DHEA improves depressed mood but not symptoms of cognitive impairment or schizophrenia

What it is and how it works in the brain

Dehydroepiandrosterone (DHEA) is a precursor of testosterone and other hormones. The sulfated form of DHEA—DHEA-S—is the most abundant steroid in the body. DHEA is an important neuroactive steroid and modulates neuronal excitability by acting as an antagonist at the GABA receptor complex. Preclinical animal studies suggest that mood-enhancing effects of DHEA are mediated through androgen receptors, estrogen receptors, serotonin, GABA, NMDA, and possibly norepinephrine. DHEA’s antipsychotic effects may involve increased dopamine release in the frontal cortex and increased activity of NMDA and sigma receptors.

DHEA for depressed mood

In a small six-week study (22 subjects), depressed patients were randomized to DHEA in an escalating dose (30 mg per day for two weeks, followed by 30 mg twice daily for two weeks and 30 mg thrice daily for two weeks) versus placebo. Half of the patients in the DHEA group improved by 50 percent or more on standardized rating scales. In a six-week placebo-controlled trial (46 subjects), moderately depressed adults off antidepressants were randomized to 90 mg per day of DHEA for three weeks, followed by 450 mg per day of DHEA (150 mg thrice daily) for three weeks versus placebo. The majority taking DHEA reported a 50 percent or greater reduction in depressive symptoms and improved sexual functioning. Most patients who responded to DHEA remained asymptomatic at the 12 months follow-up. More studies are needed to replicate these findings, evaluate DHEA for severe depressed mood, and clarify the mechanism for a putative synergistic or independent antidepressant effect. In a small placebo-controlled trial (30 subjects), inpatients with schizophrenia treated with 100 mg per day of DHEA in addition to their conventional antipsychotic medications experienced significant improvements in depressed mood, anxiety, and negative psychotic symptoms. Women improved more than men, and serum cortisol levels did not change during treatment.

DHEA for cognitive decline in normal aging

DHEA is used in Europe and North America to self-treat decline in cognitive functioning associated with normal aging, however, limited research findings support this use. Small pilot studies suggest that DHEA (25 to 50 mg per day) improves memory and enhances general cognitive functioning in healthy adults. However, most findings are inconsistent, and negative findings have been reported at doses less than 90 mg per day. A systematic review of studies on DHEA or DHEA-S in healthy older adults found no evidence of improved memory or cognitive functioning. Large studies of at least one year or longer are needed to fully explore claims of long-term beneficial effects of DHEA.

DHEA for dementia

DHEA may improve memory in elderly patients who have low DHEA serum levels more than in healthy adults with normal serum levels. However, no correlations were found between serum DHEA-S levels and severity of cognitive impairment or cumulative mortality in a large cohort of individuals newly diagnosed with Alzheimer disease. Preliminary findings suggest that 200 mg per day of DHEA may improve symptoms of cognitive impairment in multi-infarct dementia. However, no controlled trials on DHEA in Alzheimer disease have been completed. In a six-month placebo-controlled trial (47 subjects), men with mild dementia and healthy men aged 50 years and older were randomized to receive 75 mg of testosterone (in the form of a dermal gel) versus placebo together with their usual medications. Quality-of-life measures improved in men with mild dementia and healthy men taking testosterone, and fewer men with mild dementia who received testosterone experienced declines in overall functioning and visuospatial abilities.

DHEA for schizophrenia

In a six-week placebo-controlled trial (30 subjects), inpatients diagnosed with schizophrenia randomized to DHEA at 100 mg per day in addition to their regular antipsychotic medications experienced significant improvements in negative psychotic symptoms, including reduced apathy and social withdrawal. However, there were no significant changes in positive psychotic symptoms, including auditory hallucinations and delusions. Findings of another small study (30 subjects) suggest that augmentation of antipsychotics with DHEA (100 mg day for six weeks) may significantly reduce negative symptoms and may be especially effective in women. However, a systematic review of three small placebo-controlled studies (126 total subjects) on DHEA or testosterone as adjunctive therapies to antipsychotics found equivocal evidence for an augmentation effect on measures of positive and negative symptoms, global functioning, and quality of life.

Huperzine: A Chinese Herbal for Mild Cognitive Impairment (MCI) and Dementia

What it is and how it works

Huperzine-A is an alkaloid compound derived from the herb Huperzia serrata and is an ingredient of herbal formulas used in Chinese medicine to treat Alzheimer disease and age-related cognitive decline. Animal studies show that huperzine-A reversibly inhibits acetylcholinesterase (the brain enzyme that breaks down the neurotransmitter acetylcholine), slows age-related neurotoxicity, regulates the secretion of nerve growth factor, and protects against oxidative stress and neuronal cell death associated with β-amyloid formation. All of these mechanisms probably contribute to the beneficial effects of huperzine-A on cognition and memory.

Summary of research evidence

Findings from preclinical animal studies suggest that huperzine-A may have a longer duration of action, better penetration of the blood–brain barrier, and be a more potent and more specific inhibitor of acetylcholinesterase than available prescription cholinesterase inhibitors–the principal treatments of dementia in Western countries. Placebo-controlled human trials report consistent beneficial effects of huperzine-A in age-related memory loss, Alzheimer disease, and vascular dementia at very small doses–between 200 and 400 micrograms per day. A meta-analysis of eight placebo-controlled randomized controlled trials (733 total subjects) on huperzine-A in Alzheimer disease and two placebo-controlled randomized controlled trials on huperzine A in vascular dementia reported improved global mental functioning as measured by changes in mini-mental status exam (MMSE) and improvements in daily activities. The significance of these findings is limited by small study size and poor methodological quality of some studies included in the meta-analysis.

Safety issues

Infrequent adverse effects include transient dizziness, nausea, and diarrhea. To learn more about huperzine-A and other complementary and alternative approaches for treating mild cognitive impairment (MCI) or dementia read my e-book “Dementia and mild cognitive decline: The Integrative Mental Health Solution.”

Virtual Reality Graded Exposure Therapy (VRGET) for PTSD and Phobias

Virtual Reality Graded Exposure Therapy (VRGET)–What it is and how it works

VRGET is a technology-based exposure therapy with important implications for the management of post-traumatic stress disorder (PTSD) as well as severe phobias that are difficult to treat using conventional psychological therapies and medications. VRGET combines advanced computer graphics, three-dimensional visual displays, and body-tracking technologies to create realistic virtual environments with the goal of simulating feared situations or objects. Virtual environments have been designed to provide visual, auditory, tactile, vibratory, vestibular, and olfactory stimuli to patients in highly controlled settings. During a virtual exposure session, the therapist closely tracks the patient’s state of arousal by monitoring physiological indicators of stress, including heart rate and respirations. Many individuals are readty to take the next step and engage in real life (i.e., in vivo) exposure to the feared object or situation after they have been desensitized to a virtual environment.

VRGET is more effective than conventional exposure therapy

VRGET is more effective than conventional imaginal exposure therapy and has comparable efficacy to in vivo exposure therapy for the treatment of specific phobias, agoraphobia, panic disorder, and PTSD. Like in vivo and imaginal exposure therapy, VRGET desensitizes the patient to a situation or object that would normally cause anxiety or panic. In a randomized controlled trial, VRGET and conventional cognitive behavioral therapy (CBT) were equally effective treatments of panic disorder with agoraphobia, and patients who underwent VRGET required 33 percent fewer sessions to achieve similar results. Studies also confirm that VRGET is an effective treatment of fear of flying, fear of heights, fear of small animals, fear of driving, and other phobias. VRGET is as effective as and more cost-effective than conventional exposure therapy for fear of flying because patient and therapist avoid the cost and inconvenience of airplanes. A virtual environment simulating the devastation of the September 11, 2001, attacks on the World Trade Towers has been successfully used to treat individuals diagnosed with severe PTSD following the attacks.

VRGET reduced PTSD symptoms in combatants who do not respond to conventional exposure therapy

Findings of a study on combined multisensory exposure and VRGET reported significant reductions in severity of PTSD symptoms in active duty combatants who had failed to respond to other forms of exposure therapy. Several subjects reported significant improvement following only five VRGET sessions; however, there was considerable variability in the number of VRGET sessions needed to reduce symptom severity to the same level.

VRGET is being used to screen individuals at high risk of developing PTSD

Research studies are being aimed at developing virtual reality tools for assessing and preventing combat-related PTSD. STRIVE (Stress resilience in virtual environments) is a highly integrative “stress resilience training” program aimed at enhancing emotional coping strategies prior to active deployment. STRIVE employs an immersive VR environment to simulate combat situations that includes a “virtual mentor” who guides the combatant through a virtual experience while coaching him or her in relaxation and emotion self-regulation skills. The intensity of the virtual stimulus used is determined by the individual’s habituation based on HRV and other measures of autonomic arousal. Physiological biomarkers of stress response are measured before and after VRGET sessions. The STRIVE system permits users to be immersed in stressful combat scenarios and interact with virtual characters for training in a variety of coping strategies that may enhance resilience in the face of extreme stress. The STRIVE protocol may provide a useful tool for predicting the risk of developing PTSD or other psychiatric disorders in new recruits prior to actual combat exposure. Recruits who display high resilience and thus presumably at relatively lower risk of developing PTSD might be more suitable for direct combat roles while individuals who display low resilience might preferentially be assigned to noncombat roles.

Future innovations will integrate VRGET with biofeedback and broadband internet connections permitting in-home therapy

Future integrative approaches to phobias, panic attacks, and other severe anxiety disorders will combine VRGET with biofeedback in outpatient settings or in the patient’s home via broadband Internet connections, with CBT, relaxation, mind–body practices, and appropriate medications. Combining VR environments with real-time feedback based on neurophysiological responses to stress may permit each unique patient to optimize the level and type of VR exposure to enhance resiliency training and speed the rate of recovery from PTSD. Human–computer interface (HCI) systems based on CBT and biofeedback are being developed for resilience training in individuals at risk of developing PTSD following exposure to trauma. Larger studies on patient populations diagnosed with PTSD using headmounted displays and other technologies that create more immersive virtual environments are needed to determine whether combining VRET and EEG biofeedback is practical in clinical settings and yields superior outcomes compared to either approach alone.

Few safety problems

Infrequent cases of disorientation, nausea, dizziness, headache, and blurred vision have been reported following VRGET. Intense sensory stimulation during VRGET can trigger migraine headaches, seizures, or gait abnormalities in individuals who have these disorders. Patients with schizophrenia should not use VRGET because immersion in a virtual environment can exacerbate delusions.

To learn more about VRGET and other non-pharmacologic treatments of PTSD check out my e-book “Post-traumatic stress disorder: the integrative solution.”

High-density negative ions for seasonal affective disorder (SAD)

Regular exposure to high density negative ions may be as effective as bright light therapy for seasonal depressed mood

I recently posted a blog on the health benefits of light. In addition to bright full-spectrum light and (to a lesser extent) dim blue or red light, emerging evidence suggests that regular daily exposure to high-density negative ions may be an effective treatment of seasonal depressed mood and may have comparable efficacy to bright light exposure for this condition.

Twenty-five depressed patients with seasonal depressed mood were randomized to high-density negative ions (2.7 × 106 ions/cm3) versus low-density negative ions (1 × 104 ions/ cm3) using in-home ion generators 30 minutes daily for 3 weeks. Fifty-eight percent of patients exposed to high-density negative ions experienced significant improvements in mood on standardized rating scales, compared to 15 percent of patients exposed to low-density negative ions. In a 2-week randomized-controlled trial (158 subjects), patients with seasonal depressed mood were randomly assigned to bright light exposure (10,000 lux) versus high-density or low-density negative ions. Patients exposed to high-density negative ions or bright light experienced significant and equivalent improvements in mood. In another controlled trial (128 subjects), bright light exposure, a pleasing auditory stimulus, and high-density negative ions resulted in equivalent and rapid improvements in mood and alertness in mildly depressed and non-depressed adults.

No adverse effects

Adverse effects have not been reported with regular daily exposure to negative ions following the approaches used in published studies.

Integrative mental health care

To learn more about non-pharmacologic therapies of depressed mood and other mental health problems read my e-books on integrative mental health care.

Urgent Need for Transforming Mental Health Care

Existing models of care and conventional therapies are limited

Existing models of care and available conventional treatment approaches fail to adequately address the global crisis of mental health care. Mental illness accounts for about one-third of the world’s disability caused by all adult health problems, resulting in enormous personal suffering and socioeconomic costs. Severe mental health problems including major depressive disorder, bipolar disorder, schizophrenia, and substance use disorders affect all age groups and occur in all countries, including the US, Canada, the European Union countries, and other developed and developing countries. Mental illness is the pandemic of the 21st century and will be the next major global health challenge. There is a large and growing gap between mental health care needs of the population and available resources.

Weak evidence and safety problems affect many psychotropic medications

Many individuals diagnosed with bipolar disorder, major depressive disorder, and schizophrenia depend on medications to function and be productive members of society. However, after decades of research and billions of dollars of industry funding, the evidence supporting pharmacologic treatments of major depressive disorder, bipolar disorder, and other psychiatric disorders is not compelling. Many commonly prescribed psychotropic medications including antidepressants and antipsychotics are associated with serious adverse effects, including weight gain, increased risk of diabetes and heart disease, neurologic disorders, and sudden cardiac death. Metabolic syndrome associated with weight gain and increased risk of diabetes and coronary artery disease is a well-documented adverse effect of antipsychotics and other psychotropic agents. Poor treatment outcomes owing to limited efficacy of antidepressants, mood stabilizers, antipsychotics, and other psychotropic medications result in long-term impaired functioning, work absenteeism, and losses in productivity.

CAM therapies can help improve outcomes

In the context of the limitations of available conventional biomedical treatments, accumulating research findings are providing evidence for both safety and efficacy of select complementary and alternative (CAM) treatments of depressed mood, anxiety, and other mental health problems, including select pharmaceutical-grade natural products, lifestyle modifications (Lifestyle Medicine), mind-body approaches, and nonallopathic whole-system approaches such as traditional Chinese medicine and Ayurveda. Examples of natural supplements being investigated as nonpharmacologic therapies include S-adenosyl methionine for depressed mood; the adjunctive use of nutraceuticals (ie, botanicals and other natural product supplements) as stand-alone therapies or in combination with psychotropics such as omega-3 fatty acids, folic acid (especially its active form l-methyl-folinic acid), 5-hydroxytryptophan, and n-acetyl cysteine for mood disorders; a standardized extract of the herbal kava; and the amino acid l-theanine.

To read more click here.

Light therapy for depressed mood and insomnia

How light therapy works

Light of different intensities and colors is used in conventional biomedicine and many nonconventional systems of medicine to treat both medical and psychiatric disorders. Diverse mechanisms of action are probably involved, including regulation of melatonin and neurotransmitters. Entrainment of sleep–wake cycles by external bright light cues and the associated suppression of melatonin production by the pineal gland is the established mechanism of action underlying the therapeutic benefits of light exposure on sleep and daytime fatigue.

Bright light therapy for depressed mood

Exposure to natural sunlight, especially in the early morning, has significant antidepressant benefits and may reduce the length of hospital stays in severely depressed patients who are hospitalized. A systematic review of controlled studies confirmed an antidepressant effect of bright light (10,000 lux) exposure therapy in seasonal depressed mood but provided only limited evidence supporting bright light as a treatment of nonseasonal depressed mood. A more recent meta-analysis of controlled studies concluded that bright light exposure or dawn simulation for seasonal depressed mood and bright light exposure (but not dawn simulation) for nonseasonal depression had comparable efficacy to antidepressants. Findings of a small randomized controlled trial suggested that bright light therapy may be an effective alternative to antidepressants in pregnant depressed women.

Dim red or blue light for seasonal depressed mood

Recent studies suggested that regular exposure to dim red or blue light might be as efficacious as bright light, especially in the management of seasonal depressed mood. In a 4-week single-blind study (57 subjects), patients diagnosed with seasonal affective disorder (SAD) were randomized to daily bright light versus dim red light exposure. Both groups experienced an equivalent and significant (40 percent) reduction in symptoms. Preliminary findings suggest that antidepressant effects of early-morning exposure to narrow spectrum blue or green light may be equivalent to benefits obtained from full-spectrum bright light exposure. Exposing depressed patients to low-intensity artificial light approximately 2 hours before they would naturally be exposed to early-morning daylight increased the speed of response to conventional antidepressants. Thirty depressed inpatients treated with citalopram at 40 mg per day were randomized to early-morning dim green light, 400 lux, versus a sham, non–light-emitting device during the first 2 weeks of drug treatment. Patients in the combined citalopram–light exposure group reported significantly greater and more rapid improvements in mood compared to the citalopram only group. No adverse effects have been reported with regular exposure to dim light.

Light therapy for sleep disorders

An expert consensus report on light treatment for sleep disorders concluded that there is compelling evidence for the efficacy of bright light exposure in the management of circadian rhythm sleep problems but not for other types of insomnia. Most protocols recommend 30 to 40 minutes of bright light exposure daily for beneficial effects in shifting circadian rhythms and changing sleep–wake cycles. Beneficial effects of bright light exposure therapy are usually noticeable within a few days, and an appropriate treatment plan often resynchronizes the patient’s sleep–wake cycle with his or her time zone in 2 to 3 weeks. Correct timing of light exposure is essential for successful treatment of circadian sleep problems, and bright light exposure between the hours of late morning and late afternoon probably has no effect on circadian rhythm phase. Preliminary findings suggest that melatonin used in conjunction with bright light exposure may achieve more rapid normalization of the sleep–wake cycle.

Safety issues

Individuals interested in trying light therapy for depressed mood or a sleep disorder should avoid using sun lamps (which emit harmful ultraviolet rays) and keep the eyes open while viewing the light fixture at an oblique (approximately 45 degrees) angle to avoid excessive eye strain. Some individuals exposed to bright morning light at 10,000 lux on a regular basis report transient side effects, including mild jitteriness or headaches (10 percent) and mild nausea (16 percent). Sporadic cases of hypomania have been reported, especially in winter depressives or bipolar patients exposed to early-morning bright light. Almost two-thirds of patients who use bright light exposure therapy in the evening report insomnia.

Ginkgo for cognitive decline and dementia: the verdict is still out

How Ginkgo works

Ginkgo (Ginkgo biloba) extract is used in Europe and North America to treat dementia and other neurodegenerative diseases. Most commercially available preparations are standardized to two active ingredients: flavone glycosides and terpenoids. The flavonoid constituent is a strong antioxidant and is believed to have a general neuroprotective benefits. The terpenoid fraction interferes with platelets and helps individuals recover following a stroke by decreasing the risk of blood clots in the brain and reducing nerve cell death associated with stroke. Constituents of Ginkgo may also inhibit neurotoxicity and nerve cell death caused by nitric oxide.

Ginkgo may improve cognitive functioning in both healthy and cognitively impaired non-demented adults

Two placebo-controlled trials found that a compound herbal product containing both Ginkgo biloba (160 or 320 mg) and Panax ginseng (400 mg) resulted in transient improvement in recall performance in healthy adults. Enhanced cognitive functioning appears to reach its peak approximately 6 hours after the herbal preparation is taken. Preliminary findings suggest that combining Ginkgo with another traditional Chinese herbal, dangshen (Codonopsis pilosula), may improve cognitive performance in healthy adults more than either herbal alone. A meta-analysis of 11 clinical trials on standardized ginkgo extracts in elderly cognitively impaired individuals who did not meet full criteria for dementia suggested consistent cognitive enhancing effects.

Inconsistent findings for Ginkgo as a treatment of dementia

Early systematic reviews of randomized controlled trials on ginkgo in dementia concluded that ginkgo preparations in doses between 120 and 600 mg per day taken over several weeks to 1 year result in modest improvements in memory, general cognitive functioning, and activities of daily living in mild to moderate Alzheimer dementia and multi-infarct dementia. However, a systematic review of all randomized controlled trials published up to 2006 on ginkgo in the treatment of dementia and other types of acquired cognitive impairment found inconsistent evidence, noting that early trials were generally small or methodologically flawed, including the absence of standardized preparations and the use of different dementia rating scales across studies. In a 24-week, double-blind placebo-controlled trial, patients with mild to moderate dementia were randomized to a standardized ginkgo extract (160 mg per day) versus the cholinesterase inhibitor donepezil (5 mg per day) or placebo. At 24 weeks, patients taking ginkgo and donepezil experienced equivalent improvements in cognitive performance and global functioning. The findings of one study suggest that the rate of overall cognitive decline is moderately slowed in severe dementia.

Ginkgo has safety issues related to interference with normal blood clotting

Ginkgo is generally well tolerated. Mild transient adverse effects include upset stomach, dizziness, and headaches. Cases of spontaneous bleeding have been reported. Ginkgo should be avoided in individuals taking aspirin, or anticoagulants like warfarin, or heparin. G. biloba preparations should be discontinued at least 2 weeks prior to surgery. G. biloba may cause elevation of hepatic enzymes, and there are case reports of possible serotonin syndrome when taken with SSRIs.

Omega-3s in Mental Health Care: Part 2

Part 1 reviewed the evidence for omega-3 supplementation in the treatment of depressed mood. This post concisely reviews the evidence for omega-3s in treating schizopohrenia, dementia, ADHD, PTSD and borderline personality disorder.

Omega-3s for symptoms of schizophrenia and other psychotic disorders

Augmentation with the omega-3 fatty acid EPA may be an effective preventive strategy in individuals at high risk for developing schizophrenia or in the early phase of psychotic illness but not as a treatment of established cases of schizophrenia. The neuroprotective role of omega-3s during the early so-called prodromal phase of schizophrenia may be related to general effects on the brain’s antioxidative intracellular defense mechanisms or direct interactions between EPA and the glutamate receptor system. EPA augmentation may be especially appropriate for younger or antipsychotic naïve individuals in the early phase of illness or cases in which metabolic or sexual adverse effects may result in poor medication adherence and symptomatic worsening. Limited findings suggest that a combination of EPA and DHA may reduce the rate of progression to full-blown schizophrenia in high-risk populations including individuals who chronically abuse substances or already have impairments in neuropsychological functioning. In contrast to positive findings of studies on EPA augmentation in the prodromal phase of schizophrenia, a meta-analysis of placebo controlled studies on EPA augmentation on symptom severity in patients with chronic schizophrenia or other psychotic disorders found no evidence for greater benefit of EPA augmentation over antipsychotic medications alone. All studies included in the meta-analysis lasted 12 weeks and used EPA doses between 2 and 3 g per day. Possible explanations of reported negative findings include small study size, absence of clinical efficacy of EPA supplementation in chronic schizophrenia, a “ceiling effect” on response to EPA augmentation associated with concurrent treatment with antipsychotics, combinations of different fatty acids may be more effective than EPA alone, and dietary differences and other socio-demographic factors that may have confounded findings.

DHA supplementation for treatment of cognitive decline and dementia

Systematic reviews and meta-analysis of studies on the effects of omega-3 supplementation on cognitive development, function, and decline throughout the life span concluded that omega-3 supplementation—especially DHA—may significantly improve cognitive development in infants but not in children, adolescents, adults, or the elderly. Omega-3 supplementation was not associated with a reduced rate of cognitive decline in healthy elderly adults or with a slowing in the rate of progression of Alzheimer disease.

Inconclusive evidence for omega-3s in ADHD

Although individual studies on omega-3s in ADHD report positive findings, a systematic review and meta-analysis of placebo-controlled trials on omega-3s in the treatment of ADHD in children and adolescents reported inconclusive findings due to methodological problems including small sample sizes, variability of selection criteria, and type and dosage of supplements and short-term follow-ups.

Recent studies have investigated the role of omega-3s in PTSD. These studies are based on the observation of increased rates of neuronal regeneration in the hippocampus soon following trauma. It is hypothesized that increased neuronal regeneration following trauma may result in more rapid clearance of fear memories and prevent immediate post-trauma memories from becoming long-term memories, reducing the risk of developing PTSD. In fact, animal studies support that omega-3 fatty acids increase hippocampal neurogenesis. Studies done in Japan following the 2011 tsunami investigated the effectiveness of pre-treatment with omega-3s in preventing the development of PTSD following exposure to trauma in first medical responders.

Symptoms of borderline personality disorder may improve with omega-3 supplementation

In a small, 8-week controlled trial (N = 30), women diagnosed with moderately severe borderline personality disorder randomized to ethyl-EPA (1 g per day) versus placebo reported less severe symptoms of aggression and depressed mood compared to the placebo group.

Omega-3s have few mild safety issues

Omega-3 fatty acids are generally well tolerated and pose few safety issues. Transient mild gastrointestinal distress is sometimes reported by patients who take omega-3 fatty acids. There is one case report of possible hypomania induced by omega-3 fatty acids. Rare cases of increased bleeding times have been reported in patients who take aspirin or anticoagulants together with omega-3s.

The amino acid L-theanine has beneficial effects for generalized anxiety

L-theanine increases brain levels of several neurotransmitters

The amino acid l-theanine found in green tea is widely used in China, Japan, and other Asian countries to treat anxiety and depressed mood. Animal studies confirm that l-theanine increases brain levels of serotonin, dopamine, and gamma-amino-butyric acid (GABA) (an important inhibitory neurotransmitter) and may have general neuroprotective effects.

L-theanine reduces anxiety by increasing alpha brain wave activity

Anxiety-reducing effects of l-theanine are believed to be mediated by enhanced alpha brain wave activity in the occipital and parietal regions that are dose dependent and similar to EEG changes observed during meditation. Calming effects may last 8 to 10 hours and are usually experienced within 30 minutes following ingestion of l-theanine at doses between 50 and 200 mg.

Promising research findings need to be confirmed

However, findings of clinical research studies on l-theanine in anxiety are inconsistent. In one small placebo-controlled study (16 patients), healthy adult volunteers randomized to the prescription medication alprazolam (1 mg) versus l-theanine (200 mg) or placebo experienced equivalent and non-significant anxiety reducing effects during an experimentally induced anxiety state. In another small placebo-controlled study (12 patients), individuals taking l-theanine experienced relatively greater reduction in acute stress response as measured by changes in heart-rate variability (HRV) and salivary immunoglobulins (s-IgA) compared to the placebo group. These findings suggest that stress-reducing effects of l-theanine may be mediated by inhibition of cortical neuron excitation. In a crossover study, healthy adults were randomized to l-theanine (250 mg) alone or in combination with caffeine (150 mg). Compared to the l-theanine–only group, the combination group experienced improved visual information processing, reduced mental fatigue, faster reaction time and faster working memory, generally increased alertness, and fewer headaches. Moderately severe anxiety symptoms may respond to l-theanine taken at a dose of 200 mg twice daily however more severe anxiety may require doses up to 600 to 800 mg per day divided into 200-mg increments every 3 to 4 hours. ​Large well designed placebo-controlled studies on l-theanine are needed before more definitive comments can be made about its anti-anxiety benefits.

No safety problems

l-Theanine is generally well tolerated, and there are no published reports of serious adverse side effects or interactions with other natural products or conventional prescription medications

Widespread Use of Complementary and Alternative Medicine

In the North America, Europe, and other industrialized world regions, an increasing percentage of the population is using complementary, alternative, and integrative approaches to treat or selftreat medical and mental health problems. A large patient survey (N = 7,503) found that females, college graduates, and persons who believed that they received poor health care were more likely to use CAM, and only one-half of individuals who used CAM notified their health care providers. The majority of CAM users are well educated, committed to personal growth, satisfied with the conventional care provided by their physician or other health care provider, and use both prescription medications and CAM approaches for the same problem. An increasing number of medical schools, nursing schools, and psychology graduate programs offer courses on CAM. Symposia on CAM modalities are included in the annual meetings of the American Medical Association (AMA), the American Psychiatric Association (APA), and other professional medical associations. Approximately half of US physicians—and the majority of European physicians—believe that acupuncture, chiropractic, and homeopathy are valid therapeutic modalities and refer patients to practitioners of these therapies. Increasing numbers of primary care physicians are becoming certified to practice massage, acupuncture, herbal medicine, homeopathy, and other nonallopathic modalities.