Transcript Document

SYNTHETICS, OPIOIDS, AND MARIJUANA,
OH MY!
November 19, 2013
ACT Missouri
Substance Abuse and Prevention Conference
Sgt. Jason J. Grellner
Missouri Narcotics Officers Association
Designer Drugs
These drugs are perceived as being ‘legal’ alternatives to
marijuana, cocaine, methamphetamine, and MDMA
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
.
Proliferation of Designer Drugs
• Increasingly popular among
recreational drug users
• Internet sales
• Head shops/Smoke shops
• Promoted by discussion
boards – self studies
Armed with medical research and fueled by Chinese factories
And YouTube, a band of outlaws has
Created a dangerous multibillion-dollar industry
7/6/2015
3
Designer Drugs:
Where did they come from ?
A highly regarded Medicinal Chemist Dr. F. Ivy
Carroll and colleagues stated in a recent
publication:
Throughout the drug discovery process, pharmaceutical companies,
academic institutions, research institutions, and other organizations
publish their studies in scientific journals, books, and patents. This
information exchange, which is essential to the legitimate scientific
enterprise, can be, and is, used by clandestine chemists who duplicate
the technical sophistication used by the research community to
manufacture and market a seemingly endless variety of analogs of socalled designer drugs.
7/6/2015
4
Designer Drugs: Novel Psychoactive
Substances
•
Clandestinely produced to mimic the effects of a controlled
substance (a substance with an abuse potential)
•
Scientific literature excavated to identify substances
 No industrial or medical use for these substances
– Substances rejected due to poor therapeutic potential
– Characterization as being “research chemicals,” the only
research being undertaken is to their abuse liability and toxicity
•
Challenge
– Change public misperception as to legality and hazards
– Minimize appeal, a result of devious and aggressive marketing
7/6/2015
5
Synthetic Cannabinoids
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cannabinoids:
• A ‘‘cannabinoid’’ is a class of chemical compounds in the
marijuana plant that are structurally related.
• ‘‘Synthetic cannabinoids’’ are a large family of chemically
unrelated structures functionally (biologically) similar to THC,
the active principle of marijuana.
• They may have less, equivalent or more pharmacologic
(psychoactive) activity than THC.
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cannabinoids
• Synthetic Cannabinoids are sold in retail stores, on the
internet, and in “head shops” as “Herbal Incense” or
“Potpourri”
• Smoked alone or as a component of herbal products
• Abusers report a potent cannabis-like effect
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Adverse Health
Effects
Multiple deaths have
been connected to
the abuse of these
substances alone and
with other
substances on-board.
7/6/2015
Psychological
Anxiety, aggressive behavior,
agitation, confusion, dysphoria,
paranoia, agitation, irritation,
panic attacks, intense
hallucinations
Neurological
Seizures, loss of consciousness
Cardiovascular
Tachycardia, hypertension, chest
pain, cardiac ischemia
Metabolic
Hypokalemia, hyperglycemia
Gastrointestinal
Nausea, vomiting
Autonomic
Fever, mydriasis
Other
Conjunctivitis
9
Synthetic Cannabinoids
• Unregulated and unlicensed industry (many
manufacturers)
• Full disclosure of ingredients typically not present
• Batch to batch variance (i.e. “Hot Spots”)
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cathinones
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cathinones
• Structurally and pharmacologically similar to
amphetamine, Ecstasy (MDMA), cathinone, and other
related substances.
• Are central nervous system (CNS) stimulants and have
stimulant and psychoactive properties similar to schedule
I and II amphetamine type stimulants.
• Synthetic cathinones are sold in retail stores, on the
internet, and in “head shops” as “bath salts”, “plant
food”, or “jewelry cleaner”
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Adverse Health
Effects
Synthetic cathinone
users commonly
report cardiac,
psychiatric, and
neurological signs
and symptoms with
death.
7/6/2015
Cardiovascular
palpitations, tachycardia, chest pain,
vasoconstriction, my0cardial infarction
Psychological
Aggressive behavior, anger, anxiety, agitation,
auditory and visual hallucinations, depression,
dysphoria, empathy, euphoria, fatigue,
formication, increased energy, concentration,
panic attacks, paranoia, perceptual disorders,
restlessness, self-mutilation, suicidal ideation
Neurological
Seizures, tremor, dizziness, memory loss,
cerebral edema, headache, lightheadedness
Musculoskeletal
Arthralgia, extremity changes (coldness,
discoloration, numbness, tingling), muscular
tension, cramping
Gastrointestinal
Abdominal pain, anorexia, nausea, vomiting
Pulmonary
Shortness of breath
Ear Nose Throat
Dry mouth, nasal pain, tinnitus
13
Synthetic Cathinones
• Like the cannabinoids, unregulated and unlicensed industry
(many manufacturers)
• Full disclosure of ingredients typically not present
• Significant batch to batch variances “Hot Spots”
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Other Synthetic Compounds
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Categories
• 2C Series
– Category of phenethylamines
– Contain 2,5-dimethyoxy
• Piperazines
– Used as industrial chemicals
• Tryptamines
– Occur naturally in plant species
– Produced synthetically
• Arylcylohexamines
DEA Office of Diversion Control
2C Series: 25I-NBOMe & 25C-NBOMe
• Hallucinogens, abused orally
• Encountered on blotter paper
and in dropper bottles
• Possibly mistaken for LSD
• Linked to recent deaths
• “N-BOMB”, “Smiles”
7/6/2015
17
Piperazines
• Stimulant and
hallucinogenic properties
• Often referred to as
amphetamine-like
• Examples: BZP, TFMPP,
mCPP, and MeOPP
• Tableted
• BZP-TFMPP combination
abused to mimic the
effects of ecstasy
7/6/2015
18
Tryptamines
• Hallucinogenic
• “reality distorting”
• Powders, tablets, or blotter
paper
• Examples: 5-MeO-DALT, 5MeO-DIPT, AMT and many
more……
7/6/2015
19
Arylcylohexamines:
Methoxamine (MXE)
• Dissociative (mind altering
effects) and depression of
pain
H 3CO
NH
O
Methoxamine (MXE)
2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone
N
PCP
• Effects similar to PCP
• Encountered on designer
drug market
– International increase in
ketamine abuse
• Deaths attributed to the
substance
CBP Photo
7/6/2015
20
Arylcylohexamines:
Methylhexanamine (DMAA)
• Stimulant
• Encountered on designer
drug market as a cathinone
replacement. Also found on
the dietary supplement
market
• Deaths attributed to the
substance
• April 27th, FDA challenges
marketing of DMAA
products for lack of safety
evidence
7/6/2015
21
Problems with All Synthetic / Designer Drugs
 Marketed to teens and young adults
 Easily attainable in retail environments and via the internet
 Unknown ingredient(s)
 No consistency in manufacturing process
 Not tested for human consumption / Unknown short &
long term effects!!
 No known dosage – not FDA approved
 Synergistic effects likely when mixed with other drugs or alcohol
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Scope of the Problem
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Global Emergence of NPS
•
Of the nations surveyed, 87 % (70 out of 80)
indicate that NPS are available in their
respective drug markets.
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cannabinoid & Cathinone
Reporting to NFLIS
Year
2009
2010
NFLIS Reports
Number of substances from
structural class
Synthetic cannabinoids
23
2
Synthetic cathinones
26
4
3,285
19
729
10
Synthetic cannabinoids
22,989
39
Synthetic cathinones
6,772
21
Synthetic cannabinoids
32,504
51
Synthetic cathinones
11,275
31
Class
Synthetic cannabinoids
Synthetic cathinones
2011
2012
As of January 31, 2013
7/6/2015
25
Identified Synthetic Compounds in the U.S.
As of May 2, 2013, the NFLIS system shows U.S. law
enforcement encountering :
• 51 cannabinoids
• 31 cathinones
• 87 “other” compounds (i.e., 2C compounds,
tryptamines, piperazines, etc.)
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Synthetic Cannabinoids
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
A-796,260
AB-001
AKB48
AKB48 N-(5-FLUOROPENTYL)
AM-1220
AM-1241
AM-1248
AM-2201
AM-2201 N-(4-FLUOROPENTYL)
AM-2233
AM-679
AM-694
CB-13
CP 47,497
CP 47,497-C8-HOMOLOG
CP 47,497-C9-HOMOLOG
EAM-2201
HU-210
HU-308
JWH-015
JWH-018
JWH-018 ADAMANTYL CARBOXAMIDE
JWH-019
JWH-022
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
JWH-073
JWH-081
JWH-122
JWH-122 N-(4-PENTENYL) ANALOG
JWH-200
JWH-201
JWH-203
JWH-210
JWH-250
JWH-251
JWH-267
JWH-302
MAM-2201
RCS-4
RCS-4, C4 HOMOLOG
RCS-8
STS-135
UR-144
UR-144 N-(5-CHLOROPENTYL) ANALOG
URB597
URB602
URB754
XLR-11
NFLIS: 1/8/2013
Synthetic Cathinones
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
3,4-DMMC
3-MEC
4-FLUOROISOCATHINONE
4-MEC
4-MePPP
4-METHYLBUPHEDRONE
alpha-PBP
alpha-PVP
BUPHEDRONE
BUTYLONE
DIBUTYLONE
DIMETHYLONE
ETHYLCATHINONE
ETHYLONE
FLUOROMETHCATHINONE
•
•
•
•
•
•
•
•
•
•
•
•
•
•
ISOPENTEDRONE
MABP
MDPBP
MDPPP
MDPV
MEPHEDRONE
METHEDRONE
METHYLONE
MOPPP
MPHP
NAPYRONE
N-ETHYLBUPHEDRONE
PENTEDRONE
PENTYLONE
DEA Office of Diversion Control
NFLIS: 1/8/2013
2C/25 Series
•
•
•
•
•
•
•
•
•
•
2C-B
2C-B-Fly
2C-C
2C-D
2C-E
2C-G
2C-H
2C-I
2C-N
2C-P
•
•
•
•
•
•
•
•
•
•
2C-T-4
2C-T-7
2C-T-21
25B-NBOMe
25C-NBOMe
25D-NBOMe
25E-NBOMe
25G-NBOMe
25H-NBOMe
25I-NBOMe
DEA Office of Diversion Control
Piperazines
•
•
•
•
•
•
•
•
•
•
BZP
DBZP
mCPP
MBZP (1-methyl-4-benzylpiperazine)
2-MeOPP
4-MeOPP
MOPIP (1-(2-methoxyphenyl)-piperazine
TFMPP
pCPP
pFPP
DEA Office of Diversion Control
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Red = Controlled substance
Yellow = Positional isomer, controlled by definition
Green = Determined to be controlled substance analogue
Designer Drugs
Phenylalkylamines
Piperazines
Benzodiazepines
phenazepam
Benzylpiperazines
BZP
MDBP
4-Bromo-2,5diMeO-BZP
MBZP
MDBZP
Tryptamines
Arylcyclohexamines
Phenylpiperazine
s:
mCPP
TFMPP
MeOPP
pFPP
PCPR
PCMPA
PCMEA
PCEEA
PCEPA
5-MeOPCP
MXE
4-Me-PCP
3-MeOPCE
Dimethoxy derivatives:
b-Ketophenethylamines
Mephedrone
MDPV
Methylone
Ethylone
Butylone
Flephedrone
Methcathinone
Ethcathinone
bk-MDDMA
Naphyrone
4-MEC
4-EMC
a-PVP
4-MePPP
a-PBP
buphedrone
7/6/2015
D-Series-2,5dimethoxy-phenylpropanamines:
2,5-DMA
3,4-DMA
DOB
DOC
DOET
DOF
DOI
DOM
DON
DOPR
MDOB
2C Series – 2,5dimethoxyethanamine:
2C-B
2C-C
2C-D
2C-E
2C-H
2C-I
2C-N
2C-P
2C-T-2
2C-T-4
2C-T-7
2C-T-21
25I-NBOMe
Modified from Wohlfarth and Weinmann, Bioanalysis, 2010
Trimethoxy
derivatives:
3,4,5-TMA
TMA-2
TMA-3
TMA-4
TMA-5
TMA-6
AMT
DMT
DET
DPT
DBT
DiPT
MiPT
4-OH-DiPT
4-OH-MiPT
4-OH-MET
5-MeO-AMT
5-MeO-DMT
5-MeO-DiPT
5-MeO-MiPT
5-MeO-EiPT
5-AcO-DiPT
5-MeO-DPT
5-MeO-DALT
4-MTA
homologs
4-MTA
4-MTMA
4-MTEA
4-MTPA
4-MTBA
4-MTDMA
32
Ecgonine Derivatives
Anabolic agents
Synthetic Cannabinoids
4-Fluorotropacocaine
b-CFT
p-FBT
Classic
cannabinoids
HU-210
IP-751
Parahexyl
and many
others
Monomethoxy
derivatives
PMA
PMMA
N-ethyl-PMA
Cyclohexylphenols
CP-47,497
CP-47,497-C8
CP-55,950
Steroids:
THG
Many
examples
Indoles/Pyrro
les
JWH-018
AM2201
JWH-200
JWH-081
JWH-250
AM694
RCS-4
SR-18
UR-144
XLR11
Difurnanyl
compounds
Bromodragonfly
2C-B-fly
Eicosanoids:
Anandamide
Oleamide
Fluoro-containing
compounds
4-FA
3-FA
2-FA
N-Methyl-4-FA
N-Ethyl-4-FA
3-F-4-MeO-A
SARMs:
Andarine
LGD-2226
Mk-2866
Others
AKB48
URB597
CB-13
Others
MDDMA
Ethylamphetamine
N-OH-MDMA
MDDM
N,N-Dimethyl-1phenyl-2ethanamine
1-phenyl-2butylamine
MDA
32
Where are People Getting their
Information ? / Example: Erowid
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
“The Plant Feed Shop”
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
“PREMIUM BLEND HERBAL.COM”
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Public Safety Concerns
• Driving Under the Influence of Drugs (DUIDs) with
fatalities
• Suicides
• Homicide-Suicide
• Overdoses
– Emergency Department visits
– First Responders
• Drugs abused to evade drug screens
– 30-35% of juveniles in drug court tested positive
– Individuals subjected to routine drug screens
• Probationer / parolees
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
U.S. Synthetic Drug Abuse and
Prevention Act 2012
Cannabinoids
1)
2)
3)
4)
5)
6)
7)
AM2201
AM694
CP-47,497
CP-47,497 –
C8 homologue
JWH-018
JWH-073
JWH-081
DEA Office of Diversion Control
8)
9)
10)
11)
12)
13)
14)
15)
JWH-200
JWH-019
JWH-250
JWH-122
JWH-203
JWH-398
SR-19
SR-18
Cathinones
1)
2)
Mephedrone
MDPV
Phenethylamines
1)
2)
3)
4)
5)
6)
7)
8)
9)
2C–E
2C–D
2C–C
2C–I
2C–T–2
2C–T–4
2C–H
2C–N
2C–P
Why are these synthetic compounds
marketed the way they are (i.e. not for
“Human Consumption”)?
• Synthetic cannabinoids are sold as “potpourri” or “incense” products
at retail outlets and on the Internet
• Synthetic cathinones are sold as “bath salts”, “jewelry cleaner” and
“plant food” at retail outlets and on the Internet
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
The Controlled Substance Analogue Act
21 USC 813 – A Controlled Substance
Analogue, shall, to the extent intended
for human consumption, be treated for
the purposes for any Federal law as a
controlled substance in Schedule I
21 USC 802(32) – chemical structure is
substantially similar to a controlled
substance in schedule I or II and has a
similar pharmacologic effect.
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Operation “Log Jam” (July 2012)
Goals of Operation
 Target manufacturers, wholesale distributors, and retail
distributors
 Develop information about foreign sources of supply
 Raise public awareness
 Develop leads for Phase II initiative
• 66 State & Local LE and DEA Investigations
• 15 ICE/HSI Investigations
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Operation “Log Jam” (July 2012)
Results of Operation













97 Arrests
265 Search warrants
1,085 pounds raw synthetic cathinones
167,712 packets of synthetic cathinones
5.3 million packets of synthetic cannabinoids
1,909 pounds raw synthetic cannabinoids
10,487 pounds of treated plant material
48,253 pounds of untreated plant material
More than $40,000,000 US Currency/bank accounts
Vehicles/value 57/$1,973,500
Other Assets $5,688,500
47 Firearms
1096 gallons of acetone seized
U.S. Drug Enforcement Administration / Operations
Division / Office of Diversion Control
Opioids for Chronic
Non-cancer Pain
Increased
Prescribing
of Opioids
Increased
Abuse of
Opioids
Pharmaceutical
Marketing
National Crisis
Opioids
• Derived from the opium poppy (or synthetic
versions of it) and used for pain relief.
• Examples include hydrocodone (Vicodin®),
oxycodone (OxyContin®, Percocet®), fentanyl
(Duragesic®, Fentora®), methadone, and
codeine.
Myth # 1
• Opioids have been proven safe and effective for
chronic, non-cancer pain.
• Fact: Opioid treatment for chronic, non-cancer
pain has never been proven safe or effective.
Myth # 2
*
• Addiction is rare when patients with legitimate
pain receive long-term treatment with opioids.
• Fact: addiction is extremely common in patients
receiving long-term opioids for CNCP(25%).
Myth #3
• Opioid therapy can be easily discontinued
• Fact: No drug that has an addiction rate of 25%
can be easily discontinued!
• If this statement were true, the death rate would
not be increasing!
Myth # 4
• Effective chronic pain treatment is impossible
without opioids.
• Fact: chronic pain treatment is almost always
made worse by opioids!
The prescription drug crisis is the
result of prescriptions!
Per Capita Opioid Sales in
Morphine Equivalents
96 mg per
person
1997
700 mg
per person
2007
600%
increase
100mg/day is high dose opioid therapy
(DEA, ARCOS Report, 2009)
Deaths: Prescription
Opioid Related
2,000
deaths
1998
14,800
deaths
2008
(CDC Vital Signs, November 2011)
*
600%
increase
Unintentional Drug Overdose Death Rate in
United States 1970-2007
*
37, 485 drug overdose deaths in 2009
Heroin
Cocaine
Compare to heroin and cocaine epidemics in the 70s and 80s
2010 Opioid Deaths:
For every opioid overdose death in 2010
9 treatment admissions2
35 ER visits3
161 people with drug abuse or addiction4
461 nonmedical users of opioids4
(CDC MMWR, January 13, 2012)
*
Marijuana as Medicine
Policing the “Doctors”
ASAM
American Society of Addiction Medicine
• THE national organization of physicians
specializing in addiction medicine including
research, prevention and treatment
• Uniquely qualified to make recommendations
concerning treatments for addiction and policies
for drugs that are abused, including marijuana
ASAM Public Policy Statement on Medical
Marijuana
• ASAM asserts that cannabis, cannabis-based products,
and cannabis delivery devices should be subject to the
same standards that are applicable to other
prescription medications and medical devices
• ASAM asserts that products should not be distributed
or used unless and until they have received marketing
approval by the Food and Drug Administration (FDA)
(ASAM, 2010)
ASAM Public Policy Statement
• ASAM rejects approval of medicines through
States and local ballot initiatives
• ASAM recommends its members and other
physician organizations reject responsibility for
providing access to cannabis and cannabis-based
products until they receive FDA approval
(ASAM, 2010)
Bypassing the FDA Process
Before FDAapproves a drug as medicine, testing is done to:
Determine the
benefits and risks
of the drug
Determine how it
may interact with
other drugs
Determine the
appropriate
dosage levels
Identify and
monitor side
effects
59
Assure
standardization
of the drug
Identify safe
drug
administrati
on
Data from states reporting indicates that although pushed for HIV, cancer
& glaucoma, reality is most are using for undefined “pain’
(Due to some users reporting in multiple categories, columns may total more than 100%)
60
California data is insufficient to determine
what is being treated
• There is no requirement for users
to register so it is unknown how
many are using medical marijuana
but estimates are 300,000-400,000
statewide
• There is no statewide database on
users
• The most solid data is in San
Diego
 98% are treating “pain”
 2% are treating AIDS, cancer
and/or glaucoma
 12% of users are under 21
Pain
AIDS
cancer
glaucoma
61
Compassionate care or
increased access to marijuana?
>80%
•Most card holders in
CA and CO are white
men between the
ages of 17 and 35
•No history of
chronic illness
•History of Alcohol
and Drug Use
62
Marijuana
• The number and percentage of persons aged 12 or
older who were current marijuana users in 2011
were 18.1 million or 7% - similar to 2009 and 2010
rates, but higher than those in 2002 through 2008.
• From the late 1990s until the mid-2000s
marijuana use by adolescents (8th – 12th graders)
declined, however they started to rise again
in 2006.
• In 2012, 22.9% of 12th graders used marijuana in
64
the past month – an increase
from 18.8% in 2007.
65
Marijuana and Kids
The adolescent brain is especially
susceptible to marijuana use.
That means that when kids use, they have a
greater chance of addiction since their
brains are being primed.
66
More Drug Use Means More
Problems
Heavy Marijuana Use Lowers IQ1
• A recent study found that those who used cannabis
heavily in their teens and continued through
adulthood showed a permanent drop in IQ of 8 points.
• A loss of 8 IQ points could drop a person of
average intelligence into the lowest third of the
intelligence range.
1M.H.
Meier, Avshalom Caspi, et al. 2012. “Persistent cannabis users show
67 neuropsychological decline from childhood to midlife.”
Proceedings of the National Academy of Sciences
“If Only We Treated It Like Alcohol…”
2.7 million
847,000
Arrests for alcohol-related crimes in
2008
(Does NOT include violence;
Includes violations of liquor laws and
driving under the influence)
Marijuana-related arrests in
2008
68
Kevin A. Sabet, Ph.D., www.kevinsabet.com
Alcohol & Tobacco
Money Makers or Dollar Drainers
Alcohol
Costs
Tobacco
$200
billion
$185
billion
$25
billion
Revenues $14
billion
69
Kevin A. Sabet, Ph.D., www.kevinsabet.com