2015

Merry Christmas and happy New Year!

What are your professional plans for the new year?

My main plan for 2015 is to become better with time management.

It's my hope that with more honed time management skills, I can:

• Publish more. We currently have a few papers in process, but we really need to up the ante this year in our subfield. Two papers in 2012, one paper in 2013, and one paper in 2014. The aim is for 4 papers in 2015. Collaboration is key. Anything less will be a disappointment. Anything more is just gravy.
• Mentor. Take a junior scientist (or two) under my wing and get her to the point of going after a first author paper. It's time for this.

Here's to a good start to 2015!

Notice of Intent – 3 More Synthetic Cannabinoids into Schedule I

Today, December 19, 2014, the United States Drug Enforcement Administration (DEA) filed a notice of intent for placement of three new synthetic cannabinoids into Schedule I of the Controlled Substance Act (CSA).

These three substances are:

AB-CHMINACA, AB-PINACA, and THJ-2201

All three of the substances have been discussed at one time or another here on TDMTP and are suspected to be CB1/CB2 receptor agonists, but true pharmacological and toxicological evidence does not exist.

 

AB-PINACA is N-(1-amino-3-methyl-1-oxyobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide. The “alphabet soup” name seems to reside in the following generic name: AminomethloxoButanePentylINdAzoleCarboxAmide. This synthetic cannabinoid was first encountered in March 2013 (reported by the National Forensic Laboratory Information System or NFLIS) and June 2013 (reported by the System to Retrieve Information from Drug Evidence or STRIDE). States reporting detection of this substance in products include AL, AR, AZ, CA, CO, CT, FL, GA, IA, ID, IL, IN, KS, KY, LA, MA, MI, MN, MO, MS, ND, NE, NH, NJ, NV, NY, OH, OK, OR, PA, SC, TN, TX, UT, VA, WA, WI, WV, and WY. From March 2013 to September 2014, there were 4 seizures of this compound (6 kg). Adverse effects from using the substance (as well as AB-CHMINACA discussed below) were seizures and convulsions, unconsciousness and coma, agitation, motor function loss, and respiratory issues. The DEA also reports that there have been at least 3 documented deaths involving AB-PINACA.

Some literature references for AB-PINACA:

Takayama et al. (2014) UPLC/ESI-MS/MS-based determination of metabolism of several new illicit drugs, ADB-FUBINACA, AB-PINACA, QUPIC, 5F-QUPIC, and Alpha-PVT, by human liver microsome. Biomedical Chromatography, 28, 831-838. PMID 24861751.

Thomsen et al. (2014) Synthetic cannabimimetic agents metabolized by carboxylesterases. Drug Testing and Analysis, Article in Press, doi: 10.1002/dta.1731, PMID 25346527.

Shanks et al. (2014) “Case Reports: Fatalities Associated with the Synthetic Cannabinoid, AB-PINACA”, Society of Forensic Toxicologists (SOFT) annual meeting abstract proceedings, Grand Rapids, MI, 2014

AB-CHMINACA is N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide.  The “alphabet soup” name seems to reside in the following generic name: AminomethloxoButaneCycloHexylMethylINdAzoleCarboxAmide. This synthetic cannabinoid was first encountered in February 2014 (NFLIS) and March 2014 (STRIDE). States reporting detection of this substance in products include AR, AZ, CA, CO, GA, IA, IN, KS, KY, LA, MO, ND, NJ, OH, OK, PA, TN, TX, and WI. From February 2014 to September 2014, there were 17 seizures of this compound (15.825 kg). The DEA also reports that there have been at least 4 documented deaths involving AB-CHMINACA.

A literature reference for AB-CHMINACA:

Hasegawa et al. (2014) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicology, Article in Press, doi: 10.1007/s11419-014-0245-6

THJ-2201 is [1-(5-fluoropentyl)-1H-indazol-3-yl)naphthalene-1-yl)methanone. This synthetic cannabinoid was first encountered in September 2013 (STRIDE) and January 2014 (NFLIS). States reporting detection of this substance in products include AR, AZ, CT, GA, IA, IL, IN, KS, KY, MN, MO, ND, NE, NH, NJ, OH, PA, TN, and WI. From September 2013 to September 2014 there were 6 seizures of this compound (5.5 kg). The DEA did not report any information on deaths associated with this compound.

A literature reference for THJ-2201:

Shevyrin et al. (2014) 3-Naphthoylindazoles and 2-naphthoylbenzoimidazoles as novel chemical groups of synthetic cannabinoids: chemical structure elucidation, analytical characterists and identification of the first representatives in smoke mixtures. Forensic Science International, 242, 72-80. PMID 25036783.

So, now after legislation and a few rounds of emergency scheduling, there are 25 synthetic cannabinoid compounds explicitly listed as federally controlled Schedule I substances:

January 2013

AM2201, AM694, CP-47,497, CP-47,497 (C8), JWH-018/AM678, JWH-019,JWH-073, JWH-081, JWH-122, JWH-200, JWH-203, JWH-250, JWH-398, RCS-4/SR-19,RCS-8/SR-18

May 2013

AKB48, UR144, XLR11

February 2014

5F-PB-22, AB-FUBINACA, ADB-PINACA, PB-22

December 2014

AB-CHMINACA, AB-PINACA, THJ-2201

 

Wonder what will be next? Maybe the AMB series? We’ll see. As always, the beat goes on.

Case Report - Synthetic Cannabinoid NNEI Related Death

A case of death caused by abuse of a synthetic cannabinoid N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide
Sasaki C, Saito T, Shinozuka T, Irie W, Murakami C, Maeda K, Nakamura N, Oishi M, Nakamura S, Kurihara K
Forensic Toxicology (2014) DOI 10.1007/S11419-014-0246-5
http://link.springer.com/article/10.1007/s11419-014-0246-5

This case was reported out of the Department of Legal Medicine, Kitasato University School of Medicine; the Department of Emergency and Critical Care Medicine, Tokai University School of Medicine; and the Department of Pathophysiology, Yokohama College of Pharmacy in Japan. The report describes a death associated with the synthetic cannabinoid, N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide.

This synthetic cannabinoid is also known as NNEI and is an indole carboxamide structural variant. NNEI is compared to other synthetic cannabinoid structures below.

A male (age was described as “in his twenties”) was found deceased on the floor in his bedroom. A package of “Fairy Evolution” herbal product was found in the vicinity. No medical history was known.

The Fairy Evolution herbal product was tested and NNEI was the only substance detected.

Exhaustive toxicological analyses were undertaken. Plasma, whole blood, urine, brain, heart, lung, liver, kidney, hair, and adipose tissue were analyzed. Femoral blood concentrations were 0.99 and 0.84 ng/mL (right and left vein respectively). NNEI was detected in all specimens analyzed, except urine. No other drugs or metabolites were detected in any biological specimens. Disposition of drug is discussed in the paper.

Pulmonary edema was detected at autopsy. The total weight of the lungs was 1,750 grams. Organs showed considerable congestion.

Arteriolar wall hypertrophy, slight interstitial fibrosis and contraction bands were detected in the heart.

Marked congestion and alveolar macrophage infiltrations were observed in the lungs.

Slight lymphocytic infiltrations were observed in liver.

Arteriolar hyalinization and severe splenic congestion was observed.

Corporal amylacea were observed in the corpus callosum in the brain.

No other remarkable findings were observed.

The authors determined cause of death to be associated NNEI and concluded that the acute circulatory disturbance to be induced by “NNEI poisoning”.  Manner of death was not disclosed in the paper, but my assumption is that it would be accidental or undetermined.

It is interesting to note that New Zealand preemptively banned NNEI from the market in 2012 due to the hypothesized formation of possible carcinogenic metabolites. It was hypothesized that the amide linkage could be hydrolyzed by carboxylesterases resulting in formation of 1-aminonaphthalene, a known carcinogenic substance. This was previously covered here. It has now been shown in in vitro experiments published by Thomsen et al. that carboxylesterase 1 (CES1) is the major hepatic and pulmonary enzyme that is responsible for the amide hydrolysis during metabolism of the indazole carboxamide synthetic cannabinoids AB-FUBINACA and AB-PINACA. As you can see from the structure representation above, AB-PINACA and NNEI share this same amide linkage. It is logical that NNEI would be metabolized via the same pathway.

Ultimately, I am ecstatic that we have seen a few papers published lately that describe case history + pathology/physical findings at autopsy + toxicology findings and analytical confirmation of substance.

Chemicals? Everything is chemicals! Part 26

I found this item in the grocery store today.

Introducing the chemical free way to remove dust, dirt, smudges, and fingerprints!

Cool! Chemical free, eh?

Let's take a closer look at the constituents.

 

So this "chemical free" cleaner is comprised of:

• An 84% Polyester and 16% Polyamide optical microfiber
• An 88% Polyester and 12% Polyamide cleaning microfiber
• A 100% Polyurethane foam core
• A 100% silicone ring band

Yeah, those aren't chemicals.

Oh wait. They are.

Polyester is a chemical. Polyamide is a chemical. Polyurethane is a chemical. Silicone is a chemical.

All chemicals.

Folks, don't buy into the "chemical-free" hype.

Tim Minchin: ...everything organic and natural is good, ignoring the fact that organic natural substances include arsenic and poo and crocodiles...everything chemical is bad...ignoring the fact that EVERYTHING is chemicals!

Case Reports of Synthetic Cannabinoid-Related Deaths

Several case reports of synthetic cannabinoid-related presentations to the emergency department in clinical toxicology have been published, but more often than not (for valid and invalid reasons), analytical confirmation of drug in the blood is not even attempted. In postmortem toxicology, these reports are exceedingly rare as only few case reports have been published surrounding circumstances of death.

There have been three case report papers published in 2013-2014 describing synthetic cannabinoid-associated deaths in conjunction with analytical confirmation of the specific substance and discussion of any associated pathology or physical findings at autopsy. This combination is what I call the "holy grail" of forensic toxicology. And no, this isn't a Monty Python sketch...

 

Case history + Analytical Confirmation + Autopsy Findings

It is through these case reports and those like them that we will begin to understand the postmortem toxicology of synthetic cannabinoids.

Case 1

An Accidental Fatal Intoxication with Methoxetamine

Maria Wikström, Gunilla Thelander, Maria Dahlgren, and Robert Kronstrand
Journal of Analytical Toxicology (2013) 37: 43-46
http://jat.oxfordjournals.org/content/37/1/43.full?sid=ef151e1d-5fb9-4d13-b802-70034953209b

This case was reported out of out of Sweden by the Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, and the Division of Drug Research, Linkoping University and describes a fatal intoxication with methoxetamine, AM-694, AM-2201, and JWH-018.

A 26 year old male was found lying deceased on the floor in his apartment. There were several bags found in the residence. One bag was labeled “2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone”, which is the chemical name for methoxetamine, and another bag was labeled as “Haze”.

Femoral blood toxicological findings consisted of methoxetamine (8.6 mcg/g), AM-694 (0.00009 mcg/g, AM-2201 (0.003 mcg/g), JWH-018 (0.00005 mcg/g), venlafaxine (0.3 mcg/g), O-desmethylvenlafaxine (0.4 mcg/g), and THC (0.001 mcg/g) . Pulmonary edema was observed at autopsy with no other remarkable findings reported. Cause of death was determined to be acute intoxication with methoxetamine. Manner of death was accident.

It is of interest to me that methoxetamine was determined to be the substance at play in the cause of death. While not specifically included in the cause of death ruling, the authors do make note in the paper that it is possible the synthetic cannabinoids detected may have played a role in contributing to cause of death. Venlafaxine and metabolite were detected at “therapeutic” concentrations.

Case 2

Toxicological Findings of Synthetic Cannabinoids in Recreational Users

Robert Kronstrand, Markus Roman, Mikael Andersson, and Arne Eklund
Journal of Analytical Toxicology (2013) 37: 534-541
http://jat.oxfordjournals.org/content/37/8/534.full?sid=5ea03ea0-f2d2-4bd4-89c9-05841794bcc2

This case was reported out of Sweden by the Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, and the Division of Drug Research, Linkoping University and describes a fatal intoxication with JWH-210.

A 17 year old male was found dead outdoors. An herbal potpourri product named “Smoke XXX” was found in his clothes pocket. Witness reports describe the smoking of the product. A ‘friend’ took two puffs, felt dizzy, and lost “his perception of touch” in his hands. The friend decided to move indoors while the deceased continued to use the product outdoors.

Femoral blood toxicological findings consisted of only JWH-210, which was at a concentration of 12 ng/g. Pulmonary edema was detected at autopsy. The total weight of the lungs was 1,264 grams. No other remarkable findings were observed. Cause of death was determined as hypothermia in combination with psychotropic substances. Manner of death was accident.

Case 3

Four Postmortem Case Reports with Quantitative Detection of the Synthetic Cannabinoid, 5F-PB-22
George Behonick, Kevin G. Shanks, Dennis J. Firchau, Gagan Mathur, Charles F. Lynch, Marcus Nashelsky, David J. Jaskierny, and Chady Meroueh
Journal of Analytical Toxicology (2014) 38: 559-562
http://jat.oxfordjournals.org/content/38/8/559.full

These cases were reported out of the University of Iowa Hospitals and Clinics; Department of Pathology and Laboratory Medicine, Mercy Medical Center; Physicians Laboratory, PC; and AIT Laboratories. The case reports describe a series of fatal intoxications with 5F-PB-22.

Case 3.1

A 17 year old male was using drugs (including ethanol) with a friend. During the early morning hours, he “began to gasp for air” and collapsed to the ground. After failed resuscitative attempts by EMS, he was pronounced dead.

Femoral blood toxicological findings consisted of 5F-PB-22 (1.1 ng/mL), ethanol (0.033%), amiodarone, and caffeine. Upon autopsy, no remarkable findings were observed. Cause of death was determined to be 5F-PB-22 intoxication. Manner of death was accident.

Case 3.2

A 27 year old male was brought to the ER with illness and diaphoresis. Upon admission he was diagnosed with acute liver and kidney injuries. After admission to ICU, he was diagnosed with “severe liver injury, severe coagulopathy, acute kidney injury, acute respiratory failure, hypoxemia, severe anion gap metabolic and lactic acidosis”. The patient’s condition deteriorated rapidly over the next half day and he experienced cardiac arrest and “pulseless electrical activity and poor oxygenation secondary to acute respiratory distress syndrome likely the result of aspiration and pulmonary contusions following chest compressions”. Failure of the circulatory system, respiratory system and central nervous system followed along with severe metabolic derangement.

An antemortem serum specimen obtained approximately 7 hours prior to death was positive for 5F-PB-22 (1.3 ng/mL). The only other drugs detected were THC-COOH and drugs administred during medical intervention (piperacillin, levofloxacin, and lorazepam). Cause of death was determined to be fulminant liver failure in the setting of THC and 5F-PB-22. Manner of death was undetermined.

Case 3.3

 

After a night of partying with friends, an 18 year old male decided to go to sleep at 9:45 am. He was found in bed unresponsive, pulseless, not breathing, and cool to the touch at 1:42 pm.

Postmortem Iliac blood toxicological findings consisted of only 5F-PB-22 (1.5 ng/mL). Bilateral pulmonary vasocongestion and congestion of the liver, spleen, and kidneys was observed at autopsy. No other remarkable findings were observed. Cause of death was sudden death in association with synthetic cannabinoid use. Matter of death was accident.

Case 3.4

 

After a night of partying, a 19 year old male returned home and indicated to his family he felt lightheaded. Around 12 noon, he decided to go to sleep. He was discovered deceased in his bed the next morning.

Postmortem superior vena cava blood was positive for 5F-PB-22 (1.5 ng/mL). No other drugs were detected. Remarkable findings at autopsy included bilateral pulmonary edema, necrotizing granulomatous inflammation with histoplasma microorganisms, and visceral congestion. Cause of death was acute drug intoxication with the synthetic cannabinoid, 5F-PB-22. Manner of death was accident.

It is of great importance to recognize that in the vast majority of the cases reported, relatively nonspecific pathological findings were observed at autopsy. These include pulmonary edema and various visceral congestion. In 83.3% of cases (cases 1, 2, 3.1, 3.3, and 3.4), these were the only physical findings observed.

I hope to see more of these types of case reports published. In my opinion, it is not enough to just publish a case without analytical confirmation AND without at least some discussion of pathology/findings at autopsy.

 

 

Movie Review in a Few Words: Big Hero 6

Big Hero 6

I didn't know too much about this series before watching the movie, but I have to say it was extremely well done (and not in the overcooked and burnt steak way).

Action and adventure? Yes.

Tragedy and sadness? Yeah, a bit.

Superheroes? Yup.

Villains? Of course.

Science? Hell yeah.

Humor? Goes without saying.

Fun? Definitely.

I highly recommend this movie for both kids and adults. Go watch it. You'll love it. Plus, at the beginning is a cute short (Feast) about a dog and his human friend.

Another day, another new synthetic cannabinoid...

The state of Louisiana has just banned another new synthetic cannabinoid derivative which has been associated with greater than 125 hospitalizations in the Baton Rouge vicinity since October 3, 2014 (I am not sure if these were analytically confirmed in blood/urine; I'm assuming not - I do not know any person or lab that is analyzing for this compound).

The newer synthetic cannabinoid is named MAB-CHMINACA, but is probably more widely known as ADB-CHMINACA.

ADB-CHMINACA (pictured above with other chemical structure derivatives) is a member of the now prevalent indazole carboxamide family of synthetic cannabinoids. Its chemical name is N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide. Chemical formula is C21H30N4O2.

The alphabet soup naming convention is defined as:

AminoDimethyloxoButaneCycloHexylMethylINdAzoleCarboxAmide

Even though it is suspected to be a synthetic cannabinoid receptor 1 and 2 agonist, the pharmacology and toxicology of this compound is unknown at this time. This compound's emergence on the designer drug market is just another part of the cat-and-mouse game that we've seen over the last several years.

"And the beat goes on, the beat goes on
Drums keep pounding a rhythm to the brain..."

____________________________________

The emergency rule issued by the State of Louisiana Department of Health and Hospitals can be found here.

News reports about the ban can be found here and here.

Quick Thought for the Night

The Society of Forensic Toxicologists (SOFT) annual conference is wrapping up tomorrow. I'll be glad to get home to my family, bed, and shower, but I cannot express how grateful I am to hold membership in a wonderful organization. SOFT is quite a bit of fun, but it is always a tremendous learning experience.  Here's to 2015 in Atlanta.

New Proposed US Federal Legislation on "Synthetic Drugs"

The Protecting Our Youth From Dangerous Synthetic Drugs Act of 2013, also known as S.1323, was introduced into the United States’ Senate on July 18, 2013. It is sponsored by Sen. Dianne Feinstein (D-CA) and cosponsored by Sen. Amy Klobuchar (D-MN), Sen. Joe Manchin (D-WV), Sen. Charles Schumer (D-NY), Sen. Al Franken (D-MN), Sen. Rob Portman (R-OH), Sen. Sheldon Whitehouse (D-RI), Sen. Mark Begich (D-AK), Sen. Barbara Boxer (D-CA), Sen. Kelly Ayotte (R-NH), and Sen. Jeanne Shaheen (D-NH). It was referred to the Senate Judiciary Committee on introduction in 2013 and to the International Narcotics Control Caucus for a hearing on May 14, 2014.

The bill is intended to make it easier for the United States government to control so-called designer drug or “synthetic drug” substances through the process of controlled substance “analogue” (CSA) determination.

A synthetic cannabinoid blend from 2012-2013

So, how does the bill actually propose to do this?

Through the establishment of a Controlled Substance Analogue Committee that will:

§  Be headed by the Administrator of the Drug Enforcement Administration (DEA)

§  Be comprised of chemistry and pharmacology experts from the DEA, National Institute on Drug Abuse (NIDA), the Centers for Disease Control and Prevention (CDC), and any other Federal agency that the Attorney General and Secretary of Health and Human Services deems appropriate

The CSA Committee will establish and maintain a list of CS analogues based on a substance’s similarity in chemical structure OR predictive pharmacological effect on the body to already established Schedule I and II substances. The "OR" is important as the Analogue Enforcement Act in its current form is interpreted as an "AND" clause with both chemical structure AND pharmacological effect similarity needing to be met. A second important statement included in the text is that evidence of human consumption is NOT NECESSARY before a substance is designated as a CS analogue. Currently, in order to be deemed an "analogue", a substance has to be for human consumption or at least sold as such.

The bill also details rules on importation of substances determined to be CS analogues by making it unlawful to import said CS analogues as well as the overall process of offically making a substance an "analogue".

It’ll be interesting to follow this bill as it moves through the process. Considering it was introduced 15 months ago, I’m sure the legislation will continue to proceed slowly and deliberately, yet I have no doubts it’ll eventually pass. There have been a few recent media reports surrounding the legislation and its possibility of banning substances in one quick motion with quotes from Sen. Schumer. I do caution - have we learned anything from the past? Let’s remember that the reactionary act of banning substances such as synthetic cannabinoids or substituted cathinones has contributed to the emergence and prevalence of compounds with truly unknown pharmacological and toxicological profiles. Legislation has led to the mess in which we find ourselves. Many of these newly emerging compounds currently have “mix-and-match” chemical structures from previous generations of substances. I’ve used the term “chemical grab bag” to describe them  in the past and I do think this description is entirely accurate. We know little to nothing of these compounds and their absorption, distribution, metabolism, and excretion in the human body. We know little to nothing of their pharmacology and toxicology. Acute effects? Nothing. Chronic effects? Nothing.

Nothing. Nothing. Nothing. We know nothing.

Regardless of what the government does, I don't see this cat-and-mouse game going away. It is here to stay. Will this legislation minimize the game or simply make it worse?

We'll see.

From Russia with love? Report on a new synthetic cannabinoid

Russia’s Health Ministry has recently reported on 25 synthetic cannabinoid-related deaths, along with more than 700 hospitalizations. The substance in question is simply described as MDMB N-Bz F. Average age of the hospitalizations is estimated at 24. According to this article, the substance has sent users “into vegetative state, provoking dementia and even respiratory arrest.” Other reports of this substance include a male who stabbed himself several times after smoking the synthetic cannabinoid product.

Russia’s Federal Drug Control Service (FDCS) has taken steps to control the substance (as well as any other substance “for a year the moment they are discovered”).

So, what is MDMB N-Bz-F?

Well…

No one really knows for sure.

MDMB-CHMINACA is a synthetic cannabinoid derivative of AB-CHMINACA, which is itself a derivative of AB-FUBINACA, which is a derivative of AB-PINACA.

Could MDMB N-Bz-F be a Benzyl Fluoro- derivative? This fluorobenzyl group is also found in FDU-PB-22, FUB-AMB, AB-FUBINACA, ADB-FUBINACA, and FUB-144.

 

 

Maybe. Maybe not.

With these ridiculous and illogical alphabet soup naming conventions for substances, I’m not sure we can make many, if any, inferences about the chemical structure for MDMB-N-Bz-F simply from the abbreviation itself. Ultimately, this substance is merely part of the cat-and-mouse game that we've seen over the last several years.

We’ll see if more is reported on this compound. Since I am having difficulty finding any information on this substance from a chemical structure perspective, I’m honestly not sure how this substance was analytically identified by the Russian authorities. If any Russian friends are reading this blog, please chime in. I’d love your perspective on this one.

Cheers,

FTG

Update on NH Synthetic Cannabinoid Illnesses - July/August 2014

As covered previously, the state of New Hampshire issued a state of emergency regarding an outbreak of illnesses and hospitalizations surrounding a synthetic cannabinoid-containing bubblegum flavored product named "Smacked!" In my last blog post about this topic, we covered why it may take so long to release this type of information (chain of custody, instrumental analysis, QC, goverment-lab workflow, this ain't CSI, etc.)

According to a release (dated August 22, 2014) by the New Hampshire Department of Safety, Division of State Police Forensic Laboratory (provided to me by Ryan Lessard, correspondent at NH Public Radio, @Ryan_Lessard), one package of the "Smacked!" product contained ADB-FUBINACA and a second package of the same product contained PB-22 and XLR11. As we've mentioned before, there is no uniformity between products of the same brand! QA/QC? Who needs stinkin' QA/QC? Obviously, these vendors and manufacturers do not.

XLR11 was made a Schedule I controlled substance at the Federal level on May 15, 2013 and ADB-FUBINACA and PB-22 were made Schedule I on February 20, 2014.

The lab also identified AB-CHMINACA and FUB-PB-22 in packages of Ultra 2014 and Scooby Snax.

It is most interesting to me that the product manufacturer would knowingly use already federally controlled substances in the products. My previous speculation was that the compound would turn out to be an INACA series substances, so I was partially correct on that one (ADB-FUBINACA). I have a copy of the NH release, so if anyone wants it, please contact me at forensictoxguy AT gmail DOT com. I'm having trouble uploading a PDF version of it at this time.

By the  way, the NH state of emergency has expired.

Many of these compounds have been previously covered here on the blog:

The new synthetic cannabinoids on the block...

Alphabet soup compounds

Fair is foul and foul is fair...

Notice of Intent - 4 synthetic cannabinoids into Schedule I

Synthetic cannabinoids in New Zealand

The game is afoot!

Outbreak of Illnesses in Louisiana

AMB series of synthetic cannabinoids and comparison to the INACA series


Cheers,

FTG


UPDATE on 9/10/2014:

@Infectiouschris has uploaded the information from New Hampshire. It can be found here.

Standard operating procedures exist in our world!

On August 14, 2014, the state of New Hampshire (NH) issued a state of emergency resulting from a series of synthetic cannabinoid-related illnesses. No actual adverse effects were described in Governor Hassan’s press release, but the alleged product was identified as the bubblegum flavor of “Smacked!”. According to reports, starting on August 11, 2014, the product was responsible for adverse effects in at least 41 people across the state of NH. InfectiousChris over at the Dilatant Pharma blog has the overall timeline covered extremely well and also notes that original New York (NY) press release mentions the product name “Smacked!”. I don’t know if this mention means that the "Smacked!" product was actually implicated in the NY illnesses or if it simply was an example of historical product names (similar to K2 and Spice).

K2 Blue, circa 2010-2011 - smelled like blueberry!

It has been 12 total days since the beginning of the NH illnesses and 30 days since the reported NY illnesses. We still have not heard if a specific synthetic cannabinoid has been identified by the DEA or local authorities in NH or NY.

As a drug chemist and forensic toxicologist, I have analyzed tens of thousands of drug samples and biological samples over the course of my career and have focused narrowly on new psychoactive substances over the last 4 or so years. The testing process can be very time consuming and complex. The procedures utilized in the real forensic lab are not reminiscent of those seen on television shows such as CSI or NCIS. We don’t have an Abby Sciuto that shoves the plant material directly into an GC/LC autosampler injector or mass spectrometer ion source (or I don't hope we have her on staff!). Standard operating procedures exist in our world. Chain of custody and documentation is a rule that isn't broken (remember these types of cases and resulting reports have a high probability of ending up as evidence in a criminal trial). Certified reference standards must be in hand. Sample weights must be ascertained via analytical balance. Organic extractions must take place using pH buffers solutions and solvents. Quality control samples must be prepared and then verified. Instrument calibration must be completed. Then we can finally run our case samples! Many times a sample is run twice via separate aliquots on complementary instrumentation to achieve an authentic screen result and a confirmed result. True unknown analysis and structural elucidation is more difficult but can be undertaken as well (if a lab has the analytical capabilities and ultimately time and money).

So, while I am disappointed that the identity of the specific synthetic cannabinoid has yet to be released, I am eagerly awaiting the news. I and others, including InfectiousChris, have placed phone calls and email messages to various people in NH government. Stay tuned for any further updates. But do remember that  even though this is a matter of public health and time is of the essence, the government typically moves at a snail's pace. And there really is no getting around that fact.

If anyone is reading this from NY or NH and needs help in analytical confirmation of any synthetic cannabinoid compound in either product or blood specimen, then please contact me. Either I can try to help or recommend a reputable lab that can help.

If you want my one and a half cents speculation, the offending compound may be an INACA-based synthetic cannabinoid, such as AB-CHMINACA or AB-PINACA (or others pictured above). But that is 100% my own rambling speculative thoughts based on what I know about the current prevalance of these compounds.

Stay safe.

FTG

Synthetic Cannabinoid Illnesses in NH - August 2014

New Hampshire Governor Maggie Hassan has issued a state of emergency after a rash of overdoses on synthetic cannabinoids. On Monday night in Manchester, NH, there were 17-25 reported illnesses. There were 9 reported synthetic cannabinoid-related illnesses on Tuesday night. There have been at least 3 illnesses in Concord, NH in the last 24 hours.

Some of these incidents were allegedly associated with a bubblegum flavored herbal incense product named "Smacked!". Two other products named in the press release were "Crazy Monkey" and "Green Giant", though it was noted they weren't involved in the illnesses. The identification of any specific synthetic cannabinoids have not been confirmed.

As always, stay safe.

FTG

MDMA isn't an amphetamine?

Dallas Cowboys' defensive back Orlando Scandrick was suspended today for four games due to a positive urine test for MDMA. Scandrick’s story consists of an excuse that he was in Mexico on vacation and was persuaded by a friend to add a substance to the beverage that they were consuming. Allegedly he did not know the identification of the substance he ingested.

In an article from ESPN.com, it is stated:

“While MDMA alone would be considered a drug of abuse and would not subject Scandrick to suspension for a first-time positive test, the drug sometimes contains an amphetamine component, which does fall under the league’s PED policy and led to Scandrick’s punishment.”

What?

I do not pretend to know the specifics of the NFL drug testing policy and it seems that amphetamine–family drugs are banned under the performance enhancing drug (PED) section of policy (why it is covered there is really a discussion for another day). Even with that said, the given reasoning absolutely makes no logical sense.

MDMA is an amphetamine derivative! D’oh!

MDMA, otherwise known as 3,4-methylenedioxymethamphetamine, is a substituted derivative of methamphetamine. It was first synthesized by Merck in 1914 and its widespread recreational use in the 1970s and 1980s caused it to be placed into Schedule I of the Controlled Substances Act (CSA) by the DEA on July 1, 1985.

In a toxicology laboratory, the presence of MDMA and MDA in urine is commonly monitored via an immunoassay screening analysis (with amphetamine or methamphetamine as a target compound) and a confirmatory analysis utilizing either gas chromatography with mass spectrometry (GC/MS) or liquid chromatography with tandem mass spectrometry (LC/MS/MS). MDMA’s chemical formula is C11H15NO2 and its molecular weight is 193.2 g/mol. MDMA is extensively biotransformed and excreted as multiple metabolites in the urine, including 3,4-methylenedioxyamphetamine (MDA). MDMA is detectable in the urine for 1-5 days after administration of the drug. Drug detection windows are variable and approximate. They ultimately depend on a myriad of factors including the nature of the drug consumed, the route of administration, the individual's metabolism, the dosage of drug consumed, and the hydration state of the individual.

As reported many other places, supposed Ecstasy or MDMA may contain other stimulant compounds (such as PMA, methamphetamine, or methylone), but this does not seem to be the case in this situation. I would expect that if Scandrick tested positive for an additional compound, then that information would have been released along with the MDMA result.

Cheers,

FTG

Synthetic Cannabinoid Illnesses in Indiana - August 2014

There are reports out of Fort Wayne, Indiana regarding six people hospitalized in a 12 hour period after using a synthetic cannabinoid product. While the overall number of people presenting is small, it was enough to garner some attention. No product names are given and no synthetic cannabinoids are named. Indiana has some strong laws around these compounds, including an exhaustive list of explicitly banned compounds and structural classes. The state also employs an analog clause and an "imitation" or "lookalike drug" language. Pretty much if it is a synthetic cannabinoid or sold as such, then it is banned one way or another.

I'm going to check into this one some more and see what I can find out.

Cheers,

FTG

Synthetic Cannabinoid Illnesses in NY - July 2014

Officials in New York are issuing a warning with regards to a small outbreak of synthetic cannabinoid illnesses which have sent at least 15 people to the emergency room in East and Central Harlem and Chelsea over the last few days.

The report also stated that in New York synthetic cannabinoid associated visits to the emergency department have increased by 220% (assuming this is in comparison to 2013).

New York legislation doesn't explicitly control any of the newer waves of synthetic cannabinoid receptor agonists, but it does broadly define what a synthetic cannabinoid is and what a synthetic cannabinoid analog is.

This report seems on the small side especially when compared to recent reports in Colorado, Louisiana, Texas, and Florida, but these things always start small and increase rapidly. I'll update if I see any more information.

UPDATE / July 28, 2014 at 1:30 pm:

Here is the actual NY Department of Health and Mental Hygiene press release.

Also, here is a link from a story over at the Village Voice Blogs. I simply love the title (minus the "fake weed" terminology).

I still don't see any reports on what specific adverse effects have been encountered. Or of course no mention of analytical confirmation at this point.



Stay safe.

FTG

Thought for the Weekend

While writing up case reports regarding synthetic cannabinoid-associated deaths and reading other reports, this thought occurred...

Synthetic cannabinoid receptor agonists (especially newer generation compounds from 2013+) are a diverse chemical grab bag o' "fun". 

Fun is defined here as adverse effects including tachycardia, seizure, nephrotoxicity, and death.

If you choose to partake in the substances, then keep that in mind. And no, I do not recommend or condone using synthetic cannabinoid containing products, so don't ask me what substances I would recommend using (seriously I get those kinds of questions).

Cheers,

FTG