RX462 Drug Abuse & Society PresentationsBrian J. Piper, Ph.D., M.S.

Department of Basic Pharmaceutical Sciencespsy391@gmail.com or piperbj@husson.edu

ContentsDrug Author Slide #

LSD Sarah Moore 3 to 29

Peyote Anonymous* 30 to 50

Amanita Mushrooms Priyank Mandalia 51 to 68

Salvia divinorum Anonymous* 69 to 90

Ketamine Anonymous* 91 to 112

Bath salts Lindsay Pelletier 113 to 137

Gamma-hydroxybutyrate (GHB) Anonymous* 138 to 161

Nitrous oxide Curtis Cyr 162 to 178

K2 or Spice (synthetic cannabinoids) Anonymous* 179 to 198

Methylphenidate Anonymous* 199 to 210

Cocaine Anonymous* 211 to 229

Oxycontin Anonymous* 230 to 263

*Name removed at student’s request

Each presenter was instructed to include history, pharmacodynamics, pharmacokinetics includingcommon routes of administration, risk of overdose, and epidemiology.

Lysergic Acid Diethylamide

Sarah R. Moore

Hallucinogen10

Powerful mental amplifier that has the ability to enhance reality; makes a person incredibly sensitive to their current environment (physical and mental setting).

http://www.ugo.com/movies/inception-list

History1

• Albert Hoffman (1906-2008)

• Psychedelic (“soul-opening”)

• Synthetic drug made from ergot alkaloids (fungus from rye)

• Synthesized in 1938• Illegal in 1967, categorized

as Schedule I drug.

http://www.acidprogram.com/albert/hofmann.htmlhttp://www.erowid.org/culture/characters/hofmann_albert/

History2

• Carey Grant was a fan of the drug, dropping acid a few hundred times in the 1940s.

• Very popular in 1960s before and after it was illegal.

• CIA used acid as a “mind control drug” for their MKULTRA experiments.

• Paid prostitutes to dose people of interest and record their admissions.

http://badassdigest.com/2012/04/22/when-lsd-was-legal-and-cary-grant-was-tripping/

LSD: My Problem Child3,4

• LSD, not LAD German word for “acid” is “saeure”.

• Originally synthesized as a hemostatic for use after childbirth.

• Also had good qualities in treating migraines.

• 1943, accidental ingestion• 1950s, used the drug as a

research tool• Greatly improved

psychotherapy processes

http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM

Epidemiology5

• In 2009: 779,000 people age 12 and older have used LSD at least once in the last 12 months.

• 1.2% 8th graders, 1.9% 10th graders and 2.6% 12th graders have used LSD in the last 12 months.

• The perceived risk of harm from using LSD is steadily declining.

http://www.drugabuse.gov/drugs-abuse/lsd-acid

SOURCE: University of Michigan, 2008 Monitoring the Future Study

0

20

40

60

80

100

93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08

8th Grade 10th Grade 12th Grade

Percent Perceiving Great Risk of Taking LSD Regularly

Denotes significant difference

between 2007 and 2008.

www.cadca.org/files/Recent_Drug_Trends.pp

www.cadca.org/files/Recent_Drug_Trends.pp

LSD Use Outside of U.S.6

• Canada: Schedule III drug (requires Rx or license)

• Most black-market sale of drug is out of United Kingdom.

• LSD is ILLEGAL to possess without a special license in Belgium, Canada, Greece, the Netherlands, Norway, Russia and the UK.

• Personal possession LEGAL in Mexico (up to 15μg) and Portugal (up to 500μg)

http://www.worldpress.org/map.cfm

Common Dosage Forms9

• Powder• Blotter paper• Liquid• Sugar cubes• Pill• Gelatin

http://www.pactnow.ca/substance-identification.html

http://scienceblogs.com/retrospectacle/2007/10/09/science-vault-60s-flashback-ls/

ACIDBLOTTERCALIFORNIA SUNSHINEDOTSELECTRIC KOOL-AIDLOONIE TOONSHEAVENLY BLUEGOLDEN DRAGON

Street Names for LSD9

Psychological Effects of LSD3

• Dose: 40-150 mcg per blot• Effects are proportional to

dose taken, but duration of trip is the same regardless of dose.

• Dreaming, mystical experiences

• Intense hallucinations • Auditory, visual and tactile

http://www.world-science.net/othernews/070129_hallucinogen.htm

http://www.lsdabusehelp.com

PHYSICAL EFFECTS OF LSD

http://knowingshine.blogspot.com/2010_10_01_archive.html

Pharmacodynamics1,3,12

• *Decreases spontaneous firing, increases excitation and sensory stimulation (NE).

• Hyperresponsiveness to visual, auditory and tactile stimulation.

• 5-HT agonists (2A and 2C), by way of inhibiting 5-HT autoreceptors.

• Serotonin-like indoleamine group, including psylocybin and DMT.

• *Locus coeruleus (norepinephrine)—sends information to sensory cortex.

• Raphe nuclei (serotonin)—shuts down firing of serotenergic neurons. http://depositphotos.com/12099293/stock-illustration-LSD-structural-formula.html

Pharmacodynamics13 • Genesis of hallucinations.• Affects the way the retinas

respond to stimuli and carry that information back to the brain.

• No evidence of interaction with dopamine reward pathway.

• No physical addiction• No withdrawal

http://www.dericbownds.net/bom99/Ch10/Ch10.html

http://www.sciencedirect.com/science/article/pii/S0378434799001899

Pharmacokinetics11

• t1/2= 3 hours

• Effects begin within an hour and last 8-12 hours.

• Peak happens around 3-5 hours.• 80% of drug is taken up in small

intestine and eliminated by liver and bile.

• Only 1-10% is eliminated unchanged.

• The remainder is excreted as metabolites.

• Taking “acid” with other drugs (alcohol, anti-depressants, heroine, cocaine) can cause temporary psychosis.

http://www.sciencedirect.com/science/article/pii/S0378434799001899

Gender Differences7,8

• Concentrations of LSD in urine following oral administration of a 4-μg/kgdose to a female subject ( ) and a male subject (×).▵• A study conducted with rats showed male rats who were administered dosesof LSD were more likely to revisit the area of their cage where the LSD wasadministered than female rats.

: http://www.sciencedirect.com/science/article/pii/S0378434799001899

Psychological Effects of LSD10

• Typical adverse reaction is the sensation of a “bad trip”, or temporary episodes of panic.

• Frightening and traumatic

• Impossible to detect actual dosage (from the street) in blotter paper.

• Heat, air and light will degrade the drug

• Flashbacks or reliving of a “trip”

• Hallucinogen Persisting Perception Disorder (HPPD)

• Trails, halos, shapes, flashes in peripheral vision

• Can last for weeks or years after taking the drug.

http://furthurtothefuture.blogspot.com/2012/04/why-you-shouldnt-do-lsd.html

ToxicologyLysergic Acid Diethylamide11• Halucinogen Persisting Perception

Disorder (HPPD)• Exacerbations of underlying mental illness• Users may attempt to hurt themselves• May make users feel “invincible”

LSD Oral Dosages

Threshold 20 μg

Light 25-75 μg

Common 50-150 μg

Strong 150-400 μg

Heavy 400+ μg

LD50 (Lethal Dose) 12,000 μg

http://www.erowid.org/chemicals/lsd/lsd_dose.shtml

LSD Use in Healthcare6,14,15

• Terminally ill patients• Alcoholism• Narcotic drug addicts• “Model psychosis” for

schizophrenia• Sociopaths• Criminal psychopaths• Psychotherapy adjunct

http://www.lybba.org/blog/mind-over-matter-psychotherapy-for-cancer-care/

Schizophrenia vs. LSD “Trip”16

Schizophrenia• Permanent mental

illness• Unpleasant and

uncomfortable positive symptoms

• Near complete separation from reality and lack of control

• Physical implications• Resistant to suggestion• Disturbed thinking

LSD “Trip”• Temporary hallucinations• Pleasant and euphoric• No separation from

reality• No permanent brain

damage• Highly suggestable• Altered perception• KEY difference: 2AR-

mGluR2 receptor complex

Legal Implications17

• Using LSD will not get you federally prosecuted.

• Making, trafficking and selling LSD is federally punishable.

• Penalties for trafficking depend on the amount in question.

• Possession with intent to sell: 3-15 years in jail, $2,000 - $300,000 fine.

• Possession for personal use: 1-3 years in jail, $1,000 - $20,000 fine.

• More than 2 prior offenses can get you put in jail for life.

http://clovisindependent.com/2011/05/09/clovis-woman-45-held-in-store-robbery/handcuffs/

Abuse10

• LSD presents no physical addiction potential.

• Psychological addiction• Tolerance happens very

quickly, often within 3 days.

• The high dissipates quickly after tolerance without withdrawal, addiction or cravings.

• No associations with dopamine reward pathways.

http://drugs.blurtit.com/q3150977.html

Impacts on Life2,11

• Neglect personal hygiene• User may attempt to hurt

him or herself due to a “bad trip”.

• Some users report that the drug SAVED their marriage (Clare Booth Luce).

• Some report that it was the cause of their divorce (Cary Grant).

• Some users report enhancement of personal relationships.

http://www.marmalade-skies.co.uk/beatles.htm

Questions???

http://thejosevilson.com/wp-content/uploads/2007/10/beatles.jpghttp://www.tumblr.com/tagged/beatles%20art

REFERENCES

1. Hunt, Jenny. "Your Brain on Drugs: LSD." Palm Partners Recovery Center. Palm Partners Drug Rehab Center, 01 Jan 2013. Web. 23 Feb 2013. <http://www.drugs-forum.com/forum/showwiki.php?title=Lsd >.

2. Faraci, Devin. "When LSD Was Legal (And Cary Grant Was Tripping)." Badass Digest. Badass Digest, 22 Apr 2012. Web. 23 Feb 2013. <http://badassdigest.com/2012/04/22/when-lsd-was-legal-and-cary-grant-was-tripping/>.

3. "LSD: A Psychedelic Hyperdimension." Understanding Drugs. GaianXaos, n.d. Web. 23 Feb 2013. <http://www.gaianxaos.com/lsd.htm>.4. Hoffman, Albert. LSD: My Problem Child. New York, NY: McGraw-Hill Book Company, 1980. eBook. <http://www.psychedelic-library.org/child1.htm>.5. "LSD (Acid)." National Institute on Drug Abuse: The Science of Drug Abuse and Addiction. National Institute on Health, n.d. Web. 11 Mar 2013.

<http://www.drugabuse.gov/drugs-abuse/lsd-acid >.6. "LSD Today." The Substance. Ventura Film SA, n.d. Web. 11 Mar 2013. <http://www.thesubstance-themovie.com/about/about_page6/ >.7. Reuschel, S. et al. Recent advances in chromatographic and mass spectrometric methods for determination of LSD and its metabolites in physiological

specimens. The Journal of Chromatography B: Biomedical Sciences and Applications. 1999; 733: 145-159.8. Elis, Lee. Sex Differences: Summarizing More Than a Century of Scientific Research. New York, NY: Psychology Press, 2008. 569. Print.9. "What Is An Hallucinogen?." The Truth About LSD. Foundation for a Drug-Free World, n.d. Web. 11 Mar 2013.

<http://www.drugfreeworld.org/drugfacts/lsd/street-names-for-lsd.html>.10. "LSD Dangers." TheGoodDrugsGuide.com. TheGoodDrugsGuide.com, n.d. Web. 11 Mar 2013. <http://www.thegooddrugsguide.com/lsd/dangers.htm

>.11. "Myth Debunking: LSD Does Not Stay In Your Body Forever." The Vaults of Erowid. Erowid, n.d. Web. 11 Mar 2013.

<http://www.erowid.org/chemicals/lsd/lsd_myth1.shtml >.12. "How Drugs Cause Hallucinations." World Science. World Science, 3 Aug 2010. Web. 11 Mar 2013.

<http://www.world-science.net/othernews/070129_hallucinogen.htm >.13. Hunt, Jenny. "Your Brain on Drugs: LSD." Palm Partners Blog. Palm Partners Recovery Center, 30 Jan 2013. Web. 11 Mar 2013.

<http://blog.palmpartners.com/your-brain-on-drugs-lsd/ >.14. "LSD Breakthrough for mental health patients." The Journal of Thelemic Sciences. The Journal of Thelemic Sciences, 24 Feb 2008. Web. 11 Mar 2013.

<http://thelemicstudies.com/?q=node/16 >.

References15. Szalavitz, Maia. "LSD May Help Treat Alcoholism." Time Magazine: Health and Family. Time Inc., 09 Mar 2012. Web. 11

Mar 2013. http://healthland.time.com/2012/03/09/lsd-may-help-treat-alcoholism/ .16. Aron, Paul. "Hallucinogens and Schizophrenia." . N.p.. Web. 11 Mar 2013.

<http://www.users.totalise.co.uk/~paul.aron/Hallucinogens.pdf >.17. LaMance, Ken. "LSD: Penalties for Sale and Possession." Legal Match. LegalMatch.com, 09 Nov 2011. Web. 13 Mar

2013. <http://www.legalmatch.com/law-library/article/lsd-penalties-for-sale-and-possession.html >.

Peyote (Mescaline)

AnonymousPharmD Candidate

4/9/2013

http://thedukesplayground.wordpress.com/2012/02/16/thepeyotewaychurchofgod/

http://www.mclean.harvard.edu/news/pressreleases/peyote3.php

What is Peyote?1,4,8

• Is a small, green, and spineless cactus found primarily in northern Mexico and southwestern United States called Lophophora williamsii

• Primary active ingredient making peyote a hallucinogen is Mescaline– Many other compounds present

• Hallucinogens produce a feeling of separation from one’s body

– Can last from minutes to hours

Common Names2

• Devil's Root • Dumpling Cactus• Magic Mushrooms• Mescal Buttons• Mescaline• Pellote• Peyotl• Sacred Mushroom

History1,3

• Used for thousands of years by indigenous peoples of North and South America (Mexico and some North American tribes)– Shamans of Huichol in Mexico

• 1638 – Hernandez gave peyote its’ first scientific name Peyotl zacatensis

• 1840 – Lemaire used Echinocactus williamsii• 1894 – Then Coulter namned it Lophophora williamsii

History (cont’d)1

• North American tribes adopted peyote in the late 19th century

• The use in religious ceremonies has evolved with time to be used primarily in the Native American Church

http://theesperanzaproject.org/tag/wirikuta/

Cultivation1,7,8

• The top or “button” of the plant is removed and dried, powdered, or made into a tea

• Usually the dried top is chewed and swallowed where it is absorbed gastrointestinally – Typical dose is 6-12 buttons– Less commonly smoked

• Purpose is to induce religious visions

Different parts of Peyote

How it is Cultivated - 1

How it is Cultivated - 2

Dried Peyote “buttons”

Epidemiology5

• Difficult to determine exact percentages, but is not common

• Generally abuse, if it occurs, happens more frequently in native Americans

• A retrospective chart review of the California Poison Control System (CPCS) electronic database for cases from 1997-2008 was performed– 31 patients in 12 years

• Most young, male patients who took peyote orally• 26 received medical treatment in emergency room• Mild to moderate effects lasting <24 hours

– Concluded that overdose is uncommon, considered mild-moderate, and unlikely to result in death

Epidemiology (cont’d)9

• Investigated illicit (ie. nonceremonial) peyote use in American Indians (AIs) – 89 AI adolescents in a tribally operated residential substance abuse

treatment program (RSATP) from 1998-2001– Most were male, from single parents homes, with low self-esteem– 10 reported illicit use of peyote

• 8 used once or twice in their lifetime

• Concluded peyote use is low in AI adolescents with prior substance abuse problems

Pharmacodynamics1

• Physical (Amphetamine-like effects)– Increased heart rate – Increased blood pressure– Dilated Pupils

• Psychological (LSD-like) – Time and space distortion– “feel outside themselves”

• Other – Nausea– Vomiting– Euphoria

• Larger Doses– Increase sensitivity to sensory images– Flashes color– Geometric patterns

Pharmacokinetics4,7

• Rapidly absorbed from the G.I. tract

• Onset: 30 minutes – 2 hours

• Peak Serum Concentrations: 2 – 4 hours

• Peak Effect: 4 – 6 hours

• Symptoms Last: ~6 - 12 hours

• Not bound to albumin

• Large volume of distribution

• Hepatic metabolism with 60% excreted unchanged in the urine

Mechanism of Action & Drug Interactions4,7

• Mechanism– Generally not known– Amphetamine-like– Peyote is a exogenous phenylethylamines

• Ex. Endogenous phenylalkaloids are norepinephrine and dopamine

• Drug Interactions (Stimulants)– Nicotine – Cocaine – Sympathomimetic amines,– Amphetamines

Toxicology1, 4, 10

• Peyote (mescaline) has no reported cases of death due to overdose

• Dose– 3 - 5 mg/kg (All effects can lead to self-inflicted or accidental injury)

• Psychic effects and visual hallucinations• Anxiety• Paranoia• Fear• Emotional Instability

– >20 mg/kg• Hypertension• Bradycardia• Respiratory Depression• Death

• Treatment– Symptomatic– Benzodiazepines or antipyschotics

(Ex. droperidol)

Law1

• Peyote is considered a schedule 1 substance in the United States under the Controlled Substances Act and therefore is illegal to possess or use

• However, it has been legalized to use in native American rituals under an exemption in the law (to protect religious use for Native American Church members)

• Canada – Peyote is classified as a schedule 3 substance

Law (cont’d)• TITLE 21 - FOOD AND DRUGS • CHAPTER II—DRUG ENFORCEMENT ADMINISTRATION• DEPARTMENT OF JUSTICE• PART 1307: MISCELLANEOUS• Special Exempt Persons• Sec. 1307.31 Native American Church.

• The listing of peyote as a controlled substance in Schedule I does not apply to the nondrug use of peyote in bona fide religious ceremonies of the Native American Church, and members of the Native American Church so using peyote are exempt from registration. Any person who manufactures peyote for or distributes peyote to the Native American Church, however, is required to obtain registration annually and to comply with all other requirements of law.

Long Term Effects4,6

• Not completely known

• Tolerance to peyote – Cross tolerance to LSD and psilocybin

• Study with 3 groups of Navajo Native Americans – Members of Native American Church with regular consumption– People with past alcohol abuse (sober <2 months)– Minimal use of peyote

• We administered the Rand Mental Health Inventory (RMHI), and ten standard neuropsychological tests of memory and attentional/executive functions.

• Concluded no long term effects on either peyote groups but there were for alcoholic patients

Mescaline-Like Drugs1

• Other plants– San Pedro Cactus– Peruvian Torch Cactus

• Artificially Produced– DOM– MDA– DMA– MDMA

• Spices– Nutmeg (myristicin and elemicin) http://www.herbalfire.com/peruvian-torch-cactus-trichocereus-peruvianus.html

References• 1. Kuhn C, Swartzwelder S, Wilson W. Buzzed. 3rd edition. 90-105.• 2. “Peyote”. Natural Medicines Comprehensive Database. Accessed from AccessPharmacy April 8, 2013• 3. Kapadia G and Fayez M. Peyote Constitutents: Chemistry, Biogenesis, and Biological Effects. Journal of Pharmaceutical

Sciences. December 1970;59(12):1699-1727. Accessed April 8, 2013.• 4. Plants-Peyote/Mescaline. Micromedex. Accessed April 8, 2013.• 5. Carstairs S, Cantrell F. Peyote and mescaline exposures: a 12-year review of a statewide poison center database. Clinical

Toxicology (15563650) [serial online]. April 2010;48(4):350-353. Available from: Academic Search Complete, Ipswich, MA. Accessed April 9, 2013.

• 6. Halpern J, Sherwood A, Hudson J, et al. Psychological and Cognitive Effects of Long-Term Peyote Use Among Native Americans. Biological Psychiatry. 15 October 2005;58(8):624-631. Accessed April 8, 2013

• 7. Delgado J, Traub S, & Grayzel J. Intoxication from LSD and other common hallucinogens. Up to Date. Reviewed June 15, 2011. Accessed April 8, 2013.

• 8. Babu KM. Chapter 82. Hallucinogens. In: Babu KM, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6522465. Accessed April 9, 2013.

• 9. Fickenscher A, Novins D, & Manson S. Illicit peyote use among American Indian adolescents in substance abuse treatment: a preliminary investigation. Subst Use Misuse. 2006;41(8):1139-54. Accessed April 8,2013.

• 10. Kelsey F. The Pharmacology of Peyote. Department of physiology and pharmacology state university of south dakota. June 1959. Accessed April 8, 2013

Amanita Mushroom- Priyank Mandalia

http://wallpaperswide.com/alice_in_wonderland_movie-wallpapers.html

Amanita muscaria1,2

http://www.geog.ucsb.edu/img/news/2011/1024px-Amanita_muscaria_3_vliegenzwammen_op_rij.jpg

• Amanitai: Mount Amanus in northern Syria

• Musca: Latin word for fly

• It is commonly referred to as fly agaric

• Medieval belief that it repelled flies,

• Alternative hypothesis proposesthat the term “fly” refers not to insects,but the delirium resulting fromconsumption of the fungus.

History3

• 1200 BCE: Multiple indications in religious literature wide-spread Asia • 1291: Fresco in France depicts Adam and Eve standing beside a Tree of

knowledge• 1960 – 65: Appears in United states urban subcultures• 1968: R. Gordon Wasson proposed the fly agaric was in fact the Soma

talked about in the ancient Rig Veda texts of India• 1980s: Several books and scientific journal articles appear describing

modern and traditional use as an inebriant across the globe

History (Cont.)3

• Jul 20-23, 2000: Consciousness Technologies• Aug 23-26, 2001: Telluride Mushroom Festival;

encourage individuals in expanding their knowledge regarding diverse species and their cultivation

• 2002: Clark Heinrich argues a key role of A. Muscaria in many world religions including Hindusin, Judaism and Christianity

• Dec 5-6, 2009: Mycological Society of San Francisco Annual Fungus Fair

Description4,5

• Wide variety among the species; • Var. muscaria: the typical red-and-white spotted variety;

Siberian origin, which spreaded outward across Asia, Europe and North America

• Var. flavivolvata: red w/ yellow to yellowish-white warts found from southern Alaska down through Rocky Mountains

• The cap is covered with numerous small white to yellow pyramid-shaped warts; As the fungus grows, the red colour appears through the broken veil and the warts become less prominent

• Fully grown cap is usually around 8–20 cm (3–8 in) in diameter

http://www.flickr.com/photos/blackdiamondimages/2117813326/in/set-72157601716027470

Fun Facts6,7

• Death's head • Fly agaric • The woodpecker of Mars• Price: Dried A. muscaria averages around ~$52 per ounce

on ethnobotanical vendor web sites. Psychoactive amanitas are rarely found in underground markets.

• Law: Amanita mushrooms and their active ingredients are uncontrolled in the United States and in most countries. If sold for consumption as a food or drug, sales are regulated by the FDA in the US.

http://tinyurl.com/ccosc3k

Fun Facts8

Administration Methods: • Simmering a few mature dried caps in water

for a half hour and then drinking the tea slowly over a period of a couple of hours

• Tear off little pieces of dried cap and roll them into little pills; swallow these without chewing, with as little water as possible

• Some claims that it can be smoked as well

Amanita Muscaria Dosage and PK9

• Light: 1 - 5 g (1 medium cap) • Common: 5 - 10 g (1 - 3 medium caps) • Strong: 10 - 30 g (2 - 6 medium caps)• Onset : 30 - 120 minutes

Peak : 1 - 2 hoursDuration : 5 - 10 hours (higher doses seem to last longer)

Pharmacokinetics10

• Absorption: A. muscaria from the gastro-intestinal tract seems to be rapid. However, the exact rate and the proportion of absorption is still unknown.

• Distribution: Muscimol and ibotenic acid, cross the BBB. Neither muscimol nor ibotenic acid is removed from the receptor by the GABA or glutamate active uptake system.

• Half-life: Ibotenic acid and muscimol detected in urine within one hour after the ingestion. Peak excretion of ibotenic acid occurs two hours after ingestion.

Pharmacodynamics10,11

• The primary active chemicals known in Amanita muscaria : Muscimol, Ibotenic Acid, Muscazone, and Muscarine.

• Muscimol: Primary action is at GABA receptor sites as a potent GABA-A agonist; active in several parts of the brain including the cerebral cortex, hippocampus, and cerebellum.– Psychoactive dose of muscimol is around 10-15 mg; LD50 in mice

and rats respectively 3.8 mg/kg SC and 45 mg/kg orally• Ibotenic Acid: The current view is that some Ibotenic Acid

does cross the blood brain barrier unchanged. Ibotenic acid is structurally similar to the stimulatory neurotransmitter glutamic acid.

Pharmacodynamics10,11

• Muscarine: Affect acetylcholine levels and acts at muscarinic receptors. – While the levels of muscarine in A. muscaria are quite low

(.002% - .003% by dry weight), some of the effects of A. muscaria are characteristic of cholinergic involvement.

• Muscazone: The existence of ibotenic acid isomer muscazone in some A. muscaria may clue to the biosynthesis of ibotenic acid. Possible breakdown product of Ibotenic Acid and Ott describes it as a possible "artifact of isolation procedures" which is "of dubious psychoactivity".

Acute Poisoning12

• Drowsiness• Confusion • Dizziness • Ataxia• Euphoria• Hangover (same day)• Delirium

• Visual and auditory disturbances with hallucinations

• Muscle cramps and spasms

• Gastrointestinal disturbancesand convulsions may alsobe seen

• Increased salivation and Prespiration

• Death (rare)

Clinical Effects12,13

• Cardiovascular: Pulse and B.P. are usually normal. One case of patient developing cardiac fibrillation

• Respiratory: Over-dose can cause respiratory depression• CNS: Depression and stimulation might alternate.

Symptoms begin with drowsiness followed by confusion, with dizziness, euphoria resembling alcohol intoxication and proceeds to illusions or manic excitement– Periods of excitement may alternate with periods of

somnolence– Illusions are misinterpretation of sensory stimuli such as

changes in color vision

Clinical Effects12,13

• Musculoskeletal: Muscle twitching, fasciculation and spasms

• Gastrointestinal: Dyspepsia and vomiting• Metabolic: Light or milddehydration may be observed• Meiosis as well as mydriasis

http://www.funnyjunk.com/funny_pictures/3132057/MARIO+S+MUSHROOMS/

Toxicity Management14

• Treatment of signs and symptoms of intoxication• Supportive care• Administration of activated charcoal, most effective

within an hour of ingestion• No specific antidote

Questions?

http://www.funnyjunk.com/channel/toonhole/Mushrooms/NfgnGAs/

References

• Arora, D. (1986). Mushrooms demystified: A comprehensive guide to the fleshy fungi. Berkeley: Ten Speed Press. 959 pp

• "Psychedelic Mushrooms." UC Santa Barbara Geography / News & Events / Department News. N.p., n.d. Web. 18 Apr. 2013. <http://www.geog.ucsb.edu/events/department-news/968/is-santa-the-personification-of-a-psychedelic-mushroom/>.

• "Psychoactive Amanitas Timeline." Erowid Psychoactive Amanitas (A. Muscaria & A. Pantherina) Vault : Timeline. N.p., n.d. Web. 18 Apr. 2013. <http://www.erowid.org/plants/amanitas/amanitas_timeline.php>.

• Tulloss, R. E. (2012). "Amanita muscaria (L.: Fr.) Lam. var. muscaria". Studies in the Genus Amanita Pers. (Agaricales, Fungi) – Tulloss RE, Yang Z-L.

• Arora, D. (1986). Mushrooms demystified: a comprehensive guide to the fleshy fungi (2nd ed.). Berkeley: Ten Speed Press. pp. 282–83. ISBN 0-89815-169-4.

• "AMANITA MUSCARIA." AMANITA MUSCARIA | Recreational Drugs. N.p., n.d. Web. 18 Apr. 2013. <http://www.drugtext.org/Recreational-Drugs/amanita-muscaria.html>.

• "Psychoactive Amanitas." Erowid Psychoactive Amanitas (A. Muscaria & A. Pantherina) Vault: Basics. N.p., n.d. Web. 18 Apr. 2013. <http://www.erowid.org/plants/amanitas/amanitas_basics.shtml>.

References(Cont.)

• "Preperation." Erowid Psychoactive Amanitas (A. Muscaria & A. Pantherina) Vault : Amanita Muscaria Preparation for Beginners. N.p., n.d. Web. 18 Apr. 2013. <http://www.erowid.org/plants/amanitas/amanitas_info8.shtml>.

• "Dosage." Erowid Psychoactive Amanitas Vault : Dosage. N.p., n.d. Web. 18 Apr. 2013. <http://www.erowid.org/plants/amanitas/amanitas_dose.shtml>.

• "Amanita Muscaria, Amanita Pantherina and Others." AMANITA MUSCARIA | Recreational Drugs. N.p., n.d. Web. 18 Apr. 2013. <http://www.inchem.org/documents/pims/fungi/pimg026.htm>.

• Chilton WS (1978). Chemistry and mode of action of mushroom toxins. In: Rumack, B.H. & Salzman, E, Eds. Mushroom poisoning: Diagnosis and Treatment. West Palm Beach (Florida), CRC Press Inc. 87:124.

• Lampe KF (1978). Pharmacology and therapy of mushroom intoxications, In: Rumack BH, & Salzman. E, Eds. Mushroom poisoning: Diagnosis and treatment. West Palm Beach (Florida), CRC Press Inc, 125-169.

• Page LB (1984). Mushroom toxins and the nervous system: some facts and speculations. McIlvainea, 6, 39-43.

• Mitchel DH & Rumack BH (1978). Symptomatic diagnosis and treatment of mushroom poisoning. In: Rumack, BH & Salzman E, Eds. Mushroom poisoning: Diagnosis and Treatment. West Palm Beach (Florida), CRC Press Inc, 171-179.

Salvia Divinorum

Anonymous

History1

• First noted by Jean Johnson in 1938, he heard of use by the Mazatec Indians (Mexico).

• Mazatecs made tea with the leaves or chewed the leaves to “predict the future”

• Gordon Wasson found salvia while researching hallucinogenic mushrooms. He was not allowed to bring the plant back to the U.S.

• The first plant wasn’t acquired until 1962 by Gordon Wasson and Albert Hofman. They described salvia as a less desirable substitute for mushrooms.

• The plant can grow up to 1.5 meters tall

Street names2

• Maria Pastora• Sage of the Seers• Diviner’s Sage• Sally-D• Magic Mint • The use of street names is not common

because of it being legal in many states, and it is easily purchased online.

Methods of administration1

• The active ingredient is salvinorin A, many methods can be used to get this substance into the body.

• Smoking (pipe, bong, joint)- extreme effects last a maximum of 15 minutes (most common)

• Chewed (quid)- effects last 1-2 hours• Vaporized• Consumed in a tea (traditional)

Genius mind of the abusers3

• Using the leaves directly off of the plant would be considered a 1X strength. People have made ways to extract the salvinorin A to increase the concentrations.

• 5X- 100X• 100X means that 1 gram of salvia has the

amount of salvinorin A as 100 grams.

Recipe4

• 1) crush 90g of leaves• 2) add rubbing alcohol (solvent)• 3) let sit for 16 hours• 4) evaporate solvent• 5) add solvent, let stand for 5 minutes, remove

top 2/3 of mixture and discard (x5)• 6) combine extract with 10g of leaves• 7) you just made 10X salvia

The Salvia Scale3

• Level-1: Subtle effects• Level-2: Altered Perception• Level-3: Light visionary state• Level-4: Vivid visionary state• Level-5: Immaterial existence• Level-6: Amnesiac effects

http://www.youtube.com/watch?v=UTUY-KE4NR8 23-seconds

Epidemiology5,6

• 2.8% of a group study reported using salvia at least once in their life.

• 6.1% of people between the ages of 18 and 25 reported usage.

• Almost 20% admitted doing “risky” behavior such as selling illegal items, stealing, carrying firearms, fighting with intent to seriously injure.

• At risk- white, male, heavy drinkers, frat guys. • 83% increase between 2006 and 2008.

Usage6

Before 2008

2009 2010 2011

8th ---- ---- 1.7 1.6

10th --- --- 3.7 3.9

12th --- 5.7 5.5 5.9

Monitoring the future:

Schedule 1?7

• Addiction?- none• Withdrawal?- none• Tolerance?- none• Salvia is currently under state control, many

states have made it a schedule 1, while others have made it legal to those over 18.

As of August 2011

Pharmacodynamics8

• MOA: Selective to the kappa opioid receptor.• No 5-HT2a activity.• Study done in mice shows lower DA levels in

the nucleus accumbens.• Originally thought there could be anti-

depressant properties.• Mice showed depressive characteristics while

on salvia.

Pharmacokinetics8

• Salvinorin A is degraded in the GI, if contact with mucosa membranes doesn’t occur, the effects will not be seen.

• Metabolized into Salvinorin B• Excreted renally • T1/2- 56.6 minutes • A study in rats showed peak effects occurring at

5-15 minutes, and the effects wore off by the 2 hour mark.

Baboon brain

Toxicity2

• Little information as this drug is relatively new in terms of recreational use.

• Zero deaths from over dose have been recorded.

• AAPCC has received 35 calls due to adverse effects.

• LD50- 340mg/kg• Naloxone may be an antidote; however it is not

FDA approved

Experiences • “I was looking at my trip-sitter, and he had turned into an alien-like form.

He looked a lot like himself, only gray, and no nose, or ears, or hair. All I could manage to say was, wtf man.. wtf man.. over and over and over again, apparently throughout the entire trip. Seconds after that realization, I (apparently) had gotten stuck in the curtain I was sitting against it. In my mind, I had become the wall”

• “I felt like I was being ripped in half by a thousand little men”

• “I tried to stand up, but instead just fell over a bed. At that point, I became the floor, and started thinking about how lame life is to be a floor.”

• Most people said it was something they would not do again.

Recommendations for use

• Sitter

• Safe place

Questions?

References• 1) "Salvia Divinorum | CESAR." Salvia Divinorum | CESAR. University

of Maryland, 2006. Web. 4 Apr. 2013.http://www.cesar.umd.edu/cesar/drugs/salvia.asp

• 2) "SALVIA DIVINORUM AND SALVINORIN A." Drug Enforcement Administration. N.p., July 2012. Web.http://www.deadiversion.usdoj.gov/drug_chem_info/salvia_d.pdf

• 3) "The Salvia Dream." The-salvia-dream. Salvia Dreaming Creations, 2007. Web. http://www.the-salvia-dream.com/salvialeaves.html

• 4) "How To Make Salvia Divinorum Extract." Synchronium. N.p., 2008. Web. 04 Apr. 2013. http://www.synchronium.net/2008/12/22/how-to-make-salvia-divinorum-extract/

References cont.

• 5) Perron BE, Ahmedani BK, Vaughn MG, Glass JE, Abdon A, Wu LT. Use of Salvia divinorum in a nationally representative sample. Am J Drug Alcohol Abuse. 2012;38(1):108-13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408869/+

• 6) Muscari, Mary E. "What Are the Effects of Salvia Use in Adolescents?" Medscape. N.p., 4 Apr. 2011. Web. 08 Apr. 2013.http://www.medscape.com/viewarticle/739840_2

• 7) "Monitoring the Future." National Institute on Drug Abuse, 2011. Web. 8 Apr. 2013.http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2011.pdf

• 8) Erowid. "Erowid Salvia Divinorum Vault: Basics." Erowid Salvia Divinorum Vault: Basics. N.p., 2000. Web. 08 Apr. 2013. http://www.erowid.org/plants/salvia/salvia_basics.shtml

Picture references

• En.wikipedia.org• www.the-salvia-dream.com• commons.wikimedia.org• http://www.healthlytrends.com/naturaltrends/

salvia-effects-divinorum/• commons.wikimedia.org• http://www.bnl.gov/newsroom/news.php?a=1779• www.sodahead.com

Ketamine

AnonymousDrug Abuse

April 23, 2013

History¹

• 1962: First developed in the United States

• 1966: Patented by Parke-Davis

• 1967: Dispensed by underground chemists from Michigan

• 1970: During the Vietman war, ketamine was used as an anesthetic & FDA approved the use in children and the elderly

• 1978: FDA reported abuse of ketamine

History (cont’d)¹

• 1980s & 1990s: Recreational use of ketamine became the popular way

• 1997: NY passed a law prohibiting sale/possession of ketamine

• 1999: DEA named ketamine a schedule III drug & became illegal to possess for recreational and nonmedical purposes

Slang terms³

• Bump• Cat killer• Cat valium• Green• Jet• Honey oil• Kit Kat• Purple• Special K• Special la Coke

Images retrieved from: http://drug-effects.us/what-is-ketamine, http://news24now.com/ketamine-crazy300000-risk-death-by-taking-horse-sedative/1328

Epidemiology of Recreational Use⁴

• First reported abuse was of medical professionals

• Associated with the “post-rave” clubbing and youth dance culture– “club drug” alongside ecstasy, cocaine, or GHB

• Most common in East and South-East Asia– Possibly due to low price

Epidemiology (cont’d)⁴

• Four main groups commonly abusing ketamine– Regular drug users – Gay club/party scene– Heroin users– Self-exploratory people

Data retrieved from: http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2011.pdf

Chemical Structure²

• 2-(o-chlorophenyl)-2-(methylamino) cyclohexanone (hydrochloride)

• Molecular Weight: 238 g/mol

• Racemic mixture

• Prepared in many concentrations– 10 mg/mL

– 50 mg/mL

– 100 mg/mL

• Benzethonium chloride as

the preservative

Images retrieved from: http://greggordon.org/edu/ivanes/ketamine3.htm & http://www.sunshinecoasthealthcentre.ca/hallucinogens.html

Pharmacodynamics⁵

• Rapid acting general anesthetic, hallucinogen, psychotomimetic

• Not well understood– Block NMDA receptors?

– Interact with opiate receptors?

– Sympathomimetic effects?

– Dopamine uptake inhibitor?

• Known that ketamine does NOT interact with GABA receptors, unlike many anesthetics

Pharmacodynamics (cont’d)⁶

• NMDA antagonist – Associated with analgesic effects– 10 to 50 times less potent in blocking NMDA receptors

compared to PCP• Opiate receptors

– Analgesia and dysphoric effects• Sympathomimetic effects

– Enhanced central and peripheral monoaminergic transmission• Dopamine uptake inhibitor

– Elevates DA levels

Pharmacokinetics²⁷

• Elimination half life: 2 to 3 hours• Bioavailability

– Intramuscular – 93%– Intranasal – 25 to 50%– Oral – 20 ± 7%– Clearance: 12 to 17 ml/kg/min

• Metabolized to norketamine by:– Hydroxylation– Conjugation– Dehydration– Demethylation

Image retrieved from: http://www.anesthesia2000.com/General/Pharmacokinetics/kinobj4.htm

Pharmacokinetics (cont’d)⁶ ⁸

• Metabolized to norketamine by CYP3A4 with minor contributes from CYP2B6 and CYP2C9 isoforms– N-demethylation

• Inhibitors of these CYP450 isoenzymes could decrease the rate at which ketamine is eliminated

Pharmacokinetics (Cont’d)²

• The therapeutic range for ketamine is 0.7 to 2.2 mcg/mL with awakening occurring below 0.5 mcg/mL

• Usually dosed on a 2.0 mg/kg basis Image retrieved from: http://greggordon.org/edu/ivanes/ketamine4.htm

Clinical Use⁶

• Anesthetizing patients who are at risk for hypotension, bronchospasm and in pediatric procedures

• Produces a hypnotic state unlike other anesthetics– Profound analgesia– Unresponsiveness to commands– Amnesia

• Given to patients with tolerance to opioids• Primarily used in veterinary procedures

Recreational Use⁹¹⁰

• As a psychedelic agent

• Can be injected, snorted, orally ingested, or rectally administered– Heated to remove the water and form a white powder

• Can be added to tobacco or marijuana cigarettes and smoked for entry– Similar to PCP

Image retrieved from: http://frontpsych.com/2011/12/01/the-ten-best-psychedelic-albums-of-2011/

Recreational Use (cont’d)⁹

• Recreational dosing– Intramuscular – 25 to 50 mg– Snorting – 30 to 75 mg– Oral – 75 to 300 mg

• Effects– Dreamy effect– “K-hole”– Drowsiness– Perceptual distortions

Psychological Effect¹¹¹²

• Decreased awareness of environment in which they are in

• Sedation• “Dream-like” state• Vivid dreams• Increased distractibility• Disorientation• Uncommunicative• Hallucination, impaired thoughts, out-of-body

experiences, delirium

Duration of “high”⁴

• Effects are seen:– within seconds when smoked– 1 to 5 minutes when injected– 5 to 10 minutes when snorted

• Effects last:– 30 to 45 minutes when injected– 45 to 60 minutes when snorted– 1 to 2 hours when ingested/smoked

Toxicology⁵¹³

• Wide margin of safety– Several times been administered 10-times the

appropriate dose with complete recovery

• Respiratory depression may occur with OD or too rapid rate of administration– May require use of ventilator

• Withdrawal symptoms may be seen with chronic use of ketamine

Toxicology (cont’d)¹⁰

• “Daily intravenous injections in rats of five times the average human intravenous dose and intramuscular injections in dogs at four times the average human intramuscular dose demonstrated excellent tolerance for as long as 6 weeks”.

• “Twice weekly anesthetic sessions of one, three, or six hours’ duration in monkeys over a four- to six-week period were well tolerated”.

References1. Lankenau SE, Clatts MC. Ketamine Injection among High Risk Youth: Preliminary Findings

from New York City. J Drug Issues. 2002;32(3):893-905.2. Gordon, G. MD. Ketamine from http://greggordon.org/edu/ivanes/ketamine2.htm.

February 12, 2012.3. Center for Substance Abuse Research. Ketamine. University of Maryland. Updated on May

2, 2005. http://www.cesar.umd.edu/cesar/drugs/ketamine.asp4. Kalsi, S., Wood, D., & Dargan, P. (2011). The epidemiology and patterns of acute and

chronic toxicity associated with recreational ketamine use.Emerging Health Threats Journal, 4. doi:10.3402/ehtj.v4i0.7107

5. Drug Bank. Ketamine. Updated on February 8, 2013. http://www.drugbank.ca/drugs/DB01221#transporters

6. Patel PM, Patel HH, Roth DM. Chapter 19. General Anesthetics and Therapeutic Gases. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=16664636. Accessed April 20, 2013.

7. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically.

References (cont’d)8. Adams VHA. The mechanisms of action of ketamine. Anaesthes Reanim 1998;23(3):60-

3.9. National Highway Traffic Safety Administration. Drugs and Human Performance Fact

Sheets. Ketamine. http://www.nhtsa.gov/people/injury/research/job185drugs/ketamine.htm

10. DailyMed. Ketamine Hydrochloride. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bb912318-2e22-4469-b0a2-774803ee1bb8#nlm34088-5

11. Grant IS, Nimmo WS, Clements JA. (1981) Pharmacokinetics and analgesic effects of i.m. and oral ketamine. Br J Anaesthes 1981;53(8):805-10.

12. Curran HV, Morgan CA. Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later. Addiction 2000;95(4):575-90.

13. Trevor A.J., Katzung B.G., Kruidering-Hall M.M., Masters S.B. (2013). Chapter 25. General Anesthetics. In A.J. Trevor, B.G. Katzung, M.M. Kruidering-Hall, S.B. Masters (Eds), Katzung & Trevor's Pharmacology: Examination & Board Review, 10e. Retrieved April 21, 2013 from http://www.accesspharmacy.com/content.aspx?aID=56981944.

Bath Salts

Lindsay A. PelletierDrug Abuse & Society

Spring 2013

Photo From: http://upload.wikimedia.org/wikipedia/en/c/cb/Bath_salts_(drug).jpg

Overview1

• Not the bath salts you use in your tub!

• Designer drug that contains substituted cathinones

• Methylenedioxypyrovalerone (MDPV), mephedrone & methylone most commonly used

• Classified as Schedule I substance in October 2011

• Cathinone: found naturally in the plant Catha edulis (khat)– Beta-keto analog of amphetamine

• 1st synthetic cathinones synthesized in late 1920s

• Limited therapeutic use due to serious side effects

• Emerged as popular designer drugs of abuse in 2000s

History2

Photo From: http://www.botanypictures.com/plantimages/catha%20edulis%2004%20NL%20uithof%20greenhouse.jpg

• Ocean Snow• Lunar Wave• Vanilla Sky• White Lightning• Scarface • Hurricane Charlie• Bliss• Energy-1• Stardust• Insect Repellent

• Ivory Wave• Purple Wave• Red Dove• Blue Silk• Zoom• Bloom• Cloud Nine• Drone• Meow Meow• Plant Fertilizer

Common Names3,4

• Most popular between ages of 20 and 295

– Reports between ages <6 to 59 years of age• Mephedrone drug of choice in Europe2

• MDPV drug of choice in United States2

• 20115

– 6,138 bath salt calls reported to AAPCC• Jan to July 20116

– 87 bath salt calls from Maine to Northern New England Poison Center

• 20125

– 2,654 bath salt calls reported to AAPCC

Epidemiology

Sept 2012 Oct 2012 Nov 2012 Dec 2012 Jan 2013 Feb 20130

20

40

60

80

100

120

140

AAPCC Reported Bath Salt Exposures

Number of Exposures

Pelletier. Adapted from: http://www.aapcc.org/alerts/bath-salts/.

Chart From: http://bangordailynews.com/2013/03/01/news/bangor/interactive-bath-salt-overdoses-in-maine-2010-2012/?ref=search

• White or brown crystalline powder• Sold in small foil or plastic packets• “Not for human consumption”

Appearance1

Photo From: http://www.cnn.com/video/crime/2011/02/16/feyerick.bath.salt.drugs.cnn.640x360.jpg

Photo From: http://blogs.riverfronttimes.com/dailyrft/bath-salts-drug.jpg

• Most Common Routes– Insufflation (snorting)– Ingestion

• Other Routes– Inhalation– Sublingual– Rectal Administration– Intravenous– Intramuscular

Routes of Administration2

Photo From: http://www.tokeofthetown.com/2012/06/07/BathSaltsDetail.jpg

• Cocaine• Amphetamines• Methamphetamines• Caffeine• Hallucinogenes• Kratom• Other synthetic

cathinones• Alcohol

Drugs Used with Bath Salts2

Beta Blockers Zopiclone Pregabalin Famotidine Omeprazole Domperidone Opiates Cannabis Benzodiazepines

• Like other stimulants, bath salts Inhibit monoamine uptake transporters leading to increased concentrations of catecholamines (DA, 5HT, NE) in synapses

• Less able to cross blood-brain barrier compared to amphetamines due to beta-keto group which increases polarity

Mechanism of Action2

Figures From: http://www.nature.com/npp/journal/v38/n4/fig_tab/npp2012204f1.html

MDPV Effects on Catecholamines7

Figure From: http://www.nature.com/npp/journal/v38/n4/fig_tab/npp2012204f2.html

• MDPV found to be 10 times more potent than cocaine in producing:– Locomotor activation– Tachycardia – Hypertension

• MDPV shown to be a monoamine transporter blocker• Increased potency and selectivity for catecholamines

compared with cocaine• Robust stimulation of dopamine transmission helps

explain adverse effects seen in humans and demonstrates serious potential for abuse

MDPV Study7

• Increased sociability• Increased energy• Increased libido• Increased work capacity• Limited euphoria• Limited empathy• No pain threshold• Superhuman strength

Reported Desired Effects2

Adverse Effects2

◦Prolonged Panic Attack◦Tremor◦Agitation◦ Insomnia◦Nausea◦Headache ◦Tinnitus◦Vertigo◦Muscle Twitching

◦Dizziness◦Elevated Heart Rate◦Altered Vision◦Confusion◦Short-term Memory

Loss◦Anhedonia◦Depression◦Suicidal Thoughts◦Psychosis

• Typical dose of MDPV ranges from 5 to 30 mg • Tolerance reported with doses >200 mg in a single session• Withdrawal syndrome has been reported after abrupt

cessation following long-term use– Depression– Anergia– Anhedonia– Anxiety– Sleep Disorders– Fatigue– Cravings

Tolerance and Dependence2

• No treatment available to reverse effects of bath salts

• Main goal: protect patient from harm and from doing harm to others

• Local hospitals using midazolam – Provides sedation and relieves anxiety

• Ketamine also used in extreme cases• Patients with excited delirium placed into

medically induced sleep

Treatment8

• Limited data on number of deaths resulting from bath salts due to concurrent drug use2

• Mephedrone Related Deaths2

– Blood concentration = 0.13 to 22 mg/L

• MDPV Related Death9

– Urine concentration = 670 ng/mL– Blood concentration = 82 ng/mL

Fatalities

Legislation1

• October 2011: U.S. Drug Enforcement Administration places emergency ban on

MDPV, medphedrone & methylone

• July 2012: Legislation signed making mephedrone and MDPV permanently illegal

• After United Kingdom banned mephedrone in 2010, naphyrone quickly replaced it

Photo From: http://tothemaximusblog.org/wp-content/uploads/2012/07/url.jpeg

• Bangor man arrested after running around and yelling at people on Center Street in Bangor

• Claimed to be on bath salts and wanted to get off them

• Charges: disorderly conduct, criminal mischief & resisting arrest

• Stops breathing while in jail• Resuscitated and brought to hospital• Ultimately dies at hospital

Local Stories – 1st Death10

• 19 year-old male brought to Pen Bay Medical Center to “get clean”

• Causes $30,000 worth of damage to special care unit after becoming agitated

• Pen Bay increases police presence as a result

• Protocol change: extreme cases sent to EMMC

Local Stories – Pen Bay Incident11

• “Jesse” – 10 year opiate user looking for new way to get “high”

• Found bath salts “everywhere” in Bangor• Injected bath salts and spent 3 hours searching for four

leaf clovers• Didn’t sleep for 12 days straight• Went from 140 pounds to 105 pounds• Arrested for drug paraphernalia• Considers bath salts to be most destructive drug he’s

ever done

Local Stories – Former User12

• Four people arrested in January 2013 after largest bath salt bust in Maine

• 24 ½ pounds of bath salts seized

• Estimated street value of $1.7 million

• Mailed to Maine from China

Local Stories – Hermon Bust13

1. Drug Facts: Synthetic Cathinones (“Bath Salts”). National Institute on Drug Abuse Web site. http://www.drugabuse.gov/publications/drugfacts/synthetic-cathinones-bath-salts. Accessed March 13, 2013.

2. Coppola M, Mondola R. Synthetic Cathinones: Chemistry, pharmacology and toxicology of a new class of designer drugs of abuse marketed as “bath salts” or “plant food”. Toxicology Letters. 2012;211(2):144-149.

3. Messages From the Director. National Institute on Drug Abuse Web site. http://www.drugabuse.gov/about-nida/directors-page/messages-director/2011/02/bath-salts-emerging-dangerous-products. Accessed March 13, 2013.

4. Bath Salts. The Partnership at DrugFree.Org Web site. http://www.drugfree.org/drug-guide/bath-salts. Accessed March 13, 2013.

5. Bath Salts. American Association of Poison Control Centers Web site. http://www.aapcc.org/alerts/bath-salts/. Accessed March 13, 2013.

6. Bath salts and K2 in Maine. Alcoholism & Drug Abuse Weekly [serial online]. August 29, 2011;23(33):7-8. Available from: Academic Search Complete, Ipswich, MA. Accessed March 13, 2013.

7. Baumann M, Partilla J, Schindler C, et al. Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive 'Bath Salts' Products. Neuropsychopharmacology. March 2013;38(4):552-562.

References

8. EMMC developed bath salts protocol by trial and error. Bangor Daily News Web site. http://bangordailynews.com/2012/01/06/health/emmc-developed-bath-salts-protocol-by-trial-and-error/. Accessed March 13, 2013.

9. Murray B, Murphy C, Beuhler M. Death Following Recreational Use of Designer Drug 'Bath Salts' Containing 3,4-Methylenedioxypyrovalerone (MDPV). Journal Of Medical Toxicology [serial online]. March 2012;8(1):69-75. Available from: Academic Search Complete, Ipswich, MA. Accessed March 13, 2013.

10. Bangor bath salts user first confirmed death in Maine, medical examiner’s office says. Bangor Daily News Web site. http://bangordailynews.com/2012/01/11/news/bangor/bangor-bath-salts-user-first-confirmed-death-in-maine-from-the-drug-medical-examiners-office-says/?ref=search. Accessed March 13, 2013.

11. Pen Bay hospital increases police presence to deal with violent patients. Bangor Daily News Web site. http://bangordailynews.com/2011/11/04/news/midcoast/rockport-police-increase-watch-at-pen-bay-due-to-bath-salts/?ref=relatedBox. Accessed March 13, 2013.

12. Bath Salts: A Former User’s Story. WABI TV 5 Web site. (http://www.wabi.tv/news/25141/bath-salts-a-former-users-story). Accessed March 13, 2013.

13. Judge revokes bail of man charged in state’s largest bath salts seizure. Bangor Daily News Web site. http://bangordailynews.com/2013/02/22/news/bangor/judge-revokes-bail-of-man-charged-in-states-largest-bath-salts-seizure/?ref=search. Accessed March 13, 2013.

References (Cont’d)

γ-Hydroxybutyrate (GHB)

AnonymousDrug Abuse and Society

Image: http://www.watchdocumentary.tv/rave-on-the-rave-culture-of-the-late-eighties-still-affects-the-world-today/

Overview of Topics

• History• Epidemiology• Pharmacokinetics• Pharmacodynamics• Toxicology• Prescription vs Non-Prescription Use• Expectations for Future Use (my opinion)

Image: http://onwardstate.com/2012/01/25/psma-rave-to-hit-alumni-hall/

History 1, 2, 3

• Synthesized in 1960 by Dr Henry-Marie Laborit– Analogue for GABA

• Originally used for its anesthetic properties• 1970’s

– Underwent investigational new drug testing for narcolepsy and other sleep disturbances

• 1980’s/90’s– Used by body builders– Became a popular “club drug”

Image: www.chemheritage.org/discover/online

History (Cont.) 1, 3

• 1990– FDA banned non-prescription use of

GHB• sexual assault AKA “date rape”

– Chemical Precursors• γ-butyrolactone (GBL)• 1,4-butanediol (1,4-BD)

• 2000– DEA classified GHB and precursors as schedule I substances

• Illegal to buy, possess, or distribute without a DEA license

– Prescription sodium oxybate (Xyrem) listed as schedulle III agent

Image: http://jjie.org/kindergartner-placed-handcuffs-arrested-after-tantrum-class/82440

Epidemiology 1, 4

• National statistics show increased use in the US during the 90’s

• Use has declined since 2000– DAWN:

• 64% increase 1999-2000, 33% decrease 2000-2001, no change 2001-2002, then 44% decrease in 2003

• 1,861 ED visits in 2005 vs 2,340 in 2004

– AAPCC: • 485 cases in 2006 vs 1,386 in 2002

– MtF:• College students: 29% decrease in use in 2003• 8th, 10th, 12th grade: 0.5-1.5%

Epidemiology (Cont.) 1, 5

• Outside the US:– Increase use has been reported in Europe

• Denmark, Sweden, and Norway

– Also, Australia• Number of GHB-related ambulance calls increased 4%

per month from 2001 to 2005

http://www.worldpress.org/map.cfm

Trends in Use and Abuse 4

• 5 year study (1999-2003) analyzing data from California Poison Control System– 1,331 cases– 55% men– Proportion of women increased 38% to 60% in 1999 to 2003– No statistically significant difference between men and women– Mean age 27±9 years– Death in 11% of cases– Self-reported co-ingestion of ethanol, MDMA, amphetamines,

cocaine, marijuana, benzodiazepines, etc. in 21% of cases

Trends in Use and Abuse (Cont.) 4

Anderson IB, Kim SY, Dyer JE et al. Trends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003. Annals of Emergency Medicine. 2006

Trends in Use and Abuse (Cont.) 4

• 76% decrease in exposure to GHB observed from baseline– Decrease in cases of abuse– Significant increase in cases of

malicious intent (“date rape”)• 87% involved females• 43% involved co-ingestion with

ethanol• 47% occurred at a night club, bar,

or similar venueImage: http://www.envisioncounsellingcentre.com/date-rape-drugs.html

Pharmacokinetics6, 7

• Street Names– “G”, “Liquid Ecstasy,” “Scoop,” “Easy Lay,” “Georgia

Home Boy,” “Grievous Bodily Harm,” “Liquid X,” “Goop,” “Gib,” “Soap,” and “Nitro”

• May be produced using industrial chemicals– Kits used to be sold on the internet

• Routes of Administration:– IV liquid for anesthesia– PO

• Clear liquid• White powder (dissolved in water)• Tablet or capsule

http://www.harvarddapa.org/drug-ipedia/sedatives/ghb/

Pharmacokinetics (Cont.) 6, 7

• PO Administration– Often of salty powder dissolved in water

• Strength often unknown = increased risk of OD• Salty taste that is masked by flavored or alcoholic beverage

– Clinical effects within 15-30 min• Peak 20-60 minutes

• DDI– Additive Effects

• CNS depressants and alcohol

– Increased Toxicity• Protease Inhibitors due to CYP450 inhibition

Image: http://www.csus.edu/alcohol/predatory_drugs.html

Pharmacodynamics 7, 8

• Structurally similar to GABA– Has effects on sleep-wake cycle, body temperature,

cerebral glucose metabolism and memory (amnesia)• Occurs endogenously and exogenously• Endogenous GHB

– Neurotransmitter or neuromodulator• Receptors

– GHB receptors (endogenous and exogenous)• Hippocampus, cortex, limbic system, and thalamus

– GABAB receptors (exogenous only)• Cerebral cortex, cerebellum, and thalamus

Pharmacodynamics (Cont.) 7, 8

• Receptor Stimulation– GHB Receptor: Increased synthesis of DA via tyrosine

hydroxylase• Striatum and cortex

– GABAB Receptor: Activation of Ca2+ and G-protein coupled Kir channels leads to decreases in DA release and ACh concentration

• Responsible for producing CNS depressant effects

• GHB Precursors– GBL converted to GHB by γ-lactonase– 1, 4-BD concerted to GHB by aldehyde dehydrogenase

MOA of GHB and its Precursors 8

Carter L, Koek W, France C. Behavioral analyses of GHB: Receptor mechanisms. Pharmacology & Therapeutics. 2009; 121 (1): 100-114.

Tolerance and Dependence 1, 9

• Case Reports– Occurs after q 2-4 hour administration over 2

months-4 years with daily doses > 10 g• Rat Studies

– Tolerance observed after 6 days of receiving GHB every 3 hours

• Mechanisms of tolerance– Increased GHB metabolism– Reduction in CNS sensitivity

Withdrawal 1, 7, 10

• Withdrawal s/s– Insomnia, cramps, n/v, paranoia, hallucinations,

tremor, anxiety, HTN, tachycardia, and seizures

Wojtowicz J, Yarema M, Wax P. Withdrawal from gamma-hydroxybutyrate,1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM: Canadian Journal Of Emergency Medicine. 2008; 10 (1): 69-74.

Intoxication 1, 7, 10

• Intoxication s/s– Bradycardia, hypotension, slowed respiration, and

hypothermia

Dose Clinical Effect20-30 mg/kg Euphoria, amnesia, and

somnolence40-60 mg/kg Unconsciousness and coma

Toxicology 1, 11

• S/s of Toxicity– CNS depression/coma, respiratory depression,

salivation, vomiting, myoclonus, death– Salivation and vomiting aspiration

• Recovery– Occurs in 6-8 hours following OD

• No harm unless aspiration or hypoxia has occurred

• Narrow Therapeutic Window– Made smaller with co-ingestion of other CNS

depressants (EtOH) = increased risk of OD

Toxicology (Cont.) 11, 12

• LD50– Rats: 1.7 g/kg– Dogs: 3.3 g/kg– Death occurs due to respiratory depression

• Treatment– Supportive Care

• IV NS prn hypotension• Intubation (with or without adjunctive etomidate) if

severe respiratory depression present• Atropine if severe bradycardia (often not needed)

Image: http://www.mastersext.com/pest-control-rats.html

Treatment (Cont.) 1, 12

• Not indicated for treatment– Activated Charcoal

• GHB undergoes rapid absorption from GI tract• May increase n/v = increased risk of aspiration

• Antidote– Many candidates, but no evidence– AEDs (clonazepam, PHT, phenobarbital, and

diazepam) do not reverse coma– GABA receptor antagonist (flumazenil) does not

reverse respiratory depression– Others: physostigmine (increased seizures), naloxone

(no evidence of clinical improvement)

Illicit vs Prescription GHB 13

Illicit GHB Sodium Oxybate• Production and sale not

regulated– Purity and strength not

guaranteed– One capful of liquid may

contain 5 g of GHB

• Much higher rate of abuse• GHB notoriously used for

sexual assault (“date rape”)– Negative attention from

media and law enforcement– US, Europe, and Australia

• Production follows Good Manufacturing Practices – Dose is exactly 500 mg/mL– Pt takes 4.5-9 g nightly using

calibrated device

• Abuse much lower due to extensive risk management program– Xyrem Success Program:

Physician and patient registry that limits distribution

• Sexual assault: Much lower– Involves physician assaulting a

patientImage: http://fmcfsme.com/drug_sodiumoxybate.php

Expectations for Future Use

• My Opinion– With increased public awareness of the dangers of

GHB use and abuse via the media and law enforcement, I predict that the use of GHB will continue to decline (at least in the US)

http://www.addiction-treatment.com/research/ghb/

References1. Farmer BM. Chapter 80. -Hydroxybutyric Acid. In: Farmer BM, ed. Goldfrank's Toxicologic Emergencies.

9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6522118. Accessed March 13, 2013.

2. Andresen H, Stimpfl T, Sprys N et al. Liquid Ecstacy – A significant Drug Problem. Deutsches Arzteblatt International. 2008; 105 (36): 599-603. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680564/. Accessed March 14, 2013

3. Wood D, Warren-Gash C, Dargan P, et al. Medical and legal confusion surrounding gamma-hydroxybutyrate (GHB) and its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD). QJM: An International Journal of Medicine. 2008; 101 (1): 23-29. http://qjmed.oxfordjournals.org/content/101/1/23.long. Accessed March 14, 2013.

4. Anderson IB, Kim SY, Dyer JE et al. Trends in γ-Hydroxybutyrate (GHB) and Related Drug Intoxication: 1999 to 2003. Annals of Emergency Medicine. 2006; 47 (2): 177-183. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2246009/. Accessed March 14, 2013

5. Dietze PM, Cvetkovski S, Baratt MJ, Clemens S. Patterns and incidence of γ-hydroxybutyrate (GHB)-related ambulance attendances in Melbourne, Victoria. The Medical Journal of Australia. 2008; 188 (12): 709-711. https://www.mja.com.au/journal/2008/188/12/patterns-and-incidence-hydroxybutyrate-ghb-related-ambulance-attendances. Accessed March 14, 2013

6. Gahlinger PM. Club Drugs: MDMA, Gamma-Hydroxybutyrate (GHB), Rohypnol, and Ketamine. American Family Physician. 2004; 69 (11): 2619-2627. http://www.aafp.org/afp/2004/0601/p2619.html. Accessed March 14, 2013

7. Curry SC, Mills KC, Ruha A, O'Connor AD. Chapter 13. Neurotransmitters and Neuromodulators. In: Curry SC, Mills KC, Ruha A, O'Connor AD, eds. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=6504366. Accessed March 14, 2013.

References (Cont.)8. Carter L, Koek W, France C. Behavioral analyses of GHB: Receptor mechanisms.

Pharmacology & Therapeutics. 2009; 121 (1): 100-114. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2631377/. Accessed March 14, 2011

9. Chakraborty K, Neogi R, Basu D. Club drugs: review of the 'rave' with a note of concern for the Indian scenario. Indian Journal Of Medical Research. 2011; 133 (6): 594-604. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135986/. Accessed March 14, 2013

10. Wojtowicz J, Yarema M, Wax P. Withdrawal from gamma-hydroxybutyrate,1,4-butanediol and gamma-butyrolactone: a case report and systematic review. CJEM: Canadian Journal Of Emergency Medicine. 2008; 10 (1): 69-74. http://www.cjem-online.ca/v10/n1/p69. Accessed March 14, 2013

11. Doweiko HE. Concepts of Chemical Dependency. 8th ed. Cengage Learning. 2011: 498-499. http://books.google.com/books?id=61WtimqNyVIC&pg=PA498&lpg=PA498&dq=LD50+of+GHB&source=bl&ots=TYdSabVOY&sig=lem2jC13oM2SDYrjMtiYwhBarJs&hl=en&sa=X&ei=8V5DUbnpDqfE4AP3n4DQCg&ved=0CEwQ6AEwAw#v=onepage&q=LD50%20of%20GHB&f=false. Accessed March 14, 2013

12. Mason PE, Kerns WP. Gamma Hydroxybutryic Acid (GHB) Intoxication. Academic Emergency Medicine. 2008; 9 (7): 730-739. http://onlinelibrary.wiley.com/doi/10.1197/aemj.9.7.730/pdf. Accessed March 14, 2013

13. Carter L, Pardi D, Gorsline J, Griffiths R. Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): Differences in characteristics and misuse. Drug & Alcohol Dependence. 2009; 104 (1/2): 1-10. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/. Accessed March 14, 2013

Nitrous OxideCurtis Cyr

http://upload.wikimedia.org/wikipedia/commons/thumb/d/d5/Priestley.jpg/250px-Priestley.jpg

http://www.fantes.com/images/7118whipped_cream.jpg

Nitrous Oxide (N2O) 1,7

• Laughing gas• Happy gas• Whippets• Nossies• Nangs • NOS• Hippy Crack • Cartridges

• Colorless, non-flammable,

slightly sweet• Boiling Point= -127.3 F

History 1,2

• Discovered by Joseph Priestly in 1772– Heated iron filings with nitric acid

• 1799 – Humphrey Davy experimentations. Coined the term ‘laughing gas’

• 1800-1840 nitrous available to the public for a fee at carnivals and medicine shows

• 1845- Dr. Horace Wells demonstrated dental application of nitrous for anesthesia

• 1863- nitrous used regularly in dentistry by Dr. Gardner Colton

• 1880- Anesthesia (chloroform, ether, nitrous) generally accepted for surgery and dentistry

Nitrous Uses 1,2,3

• Adjunct anesthetic and analgesic in dentistry and surgery• Oxidizer to increase power in motor racing and rocketry

(contains sulfur dioxide)• Food additive

– Canned whipped cream– Cooking sprays– Potato chips

• Treatment of alcohol withdrawal?

http://www.erowid.org/chemicals/nitrous/images/archive/nitrous_collage2.jpg

Mechanism of Action1,4

• Not completely understood• GABA inhibition• Opioid agonist• NMDA inhibition

Pharmacodynamics1

• Analgesia• Anesthesia• Anxiolytic• Euphoria• Noxious feeling after• Tolerance• May be habit forming

Pharmacokinetics5,8

• Onset of action (inhalation)= 2-5 minutes• T½ = 5 minutes• Blood/gas partition coefficient = 0.47• Excreted unchanged by the lungs, minimally through the skin• Very little (0.004%) metabolized• Toxicology - LC50 = 160 mg/m3 (rat)

Nitrous Risks1

• Risk of overdose very low– Lack of oxygen is major risk– Gas delivery related injury– Toxicity if combined with other NMDA antagonists– Accidents (driving, standing)– Very little effects on:

• Respiration• Brain blood flow• Liver, kidney, GI

Long Term Nitrous Risks4

• B12 deficiency– May lead to destruction of nerve fibers– Numbness, tingling– Methionine synthase inhibited– Neurologic/genotoxic/hematologic effects

• Immune effects• Megaloblastic anemia• Myocardial effects – increased homocysteine• At occupational exposure limits (OEL), no conclusive evidence

of toxicities

Occupational Hazard4,6

• Long term exposure to NOS by medical staff may have health effects– Congenital abnormalities, spontaneous abortion– Decreased fertility– Pernicious anemia– Neuropathies

Epidemiology9

• Monitored 50 midwives, environmental concentration and breath tests– 15 had levels below OEL(UK)– 35 showed high exposure (28 very high exposure)

Lifetime prevalence of use of inhalants in teens 10

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

8th grade 15.2 15.8 17.3 17.1 16.1 15.6 15.7 14.9 14.5 13.1 11.8

10th grade

13.5 12.7 12.4 13.1 13.3 13.6 12.8 12.3 12.0 10.1 9.9

12th grade

11.7 11.2 10.9 11.4 11.1 10.5 9.9 9.5 9.0 8.1 7.9

Study on NO in adolescents11

• Residents (N = 723) of Missouri Division of Youth Services were assessed with standardized psychosocial measures– Lifetime prevalence of use= 15.8%

• Used whipped cream chargers= 57.0%• Used whipped cream cans = 38.6%• Other methods = 39.5%

– Mostly white, male, small town– Psychiatric disorders, polydrug use, and temperamental

fearlessness were correlated with NO use

The Law

• Regulated by the FDA• Possession is not illegal, but selling for human consumption

can be prosecuted• Illegal in many states to use recreationally and to sell to a

minor• Available over-the-counter in kitchen stores and head shops

Maine Law12• Unlawful use or possession of inhalants • 1. Prohibited acts. A person may not intentionally or knowingly:

– A. Inhale, ingest, apply or smell the gases, vapors or fumes of any gas, hazardous inhalant, substance containing a volatile chemical or substance containing a chemical material capable of releasing toxic vapors or fumes for the purpose of causing intoxication, euphoria, inebriation, excitement, stupefaction or the dulling of that person's brain or nervous system

– B. Possess any gas, hazardous inhalant, substance containing a volatile chemical or substance containing a chemical material capable of releasing toxic vapors with the intent to violate paragraph A.

• 2. Exclusions. Nothing in this section applies to the inhalation of anesthesia for medical or dental purposes or the inhalation of the vapors or fumes of an alcoholic beverage, the sale and consumption of which is authorized by law.

References

1. Kuhn, C., Swartzwelder, S., and Wilson, W. (2003). Buzzed: the straight facts about the most used and abused drugs from alcohol to ecstasy. The Duke University Medical Center. New York, NY: W.W. Norton & Company.

2. Keys TE. "The_Development_of_Anesthesia". Anesthesiology. 1941;2: 552–574. 3. Gillman M.A, Lichtigfeld, F.J. Enlarged double-blind randomised trial of benzodiazepines against psychotropic

analgesic nitrous oxide for alcohol withdrawal, Addictive Behaviors, Volume 29, Issue 6, August 2004, Pages 1183–1187

4. Sanders RD, Weimann J, Maze M. “Biologic effects of nitrous oxide: a mechanistic and toxicologic review.” Anesthesiology. 2008 Oct;109(4):707-22.

5. Browne DR, Rochford J, O'Connell U, Jones JG. The incidence of postoperative atelectasis in the dependent lung following thoracotomy: the value of added nitrogen. Br J Anaesth. Apr 1970;42(4):340-6.

6. Sethi NK, Mullin P, Torgovnick J, Capasso G. Nitrous oxide "whippit" abuse presenting with cobalamin responsive psychosis. J Med Toxicol. Jun 2006;2(2):71-4.

7. Nitrous Oxide. Erowid. http://www.erowid.org/chemicals/nitrous/. Accessed 3/26/13.8. Nitrous Oxide Material Safety Data Sheet. Hynote Gas. http://www.hynotegas.com/Laughing%20Gas-MSDS.pdf.

Accessed 3/26/13.9. Henderson KA, Matthews IP. “Biological monitoring of midwives' exposure to N2O using the Bio-VOC breath

sampler”Journal of Exposure Analysis and Environmental Epidemiology . 2002;12: 309–312.10. Monitoring The Future. Table 1. http://www.monitoringthefuture.org/data/12data/pr12t1.pdf. Accessed 3/20/13.11. Garland EL, Howard MO, Perron BE. “Nitrous Oxide Inhalation Among Adolescents: Prevalence, Correlates, and Co-

Occurrence with Volatile Solvent Inhalation.” J Psychoactive Drugs. 2009 December; 41(4): 337–347.12. Maine Legislature. Title 22: HEALTH AND WELFARE Subtitle 2: HEALTH Part 5: FOODS AND DRUGS Chapter 558 http

://www.mainelegislature.org/legis/statutes/22/title22sec2383-C.html

K2 or Spice

Anonymous

• History• Epidemiology• Pharmacokinetics• Pharmacodynamics• Legal Implications

Overview of Topics

John W. Hoffman synthesized in the 80s• JWH-018• JWH-073Pfizer developed in 1980s • CP47,497Hebrew University Israel in 1988 • HU-210 • HU-211

History5

www.clemson.edu

• 2000- Used as Incensed • 2002-THC Pharm• 2004- Used recreationally in Europe• 2008- Used started in the U.S.• 2009-2010- DEA temporarily listed the 5

synthetic cannabinoids as controlled substance

• 2011- Listed Schedule 1

History1,7

Street Names1

• Black Mamba• Zombie World• Bad to the Bone• Blaze• Fire and Ice • Dark Night• Earthquake• Berry Blend • The Moon and G-Force

http://www.forbes.com

Herbal Plants used in K21,2

• Canavalia rosea• Nymphaea caerulea• Scutellaria nana• Pedicularis densiflora• Leonotis leonurus• Zornia latifolia• Nelumbo nucifera• others

Methods of Administration1

• smoked in joints • Water pipes• some users make it into a tea

http://www.radicalparenting.com/

http://wesmokeweed.com/

Monitoring The Future5

AAPCC4

AAPCC4

Epidemiology6

• College Students: K2 +cigarette/joint= 61 (88%) K2+hookah = 25( 36%)

• Gender Male 47(10%) female 22(6%)

• Ethnicity White (59%), Hispanic (17%), African American (8%), Asian/Pacific Islander (13%) and other (3%

Epidemiology/Pk10

• Smoke 0.3g of K2 citron

• 3 inhalations over 30 mins

Epidemiology/Pk10

• Cannabinoid receptors cb1-Hippocampus, basal ganglia, cerebellum, medulla cerebral cortex. cb2- peripheral • GABA• Dopamine

Pharmadynamics11

• Paranoia• Panic attacks• Giddiness• Psychotic episodes• Hallucinations• Elevated mood• Relaxation• Altered perception

Psychological Effects2,10

• Tremor• Seizures• Nausea• Vomiting• Increased heart rate• Increased blood pressure• Mycardial ischemia• Heart attack

Physiological Effects2,10

• Supportive care• Benzodiazepine• Typical Antipsychotic

Treatment9

• Report of Death• 19 yo male went out with his friends partying.

They reported smoking marijuana and k2. Becomes disoriented and returned home later in the evening. Was found dead in bed the following morning. No anatomic cause of death

• Toxicology report. (cardiac)THC 13ng/mlJWH 0.71ng/ml

Case10

• A 19-year-old man was brought to the ED by paramedics for possible seizure. The patient's mother heard him scream, and then ran to his room to find him "hallucinating," swinging his fists and having the appearance of being frightened. Subsequently the mother described seizure-like activity, followed by "foaming at the mouth," cyanosis, and unresponsiveness. Approximately 20 min earlier he had returned home after smoking "K2" with a friend. His mother stated that he had been smoking this substance for 2 months. Paramedics initially found the patient lying prone, but he soon became combative, requiring four-point restraints. Pre-hospital pulse was recorded as 220 beats/min. On arrival in the ED, he appeared somnolent and had a pulse rate of 180 beats/min. The patient had a history of heavy cannabis abuse and had recently lost his job due to a positive urine drug screen for THC metabolites. He was admitted to the hospital and had an uneventful course. His urine drug screen was positive for THC (184.7 ng/mL). He was discharged on the second hospital day.

Case10

1. Paul Cary. Spice, K2 and the Problem of Synthetic Cannabinoids. National Drug Court Resource Center. July 14, 2010. http://www.ndcrc.org/sites/default/files/PDF/NDCRC%20Spice%20and%20Problem%20of%20Cannabinoids.pdf

2. NMS Labs. K2 and the Synthetic Cannabinoids: Pharmacology, Effects, and Chemical Analyses. September 10, 2010. Web April 22, 2013-http://www.slideshare.net/nmslabs/k2-and-synthetic-cannabinoids-pharmacology-effectschemical-analysis

3. Drug Fact Sheet. K2 or Spice. Drug Enforcement Administration. Web April 22, 2013. http://www.justice.gov/dea/druginfo/drug_data_sheets/K2_Spice.pdf

4. American Association of Poison Control Centers. Synthetic Marijuana. March 13, 2013. Web April 22, 2013.

5. Clemson University :: Department of Chemistry". Clemson.edu. Retrieved 2010-08-23.

6. Xingdi Hu, Brian A. Primack, et al. College students and use of k2: an emerging drug of abuse in young persons. 2011 july. [PubMed]

7. Office of National Drug Control Policy. Synthetic Drugs (a.k.a. K2, Spice, Bath Salts, etc.). The White House. Web-April 24, 2013.

8.  Gefährlicher Kick mit Spice (German). Web-April 24, 2013

9. National Library of Medicine. Cannabicyclohexanol. Toxicological Data Network. Retrieve from http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+8002. April 24, 2013.

10. NMS LabK2 and the Synthetic Cannabinoids: Pharmacology, Effects and Chemical Analysis. January 18, 2011. http://www.slideshare.net/nmslabs/k2-and-synthetic-cannabinoids-pharmacology-effectschemical-analysis.

11. Barry E. Gustin. “Spices” and Synthetic Cannabinoids. Toxicology Consultant. http://www.toxicologyexpert.net/index.php/Dr.-Gustin-s-Blog/qspicesq-and-synthetic-cannabinoids.html

Reference

MethylphenidateAnonymous

History1,2,3

• Synthesized in 1944 in Basel, Switzerland by chemist Leandro Panizzon

• Patented in 1954 for treating psychological disorders• First marketed by Ciba-Geigy Pharmaceutical Company as Ritalin• First used in 1955 to reverse drug induced coma.• FDA approved in 1955 and introduced in the United states in 1956• Initially approved to treat a variety of conditions including

narcolepsy, low blood pressure, depression, senile behavior, lethargy, and Mohr’s syndrome

• 1980’s ADHD recognized as childhood syndrome – sales of methylphenidate increased

• 1980’s – 1990 lawsuits filed due to negative side effects

Methylphenidate Overview1,2,4

• Central nervous system stimulant – Amphetamine related

• FDA approved for the treatment of attention deficit/ hyperactivity disorder (ADHD) and narcolepsy

• Schedule II controlled substance• Typical dose for ADHD 10-60mg daily ;

not to exceed 72mg daily• Currently available from Novartis

Pharmaceuticals

Image: http://www.wcdtf.org/education/drugs/stim.htm

Methylphenidate overview5

• Administration– Immediate release – Solution, tablets, capsules, chewable tablets– Extended release – Solution, tablets, capsules, transdermal patch

• Brand Names– Concerta– Metadate ER, CD– Methylin, ER– Ritalin, LA, SR– Daytrana (transdermal)

• Black Box Warnings:– High potential for abuse and dependence

Image:www.daytrana.com

Chemical Components3

• Chemical Name: α-phenyl-2-piperidineacetic• Molecular Formula: C14H19NO2

• Molar Mass: 233.3 g/mol• Composition: C(72.1%) H(8.2%) N(6%) O(13.7%)• Melting Point 35°C, 224° for hydrochloride salt• Piperidine derivative• First Synthesized from benzyl cyanide and 2-

chloropyridine• Concerta approved in 2000• Ritalin LA approved in 2002

Image:http://chemistry.about.com/od/factsstructures/ig/Chemical-Structures---R/Ritalin-or-Methylphenidate.htm

Pharmacodynamics1,2,3

• Mechanism of Action– Dopamine(primary)– Norepinephrine– Serotonin(minor)

• Pharmacodynamics:– Racemic mixture

comprised of d- and l- isomer

– d-isomer more active than l-isomer

Pharmacokinetics2

Abuse6,7,12

• Similar effects to cocaine when taken in normal or slightly higher than prescribed doses– “High” feeling and euphoria– Appetite Suppression– wakefulness– heightened alertness– impairment of voluntary movements– headaches– irregular or rapid heart rate– Nausea and vomiting– drowsiness

• Common routes of administration when abused– Orally – even the transdermal patch– Intravenously– Intranasally

• Commonly abused by college students– concentration– alertness

Abuse & Toxicology9,10,11,12

• LD50 in mice: 190mg/kg• Effects at higher doses:

– Exhilaration and excitation– Dilation of pupils– Confusion– Hallucinations, paranoia, delirum– Increased blood pressure and pulse

rate– Dry mouth– Vomiting– Fever, sweating, flushing– Seizures, coma– Anxiety, restlessness, agitation– Excessive repetition of movements

and meaningless tasks, muscle twitching

• American Association of Poison Control Centers’ Toxic Exposure Surveillance System database for deaths from ingestion of methylphenidate from 2000 to 2005: 2

• Patients reporting to poison center over 2 year period: 289

Monitoring the Future8

• Use and Availability of Amphetamines

• “uppers, speed, Adderall, Ritalin, etc.”

Trends in Annual Prevalence of Use of Ritalin (%)

Case Report10,11

• …

References1. Morton AW, Stockton GG. Methylphenidate abuse and psychiatric side effects. Primary Care Companion to the Journal of

Clinical Psychiatry 2000;2(5):159-1642. Concerta prescribing information. Janssen Pharmaceuticals, Inc. March 20123. Myers RL. Methylphenidate (Ritalin). In: The 100 Most Important Chemical Compounds: A Reference Guide. Westport, CT:

Greenwood Publishing Group; 2007:178-1804. National Institute of Health: National Institute on Drug Abuse. Drug facts: stimulant ADHD medications – methylphenidate and

amphetamines. http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines. Updated 2009

5. Micromedex Healthcare Series. Greenwood Village, Colo: Thomson Healthcare. Updated periodically6. Sembower MA, et al. Surveillance of diversion and nonmedical use of extended-release prescription amphetamine and oral

methylphenidate in the United States. Journal of Addictive Diseases 2013;32:26-387. University of Maryland: Center for Substance Abuse Research. Ritalin. http://www.cesar.umd.edu/cesar/drugs/ritalin.asp.

Updated 20058. Johnston, LD, O’Malley, PM, Bachman JG, & Schulenberg JE. Monitoring the Future national results on adolescent drug use:

Overview of key findings, 2011. Ann Arbor: Institute for Social Research, The University of Michigan. 20129. Bruggisser M, Bodmer M, Liechti ME. Severe toxicity due to injection but not oral or nasal abuse of methylphenidate tablets.

Swiss Medical Weekly 2011;141:w1326710. Klampfl K, et al. Case report: intoxication with high dose of long-acting methylphenidate (Concerta) in a suicidal 14-year-old girl.

ADHD Attention Deficit Hyperactivity Disorder 2010;2:221-22411. Ozdemir E, Karaman MG, Yurteri N, Erdogan A. A case of suicide attempt with long-acting methyphenidate (Concerta). ADHD

Attention Deficit Hyperactivity Disorder 2010;2:103-10512. Vastag B, et al. Pay Attention: Ritalin acts much like cocaine. Journal of the American Medical Association 1998;286(8):905-906.

Anonymous

Cocaine

History of Cocaine 1

• Cocaine is contained in the leaves of Erythroxylum coca.

• Grows abundantly in Colombia, Peru, Bolivia, the West Indies, and Indonesia.

• In the 6th century, the inhabitants of Peru chewed or sucked on the leaves for social and religious reasons.

• In the 1100s, the Incas used cocaine-filled saliva as local anesthesia for ritual trephinations of the skull.

History of Cocaine 1,2

• Albert Niemann isolated cocaine as the active ingredient of the plant in 1860.

• Karl Koller introduced cocaine as an effective local anesthetic for eye surgery.

• Sigmund Freud, wrote extensively on the psychoactive properties of cocaine.

• Merck, main cocaine producer in Europe, increased production from less than 0.75 pounds in 1883 to more than 150,000 pounds in 1886.

• Recreational cocaine use was legal in the United States until 1914. • The first cocaine-associated myocardial infarction was reported in

the United States in 1982.

Epidemiology 2

• Recreational use of cocaine remains a significant problem.

• It is estimated that, almost 34 million Americans have used cocaine at least once, with 1.7 million of those dependent or addicted.

• European Union statistics estimate that cocaine has been used at least once by more than 12 million Europeans, representing almost 4% of all adults.

Epidemiology 3

• NSDUH estimates that in 2008 there were 1.9 million current (past-month) cocaine users.

• Approximately 359,000 were current crack users.• Adults aged 18 to 25 years have a higher rate of current

cocaine use. • Men report higher rates of current cocaine use than

women.• Data from the 2008 Drug Abuse Warning Network (DAWN)

report showed that cocaine was involved in 482,188 of the nearly 2 million visits to emergency departments for drug misuse or abuse.

Monitoring the Future survey in 2009 3

Common routes of administration 2

• Oral• Intranasal• Intravenous• Inhalation• Bioavailability exceeds 90% with intravenous and

smoked cocaine.• It is approximately 80% following nasal application.• Data for ingested cocaine and application to other

mucus membranes such as the urethra, vagina, or rectum are inadequately documented.

Interactions 4

• Ethanol• Heroin• Opiates• Antidepressant/antipsychotic medications• Antihistamine data showed that there may be

relationship between increased toxicity ???

Pharmacodynamics 5,6

• Pharmacologic effect of cocaine occurs in CNS.• Cocaine blocks reuptake of catecholamine

neurotransmitters: -norepinephrine -dopamine -serotonin

Tolerance, Dependence, and Withdrawal 7

• Sensitization is shown in animal studies and manifested as behavioral hyperactivity.

• In human, the euphoric effect typically is not subject to sensitization.

• Most chronic users become desensitized and, over time, require more cocaine to obtain euphoria, i.e., tolerance develops.

• Chronic users go through frequent periods of withdrawal.• Cocaine Withdrawal Symptoms and Signs : - dysphoria, depression, sleepiness, fatigue and bradycardia.

• Overdoses with cocaine commonly result in fatalities from:

-arrhythmias. -seizures, or respiratory depression. -cardiac toxicity. -severe hypertensive episodes. • No specific antidote is available.

Toxicology 8

Agents used by health professionals 9

• IV diazepam• IV propranolol • Others approaches include: -Individual and group psychotherapy. -family therapy, and peer group assistance programs.

Societal Perspective of Cocaine 10

• Some people in the society believe that, cocaine addicts and users are:

-deviants -criminals • Cocaine is illegal but can be use for medical

purpose.

• Ear procedures• Nose procedures• Throat procedures

Clinical use of cocaine 11

• Constricts blood vessels• Dilates pupils• Increases body temperature ,heart rate, and

blood pressure.• Headaches and gastrointestinal problem• Decrease appetite • HIV/AIDS and other blood-borne diseases

Impact of Cocaine on Health and Life 12

Future expectations for abuse of cocaine 12

 8th-

Graders

10th-Graders

12th-Graders

Lifetime**

2.6% 4.6% 6.0%

Past Year

1.6 2.7 3.4

Past Month

0.8 0.9 1.3

Future expectations for abuse of Cocaine 12

 8th-

Graders

10th-Graders

12th-Graders

Lifetime**

1.7% 2.1% 2.4%

Past Year

1.1 1.2 1.3

Past Month

0.5 0.4 0.6

Reference1.Wax PM. Chapter 1. Historical Principles and Perspectives. In: Wax PM, ed. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 20112.Hoffman RS, Prosser JM. Chapter 76. Cocaine. In: Hoffman RS, Prosser JM, eds. Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011.3.http://www.drugabuse.gov/publications/research-reports/cocaine-abuse-addiction/what-scope-cocaine-use-in-united-states4.Molina DK, Hargrove VM. Fatal cocaine interactions: a review of cocaine-related deaths in Bexar County, Texas.Am J Forensic Med Pathol.2011 Mar;32(1):71-7 5.http://www.drugabuse.gov/publications/research-reports/cocaine-abuse-addiction/how-does-cocaine-produce-its-effects.6.Doering PL. Chapter 74. Substance-Related Disorders: Overview and Depressants, Stimulants, and Hallucinogens. In: DiPiro JT, Matzke GR, Posey LM, Talbert RL, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011.

Reference7.O'Brien CP. Chapter 24. Drug Addiction. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12nd ed. New York: McGraw-Hill; 2011.8.Trevor AJ, Katzung BG, Kruidering-Hall MM, Masters SB. Chapter 32. Drugs of Abuse. In: Trevor AJ, Katzung BG, Kruidering-Hall MM, Masters SB, eds. Katzung & Trevor's Pharmacology: Examination & Board Review. 10th ed. New York: McGraw-Hill; 2013.9.Mello NK, Mendelson JH. Chapter 394. Cocaine and Other Commonly Abused Drugs. In: Fauci AS, Kasper DL, Jameson JL, Longo DL, Hauser SL, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. 10.National Institute on Drug Abuse. RESEARCH. MONOGRAPH SERIES. Cocaine. Treatment: Research and. Clinical. Perspectives. 135. U.S. Department of Health and Woman Services. 11.Drasner K, Drasner K. Chapter 26. Local Anesthetics. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology. 12nd ed. New York: McGraw-Hill; 2012. 12.http://www.drugabuse.gov/publications/drugfacts/cocaine

Oxycontin

AnonymousDrug Abuse

Dr Piper03/28/2013

Outline

• Structure of oxycontin• History and Background• Epidemiology• Mechanism of action• Pharmacokinetics • Pharmacodynamics• Tolerance and withdrawal• Toxicology• Legal consequences• Impact of abuse of this drug on the user’s life and health• Treatment for abuse.• Conclusion

Structure

The chemical name is 4,5ɑ-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride.

source:http://app.purduepharma.com/xmlpublishing/pi.aspx?id=o

History and Background of Oxycontin1

• Oxycontin is an opioid analgesic. • Synthesized from opium-derived thebaine.• Used to treat moderate to severe pain. • Oxycontin is a controlled-release form of oxycodone.• Oxycontin was created by scientists from Germany in 1916

after the pharmaceutical firms stopped the production of heroin as a drug to cure all diseases.

• The clinical use of the drug was documented in 1917, a year after its development.

• The first medications in Europe that contained Oxycodone were Eucodol, Eukodol, and Dinarkon (Seppala et al. 12).

History and Background of Oxycontin1

• The drug was initially thought to be more safe, less addictive, and more effective at treating pain than heroin.

• In the United States, oxycodone was first introduced to the market in early May of 1938.

• Although it is not easy to establish the exact year of the development and release of Oxycontin, it is believed that the drug was originally prescribed during the early 1990s.

• In 1995, a Stamford Connecticut pharmaceutical firm called Purdue Pharm began producing the drug.

• The ingredient in the drug was, however, was not new at all.

History and Background of Oxycontin1

• Prior to the release of Oxycontin, oxycodone had been around for over six decades. – However, the formulation and delivery of the drug was new.

• Prior to the introduction of Oxycontin, a number of painkillers were used to ease the suffering of individuals with severe pain as a result of cancer or surgery recovery. – Patients were advised by doctors to keep pain relievers in their bloodstream

at all times to stave off the pain. – The challenge was that painkillers, including morphine, only relieved a

person’s pain for an average time of 2-3 hours. – This entailed that people had to take several pills every day to keep their

plasma concentration at an effective level.• Oxycontin was able to solve this problem by distributing its active

ingredient over a 12 hour period (Seppala et al. 15).

Epidemiology2,3

• Epidemiology refers to “the study of the determinants and distribution of health-associated events or states, and the use of this study to the control of illnesses and other health-related problems.”

• Oxycontin doses start low and are progressively increased as an individual’s tolerance to opioids builds.

• However, how much Oxycontin is too much? – This largely depends on various personal factors including age,

medical condition, present exposure to opioids, and other medications taken by individual.

• There are people who are at higher risk of adverse events from the drug, which can be explained by looking at the precautions of using the drug.

Epidemiology Cont’d2,3

• The product might contain inactive ingredients that can cause allergic reactions (Gitlow 172). – Therefore, it might not be prescribed for individuals with

certain types of allergies. • Additionally, people with a history of medical problems

like brain disorders, breathing disorders, kidney and liver disease may require a specialized dose that will work for them.

• Since the drug may make patients feel drowsy or dizzy, it is not good for people to perform activities such as driving, using heavy machinery until they know how the drug affects them.

• Those who drink alcoholic beverages should avoid taking this medication.

Epidemiology cont’s2,3

• Older individuals may be more sensitive to the effects of Oxycontin, especially drowsiness, dizziness, urinary problems, or slow breathing.

• In terms of sex differences, pregnant women and women of childbearing age should talk with healthcare providers as they may be at higher risks of adverse events when using the drug.

• In times of pregnancy, the drug should only be used when conditions deem it necessary.

Epidemiology cont’s2,3

• According to Alex (15), the use of Oxycontin has changed, especially after Purdue Pharma, the drug’s manufacturer, changed the formula.

• The formulation what changed because people were abusing the drug by crushing and inhaling the pills.

• Although the formula stopped users from abusing the drug, a considerable percentage of individuals are turning to harder drugs including heroin and other stronger opioids.

• The use of the drug in other countries outside Europe and the U.S.A. is not common.

Epidemiology

Oxycontin use has risen by almost 40% among 12th graders since 2002.

Epidemiology

MOA of Oxycontin4

• Oxycodone acts as a weak agonist at mu, kappa, and delta opioid receptors in the central nervous system (CNS).

• Oxycodone mainly target mu-type opioid receptors.• Mu opoid receptor are attached with G-protein receptors and

function as both positive and negative modulators, of synaptic transmission via G-proteins that activate effector proteins.

• Binding of the oxycontin stimulates the exchange of GTP for GDP on the G-protein complex.

• As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, oxycontin decrease intracellular cAMP by inhibiting adenylate cyclase (Preissner,2009).

MOA of Oxycontin4

• The release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited.

• Oxycodone also inhibit the release of vasopressin, somatostatin, insulin, and glucagon.

• Oxycodone close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (mu and delta receptor agonist).

• End up with decreased nerve conduction and reduced neurotransmitter release, which blocks the perception of pain signals (Preissner ,2009).

Pharmacodynamics5

• “The action of a certain drug in the body over a period of time and includes processes of absorption,

• localization in tissues, • distribution, • biotransformation, • and excretion.”• In other words, it is “the process by which a drug is

absorbed, distributed, metabolized, and excreted by the body” (Jusko 115).

Pharmacodynamics5

• The biological activity of Oxycontin is due to the active ingredient, oxycodone.

• This drug is designed to give delivery of the primary ingredient over 12 hours.

• The following impair the delivery mechanism and may lead to faster release and absorption of oxycodone, and may be fatal:– Breaking– Cutting– Crushing– Dissolving

• The release of oxycodone from Oxycontin does not depend on pH.

Pharmacokinetics5

Controlled-release version of the drug taken every 12 hours with an immediate release version taken every six hours. The CR version featured fewer peaks and

valleys. Oxycontin doses peak quickly and then plateau in the blood stream, providing constant levels

of pain relief.

Pharmacokinetics5

• Oxycodone’s oral bioavailability is 60 to 87%.• The relative bioavailability from release of the

oral dosage form is 100%. • Oxycodone is intensively metabolized and

excreted in the urine as metabolites. • Upon absorption, the high oral bioavailability is

caused by low pre-systemic metabolism. • Food has no considerable effect on the degree

of absorption of the drug.

Pharmacokinetics5

• Once absorbed, the drug is distributed to muscles of the skeleton, intestinal tract, lungs, liver, brain, and the spleen.

• For women, the active ingredient has been found in breast milk.

• Oxycodone, as well as its metabolites are excreted through the kidney.

• Oxycontin binds to opiate mu receptors in the brain, eliminating or numbing feelings of pain.

Tolerance and withdrawal5

• Oxycontin develops tolerance in that some individuals may cause them to feel that the drug is not effective, and they may take more than the amount prescribed in order to feel its effects.

• The development of tolerance requires stopping or cutting back on the amount taken by an individual as the body needs time to recover and adjust.

• Thus, withdrawal symptoms may result. • The withdrawal symptoms of the drug may vary from mild

to severe, depending on the amount and length an individual has taken the drug (Jusko 116).

Tolerance and withdrawal5

• However, some people may not realize that they are experiencing withdrawal and may report having a normal flu.

• These symptoms normally start after six to thirty hours after the last use of Oxycontin.

• The early symptoms include anxiety, agitation, increased tearing, muscle aches, insomnia, sweating, runny nose, and yawning.

• On the other hand, abdominal cramping, goose bumps, diarrhea, nausea and vomiting, and dilated pupils are later withdrawal symptoms of the drug.

Toxicology6

• The LD50 does not scale accurately since people vary. • The consumption of the drug more than the prescribed might cause

death to a non-tolerant person. • However, tolerance is a significant factor in computing LD50. • People who are tolerant are able to have a significant amount of the

drug without any significant effects. • Oxycontin LD50 has been characterized for mice species. • Overdose occurs when an individual accidentally or intentionally takes

too much of the drug. • The reasons for overdose vary from one individual to another. • The drug has ingredients including oxycodone and hydrocodone, which

may become poisonous at higher-than-prescribed doses (Breguet 10).

Toxicology6

• Overdose can cause death or severe symptoms. • The frequency of overdose of the drug depends on

age, sex, and other personal factors of an individual. • Doctors and other healthcare providers use some

agents in order to prevent lethality associated with the drug.

• The use of oral softening agents such as laxatives and/or cathartics is advised used by healthcare providers to as they reduce lethality of Oxycontin.

Legal consequences

Legal Consequences7

• Using Oxycontin illegally has some social consequences. • First, the offender might receive a jail penalty which varies

from months to years depending on the offense (Lofwall, 600). • Additionally, there might be the imposition of a fine for an

individual or institution that uses the drug illegally. • However, this differs from one state to another and the

number of times of the offence. • For instance, if it is a person who used it for the first time, he

or she might be discharged to a rehabilitation center or probation.

• The legal consequences also depend on the jurisdiction.

Indication7

• Oxycontin is used to relieve pain from:– Cancer.– Arthritis.– Other conditions.

• The drug is effective at relieving pain for 12 hours. • Abuse of Oxycontin may occur where individuals might accidentally or

intentionally take too much of the drug (Lofwall 603). • The high content of oxycodone is what makes the drug popular on the

street. • Some individuals who abuse Oxycontin crush the tablet and snort or

swallow it while others inject it or dilute it in water. • This disrupts the time-release mechanism and allows the to user get

the full effects of the narcotic.

Indication7

• Most users of the drug compare the high with the euphoria associated with heroin use.

• What makes the drug dangerous is not only the fact that it is addictive, but it can also be fatal as it makes individuals feel that they can tolerate more.

• However, it can lead to failure of the respiratory system, especially when used in combination with other drugs including benzodiazepines and alcohol.

• This is what differentiates medical indication versus abuse.

Impact of abuse of this drug on the user’s life /health8

• Just like all drugs, the abuse of Oxycontin has significant short-term and long-term effects on the health and life of an individual.

• One of the major effects of abusing the drug is physical dependence.

• This occurs due to continued use of the drug, which in turn leads to individual’s tolerance to the drug.

• According to Levy, (272) the person’s body gets used to changes made by Oxycontin.

Impact of abuse of this drug on the user’s life /health8

• These might lead to withdrawal symptoms including fever, nausea, anxiety, and insomnia.

• Users may also begin to have cravings for the drug.

• Abuse of the drug can lead to breathing difficulties.

• Abuse affects the behavior and mood of an individual depending on the circumstances.

Impact of abuse of this drug on the user’s life /health8

• Abusers may have mood swings such as becoming happy, but getting aggravated quickly (Sees 20).

• Neurological and cardiovascular effects are problems also associated with the abuse of Oxycontin. – These create significant problems of the brain and heart. – Blood pressure and heart failure can also result.

• At the extreme, abuse of Oxycontin can cause death (Sees 21).

• The future expectation for abuse of the drug is low as since the formula was changed in 2010 abusers have turned to other drugs.

Treatment for Oxycontin9

• A long-acting Naltrexon.• Naloxone (Short acting) administration also

provokes an acute withdrawal syndrome in a dependent person who has recently taken an opioid

• Methadone once daily.• Termination of methadone suddenly results in

withdrawal syndrome that is, the subject on substitution therapy remains dependent.

Conclusion

• Oxycontin is an opioid analgesic use to relieve chronic pain.

• Many develop tolerance for oxycontin which results in its abuse.

• People can get into legal problem if found selling or abusing oxycontin.

• antidote for oxycontin abuse is available to curtail use.• There are also many side effects associated with the use of

oxycontin. • Some of these side effects can lead to death of an

individual abusing oxycontin if care is not taken.

Works Cited

1. Seppala, Marvin D, and Mark E. Rose. Prescription Painkillers: History, Pharmacology, and Treatment. Center City, Minn: Hazelden, 2010. Internet resource

2. Gitlow, Stuart. Substance Use Disorders: A Practical Guide. Philadelphia: Lippincott Williams & Wilkins, 2007. Internet resource.

3. Crees, Alex. Oxycontin users switching to heroin after drug is redesigned (2012)4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R:

SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Jusko, William. "Pharmacokinetics." Journal of Pharmacokinetics and Pharmacodynamics Journal of Pharmacokinetics and Pharmacodynamics 10928.1 (2012): 115-119. Print.

6. Breguet, Amy. Vicodin, Oxycontin, and Other Pain Relievers. New York: Chelsea House, 2008. Print.7. Lofwall, R, E Moody, B Fang, A Nuzzo, and L Walsh. "Pharmacokinetics of Intranasal Crushed OxyContin and Intravenous

Oxycodone in Nondependent Prescription Opioid Abusers." Journal of Clinical Pharmacology 52.4 (2012): 600-606. Print.8. Levy, Michael. "An Exploratory Study of OxyContin Use Among Individuals with Substance Use Disorders." . Journal of

Psychoactive Drugs 39.3 (2007): 271-276. Print.9. Luscher C, Luscher C. Chapter 32. Drugs of Abuse. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic & Clinical Pharmacology.

12nd ed. New York: McGraw-Hill; 2012. http://www.accesspharmacy.com/content.aspx?aID=55826407. Accessed March 26, 2013.

Questions