Misuse and Abuse Issues Related to Supplements Taken Clinically

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
• 60,000 year old Neanderthal burial site
• With phytobotanicals present
• Writings of Chinese emperor Huang Di
• Relaxing effects of Valerian
• Assyrian medical practice
• Multiple preparations
• Hippocrates
• Valerian root for UTIs
• Ancient Greek
• St. Johns Wort for insomnia

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Clinical Use of Botanicals

• Common and growing
• 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
• In developing countries as many as 8 in 10
• Out of pocket costs
• CAMs
• 21.2 billion
• Traditional Medical Care
• 29.3 billion

St. Johns Wort 1995 20 million 1997
200 million 1998 400 million
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.
Johns Wort Fact Sheet PubZ-02 NIH Mackenzie,
et al., 2003. Altern Ther Health Med. 9(4) 50-56.
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Who Is Using CAMs

• Multiple studies have long supported differences
  between CAM users and Non-users
• Common CAM User
• Age 35-54
• Gender female
• Education over high school
• Income mid to upper
• Service utilization higher than non-users
• Use phytobotanical as complementary agent not
  alternative
• Perception of CAM botanicals as less drug-like
• Medical conditions not easily treated (chronic
  pain, mental health, cancer, HIV)

Astin, JAMA. 19982791548-1553 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.
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Who is Using CAMs

• But there is another group of CAM users we are
  just beginning to understand
• Underserved population groups
• Self-assessed low health status
• Limited to no healthcare access
• Self medicating/ self diagnosing
• Almost all for psychiatric related concerns
• Examples
• CAM use in IV drug users
• 45 use a CAM regularly
• Homeless street kids
• 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.
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Who is Using CAMs

• At risk groups taking medicinal herbs
• Mentally ill at risk for mental illness
• Three of top ten conditions for which people take
  CAMs
• Depression, anxiety, substance abuse
• 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
• CAM use highest in individuals with unmeet mental
  health needs
• 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
Psychiatry158(2) 289-94. Sturm, et al. 2001. J
Behav Health Res,28(1)81-8
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Who is Using CAMs

• CAM Use is also Significant among Children
• 12 - 21 of children age 4-18
• Factors influencing use
• Maternal age lt 31 years
• Parent/caregiver born outside USA
• Use of CAM by parents
• Most common CAM
• Herbals 41
• 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.
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Do Not Report CAM use to Providers

• 66-72 Do not report use
• Reasons for non-disclosure
• It wasnt important for the doctor to know
  61
• The doctor never asked 60
• It was none of the doctors business 31
• The doctor would not understand 20
• The doctor would disapprove 14
• 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.
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Clinical Use of Botanicals

• Widespread use of botanicals
• Little participation with health care system
• Questions about
• Quality, safety and efficacy of these products
• Opens potential for misuse and abuse
• Many phytobotanicals easily available
• Lots of advise and thought available
• Little evidence available to providers or
  patients
• Some phytobotanicals dangerous
• Some exotic
• Substance use migrates from traditional cultural
  areas of use
• Abuse potential of non-culturally bound use is
  area of concern

Eisenberg, et al. 1998. JAMA. 2801569-75.
Mahady 2001J Nutr131(3s)1120S-3S.
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Hard for providers to get information

• Amount of reliable information is limited
• Few authoritative sources
• Searching databases is challenging
• Inconsistent use of controlled vocabulary and
  indexing procedures
• Lack of standardized terminology
• Multiple names of several botanicals
• Kava, Yaqona, Grog
• Khat, Qat
• Study of health professionals
• Of those seeking CAM references
• 26 Internal Medicine/ primary care 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.
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Framing the Issues

• Botanical CAM use is high
• Users of Cams fall roughly into two categories
• 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

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Misuse and Abuse

• Spectrum
• Misuse
• Self medicated/ regulated
• Over treated, under treated, wrong treatment
• Unintended consequences of use
• Unintended synergism
• Clinically significant botanical-drug
  interactions
• Abuse
• Psychoactive
• Intentional synergism
• Addictive?
• Difficult to find reliable data on the abuse
  potential of phytobotanicals
• Makes rational, evidence-based decision-making
  difficult in clinical settings

International Centre for Mental Health Policy
Hum Psychopharmacol. 2002 Apr17(3)131-40.
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Misuse

• Unintended consequences of use
• Unintended synergism clinically significant
  botanical-drug interactions
• Consequences
• Physical
• Hepatotoxicity - potential risk of severe liver
  injury with KAVA
• Psychiatric
• Neurotoxicity potential risk of mania from St.
  Johns wort
• Genetic
• Mutagenic genotoxicity- Betel quid and Khat

(Li JH, Lin LF., 1998 Genetic toxicology of
abused drugs a brief review Nov13(6)557-65.)
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Misuse

• Phytobotanicals with no clear addictive potential
• Example
• Vitamin supplements in self-medication
• Long History Documented Misuse
• Rational for use
• Attempts to compensate for an unhealthy life
  style
• Attempts to maximize health or performance
• 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
• Potential consequences
• Toxicity in vitamins such as vitamin A and
  vitamin D
• 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. 25309(8)488-90 Can Med Assoc,
  1971. The use and abuse of vitamin An Can Med
  Assoc J. 20104(6)521-2. Maitai, 1984. The
  craze for additional vitamin intake. East Afr Med
  J. 61(9)661-2.

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Abuse Psychoactive Botanicals

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

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Misuse and Abuse All Categories of Substances

• Psychoanaleptic (stimulant)
• Psychodysleptic (hallucinogenic)
• Psycholeptic (anxiolytic)

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Psychoanaleptic (stimulant)
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Psychoactive CNS action of botanicals

• Psychoanaleptic (stimulant)
• Uses
• Weight reduction
• Adaptogenic uses
• Chronic fatigue secondary to MDD
• Adult ADHD
• Guarana (Paullinia cupana)
• Ma Huang (Ephedra spp.)
• Khat Qat (Catha edulis Forssk)

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Psychoanaleptic

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

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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.
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Psychoanaleptic Ma Huang

• Widely promoted as weight reduction and energy
  enhancement herb
• Form
• Dietary supplements available on web sites and in
  dietary shops
• Chinese ephedra
• Black Caffeine
• Ma Huang alone or combined
• With Guarana, St John's wort
• Numerous reports of adverse reactions and acute
  intoxication related to product use
• Resulted in permanent injury and death
• 47, CV 18 CNS
• 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
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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
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Psychoanaleptic Khat

• Stimulating effect of leaves of the Khat bush
• Leaves contain a variety of sympathomimetics
• Alkaloid cathinone is main active principle of
  this drug
• Similar in structure and pharmacological activity
  to amphetamine
• 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

(Giannini, Miller, Turner 1992. J Subst Abuse
Treat 9(4)379-82. )
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Khat

• 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
• Became popular alternative recreational drug
• Increasingly prohibited
• Importation of qat is illegal in France and
  Switzerland
• But legal in the United States, Great Britain and
  most African countries
• Growing concern with addictive potential
• Extensive literature base of support
• 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.
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Psychodysleptic (hallucinogenic)
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Psychoactive CNS action of botanicals

• Psychodysleptic (hallucinogenic)
• Used to achieve mind distortion states
• Visionary
• Phenethylamines
• Indole alkaloids
• Isoaxzoles
• Imagery
• Coumarins
• Dibenzyopyrans
• Trance-like
• Ergolines
• Opiates
• Delirium-like
• Tropane Alkaloids

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Psychodysleptic

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

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Psychodysleptic Tabernanthe iboga

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

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Psycholeptic (anxiolytic)

• Most familiar
• Most common

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Psychoactive CNS action of botanicals

• Psycholeptic
• Used to achieve analgesic or anxiolytic affect
• Valeriana officinalis L.
• Piper methysticum
• Betel nut

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Psycholeptic

• Valerian
• Strong neuropsychiatry use
• High-affinity dopamine reuptake inhibitor
• Synthesized in the late 1970s
• Initially tested in Europe as a potential
  antidepressant
• Common uses
• Insomnia
• Anxiety
• Depression
• Little data for abuse
• Some reports hangover effect
• No reports associated with habituation or abuse
• Rare questionable reports of withdrawal symptoms

Krystal ressler, 2001. CNS Spectrum6(10)
841-47.
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Psycholeptic

• Piper methysticum (kava kava)
• Plant native to the Pacific Island region
• 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
• Found to have significant analgesic and
  anesthetic effects via non-opiate pathways
• Common uses
• Natural anxiolytic, comparing favorably in
  several studies to a number prescription
  medications, including benzodiazepines
• Known to produce severe motor and psychiatric
  responses
• These are not well-understood
• Include psychotic and severe dystonic reactions
• Yet without interruption in normal cognitive
  processes

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Micronesia
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(No Transcript)
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Kava Bar
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After Hours Hut
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Kava

• Action is unclear
• GABA-receptor-binding capacity found to occur in
  some studies
• In vitro kava has been found to block
  norepinephrine uptake
• Appears to have some anti-convulsant capabilities
• Mediated by Na channel receptor sites
• 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
• Most common side effect of use
• Usually seen only with long-term, heavy usage of
  the herb
• Include
• Scaly skin rash called "kava dermopathy."
• Potentiate other medications such as barbiturates
  and Xanax
• Raising fast in Club Drug Scene

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Multiple Forms
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KAVA

• Abuse Potential
• Physical affects of sustained use /abuse
• Dermopathy characteristic of heavy use
• Abnormally low body mass index (BMI)
• Low blood lymphocytes
• Abnormally high gamma-glutamyl transferase (GGT)
• These acute effects emerge at average consumption
  levels of from 310-440 g/week of kava powder.
• Economics of abuse well documented
• Average consumption of 240-425 g/week
• 19 of available cash resources were spent on
  kava
• 11 of cash resources leaving the local community
  economy
• 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
• These parameters may be useful to monitor kava's
  adverse health, social and economic effects

(Clough 2003, Drug Alcohol Rev.22(1)43-51. )
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KAVA

• Increasingly widespread use of kava
• Intentional mixing in club drug scene
• 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 Oct36(5)657-62.
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Betel Nut

• Pan Asian problem
• Uses
• Improved concentration
• Intestinal parasites
• Social setting symbol
• Areca catechu (nut) Piper betel (leaf)
• Arecoline Piperine alkaloids
• Unclear action
• Effects thought to be related to the actions of
  Arecoline
• However the actual chewing may produce complex
  reactions and interactions
• Commonly chewed in the presence of lime
• Arecoline and guvacoline in Areca nut
• Hydrolyzed into arecaidine and guvacine
• Are strong inhibitors of GABA uptake
• 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
• Thus, betel chewing may affect parasympathetic,
  GABAnergic and sympathetic functions.

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Betel Nut

• Chewing betel chewing mainly affects the central
  and autonomic nervous systems producing
• Sense of well-being
• EEG shows widespread cortical desynchronization
  indicating a state of arousal
• Euphoria
• Increases plasma concentrations of norepinephrine
  and epinephrine
• Increase in heart rate, blood pressure
• Heightened alertness
• Sweating with increased temperature
• Salivation
• Hot sensation in the body
• Increased capacity to work
• Chewing also leads to habituation, addiction and
  withdrawal
• Mechanisms underlying these effects remain poorly
  understood
• Betel nut withdrawal syndrome well documented in
  Pacific Medical Literature

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
20146(8)453. )
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Betel Quid

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

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Conclusions

• 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
• Often intentionally do not inform providers
• Information is hard for providers to obtain
• Very little evidence on which to base clinical
  decision making
• 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

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Thank You