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Synthetic Drugs: Dangers, Detection, & Trends Presented by Problems & Challenges Posed by Spice/K Synthetic Drugs: Dangers, Detection, & Trends Presented by Problems & Challenges Posed by Spice/K 2, Bath Salts, Heroin, Painkillers, Oxy, Bup, etc. Vinnie Happ Redwood Toxicology Laboratory October, 2014

Drug Testing: Synthetic THC / K 2 n n n Rapid, onsite instant test Drug Testing: Synthetic THC / K 2 n n n Rapid, onsite instant test Laboratory-based screening test (becoming more widespread) Most Laboratories are employing LC/MS/MS technology Primarily via urine, however some labs can test via oral fluid and or blood $$$ varies greatly Onsite vs Laboratory testing is very different

On-site vs Laboratory testing for K 2 On-site K 2 test n JWH-018 & On-site vs Laboratory testing for K 2 On-site K 2 test n JWH-018 & JWH-073 primary strucuture n n n Laboratory K 2 test JWH-018, 073, plus *28 other synthetic cannabinoid structures: JWH-019, 081, 122, 200, 203, 210, 250, 398, AM 2201, MAM 2201, RCS 4, RCS 8, AM-694, AM-1248, AKB-48, UR -144, XLR-11, 5 -Fluro AB-PINACA, 5 -Fluoro ADBPINACA 5 -Fluoro ADBICA, 5 -Fluoro AKB-48, 5 -Fluoro PB-22, AB-PINACA, AB-FUBINACA, ADB-PINACA, ADBICA, PB-22, BB-22 n Cut-off 1 ng/ml or less Cut-off at 25 or 50 ngs/ml Higher threshold to trigger + Greater chance for false +/- n Detecting presence n Confirmatory technology Screening technology *Redwood Toxicology Laboratory

FAX CESAR September 8, 2014 Vol. 23, Issue 13 A Publication from the Center FAX CESAR September 8, 2014 Vol. 23, Issue 13 A Publication from the Center for Substance Abuse Research University of Maryland, College Park Study of Patients in a Midwestern Residential Treatment Program Finds 71% of Those Reporting Synthetic Cannabinoid Use Report Using to Avoid Positive Drug Test Self-Reported Reasons for Using Synthetic Cannabinoids (N=150 Adult Residential Substance Use Disorder Treatment Patients Reporting Lifetime Synthetic Cannabinoid Use) SOURCE: Adapted by CESAR from Bonar, E. E. , Ashrafioun, L. , and Ilgen, M. A, “Synthetic Cannabinoid Use Among Patients in Residential Substance Use Disorder Treatment: Prevalence, Motives, and Correlates, ” Drug and Alcohol Dependence, In Press, 2014. For more information, contact Erin Bonar at [email protected] umich. edu. 301 -405 -9770 (voice) 301 -403 -8342 (fax) [email protected] edu www. cesar. umd. edu The CESAR FAX is independently funded by CESAR and may be copied without permission. Please cite CESAR as the source.

MDPV (Methylenedioxypyrovalerone) n n n a psychoactive drug with powerful stimulant properties which acts MDPV (Methylenedioxypyrovalerone) n n n a psychoactive drug with powerful stimulant properties which acts as both a norepinephrine & dopamine reuptake inhibitor (NDRI). “A two for” usually snorted like cocaine duration of effect 2 -3 hours /adverse effect 6 -8 hrs MDPV - no history of FDA approved medical use adverse medical or psychiatric ramifications

Mephedrone (Methylmethcathinone) n n n amphetamine-like properties, powerful stimulant “rediscovered” by synthetic chemists in Mephedrone (Methylmethcathinone) n n n amphetamine-like properties, powerful stimulant “rediscovered” by synthetic chemists in 2003 reformulation of cathinone, a chemical found in the khat plant of Eastern Africa khat existence traced to 15 th C. Ethiopia khat is banned in the U. S.

Methylone (3, 4 -methylenedioxy-N-methylcathinone) n n n very similar to MDMA stimulant phenethylamine, amphetamine, Methylone (3, 4 -methylenedioxy-N-methylcathinone) n n n very similar to MDMA stimulant phenethylamine, amphetamine, and cathinone properties euphoria and increased sociability insomnia and restlessness hallucinations and psychosis

MDMA – Ecstasy / Molly • MDMA, was patented by Merck pharmaceuticals in 1912 MDMA – Ecstasy / Molly • MDMA, was patented by Merck pharmaceuticals in 1912 • Used in the 70/80’s as a psychotheraputic tool • Became popular “club drug” in 90’s then fell out of favor, too may additives. Come back in last couple of years • capsules sell for $8 to $40. • the most common Molly additives are bath salts, including methylone and mephedrone. • DEA's New York division highlighted the results of 143 lab tests over the past four years of substances suspected of being Molly. Only 13% of the drugs were MDMA, while 41% were 4 -MEC, and 20% were methylone (bath salt materials).

Pharmacological Effects of “Bath Salts” n n n n n increase heart rate & Pharmacological Effects of “Bath Salts” n n n n n increase heart rate & blood pressure pupil dilation, rapid speech hyperactivity, arousal, & over stimulation increased energy & motivation euphoria - agitation dizziness, nausea hallucinations, seizures, convulsions breathing difficulties!!! diminished perception of the requirement for food and sleep

Testing for Bath Salts? ? Yes! However: n n No on-site, rapid, instant tests Testing for Bath Salts? ? Yes! However: n n No on-site, rapid, instant tests No laboratory-based screening tests Laboratories employing GC/MS and LC/MS/MS technologies Detection times remain unknown

 Bath Salts and beyond!!! Expanded Synthetic Stimulant Panel α-PVP BZP Butylon Buphedrone Cathinone Bath Salts and beyond!!! Expanded Synthetic Stimulant Panel α-PVP BZP Butylon Buphedrone Cathinone Ethylone Flephedrone MBDB m. CPP MDA MDEA MDMA MDPV Mephedrone Methcathinone 4 -Methylethcathinone- (4 MEC) Methylone Pentedrone Pentylone Pyrrolidinopentiophenone TFMPP

CESAR FAX August 12, 2013 Vol. 22, Issue 32 A Weekly FAX from the CESAR FAX August 12, 2013 Vol. 22, Issue 32 A Weekly FAX from the Center for Substance Abuse Research University of Maryland, College Park Number of Calls to U. S. Poison Control Centers About Exposure to Synthetic Marijuana and Synthetic Cathinones Stable at Lower Levels Than Recent Years .

Narcotics / Opiate Family Opiates and Opioids: Heroin Morphine Codeine Hydrocodone - (Vicodin, Loratab, Narcotics / Opiate Family Opiates and Opioids: Heroin Morphine Codeine Hydrocodone - (Vicodin, Loratab, Zohydro. ER, Targiniq. ER) Hyrdomorphone - (Dilaudid) Oxycodone – (Oxy. Contin, Percocet, Roxicodone) Oxymorphone – (Opana, Opana. ER) Fentanyl Methadone Buprenorphine – (Suboxone) Tramadol – (Ultram)

- Philip Seymour Hoffman's heroin overdose exposes 100 percent RISE in 'epidemic' across US - Philip Seymour Hoffman's heroin overdose exposes 100 percent RISE in 'epidemic' across US since 2007 - More than 660, 000 Americans used heroin in 2012 - Resurgence attributed to crackdown on illegal 'pill mills' producing prescription drugs like Oxy. Contin, which gives same high as heroin - Pill addicts have turned to heroin because its cheaper and available - Popular in rural and suburban areas, not just inner city - Users buying single hits of heroin for as little as $4 - Drug cartels pushing ever-larger amounts across the Southwest border

New York hospital pharmacist charged in theft of 200, 000 pills JULY 9, 2014 New York hospital pharmacist charged in theft of 200, 000 pills JULY 9, 2014 Tuesday, June 8, 2014 photo shows Anthony D'Alessandro. The former pharmacy chief for Mount Sinai Beth Israel hospital in Manhattan allegedly stole nearly 200, 000 oxycodone pills from the medical center over more than five years. Prosecutors are still investigating what became of the drugs but believe the medications ended up on the thriving black market for prescription narcotics, where the more than 193, 000 missing pills could fetch a total of about $5. 6 million.

Ex-sheriff's wife released from prison early Jul 08, 2014 WAUSAU (WI) – A one-time Ex-sheriff's wife released from prison early Jul 08, 2014 WAUSAU (WI) – A one-time state probation agent and wife of a former Marathon County sheriff has been released from prison about seven months early, according to the state Department of Corrections. Last August, Kim Hoenisch, now 42, was sentenced to 18 months in prison and six years probation after she was convicted of three felonies -burglary, misconduct in office and possession of narcotic drugs - and two misdemeanors. Hoenisch was fired from her job after a state investigation concluded she had stolen prescription drugs, including Vicodin and oxycodone, from one of her clients.

One in Four Americans Admits Abusing Prescription Drugs, Says Find. Law. com Survey One One in Four Americans Admits Abusing Prescription Drugs, Says Find. Law. com Survey One in four Americans admits that they have abused prescription drugs, according to a new national survey by Find. Law. com, the most popular legal information website. EAGAN, Minn. , Aug. 5, 2014 - Prescription drug abuse involves taking a drug for reasons other than the drug's intended usage or use of a drug by someone other than the person listed on the prescription. The drug abuse can either be an attempt to self-medicate a medical condition, or for purposes such as getting high.

How bad is the painkiller prescription problem? ? How bad is the painkiller prescription problem? ?

FDA Toughens Warning on Pain Drugs Agency Cites Serious Risks Associated With Pills Such FDA Toughens Warning on Pain Drugs Agency Cites Serious Risks Associated With Pills Such as Oxy. Contin 
USA TODAY - September 10, 2013 The FDA said that long-acting forms of "opioid" painkillers, such as Oxy. Contin, should be used only when there is no alternative. The new drug label drops the word "moderate" and says it should be used only to manage "pain severe enough to require daily, around-the clock, long-term treatment. ” The new warnings only relate to extended-release forms of the drugs, which are often prescribed for months or years to treat chronic pain. They don't affect immediate-release forms, which include Vicodin or Percocet and are often used to treat acute pain, such as after surgery. The FDA is also considering whether to tighten restrictions on hydrocodone products like Vicodin.

Doctors urge FDA to reverse approval of Zohydro, controversial new pain drug The potent Doctors urge FDA to reverse approval of Zohydro, controversial new pain drug The potent drug has drawn widespread concern from addiction experts and state attorneys general, who fear it will fuel opioid abuse and overdose. FEBRUARY 28, 2014 REUTERS Zohydro. ER contains a higher dosage of pure hydrocodone than Vicodin. Unlike Vicodin, the drug does not contain aspirin or acetaminophen. Acetaminophen was removed because of liver-damage concerns. Zohydro's labeling will feature warnings about abuse, addiction and misuse. Zogenix is working on an abuse-deterrent version of Zohydro that should become available in three years March/April, 2014 Purdue Pharma announces & then submits NDA to FDA for its abuse-resistant, extended-release hydrocodone product. July 2, 2014 -- Zogenix, Inc. (ZGNX) today announced an update on its development programs focused on the introduction of abuse deterrent formulations of Zohydro(R) ER Application for Next Generation of Zohydro(R) ER to be filed by October 2014

Extended-Release Opioid Receives FDA Approval July 24, 2014 The Food and Drug Administration (FDA) Extended-Release Opioid Receives FDA Approval July 24, 2014 The Food and Drug Administration (FDA) announced its approval of Targiniq ER, an extended-release opioid combining the effects of oxycodone and a drug commonly used to reverse the effects of opioid overdose, known as naloxone. Purdue Pharma L. P. , which originally marketed a harder to crush version of their opioid Oxy. Contin in 2010, created Targiniq ER. When Targiniq ER is crushed and snorted, or dissolved and injected, the typical euphoric effects of oxycodone are blocked by naloxone.

Mexico Trades Marijuana for Heroin April 2014 -The Washington Post has printed a grim Mexico Trades Marijuana for Heroin April 2014 -The Washington Post has printed a grim exposé on the shift from Mexican marijuana to Mexican heroin. Mexican marijuana has dropped from $100 per kilogram to just $25 per kilogram. Said Rodrigo Silla, 50, a lifelong cannabis farmer. “I wish the Americans would stop with this legalization. ” The DEA paints a picture of shrewd Mexican cartels reacting to their cut in marijuana business by sowing more heroin addicts. DEA claims cartels send their heroin pushers to work in the cities with the worst prescription pill epidemics and have them “set up right outside the methadone clinics. ”

Heroin-fentanyl mix plaguing many states January 31, 2014 Pittsburgh Post-Gazette Heroin-fentanyl mix plaguing many states January 31, 2014 Pittsburgh Post-Gazette

Police: 2 dead after chewing on pain patches to get high July 2014 - Police: 2 dead after chewing on pain patches to get high July 2014 - Authorities in Athens, Tenn. , say two of three men who died Friday of apparent drug overdoses had misused the pain medication Fentanyl. Harold “Marty” Coleman, 48, of 1004 South Jackson Street, Athens, was found lying in the driveway at his mobile home. He had a pain patch in his mouth. Coleman had a prescription for the patches and other narcotics found inside the residence. While emergency medical officials were preparing to transport Coleman's body, authorities found 46 -year-old Donald Sturdivant in the laundry room of the home unconscious but breathing, the detective said. Sturdivant died a short time later after he was taken to the hospital.

Screening vs Confirmation testing of Opiates Typical Screening test n Primarily targets: Morphine/Codeine Confirmation Screening vs Confirmation testing of Opiates Typical Screening test n Primarily targets: Morphine/Codeine Confirmation Testing (GC/MS) n Morphine n Codeine n Hydrocodone n Hydromorphone n 6 -MAM (heroin marker) n Oxycodone Drugs not detected n Buprenorphine n Methadone n Fentanyl n Tramadol - Ultram n Soma

Opiate vs Oxycodone Screen why you should consider splitting them out when testing Opiate Opiate vs Oxycodone Screen why you should consider splitting them out when testing Opiate Screen @ 300 ng n Primarily targets morphine and codeine n Oxycodone – 30, 000 ng u u n Needed to trigger a positive Miss the chippers, O. O. U. Opana – Oxymorphone u 100, 000 ng needed to trigger positive on onsite Opiate test Oxycodone Screen @ 100 ng n Oxycodone – 100 ng u u n n Needed to trigger a positive Detect the chippers Will detect oxymorphone and hydrocodone if 1562 ngs Oxymorphone – Opana / ER u Oxycodone lab EIA screen has 100% cross reactivity to Oxymorphone

From: Tracy, Carrie Sent: Tuesday, August 05, 2014 11: 31 AM To: Happ, Vinnie From: Tracy, Carrie Sent: Tuesday, August 05, 2014 11: 31 AM To: Happ, Vinnie Subject: false positive question Hi Vinnie. Wondering if someone that is prescribed Vicodin and taking it regularly would all of the sudden test positive for Oxycodone on 3 occasions and then miraculously test negative for Oxycodone when confronted about possible use. Thanks. Carrie L. Tracy Senior Probation Officer

Take away comments n n If positive on an Opiate screening test – an Take away comments n n If positive on an Opiate screening test – an Opiate family member most likely detected Confirmation testing will specifically identify the member If 6 -AM (6 -Acetylmorphine) detected at the Lab: u heroin use If confirmed positive just for Morphine u metabolized heroine to morphine and or u morphine use i. e. from a prescription medication, u poppy seed use

Sharp rise in ER visits tied to abuse of sedative May 22, 2014 (Health. Sharp rise in ER visits tied to abuse of sedative May 22, 2014 (Health. Day News) -- There's been a steep increase in the number of Americans being treated at emergency departments for abuse of the sedative alprazolam, best known as Xanax. The number of emergency department visits related to abuse of climbed from more than 57, 000 in 2005 to nearly 124, 000 in 2011, according to the U. S. Substance Abuse and Mental Health Services Administration (SAMHSA). Xanax abuse "is especially concerning in light of the dramatic rise in nonmedical use of opioid painkillers like oxycodone [Oxy. Contin] and Vicodin, because these increases in nonmedical use parallel the rapid rise in accidental overdose deaths in our country, " Collins said.

Suboxone-Buprenorphine n n n FDA approved in 2002 used to treat opiate addiction alternative Suboxone-Buprenorphine n n n FDA approved in 2002 used to treat opiate addiction alternative to methadone partial agonist (ceiling) in pill, film, patch 2 mg & 8 mg doses will not test positive on an opiate test significant diversion contains naloxone- guard against misuse subutex – no naloxone individuals will get high on this stuff

What’s the attraction to Bup? n n n user’s experience euphoria effect if taken What’s the attraction to Bup? n n n user’s experience euphoria effect if taken in conjunction with other sedative drugs like alcohol, sleeping pill (ambien) or a benzodiazepine (klonopin)- extreme sedation, drowsiness, unconscious, or even death may occur method of ingestion – typically sublingual (under tongue), pill format going away, reports of snorting & injecting self medication and or currency in W/R or C/R setting only test positive if specifically testing for buprenorphine incredibly easy to smuggle

Endo and Bio. Delivery Sciences announce positive top-line results from the Phase III clinical Endo and Bio. Delivery Sciences announce positive top-line results from the Phase III clinical trial of BEMA® buprenorphine in opioid-experienced patients with chronic pain July 7, 2014 /PRNewswire/ -- Endo Pharmaceuticals Inc. and Bio. Delivery Sciences International, Inc. announced today positive top-line results from its pivotal Phase III efficacy study of BEMA buprenorphine in opioid-experienced patients. BEMA buprenorphine is being developed for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in both patients who are opioid naive and opioid experienced.

Top 17 Abused Prescription Drugs of 2013 Below is a list of 17 abused Top 17 Abused Prescription Drugs of 2013 Below is a list of 17 abused prescription drugs as listed by CDC, FDA, the U. S. Drug Enforcement Agency (DEA), and non-government nonprofit sources on public websites. Oxy. Contin- oxycodone Suboxone - buprenorphine Ambien - sedative Ritalin - stimulant Zoloft – antidepressant Lunesta -sedative Adderall -amphetamine Opana - oxymorphone Xanax - benzodiazepine Klonopin – benzodiazepine Fentora - fentanyl Percocet - oxycodone Ativan - benzodiazepine Soma - sedative Valium - benzodiazepine Vicodin -hydrocodone

July 2, 2014 SUMMARY With the issuance of this final rule, the Deputy Administrator July 2, 2014 SUMMARY With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration places the substance 2[(dimethylamino)methyl]-1 -(3 -methoxyphenyl)cyclohexanol (tramadol), including its salts, isomers, and salts of isomers, into schedule IV of the Controlled Substances Act.

Corrective measures in other States Corrective measures in other States

Emerging Drugs or Media Hype? ? Smiles, NBOMe, Krokodil, and Kratom Emerging Drugs or Media Hype? ? Smiles, NBOMe, Krokodil, and Kratom

(2 C-I) Nicknamed Smiles n n n n popular among teens, responsible for dozens (2 C-I) Nicknamed Smiles n n n n popular among teens, responsible for dozens of overdoses and deaths. white crystalline powder, typically snorted or ingested. high and effects can last a few hours to a few days a combination of MDMA and LSD, only more intense. 2 C-I is being made by dealers and “hobbyists, ” chemicals can be obtained over the internet 2 C-I overdoses can cause seizures, kidney failure, and fatally high blood pressure.

NBOMe – Synthetic LSD BRAND NAMES 2 C-C-NBOMe = (25 C-NBOMe; NBOMe-2 C-C); 2 NBOMe – Synthetic LSD BRAND NAMES 2 C-C-NBOMe = (25 C-NBOMe; NBOMe-2 C-C); 2 C-I-NBOMEe = (25 I-NBOMe; NBOMe-2 C-I); EFFECTS CLASSIFICATION Psychedelic; Stimulant; Euphoriant DESCRIPTION The NBOMe series of chemicals are primarily N-o-methoxybenzyl analogs of the 2 CX family of phenethylamines, and are (serotonin 2 A) receptor agonists. This group are active at very low sub-milligram doses. These chemicals have nearly no history of human use prior to 2010 when they first became available online. DEA declared three N-bomb variants— 25 I-NBOMe, 25 C-NBOMe and 25 B-NBOMe to be illegal Schedule I drugs under the Controlled Substances Act.

Pharmacological Effects n n n n Dilated pupils Sweating Dry mouth Rapid speech Rapid/frequent Pharmacological Effects n n n n Dilated pupils Sweating Dry mouth Rapid speech Rapid/frequent mood swings Hyperactivity/ Elevated BP Hair standing on end Nasal passage irritation

Behind the Krokodil Panic Nov 7, 2013 - The Daily Beast Relax! The home-brewed Behind the Krokodil Panic Nov 7, 2013 - The Daily Beast Relax! The home-brewed Russian drug isn’t invading America. Cases popped up in at least six states and the media went wild. But here’s the catch: not one of the dozens of suspected cases tested positive for desomorphine, the drug's official name. In fact, according to public-health experts and federal officials, the great Krokodil scare of 2013 is really just the latest symptom of a true epidemic long in the making: American’s growing dependence on heroin and prescription painkillers. The drug, a morphine analogue that acts similarly to heroin but with a shorter high, is made by combining codeine, paint thinner, and lighter fluid (among other things) in small batches. An April 2013 article from the International Journal of Drug Policy titled “Breaking Worse” explains the dangers of the homemade drug. “Desomorphine may be the opioid that the cooks intend to produce, but it is not what they necessarily end up with, ” the article reads. The “bootleg chemistry” results in a drug that is notoriously impure and often contains a lethal mix of toxins. But for American’s who can buy heroin much more easily than they can codeine, Krokodil use just doesn’t make sense.

OP/ED 1/10/2014 Forbes Krokodil Crock: How Rumors Of A 'Flesh-Eating Zombie Drug' Swept The OP/ED 1/10/2014 Forbes Krokodil Crock: How Rumors Of A 'Flesh-Eating Zombie Drug' Swept The Nation “A lot of people want to call it a trend, but we’re not seeing it, ” says Joseph Moses, a spokesman for the Drug Enforcement Administration (DEA). In fact, Moses says, “I’m not aware of any forensic laboratory that has come up with a desomorphine sample. A report by two St. Louis doctors who claimed to have treated a man with krokodil-related symptoms, published online by The American Journal of Medicine in November 2013, was removed from the journal’s website a week later after the paper received strong scientific criticism NMS Labs had approximately forty toxicology cases of suspected Krokodil from around the US submitted in the last six months. All have been negative. “To our knowledge there is not a single confirmed Krokodil death through either toxicological testing or through testing of associated paraphernalia, in the US. ”

KRATOM n n not a synthetic but a plant derived drug main alkaloids responsible KRATOM n n not a synthetic but a plant derived drug main alkaloids responsible for the effect are mitragynine and 7 -hydroxymitragynine. at low doses causes a stimulating effect at high concentrations causes an opiate like sedative effect

From the website: buykratom. us Your Price: $14. 99 This is our newest addition From the website: buykratom. us Your Price: $14. 99 This is our newest addition and we are very excited about offering another Bali'esque type strain. This strain is harvested from the Kalimantan Region, using only mature leaves and then finely ground. You must be 18 years of age to purchase any products on the website. All products on the website are sold not for human consumption, and are for incense or ethnobotanical research purposes only.

Kratom Products: The Best Option to Wean Off Opiate and Heroin Addiction June 11, Kratom Products: The Best Option to Wean Off Opiate and Heroin Addiction June 11, 2014 Livermore, CA – To clarify the majority’s misconceptions on kratom (Mitragyna Speciosa), it is not an opiate. It is not a drug, and it does not give that high that one is getting from heroin. Kratom soothes the “needy” receptors, easing through natural stimulation back into a more balanced state. The use of kratom for opiate withdrawal began to appear in 1987, when Henry Nicholas Ridley published the book “Malay Plant Names” and stated that the plant can be used to wean opium addicts. Nowadays, kratom is often used in methadone detox programs. Hospitals like the National Institute of Thai Traditional Medicine in Bangkok are endorsing kratom as a course of action against drug addiction withdrawal. Recent research points to the plant’s alkaloids, 7 -hydroxymitragynine as possibly the major agonist accountable for soothing withdrawing receptors.

Erowid. org “Documenting the complex relationships between humans and psychoactives” n n n Great Erowid. org “Documenting the complex relationships between humans and psychoactives” n n n Great resource for information Take with a grain of salt Your clients are probably aware of this site as well

Thank you for your time. Vinnie Happ - vhapp@redwoodtoxicology. com Thank you for your time. Vinnie Happ - [email protected] com