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Nagamani Kopparapu et al. / Journal of Pharmacy Research 2012,5(10),4950-4956 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Natural sleep Aids; Boon or Bane Nagamani Kopparapu*, D.S Puranik, L.V.G Nargund, Beulah Samuel, A.A Shahapurkar, Vinod.K Mathew. Nargund College of pharmacy, Dattatreya nagar 2nd main, 100 ft ring road, BSK III stage, Bangalore, Karnataka, India Received on:12-06-2012; Revised on: 17-07-2012; Accepted on:26-08-2012

ABSTRACT Sleep and sleep disorders play a role in a large number of human disorders and affect almost every field of medicine. Common medical problems are often associated with abnormalities of sleep. Patients with chronic medical disorders often have fewer hours of sleep and less restorative sleep compared to healthy individuals, and this poor sleep may worsen the subjective symptoms of the disorder.World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Many herbal remedies are available over-the-counter in pharmacies and health food shops are still lacking important information needed for safe use. Herbal sedatives also have some evidence for efficacy; the observations that certain compounds bind to receptors adds interest to their use. and have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows effects. German chamomile, lavender, hops, , California poppy, American skullcap and passionflower are reputed to be mild sedatives. Tryptophan and melatonin are used as supplements in the sleep aids. In this review we focused on precautions, possible interactions and adverse effects of these natural sleep aids with other prescription drugs.

KEY WORDS: Sleep, Interaction, Herb, Sleep disorders

INTRODUCTION: Healthy sleep can be defined as the quantity and quality of sleep needed to alone) dead and about $12.5 BILLION worth of property damage each year. maintain optimal alertness during desired waking hours. [1] Sleep appears Statistics also show that US industry loses about $150 billion each year essential for brain repair, memory maintenance, brain development, and detoxi- because of sleep deprived workers. Absenteeism and low productivity also fication. [2] Sleep loss may also influence metabolism in a manner that con- caused by sleep problems is costing companies a fortune. [4, 5] tributes weight gain, and diabetes risk involves the following multiple path- ways: (1) alterations in glucose levels; (2) up-regulation of appetite; and (3) With such staggering numbers, leaders in the health sector are granting more decreased energy expenditure. [3] funds for research each year for the development anti-insomnia drugs. But there are questions about the side effects of these drugs and many have HEALTH COSTS & PREVALENCE: begun to turn to herbal sleep aids as efficient insomnia remedy. Many people around the world, Men, Women and Children experience sleep- less nights. Night after night they stay awake in their beds. Statistics show NATURAL SLEEP AIDS that One in three people suffer from some form of insomnia during their Natural Sleep Aids have enjoyed recent attention in the media. Some of these lifetime, between 40% and 60% of people over the age of 60 suffer from ads even claim that their products can cure insomnia. Many of these sleep insomnia. Among them women are as twice more likely to suffer than men. aids are made from , roots and even the bark of trees and have been The major cause for Insomnia is depression, & / or stress. Approxi- effective for thousands of years. When these natural sleep aids became popu- mately 10 million people in the U.S. use prescription sleep aids. People who larized in the West, many embraced them and some claimed they worked suffer from sleep deprivation are 27% more likely to become overweight or wonders. To the surprise of most medical practitioners, these herbal sleep obese. There is also a link between weight gain and sleep apnea. A National aids had no attendant side effects associated with regular allopathic drugs Sleep Foundation Poll shown that 60% of people have driven while feeling used to treat sleep disorders. Interactions of these sleep aids with other drugs sleepy (and 37% admit to having fallen asleep at the wheel) in the past year. leading to potential harm are slowly beginning to appear in the literature. The People who suffer from sleep deprivation are 27% more likely to become current review article will focuses on consolidation of such reports with the overweight or obese. aim of assisting the development of a strategies that can be useful in the assessment of risk/ benefit associated with the use of herbal sleep aids with The Institute of Medicine estimates that hundreds of billions of dollars are allopathic medications. spent annually on medical costs that are directly related to sleep disorders. US Surgeon General stated that insomnia costs in the U.S. Government are SLEEP DISORDERS more than $15 billion per year in health care costs. The most common sleep disorders include insomnia, sleep apnea, restless legs syndrome, and narcolepsy. The side effects of this problem as per the National Highway Traffic Safety Administration indicated that auto accidents which leave about 1,550(US Insomnia Insomnia (or sleeplessness) is an individual’s report of sleeping difficulties. *Corresponding author. While the term is sometimes used in sleep literature to describe a disorder Nagamani Kopparapu demonstrated by polysomnographic evidence of disturbed sleep. [6] Thus, Nargund College of Pharmacy, insomnia is most often thought of as both a sign and a symptom that can Dattatreya nagar 2nd main, accompany several sleeps, medical, and psychiatric disorders, characterized 100 ft ring road, BSK III stage, by persistent difficulty falling asleep and/or staying asleep or sleep of poor quality. [6, 7]Insomnia is typically followed by functional impairment while Bangalore, Karnataka, India awake. One definition of insomnia is “difficulties initiating and/or maintain-

Journal of Pharmacy Research Vol.5 Issue 10.October 2012 4950-4956 Nagamani Kopparapu et al. / Journal of Pharmacy Research 2012,5(10),4950-4956 ing sleep, or nonrestorative sleep, associated with impairments of daytime insomnia. The chance of risk for these problems varies among different functioning or marked distress for more than 1 month”. [8] Insomnia can occur drugs. at any age, but it is particularly common in the elderly. [9]Chronic insomnia has a significant impact on society because it is associated with frequent use include , , and . of health care services,[10,11] chronic health problems,[12,13] increased medica- Benzodiazepines may cause psychological and physical dependence. Physi- tion use,[10,11] and perceived poor health.[14] Growing evidence suggests that cal withdrawal symptoms may occur if the drug is not carefully tapered chronic, unremitting insomnia may predispose individuals to the develop- following long-term use. Most common side effects of benzodiazepines ment of psychiatric disorders and lead to substantial economic burden.[15,16] include drowsiness, impaired coordination, fatigue, confusion and disorien- tation, dizziness, decreased concentration, short-term memory problems, Sleep Apnea dry mouth, blurred vision, and irregular heartbeat. These drugs also show Sleep Apnea is a sleep disorder characterized by abnormal pauses in breath- rebound insomnia. ing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may Another class of sedative hypnotic medications includes the non-benzodiaz- occur 5 to 30 times or more an hour.[17] There are three forms of sleep apnea: epine, benzodiazepine receptor agonists. These newer medications appear central (CSA), obstructive (OSA), and complex or mixed sleep apnea (i.e., a to have better safety profiles and fewer adverse effects than the benzodiaz- combination of central and obstructive) constituting 0.4%, 84% and 15% of epines. They are also associated with a lower risk of abuse and dependence cases respectively. [18] In CSA, breathing is interrupted by a lack of respira- than the benzodiazepines, although abuse and dependence do occur. Ex- tory effort; in OSA, breathing is interrupted by a physical block to airflow amples of medications in this class include , and despite respiratory effort, and snoring is common. The elderly are more . likely to have OSA than young people. Men are more likely to suffer sleep apnea than women and children are, though it is not uncommon in the last Over-the-counter (OTC) antihistamines may be used short term for insom- two population groups. [19] An estimated 18 million Americans have sleep nia. Diphenhydramine is the most commonly used OTC antihistamine sleep apnea. aid. Diphenhydramine can cause sedation, dry mouth, and constipation. In the elderly, diphenhydramine can cause confusion and over sedation. Do not Restless Legs Syndrome (RLS) combine OTC remedies with your prescription sleep aids. Rest legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move one’s body to stop uncomfortable or odd sensa- are sometimes used to treat insomnia that may be caused by tions.[20] It most commonly affects the legs, but can affect the arms, torso, depression (secondary insomnia). In addition, some antidepressants with and even phantom limbs.[21] Moving the affected body part modulates the sedating properties are prescribed for the treatment of primary insomnia. sensations, providing temporary relief. For example, has been frequently prescribed in low doses as a hypnotic to induce sleep. Other antidepressants used for insomnia include RLS sensations could be pain, an aching, an itching or tickling in the muscles, , , , and mirazipine. Care should be taken like “an itch you can’t scratch” or an unpleasant “tickle that won’t stop”, or in the use of trazodone and other sedating antidepressants in elderly pa- even a “crawling” feeling. The sensations typically begin or intensify during tients, due to the risk for side effects (daytime sleepiness, dizziness, and quiet wakefulness, such as when relaxing, reading, studying, or trying to priapism) and drug interactions. [5, 28-30] sleep.[22] In addition, most individuals with RLS have limb jerking during sleep, which is an objective physiologic marker of the disorder and is associ- HERBS AND SUPPLEMENTS ated with sleep disruption.[23] Some controversy surrounds the marketing of drug treatments for RLS. It is a “spectrum” disease with some people expe- Melatonin riencing only a minor annoyance and others experiencing major disruption of Melatonin is the most studied dietary supplement for insomnia. It appears sleep and significant impairments in quality of life. [24] to reduce the time to fall asleep (sleep onset) and the time spent asleep (sleep duration). [31] Melatonin appears to promote sleep by producing corrective Nacrolepsy: circadian phase shifts, thereby improving the alignment of the endogenous Narcolepsy, with an estimated prevalence of about 50/ 100,000, is a disabling sleep propensity rhythm with the desired sleep schedule. Melatonin may disorder that may result in more daytime somnolence than any other major also have a direct soporific effect, especially when administered during the sleep disorder. [25] In addition to the daytime somnolence, it is characterized day. [32] Melatonin should be avoided in patients with a history of seizures, by rapid switches from waking to sleeping states, sleep paralysis, and hyp- as it lowers the seizure threshold. It should also be avoided during pregnancy [26] nagogic hallucinations. Not only do patients feel drowsy, but also they because of its potential to alter pituitary-ovarian function, induce uterine rapidly switch from waking to sleeping or cataplectic states—the sudden contractions, or cause developmental disorders in the fetus. Classes of drugs loss of all skeletal muscle control. Decrements in performance, including that may interact with melatonin include antiplatelets/anticoagulants, oral vigilance, and attentional and complex cognitive functioning problems, may hypoglycemic agents, antihypertensives, sedatives and anticonvulsants. [33] be direct consequences of sleepiness. [27] Tryptophan MEDICATIONS: Tryptophan is an amino acid used in the formation of the neurotransmitter Over-the-counter or nonprescription medications make use of the drowsi- serotonin, which is associated with healthy sleep. Tryptophan is an immedi- ness caused by some common medications. Prescription drugs used specifi- ate precursor of the neurotransmitter serotonin (5-HT), which regulates cally for improving sleeping are called sedative hypnotics. These drugs in- mood and emotion. Most of antidepressants increase the level of neurotrans- clude benzodiazepines and non-benzodiazepines. mitters (eg, serotonin, dopamine, and norepinephrine) at the neuronal syn- apse. Therefore, if a patient is taking a selective serotonin reuptake inhibitor Sedative hypnotics carry risks for withdrawal, dependency, and rebound (SSRI) or monoamine oxidase inhibitor (MAOI) along with tryptophan, the

Journal of Pharmacy Research Vol.5 Issue 10.October 2012 4950-4956 Nagamani Kopparapu et al. / Journal of Pharmacy Research 2012,5(10),4950-4956 level of serotonin in the synapse may increase significantly. This could Levodopa — There has been at least one report that kava may reduce the precipitate a pharmacodynamic interaction known as serotonin syndrome. effectiveness of levodopa, a medication used to treat Parkinson’s disease. However, patients with liver cirrhosis should also avoid this combination, Therefore, one should not take this herb if they are taking any medications because the activity of tryptophan pyrrolase will be reduced by more than containing levodopa or if you have Parkinson’s disease. [50] 20%, leading to higher levels of tryptophan and decreased clearance of the amino acid. These patients are even at higher risk for the development of Valerian (Valeriana officinalis) serotonin syndrome. [34-37] In 1989, the FDA recalled products containing L- Valerian has been widely used in Europe since the 17th century and was tryptophan, which were linked to 1543 cases of eosinophilia-myalgia syn- formerly in the United States Pharmacopoeia. This herb has been used for a drome (EMS) and 28 deaths. [33, 38] long time as an herbal sleep aid. [51] Valerian is the most popular herb for insomnia and it is the natural source of Valium. It eases nervous tension, NATURAL HERBS muscle tension and anxiety. It can be used as an occasional treatment for restlessness, but may be most beneficial for insomnia treatment over the long kava kava (piper methysticum) term. It works well in combination with other sedative herbs. A series of non- Kava kava is often used as an herbal insomnia remedy. As natural sleep aids, glycosidated iridoids called valepotriates have been proposed as active con- kava kava can impart a natural calm feeling, as it helps relax the body, as well stituents. Metabolites of these, baldrinal and homobaldrinal, show mutagenic as enhance dreaming. This herb for insomnia is also often recommended for activity in vitro but are lacking in typically used aqueous extracts and are chronic fatigue. Research indicates that kava acts as a central nervous system rapidly detoxified in the liver; they probably do not pose clinical risks. [52] depressant, and possesses muscle relaxant and analgesic activity in animals. is a sesquiterpene compound which may represent an active [40] The kava pyrones or (including , , compound and is used in standardization. Sedative properties of valerian are and dihydrokawain) have been shown to be responsible for these activities. attributed to benzodiazepine-like activity and effects on GABA. Research in [41] Recent studies have indicated that these compounds may influence GABA Germany revealed that valerian extracts bind to benzodiazepine receptors in binding in certain areas of the brain. [42] Numerous studies have investigated vitro. [53] Later studies reported increased GABA concentrations in the syn- the use of kava in the treatment of anxiety disorders. A purified kava prepa- aptic cleft after valerian extract administration, [54] but this was complicated ration (standardized to 70% kava lactones) proved effective in some studies by the presence of endogenous GABA in the aqueous extract used. with bioactivity comparable to benzodiazepines. [43-45] The effectiveness of kava as a sleep aid has also been studied and it is reported to improve sleep Reports of valerian toxicity are rare: a suicide attempt using 20 g of valerian quality. (10 times the normal dosage) resulted in cramping and fatigue, and was resolved with activated charcoal. Use in near conception and during preg- Due to the increasing use of kava preparations, a short term and long-term nancy and lactation is not recommended due to possible mutagenic effects of clinical trails were conducted to in concern to adverse effects. valepotriates. [52]

Short-term clinical studies have shown that kava treatment (up to 600 mg) Precautions: does not interfere with cognitive performance; psychometric tests show Valerian is generally regarded as safe. small but perceptible increases in cognitive function, evident in increased Do not use valerian while driving, operating heavy machinery, or doing other vigilance and enhanced memory. [46-48] things that require you to be alert.

Long-term clinical studies using a purified kava extract reported no adverse Do not use valerian for longer than 1 month without your health care provider’s reactions to the extract. However, some reports describe a severe but revers- approval. ible dermopathy and yellowish skin discoloration among members of Pacific island and Australian aborigine cultures with prolonged use of kava in dos- Possible Interactions: ages 10–100 times those used clinically. [49] Medications broken down by the liver — Valerian may slow down how quickly certain drugs are broken down by the liver. Many medications rely Interactions: on the liver to break them down, so it’s possible that in some cases too much Do not take kava unless you are under the supervision of a qualified health of these drugs could build up in the body. To be safe, ask your doctor before care provider, especially if you are being treated for any disease. Do not take taking valerian if you are also taking any other medications. kava with any prescription and non-prescription medications. Sedatives — Valerian can increase the effect of these drugs,Anticonvulsants: Anticonvulsants — Kava may increase the effects of medications used to , valproic acid and . treat seizures. Benzodiazepines: and . — Do not use kava and alcohol together. The risk of impairment and Drugs to treat insomnia: zolpidem, zaleplon, eszopiclone, and ramelteon. the risk of liver damage are greatly increased. Tricyclic antidepressants: Amitriptyline and Alcohol. Anxiety agents — Kava may increase the effects of CNS depressants such as benzodiazepines, used for sleep disturbances or anxiety (particularly Other drugs — Because valerian is broken down by certain liver enzymes, it alprazolam), and barbiturates (such as ) which are used for may interact with other drugs that are broken down by the same enzymes. sleep disorders and seizures. Those drugs may include: Antipsychotic medications — Kava may increase the risk of side effects Antihistamines, Statins and Some antifungal drugs associated with phenothiazine medications (often used for the treatment of Anesthesia — Valerian may increase the effects of anesthesia. It is important schizophrenia), including chlorpromazine and promethazine. to consider in surgery. [50]

Journal of Pharmacy Research Vol.5 Issue 10.October 2012 4950-4956 Nagamani Kopparapu et al. / Journal of Pharmacy Research 2012,5(10),4950-4956 Chamomile (Matricaria recutita) Monoamine oxidase inhibitors (MAOIs) — Isocarboxazid, and Chamomile has been used for centuries as an herbal sleep aid. It is a very Tranylcypromine. [50] gentle herb and is considered safe both for adults and children. As an herb for insomnia is most often drunk as a tea, which has a mild, pleasant flavor. It has California poppy (Eschscholzia californica) a mild soothing effect which aids sleep and reduces restlessness. It also has a Natural herb commonly used as herbal insomnia remedy. California poppy positive effect on digestion. The active ingredients in chamomile include a leaves were used medicinally by Native Americans, and the pollen was used volatile oil and a flavonid , shows effect by binding to benzodiaz- cosmetically. The seeds are used in cooking. [65] Aqueous extract has sedative epine receptors. [55] It has anxiolytic activity, anticonvulsant activity and and anxiolytic action. [66] Extract from the California poppy acts as a mild CNS depressant activity. [56, 57] Chamomile is a very mild herb and does not sedative when smoked. The effect is far milder than that of opium. California lead to dependency and allergic reactions. It has not been shown to have any poppy contains a different class of alkaloids.[67] It has been reported to side effects. It may increase the effects of other sleep aids and should be used posses an affinity for the benzodiazepine receptor.[68] California poppy can with caution when combined with other drug therapies. be found in many herbal sleep aids sold in the United States today.

Interactions: Precautions: If you take any of the following drugs, you should not use German chamo- California poppy appears to be safe for most people when taken appropri- mile without first talking to your health care provider: ately by mouth for three months or less. There isn’t enough information to know if California poppy is safe for longer term use. Anticoagulants (blood-thinning medication) — Chamomile may increase the risk of bleeding when taken with anticoagulant drugs such as warfarin. Pregnancy and breast-feeding: Not enough is known about the use of Sedatives — Chamomile can increase the effect of drugs that have a sedating California poppy during pregnancy and breast-feeding. Stay on the safe effect, including: side and avoid use.

Anticonvulsants: Phenytoin and valproic acid Surgery: California poppy can slow down the central nervous system, Barbiturates causing sleepiness and other effects. It is important to consider in surgery. Benzodiazepines: Alprazolam and diazepam. [69] Drugs to treat insomnia: zolpidem, zaleplon, eszopiclone, and ramelteon. Possible interactions: Tricyclic antidepressants: Amitriptyline and Alcohol. Other drugs — Because chamomile is broken down by certain liver en- Sedative: zymes, it may interact with other drugs that are broken down by the same California poppy might cause sleepiness and drowsiness. Drugs that cause enzymes. Those drugs may include: Fexofenadine, Statins, Birth control sleepiness and drowsiness are called sedatives. Some of these sedative medi- pills and some antifungal drugs. [50] cations include , diazepam, , and others.

Passion flower (Passiflora incarnata) CNS depressants: Passionflower (Passiflora incarnata) was used traditionally in the Americas California poppy might cause sleepiness and drowsiness. Medications that and later in Europe as a calming herb for anxiety, [58-60] insomnia, [61] seizures, cause sleepiness are called sedatives. Some sedative medications include [62] and hysteria. [63] It is still used today to treat anxiety and insomnia. clonazepam, lorazepam , , zolpidem, and others. [69] Scientists believe passionflower works by increasing levels of a chemical called gamma amino butyric acid (GABA) in the brain. GABA lowers the American Skullcap () activity of some brain cells, making you feel more relaxed. [64] Skullcap is used in the treatment of a wide range of nervous conditions including epilepsy, [70] insomnia, [71] hysteria, anxiety, [71, 72] delerium tremens, Precautions: withdrawal from barbiturates and tranquilizers. Some valuable constituents Do not take passionflower if you are pregnant or breastfeeding. found in the plant are Scutellarin, Catalpol, other Volatile oils, bitter iridoids For others, passionflower is generally considered to be safe and nontoxic in and Tannins. Scientific studies are proving this to be a valuable plant in many recommended doses. areas for mental disorders.The infusion is given for nervous headaches, neu- ralgia and in headache arising from incessant coughing, pain, and inducing Possible Interactions: sleep when necessary, without any unpleasant symptoms following. Skull- Sedatives (drugs that cause sleepiness) — Because of its calming effect, cap is currently being used as an alternative medicine to treat number of nerve passionflower may make the effects of sedative medications stronger. These disorders. Traditionally used for restless leg syndrome and other causes of medications include: insomnia. It should be used with caution, because in overdose it causes giddiness, stupor, confusion and twitching. Anticonvulsants: phenytoin Barbiturates Precautions: Benzodiazepines: Alprazolam and diazepam In the past, American skullcap has been contaminated with germander Drugs for insomnia: zolpidem, zaleplon, eszopiclone and ramelteon. (Teucriumsp.), a group of known to cause liver problems. It is impor- Tricyclic antidepressants: amitriptyline, amoxapine, doxepin, and nortrip- tant that American skullcap be obtained from a reliable source. tyline High doses of the tincture may cause giddiness, stupor, mental confusion, Antiplatelets and anticoagulants (blood thinners) — Passionflower may in- twitching, irregular heartbeat, and seizures. crease the amount of time blood needs to clot, so it could make the effects of blood thinning medications stronger and increase your risk of bleeding. Blood American skullcap should not be used during pregnancy and breastfeeding. thinning drugs include: Clopidogrel, Warfarin and Aspirin

Journal of Pharmacy Research Vol.5 Issue 10.October 2012 4950-4956 Nagamani Kopparapu et al. / Journal of Pharmacy Research 2012,5(10),4950-4956 and thyroid medications. If you are taking sedatives (for insomnia or anxiety) Possible Interactions: or medications to regulate your thyroid, ask your doctor before taking lemon Sedatives — American skullcap can increase the effect of drugs that have a balm. sedating effect, including: Anticonvulsants: phenytoin and valproic acid HIV medications — It is not clear whether lemon balm interacts with antiretroviral agents. At this time, avoid use of lemon balm if you’re taking Barbiturates medication for HIV. [50] Benzodiazepines: Alprazolam and diazepam Lavender ( angustifolia) Drugs used to treat insomnia: zolpidem , zaleplon, eszopiclon , and ramelteon. In folklore, linen bags were filled with lavender flowers and placed under the Tricyclic antidepressants: Amitriptyline and Alcohol. [50] pillow to prevent problems in falling asleep. There is suggestive evidence that lavender essential oil may be helpful in management of certain sleep Hops (Humulus lupulus) disorders. [80]Lavender oil therapy is typically given by breathing the volatil- Hops is reputed as central nervous system (CNS) depressant, traditionally ized oil, referred to as ‘‘aromatherapy’’. The main chemical constituents of used to relief insomnia, anxiety, excitability and restlessness associated with lavender are camphor, linalyl acetate, linalool, beta-ocimene, and eucalyptol. tension headache and gastrointestinal spasms.[73] Hops were considered to The herb also contains up to 12% tannins. Animal studies shown neurotro- promote sleep after noting that hop pickers tired easily, apparently due to pic effect (shortening of time of getting to sleep, prolongation of dormancy) the transfer of hop resin from their hands to their mouths. [74] In addition and reduction of motoric activity. [81] In humans evidence was found, that the among female pickers of hops there was evidence of menstrual disturbances essential oil of lavender shows a sedative effects upon the limbic system, and in Germany hop baths have been used to reduce hot flashes in meno- comparable to . [82] pausal women. The plant is also thought to promote health. [75] Many herbal preparations for insomnia combine hops with more potent sedative herbs, CONCLUSION: such as valerian. [75, 76] The relaxing effect of hops may be due, in part, to the Sleep disorders are commonly associated with psychiatric conditions such specific chemical component dimethylvinyl carbinol. The efficacy of vale- as depression and bipolar disorder. Patients with common medical disorders rian and hop extract combination in the treatment of sleep disorders was often complain to their physician about sleep problems. Natural sleep aids demonstrated in healthy human volunteers. [75, 77] are available as different brands in today’s market. These sleep aids become drug of abuse. Generally, manufacturers of herbal remedies and dietary supple- Precautions: ments do not need FDA approval to sell their products. Just like a drug, Pregnancy and breast-feeding: Not enough is known about the use of hops herbs and supplements can affect the body’s chemistry, and therefore have during pregnancy and breast-feeding. Stay on the safe side and avoid use. the potential to produce side effects that may be harmful. There have been a Depression: Hops may make depression worse. Avoid use. number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any Surgery: Hops might cause too much sleepiness when combined with herbal remedies or dietary supplements. There is particularly high use of anesthesia and other medications during and after surgical procedures. Stop hypnotic medicine in the elderly, yet this group is more at risk of adverse taking hops at least 2 weeks before a scheduled surgery. events. In cases where drug treatment cannot be avoided, as non-drug thera- pies alone are not effective, patients should be prescribed the lowest effec- Possible interactions tive dose for the shortest duration and educated on the adverse effects of Alcohol can cause sleepiness and drowsiness. Hops might also cause sleepi- hypnotic medicines. Initial prescriptions should be limited to less than ten ness and drowsiness. Taking large amounts of hops along with alcohol might days. The underlying goal of pharmaceutical care is to get the right medica- cause too much sleepiness. tion to the right person at the right strength for the right condition. This can also be achieved by taking patient medication history while prescribing the Sedative: Hops might cause sleepiness and drowsiness. Medications that sleep -aids. cause sleepiness are called sedatives. Taking hops along with sedative medi- cations might cause too much sleepiness. Some sedative medications include REFERENCES clonazepam , lorazepam, phenobarbital, zolpidem , and others.[78] 1. National Commission on Sleep Disorders Research. Wake Up America: A National SleepAlert, Volume One, Executive Summary Lemon balm (Melissa officinalis), and Executive Report. Washington, D.C.: U.S. Government Printing Lemon balm a member of the mint family is considered a calming herb. It was Office, 1993. used as far back as the Middle Ages to reduce stress and anxiety, promote 2. Why we sleep: the evolutionary pathway to the mammalian sleep sleep, improve appetite, and ease pain and discomfort from indigestion (in- M.C. Nicolaua, M. Akaaà rir a, A. Gamundõ a, J. Gonza lez b, cluding gas and bloating, as well as colic). It inhibits the break down of R.V. Riala, Progress in Neurobiology 62 (2000) 379±406 sedative neurotransmitter GABA and possibly acetyl choline. [79] Today, 3. Sleep Loss and Sleepiness* Current Issues Thomas J. Balkin, PhD; lemon balm is often combined with other calming, soothing herbs, such as Tracy Rupp, PhD; Dante Picchioni, PhD; and Nancy J. Wesensten, valerian, chamomile, and hops, to help promote relaxation. It is also used in PhD Chest 2008;134;653-660 DOI 10.1378/chest.08-1064 creams to treat cold sores (oral herpes). 4. http://www.better-sleep-better-life.com/insomnia-statistics.html 5. www.sleepfoundation.org — National Sleep Foundation Precautions: 6. Roth, Thomas (15 August 2007). “Insomnia: Definition, Preva- Pregnant and breastfeeding women should not take lemon balm. lence, Etilogy, and Consequences”. J Clin Sleep Med 3 (5 Suppl): S7–S10.. Possible Interactions: 7. Hirshkowitz, Max (2004). “10, Neuropsychiatric Aspects of Sleep Lemon balm may potentially interact with the following medications: and Sleep Disorders (pp. 315–340)”. In Stuart C. 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