taking advantage of these CAM therapies. Despite this, the commonly used treatment for depression (herbal medicine) had a high satisfaction level. For this reason, physicians may need to enhance their understanding of various complementary alternative medicines. [NPID: complimentary, herbs, borage, chamomile, lavender, depression]

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, anxiety, herbal, disorder, Withania Somnifera]

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, motor, aromatherapy, Bergamot, serotonin, neurotransmission]

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.

Since the aqueous extract of Gladiolus dalenii (AEGD) has shown its antidepressant-like activity in previous rodent studies, Fotsing et al. (2017) theorized that AEGD can protect rats from behavioral, neurochemical, and reproductive changes induced by stress. To test this theory, rats were put under chronic immobilization stress to induce female reproductive and behavioral dysfunctions, before a proportion of the population were fed the G. dalenii plant extract every day for 28 days. The scientists obtained daily vaginal smear samples to assess duration of specific phases of the estrous cycle and monitored the rats’ behaviors at the end of the 28-day period of chronic immobilization stress. In addition, the reproductive organs were sacrificed and weighed, and assessments of biochemical parameters were carried out. The rats that received the plant extract had lower corticosterone, progesterone, and prolactin levels than those stressed rats that did not receive treatment. Furthermore, the readings for serotonin, triglycerides, adrenaline, cholesterol, glucose estradiol, follicle stimulating hormone and luteinizing hormone were significantly higher in the rats that were administered with G. dalenii, diazepam, as well as those treated with a combination of both plant extract and diazepam. Moreover, the G. dalenii was found to reduce the marked differences in estrous cycle phases induced by stress (identified by comparing stressed vs. vehicle control rats). Finally, G. dalenii extract blocked the reproductive, behavioral, and neurochemical alterations induced by stress. [NPID: Gladiolus dalenii, biochemical, estrous, neurochemical, restraint, stress]

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: depression, Fluoxetine, herbal, lavandula angustifolia, melissa, persian]

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: animal depression, hesperidin, kynurenine, social, defeat]

Ng et al. (2017) highlight the lack of large meta-analyses recently conducted on St John’s wort’s use in depression, despite the existence of conflicting evidence on its benefits and risks. St John’s wort is a popular herbal remedy that is licensed and widely prescribed for depression in many European countries. This present meta-analysis reviewed a total of 27 clinical trials (producing a dataset of 3808 patients) that compared the use of St John’s wort to other antidepressants such as the serotonin selective reuptake inhibitors (SSRIs). The response and remission rates were similar between the two agents, with significantly less participants who took St John’s wort stopping treatment or dropping out of the study, compared with those who took SSRI antidepressants. The data also demonstrated the clinical efficacy of St. John’s wort in reducing depressive symptoms. As all the studies ranged between 4 to 12 weeks, evidence on the long-term efficacy and safety of St. John's wort is limited. Another limitation was the lack of data on St John's wort’s impact on severe depression, high suicidality, and suicide risk. To summarize the findings of this meta-analysis, St John's wort has an efficacy and safety profile comparable to SSRI antidepressants in the treatment of mild-to-moderate depression.

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, depressive, anxiety, rhodiola, crocus]

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, helichrysum, anxiety, herbal, hippocampus, medicinal, noradrenergic neurons]

This 2020 trial tested the antidepressant effect of chamomile in patients with generalized anxiety disorder (GAD) with and without depression. Amsterdam et al. hypothesized that the anxiolytic impact of chamomile will be similar between patients with and without depression, but the antidepressant activity will be better in GAD sufferers with depression than those without. A dose of 1500mg chamomile extract was taken by a set of randomly selected participants for 8 weeks. In total, 179 adults (aged 18 years and above) were recruited. The results showed that the anxiolytic ability of chamomile was similar over time in both subgroups. However, depressive scores dropped significantly more in the GAD patients with comorbid depression when compared with those without depression (evident in several depressive assessments). In conclusion, chamomile extract may have particularly strong antidepressant properties (in addition to its anxiolytic activity) in subjects with generalized anxiety disorder and comorbid depression. [NPID: Matricaria, chamomilla, antidepressant, anxiety, anxiolytic, chamomile, depression]