Presentation on theme: "The Designer Drug – What You Always Wanted to Know"— Presentation transcript:
1 The Designer Drug – What You Always Wanted to Know Steven Kipnis MD, FACP, FASAMMedical Director, NYS OASAS
2 Thanks to:Paul L. Cary Toxicology Laboratory University of Missouri Steve Hanson Acting Associate Commissioner - NYSOASAS
3 CASEA healthy 48-year-old man has a generalized convulsion after ingesting a powder he purchased through the Internet. The powder was sold with the wording “not for human consumption” listed on the packaging. The seizures continue in the pre-hospital setting, as well as in the ED, for approximately 15 minutes in total before ceasing after administration of lorazepam 4 mg IV. Initial vital signs after cessation of his seizures include a blood pressure of 140/88 mm Hg; pulse, 106 beats/min; respiratory rate, 22 breaths/min; temperature, 37.7°C. Physical examination is notable for mydriasis and diaphoresis with 5 beats of myoclonus in the bilateral lower extremities. Shortly after arrival in the ED, the patient is intubated for airway control. Finding on noncontrast CT of the brain are unremarkable, and EEG results are normal. Initial pertinent laboratory values include normal electrolyte, creatinine, and glucose levels. His creatine phosphokinase level is elevated, at 2,500 U/L. Toxicology screening does not detect acetaminophen, ethanol, or salicylates
4 CASEA healthy 48-year-old man has a generalized convulsion after ingesting a powder he purchased through the Internet. The powder was sold as “research grade JWH-018 – synthetic cannabinoid,” with the wording “not for human consumption” listed on the packaging. The seizures continue in the prehospital setting, as well as in the ED, for approximately 15 minutes in total before ceasing after administration of lorazepam 4 mg IV. Initial vital signs after cessation of his seizures include a blood pressure of 140/88 mm Hg; pulse, 106 beats/min; respiratory rate, 22 breaths/min; temperature, 37.7°C. Physical examination is notable for mydriasis and diaphoresis with 5 beats of myoclonus in the bilateral lower extremities. Shortly after arrival in the ED, the patient is intubated for airway control. Finding on noncontrast CT of the brain are unremarkable, and EEG results are normal. Initial pertinent laboratory values include normal electrolyte, creatinine, and glucose levels. His creatine phosphokinase level is elevated, at 2,500 U/L. Toxicology screening does not detect acetaminophen, ethanol, or salicylates
5 A 36-year-old male in the Netherlands became acutely agitated and enraged after ingesting mephedrone along with cocaine, and subsequently lost consciousness and died despite resuscitation efforts.A 29-year-old male found unresponsive at a nightclub died of cerebral edema and brainstem herniation. Serum sodium wasnoted to be 125 mmol/L, later suggested by laboratory data to have resulted from water intoxication.The first synthetic cathinone-related death in the United States, described in the scientific literature, involved a 22-year-old male who was found unresponsive and subsequently died at the receiving hospital.One case of mephedrone-related myocarditis has also been reported in the literature. A 19-year-old male presented with crushing chest pain after ingesting mephedrone sold as ‘‘not for-human-consumption’’ plant food.
6 Drive to Get HighPeople will seek any means to alter their state of consciousness
9 Designer Drugs:Created (or reformulated, if the drug already existed) to get around existing drug laws (Controlled Substance Act), usually by modifying the molecular structures of existing drugs to varying degrees.
10 Designer Drugs:Second International Opium Convention in 1925 which specifically banned alternative esters of morphine1960s s, new synthetic hallucinogens (modifications of LSD & PCP)“Designer drug” was first coined by law enforcement in the 1980s1980s s, design of MDMA (ecstasy) & methcathinone, derivatives of psilocybin & mescaline, anabolic steroidsEuropean authorities have identified 41 new psychoactive drugs in 2010 alone
11 What Drives the Production Designer Drugs ? Consumer preferencesLaw enforcement control
12 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)
13 Why Change the Key? Prolong the effect of the drug Increase the potency of the drug“Select” the desired effectMake the drug more difficult to detectAvoid patent infringementMake an illegal drug “legal”Drug
14 Spice/K2 and Synthetic Cannabinoids (HMA – Herbal Marijuana Alternatives)
21 “Listed” Ingredients in Spice Canavalia rosea: beach bean or bay beanNymphaea caerulea: Blue Egyptian water lilyScutellaria nana: Dwarf skullcapPedicularis densiflora: Indian warriorLeonotis leonurus: Lion's Tail and Wild DaggaCannabis – like effectZornia latifolia: is a perennial herbNelumbo nucifera: LotusLeonurus sibiricus: Honeyweed or Siberian motherwortVanillaHoney
22 Preparation of the “incense”: Botanicals (vegetable matter) are sprayed with liquid preparations of:HU-210HU-211CP 47,497JWH-018JWH-073
23 Origins of Synthetic Cannabinoids CP 47,497 - developed by Pfizer in 1980 as an analgesicHU-210 & HU synthesized at Hebrew University, Israel in HU-210 is an anti-inflammatory; HU-211 as an anestheticJWH-018 & JWH synthesize by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffmanmore than 100 different synthetic cannabinoids have been created
24 Usage Very little known about the extent of use 2009 Survey in FrankfurtSurveyed 1463 students aged between 15 and 18 at schools providing general and vocational training.Prevalence of use was 6% of respondents reported using Spice at least onceNational Poison Data System in 2010 (Aurora, CO)During the 9 month study period, there were 1898 exposures reported with a mean age of 22.5 years oldMost cases reported were in men.Community Epidemiologic Work Group (CEWG) noted K2 epidemic in Midwest US in 2010Appears to be shifting from marijuana to synthetics
25 UsageMode of use:SmokedDrink as an infusion/herbal tea
26 Availability Sold in metal-foil sachets Sold in: Typically contain 3 g of smoking mixture sufficient for 8 jointsTypical cost is 20 – 60 dollars per packSold in:Internet sitesTobacco storesHead shopsSome gas stationsOften sold as “incense” labeled with disclaimer: not for human consumption
27 Smoking Cannabinoids What does CB1 receptor control? Basal Ganglia: motor control, learningHippocampus: memory, spatial navigationCerebrum: cognitive functions - attention, language, emotions*CB2 found in blood cells, immune tissue and spleen. ? in CNS
28 Dual effects: Herbs (very little medical literature of effects) Synthetic cannabinoid
29 Pharmacological Effects of Synthetic Cannabinoids are Similar to THC Mental (these affects predominate):Altered state of consciousnessMild euphoria and relaxationPerceptual alterations (time distortion)Intensification of sensory experiencesPronounced cognitive effectsImpaired short-term memoryAnxietyParanoiaAvoidant eye contactAgitationDelusions (paranoid, grandiose)Psychosis
30 Pharmacological Effects of Synthetic Cannabinoids are Similar to THC Physical:Increase heart rate & blood pressureDry eyesDiaphoresisMild decrease in potassiumSeizuresReduction in motor skill acuityIncrease in reaction times
31 Dependence Syndrome Similar to Marijuana Withdrawal:“Inner unrest”Drug cravingNightmaresProfuse sweatingNauseaTremorHeadacheHypertensionIncreased HR
32 Reported Effects of Synthetic Cannabinoids are Different Than THC Production inconsistenciesHerbal incense blends are harsher to inhaleEffect on appetite is non-existentIncreased restlessness & aggressive behaviorHerbal incense produces a shorter “high” (perceptual alterations & sensory effects are limited)Doesn’t mix well with alcohol (hangovers)Incense costs more than marijuana
34 Percentage of U.S. 12th Grade Students Reporting Past Year Use of Drugs* Other Than Alcohol and Tobacco, 2011 (N=approximately 14,900)Marijuana and synthetic marijuana are the most prevalent illicit drugs used by 12th graders, according to recent data from the 2011 Monitoring the Future (MTF) survey. Slightly more than one-third (36.4%) of high school seniors reported using marijuana in the past year, including 11.4% who reported using synthetic marijuana, compared with less than 10% for all other illicit drugs.
35 Legal Status of Synthetic Cannabinoids (DEA) March 1, 2011, the DEA, issued final notice to temporarily place five synthetic cannabinoids into the Controlled Substances Act (CSA) for at least one yearSynthetic cannabinoids treated as Schedule 1 drugsA drug that has a high potential for abuseA drug that has no currently accepted medical use in treatment in the United StatesThere is a lack of accepted safety for use of the drug under medical supervision
36 Legal Status of Synthetic Cannabinoids (DEA) DEA took action - imminent hazard to the public safetyImposes criminal sanctions and regulatory controls of Schedule I substances under the CSACovers the manufacture, distribution, possession, importation, and exportationUS Senate considering a bill permanently banning these drugs
37 State LawsSome states have passed their own laws banning the substanceNew York has pending legislation
38 Synthetic Cannabinoids “Banned” by the (DEA) Synthetic cannabinoids covered under the DEA’s new rule includes the following:JWH-018 *JWH-073 *JWH-200CP-47,497CP-47,497 (C-8 homologue)
40 Can synthetic THC chemicals be detected by drug testing?
41 Drug Testing: New on-site, rapid, instant tests Numerous laboratories employing LC/MS/MS technology$$$ per sampleMany unknowns regarding this testing
42 While parent drugs are detectable, metabolites of synthetic cannabinoids may be the only detectable compounds foundCan use blood and urine as sample
43 Unresolved Issues of Concern: What synthetic compounds (or metabolites) are being tested by these laboratories?No standardized urine cutoff levelsNo standardized methods (LC/MS/MS)Tests detect metabolitesNo independent quality control materialsNo proficiency testingDetection window unknownMay be 48 – 72 hours
54 What’s in Bath Salts Cathinone Known for centuries Active metabolite is cathineFound in leaves and twigs of Khat plant (Catha edulis)Original synthetic cathinone is methcathinoneProduced in 1928Public Health hazard as per League of Nations in 1933Schedule I drug in 1993
55 MephedroneReformulation of cathinone is a chemical found in the khat plant of Eastern AfricaKhat existence traced to 15th C. EthiopiaGrown in Somalia, Yemen, Kenya, EthiopiaKhat is banned in the U.S.
56 Methylmethcathinone (Mephedrone) Designer drug chemically similar to cathinoneFirst synthesized in 1929Amphetamine-like propertiesPowerful synthetic stimulant“Rediscovered” by synthetic chemistsin 2003Widespread in Europe, Australia, US
57 What’s in Bath Salts:Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties which acts as both a norepinephrine-dopamine reuptake inhibitor (NDRI).MDPV has four times the potency of RitalinMDPV - no history of FDA approved medical useSold since 2007 as a research chemicalSeptember 2011 – DEA Schedule I (mephedrone, methylone and MDPV)
58 MDPV: Currently popular in Europe, UK & Australia Is usually snorted - similar to cocaineConsidered extremely addictiveMDPV was “legal” – now Schedule IAdverse medical/psychiatric ramificationsNo on-site or screening drug tests
59 4-methylethcathinine (4-MEC) Found commonly used as the active ingredient in "Ecstasy" pills in some countries such as New ZealandReferred to as “Molly”
60 Usage UK online study of club-goers reported: 41% tried methedrone 10% tried methylone33% used in the last month14% used it weeklyBlood samples from Finland were taken from 3000 drivers suspected to be under the influence286 (8.6%) had positive for bath salts
61 Administration – white/brown powder; capsules and tablets also available Oral (mouth, “bombing”)Intranasal (snorting, “keying”)IntramuscularIntravenousRectalGingivalInhalation via smoking
65 Pharmacological Effects of “Bath Salts”: Mental:Hyperactivity, arousal & over stimulationIncreased energy & motivationEuphoria - agitationDiminished perception of the requirement for food and sleepTalkativenessIncreases sexual arousalCrave to redose frequently
69 DependenceLike amphetamines – induce tolerance and dependency in at least 30 percent of users with craving and impaired control
70 Long Term Effects Little is know as relatively recent use Potential neurotoxicity with decrease dopamine transporter activity in the basal ganglia leading to a parkinson’s like disorder
71 Detection Not detected in routine urine Elisa testing May cause false positive methamphetamine screenGC-MS test available for mephedrone, MDPV, methylone
72 Management No specific antidote exists Supportive care Aggressive sedation with benzodiazepines for increased heart rate, seizures, agitation and hypertensionAvoid beta blockade due to potential exacerbation of hypertension due to unopposed alpha-adrenergic stimulationHyperthermia may require coolingIf severe (persistent vital sign elevation, neuro and psychiatric abnormalities), all patients should be admitted and have:EKGSerial temperature checksCPKLytesRenal/liver functions
73 On September 8, 2011, the Drug Enforcement Administration (DEA) published a Notice of Intent to place three synthetic cathinones into Schedule I of the Controlled Substances Act (CSA)mephedrone,3,4 methylenedioxypyrovalerone (MDPV)methylone
76 The Next Wave (or a repeat of an old wave repackaged)?
77 Kratom Legal plant product – Mitragyna speciosa Korth South Eastern Asia treeUsed to treat opioid withdrawalAccess via internet without prescriptionDual properties of stimulation and analgesia
78 M. Speciosa Korth Plant with greater than 25 alkaloids Mitragynine responsible for opioid effectWorks at the mu and delta supraspinal opioid receptors, serotonin and noradrenergic pathways in spinal cord
79 Mitragynine 13 times more potent than morphine Powder, leaves, gum Smoked or tea
84 The New “Designer Drugs” Hallucinogens - This class has many different compounds that can be used for this purpose. These include:Salvinorin A (Salvia divinorum)Lysergic Acid AmideLeunorine (Lion’s Ear)Tropane Alkaloids (atropine, scopolamine)Datura stramoniumAtropa BelladonnaPsilocybinMuscarineN,N-Dimethyltryptamine
85 The New “Designer Drugs” HallucinogensSalvinorin A:Street names include: Magic Mint, Seer’s Sage, Lady SD, and Sally D.used for centuries by the Mazatec shamans in Oaxaca Mexico for spiritual healingused by chewing the fresh leaves, ingesting a tincture or juice from the leaf, or smoking dried leavesThe psychoactive component is neoclerodane diterpene Salvinorin A.It is the most potent of all naturally occurring hallucinogens and is equal to LSD.Unlike LSD which acts on the serotonin receptors, this works at the Kappa Opioid receptor as an agonist.There is rapid onset when smoking (one minute) to ten minutes seen with buccal (oral) absorption.It has a short half-life as the effect usually lasts 20 minutes
86 The New “Designer Drugs” HallucinogensSalvinorin A:Users state that they “enter another reality”, have improved mood, are calm, have increased insight and have a floating feeling. There are visual and auditory hallucinations that occur with use.Adverse effects have included:Sweatsmind racingYawninganxietyirritabilityinsomniadizzinessfatigueloss of coordinationmental slowness
88 ManagementSupportiveNo antidote?? if naloxone can reverse effects
89 The New “Designer Drugs” HallucinogensLysergic Acid Amide (LSA):ergot and fungi infected plants and produceten times less potent than LSD (Lysergic Acid Diethylamide)Seeds are crushed and eaten or soaked in water or alcohol and eaten.The effects last four to eight hours and can include: auditory and visual hallucinations; elevated blood pressure and heart rate; memory loss; anxiety; panic attacks; acute psychosis; and suicidal thoughts.
91 Molly Hallucinogenic amphetamine Similar effects to MDMA and methamphetamines$50 - $100 per gram
92 2C-E Nicknamed "Europa" synthesized in 1970’s -1980’s psychedelic phenethylaminetaken orallypowerful hallucinogenic effectshigh can last hourssold through European sourcesone death reported in MN on March 11, 2011
93 2C-E Nicknamed "Europa" synthesized by Alexander Shulgin popularized MDMA (Ecstasy)2C-I another phenethylamine available2C-E is chemically related to other 2C phenethylaminesexact legal status is unclear - 2C-B banned under CSA
94 Methoxetamine Access via the internet “Legal ketamine” – ketamine analogDiscovered in 2010
95 Piperazine Derivatives Amphetamine like – originally developed as an antihelminthicBZP, TMFPP – “legal ecstasy”Schedule I in 2004
96 BZP Antidepressant Inhibits serotonin transporter Pills/powder Effect lasts 6 – 8 hoursTakes 2 hours to get first effectManagement:BenzodiazepinesFluidsCoolingEKG
97 “Krokodil”Desomorphine (Dihydrodesoxymorphine) is an opiate analogue invented in 1932 in the United States that is a derivative of morphineDesomorphine has attracted attention in Russia due to its simple production, utilizing codeine, iodine, gasoline, paint thinner, hydrochloric acid, lighter fluid and red phosphorus.The street name in Russia for home-made Desomorphine made in this way is "krokodil" (crocodile), reportedly due to the scale-like appearance of skin of its usersSince the mix is routinely injected immediately with little or no further purification, "Krokodil" has become notorious for producing severe tissue damage including injury to the veins (phlebitis) and gangrene. Other consequences of use have included severe withdrawal, spread of HIV through the use of contaminated needles and death.
98 Pump-it! Powder: Methylhexanamine Source - found naturally in the geranium plantIt is not scheduled by the DEA - legalBanned in athleticsStimulantNot widely studied
99 Wet Marijuana Embalming Fluid-Soaked Marijuana: The trend of smoking marijuana soaked in embalming fluid is gaining popularity throughout the United States. The syndrome of intoxication looks nearly identical to that seen following phencyclidine (PCP) use, with agitation, disorganized speech and thoughts, and diminished attention. The authors believe that this new trend in drug use involving marijuana also presents a resurgence in PCP use.Soaked in water – uneven burnMixed with THC: wet, fry, crystal joint, supergrass
101 “Jenkem”: Fermentation of human waste Feces and urine stored in tight container for several daysReaction produces methane gasMethane major component of natural gas“Huffed” by users producing anoxia
102 Growth of Designer Drugs What’s different today then in the 1970’s when the drug Ecstasy (MDMA) was popularized?What has changed to fuel the rapid development and distribution of designer drugs?
108 Unfortunate Truisms:Legal controls that prohibit designer drugs will always lag behind their productionDrug detection methods for the identification of designer drugs may also not be available when these compounds become popular
110 Designer Drugs: Designer drugs are here to stay Rapid evolving landscapeTesting will nearly always lag behindLegal controls with be challenging and delayedGrowing evidence of adverse effectsSome become fads, others stay around (MDMA)
112 Legislation 2012The Synthetic Drug Control Act of 2012 (US Senate .3189) amends the Control Substance Act to add two classes of substances to schedule 1 – most addictive and most restrictive use with the highest legal implications if found to be using or selling:Cannabimimetic substances and analogs- all analogs of cannabinoid receptor agonists (CB1). This is the class of THC which stimulates the cannabinoid type 1 receptors in the brainStimulants (bath salts are in this class) and all the isomers and analogs:MethedroneMDPVMethyloneNaphyroneFlephedroneEthcathinoneButyloneAlpha-PPPMOPPPMDPPPAlpha-PVPMDAIMPBP
113 Legislation 2012FDA Safety and Innovation Act (Reauthorization Bill)will change emergency scheduling of drugs from one year with a possible 6 month extension to 2 years with a possible 1 year extension.All future analogs of synthetic drugs (structure and/or function) will be schedule 1 if the bill is signed by the President.
114 ONDCP will be unveiling a Synthetic Drug Prevention Toolkit, which we hope will serve as a resource for communities dealing with this issue.
115 Governor Cuomo Announces State Makes it Illegal to Sell or Possess Bath Salts or Synthetic Drugs (August 7, 2012)Governor Andrew M. Cuomo today announced that the New York State Department of Health (DOH) has issued new regulations to crack down on the increasingly widespread use of bath salts and other synthetic drugs.The new regulations, issued today by DOH and approved by the Public Health and Health Planning Council, will expand the existing list of prohibited drugs and chemicals to include dozens more substances that are now used to make synthetic drugs, better ensuring that distributors can no longer skirt the law by simply modifying the drug's ingredients. In addition, the regulations will allow for the first time an owner of an establishment and/or an employee selling synthetic drugs to be charged with possession of an illicit substance. Further, to support enforcement, the regulations will increase the criminal penalties for those who violate the rules. Violators will face fines up to $500 and potentially up to 15 days in jail.The Governor also announced a new toll-free hotline SALTS ( ). Individuals with information about illegal distribution of bath salts or synthetic drugs are encouraged to call this hotline.