designer drugs – what you need to know the fundamentals

Designer Drugs – What You Need to Know

The Fundamentals

By: Paul L. CaryToxicology LaboratoryUniversity of Missouri

March 1, 2011 DEA “Banned” Five Synthetic Cannabinoids

synthetic cannabinoids covered under the DEAsynthetic cannabinoids covered under the DEA’’s new rule includes the following:s new rule includes the following: JWH-018 *JWH-018 * JWH-073 *JWH-073 * JWH-200JWH-200 CP-47,497CP-47,497 CP-47,497 (C-8 homologue)CP-47,497 (C-8 homologue)

On October 21, 2011, the Drug Enforcement Administration (DEA)

“banned” three synthetic cathinones by placing them into Schedule I of the Controlled Substances Act (CSA)

mephedrone mephedrone 3,4 methylenedioxypyrovalerone 3,4 methylenedioxypyrovalerone

(MDPV)(MDPV) methylonemethylone

Bath Salts

DEA Actions:

DEA took action - imminent hazard to the public DEA took action - imminent hazard to the public safetysafety

imposes criminal sanctions and regulatory imposes criminal sanctions and regulatory controls of Schedule I substances under the CSA controls of Schedule I substances under the CSA

covers the manufacture, distribution, possession, covers the manufacture, distribution, possession, importation, and exportationimportation, and exportation

RAMIFICATIONS?RAMIFICATIONS?

The Story of Designer Drugs

Designer Drugs:

drugs, which are created (or drugs, which are created (or reformulated, if the drug already reformulated, if the drug already existed) to get around existing existed) to get around existing drug laws (CSA), usually by drug laws (CSA), usually by modifying the molecular modifying the molecular structures of existing drugs to structures of existing drugs to varying degreesvarying degrees

An agonist is a chemical that binds to a receptor and triggers a

response – often mimicking the action of a naturally occurring

substance.ReceptorDrug (agonist)

Why Change the Key?• prolong the effect of the prolong the effect of the

drugdrug• increase the potency of the increase the potency of the

drugdrug• ““selectselect”” the desired effect the desired effect• make the drug more difficult make the drug more difficult

to detectto detect• avoid patent infringementavoid patent infringement• make an illegal drug make an illegal drug ““legallegal””

Spice/K2 and Synthetic

Cannabinoids

Preparation of the “incense”: botanicals are sprayed with liquid botanicals are sprayed with liquid

preparations of:preparations of: HU-210HU-210 HU-211HU-211 CP 47,497CP 47,497 JWH-018JWH-018 JWH-073JWH-073

Origins of Synthetic Cannabinoids

HU-210 & HU-211 - synthesized at HU-210 & HU-211 - synthesized at Hebrew Hebrew UniversityUniversity, Israel in 1988. HU-210 is an anti-, Israel in 1988. HU-210 is an anti-inflammatory; HU-211 as an anesthetic inflammatory; HU-211 as an anesthetic

CP 47,497 - developed by Pfizer in 1980 as an CP 47,497 - developed by Pfizer in 1980 as an analgesicanalgesic

JWH-018 & JWH-073 - synthesize by a researcher at JWH-018 & JWH-073 - synthesize by a researcher at Clemson (1995) for use in THC receptor research - Clemson (1995) for use in THC receptor research - John W. HuffmanJohn W. Huffman

more than 100 different synthetic cannabinoids more than 100 different synthetic cannabinoids have been createdhave been created

Smoking Cannabinoids

BG: motor control, learningBG: motor control, learning Hippo: memory, spatial Hippo: memory, spatial

navigationnavigation CB: cognitive functions - CB: cognitive functions -

attention, language, attention, language, emotionsemotions

What does CBWhat does CB11 receptor receptor control?control?

Pharmacological Effects of Synthetic Cannabinoids are Similar to THC

increase heart rate & blood pressure altered state of consciousness mild euphoria and relaxation perceptual alterations (time distortion) intensification of sensory experiences pronounced cognitive effects impaired short-term memory reduction in motor skill acuity increase in reaction times

Public Perception of “Legal Highs”

Synthetic cannabinoids Synthetic cannabinoids are as safe as marijuana.are as safe as marijuana.

Forensic Science Review Volume: Twenty-Six

Number OneJanuary 2014

25 pages

Synthetic Cannabinoids: Physical Effects

kidney damage (XLR-11) pulmonary effects (lung dysfunction) cardiovascular issues (tachycardia), increases in

blood pressure GI problems (pain, nausea, vomiting) seizures (6 cases) chemically-induced psychosis ** DUID (12 reported cases) ** three reported deaths (cardiac, suicide, OD)

More dangerous than we first thought?

Synthetic Cannabinoids: Physical Effects

kidney damage (XLR-11) pulmonary effects (lung dysfunction) cardiovascular issues (tachycardia), increases in

blood pressure GI problems (pain, nausea, vomiting) seizures (6 cases) chemically-induced psychosis ** DUID (12 reported cases) ** three reported deaths (cardiac, suicide, OD)

Evolutionary Landscape

appearing & disappearingappearing & disappearing whatwhat’’s popular today cycles out to be s popular today cycles out to be

replaced by new synthetic THC analogsreplaced by new synthetic THC analogs labs testing for common compounds a labs testing for common compounds a

few months ago may not be testing for few months ago may not be testing for same chemicals nowsame chemicals now

on-site, POC devices cannot keep pace on-site, POC devices cannot keep pace

Lab-Based Drug Testing (2010):

Lab-Based Drug Testing (2012):

Acknowledgment:

Dr. Barry LoganNational Medical ServicesWillow Grove, PA

July – December 2010

Prevalence – 2010

Oct 2011 – April 2012

Prevalence – 2012

Evolutionary Landscape

Ingenuity of Designer Chemists:

Drug Testing for Synthetic

Cannabinoids

Drug Testing – On-Site:

rapid, instant, POC testsrapid, instant, POC tests testing for JWH-018/JWH-073testing for JWH-018/JWH-073 cutoff 50-75 ng/mLcutoff 50-75 ng/mL lab testing - cutoff 0.5 ng/mLlab testing - cutoff 0.5 ng/mL false negativesfalse negatives

Drug Testing – Laboratory:

rapidly changing landscaperapidly changing landscape constantly updating menusconstantly updating menus lack of standardslack of standards some labs developing screening some labs developing screening

teststests not all lab-based testing is equalnot all lab-based testing is equal

Unresolved Issues of Concern: what synthetic compounds (or what synthetic compounds (or

metabolites) are being tested by these metabolites) are being tested by these laboratories?laboratories?

no standardized urine cutoff levelsno standardized urine cutoff levels no standardized methods (LC/MS/MS)no standardized methods (LC/MS/MS) tests detect metabolitestests detect metabolites no independent quality control no independent quality control

materialsmaterials no proficiency testingno proficiency testing detection window unknowndetection window unknown

More dangerous than we first thought?

Designer Stimulants (Novelty Powders)

Designer Stimulants:

bath salts/bath bubblesbath salts/bath bubbles plant foods/plant vitaminsplant foods/plant vitamins glass cleaners/pond glass cleaners/pond

cleanerscleaners soft drink additivesoft drink additive ““novelty collectors itemnovelty collectors item””

MDPV: Methylenedioxypyrovalerone (MDPV) - a Methylenedioxypyrovalerone (MDPV) - a

psychoactive drug with stimulant psychoactive drug with stimulant properties which acts as both a properties which acts as both a norepinephrine-dopamine reuptake norepinephrine-dopamine reuptake inhibitor (NDRI). inhibitor (NDRI).

often snorted - similar to cocaine often snorted - similar to cocaine considered extremely addictiveconsidered extremely addictive adverse medical/psychiatric ramificationsadverse medical/psychiatric ramifications

designer drug chemically similar to designer drug chemically similar to cathinonecathinone

first synthesized in 1929first synthesized in 1929 amphetamine-like propertiesamphetamine-like properties powerful synthetic stimulantpowerful synthetic stimulant adverse medical/psychiatric ramificationsadverse medical/psychiatric ramifications

Methylmethcathinone (Mephedrone)

DMAAMethylhexanamine

(1,3-dimethylamylamine)

February, 2014 - Bath Salt Data

Growth of Designer Drugs

WhatWhat’’s different today then in the s different today then in the 19701970’’s when the drug Ecstasy s when the drug Ecstasy (MDMA) was popularized?(MDMA) was popularized?

What has changed to fuel the rapid What has changed to fuel the rapid development and distribution of development and distribution of designer drugs? designer drugs?

3 billion users

The Internet!

Average 58 million

per day

1.2 billion users

What does the Internet offer?

improved accessibilityimproved accessibility increased affordabilityincreased affordabilityenhanced anonymity

Unfortunate Truisms:

legal controls that prohibit legal controls that prohibit designer drugs will always lag designer drugs will always lag behind their productionbehind their production

drug detection methods for the drug detection methods for the identification of designer drugs identification of designer drugs may also not be available when may also not be available when these compounds become these compounds become popularpopular

Legal Status of Control Strategies

Federal & State Law:Scheduled Drugs

Federal Analog Statutes

substantially chemically similarsubstantially chemically similar equivalent pharmacological activityequivalent pharmacological activity intended for human consumptionintended for human consumption

New Legal Approach: Deceptive Trade Practices ActDeceptive Trade Practices Act

false & misleadingfalse & misleading deceptive sales deceptive sales

rather that criminal chargesrather that criminal charges large civil monetary fineslarge civil monetary fines

Outlook for the 2014 and

Beyond

Trend lines?

Trend lines?

Trend lines?

Trend lines?

August, 2013

Two Web Sites You Need to

Know

www.erowid.org

www.designerdrugtrends.org

www.designerdrugtrends.org

email address:

carypl@health.missouri.edu