Stress, Insomnia, Depression & Herb Treatment

Dr. James Manos (MD)
July 5, 2019

Treating stress, insomnia & depression with herbs & dietary supplements

Treating stress, insomnia & depression with herbs & dietary supplements

·     Herbal teas, such as chamomile, mountain tea, linden, passionflower, sage, tisane, Melissa (lemon balm), and peppermint, help patients with stress and insomnia and can be found at the supermarket.

·   Warm milk with honey before bed helps to sleep, provided you do not have lactose intolerance that brings you bloating in the gut when drinking milk; in that case, prefer lactose-free milk that you find in a supermarket.

·     Relaxing music (such as the music of ‘Yanni’ or classical music - especially piano and/or wind; or special music for relaxation) helps patients with stress.

·        Sex is an excellent anti-stress activity! It also offers longevity!

·         Aromatherapy with essential oils drops in the water of a special aromatherapy lamp or added in the warm water in your bathtub or as a massage to help with relaxation. There is special aromatherapy for essential oils that are calming, such as Ylang Ylang and rose; some also add lavender. However, it is intense. Vanilla is awesome. Aromatherapy is contraindicated on people with epilepsy.

·      Aerobic exercises like jogging and swimming help with relaxation by increasing endorphins and natural painkillers like morphine! 

·        Medications such as benzodiazepines, barbiturates, and hypnotics are addictive (they make the patient junkie!), while other drugs such as venlafaxine (‘Effexor’) are used only for depression and have many side effects. Tricyclic antidepressants (TCAs) have many side effects. Psychotropic drugs must be given only by a psychiatrist and not another medical specialty.

·  Many psychological problems (e.g., general anxiety disorder, depression, and even schizophrenia) can be treated with cognitive-behavioral therapy (CBT) by a psychologist.

·      For depression, the herb St John’s Wort helps. Still, it has, like all herbs, contraindications and side effects. It interacts with many medications, such as antidepressants, SSRIs (e.g. paroxetine or fluoxetine), anticoagulants (such as warfarin), oral contraceptives, and theophylline (for asthma).

·   St John’s Wort is contraindicated in people with liver problems and patients receiving antiepileptic drugs.

·         Hawthorne (crataegus) is a herb for heart problems (such as heart failure).

·     Valerian (used for sleep and stress) is often combined with Passiflora (passionflower), vitamins B1, B2, B3, and wild lettuce.

·         Bach Flower Remedies help to deal with stress, insomnia, and other mood problems. They are usually used as sublingual (under the tongue) drops.

Herbs & dietary supplements with anxiolytic effects (that reduce anxiety)/ anti-stress effects

(with green color are the herbs & dietary supplements that I personally consider more important for this issue)

·         Chamomile

The results of a human study suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate generalized anxiety disorder (GAD).

The preliminary findings of a long-term, randomized, placebo-substitution study of chamomile for the prevention of recurrent Generalized Anxiety Disorder (GAD) are consistent with the authors’ previous RCT (randomized controlled trial) finding that over 50% of subjects with moderate or severe GAD symptoms respond to chamomile – the 1 500 mg dose of oral chamomile extract appears to be safe.

·         Ginger

·         Hawthorn  

A pilot study investigated the hypotensive potential of hawthorn extract and dietary magnesium supplements individually and in combination, compared with a placebo. Thirty-six mildly hypertensive subjects completed the study. Compared with the other groups, the factor analysis in ANOVA showed a promising reduction in the resting diastolic blood pressure at week ten in the nineteen subjects assigned to the hawthorn extract. Also, a trend towards a reduction in anxiety was also observed in those taking hawthorn compared with the other groups.

A study was carried out to test the free-radical-scavenging and anxiolytic activity of Crataegus nigra fruits. The anxiety effect, expressed as the difference in time spent in the open and closed arms, was measured and compared between groups. The results showed an anxiolytic effect. Species Crataegus nigra fruits hydroalcoholic extract showed antioxidant and anxiolytic activity.

·         Kava

Some clinical studies have found kava to be effective in treating symptoms associated with anxiety.

Several clinical studies, though not all, have found kava to be effective in treating symptoms associated with anxiety. In a review of 7 scientific studies, researchers concluded that a standardized kava extract was significantly more effective than a placebo in treating anxiety. Another study found that kava substantially improved symptoms after only 1 week of treatment. Other studies show that kava may be as effective as some prescription anti-anxiety medications. According to one study, kava and diazepam (Valium) cause similar changes in brain wave activity, suggesting that they may work in the same ways to calm the mind. Research on using kava for anxiety has decreased because of reports of liver toxicity. A 2004 study found that 300 mg of kava may improve mood and cognitive performance. That is significant because some prescription drugs used to treat anxiety, such as benzodiazepines (like Valium and alprazolam or Xanax), tend to decrease cognitive function.

Kava is possibly effective for anxiety. Most of the evidence shows that certain kava extracts standardized to 70% kavalactones can lower anxiety and might work as well as prescription low-dose benzodiazepines (anti-anxiety medications). But it might take up to 8 weeks of treatment to see improvement.

A Cochrane review assessed the effectiveness and safety reported in rigorous clinical trials of kava extract compared with a placebo for treating anxiety. To be included, studies were required to be randomized, controlled trials (RCTs). The authors concluded that compared with a placebo, kava extract is an effective symptomatic treatment for anxiety, although, at present, the size of the effect seems small. The effect lacks robustness and is based on a relatively small sample. The data available from the reviewed studies suggest that kava is relatively safe for short-term treatment (1 to 24 weeks), although more information is required. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Also, long-term safety studies of kava are required.

Kava (Piper methysticum) is a plant-based medicine previously shown to reduce anxiety. A total of seventy-five participants with a generalized anxiety disorder (GAD) and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on the response) versus a placebo. In conclusion, standardized kava may be a moderately effective short-term option for the treatment of generalized anxiety disorder (GAD). Furthermore, specific GABA transporter polymorphisms appear to potentially modify the anxiolytic response to kava.

A 5-week randomized, placebo-controlled, double-blind study investigated the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension, and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg daily, and pretreatment with benzodiazepines tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA), a subjective well-being scale (Bf-S), and the benzodiazepine withdrawal symptoms. Forty patients (2x20) were included in the study. The study concluded the anxiolytic (anxiety-relieving) efficacy and good kava-kava special extract WS1490 tolerance. It showed that further symptom reduction is possible after a change-over from benzodiazepine treatment.

In another 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava, 101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included. The results showed that in the main outcome criterion, the Hamilton Anxiety Scale (HAMA), the test drug had a significant superiority starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. Adverse events were rare and distributed evenly in both groups. The study concluded that the special extract of kava-kava WS 1490 is a treatment alternative to tricyclic antidepressants (TCAs) and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclic antidepressants and benzodiazepines.

A systematic review and meta-analysis assessed the evidence for or against the efficacy of kava extract as a symptomatic treatment for anxiety. Double-blind, randomized, placebo-controlled trials of oral kava extract for the treatment of anxiety were included. The methodologic quality of all trials was assessed. All seven reviewed trials suggested the superiority of kava extract over placebo. The meta-analysis of three trials suggests a significant difference in reducing the total score on the Hamilton Rating Scale for Anxiety in favor of kava extract. The review/ meta-analysis concluded that kava extract is superior to placebo as a symptomatic treatment for anxiety. Therefore, kava extract is an herbal treatment option for anxiety worthy of consideration.

The Kava Anxiety Depression Spectrum Study, a 3-week placebo-controlled, double-blind crossover clinical trial, assessed the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. The trial recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed, containing 250 mg of kavalactones daily. The study concluded that the aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression.

Note from the writer: Kava is not safe to use.

Note: Because some people have developed severe liver damage, even liver failure, after taking kava, it should only be taken under a doctor's close supervision. People with liver disease (such as cirrhosis or hepatitis) should not take kava. People should not use kava and alcohol together because the risk of impairment and the risk of liver damage is greatly increased. Kava is possibly unsafe when taken by mouth, and people should not use it. Serious illness, including liver damage, has occurred even with short-term use of normal doses.

·         Lemon balm

Lemon balm combined with other calming herbs (such as valerian, hops, and chamomile) may help reduce anxiety and promote sleep.

Few studies have examined lemon balm alone, except for topical use.

A study showed that the 600 mg dose of Melissa ameliorated the negative mood effects of the Defined Intensity Stressor Simulation (DISS), with significantly increased self-ratings of calmness and reduced self-ratings of alertness.

Another study concluded that a combination of Melissa officinalis (lemon balm) and Valeriana officinalis (Valerian) possesses anxiolytic properties that deserve further investigation.

·         Passiflora incarnata [Passionflower)

There is some evidence that passionflower can reduce symptoms of anxiety, sometimes as effectively as some prescription medications.

A study concluded that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam (a benzodiazepine anxiolytic) is an advantage.

A recent study found that patients given passionflower before surgery had less anxiety but recovered from anesthesia just as quickly as those given a placebo.

Chrysin, a Passiflora extract, may have anxiolytic properties like midazolam (a benzodiazepine sedative) but to a lesser magnitude at the 2 mg//kg doses used in a study.

·         Phosphatidylserine

A study showed that Treatment with soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) resulted in a pronounced blunting of both serum ACTH and cortisol and salivary cortisol responses to the Trier Social Stress Test (TSST). These data provide initial evidence for selective stress dampening the effect of PAS on the pituitary-adrenal axis, suggesting PAS's potential in treating stress-related disorders.

·         Rhodiola rosea

It may be effective for improving mood, and it also may improve depression.

A study demonstrated a significant improvement in generalized anxiety disorder (GAD) symptoms with Rhodiola rosea, with a reduction in Hamilton Anxiety Rating Scale (HARS) scores similar to that found in clinical trials.

·         Rosemary essential oil

A study suggests that rosemary and other aromatic (pleasant-smelling) oils may help reduce anxiety. However, in another study, people who inhaled rosemary said they felt more anxious than those who inhaled lavender and did not inhale a scent.

Note from the author: essential oils should not be ingested. They are also contraindicated in people with epilepsy.

·         American skullcap (Scutellaria lateriflora)

A number of the flavones found in S. lateriflora have been reported to selectively bind with high affinity to central benzodiazepine receptor sites, something that may explain the fact that these flavones exert anxiolytic effects in rats.

A study demonstrated noteworthy anxiolytic effects.

Another study in rats showed significant increases in the number of entries into the center of an ΄΄open-field arena΄΄, the number of unprotected head dips, the number of entries, and the length of time spent on the open arms of the Elevated Plus-Maze, and identified the flavonoid, baicalin and its aglycone baicalein, as well as the amino acids GABA and glutamine – these compounds may play a role in anxiolytic activity since baicalin and baicalein are known to bind to the benzodiazepine site of the GABAA receptor and since GABA is the main inhibitory neurotransmitter).

·         Chinese skullcap (Scutellaria baicalensis)

Chinese skullcap contains wogonin, a flavone found in one study to have anxiolytic properties in mice at doses of 7.5 to 30 mg//kg, without exhibiting the sedative and muscle-relaxing properties of benzodiazepines.

·         Valerian

Valerian is used for insomnia and other disorders as an alternative to benzodiazepines (also sedative and anxiolytic) and as a sedative for nervous tension, stress, sleeping disorders, restlessness, anxiety, and muscle relaxant.

A human study suggested valepotriates (valerian extract) may have a potential anxiolytic effect on the psychic symptoms of anxiety.

Another study in rats concluded that Valeriana officinalis was a potential alternative to the traditional anxiolytics as measured by the elevated plus maze// another study in rats & mice proposed that not sedative but anxiolytic and antidepressant activity, which was elaborated particularly in the special extract phytofin Valerian 368, considerably contribute to the sleep-enhancing properties of valerian.

·         Chromium

A study in rats investigated the effects of chromium picolinate (CrP) on elevated plus maze and spontaneous alternation behavior paradigm as a measure of anxiety and memory, respectively; the results showed that CrP significantly increased percentage preference to open arm in the elevated plus maze in diabetic and normal rats – the possible anxiolytic effect of CrP might be related to its effect on serotonergic transmission.

·         Dark chocolate

In a study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg, or 0 mg of polyphenols (placebo) in a parallel-groups design. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to the placebo. The study demonstrated the positive effects of cocoa polyphenols on mood in healthy participants. It provided a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

·         Ginkgo biloba

People with generalized anxiety disorder and adjustment disorder who took a specific extract of ginkgo had fewer anxiety symptoms than those who took the placebo.

Preliminary clinical research shows that a specific ginkgo extract (EGb 761, Tanakan) can reduce symptoms of anxiety in adults with a generalized anxiety disorder or adjustment disorder with anxious mood.

·         Damiana (Turnera diffusa)

·       Turnera aphrodisiaca (a variety of Turnera diffusa) (Turneraceae) has been traditionally used for the treatment of anxiety neurosis and as an aphrodisiac. Mother tinctures (85% ethanol extracts) of T. aphrodisiaca have also been used for the treatment of central nervous system disorders. In a study, T. aphrodisiaca mother tinctures formulated by three reputed manufacturers of homeopathic medicines (NLK, DWSG, and SBL) were evaluated for their anxiolytic activity. Mother tinctures of T. aphrodisiaca available in the market have significant anxiolytic activity. Amongst the three mother tinctures of T. aphrodisiaca analyzed, the dry residue of NLK possesses the highest amount of anxiolytic constituent(s).

·        Achillea millefolium (yarrow)

The results of a study in mice indicate that the orally (by mouth) administered hydroalcoholic extract of Achillea millefolium L. exerted anxiolytic-like effects that likely were not mediated by GABA(A)/benzodiazepine (BDZ) neurotransmission and did not present tolerance after short-term, repeated administration.

·         Gotu Kola (Centalla asiatica)

Gotu kola has chemicals called triterpenoids that decrease anxiety and increase mental function in mice. One human study found that people who took Gotu kola were less likely to be startled by a new noise than those who took the placebo. Since the "startle noise" response can be a way to tell if someone is anxious, researchers think that Gotu kola might help reduce anxiety symptoms. However, the dose used in this study was exceedingly high, so it's impossible to say how gotu kola might be used to treat anxiety.

A study in mice demonstrated the anxiolytic (amelioration of anxiety) effect of ECa 233, a standardized extract of Centella asiatica (Gotu kola) containing triterpenoids not less than 80%, in both acutely and chronically stressed animals (mice). These effects could be mainly accounted for by madecassoside and asiaticoside, suggesting a possible use of ECa 233 for the treatment of both acute and chronic anxiety in the pathological state

·  5 – HTP (5 – Hydroxytryptophan; serotonin synthesis precursor; produced commercially from the seeds of the African plant Griffonia simplicifolia)

The seeds of Griffonia simplicifolia Baill., a tropical shrub native to West Africa, are rich in 5-hydroxy-l-tryptophan (5-HTP), a direct precursor in the synthesis of serotonin (5-HT). A study investigated the effect of Griffonia simplicifolia seed extract on anxiety behavior. Griffonia simplicifolia seed extract, dosed at 1, 5, 10, and 25 mg/kg, was administered orally (by mouth) in rats submitted to the dark-light and open field tests 60 min after the treatment. The results showed that in the dark-light test, the administration of the extract at 10 and 25 mg/kg doses significantly increased the time spent in the light compartment. In the open field test, the extract dosed at 5, 10, and 25 mg/kg induced an anti-tigmotactic effect, as indicated by a significant increase in time spent in the central area of the open field. In conclusion, these findings indicate that Griffonia simplicifolia seed extract exerts an anxiolytic-like effect in rats and highlights its potential usefulness for the treatment of anxiety in humans.

Note: 5-Hydroxytryptophan (5-HTP; serotonin synthesis precursor) is possibly unsafe. There is concern that it can cause a serious side effect called eosinophilia-myalgia syndrome. Some people think this side effect is only caused by a contaminant in some 5-HTP products, but there is not enough scientific evidence to know if it is caused by 5-HTP, a contaminant, or some other factor. Until more is known, 5-HTP should be avoided. Side effects of 5-HTP are generally mild. At high doses, it is possible that serotonin syndrome, a dangerous condition caused by too much serotonin in the body, could develop. The author found no specific studies on PubMed (on 5 July 2014) in which Griffonia simplicifolia as a herb was implicated with the development of eosinophilic myalgia syndrome, or serotonin syndrome (at high doses) (keywords: Griffonia simplicifolia & eosinophilic myalgia syndrome /// keywords: Griffonia simplicifolia & serotonin syndrome). However, theoretically, as this herb is a source of 5-Hydroxytryptophan (5-HTP; serotonin), these adverse effects cannot be excluded after the consumption of this herb.

·         Horsetail

The petroleum ether (PE), chloroform (CH), ethanol (ETH), and water extracts of Equisetum arvense (horsetail) stems were evaluated for anti-anxiety activity in mice using an elevated plus maze model. The results suggest that the ethanolic extract of Equisetum arvense (horsetail) seems to possess an anxiolytic effect with lower sedative activity than that of diazepam (a benzodiazepine tranquilizer). The results could be attributed to the flavonoid content of the ethanolic extract.

·         Apocynum venetum/ kaempferol

A study evaluated the anxiolytic activity of an aqueous extract of Apocynum venetum L. (AV, family Apocynaceae) and bioguided its fractionation using the elevated plus maze (EPM) in mice as a model of anxiety. The anxiolytic activity of kaempferol was partially antagonized by the concomitant administration of flumazenil but not by WAY-100635. In conclusion, this study demonstrates that AV extract possesses anxiolytic-like activity and that at least one of its flavonoids, kaempferol, can elicit the same neuropharmacological activity.

·         Lysine

Dietary supplementation with an essential amino acid, L-lysine, has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. A study was carried out on one hundred eight healthy Japanese adults. The study aimed to determine whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. The authors confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, they found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympathoadrenal system) in male subjects. 

An investigation was conducted to determine whether a nutritionally essential amino acid, l-lysine, acts like a serotonin receptor 4 (5-HT4) antagonist and if l-lysine is beneficial in animal models of serotonin (5-HT)-induced anxiety, diarrhea, ileum contractions, and tachycardia and in stress-induced fecal excretion. The radioligand-binding assay was used to test the binding of l-lysine to various 5-HT receptors. The effects of l-lysine on 5-HT-induced contractions of isolated guinea pig ileum were studied in vitro. The results showed that an increase in the nutritional load of l-lysine might be a useful tool in treating stress-induced anxiety and 5-HT-related diarrhea-type intestinal dysfunctions.

Herbs & dietary supplements for insomnia (sleeping difficulty)

(with green color are the herbs & dietary supplements that I personally consider more important for this issue)

·         Chamomile

A study in rats concluded that chamomile extract is a herb having benzodiazepine-like hypnotic (helps to sleep) activity.

·         Kava

Preliminary evidence suggests that kava may help improve sleep quality and decrease the time needed to fall asleep. However, more studies are needed to say for sure.

Note: Because of the concerns about kava's safety and the fact that other herbs can treat sleeplessness, kava is not the best choice for treating insomnia. Because some people have developed severe liver damage, even liver failure, after taking kava, it should only be taken under a doctor's close supervision. People with liver disease (such as cirrhosis or hepatitis) should not take kava. People should not use kava and alcohol together because the risk of impairment and the risk of liver damage is greatly increased. Kava is possibly unsafe when taken by mouth, and people should not use it. Serious illness, including liver damage, has occurred even with short-term use of normal doses.

·         Lemon balm

Lemon balm combined with other calming herbs (such as valerian, hops, and chamomile) may help reduce anxiety and promote sleep.

Few studies have examined lemon balm alone, except for topical use.

·         Melatonin

Some evidence suggests that melatonin may work best for people over fifty-five who have insomnia.

Also, melatonin supplements may help with sleep problems associated with menopause.

Melatonin seems to be able to shorten the amount of time it takes to fall asleep, but only by about 12 minutes.

There is some evidence that melatonin is more likely to help older people.

In some patients with insomnia, melatonin appears to induce sleep onset.

A study concluded that prolonged-release melatonin formulation (PR-melatonin) results in significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency, and quality of life in primary insomnia patients aged 55 years and over.

·         Passiflora incarnata (Passionflower)

Passiflora extracts are an important factor in the phytotherapy of tenseness, restlessness, and irritability with difficulty falling asleep.

A study concluded that the consumption of a low dose of Passiflora incarnata, in the form of tea yields short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality).

·         American skullcap (Scutellaria lateriflora).

·         Hops (Humulus lupulus

·         Valerian

Valerian is possibly effective for insomnia.

Valerian is a popular alternative to prescription medications for sleep problems because it is considered to be both safe and gentle.

Some studies show that it helps people fall asleep faster and feel that they have better quality sleep.

A well-designed study found valerian was no more effective than a placebo for 14 days, but by 28 days, valerian greatly improved sleep for those taking it.

A human study suggests valerian might improve sleep quality without side effects.

Another human study concluded that treatment with an herbal extract of radix valerian demonstrated positive effects on sleep structure and sleep perception of insomnia patients and can, therefore, be recommended for the treatment of patients with mild psychophysiological insomnia.

A meta-analysis concluded that the qualitative dichotomous results suggest valerian would be effective for a subjective improvement of insomnia. However, its effectiveness has not been demonstrated with quantitative or objective measurements).

·        Tart cherry

A human study showed that consuming a tart cherry juice concentrate provides an increase in exogenous melatonin that improves sleep duration and quality in healthy men and women and might be beneficial in managing disturbed sleep.

The results of another human pilot study suggested that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia, with effect sizes equal to or exceeding those observed in studies of valerian and in some but not all, studies of melatonin, the two most studied natural products for insomnia].

·        Gotu Kola (Centalla asiatica)

Gotu kola acts as a sedative when given to animals in tests. Because of that, it is sometimes suggested to help people with insomnia, but no human studies have been done to see whether it works and whether it's safe.

· 

  5 – HTP (5 – Hydroxytryptophan; serotonin synthesis precursor; produced commercially from the seeds of the African plant Griffonia simplicifolia)

In one study, people who took 5-HTP went to sleep faster and slept more deeply than those who took the placebo. These researchers recommend 200 – 400 mg at night to stimulate serotonin, but it may take 6 – 12 weeks to be fully effective.

Note: 5-Hydroxytryptophan (5-HTP; serotonin synthesis precursor) is possibly unsafe. There is concern that it can cause a serious side effect called eosinophilia-myalgia syndrome. Some people think this side effect is only caused by a contaminant in some 5-HTP products, but there is not enough scientific evidence to know if it is caused by 5-HTP, a contaminant, or some other factor. Until more is known, 5-HTP should be avoided. Side effects of 5-HTP are generally mild. At high doses, it is possible that serotonin syndrome, a dangerous condition caused by too much serotonin in the body, could develop. The author found no specific studies on PubMed (on 5 July 2014) in which Griffonia simplicifolia as a herb was implicated with the development of eosinophilic myalgia syndrome, or serotonin syndrome (at high doses) (keywords: Griffonia simplicifolia & eosinophilic myalgia syndrome /// keywords: Griffonia simplicifolia & serotonin syndrome). However, theoretically, as this herb is a source of 5-Hydroxytryptophan (5-HTP; serotonin), these adverse effects cannot be excluded after the consumption of this herb.

Herbs & dietary supplements with antidepressant effects

(with green color are the herbs & dietary supplements that I personally consider more important for this issue)

·         Bacopa monnieri (Brahmi)

·         Blueberries

·         Coenzyme Q10

A human study showed that lower CoQ10 plays a role in the pathophysiology of depression and, in particular, in treatment-resistant depression and chronic fatigue syndrome accompanying depression, and it is suggested that depressed patients may benefit from CoQ10 supplementation.

·         Turmeric/ curcumin

Curcumin has shown promising efficacy in various animal models of major depression.

·         Essential fatty acids (EFA)

They have been shown to decrease the risk of depression.

·         Alpha-linolenic acid [ALA, an omega-3 fatty acid]

A study showed that ALA intake was inversely associated with depression risk.

The inverse association between ALA and depression was stronger in women with low linoleic acid (LA) intake.

·         Omega-3 fatty acids/ fish oil

Several studies have found that people who took omega-3 fatty acids in addition to prescription antidepressants had a greater improvement in symptoms than those who took antidepressants alone.

A study aimed to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression. The mean changes in scores of depression did not differ significantly between the two groups. However, analysis of covariance showed that in the fish oil group, there was a significant correlation between the change in erythrocyte DHA and the change in scores of depression.

·         Passiflora incarnata (Passionflower)

Many species have been found to contain beta-carboline harmala alkaloids, which are MAO inhibitors with anti-depressant properties.

·         Rhodiola rosea

It may be effective for improving mood, and it also may improve depression.

A study concluded that the standardized extract SHR-5 shows anti-depressive potency in patients with mild to moderate depression when administered over a 6-week period.

Another study demonstrated that Rhodiola rosea roots have potent antidepressant activity by inhibiting MAO-A and may also find application in the control of senile dementia by their inhibition of MAO B.

Another study concluded that Rhodiola rosea extract could improve 5-HT (serotonin) levels in the hippocampus in depressive rats. Low dosage Rhodiola rosea could induce neural stem cell proliferation at the hippocampus to return to normal, repairing the injured neurons at the hippocampus.

·         Saffron [dried stigmas of the plant Crocus sativus)

Animal studies have shown that the aqueous and ethanolic extracts of saffron and its constituents, crocin, and safranal, have antidepressant activities, as revealed during forced swimming tests.

A study showed that saffron was effectively like imipramine in the treatment of mild to moderate depression and concluded that saffron may be of therapeutic benefit in the treatment of mild to moderate depression.

·       SAMe [some studies suggest that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without their side effects (headaches, sleeplessness, and sexual dysfunction)// also, antidepressants tend to take 6 – 8 weeks to begin working, while SAMe’s action seems to start more quickly.

However, many of the studies have examined injectable forms of SAMe, not an oral supplement, and the quality of the studies has varied.

SAMe can be as beneficial and effective as some prescription medications for depression (tricyclic antidepressants TCAs).

Some studies also show that taking SAMe might be helpful for people who do not have a good response to a prescription antidepressant.

SAMe is superior to placebo and is as effective as tricyclic antidepressants (TCAs) in alleviating depression, although some individuals may require higher doses.

SAMe may have a faster onset of action than conventional antidepressants.

A study concluded that S-Adenosylmethionine (SAMe) may be useful for patients who cannot tolerate tricyclic antidepressants (TCAs).

·         Sesame oil (lignans)

·         Eleuthero (called wrongly by some as Siberian ΄΄ginseng΄΄)

·         St. John’s wort [Hypericum perforatum)

The available evidence suggests that the Hypericum extracts tested in the included trials are superior to placebo in patients with major depression, are similarly effective as standard antidepressants, and have fewer side effects than standard antidepressants.

There is good evidence that St. John’s wort may reduce symptoms in people with mild-to-moderate, but not severe (or major), depression.

In many studies, it seems to work as well as selective serotonin reuptake inhibitors (SSRIs), a popular type of antidepressant that doctors often prescribe first to treat depression, including fluoxetine (Prozac), citalopram (Celexa), and sertraline (Zoloft).

St. John’s wort doesn’t seem to have one of the most common side effects of antidepressants: loss of libido (sex drive).

Many studies have compared St. John's wort to Prozac, Celexa, paroxetine (Paxil), and Zoloft and found that the herb works as well as the drug.

A Cochrane review concluded that St. John’s wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants. However, findings were more favorable to St. John’s wort extracts in studies from German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries, St. John’s wort extracts seemed less effective.

A human study concluded that Hypericum perforatum (St. John’s wort) extract WS 5570 was safe and more effective than a placebo for treating mild to moderate depression/.

Another human study concluded that the Hypericum perforatum extract (St. John’s Wort) preparation was therapeutically equivalent to fluoxetine (an SSRI antidepressant) and is a rational alternative to synthetic antidepressants.

·         Valerian

A study in rats & mice proposed that not a sedative but anxiolytic and antidepressant activity, which was elaborated particularly in the special extract phytofin Valerian 368, considerably contributes to the sleep-enhancing properties of valerian.

·         Chamomile

A human study concluded that chamomile may provide a clinically meaningful antidepressant activity that occurs in addition to its previously observed anxiolytic activity.

·         Chromium

One small study found that chromium picolinate improved symptoms of depression in people with atypical depression. However, a larger study found that chromium did not help.

A study in mice demonstrated the antidepressant-like activity of chromium in the mouse forced swim test (FST) and indicates the primary role of the AMPA receptor and participation of NMDA glutamatergic and 5-HT(1) and 5-HT(2A/C) serotonin receptors in this activity.

·         Citicoline [CDP – Choline/ INN)

The findings of a human placebo-controlled trial in a dual diagnosis sample with methamphetamine use disorders suggest that citicoline may have antidepressant properties in this population; greater treatment retention with citicoline is also noteworthy in a patient population with substance dependence.

·         Dark chocolate

In a study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg, or 0 mg of polyphenols (placebo) in a parallel-groups design. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to the placebo. The study demonstrated the positive effects of cocoa polyphenols on mood in healthy participants. It provided a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.

·         Fisetin 

The findings of a study on mice indicate that the antidepressant-like effect of fisetin involves the regulation of the central serotonin and noradrenaline levels.

· 5 – HTP (5 – Hydroxytryptophan; serotonin synthesis precursor; produced commercially from the seeds of the African plant Griffonia simplicifolia)

Some small studies indicate that 5-HTP may work as well as certain antidepressant drugs to treat people with mild-to-moderate depression. Like the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs), which include fluoxetine (Prozac) and sertraline (Zoloft), 5-HTP increases the levels of serotonin in the brain. One study compared the effects of 5-HTP to fluvoxamine (Luvox; a medication that acts as SSRI and σ1 receptor agonist) in 63 people and found that those who were given 5-HTP did just as well as those who received fluvoxamine. They also had fewer side effects than the Luvox group. However, these studies were too small to say if 5-HTP works. More and larger studies are needed.

Note: 5-Hydroxytryptophan (5-HTP; serotonin synthesis precursor) is possibly unsafe. There is concern that it can cause a serious side effect called eosinophilia-myalgia syndrome. Some people think this side effect is only caused by a contaminant in some 5-HTP products, but there is not enough scientific evidence to know if it is caused by 5-HTP, a contaminant, or some other factor. Until more is known, 5-HTP should be avoided. Side effects of 5-HTP are generally mild. At high doses, it is possible that serotonin syndrome, a dangerous condition caused by too much serotonin in the body, could develop. The author found no specific studies on PubMed (on 5 July 2014) in which Griffonia simplicifolia as a herb was implicated with the development of eosinophilic myalgia syndrome, or serotonin syndrome (at high doses) (keywords: Griffonia simplicifolia & eosinophilic myalgia syndrome /// keywords: Griffonia simplicifolia & serotonin syndrome). However, theoretically, as this herb is a source of 5-Hydroxytryptophan (5-HTP; serotonin), these adverse effects cannot be excluded after the consumption of this herb.

·         Guarana

Guarana, a herbal extract from the seeds of Paullinia cupana Mart., has been evaluated in comparison with caffeine on mouse behavior in forced swimming and open field tests. The results showed that Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg, p.o.) each significantly reduced the duration of immobility in the forced swimming test, suggesting an antidepressant-like effect in mice. At these doses, neither substance affected ambulation in the open field test. However, a high dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the locomotor activity in the open–field test. Caffeine, but not guarana, could effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced increase in swimming immobility, suggesting that mechanism(s) other than the adenosinergic mechanism are involved in the antidepressant-like activity of guarana

·         Inositol

A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials (RCTs) were conducted comparing inositol for depression or anxiety disorder patients. Seven RCTs in depression (n = 242 subjects) were identified. In conclusion, the results of the meta-analysis suggest that inositol may be beneficial for depressed patients, especially those with premenstrual dysphoric disorder (PMDD). The main limitation of this report is that a small number of studies were included in this meta-analysis].

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