Drug abuse and society drug presentations: Spring 2013

RX462 Drug Abuse & Society
Presentations
Brian J. Piper, Ph.D., M.S.
Department of Basic Pharmaceutical
Sciences
psy391@gmail.com or piperbj@husson.edu

Contents
Drug 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 including
common 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.html
http://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/

ACID
BLOTTER
CALIFORNIA SUNSHINE
DOTS
ELECTRIC KOOL-AIDStreet 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/kg
dose to a female subject (▵) and a male subject (×).
• A study conducted with rats showed male rats who were administered doses
of LSD were more likely to revisit the area of their cage where the LSD was
administered 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

Lysergic 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 >.

References
15. 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)
Anonymous
PharmD 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

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 proposes
that the term “fly” refers not to insects,
but the delirium resulting from
consumption 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/2117813
6/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 hours
Duration : 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 disturbances
and convulsions may also
be 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 mild
dehydration may be observed
• Meiosis as well as mydriasis
http://www.funnyjunk.com/funny_pictures/3132057/MARIO+S+MU
SHROOMS/

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.

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.

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.

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

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

Ketamine
Anonymous
Drug 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);
• 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 Use>
• 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)>
• 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

Pharmacodynamics?
• 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)@
• 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

Pharmacokinetics<A
• 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)@ B
• 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)<
• 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 Use@
• 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 UseC;:
• 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)C
• 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”>
• 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

Toxicology?;=
• 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);:
• “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”.

References
1. 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.asp
4. 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. Pelletier
Drug 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/cath
a%20edulis%2004%20NL%20uithof%20greenhous
e.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

0
20
40
60
80
100
120
140
Sept 2012 Oct 2012 Nov 2012 Dec 2012 Jan 2013 Feb 2013
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)
Anonymous
Drug 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, benzodiaz
epines, 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 venue
Image: 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, tr
emor, 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 Effect
20-30 mg/kg Euphoria, amnesia, and
somnolence
40-60 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
patient
Image: 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/

References
1. 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.
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.
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&s
ource=bl&ots=TYdSabVOY&sig=lem2jC13oM2SDYrjMtiYwhBarJs&hl=en&sa=X&ei=8V5DUbnpDqfE
4AP3n4DQCg&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 Oxide
Curtis Cyr
http://upload.wikimedia.org/wikipedia/commons/thum
b/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

History1,2
• 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 Uses1,2,3
• 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

• History
• Epidemiology
• Legal Implications
Overview of Topics

John W. Hoffman synthesized in the 80s
• JWH-018
• JWH-073
Pfizer developed in 1980s
• CP47,497
Hebrew 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/

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

• 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/ml
JWH 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

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

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/fact
sstructures/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

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, Adde
rall, Ritalin, etc.”
Trends in Annual Prevalence of Use of Ritalin (%)

References
1. Morton AW, Stockton GG. Methylphenidate abuse and psychiatric side effects. Primary Care Companion to the Journal of Clinical
Psychiatry 2000;2(5):159-164
2. Concerta prescribing information. Janssen Pharmaceuticals, Inc. March 2012
3. Myers RL. Methylphenidate (Ritalin). In: The 100 Most Important Chemical Compounds: A Reference Guide. Westport, CT: Greenwood
Publishing Group; 2007:178-180
4. 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 periodically
6. 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;32:26-38
7. University of Maryland: Center for Substance Abuse Research. Ritalin. http://www.cesar.umd.edu/cesar/drugs/ritalin.asp. Updated 2005
8. 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. 2012
9. 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:w13267
10. 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;2:221-224
11. Ozdemir E, Karaman MG, Yurteri N, Erdogan A. A case of suicide attempt with long-acting methyphenidate (Concerta). ADHD Attention
Deficit Hyperactivity Disorder 2010;2:103-105
12. Vastag B, et al. Pay Attention: Ritalin acts much like cocaine. Journal of the American Medical Association 1998;286(8):905-906.

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-
Grader
s
10th-
Graders
12th-
Graders
Lifetim
e**
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-
Grader
s
10th-
Graders
12th-
Graders
Lifetim
e**
1.7% 2.1% 2.4%
Past
Year
1.1 1.2 1.3
Past
Month
0.5 0.4 0.6

Reference
1.Wax PM. Chapter 1. Historical Principles and Perspectives. In: Wax PM, ed.
Goldfrank's Toxicologic Emergencies. 9th ed. New York: McGraw-Hill; 2011
2.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-states
4.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.

Reference
7.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
Anonymous
Drug Abuse
Dr Piper
03/28/2013

Outline
• Structure of oxycontin
• History and Background
• Epidemiology
• Mechanism of action
• 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).

• 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.

• 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.

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).

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