New Emerging Psychoactive Drugs

Lisa Marzilli, PharmD, CDOE
Clinical Pharmacist
Research and Education
Synthetic Cannabinoids (SC)
• Stimulants
•
•Natural khat plant
•Synthetic
• Bath Salts/Ivory Wave
• Psychedelic stimulants (2CE, 2CB, 2CI…)
Salvia
• Kratom
• Various other chemicals/substances
•
1
Designer drug is a term used to describe drugs which are created in order to get around existing laws by:
 Modifying the molecular structures of existing drugs
 Developing drugs with entirely different chemical structures that produce similar effects to illegal recreational drugs
Quest for ‘Legal High’ Chemists Outfox Law, Wall Street Journal
Original
Modified
Legal
• Ritalin™
• (methylphenidate)
Ritalin™
• Nopaine
• (ethylphenidate)
• “Nopaine‐‐‐every bit as good as actual cocaine” says Mr. Llewellyn
Nopaine
2
Spice, K2, Genie, Yucatan Fire, Spice Gold, Plant food

Mixture of herbal plant products, sprayed with synthetic cannabinoids
◦ Sold as aromatic incense, potpourri, plant food…”smoking blend”
◦ Often contaminated with unidentified toxic ◦ “Natural” →››› misconception of safety

Marketing
◦ Similar in appearance to marijuana
◦ Sold in variety of colors/flavors ◦ $30‐45 per 3Gm 3


Compounds developed for research
◦ Efforts to separate psychoactive & therapeutic effects
◦ CB1 vs. CB2
◦ JWH‐018 & JWH‐073
THERE ARE OVER 100
KNOWN SYNTHETIC
◦ JWH‐250, CP‐47, 497
CANNABINOIDS
◦ HU‐210
Dr. John W. Huffman, Clemson University professor, synthesized many novel cannabinoids as part of research for National Institute for Drug Abuse (NIDA) on endogenous cannabinoid receptors‐‐‐‐had never been tested on humans, nor approved by FDA

Shipped in from China, Asia

Dosing the plant material
◦ May result in “hot spots” or inconsistencies
4
•
Similar euphoric high as THC
• Higher affinity for receptor
•Duration of action 6‐12hr??
•Detection times blood/urine ??
•
FAR MORE toxic than phytocannabinoids
•Since 2010, estimated 6,000 ER visits per year and climbing!!
◦ Unknown ingredients added to mixture
over time………
Cannabinoid Adulteration
5
Number of Exposures Per Year
Synthetic Marijuana Exposure Cases Per Year
6968
5228
4377
3682
2915
2010
2668
2011
2012
2013
2014
2015
(July 6, 2015)
• July 2012 – President signs Synthetic Drug Abuse Prevention Act of 2012 into law; 15 specific molecules
•May 2013 • DEA emergency scheduled 3 new molecules
UR‐144, XLR11, and AKB48
•Feb 2014
• 4 compounds added as Schedule I……
6
As substances are added to Schedule I and “bans” implemented….
How Do Sales continue????
7
8
•
Life threatening issues
• Supportive measures
• Stabilize organ function
•
Acute anxiety reaction
• Talk‐down technique
• HPPD or Hallucinogen Persisting Perception Disorder
• Use of clonazepam
•
Marijuana like reaction
• Physical and emotional dependence
• Physical w/d‐‐‐‐ sleep & appetite disturbance, HA, irritability, anxiety, depression, muscle discomfort
Bath Salts, Ivory Wave, Plant Food, Cloud 9, MTV, Super Coke
•
Synthetic stimulants (SS)
• Modeled after natural plant product, Khat
• MDPV (methylene‐dioxy‐pyro‐valerone)
• Mephedrone (MMC, MCAT, Meow‐meow)
• Methylone
• Similar molecular structure to amphetamines
•
Product labeling • “Not for human consumption”
loop hole to Federal analog Act
• Cost $20‐30 per packet
9
Chemical Structures

Production
◦ Illicit laboratories
 Bulk packaging (powder) imported from China and Asia
 Packages are often mislabeled to pass Customs

Warehouse distribution centers in USA, product “cut”
◦ ↑ effects vs. plant
↑ potency, ↑ ↑ ↑ ill effects

Route of ingestion
◦ Snorting most common
◦ Can be smoked or swallowed
10
•
Pharmacology
• NE/DA reuptake inhibitor
• Duration: 6‐8hrs…24hr?
•
Effects
• Rush, ↑ HR/BP
• ↑ energy, insomnia
• Hallucination, psychosis
• Violent behavior
• Seizure, kidney failure → death • Permanent neuronal damage?
Indigenous to East Africa
◦ Catha edulis bush, referred to as“African Salad”
 Harvested all year  Centuries of traditional use ◦ Captain Phillips movie starring Tom Hanks and others depict use
11
Main Constituents: cathinone, cathine
Ingested via:
 Chew
 Extracted for tincture, teas
 Crystallized and smoked


CNS stimulant, similar to methamphetamine & MDMA (Ecstasy)
MDMA
White to light brown crumbly powder
MDPV
May cause seizures, panic attacks, or psychosis
12
•
•
•
MMC, MCAT, Meow‐meow, Drone, Plant Food
Synthetic derivative amphetamine/cathinone
Jan 2010 most popular “club drug” UK
Methylone (bk-MDMA)
Ecstasy (MDMA)
Note: Molly of late 1990’s and early 2000 MDMA
Molly of 2006 contained BZP/TFMPP stimulants
Many current Molly products contain methylone,
other cathinones--- cheaper to produce
13

Gravel, Flakka

$5 or less a vial

Reports‐ surge in FL, Feb 2015
alpha-PVP
MDPV
•
Primary concerns •Lethality
•Not detectable with routine drug screens
•
Medical treatment
•Restraints, intravenous benzos for seizures
•High dose iv sedatives (2+2 lorazepam/haloperidol) •Fluids and assess for rhabdomyolysis
•Monitor and treat morbid hyperthermia promptly
14
Synthetic Cathinone Exposure Per Year
Number of Exposures
6137
2691
995
2011

2012
2013
582
2014
267
2015
(June 30, 2015)
DEA temporary ban Sept 8, 2011
o Scheduled I as of Oct 8, 2011
MDPV, Mephedrone, Methylone

Synthetic Drug Abuse Prevention Act of 2012
o Bans 31 specific compounds
oOnly included 3 synthetic stimulant
o 9 hallucinogenic compounds, 18 synthetic cannabinoids
o Conviction/penalties for sale or possession‐punishable for up to 20yrs in prison
15
•
“Cosmic Blast” or naphyrone
• Derived from pyrovalerone • Currently very little data on safety/toxicity
•
Pentedrone
• Related to pyrovalerone and mephedrone
• No reliable information as yet
•
•
3‐Flouromethcathinone4‐Fluoromethcathinone
Other common “street names”
• Jewelry Cleaner, Glass Cleaner
• Pump‐It Powder
• Plant Food….
Cathinone Adulteration
16
Other Stimulants of Concern…

Phenethylamine hallucinogens
◦ Amphetamine‐like PLUS
 Psychedelic activity
 Hallucinations
 Paranoia
◦ 2CB, 2CI, 2CT, 2CE, Bromo‐
DragonFLY
◦ Marketed as Eros, Nexus, Smiles…
17
Chemical Name
Street Name
2C‐T‐7
Tripstasy, Blue Mystic
2C‐B
Nexus
2C‐I
Smiles (also 2C‐E, ‐I, 25‐I & 25b‐Nbome)
5‐methoxy diisopropyltryptamine
Foxy, Methoxy
Alpha methyltryptamine
Spirals
N‐benxylpiperazine
BZP
Dimethyltryptamine
DMT
Bromobenzodifuranylpropylamine
Bromo‐DragonFly
COMMON & BRAND NAMES
The Bomb, N‐Bomb, NBOMe, 25’s
Blotters are placed between the gums and cheek, one on top and one on the bottom lip
Powder form is often snorted
DEA Report Jan 2011‐ Aug 2015
43 states 4,680 usage/incidence reports
18
19
Indigenous to Mexico
Diviner’s Sage



Used for centuries in healing rituals
Mazatec Indian Shamans
Kappa‐opioid receptor agonist
Partial agonist dopamine receptor (D2)
Hallucinogen
◦ Psychotomimetic, dysphoric
◦ Fast onset, duration 30‐60min (user experience days ‐‐‐ weeks)
◦ No activity 5‐HT2A serotonin receptor (site of action LSD)
Low risk dependence, low toxicity
20



Laughter, evokes childhood memories
Sensation of motion, merging, overlapping realities
S‐A‐L‐V‐I‐A
ubtle effects, relaxation
ltered perception ight, colors
ivid visionary states, “encapsulation”
mmaterial existence, dissociation
mnesia

A Drug Enforcement Administration study is still pending to determine the 8 point criteria to place Salvia on the Federal Controlled Substance Act
o Salvia is illegal in 27 States and US Military
o Controlled in some manner in Australia, Belgium, Canada, Finland, and Italy
21
Kakuam, Ithang, Thom, Kekum
Kratom is a tropical tree indigenous to
Thailand, Malaysia, and other areas of
South East Asia

Botanical Classification
◦ Genus : Mitragyna
◦ Species : speciosa
◦ Coffee in species!!
◦ Active compounds:7-hydroxymitragynine, speciogynine

Description
◦ Leaves contain MG (SG) and are chewed as an opiate substitute and stimulant in Thailand and South‐East Asia, primarily among the working class
◦ Relatively long history of human use
22
•
Stimulant effects at low dose
• Yohimbe‐like effect
• Increased alertness, physical energy, talkative and sociable • Similar effect as 1‐2 cups of coffee
•
Mu‐opioid receptor agonist
• Analgesia, euphoria, cough suppression
• CNS depressant ≡ sedation
• Quick onset and lasts ~ 1‐3hr
• Similar side effects as other opioids
•Opioid‐like, full physical addiction

Sold ◦ Raw or crushed leaves
•Various commercial concentrations 15X ‐‐‐‐ 250x extracts


Ingestion
◦ Chew; extract and brew tea or tincture
◦ Heat decreases potency so usually not smoke
Potencies and strains vary
◦ $15 to $50 per five‐gram packet
◦ $18 to $25 for about 50 capsules
◦ Doses generally 2‐10 grams.
23
Alleged 15X Concentrated
mitragynine and
7-hydroxymitragynine
extracted from Kratom leaves
24


•
Kratom is not controlled under the Controlled Substances Act, but considered an herbal drug of abuse
Banned in Thailand, Malaysia, other areas
“Dirty” cousin of morphine
• Khanka, tar‐like substance
• Desmorphine produced from codeine and
mixed w gasoline, paint thinner, ioidine, oils..…
• “Recipes” posted on web
•
Epidemic in Russia
• Seize rate ↑↑↑ 23‐fold 2009‐present
•
Few user’s survive 2 years
• Rotting at injection site, gangrene, amputation
• Significant and prompt jaw degeneration
25
Used for sedation, anesthesia, and muscle relaxation in horse and cattle
• Prevalent use in Puerto Rico
• Combination use
•
• Cocaine speedball
• “Cut” heroin
•
Ingestion
• IV
• Insufflation
•
May have severe cardiac effects
Human or Animal excrement
fermented to methane gas said
to be a ~ psychedelic?
26
•
Hallucinogens
• Psilocybin
• “Shrums”
• Disrupts natural functioning of SE system
•
Dissociatives
• DXM, Robo‐ ataxia, slurred speech
How many mgs of DXM are in 4oz Robitussin? 360 mg
• PCP‐ paranoia, aggression, hallucination
• Ketamine
• Diverted from hospital and veterinary stock rooms abused as a dissociative/psychedelic
• Dissociative anesthetic
Baker’s Brew
27
Banned in many States, new replacement is
Vapotini at Hookah Bars
Images from KCTV via New York Times
and Nub TV via YouTube Videos
28
Approved by U.S. Alcohol and Tobacco tax
and Trade Bureau in early 2014 but rescinded
its approval on 4/21/14
Alcohol Extraction
“Ear Wax” or Wax
Butane Extraction or
CO2 Extraction
“Honey Oil”
Cold Water Extraction
29
• Contain higher percent of THC
• Use some type of solvent to extract THC
1. CO2---$$$ safer
2. Butane---$ dangerous
• Not all solvent is removed
Wax
• Whipping hash oil
during purging process
• Easier to manipulate
Oil
• Sticky like honey
• Used in “vape pens”
30
Shatter
•
•
•
•
Refined version of Hash Oil
Pressure vacuum utilized
Semi-transparent
Yellow or amber color
Dab
• Technique for consuming
concentrates
• Place “dab” on heated
surface
• Inhale the vapors
• ↑ 90% THC
New Age Vape Products
31
•
Erowid (.org)
•
Grasscity (.com)
•
Psychonaut (.com)
•
Shoomery (.org)
•
Spice University (.org)
[email protected]
32