121. ACKNOWLEDGEMENTS Staff of NMS Labs - Research and Development Department Staff of NMS Labs – LC-MS/MS Department A special thanks to Matt McMullin QUESTIONS?
122. SYNTHETIC CANNABINOIDS: A CONTROLLED ADMINISTRATION STUDY Barry K Logan Fredric Rieders Family Renaissance Foundation
123. K2 Phenomenon Millard South Shooter Tests Positive for Synthetic Marijuana. Omaha, NE - Tests discover a controversial, yet legal drug, in Robert Butler Juniors' body the day he killed Doctor Vicki Kaspar then himself. So KMTV Action 3 news talked with a poison control expert. Without wanting to speculate on Butler's use he says the drug can cause suspicious behavior. "The confusion, the delirium, people can hurt themselves, they can hurt others, they can hurt other people," says Doctor Ron Kirschner with the Nebraska Regional Poison Center.
124. K2 Phenomenon Drugs part of shooter's troubles By Leslie Reed January 11, 2011. Friends hint at possible drug use — hints that may be substantiated by new drug test results that reveal the presence of K2, a synthetic marijuana substitute, in Butler's body. Authorities have said the designer drug was used by some students at Butler's former school, Lincoln Southwest, and say it's known to cause delusions and paranoia in some users.
125. K2 Phenomenon McHenry shop owner had K2 in system McHENRY – The owner of House of Glass, who was found unconscious and later died in November, had K2 along with painkillers in his system. The McHenry County Coroner’s Office, which completed its investigation this week, said there was K2 and the painkillers methadone, morphine and Lyrica in Fred Evans’ system when he died.
126. K2 Phenomenon Woman Pleads Guilty In Hit, Run That Killed Passenger Devetta Blount Created: 1/12/2011 6:00:45 … emergency workers took Watlington to Moses Cone Hospital where she died. Also, Prosecutors said that SBI Lab results revealed Neal had cocaine and … K2 or synthetic marijuana.
127. K2 Phenomenon Fake pot sickens two LVC students Lebanon Daily News Updated: 01/31/2011 Two Lebanon Valley College students were taken to the hospital last weekend for treatment of an allergic reaction to synthetic marijuana, police said. The students admitted to smoking herbal incense, which caused an allergic reaction, police said. Both were taken to Good Samaritan Hospital and released after treatment.
128. K2 Phenomenon Pain pill, not Spice, shows up in DUI-related drug test Published: Saturday, Jan. 22, 2011 SALT LAKE CITY — A man police believed to have been impaired while driving after smoking Spice, pleaded no contest Friday to driving under the influence of drugs and/or alcohol. "The question is not whether Spice is legal. The question is whether something is impairing his ability to drive safely," (his attorney) said. He was later subjected to drug testing and Engar said results indicated an opiate drug was present. Beckmann admitted to taking a pain pill in days prior. "He has a drug problem," (his attorney) said. "We're looking into the (Corrections Addictions Treatments System) program at the jail. It's just something we'd rather resolve than fight at this point."
129. K2 Phenomenon ROCK SPRINGS, WY -- Rock Springs police are reporting several cases of teens apparently overdosing on synthetic marijuana. Memorial Hospital of Sweetwater County says six people have been treated since Jan. 1 for symptoms believed to have been caused by ingesting or smoking fake pot. Three people ages 15, 16 and 17 who went to the hospital Jan. 7 were charged with violating a city ordinance against inhaling toxic vapors. Three Rock Springs High School students, all age 15, were charged Jan. 11 with the same offense after at least one teen suffered adverse symptoms.
130. K2 Phenomenon WASHINGTON | Tue Jan 25, 2011 3:20pm EST Seven midshipmen were expelled from the U.S. Naval Academy for using or having a banned marijuana-like substance known as "spice," officials said. It is considered a banned substance by the Departments of Defense and Navy, Carpenter's statement said. Officials at the Naval Academy in Annapolis, Md. learned about the allegations during the fall semester and consider the investigation to be ongoing, the statement said.
147. Missouri K2 Administration Study Subject BM Smoked “K2 Citron” 10mg/g JWH-018/073 0.3g in water pipe 3 inhalations over 30 minutes
148. Missouri K2 Administration Lab Subject BM - Urine Time JWH-018 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 +/- √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √ Time JWH-073 Mono-OH Di-OH Tri-OH Glucuronides Pre-dose X X X X X 1:15 X √ √ X √ 2:07 X √ √ √ √ 2:40 X √ √ √ √
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152. ACKNOWLEDGEMENTS Staff of NMS Labs, Research and Development and LCMS Departments Staff of the Missouri Safety Center, University of Central Missouri QUESTIONS?
Editor's Notes
Synthetic drugs that mimic the effects of cannabis through binding at the same receptors, principally the CB1 receptor, more of which about momentarily. The drugs were developed in the 1980’s and 1990’s as potential cannabinoid agonists that might possess some of the advantageous effects of cannabis, appetite stimulation, and anti- nausea properties, blood pressure, and much flaunted as adjuncts in cancer pain therapy, without the euphoric intoxicating effects for which the drug was popular recreationally. Now the drugs are sold widely on the internet and convenience stores and gas stations, smoke shops and head shops. The compounds that we will discuss are largely unregulated in most o the US but there is a rapid trend towards state or even local regulation as public concern grows. The DEA is looking to develop controls for these drugs and recently appealed for information through the SOFT newsletter.
So what do we know about this phenomenon, and what can be done to prepare for investigations of its possession and use as it is outlawed, and to answer questions about the toxicity associated with its use? Unfortunately, the K2/spice phenomenon appears to be more than just a fad, but rather represents the emergence of an industry designed to continually change its products based on attempts to regulate each new compound that comes along. We will briefly review the origins of the synthetic cannabinoids Consider what products are on sale in the K2 online and retail markets and what drugs they contain Consider their mechanisms of action and pharmacology Analytical challenges Consider what is known about their effects from published self-experimentation and some recent human administration studies And finally consider some impaired driving cases with associated toxicology results.
So what do we know about this phenomenon, and what can be done to prepare for investigations of its possession and use as it is outlawed, and to answer questions about the toxicity associated with its use? Unfortunately, the K2/spice phenomenon appears to be more than just a fad, but rather represents the emergence of an industry designed to continually change its products based on attempts to regulate each new compound that comes along. We will briefly review the origins of the synthetic cannabinoids Consider what products are on sale in the K2 online and retail markets and what drugs they contain Consider their mechanisms of action and pharmacology Analytical challenges Consider what is known about their effects from published self-experimentation and some recent human administration studies And finally consider some impaired driving cases with associated toxicology results.
Just some introductory historical perspective. Slides are self explanatory.
To complicate the matter further, these chemicals are already in circulation. As certain compounds are banned, there are plenty of replacement chemicals that quickly show up in new formulations. This list is getting bigger as more analogous materials are synthesized and distributed. We have also been seeing compounds added to these mixtures that are not synthetic cannabinoids such as 5-methoxy-dallyltryptamine (5-MeO-DALT).
No distinctive color test Duquenois-Levine did not give anything specific
Good response for HU and CP compounds While UV absorbance was observed for JWH and WIN compounds, no band was observed upon use with visualization spray
Overspraying with iodoplatinate could result in a false negative for all but JWH-200 and WIN55,212 Observable results for all compounds with UV (254nm) JWH018, 019, 073, 200 and WIN 55 also gave responses for UV (366nm) and 10% H2SO4 HU210, HU211, JWH015, 018, 019, 073, 200 and WIN 55 also gave responses with 50% Nitric No responses were observed for any compounds with Fluorescamine, Ninhydrin, Mercuric Sulfate or D-MAB visualization sprays
125x greater response from the derivatized standard
1 st picture is from the Missouri sample 2 nd picture was K2 Blonde purchased from www.k2-incense-online.com 2 separate samples tested (Missouri and www.k2-incense-online.com); both contained the same compounds
From Missouri
1 st picture is from Missouri 2 nd picture is from www.k2-incense-online.com 2 separate samples analyzed (Missouri and www.k2-incense-online.com); both contained the same compounds
From Missouri
1 st picture is from Missouri 2 nd picture is from www.k2-incense-online.com 2 separate samples analyzed (Missouri and www.k2-incense-online.com); both contained the same compounds
2 separate samples analyzed (www.topk2.com and North Carolina); both contained the same compound 1 st picture is from www.topk2.com 2 nd picture is from North Carolina
2 separate samples analyzed (www.topk2.com and www.k2-incense-online.com); both contained the same compound 1 st picture is from www.topk2.com 2 nd picture is from www.k2-incense-online.com
None Detected 774 JWH-073 Only 304 JWH-018 Only 108 JWH-018 & JWH-073 88 May not have been positive for one of the compounds because only the mono-hydroxy metabolite was present
The terminal OH is present with a fairly high intensity but the unknown is most intense. So what is this peak? It is most likely hydroxylation up the chain. This explains the intensity and the poor peak shape.
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
Every week we are seeing anecdotal reports in the news and additional reports in the scientific media
makes some of these reports circumstantial. However
Including acute intoxications, with anxiety, paranoia, gross impairment, and marked tachycardia.
more credible reports are now appearing in the medical literature also.
Including acute intoxications, with anxiety, paranoia, gross impairment, and marked tachycardia.
Sobolevsky and coworkers reported urine profiles of three subjects in Russia who had smoked a product containing JWH-018. The effetc proifile was again similar to that expected of marijuana.
They made tentative identifications of more than 13 possible metabolites in these subject’s urine. These include monohydroxylated metabolites on the indole ring, M1, M3 but could not identify the position of hydroxylation. There are actually 4 possible positional isomers of this one monohydroxylated metabolite, so considering that poly hydroxylated compounds are known, the positional isomers have not been determined. Our investigations suggest that the ring hydroxylated metabolites are very minor constituents in human urine, although standards have now been synthesized. They also report terminal hydroxylation on the N-alkyl chain, M2 which we have confirmed as a major metabolite in human urine. The major metabolite is also a mono-hydroxy, but not on any of the positions shown in the Sobolevsky paper. M4, carboxy is also present in small amounts in human urine. M6 and M7 are variants of some of the polyhydroxylated compounds. M8, through M11 are again polyhydroxylated but also reduced, now on the naphthyl ring. And M 12, 13 and other variants are N- delakylated and hydroxylated. So as we will see a complex soup of hydroxylated, reduced and oxidised compounds
Detected CP 47,497 C7 and C8 analogs and JWH-018 in the blood. No data on urine. No cross reactivity with THC-COOH immunoassay.
Teske and coworkers conducted self administration of a product containing JWH-018. They reported sickness, sedation and dry mouth, hot flushes, burning eyes, and thought disruption. No change in pupil size. But pulse and blood pressure were noticeably elevated.
They reported quantitative concentrations in in serum, with peak concentrations occurring in the range of 8-10 ng/mL within a few minutes of smoking, and concentrations falling below 1ng/mL within 3 hours. Trace concentrations were reported at 24 hours (<0.1ng/mL)
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
In July 2010 the University of Missouri sponsored a K2 administration study. Following approval by the University’s IRB, six subjects were administered low doses of smokeable products containing JWH-018, JWH-073 or CP-47,497. Subjects completed SFST’s and a DRE exam, some cognitive tests, and underwent medical assessments. Blood urine and oral fluid were collected, refrigerated or frozen and shipped to NMS labs for analysis. The K2 was analyzed for SC content and the presence of any other drugs before administration.
The data show the rapid rise, distribution and decline of the parent compounds in blood, combined with the rapid rise in blood pressure, systolic shown here. Importantly within one hour of this pharmacologically significant dose, the concentrations had dropped to less than 1ng.
Urine samples from the MO subjects were collected for between 2-5 hours. Describe One subject provided a 24 hour urine which was positive close to the method threshold. Oral fluid was collected, but had very weak positives, one hour after use. This may be a function of the collection devices and is being investigated further. Our general experience is that the SC compounds do tend to stick tightly to plastic, and glass should be used whenever possible.
The effects were no surprisingly similar to those associated with marijuana. (Read from list)