1. Misuse and Abuse Issues Related to Supplements Taken Clinically Susan McCabe EdD, RN Associate Professor East Tennessee State University

2. Clinical Use of Botanicals As old as documented history As old as documented history 60,000 year old Neanderthal burial site 60,000 year old Neanderthal burial site With phytobotanicals present With phytobotanicals present Writings of Chinese emperor Huang Di Writings of Chinese emperor Huang Di Relaxing effects of Valerian Relaxing effects of Valerian Assyrian medical practice Assyrian medical practice Multiple preparations Multiple preparations Hippocrates Hippocrates Valerian root for UTI’s Valerian root for UTI’s Ancient Greek Ancient Greek St. John’s Wort for insomnia St. John’s Wort for insomnia

3. Clinical Use of Botanicals Common and growing Common and growing Multiple Studies with range of 34-44% of adults used one or more botanical CAM within the past year Multiple Studies with range of 34-44% of adults used one or more botanical CAM within the past year 1 in 4 persons in US use botanical CAMs 1 in 4 persons in US use botanical CAMs In developing countries as many as 8 in 10 In developing countries as many as 8 in 10 Out of pocket costs Out of pocket costs CAMs CAMs $21.2 billion $21.2 billion Traditional Medical Care Traditional Medical Care $29.3 billion $29.3 billion Eisenberg, Davis, Ettner, et al.; 1998, JAMA; 280: 1569-1575; MacLennan, et al. 2000; Prev Med; 35(2): 166-73. Nat Cent Comp & Alt Med; 1999, St. John’s Wort Fact Sheet; Pub#Z-02: NIH; Mackenzie, et al., 2003. Altern Ther Health Med. 9(4): 50-56. St. John’s Wort 1995 = $20 million 1995 = $20 million 1997 = $200 million 1997 = $200 million 1998 = $400 million 1998 = $400 million

4. Who Is Using CAM’s Multiple studies have long supported differences between CAM users and Non-users Multiple studies have long supported differences between CAM users and Non-users Common CAM User Common CAM User Age 35-54 Age 35-54 Gender female Gender female Education over high school Education over high school Income mid to upper Income mid to upper Service utilization higher than non-users Service utilization higher than non-users Use phytobotanical as complementary agent not alternative Use phytobotanical as complementary agent not alternative Perception of CAM botanicals as less “drug-like“ Perception of CAM botanicals as less “drug-like“ Medical conditions not easily treated (chronic pain, mental health, cancer, HIV) Medical conditions not easily treated (chronic pain, mental health, cancer, HIV) Astin, JAMA. 1998;279:1548-1553 Blais, Maiga & Aboubacar, 1997. Can j Public Health; 88(3): 159-62.; Cauffield, 2000. Pharmacotherapy; 20(11): 1289-94.; Ni, Simile & Hardy. 2002. Med Care; 40(4): 3353-8.; Swartzman, Harsham, Burkell & Lundy, 2002. Med Decis Making; 22(5): 451-2.

5. Who is Using CAM’s Who is Using CAM’s But there is another group of CAM users we are just beginning to understand But there is another group of CAM users we are just beginning to understand Underserved population groups Underserved population groups Self-assessed low health status Self-assessed low health status Limited to no healthcare access Limited to no healthcare access Self medicating/ self diagnosing Self medicating/ self diagnosing Almost all for psychiatric related concerns Almost all for psychiatric related concerns Examples Examples CAM use in IV drug users CAM use in IV drug users 45% use a CAM regularly 45% use a CAM regularly Homeless street kids Homeless street kids 70% use a CAM regularly 70% use a CAM regularly Breuner, Barry & Kemper, 1998. Arch Pediatr Adolesc Med; 152(11): 1071-5. Gray, et al., 2002; Eff Clin Pract.; 5(1): 17-22.; Manheimer, et al. 2003. Am J Drug Abuse; 29(2): 401-13. ; Wolsko, et al., 2000. J Altern Complement Med; 6(4): 321-26.

6. Who is Using CAM’s At risk groups taking medicinal herbs At risk groups taking medicinal herbs Mentally ill – at risk for mental illness Mentally ill – at risk for mental illness Three of top ten conditions for which people take CAMs Three of top ten conditions for which people take CAMs Depression, anxiety, substance abuse Depression, anxiety, substance abuse CAMs used more than conventional therapies in individuals with anxiety & depression CAMs used more than conventional therapies in individuals with anxiety & depression 60-80% of patients seeing mental health providers self- added CAMs to treatment regimes 60-80% of patients seeing mental health providers self- added CAMs to treatment regimes CAM use highest in individuals with unmeet mental health needs CAM use highest in individuals with unmeet mental health needs No conventional care No conventional care Astin, 1998. JAMA, 279: 1548-1553.; Gray,et al., 2002; Eff Clin Pract.; 5(1):17-22.; Kessler, Soukup, Davis, Foster, et al., 2000. Am J Psychiatry;158(2): 289-94.; Sturm, et al. 2001. J Behav Health Res,28(1):81-8

7. Who is Using CAM’s CAM Use is also Significant among Children CAM Use is also Significant among Children 12% - 21% of children age 4-18 12% - 21% of children age 4-18 Factors influencing use Factors influencing use Maternal age < 31 years Maternal age < 31 years Parent/caregiver born outside USA Parent/caregiver born outside USA Use of CAM by parents Use of CAM by parents Most common CAM Most common CAM Herbals = 41% Herbals = 41% High dose vitamins = 35% High dose vitamins = 35% Ottolini, et al. 2001. Ambul Pediatr.; 1(2): 122-5.; Sawni-Sikand, et al.; 2002. Ambul Pediatr.; 2(2): 99-103.

8. Do Not Report CAM use to Providers 66-72% Do not report use 66-72% Do not report use Reasons for non-disclosure Reasons for non-disclosure “It wasn’t important for the doctor to know” = 61% “It wasn’t important for the doctor to know” = 61% “The doctor never asked” = 60% “The doctor never asked” = 60% “It was none of the doctors business” = 31% “It was none of the doctors business” = 31% “The doctor would not understand” = 20% “The doctor would not understand” = 20% “The doctor would disapprove” = 14% “The doctor would disapprove” = 14% “The doctor would not treat me anymore” = 2% “The doctor would not treat me anymore” = 2% Eisenberg, et al. 2001. Ann Intern Med.; 135(5): 344-51.; Sawni-Sikand, et al.; 2002. Ambul Pediatr.; 2(2): 99-103.

9. Clinical Use of Botanicals Widespread use of botanicals Widespread use of botanicals Little participation with health care system Little participation with health care system Questions about Questions about Quality, safety and efficacy of these products Quality, safety and efficacy of these products Opens potential for misuse and abuse Opens potential for misuse and abuse Many phytobotanicals easily available Many phytobotanicals easily available Lots of advise and “thought” available Lots of advise and “thought” available Little evidence available to providers or patients Little evidence available to providers or patients Some phytobotanicals dangerous Some phytobotanicals dangerous Some exotic Some exotic Substance use migrates from traditional cultural areas of use Substance use migrates from traditional cultural areas of use Abuse potential of non-culturally bound use is area of concern Abuse potential of non-culturally bound use is area of concern Eisenberg, et al.; 1998. JAMA. 280:1569-75.; Mahady 2001;J Nutr;131(3s):1120S-3S.

10. Hard for providers to get information Amount of reliable information is limited Amount of reliable information is limited Few authoritative sources Few authoritative sources Searching databases is challenging Searching databases is challenging Inconsistent use of controlled vocabulary and indexing procedures Inconsistent use of controlled vocabulary and indexing procedures Lack of standardized terminology Lack of standardized terminology Multiple names of several botanicals Multiple names of several botanicals Kava, Yaqona, Grog Kava, Yaqona, Grog Khat, Qat Khat, Qat Study of health professionals Study of health professionals Of those seeking CAM references Of those seeking CAM references 26% Internal Medicine/ primary care providers 26% Internal Medicine/ primary care providers 15% Psychiatric/ mental health providers 15% Psychiatric/ mental health providers Murphy, et al., 2003. BMC Complem & Altern Med; 3(3): 917-28. Owen & Fang, 2003. J Med Libr Assoc.; 91(3): 311-21.

11. Framing the Issues Botanical CAM use is high Botanical CAM use is high Users of Cam’s fall roughly into two categories Users of Cam’s fall roughly into two categories One category is arguably already at-risk for substance misuse/ abuse One category is arguably already at-risk for substance misuse/ abuse Hard for providers to get accurate information to help, advise, or monitor patients CAM use Hard for providers to get accurate information to help, advise, or monitor patients CAM use

12. Misuse and Abuse Spectrum Spectrum Misuse Misuse Self medicated/ regulated Self medicated/ regulated Over treated, under treated, wrong treatment Over treated, under treated, wrong treatment Unintended consequences of use Unintended consequences of use Unintended synergism Unintended synergism Clinically significant botanical-drug interactions Clinically significant botanical-drug interactions Abuse Abuse Psychoactive Psychoactive Intentional synergism Intentional synergism Addictive? Addictive? Difficult to find reliable data on the abuse potential of phytobotanicals Difficult to find reliable data on the abuse potential of phytobotanicals Makes rational, evidence-based decision-making difficult in clinical settings Makes rational, evidence-based decision-making difficult in clinical settings International Centre for Mental Health Policy : Hum Psychopharmacol. 2002 Apr;17(3):131-40.

13. Misuse Unintended consequences of use Unintended consequences of use Unintended synergism & clinically significant botanical- drug interactions Unintended synergism & clinically significant botanical- drug interactions Consequences Consequences Physical Physical Hepatotoxicity - potential risk of severe liver injury with KAVA Hepatotoxicity - potential risk of severe liver injury with KAVA Psychiatric Psychiatric Neurotoxicity – potential risk of mania from St. John’s wort Neurotoxicity – potential risk of mania from St. John’s wort Genetic Genetic Mutagenic genotoxicity- Betel quid and Khat Mutagenic genotoxicity- Betel quid and Khat Li JH, Lin LF., 1998Genetic toxicology of abused drugs: a brief review Nov;13(6):557-65. (Li JH, Lin LF., 1998 Genetic toxicology of abused drugs: a brief review Nov;13(6):557-65.)

14. Misuse Phytobotanicals with no clear addictive potential Phytobotanicals with no clear addictive potential Example Example Vitamin supplements in self-medication Vitamin supplements in self-medication Long History Documented Misuse Long History Documented Misuse Rational for use Rational for use Attempts to compensate for an unhealthy life style Attempts to compensate for an unhealthy life style Attempts to maximize health or performance Attempts to maximize health or performance No evidence of nutritional benefit derived from excess consumption of vitamin supplements No evidence of nutritional benefit derived from excess consumption of vitamin supplements Misuse occurs in the intentional daily intake in excess of recommended by various international and national expert committees Misuse occurs in the intentional daily intake in excess of recommended by various international and national expert committees Potential consequences Potential consequences Toxicity in vitamins such as vitamin A and vitamin D Toxicity in vitamins such as vitamin A and vitamin D To a lesser extent, vitamin C and nicotinic acid To a lesser extent, vitamin C and nicotinic acid Jarvis, 1985. Vitamin use and abuse.; Bol Asoc Med P R.; 77(4):168-70 ; Briggs & Brigggs, 1977. The use and misuse of vitamin supplements.; Aust Fam Physician; 6(2):145-7, 151-2. ; Rudman, et al., 1983. Megadose vitamins. Use and misuse. N Engl J Med. 25;309(8):488-90; Can Med Assoc, 1971. The use and abuse of vitamin An Can Med Assoc J. ; 20;104(6):521-2. ; Maitai, 1984. The craze for additional vitamin intake. East Afr Med J.; 61(9):661-2.

15. Abuse & Psychoactive Botanicals Often about ethnopharmacology Often about ethnopharmacology Movement of indigenous drugs Movement of indigenous drugs Deritualization for clinical or recreational intent Deritualization for clinical or recreational intent Movement of drug without symbolic, religious, or other cultural mediators Movement of drug without symbolic, religious, or other cultural mediators Hard for providers to get information Hard for providers to get information Often miss the abuse aspect of clinical presentation Often miss the abuse aspect of clinical presentation Phenomenon of modern age Phenomenon of modern age Service access issues Service access issues Internet Internet Travel Travel

16. Misuse and Abuse: All Categories of Substances Psychoanaleptic (stimulant) Psychoanaleptic (stimulant) Psychodysleptic (hallucinogenic) Psychodysleptic (hallucinogenic) Psycholeptic (anxiolytic) Psycholeptic (anxiolytic)

17. Psychoanaleptic (stimulant)

18. Psychoactive CNS action of botanicals Psychoanaleptic (stimulant) Psychoanaleptic (stimulant) Uses Uses Weight reduction Weight reduction Adaptogenic uses Adaptogenic uses Chronic fatigue – secondary to MDD Chronic fatigue – secondary to MDD Adult ADHD Adult ADHD Guarana (Paullinia cupana) Guarana (Paullinia cupana) Ma Huang (Ephedra spp.) Ma Huang (Ephedra spp.) Khat [Qat] (Catha edulis Forssk) Khat [Qat] (Catha edulis Forssk)

19. Psychoanaleptic Guarana Guarana Brasilian coca Brasilian coca Traditional use Traditional use Now Internet Now Internet Indicated for Indicated for Weight loss Weight loss Herbal viagra Herbal viagra Chronic fatigue Chronic fatigue ADHD ADHD

20. Guarana Naturale® is the original guarana powder ready to mix with drinks Guarana Active® is the original guarana powder but in tablet form, and is available in blister packs of 20 or 60 capsules.

21. Psychoanaleptic: Ma Huang Widely promoted as weight reduction and energy enhancement herb Widely promoted as weight reduction and energy enhancement herb Form Form Dietary supplements available on web sites and in dietary shops Dietary supplements available on web sites and in dietary shops Chinese ephedra Chinese ephedra Black Caffeine Black Caffeine Ma Huang alone or combined Ma Huang alone or combined With Guarana, St John's wort With Guarana, St John's wort Numerous reports of adverse reactions and acute intoxication related to product use Numerous reports of adverse reactions and acute intoxication related to product use Resulted in permanent injury and death Resulted in permanent injury and death 47%, CV; 18% CNS 47%, CV; 18% CNS Severe hypertension single most frequent adverse effect Severe hypertension single most frequent adverse effect Arditti J, Bourdon JH, Spadari M, de Haro L, Richard N, Valli M; Acta Clin Belg Suppl. 2002;(1):34-6

22. FDA has proposed limits on the dose and duration of use of such supplements So….. NEW….Guarana extract as a replacement for ma huang TWINLAB METABOLIFT NO MA HUANG 120 CAPS

23. Psychoanaleptic: Khat Stimulating effect of leaves of the Khat bush Stimulating effect of leaves of the Khat bush Leaves contain a variety of sympathomimetics Leaves contain a variety of sympathomimetics Alkaloid cathinone is main active principle of this drug Alkaloid cathinone is main active principle of this drug Similar in structure and pharmacological activity to amphetamine Similar in structure and pharmacological activity to amphetamine Are chewed in several East African countries and in Yemen Are chewed in several East African countries and in Yemen Since only fresh leaves are active, until recently, Khat abuse was almost unknown outside the regions where the plant grows Since only fresh leaves are active, until recently, Khat abuse was almost unknown outside the regions where the plant grows Giannini, Miller, & Turner; 1992. J Subst Abuse Treat; 9(4):379-82. ( Giannini, Miller, & Turner; 1992. J Subst Abuse Treat; 9(4):379-82. )

24. Khat Recently, however, khat has made its appearance in the United States and in several European countries Recently, however, khat has made its appearance in the United States and in several European countries U.S., American soldiers stationed in the Arabian peninsula may be exposed to it because of the alcohol interdiction during the first Gulf War U.S., American soldiers stationed in the Arabian peninsula may be exposed to it because of the alcohol interdiction during the first Gulf War Became popular alternative recreational drug Became popular alternative recreational drug Increasingly prohibited Increasingly prohibited Importation of qat is illegal in France and Switzerland Importation of qat is illegal in France and Switzerland But legal in the United States, Great Britain and most African countries But legal in the United States, Great Britain and most African countries Growing concern with addictive potential Growing concern with addictive potential Extensive literature base of support Extensive literature base of support Growing use in Club Drug Scene as a bumper drug Growing use in Club Drug Scene as a bumper drug Al-Motarreb, et al., 2002. Phytother Res. 16(5): 403-13.; Krikorian, 1984. J Ethnopharmacol. 12(2): 115-78.; Griffiths, et al., 1997. Br J Psychiatry, 170: 281-4.; Gianninni, et. Al., 1992. J Subst Abuse Treat. 9(4): 379-82.;

25. Psychodysleptic (hallucinogenic)

26. Psychoactive CNS action of botanicals Psychodysleptic (hallucinogenic) Psychodysleptic (hallucinogenic) Used to achieve mind distortion states Used to achieve mind distortion states Visionary Visionary Phenethylamines Phenethylamines Indole alkaloids Indole alkaloids Isoaxzoles Isoaxzoles Imagery Imagery Coumarins Coumarins Dibenzyopyrans Dibenzyopyrans Trance-like Trance-like Ergolines Ergolines Opiates Opiates Delirium-like Delirium-like Tropane Alkaloids Tropane Alkaloids

27. Psychodysleptic Strong religious use in indigenous cultures Strong religious use in indigenous cultures Alter thought, perception, and mood Alter thought, perception, and mood Seldom produce Seldom produce Mental confusion Mental confusion Memory loss Memory loss Disorientation Disorientation Strong History of Sacramental & Medicinal Use Strong History of Sacramental & Medicinal Use EXAMPLE EXAMPLE Cacti Cacti Peyote Peyote San Pedro (T. Terschechii) San Pedro (T. Terschechii) Salvia Divinorum (Mexican mint) Salvia Divinorum (Mexican mint) Same characteristics fuel non-sacramental use Same characteristics fuel non-sacramental use Common botanicals with wider abuse Common botanicals with wider abuse Cannabis sativa Cannabis sativa Tabernanthe iboga (Eboka) Tabernanthe iboga (Eboka) Banisteriopsis caapi (Spruce ex Griseb.) Banisteriopsis caapi (Spruce ex Griseb.)

28. Psychodysleptic: Tabernanthe iboga Eboka (Iboga) Eboka (Iboga) West African shrub West African shrub Long history cultural use of root as stimulant Long history cultural use of root as stimulant Action from complex indole alkaloids derived from tryptamine Action from complex indole alkaloids derived from tryptamine Use Use Communication with ancestors Communication with ancestors Divination of illness Divination of illness Internet availability Internet availability As aphrodisiac As aphrodisiac Memory enhancer Memory enhancer To treat active substance abuse To treat active substance abuse

29. Psycholeptic (anxiolytic) Most familiar Most common

30. Psychoactive CNS action of botanicals Psycholeptic Psycholeptic Used to achieve analgesic or anxiolytic affect Used to achieve analgesic or anxiolytic affect Valeriana officinalis L. Valeriana officinalis L. Piper methysticum Piper methysticum Betel nut Betel nut

31. Psycholeptic Valerian Valerian Strong neuropsychiatry use Strong neuropsychiatry use High-affinity dopamine reuptake inhibitor High-affinity dopamine reuptake inhibitor Synthesized in the late 1970s Synthesized in the late 1970s Initially tested in Europe as a potential antidepressant Initially tested in Europe as a potential antidepressant Common uses Common uses Insomnia Insomnia Anxiety Anxiety Depression Depression Little data for abuse Little data for abuse Some reports “hangover effect” Some reports “hangover effect” No reports associated with habituation or abuse No reports associated with habituation or abuse Rare questionable reports of withdrawal symptoms Rare questionable reports of withdrawal symptoms Krystal & ressler, 2001. CNS Spectrum6(10): 841-47.

32. Psycholeptic Piper methysticum (kava kava) Piper methysticum (kava kava) Plant native to the Pacific Island region Plant native to the Pacific Island region Has been used ceremonial for thousands of years for resolution of political and social disputes Has been used ceremonial for thousands of years for resolution of political and social disputes Active ingredients are a group of substances know as kava lactones Active ingredients are a group of substances know as kava lactones Found to have significant analgesic and anesthetic effects via non-opiate pathways Found to have significant analgesic and anesthetic effects via non-opiate pathways Common uses Common uses Natural anxiolytic, comparing favorably in several studies to a number prescription medications, including benzodiazepines Natural anxiolytic, comparing favorably in several studies to a number prescription medications, including benzodiazepines Known to produce severe motor and psychiatric responses Known to produce severe motor and psychiatric responses These are not well-understood These are not well-understood Include psychotic and severe dystonic reactions Include psychotic and severe dystonic reactions Yet without interruption in normal cognitive processes Yet without interruption in normal cognitive processes

33. Micronesia

35. Kava Bar

36. After Hours Hut

37. Kava Action is unclear Action is unclear GABA-receptor-binding capacity found to occur in some studies GABA-receptor-binding capacity found to occur in some studies In vitro kava has been found to block norepinephrine uptake In vitro kava has been found to block norepinephrine uptake Appears to have some anti-convulsant capabilities Appears to have some anti-convulsant capabilities Mediated by Na+ channel receptor sites Mediated by Na+ channel receptor sites Animal studies show that kava lactones alter neuronal excitation through direct interactions with voltage-dependent ion channels Animal studies show that kava lactones alter neuronal excitation through direct interactions with voltage-dependent ion channels Giving rise to kava's muscle relaxant, anesthetic, anxiolytic and anticonvulsive properties Giving rise to kava's muscle relaxant, anesthetic, anxiolytic and anticonvulsive properties Most common side effect of use Most common side effect of use Usually seen only with long-term, heavy usage of the herb Usually seen only with long-term, heavy usage of the herb Include Include Scaly skin rash called "kava dermopathy." Scaly skin rash called "kava dermopathy." Potentiate other medications such as barbiturates and Xanax Potentiate other medications such as barbiturates and Xanax Raising fast in Club Drug Scene Raising fast in Club Drug Scene

38. Multiple Forms

39. KAVA Abuse Potential Physical affects of sustained use /abuse Physical affects of sustained use /abuse Dermopathy characteristic of heavy use Dermopathy characteristic of heavy use Abnormally low body mass index (BMI) Abnormally low body mass index (BMI) Low blood lymphocytes Low blood lymphocytes Abnormally high gamma-glutamyl transferase (GGT) Abnormally high gamma-glutamyl transferase (GGT) These acute effects emerge at average consumption levels of from 310-440 g/week of kava powder. These acute effects emerge at average consumption levels of from 310-440 g/week of kava powder. Economics of abuse well documented Economics of abuse well documented Average consumption of 240-425 g/week Average consumption of 240-425 g/week 19% of available cash resources were spent on kava 19% of available cash resources were spent on kava 11% of cash resources leaving the local community economy 11% of cash resources leaving the local community economy The proportion of men drinking kava reached 70% and women 62% The proportion of men drinking kava reached 70% and women 62% 20% of the population spending unprecedented amounts of time (14 + hours/week) in activities where kava was consumed 20% of the population spending unprecedented amounts of time (14 + hours/week) in activities where kava was consumed These parameters may be useful to monitor kava's adverse health, social and economic effects These parameters may be useful to monitor kava's adverse health, social and economic effects Clough; 2003, Drug Alcohol Rev.;22(1):43-51. ( Clough; 2003, Drug Alcohol Rev.;22(1):43-51. )

40. KAVA Increasingly widespread use of kava Increasingly widespread use of kava Intentional mixing in club drug scene Intentional mixing in club drug scene Further investigation is necessary to gain an understanding of its immediate neuropsychiatry effects and long-term cognitive effects Further investigation is necessary to gain an understanding of its immediate neuropsychiatry effects and long-term cognitive effects Cairney S, Maruff P, Clough; Aust N Z J Psychiatry. 2002 Oct;36(5):657-62.

41. Betel Nut Pan Asian problem Pan Asian problem Uses Uses Improved concentration Improved concentration Intestinal parasites Intestinal parasites Social setting symbol Social setting symbol Areca catechu (nut) & Piper betel (leaf) Areca catechu (nut) & Piper betel (leaf) Arecoline + Piperine alkaloids Arecoline + Piperine alkaloids Unclear action Unclear action Effects thought to be related to the actions of Arecoline Effects thought to be related to the actions of Arecoline However the actual chewing may produce complex reactions and interactions However the actual chewing may produce complex reactions and interactions Commonly chewed in the presence of lime Commonly chewed in the presence of lime Arecoline and guvacoline in Areca nut Arecoline and guvacoline in Areca nut Hydrolyzed into arecaidine and guvacine Hydrolyzed into arecaidine and guvacine Are strong inhibitors of GABA uptake Are strong inhibitors of GABA uptake Piper betle flower or leaf contains aromatic phenolic compounds Piper betle flower or leaf contains aromatic phenolic compounds Have been found to stimulate the release of catecholamines in vitro are also activated by chewing Have been found to stimulate the release of catecholamines in vitro are also activated by chewing Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions.

42. Betel Nut Chewing betel chewing mainly affects the central and autonomic nervous systems producing Chewing betel chewing mainly affects the central and autonomic nervous systems producing Sense of well-being Sense of well-being EEG shows widespread cortical desynchronization indicating a state of arousal EEG shows widespread cortical desynchronization indicating a state of arousal Euphoria Euphoria Increases plasma concentrations of norepinephrine and epinephrine Increases plasma concentrations of norepinephrine and epinephrine Increase in heart rate, blood pressure Increase in heart rate, blood pressure Heightened alertness Heightened alertness Sweating with increased temperature Sweating with increased temperature Salivation Salivation Hot sensation in the body Hot sensation in the body Increased capacity to work Increased capacity to work Chewing also leads to habituation, addiction and withdrawal Chewing also leads to habituation, addiction and withdrawal Mechanisms underlying these effects remain poorly understood Mechanisms underlying these effects remain poorly understood Betel nut withdrawal syndrome well documented in Pacific Medical Literature Betel nut withdrawal syndrome well documented in Pacific Medical Literature National Science Council, ROC and S. Karger AG, Basel; Chu ;J Biomed Sci. 2001 May Jun; 8(3):229-36.; Wiesner Med J Aust. 1987 Apr 20;146(8):453.) Source: National Science Council, ROC and S. Karger AG, Basel; Chu ;J Biomed Sci. 2001 May Jun; 8(3):229-36.; Wiesner Med J Aust. 1987 Apr 20;146(8):453. )

43. Betel Quid An estimated 10% to 25% of the world's population chews betel quid An estimated 10% to 25% of the world's population chews betel quid Practice is little recognized in the United States Practice is little recognized in the United States Growing in areas of immigration Growing in areas of immigration Groups such as Groups such as Immigrants and refugees from India, New Guinea, and Southeast Asia Immigrants and refugees from India, New Guinea, and Southeast Asia Physical hazards associated with the chewing of the various ingredients of the quid include Physical hazards associated with the chewing of the various ingredients of the quid include oral cancer oral cancer addictive potential as strong as for cigarettes addictive potential as strong as for cigarettes

44. Conclusions Patients are using herbal remedies for a variety of health conditions without medical supervision Patients are using herbal remedies for a variety of health conditions without medical supervision Psychiatric mental health problems are one of the largest reasons people seek botanical CAMs Psychiatric mental health problems are one of the largest reasons people seek botanical CAMs Often intentionally do not inform providers Often intentionally do not inform providers Information is hard for providers to obtain Information is hard for providers to obtain Very little evidence on which to base clinical decision making Very little evidence on which to base clinical decision making Almost no awareness of abuse potential of several commonly used botanicals Almost no awareness of abuse potential of several commonly used botanicals More research is needed on herbal remedy use among patient populations and on outcomes in patients who use herbal remedies to treat primary health conditions More research is needed on herbal remedy use among patient populations and on outcomes in patients who use herbal remedies to treat primary health conditions

45. Thank You