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!