Download National 800 Phone Number What Are Synthetic Drugs? Synthetic

K2,JWH,2C‐E,MDPV:
theAlphabetSoupof
EmergingDrugs
National 800 Phone Number
Works just like 911
Program your
cell phone!
Partnership between Iowa Health System
and University of Iowa Hospitals and Clinics
Linda B. Kalin, RN, BS, CSPI
Director
[email protected]
24/7 Hotline: (800) 222-1222
Office: (712) 279-3710
What Are Synthetic Drugs?
 Chemicals created for recreational use to evade
drug legislation by modifying molecular structure of
existing drugs or by finding new drug classes that
will produce effects similar to marijuana, cocaine
and methamphetamine
 Based on their chemical make-up, these drugs are
commonly divided into two categories:
 Synthetic Cannabinoids (aka “K2”)
 Marketed as “fake weed” or “legal marijuana”
 Synthetic Cathinones (aka “bath salts”)
 Marketed as alternative to cocaine, ecstasy, meth
Contents Often Unknown
• Advertising/packaging is often misleading
• No quality control or oversight of manufacturing
process
 One product may contain several different chemicals
 Federal laboratories have detected both SynCann
and SynCath in the same sample
 Websites promise to protect customers by shipping
products in discreet or unmarked packages
Buyers don’t know what chemicals they’re taking!
05/01/12
24 hours a day- 7 days a week
Federally funded by HRSA
iPhone app is
now available
Synthetic Drugs
• 2nd most commonly abused worldwide behind
cannabis; ahead of cocaine and heroin
• Sold under the guise of “plant food,” “bath
salts,” “herbal incense,” “potpourri,” and more
recently “glass cleaner” and novelty powders”
• Cheap, easy to make, high profits, less
expensive distribution chain
• Found on nearly every one of the products:
 "Not intended for human consumption“
 "Not to be sold to people under 18 years of age”
Why Aren’t These Drugs Illegal?
• Most States, including Iowa, have banned
specific formulas of synthetic cannabinoids
and cathinones but drug makers can easily
sidestep these regulations
• Manufacturers adapt simply by replacing the
chemical compound of a banned substance
with a newer formulation that is not yet known
to authorities
• Poses increasing risk as users are unaware of
the reactions the new chemicals may cause
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What are Synthetic Cannabinoids?
• Synthetic cannabinoids are not organic but are
produced in a lab
 Part of a class of compounds called cannabinoids
 The cannabinoid in marijuana is the naturally
occurring delta-9 -tetrahydrocannabinol (THC)
 Cannabinoids act on the same receptors in the brain
 SynCann may be two to 500X stronger than THC
• Popular alternative to smoking marijuana
• Hundreds of different compounds on the market
Background
Appearance
• Chemicals are typically found in powder form
or dissolved in solvents (ex. acetone) before
being sprayed on the dried plant material
• Plant material may be potpourri, plants, herbs
(damiana) and even grass cuttings sprayed
with SynCanns then smoked
 “Spice” brand first became available in 2004
 December, 2008: “Spice” found to have the
synthetic cannabinoids JWH-018 and CP-47,497
Common Chemicals (banned in IA)
• JWH-018, JWH-073, JWH-200 first synthesized
in early 1990s
1-pentyl-3-(1-naphthoyl) indole (JWH-018)
1-butyl-3-(1-naphthoyl) indole (JWH-073)
 John W. Huffman: professor of organic chemistry at
Clemson University
1-[2-(4-morpholinyl) ethyl]-3-(1-naphthoyl) indole (JWH200)
 Created >400 synthetic cannabinoid compounds to
explore how drug substances latch on to receptor
sites in the brain ; research published in 1998
5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]phenol (CP-47,497)
 JWH-018 may be the most used of the JWH series
• Very potent
R(−)-7-hydroxy-delta-6-tetra-hydrocannabinoldimethylheptyl (HU-210)
11 -hydroxy-delta8-tetra-hydrocannabinol, dimethylheptyl
(HU-211)
• Easy to make
Routes of Administration
Packaging & Availability
• Usually smoked to provide marijuana-like high
• Generally sold in 1, 3, 5, or 10 gram packages
 3 G pkg (~8 joints) prices range from $5 to $50
 Often smoked in bongs
 Internet retailers offer discounts for bulk purchases
 Rolled in papers and smoked
• Blatant advertising:
 Packed into a blunt
 Hookah pipes
 “Exotic herbs that, when smoked, produce euphoria”
 Inhaled after burning as incense
 “Herbal incense products are legal marijuana”
 May display marijuana nomenclatures (ex. “Cush”)
• May be ingested or snorted
• Some users make it into a tea
05/01/12
Looks like marijuana
or potpourri
• Thought to be produced in China, India, Mexico
• Sold in smoke shops, novelty stores, internet
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Pharmacology
Lock-and-key mechanism
Lock= cannabinoid receptor sites of the brain
Key= THC (partial agonist) and JWH (full agonist)
• Agonist: A drug that activates the
receptor
THC is a partial
agonist of CB1;
Synthetic cannabinoids
are full agonists
• Both THC and JWH bind to the
cannabinoid receptors (CB1 and
CB2) to activate them
 THC weak activation of receptor
 JWH several times more powerful
than THC at activating receptor
• SynCann is NOT cannabis!
Creative Chemistry
Effects*
 AM-2201
•
•
•
•
•
•
 Potent agonist
 Fluorinated version of JWH-018
JWH
AM-2201
Treatment
• These chemically-related cannabinoids do
NOT cross-react with THC on the standard
UDT
• Identifying SynCanns as the causative agent
of the patient’s psychosis isn’t as important as
delivering effective care to help the patient
 Treat the patient, not the poison
 Good symptomatic and supportive care
 Benzodiazepines (generous use)
05/01/12
Extreme anxiety
Extreme agitation
 heart rate
 blood pressure
Disorientation
Paranoia
•
•
•
•
•
Delusions
Hallucinations
Drug-induced psychosis
Tremors, seizures (rare)
Withdrawal effects
 anxiety, depression and
psychosis
Long term effects on humans not fully known
*Effects more extreme than THC
Synthetic Cathinones*
• Often considered “legal highs”
 Sold as “bath salts”, plant food and incense
 Marketed as “legal” alternative to cocaine,
amphetamine, and ecstasy
• Derivatives of cathinone- a naturally
occurring amphetamine analogue found in
the leaves of the khat plant
*The term “synthetic cathinone”, as used in this presentation,
is not meant to refer to legal pharmaceuticals (Rx drug
bupropion is a legal synthetic cathinone)
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Khat (Catha edulis)
• Pronounced “cot”
• AKA: Abyssinian tea, qat, African
salad, bushman’s tea, somali tea
Man consuming qat in
Yemen, Jan 2009.
• Organic stimulant found in Middle
Eastern countries
• Leaves are usually chewed for
stimulant effects; may also be
smoked or brewed in tea
Bundles of qat seized by
the DEA in July, 2006
• Cathinone found primarily in fresh
leaves – Schedule I
Common SynCath Derivatives
• Most popular for use as “legal highs”:
 3,4-methylenedioxypyrovalerone (MDPV)
 4-methylmethcathinone (mephedrone, 4-MMC)
 3,4-methelendioxy- n-methylcathinone (methylone)
 4-fluoromethcathinone (flephedrone, 4-FMC)
 3-fluoromethcathinone (3-FMC)
 4-methoxymethcathinone (methedrone, BKPMMA, PMMC)
Cathinone
• Causes amphetamine-like effects ( HR,
 BP), euphoria, increased alertness
• Surge in popularity in Europe started in 2007
 Falling quality of cocaine and ecstasy
 Sold directly as mephedrone and MDPV
 Banned in Britain April, 2010
• U.S. sales started in 2009 as “bath salts”
 Mephedrone and MDPV most common
• Two cathinones banned in Iowa 2011
Appearance
• Usually supplied as a fine, white, off-white,
tan or brown clumpy powder
• May be compressed into crystal to resemble
actual bath salts
 Smaller than meth crystals; may be mistaken for
MDMA and possibly crushed meth crystals
• Can be purchased in pill or capsule form
• Little or no odor
Methylone capsule and powder
Packaging & Availability
• Generally sold in a 300-500mg package
 <10 mg considered a “normal dosage”
 Most people assume 300-500mg is a normal
dosage so they overdose
• In U.S., 1 g costs ~$20-$35
 If $30/gram, 25 pounds= street value of $ 340,000
• Available via Internet
Patterns of Use
• Most commonly snorted or ingested
• “Bombing”- mephedrone powder is wrapped in
cigarette paper and swallowed
• “Keying”- dipping a key into powder and then
insufflating (~5-8 “keys” per gram)
• Rectal/vaginal, inhalation, intramuscular or
intravenous injection have also been described
• Onset of effects: immediate to 30 min
 Research chemical websites
• Duration of effects: up to 6 hrs in “normal” dosing
 Facebook site and link to PayPal
• Not unusual for patients to be affected for days
05/01/12
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Effects
Pharmacology
• Mechanism of action
 Similar to hallucinogenic amphetamines (ecstasy)
  brain levels of stimulatory neurotransmitters
• Inhibits reuptake of serotonin, norepinephrine and dopamine
• Serotonin can elevate mood and cause a calming effect
• Norepinephrine  alertness, concentration and motivation
• Dopamine helps control the brain's reward and pleasure
centers; helps regulate movement, emotional responses
SynCath: Adverse Effects
 Heart rate
 Blood pressure
 Temp (monitor closely)
Chest pain
Vasoconstriction with
cold or blue fingers
• Hot flashes and
diaphoresis
•
•
•
•
•
• Headache (common)
• Insomnia
• Bruxism (like
ecstasy)
• Tremors
• Dizziness
• Seizures (at higher
doses)
Danger to Themselves & Others
• Euphoric high with a rush similar to cocaine,
ecstasy, or methamphetamine without causing
the hangover, “comedown” or depression
• Users report  empathy,  alertness,  energy,
 concentration and focus,  sexual stimulation,
overall sense of well-being
 Some high school/college students are using
cathinones --believe beneficial for work/studying
SynCath: Psychiatric Effects
• Aggression, anxiety, agitation, panic
attacks, confusion nightmares, insomnia
• Psychosis, time distortions, long lasting
hallucinations (A&V), paranoid delusions,
short term psychosis or mania
• Depression, impaired short term memory,
difficulty concentrating
• Potential long term effect- Parkinson’s
Disease???
Treatment
• Without provocation, may lash out
• These don’t show up on routine UDT
• Several graphic media reports
• Identifying bath salts as the causative agent of
the patient’s psychosis isn’t as important as
delivering effective care to help the patient
• May present with extreme anxiety and agitation,
combative, self-destructive, suicidal, homicidal
• Need to protect self, staff and patient from harm
• When signs and symptoms begin to resolve,
patient may experience depression, withdrawal
and suicidal thoughts
 Treat the patient, not the poison
• There are no antidotes; good supportive care
 Benzodiazepines (large doses)
 Antipsychotics if not responding to benzos
• First ensure your own safety!
05/01/12
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Lab Testing for SynCanns
• Drug identification? Yes
Lab Testing for SynCaths
• Drug identification? Yes
 Compound is compared to known standard
 Compound is compared to known standard
 ~20 known reference standards available at DCI Lab
 7 reference standards available at DCI lab
 If no reference standard available, may report
substance as “consistent with” compound found
 If no reference standard available, may report
substance as “consistent with” compound found
 Lack of validated field tests; beware of “negative” result
• Toxicology? (not found in routine UDT)
 Some private labs have the capability to test in urine
• Toxicology? Yes (not found in routine UDT)
 Cathinone
 Methcathinone
 Mephedrone
 MDPV
Current Iowa Law
• 6 SynCanns and 2 SynCaths added to Schedule I
of the CSA (also Salvia divinorum and Salvinorin A)
• Generic language:
Any substance, compound, mixture or preparation which
contains any quantity of any synthetic cannabinoid that is
not approved as a pharmaceutical (Section 18, SF 510)…
• Proposed SF 2123- mirrors Federal HR 1254
Phenethylamines
• 4-bromo-2,5-dimethoxyphenethylamine (2-CB,
DOB, Bromo)
• 2,5-dimethoxy-4-methylamphetamine (DOM)
• 4-ethyl-2,5-dimethoxyphenethylamine (2C-E)
• 2,5-Dimethoxy-4-n-propylthiophenethylamine
(2C-T-7)
 Expands law; bans many more substances
 More definitive generic language
Effects similar to amphetamines
Case Report
Case Report
• May 7, 2011 (Oklahoma)
• 8 young adults (19 to 25 yo) ingested 2C-E
while at a party (purchased online)
• March 18, 2011 (Minnesota)
• 1 died, other 7 admitted to hospitals
• 1 teen died and 10 teens and young
adults were hospitalized after ingesting
2C-E (AKA “Europa”)
• Seizures, hyperthermia, CNS depression,
apnea (3 required ventilatory support)
• Legally ordered over in the Internet for a
spring break party
05/01/12
• Samples obtained have contained TFMPP,
MDPV, PMMA, MDPBP bk-MBDB, and
other cathinone derivatives
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Piperazines
Tryptamines
• Often sold as Ecstasy
• N,N-dimethyl-tryptamine (DMT , “businessman’s lunch”)
• Benzylpiperazine (BZP)
• m-chlorophenylpiperazine (mCPP)
• N,N-dipropyltryptamine (DPT)
• Trifluoromethylphenylpiperazine (TFMPP)
• 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
 Limited effect when taken alone; usually in
combination with BZP
 Dopamine release in brain increases 5 fold when
taken in this combination
• Alpha-methyltryptamine (AMT , “spirals”)
• 5-methoxy-N,N-dipropyltryptamine (5-MeO-DIPT, “foxy”)
• 5-hydroxy-N,N-dimethyltryptamine (bufotenin)
• Effects similar to MDMA (Ecstasy)
Symptoms similar to psilocybin and psilocin
PMMA and PMA
Methoxetamine
• PMMA (paramethoxymethamphetamine) and
PMA (paramethoxyamphetamine (“Doctor Death”)
• Cases reported to ISPCC 02/22/12 (“rolfcopter’)
• PMA is active metabolite of PMMA
• Cogener of ketamine and PCP
• Structurally related to mescaline and to ecstasy
group (MDA, MDMA, MDEA)
• Methox + the “etamine” from “ketamine”
 UDT negative
• Higher toxicity & more dangerous than ecstasy
No legal
restrictions
in U.S.
 May be due to PMA’s delayed effects
 May cause life-threatening increases of BP and temp
• Not detectable in routine lab tests
Methylhexaneamine
ketamine
methoxetamine
Zannie Air Freshener
• AKA “Pump-It Powder” or “Party Pills”
• Light blue/green color liquid
• Similar to “bath salts” that contained MDPV
 Effects are amphetamine-like
• Blogs- “product is intended to be sprayed
into mouth like a breath freshener”
 Long believed to be a natural aphrodisiac
• Onset within 1 hr; may last several days
• Marketed under the name Geranamine or
DMAA (dimethylamylamine)
 Sold as dietary supplement (Jack3d, OxyElite Pro)
• Advertised to  energy, concentration and
physical performance (“similar to adrenaline”)
05/01/12
• Contains phenazepam (benzodiazepine)
 Developed in the former Soviet Union 1970s
 Used in other countries for sedation, epilepsy,
and alcohol withdrawal syndrome
 May be used to “come down” from stimulant high
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Desomorphine
Desomorphine
• AKA “Krokodil”
• Upsurge in Russia in 2010
• Synthesized from codeine tablets using
same components as for methamphetamine
• Chemicals used in synthesis rot flesh to the
bone
 10X stronger and 3X cheaper than heroin
• Teeth rot out of your head
• Known as “poor man’s heroin”
 Originally synthesized in the 1930s as alternative
to morphine
• Brain damage, tetanus, sepsis, Hep C, AIDS
and amputations are common
• Highly addictive
• “Dirty cousin of morphine”
• Skin becomes green and scaly from the
injection of the drug including contaminants
Kratom (Mitragyna speciosa)
• Average life span of user is about 2 years
Kratom (Mitragyna speciosa)
• Tree native to SE Asia
• Used in folk medicine as a stimulant
(at low doses), sedative-euphoricanalgesic (at high doses), recreational
drug, pain killer, medicine for diarrhea,
and treatment for opiate addiction
• One case reported to ISPCC (Mar 2012):
 Packaging similar to SynCanns (foil pouches)
 Labeled “Not for human consumption; must be 18 yo”
Kratom
• Illegal in Australia, Malaysia, Burma, Thailand
 Acts as mu-opioid receptor agonist in
high doses
• Fresh leaves are chewed or smoked
or brewed into a tea (with sweeteners)
• Has been used in combination with synthetic
opioid desmethyltramadol known as “Krypton”
Dried kratom leaf
“Cinnamon Challenge”
• Teens dared to swallow a spoonful
of cinnamon without drinking water
Popular dare game
Videos on Internet
• Results in the cinnamon coating
and drying mouth and throat;
makes swallowing difficult
• Causes gagging, coughing,
choking, vomiting, throat irritation
• May lead to respiratory distress
05/01/12
• Addiction and withdrawal occur with chronic use
Looking Ahead…
• Long term effects?
• Care for Chronic Users?
• Refer to drug courts
 How to monitor?
• Develop better drug screens
 Worth investing in?
• Prevention
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