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Welcome to a discussion of SYNTHETIC DRUGS, synthetic drug culture and some of the unique problems Teens bring with themYour local resources:

Dr. Thomas Walters, MD, Medical Director

Don Hassett, MA, CASAC, CPP, Director of Prevention

CASA Council on Alcohol and Substance Abuse of Livingston CountySources:We gratefully acknowledge the following institutions and sources: NFLIS, National Forensic Laboratory Information SystemDEAUpstate New York Poison Center NCADD, Rochester DAWN Drug Abuse Warning Network

With specific public material originally developed by: Upstate New York Poison CenterClinical ToxicologistAlexander Garrard, PharmDBATH SALTS/HERBAL INCENSESpice/K-2,K-3 Issue: Language -With the hundreds of new drugs (or are they chemicals) of abuse in use in various regions of this and other countries we will mostly be looking at these 2 categories of mind altering substances, as teens understand them:andThe remarketing via street names is already changing and expanding even this basic classification.Note: At the end of this presentation you will find a comprehensive list of chemical names along with their sexy street names , understand that the formulations will continually change.We will cover:Synthetics specifically, spice & bath saltsTheir originsChemical make up & derivationsPrevention and management Issues relevant to:language & terminologydrug puritycultural appeal for teensa couple of Case presentation, managementRegional to NY, varieties & namesHow synthetics fit teen cultureHow they fit into the addiction paradigm Do we know enough to judge how addictive these chemicals are?Does addictiveness depend on social & genetic factors?Some of the grass roots marketing strategy

Handouts: # 1 drug street names;#2 packaging & pictures; #3 simplified text on Spice, suitable for parent/student information.

As if terminology isnt enough of an obfuscation, consider:Very few street drugs are 100% pure Many are adulterated or contaminated Most discussion will be over pure presentation

Shrub to Bath Salts?

Catha Edulis

Khat plant geographyWhat is khat?Cathinone active alkaloid in khat leavesChewing popular in middle eastProduces amphetamine-likesympathomimetic symptoms

What are bath salts?Synthetic cathinone derivativesSynthesized as early as 1928 and studied formedical useMethcathinoneMephedroneBupropion only cathinone with medicalindicationMDPV, mephedrone, buphedrone,pentedrone, methylone, 4MEC, 4MePPP, -PVP, etc

Structures!

PharmacologySimilar to amphetaminesAffect dopamine, serotonin, and norepinephrineNeuronal stimulation due to increased post-synaptic catecholaminesIncreased release of catecholaminesBlockade of pre-synaptic uptake and storageReduced MAO activityIndirect glutamate pathway stimulationEnd result: increased chemicals in the synapsecausing increased effects

How supplied?Powder, capsules, and tabletsInsufflation, ingestion, IV use, and rectal useMephedrone: 100 200 mgMDPV: 10 15 mg

Effects within 30 mins; lasts up to 7+ hours

Patient Case30 yo male admits to using 1 2 grams ofbath salts daily x 2 monthsVS: 187/93 P129 R12-16 T 98Presents to ED shaky and anxious andhallucinating Administered lorazepamPatient returns to baseline 24 hours later

Patient Case26 yo male presents to ED after injecting bathsaltsFound agitated, altered, violent andcombative and foaming at the mouth by EMSVS: 148/66 P175 T 106.3 (rectally) Patient intubated with RSI and aggressivecooling measures institutedCK peaked at 235,377 U/L (normal < 170 U/L)

Patient Case40 yo male injected unknown amount ofbath saltsBecame aggressive, uncontrollable,delusional, removed all his clothing, andviolent behaviorTazed by police and had be physicallyrestrained by EMSVS: P 164 131/72 R24 rectal temp 105.4Declared brain dead 42 hours afterpresentation after complicated ICU stay

Clinical ManifestationsAgitation (53.3%)Tachycardia (40%) Hypertension (20%) Seizures (20%) Palpitations (13.3%) Hallucinations/delusionsParanoiaRenal failure?Cannibalism?Death

Clinical Manifestations45% of patientsexperience symptomsbeyond 24 hours postexposure30% have symptoms >48 hours post exposure Are there adulterantspresent or

contaminants?

ManagementProtect yourself!Difficult to manage patients and unpredictablebehaviorABCsNo antidoteGI decon?BZDs, BZDs, and more BZDs for agitation DPH likely wont be effectiveHaloperidol could be problematic

ManagementAll BZDs work the sameIncrease frequency of chloride channel openingleading to hyperpolarizationOnly works in conjunction with GABADiazepamMidazolamLorazepamOnsetIVQuick (min)Quick (min)5 20 minIMUnpredictable5 10 min20 30 minDurationSingle doseShortShortLongRepeated DosesLongIntermediateLong

ManagementWhat if BZDs do not work?No real ceiling to BZD dosesRespiratory depressionHaloperidolAnticholinergicQTc prolongationRisk vs benefitsBring product into ED

Synthetic Cannabinoids

Where did it come from?1960s: research into THC-like compoundsAnalgesic and anti-inflammatory minuspsychotropic effectsRecognized as drugs of abuse in early 2000sin EuropeDr. JW Huffman researched THC analoguesfor use in cancer and AIDS patientsDeveloper of JWH compounds

HU-210 from Hebrew University

What are they?Synthetic cannabinoids which work on theCB1 and CB2 receptor like THCMarketed as herbal incense, herbal smokingblends, potpourri, etc.Spice, K2, Mr. Nice Guy, Legal Funk, Tai Fun, ZenUltra, Smoke, Chaos Mint, etc. Misleading packagingNot for human consumptionCommonly smoked

Whats in them?

PharmacologyEffects likely from mixture of herbs and actualsynthetic compoundsBaybean, Beach bean, Dwarf skullcap, red clover,vanilla, honey, wild dagga and moreAffects CB1 and CB2 receptors found in CNS/PNSResponsible for elevating mood, anxiety, cognitionResponsible for reducing inflammation induced painHU-210 100-800x more potent than THC

Patient Case21 yo male smoked some K2 earlier ineveningPresents to ED tachycardic, dilated pupils andwith myoclonic jerkingGiven BZDs and symptoms resolved over 8hours

Patient Case48 yo man had generalized seizure within 30minutes of ingesting a synthetic marijuana-like product Initial vital signs were: pulse, 106/min; BP,140/88 mmHg; respirations, 22/minGCMS confirmed substance to be JWH-018

Patient Case35 yo male admits to smoking legal weed 90minutes agoC/o chest pain and dizziness Supportive care institutedPatient leaves AMA

Clinical ManifestationMost information from case reports and caseseriesPsychiatric effects predominateAnxiety, paranoia, agitation, delusions, andpsychosisPhysical manifestationsTachycardia, HTN, diaphoresis, seizures, and ????The good ol standard addictive drugs are still here. We dont yet fully understand how the new drugs fit the users needs. It is clear that they fit the network of illegal drug trade and electronic marketing of chemicals both illegal & legal.

NFLIS analyzes drug samples.

Here is what they are finding by regionNFLIS drug samples analyzed1,660,216 drug reports were submitted to State and local forensiclaboratories in the United States from January 1 through December 31, 2011 Nationally, in 2011Cannabis/THC was the most frequently identified drug (536,630 reports), followed by:Cocaine (333,645 reports), Methamphetamine (160,960 reports), and Heroin (119,765 reports).

More recently from 2010 to 2011, reports of clonazepam, buprenorphine, and amphetamine increased significantly at the national level.

Regionally, reports of oxycodone, hydrocodone, alprazolam, and clonazepam increasedsignificantly in all four U.S. census regions from the period of 2001 through 2011. Reports of buprenorphine increased significantly in the Midwest, and amphetamine reports increased significantly in the Midwest, Northeast, and South.

34NFLIS data contd. Some current, partial, context for what we should be seeing in clinics.From 2010 to 2011, reports increased significantly In the Northeastoxycodone ,

buprenorphine

Amphetamin

BUT Cannabis/THC and cocaine reports decreased significantly

In 2011, more than 70% of narcotic analgesic reports were oxycodone or hydrocodone. (while)Alprazolam accounted for 52% of identified tranquilizers and depressants.

Among identified/Hallucinogens, MDMA accounted for 23% of reports.

352001 2011 (long term Trends)

Reports of cocaine decreased significantly from the period of 2001 through 2011 in all four U.S. census regions. While cannabis/THC reports increased significantly in the Northeast.

36Foxy Methoxy: Tryptamines Will Not Fade Away 5-methoxy-N,Ndiisopropyltryptamine (5-MeO-DIPT) was ranked among the 25 most frequently identified drug samples Foxy Methoxy: Tryptamines Will Not Fade Away In 2011, for the first time ever, 5-methoxy-N,Ndiisopropyltryptamine (5-MeO-DIPT) was ranked among the 25 most frequently identified drugs in NFLIS. With over 3,000 estimated drug reports, it was the only Tryptamine to make the list. In addition to the NFLIS State and local data, 5-MeO-DIPT was one of the top 10 drugs reported by the DEA. Abused for its hallucinogenic-like effects, 5-MeO-DIPT is often administrated orally as tablets, capsules, or powder forms at doses ranging from 6 to 20 milligrams. Other routes of administration include smoking and snorting. It produces subjective effects with an onset of about 20 to 30 minutes, a peak at about 1 to 1.5 hours, and a duration of about 3 to 6 hours. Subjects who have been administered 5-MeO-DIPT are talkative and disinhibited with dilated pupils. High doses of 5-MeO-DIPT produce nausea, jaw clenching, muscle tension, and overt hallucinations with both auditory and visual distortions. The abuse of hallucinogenic substances in all-night dance parties (raves) and other venues was a major problem in the United States in the late 1990s and early 2000s. As DEA controlled various Phenethylamines and tryptamines, more designer drugs would appear. Sold as Foxy or Foxy Methoxy, the abuse of 5-MeO-DIPT began to spread in 1999. For the next four years, it was encountered by law enforcement agencies in several States. In 2003, DEA temporarily added 5-MeO-DIPT to Schedule I of the CSA to avoid imminent hazard to public safety. In 2004, this action was made permanent. Between 2010 and 2011, the number of 5-MeO-DIPT reports increased nearly 36-fold. From 2009 to 2011, the change was 56-fold. It has been found in combination with N-benzylpiperazine (BZP); 1-(3-trifluoromethylphenyl)-piperazine (TFMPP); 3,4-methylenedioxymethamphetamine (MDMA); and various synthetic cathinones. More intelligence gathering will be needed to discover why 5-MeO-DIPT has made such a resurgence. 37About: Bath salts, research chemicals, plant foodMay have originated in China and IndiaIn foreign use for about two years PowderSnorted, smoked or injectedMade of MDPV MethylenedioxyprovaleroneMethyloneMephedrone38Not your Mums Bath Salts?So what are Bath Salts anyway? They are a man-made, chemical (as opposed to organic) stimulant drug. Generally, stimulants are a class of drugs that elevate mood, increase feelings of well-being and increase energy and alertness. Amphetamines, or speed, are an example of stimulant drugs.

The technical term for Bath Salts is substituted cathinone. Khat is a plant that is cultivated and used in East Africa and the Middle East. It has a stimulant effect on the user and can be quite dangerous. Substituted cathinones are synthetic, concentrated versions of the stimulant chemical in Khat. Methylenedioxypyrovalerone (MDPV), mephedrone and methylone are the chemicals most often found in Bath Salts. They can be ingested orally or snorted through the nose.

39Bath Salts are also calledZoomlady bubblesTranquilitydoveIvory wavevanilla skyBlissWhite Girl is good for cooking like crackTranquility, better when smoked in powder formNRG not good cooked, better placed in mouth, tastes like vanilla40Roch/Buff/Syracuse markets:Molly an analogue of MDMABelieved on the street to be pure MDMAManufactured in Europe and Asia for US41Begin by looking at why kids might choose Salts For energy / alternative to illegal stimulants Perceived to be legal Not picked up on standard drug tests Available at retail outlets: convenience stores; head shops; online

they are trying to stay as legal as possible!Prevention messages, parental messages have been aimed at avoiding illegal behavior, and this is now a driver for synthetics.

42Its New & ImprovedDrugs such as synthetics, not known to be used by addicts can be used off label with out incurring the social stigma usually associated with street drugs such as cocaine or even alcohol.So no stigma and doesnt attract any attention from parents.

Actually Tide has been a ingredient in drug manufacturing for several years.Product labeling legal, not for human consumption means you cant be busted for holding.Dilemma: when, in an underground culture mind altering drugs are relabeled as insecticide (to allow for legal importation and retail sales), young adults realistically could assume any insecticide might get them high?44Again, the Effects of Bath Salts would look like:

Very severe paranoia that sometimes causes users to harm themselves or others. Speed of onset 15 minutes; Length of high 4-6 hours Long term effects: Unknown Effects reported to Poison Control Centers Suicidal thoughts Agitation; Combative/Violent; Confusion Hallucinations / psychosis Increased heart rate; Hypertension; Chest Pain Death or serious injury

users cant know except via trial or reputation, contents or dosage

45Calls To Poison Control Centers for Human Exposure to Bath Salts, 2010 to January 2012

46Poison control centers show dramatic increase in ingestion over very short period for bath salts but beginning to flatten out.In 2010, poison centers received 304 calls about exposures to Bath Salts. That number rose dramatically in 2011 when poison centers received 6,138 calls. In early 2011, calls closed in each month* spiked through June, then gradually declined and was level in November and December 2011 and January 2012.

47Synthetic Marijuana = Spice, K-2,and analoguesK2 or "Spice" is a mixture of herbs or dried, shredded plant material that is typically sprayed with chemicals that are similar to THC, the psychoactive ingredients in marijuana.

JWJ-018 (or J dub) Name refers to a key ingredient research chemical

48Synthetic (420) marijuana also known locally as:K 2blazeSpicered dawnGenie420blue49More signs of use Loss of physical control Lack of pain response Increased agitation Pale skin Seizures Vomiting Profuse sweating Uncontrolled / spastic body movements Elevated blood pressure, heart rate, and palpitations

50Physical effects Onset 3-5 minutes Length of duration 1-8 hours Short-term effects: In addition to physical signs of use, users may experience: Dysphoria the opposite of euphoria Paranoia similar to PCP / Angel Dust Delusions, hallucinations and increased agitation Long-term effects: Unknown

May report morbid and depressive mental state51High School seniors, an important demographic coming your way...one in 10 high school seniors used synthetic marijuana in the prior year (MTF)

Area students are being suspended for use but Schools have been late in the detection gameIts not usually illegal No testing to confirmParaphernalia is disguised from parental observation

At 11.4 percent, the annual prevalence of synthetic marijuana is: 41 percent greater than Vicodin (8.1 percent) Four times greater than inhalants (3.2 percent) Four times greater than cocaine (2.9 percent) Eight times greater than meth (1.4 percent)

52Bath Salts53Synthetic MarijuanaCalls to poison control centers for exposure to synthetic marijuana doubled between 2010 and 2011 and is on track to rise again in 2012. NCAD-rs.orgEmbedded video, 15 minutes54NFLIS report Feb 22, 2013Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits In Brief In 2011, there were 5.1million drug-related emergency department (ED) visits; about one half (49percent) were attributed to drug misuse or abuse with a nearly equalpercentage (45percent) attributed to adverse drug reactions

ED visits involving use of illicit drugs were relatively stable from 2004 (991,640 visits) to 2009 (974,392 visits) but increased from 2009 to 2011 (1,252,500 visits); between 2009 and 2011, the rate of visits involving illicit stimulants increased 68percent, and the rate of visits involving marijuana rose 19percent

ED visits involving misuse or abuse of pharmaceuticals increased from 2004 (626,470 visits) through 2011 (1,428,145 visits); the most commonly involved drugs were anti-anxiety and insomnia medications and narcotic pain relievers (160.9 and 134.8 visits per 100,000 population, respectively)

ED visits involving adverse reactions to drugs increased from 1,250,377 visits in 2005 to 2,287,271 visits in 2009; however, no increase occurred between 2009 and 2011 (2,301,059 visits)

55(DAWN Rept_ )Figure2 Table. Rates of Emergency Department (ED) Visits Involving Illicit Drugs among Patients Aged 12 to 24 per 100,000 Population, by Age Group: 2011 Illicit Drugs Persons Aged12 to 17 Persons Aged18 to 20 Persons Aged21 to 24 Marijuana* 240.2 443.8 446.9 Heroin** 8.5 134.6 266.1 Cocaine** 23.5 112.5 214.4 Illicit Stimulants** 23.5 89.8 141.5 Synthetic Cannabinoids** 30.2 60.8 16.3 * The differences between those aged 12 to 17 and the two older age groups were statistically significant at the .05 level.**All differences between age groups were statistically significant at the .05 level.Source: 2011 SAMHSA Drug Abuse Warning Network (DAWN).

Visits Involving Synthetic CannabinoidsSynthetic cannabinoids first appeared in DAWN records in 2009, but there were too few visits to be reported. By 2010, ED visits involving synthetic cannabinoids rose to a reportable level for the Nation (3.7 visits per 100,000 population).6 By 2011, there were 9.2 visits per 100,000 population involving synthetic cannabinoids across all age groupsabout a 150percent increase (data not shown). The rate of visits involving synthetic cannabinoids was highest among patients aged 18 to 20 (60.8 visits per 100,000 population), followed by patients aged 12 to 17 (30.2 visits per 100,000 population) (Figure2).

56Drugs of abuse and SEXY street names1-[3-(Trifluoro-methyl)-phenyl]piperazine)](Street Names: TFMPP or Molly. Often found in combination with BZP: A2, Legal E or Legal X)2,5-Dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7)(Street Names: Blue Mystic, T7, Beautiful, Tripstay, Tweety-Bird Mescaline)3,4-Methylenedioxymethamphetamine(Street Names: MDMA, Ecstasy, XTC, E, X, Beans, Adams)4-Bromo-2,5dimethoxyphenethylamine(Street Names: 2C-B, Nexus, 2s, Toonies, Bromo, Spectrum, Venus)4-Iodo-2,5-Dimethoxyphenethylamine(Street Names: 2C-I, i)4-Methylmethcathinone (Mephedrone)(Street Names: 4-MMC, meow meow, m-CAT, bounce, bubbles, mad cow)5-Methoxy-N,N-Diisopropyltryptamine(Street Names: Foxy, or Foxy methoxy)Alpha-Methyltryptamine(Street Name: Spirals)Anabolic Steroids(Street Names: Arnolds, Gym Candy, Pumpers, Roids, Stackers, Weight Trainers, Gear, and Juice)Benzodiazepines(Street Names: Benzos, Downers, Nerve Pills, Tranks)N-Benzylpiperazine(Street Names: BZP, A2, Legal E or Legal X)Buprenorphine(Trade Names: Buprenex, Suboxone, Subutex)5757Carisoprodol(Trade name: Soma)Clenbuterol(Street Names: Clen)Cocaine(Street Names: Coke, Snow, Crack, Rock)Cyclobenzaprine(Trade Name: Flexeril, Amrix)Dextromethorphan(Street Names: DXM, CCC, Triple C, Skittles, Robo, Poor Man's PCP)N,N-Dimethyltryptamine(DMT)d-Lysergic Acid Diethylamide(Street Names: LSD, Acid, Blotter Acid, Window Pane)Fentanyl(Trade names: Actiq, Fentora, Duragesic)Fospropofol(Lusedra)Gamma Hydroxybutyric Acid(Street Name: GHB, Liquid Ecstasy, Liquid X, Goop, Georgia Home Boy, Easy Lay)Human Growth Hormone(Trade Names: Genotropin, Humatrope, Norditropin, Nutropin, Saizen, Serostim)Hydrocodone(Trade Names: Vicodin, Lortab, Lorcet-HD, Hycodan, Vicoprofen)Hydromorphone(Trade name: Dilaudid; Street Names: Dust, Juice, Smack, D, Footballs))

58Jimson Weed (Datura stramonium)(Street Names: Thornapple, stinkweed, locoweed, augushka, ditch weed, devil's snare, devil's seed, devil's trumpet, Korean morning glory, Jamestown weed, angel's trumpet, beelzebub's twinkie, madhatter, and crazy tea.)Ketamine(Street Names: Special K, "K", Kit Kat, Cat Valium)Kava(Other Names: Ava, Intoxicating Pepper, Kawa Kawa, Kew, Sakau, Tonga, Yangona)Khat(Street Names: Khat, Qat, Kat, Chat, Miraa, Quaadka)Kratom (Mitragyna specious korth)(Street Names: Thang, Kakuam, Thom, Ketum, Biak)Levamisole(Ergamisol)Methamphetamine(Trade Name: Desoxyn; Street Names: Meth, Speed, Crystal, Glass, Ice, Crank, Yaba)Methadone(Trade Names: Methadose, Dolophine; Street Names: Fizzies, Amidone, Chocolate Chip Cookies)3,4-Methylenedioxypyrovalerone (MDPV)(Street Names: "bath salts," "Ivory Wave," "plant fertilizer," "Vanilla Sky," "Energy-1")Methylphenidate(Trade Names: Ritalin- (IR, LA, and SR), Concerta, Metadate- (CD and ER), Methylin- (IR and ER) and Focalin- (IR and ER))Nalbuphine Hydrochloride(Trade Name: Nubain)59Oxycodone(Trade Names: Tylox, Percodan, OxyContin)Oxymorphone(Trade Names: Opana, Opana ER; Street Names: Blue Heaven, Blues, Mrs. O, New Blues, Octagons, Oranges, Orgasna IR, OM, Pink, Pink Heaven, Pink Lady, Pink O, Stop Signs, and The O Bomb)Phencyclidine(Street Names: PCP, Angel Dust, Supergrass, Boat, Tic Tac, Zoom, Shermans)Propofol(Diprivan)Salvia Divinorum and Salvinorin A(Street Names: Maria Pastora, Sage of the Seers, Diviners Sage, Salvia, Sally-D, Magic Mint)Spice/K2 Cannabinoids CP 47,497 and homologues 2-[(1R,3S)-3-hydroxycyclohexyl]-5-(2-methyloctan-2-yl)phenolHU-210, [(6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c] chromen-1-ol)]JWH-018, 1-Pentyl-3-(1-naphthoyl)indoleJWH-073 1-Butyl-3-(1-naphthoyl)indoleUR-144 and XLR11 (TCMP-018; KM-X1) and XLR11 (5-F-UR-144)

Tramadol(Trade Name: Ultram

60Much information is simply not known, but for trial and error.

The prospect that these chemicals will ever be studied by researchers rather than experienced by teens is not likely. The cultural appeal of shared highs via blogging & tweeting, a invisible web based order system, and a virtual supply of mixtures has produced a lot of momentum.