Relaxation Drinks and Their Use in Adolescents

Abstract

Objectives:

A new class of beverages called relaxation drinks advertises calming effects and an easy way to wind down when life gets stressful. This article examines these drinks in the context of their use in adolescents.

Methods:

A review of the literature relevant to relaxation drinks and their functional ingredients was conducted.

Results:

The beverages contain ingredients such as melatonin, valerian, kava, tryptophan, and other products traditionally thought to play a role in sleep, sedation, or neurocognitive function. Studies of the efficacy and safety of these supplements are limited and many have significant methodological limitations. Despite appropriate warnings placed on the labels of relaxation drinks, marketing is cleverly designed to appeal to young consumers and often evokes the experiences produced by alcohol and drug use.

Conclusion:

Although moderate consumption of these beverages by healthy individuals is likely safe, an objective reduction in stress is improbable and associated adverse effects are possible.

Introduction

I n contrast to the stamina, alertness, and fast pace touted by caffeinated energy drinks, a new class of beverages called relaxation drinks promises calmness and an easy way to wind down when life gets stressful. Energy drinks have gained the attention of the medical field recently as concerns about their use in young people (Kaminer 2010), high caffeine content (Reisig et al. 2009), and combination with alcohol (Howland et al. 2011) have surfaced. At first glance, “anti-energy” drinks may seem like a welcome change, but these new beverages are not without the potential for negative health effects. This article will describe relaxation drinks, review the literature with regard to the documented health impacts of the supplements they contain, discuss their consumption by adolescents, and seek to establish whether they actually live up to their claims of abating stress and inducing a sense of calm.

Relaxation drinks fall under the category of functional beverages, which are any prepared drinks containing a formula of ingredients designed to have a health benefit beyond solely nutrition. This includes energy drinks, sports drinks, which are commonly thought to enhance athletic performance, and water with added vitamins and minerals, which claims to improve the immune system. In recent years, soda sales have fallen (Storey 2010), likely as the result of a number of factors, including public awareness of high sugar content in carbonated soft drinks, public health initiatives promoting wellness, and economy improvement allowing consumers to purchase more expensive beverages. In response to this, large soft drink companies as well as smaller businesses aiming to wedge into the market have been releasing nonsoda bottled drinks that are advertised as having an assortment of health advantages.

Sales of relaxation drinks began in Japan in 2005, and hit shelves in the United States in 2007. The United States now has the largest market with a retail value of over $500 million (Martinez 2011). There are well over 300 distinct bottled beverages marketed as relaxation drinks, many with hefty price tags in the range of two to three dollars per container. This success has been the market's basis for referring to these beverages as the counter-trend to energy drinks. The majority of sales do not come from the beverage aisle of the grocery store, but rather from convenience stores and the checkout lines at a variety of specialty stores where customers are likely to make impulse purchases.

Methods

A search of four databases, PubMed, MEDLINE, Ovid Journals, and the Cochrane Library, for studies relevant to relaxation beverages was performed. Publication dates through February 2011 were included. Search terms used were relaxation drinks and anti-energy drinks. The word drinks was then substituted with beverages and shots in these two phrases. The search did not yield any clinical studies, though it did produce one review article on the topic of energy drinks that included a short section on the emerging trend of relaxation beverages.

The same databases, with the addition of PubMed's Complementary and Alternative Medicine subset, were searched for publications on the safety, effectiveness, and interactions of the natural ingredients used in relaxation drinks. IBISWorld and Zenith International were used to obtain industry market research reports on the topic of relaxation drinks. These provided the names of popular brands of relaxation drinks that were then used to gather information on claims and ingredients via product labels, Web sites, and other publications.

Results

Popular relaxation beverages are listed in Table 1. The ingredients they contain that are advertised to have effects on relaxation, sleep quality, or cognition are listed along with their associated quantities. Table 2 lists the effects of these ingredients as publicized by the product companies and compares them with the available clinical evidence that supports the claims. Reported adverse effects of the supplements are also included.

Table 1.

Popular Relaxation Beverages and Their Ingredients

Beverage name	Content per serving
Bula	Kava 100 mg
	Rose hips 20 mg
	Valerian root 20 mg
Drank	Melatonin 1 mg
	Rose hips 10 mg
	Valerian 10 mg
Dream Dust™	A 412 mg “Proprietary Blend” of 5-HTP, GABA, L-theanine, Magnesium, Melatonin, Phenibut, Vitamin B6, and Zinc
Dream Water	A 150 mg “Proprietary Blend” of 5-HTP, GABA, and Melatonin
iChill	Melatonin 5 mg
	Rose hips 10 mg
	Valerian 10 mg
Jones GABA	GABA 150 mg
JUST CHILL	A 170 mg “Proprietary Chill Blend” of Ginko biloba, Ginseng, L-theanine, and Lemongrass
Malava NOVOCAINE	Kava 20 mg
Marley Mellow Mood	Chamomile 20 mg
	Hops 13.3 mg
	Lemon Balm 20 mg
	Melatonin 2 mg
	Passionflower 6.6 mg
	Valerian 20 mg
miniCHILL™	Relarian™ 780 mg, which is a blend of Valerian, GABA, L-theanine, and 5-HTP
Slow Cow™	Chamomile 75 mg
	Hops 50 mg
	L-theanine 100 mg
	Linden 50 mg
	Passiflora 75 mg
	Valerian 75 mg
Vacation in a bottle	L-theanine 90 mg
	L-threonine 60 mg

GABA=gamma-aminobutyric acid; 5-HTP=5-hydroxytryptophan.

Table 2.

Benefit of Relaxation Drink Ingredients as Stated by Product Companies, the Evidence of Statements, and Reported Side Effects of the Supplements

Ingredient	Stated purpose(s)	Evidence	Potential adverse effects
Melatonin	RelaxationImproved sleep qualityPrevention of jet lag	Strong evidence of reduction in jet lag (Arendt and Skene 2005; Buscemi et al. 2006); no clear evidence for sleep quality improvement	Nausea and headaches (Lewy et al. 2002)
GABA	TranquilityIncreased ability to focus	No evidence of benefit when used in supplement form	—
Valerian	Reduction of nervousnessImproved sleep qualityDecreased anxietyImproved concentration	Unclear evidence for improvement in anxiety, given study size (Andreatini et al. 2002) and combination with other supplements (Muller et al. 2003); studies of sleep quality have used nonscientific measurements of sleep improvement (Taibi et al. 2007)	Hepatotoxicity (MacGregor et al. 1989; Chan 1998); Accounts of withdrawal-type symptoms, including headache and dizziness, when high doses are stopped abruptly (Garges et al. 1998)
Kava	Decreased anxietyImproved depressionImproved cognition	Significant evidence for the reduction of anxiety (Pittler and Ernst 2000); effects on mental clarity are unclear (Meolie et al. 2005)	Hepatotoxicity (Escher et al. 2001; Humberston et al. 2003; Stickel et al. 2003); GI discomfort, tremor, and headache have been reported (Pittler and Ernst 2000)
Lemon balm	RelaxationDecreased stressImproved sleep quality	Subjective increase in calmness (Kennedy et al. 2003); studies of combined supplement products have demonstrated mixed results of improvement in sleep quality (Dress et al. 1996; Cerny and Schmid 1999)	—
5-HTP	RelaxationImproved sleep quality	Insufficient evidence	Possible association with eosinophilia myalgia syndrome (Michelson et al. 1994)
Passion flower	RelaxationDecreased anxiety	Unclear benefit, though sedative effects suggested by small trial (Bourin et al. 1997)	—
L-theanine	RelaxationImproved cognitionDecreased anxiety	Slight effect on relaxation in small clinical trial (Lu et al. 2004); improvement in cognition demonstrated only with caffeine/theanine combination (Rogers et al. 2008)	Decrease in blood pressure (Rogers et al. 2008)
Rose hip	Decreased stressReduction of nervousness	Insufficient evidence	—
Hops	RelaxationReduction of nervousness	Unclear benefit, as investigations of sedative effects and improvement in sleep quality were carried out with hops/valerian combination	—
Linden flower	Reduction of nervousness	Insufficient evidence	—

GI=gastrointestinal.

Discussion

In addition to the flavoring and sugar or sweeteners of most functional beverages, relaxation drinks contain herbs, amino acids, chemical compounds, and various other ingredients that are commonly or traditionally thought to play a role in sleep, sedation, or neurocognitive function. One such beverage known as Drank contains melatonin, valerian, and rose hips in a can marked, “Warning! Drank may be extremely relaxing and calming.” Another product called Slow Cow includes valerian, L-theanine, chamomile, passion flower, and hops. Its Web site states that the drink “helps in the improvement of concentration, memory, and learning capacity without causing sleepiness.”

Other brands, through advertisements including scenes of tropical islands with palm trees, make similar statements pertaining to the calming effects, tranquility, and diminished levels of stress that their beverages will produce. Many promise that despite these benefits, the consumer's mental clarity will not suffer, or will even improve. Some relaxation drinks are geared toward helping individuals wind down before bed and fall asleep, such as Dreamwater, which contains gamma-aminobutyric acid (GABA), melatonin, and 5-hydroxytryptophan. The marketing for Dreamwater empathizes with the “millions of Americans who suffer from sleep issues.”

Alongside, many declarations of lessened worries and better sleep on relaxation drink Web sites are supportive statements from individuals labeled as experts and hyperlinks to sources of supplement information ranging from WebMD to Wikipedia. The text used, like so many other products readily available today, comes across as convincing and well researched. The brand Mini Chill asserts that its trademarked blend of ingredients, created by a biochemist, has been clinically proven to enhance mood, reduce anxiety, and sharpen mental focus. A link is provided to a peer-reviewed journal containing the study's abstract (Weeks 2009). Upon reading the text of the report, however, it is clear that the study was small, lacked a control group, and that the data are subjective and self-reported.

To date, there are no other published trials investigating the effectiveness of relaxation drinks in achieving their stated benefits. This deficiency of convincing evidence is, unfortunately, not exclusive to relaxation drinks as a finished product, but also to the vast majority of the functional ingredients used to make them. Brief reviews of the evidence for the use of several relaxation drink ingredients as sedatives, hypnotics, and anxiolytics are provided below. Many herbal supplements contain as many as thousands of biochemicals, making it difficult to pinpoint those that produce the desired neurologic result. Consequently, the precise reasons for a supplement's reported benefits and adverse effects are often quite vague. While many of these products have undergone some degree of investigation for their utility in the treatment of specific diseases or conditions, their use in managing everyday anxiety and stress is largely unexplored.

Melatonin is a hormone excreted by the pineal gland in levels that vary in response to light and darkness. It acts to regulate the sleep–wake cycle and has a major influence on circadian rhythm. It is widely available as a supplement and commonly thought to induce sleep; contrary to this misconception, however, exogenous melatonin likely acts by causing a shift in the sleep phase depending on when it is taken. If used before the release of endogenous melatonin (before bed), it will shift the body toward a sleep phase (Brzezinski et al. 2005). If taken upon waking, there is a delay in phase change leading to a prolonged period of decreased alertness. The most clearly demonstrated benefit of melatonin is its utility in individuals with jet lag (Arendt and Skene 2005). On the other hand, there is little evidence suggesting that it is effective in treating most primary sleep disorders. Despite this, it is commonly used as a sleep aid. There is some evidence suggesting that large doses may be counterproductive, leading to drowsiness the next day, as well as nausea and headaches (Lewy et al. 2002). In 2010, the Food and Drug Administration (FDA) issued a warning letter to the company that makes Drank stating that melatonin was not approved as a food additive and requiring prompt action to be taken to correct the violation (Rodriguez 2010), though new melatonin-containing relaxation drinks have since come onto the market. A recent review demonstrates that the short-term use of exogenous melatonin is likely safe (Buscemi et al. 2006).

The principal neurotransmitter of the central nervous system (CNS), GABA, is also available as a supplement. It regulates many physiological and psychological processes. Dysfunction of the GABA system is known to be responsible for anxiety and mood disorders, and stress has been found to change the expression of GABA receptor subunits (Kalueff and Nutt 2006). This has led to the use of many GABAergic agents for the treatment of psychiatric conditions, though exogenous GABA itself does not cross the blood–brain barrier. While it is sometimes recommended for the treatment of anxiety and insomnia, it has not been shown to be effective.

Valerian is a root that has long been believed to have anxiolytic and sedative properties. Its probable mechanism involves increasing GABA and decreasing GABA's uptake at the synaptic cleft. Studies on the effects of valerian use in humans have been of poor quality; thus, the evidence currently available on the root's impact is limited (Taibi et al. 2007). Optimal doses and frequencies are not well established, nor is safety with long-term use. There have been case reports of hepatotoxicity with valerian, but the majority of these have involved the use of other supplements simultaneously (MacGregor et al. 1989; Chan 1998). Reported side effects of valerian have been comparable to those observed in placebo groups. In spite of this, there have been accounts of withdrawal-type symptoms, including headache and dizziness, when high doses of valerian are stopped abruptly (Garges et al. 1998).

The roots of kava, which have been consumed by natives of the Pacific islands for centuries, have been reported to promote relaxation without disturbing cognition. The roots are dried, ground, and made into beverages that have traditionally been used during celebrations and other events. In recent decades, the use of kava has spread and research has become available on its efficacy and safety. The effects of kava are attributed to kavalactones, at least one of which has the ability to bind to GABA receptors and increase GABA binding sites (Jussofie et al. 1994). Additionally, it may act as a dopamine antagonist and an inhibitor of norepinephrine uptake, contributing to its anxiolytic properties. Randomized, controlled trials have demonstrated improvement in anxiety levels with the use of kava (Pittler and Ernst 2000). There are fewer data demonstrating that kava has mild sedative properties, and its effects on mental clarity are unclear (Meolie et al. 2005). Like valerian, there have been numerous reports of hepatotoxicity associated with its use (Escher et al. 2001; Humberston et al. 2003; Stickel et al. 2003). Chronic use of kava at large doses has been linked with other adverse events, including renal dysfunction, gastrointestinal discomfort, and skin discoloration. In 2002, the FDA released a consumer advisory communicating concern of the safety of kava, and recommended that kava be used on a short-term basis only (U.S. Food and Drug Administration 2002).

Lemon balm, or melissa, is an herb that has a variety of uses in folk medicine. It has been identified as an inhibitor of GABA transminase, believed to be due to the presence of rosmarinic acid (Awad et al. 2009). Norepinephrine and serotonin pathways are also thought to be involved. Its usefulness in improving either anxiety or sleep quality has little evidence due to small studies of poor quality. There is similarly inconclusive evidence for the improvement in cognitive performance with its use (Kennedy et al. 2003). When sold as a supplement, it is frequently combined with other herbal products such as valerian and marketed as a sleep aid. Several studies have demonstrated mixed results, often via self-reports, of improved sleep quality with the use of these combination products (Dress et al. 1996; Cerny and Schmid 1999).

Other components of relaxation drinks, namely, tryptophan and its precursor 5-hydroxytryptophan, passion flower, L-theanine, rose hip, hops, linden flower, and lavender, have traditionally been used for a wide range of illnesses and complaints, including relaxation and sedation. Like the supplements described previously, scientific studies of their efficacy and safety are limited and many have significant methodological limitations. The quality of supplements, especially herbs, can vary considerably based on manufacturer and production practices. The active compounds of kava, for example, are contained within the root of the plant. Contamination with the stem or leaf of the plant is thought to be the cause of some adverse effects of the supplement (Lude et al. 2008). The location and growing conditions utilized for plant products can likewise influence supplement quality, as amounts of chemical constituents can vary. Moreover, the stated dose of a supplement is not always equivalent to the amount claimed on the product package (Gershwin et al. 2010).

Interactions of relaxation drinks with prescription drugs raise distinctive concern. As is apparent by the mechanisms described above, the simultaneous use of many psychiatric medications poses a risk. CNS depressants, in particular, have been reported to be unsafe when used with melatonin (Carman et al. 1976), valerian (Leuschner et al. 1993), and kava (Spinella 2002). These supplements are contraindicated with the use of sedatives, antidepressants including selective serotonin receptable inhibitors (SSRIs) and monoamine oxidase (MAO) inhibitors, and anxiolytics based on mechanisms of action and the risk of increased sedation and impaired neurological and psychological functioning. The potential interactions of these supplements with many other medications have been highlighted by both anecdotal evidence and theoretical risk. Due to the reports of hepatotoxicty associated with kava and valerian, the use of hepatotoxic agents in conjunction with relaxation drinks poses additional threat. The blends of ingredients used in relaxation drinks also introduce the risk for supplement interactions and additive effects. Due to the popularity of supplement combinations, often sold as “proprietary blends,” there have been a number of clinical studies investigating the use of various combinations similar to those that are found in relaxation drinks. These trials, however, are often unable to distinguish adverse effects of the combination from those of either supplement alone. Given these risks, several brands of relaxation drinks advise that buyers with any medical conditions or taking any medications consult a healthcare provider before consuming the drink. Specific warnings for those with liver disease or at risk for liver disease can be found on some beverage bottles.

Some relaxation drink manufacturers encourage the mixture of their drinks with alcohol; a few brand Web sites actually provide alcoholic drink recipes involving their product. One company claims that when their drink, Malava Novocaine, is used as an alcohol mixer, hangovers the following day will be diminished. Mini Chill advertising states that the drink's ingredients work together with alcohol to “enhance your buzz.” While it is likely true that alcohol will have additive effects when used with many of the ingredients in relaxation drinks, the detrimental results of increased sedation, impaired concentration, and delayed reactions (Boullata and Nace 2000), to name a few, could easily outweigh a better buzz. The marketing used for some relaxation drinks also evokes connections to drugs of abuse. Drank, for example, which comes in a purple can, is clearly suggestive of a recreational drug commonly called “purple drank,” which combines prescription-strength codeine cough syrup with soda. Named after a slang term for marijuana, Mary Jane's Relaxing Soda uses the phrase “euphoric relaxation” on its label and has been referred to as “weed in bottle” by the press (Courtland 2009). Given the illegal status of psychoactive drugs, these references are appealing to many adolescents who are tempted by the idea of alternative ways to achieve a “high” or otherwise altered state of mind.

Several brands warn that relaxation drinks should not be consumed by children, whereas others gear their marketing toward young consumers. The Web site for Drank asserts that kids are under a lot of pressure to excel in school, stating that the beverage can help in “recovering from this exhaustion.” The majority of relaxation drink Web sites include hyperlinks to social media sites such as Facebook, Twitter, and YouTube, allowing adolescents to quickly and easily spread the word about these products. Mini Chill, which comes with the warning that it should not be consumed by those under the age of 18, simultaneously assures student consumers that they “will get better grades” if they drink the beverage before a test or while writing a paper. Few of the supplements used in relaxation beverages have been studied in children, and safe dosages for the pediatric population have not been documented. This ambiguity is intensified by the fact that many relaxation drink labels do not provide quantities per serving of herbal ingredients.

Caution with the use of relaxation drinks in the young population should be taken for reasons beyond the safety and dosing uncertainty of the drink ingredients. Patients are unlikely to disclose to their physicians that they are using relaxation drinks, as they may not consider beverages when asked about medication and supplement use (Kennedy et al. 2008). Many believe that supplements are adequately tested and that the advertising of supplements is generally true (Blendon et al. 2001). If experiencing side effects, patients may not attribute symptoms to the use of supplements or functional drinks. As adolescents struggle to deal with fluctuating emotions, they may turn to products such as a relaxation beverage in hopes that it will improve their mood and ease negative feelings. Those with psychiatric conditions being treated with medication are then put at particular risk, as noted above.

The warnings placed on many relaxation drink labels, though aimed at safety, are likely to come across as intriguing to adolescents. For instance, the label on Mary Jane's Relaxing Soda recommends that daily consumption should not exceed two bottles; Dreamwater recommends no more than one. Some product labels advise against driving or operating machinery after the consumption of the relaxation drink. Young consumers may be more likely to use the product in excess, given its availability, and to experiment with excessive consumption to achieve a bigger effect or test the limits of the product (Buck and Davis 2010).

Conclusion

The companies making relaxation beverages have undeniably succeeded in appealing to young consumers, who may be more likely than other age groups to accept advertising claims. Investigations in adolescents have noted relationships, identity concerns, and educational issues to be causes of stress (Seiffge-Krenke et al. 2009), and sleep quantities to be inadequate (Smaldone et al. 2007). As the younger generation seeks to cope with this array of challenges, seemingly quick fixes such as relaxation drinks are understandably alluring. However, there are healthy methods to reduce stress and proven treatments for sleeping difficulties and anxiety disorders. Young patients and their guardians should be aware that reaching for functional drinks is likely not the best tactic, and that underlying medical conditions should be ruled out. Conversations on the topic of psychological health can lead to valuable counseling on exercise, sleep hygiene, therapy, or other helpful approaches to stress. If natural products are deemed an appropriate measure, a healthcare provider should monitor their use, as with medications.

As a bottom line, relaxation drinks consumed by the majority of the population in moderate quantities are likely safe. Some brands, depending on their ingredients, may provide a perceived relaxing effect. Although data on the safety and benefits of relaxation drinks would be advantageous, it is doubtful that convincing evidence is around the corner given the barriers to studies of natural products and the reliance on subjective data in the evaluation of stress and sleep quality. Forecasts of sales for relaxation drinks predict continued growth in the coming years. It is expected that as the beverage market evolves, new classes of functional drinks will also emerge. They too will likely have health and safety concerns. Using the precedent of energy drinks, which have been suggested as a “threat to public health” (Arria and Claire 2011), it would be prudent to keep a watchful eye on this industry and its young consumers.

Footnotes

Disclosures

Sylvie Stacy—no competing financial interests exist.

References

Andreatini

, Sartori

, Seabra

, Leite

. Effect of valepotriates (valerian extract) in generalized anxiety disorder: A randomized placebo-controlled pilot study. Phytother Res, 16:650–654. 2002.

Arendt

, Skene

. Melatonin as a chronobiotic. Sleep Med Rev, 9:25–39. 2005.

Arria

, Claire

. The “high” risk of energy drinks. JAMA, 305:600–601. 2011.

Awad

, Muhammad

, Durst

, Trudeau

, Arnason

. Bioassay-guided fractionation of lemon balm using an in vitro measure of GABA transaminase activity. Phytother Res, 23:1075–1081. 2009.

Blendon

, DesRoches

, Benson

, Brodie

, Altman

. Americans' views on the use and regulation of dietary supplements. Arch Intern Med, 161:805–810. 2001.

Boullata

, Nace

. Safety issues with herbal medicine. Pharmacotherapy, 20:257–269. 2000.

Bourin

, Bougerol

, Guitton

, Broutin

. A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: Controlled study versus placebo. Fundam Clin Pharmacol, 11:127–132. 1997.

Brzezinski

, Vangel

, Wurtman

, Norrie

, Zhdanova

, Ben-Shushan

, Ford

. Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Med Rev, 9:41–50. 2005.

Buck

, Davis

. Marketing risk: Emotional appeals can promote the mindless acceptance of risk. Emotions and Risky Technologies. Int Lib Ethics Law, 5:61–80. 2010.

10.

Buscemi

, Vandermeer

, Hooton

, Pandya

, Tjosvold

, Hartling

, Vohra

, Klassen

, Baker

. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: Meta-analysis. BMJ, 332:385–93. 2006.

11.

Carman

, Post

, Buswell

, Goodwin

. Negative effects of melatonin on depression. Am J Psychiatry, 133:1181–1186. 1976.

12.

Cerny

, Schmid

. Tolerability and efficacy of valerian/lemon balm in healthy volunteers; a double-blind placebo-controlled, multicentre study. Fitoterapia, 70:221–228. 1999.

13.

Chan

. An assessment of the delayed effects associated with valerian overdose. Int J Clin Pharmacol Ther, 36:569. 1998.

14.

Courtland

. Weed in a Bottle: Mary Jane's Relaxing Soda. Culvert City, CA: LA Weekly, 2009.

15.

Dress

, Kohler

, Muller

. Improvement in sleep quality with a high dose valerian-melissa preparation. Psychopharmakotherapie, 3:123–130. 1996.

16.

Escher

, Desmeules

, Giostra

, Mentha

. Hepatitis associated with kava, a herbal remedy for anxiety. BMJ, 322:139. 2001.

17.

Garges

, Varia

, Dorasiswamy

. Cardiac complications and delirium associated with valerian root withdrawal. JAMA, 280:1566–1567. 1998.

18.

Gershwin

, Borchers

, Keen

, Hendler

, Hagie

, Greenwood

. Public safety and dietary supplementation. Ann N Y Acad Sci, 1190:104–117. 2010.

19.

Howland

, Rohsenow

, Calise

, MacKillop

, Metrik

. Caffeinated alcoholic beverages: An emerging public health problem. Am J Prev Med, 40:268–271. 2011.

20.

Humberston

, Akhtar

, Krenzelok

. Acute hepatitis induced by kava-kava. J Toxicol Clin Toxicol, 41:109–113. 2003.

21.

Jussofie

, Schmiz

, Hiemke

. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of the rat brain. Psychopharmacology, 116:469–474. 1994.

22.

Kalueff

, Nutt

. Role of GABA in anxiety and depression. Depress Anxiety, 24:495–517. 2006.

23.

Kaminer

. Problematic use of energy drinks by adolescents. Child Adolesc Psychiatr Clin N Am, 19:643–650. 2010.

24.

Kennedy

, Wake

, Savelev

, Tildesley

, Perry

, Wesnes

, Scholey

. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology, 28:1871–1881. 2003.

25.

Kennedy

, Wang

, Wu

. Patient disclosure about herb and supplement use among adults in the US. eCAM, 5:451–456. 2008.

26.

Leuschner

, Muller

, Rudmann

. Characterisation of the central nervous depressant activity of a commercially available valerian root extract. Arzneimittelforschung, 43:638–641. 1993.

27.

Lewy

, Emens

, Sack

, Hasler

, Bernert

. Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period. Chronobiol Int, 19:649–658. 2002.

28.

, Gray

, Oliver

, Liley

, Harrison

, Bartholomeusz

, Phan

, Nathan

. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol, 19:457–465. 2004.

29.

Lude

, Torok

, Dieterle

, Jaggi

, Buter

, Drahenbuhl

. Hepatocellular toxicity of kava leaf and root extracts. Phytomedicine, 15:120–131. 2008.

30.

MacGregor

, Abernethy

, Dahabra

, Cobden

, Hayes

. Hepatotoxicity of herbal remedies. BMJ, 299:1156–1157. 1989.

31.

Martinez

. Alertness, Relaxation Drinks Market Passes US$500 Million. Bath, UK: Zenith International Ltd., 2011.

32.

Meolie

, Rosen

, Kristo

, Kohrman

, Gooneratne

, Aguillard

, Fayle

, Troell

, Townsend

, Claman

, Hoban

, Mahowald

. Oral nonprescription treatment for insomnia: An evaluation of products with limited evidence. J Clin Sleep Med, 1:173–187. 2005.

33.

Michelson

, Page

, Casey

, Trucksess

, Love

, Milstien

, Wilson

, Massaquoi

, Crofford

, Hallett

. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol, 21:2261–2265. 1994.

34.

Muller

, Pfeil

, von den Driesch

. Treating depression comorbid with anxiety—results of an open, practice-oriented study with St John's wort and valerian extract in high doses. Phytomedicine, 10:25–30. 2003.

35.

Pittler

, Ernst

. Efficacy of kava extract for treating anxiety: Systematic review and meta-analysis. J Clin Psychopharmacol, 20:84–89. 2000.

36.

Reisig

, Strain

, Griffiths

. Caffeinated energy drinks—a growing problem. Drug Alcohol Depend, 11:1–10. 2009.

37.

Rodriguez

. Warning Letter. White Oak, MD: U.S. Food and Drug Administration, 2010.

38.

Rogers

, Smith

, Heatherley

, Pleydell-Pearce

. Time for tea: Mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology, 195:569–577. 2008.

39.

Seiffge-Krenke

, Aunola

, Nurmi

. Changes in stress perception and coping during adolescence: The role of situational and personal factors. Child Dev, 80:259–279. 2009.

40.

Smaldone

, Honig

, Byrne

. Sleepless in America: Inadequate sleep and relationships to health and well-being of our nation's children. Pediatrics, 119:S29–S37. 2007.

41.

Spinella

. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev, 7:130–137. 2002.

42.

Stickel

, Baumuller

, Seitz

, Vasilakis

, Seitz

, Schuppan

. Hepatitis induced by kava. J Hepatol, 39:62–67. 2003.

43.

Storey

. The shifting beverage landscape. Physiol Behav, 100:10–14. 2010.

44.

Taibi

, Landis

, Petry

, Vitiella

. A systematic review of valerian as a sleep aid: safe but not effective. Sleep Med Rev, 11:209–230. 2007.

45.

U.S. Food and Drug Administration. Consumer Advisory: Kava-Containing Dietary Supplements may be Associated with Severe Liver Injury. White Oak, MD: U.S. FDA, 2002.

46.

Weeks

. Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: Relarian™ Med Sci Monit, 15:RA256–RA262. 2009.