ETR - 2018, Quarter 2

A few days ago, the DEA released its Emerging Threats Report (ETR) for the second quarter of 2018. The agency touts this report as a "quarterly snapshot of the new psychoactive substance market in the United States". There are some interesting things of note which are included in this report.

Two new synthetic cannabinoids were detected for the first time - these were the alphabet soup 5F-EDMB-PINACA and 5F-MDMB-PICA. The top two most prevalent synthetic cannabinoids (which accounted for 50% of all detections) were FUB-AMB and 5F-ADB (also known as 5F-MDMB-PINACA) - both of these compounds have remained in the top two spots since 2016. Interestingly, they both were emergency scheduled by the Federal government in 2017, so I'm not quite sure what to make of their continued stay on the list.

Regarding designer opioids, the market has pretty much shifted back to fentanyl, which made up 75% of all designer opioid detections for the quarter. The compounds 4-ANPP and acetylfentanyl were detected a summed total of 74 times, while 13 other designer opioids (valerylfentanyl, parafluorobutyrylfentanyl, benzylfentanyl, 4'-methylacetylfentanyl, 3-methylfentanyl, U48800, furanylfentanyl, U47700, cyclopropylfentanyl, carfentanil, 4-fluoroisobutyrylfentanyl, butyrylfentanyl, and methoxyacetylfentanyl) accounted for 50 total detections or approximately 10% of all detections. Fentanyl analogs and other designer opioids are still out there in the wild, but they do not seem to be as prevalent as they were for the previous 1-2 years. Illicitly manufactured fentanyl continues to be the top dog in this category - ask any forensic toxicologist and she would tell you the same thing (and do please go talk to us forensic toxicologists, it can be very lonely working in a lab).

You get fentanyl! And you get fentanyl! We all get fentanyl!

There were only a total of 24 cathinones detected, of which 15 were N-ethylpentylone (62.5%). Older compounds such as MDPV, alpha-PVP, methylone, butylone, and ethylone are nowhere to be found.

The only designer benzodiazepine detected for the quarter was one identification of flubromazolam.


The Emerging Threats Report for Quarter 2 of 2018 can be found here.

Exposure to "Fentanyl" in the Field

It's in the news everywhere.

Fentanyl.

Fentanyl and secondary exposure.

Here are some of the news headlines from the last few weeks...

From KLTV7, a Harris County, TX police officer was hospitalized after coming in contact with a fentanyl-laced paper flyer. The officer "removed the flyer, got into her car and drove away. She soon began feeling lightheaded and had other symptoms". This story was also tweeted by the official handle of the Harris County, TX Sherriff's Office.

@HCSOTexas

From KATC3, police officers in Lafayette, LA responded to a call of an unresponsive man at a residence. Upon observing the scene, two officers "showed symptoms of being exposed to the potent drug [fentanyl]".

 

From ABC13 Eyewitness News, a Houston, TX police officer checked a person's hotel room and found 50-100 pills in a plastic bag. The officer "put the baggie in the patrol car" and "he started feeling ill, shortness of breath and feeling dizzy, and he was no getting better".

From the Belleville News Democrat, two police officers were responding to a series of overdoses at a Brooklyn, IL strip club when they came into contact with fentanyl and began to feel ill. "The thing with fentanyl is the smallest amount, like if you put just less than a gram in a room, it can knock out everyone in the room. It's a pretty hardcore substance, and it's happening everywhere."

There are other stories out there.

It goes without saying that fentanyl is a potent mu-opioid receptor agonist substance that produces central nervous system depression. That is true.

 

Chemical structure of Fentanyl

Drawn by Kevin G. Shanks (2017)

It's been used as a pharmaceutical in the USA since 1968. Intravenous and intrathecal fentanyl is used for anesthesia and analgesia in a hospital setting. It is also available as a transdermal patch for chronic pain management, or as a lozenge for oral transmucosal absorption which is intended for opioid tolerant people and in the treatment of breakthrough pain in cancer. It can also be used intranasally and sublingually.

But can stories like this really happen?

No. Not from dermal absorption of powder. It's not possible. NOT. POSSIBLE.

NOT POSSIBLE.

Let's go to the facts.

The American College of Medical Toxicology (ACMT) (a really smart group of medical doctors) has issued a position paper on this topic and they brought math, science, and some much needed damned common sense to the table.

You can read their position here via the Clinical Toxicology journal website.

Go read it.

Now.

It's good. I promise.

...
...
...
...
...
...

OK. You read it?

Notice the lack of hyperbole and hysteria?

No. Not that Hysteria.

Notice the logical viewpoints?

Notice the use of math and science?

 

Lots o' numbers! You're making my head explode!
http://dx.doi.org/10.1080/15563650.2017.1373782

TL;DR.

It is impossible to dermally absorb enough powder fentanyl to produce any sort of pharmacological effect. There needs to be some sort of mechanism in place to move that fentanyl through the skin. Pharmaceutical companies invested a large amount of time, effort, and money to develop transdermal delivery systems to administer drug (e.g. transdermal patch to place on the skin). If you were to find yourself in a situation where you had powdered fentanyl on your skin, calmly walk over to the sink and wash your hands with soap and water.

Let's use facts in our discussions about drugs. Hysteria and hyperbole is not helpful to anyone. At all. In fact, it makes things worse. Much worse.

PS.

The flyers from Harris County, TX mentioned above were tested in a lab and contained no fentanyl or any other drug. Imagine that!

PPS.

Now there's this gem of a story in the news today...

From the Northwest Indiana Times, a paramedic was attempting to intubate an unresponsive man when the man coughed and snorted in his face. After doing his job and returning to the fire station, the paramedic "began to feel unwell an fell unconscious". The paramedic suspected he "was exposed to a powerful synthetic opioid, such as fentanyl".

Yeah..no.

Semi Charmed Life (1997)

Third Eye Blind's song 'Semi Charmed Life' debuted as the first single on the band's 1997 self-titled album. 

Third Eye Blind album cover art (1997)

It quickly became one of the most well known (and most played) songs of the late 90s as it made its way up the charts peaking at number 4 on the US Billboard Hot 100. The song was featured in several movies including Dirty Work (1998), Wild Things (1998), American Pie (1999), and A Lot Like Love (2006). A snippet of it can also be heard in Contact (1997). 

 

 

Music Video, Semi Charmed Life (1997), YouTube

 

It’s an upbeat catchy song right from the opening line, so much so that I can recognize the song by only 1-2 seconds being played of it.

 

Doo doo doo, doo doo-doo doo... 

 

It’s a happy song...or is it?

 

Have you really listened to the lyrics? Read them below. You'll soon find out that it isn't a happy song after all.

 

I'm packed and I'm holding

I'm smiling, she's living, she's golden

She lives for me, says she lives for me

Ovation, her own motivation

She comes round and she goes down on me

And I make her smile, like a drug for you

Do ever what you wanna do, coming over you

Keep on smiling, what we go through

One stop to the rhythm that divides you

 

And I speak to you like the chorus to the verse

Chop another line like a coda with a curse

Come on like a freak show takes the stage

We give them the games we play, she said...

 

I want something else, to get me through this

Semi-charmed kinda life, baby, baby

I want something else, I'm not listening when you say good-bye

 

Doo doo doo, doo doo-doo doo...

 

The sky was gold, it was rose

I was taking sips of it through my nose

And I wish I could get back there, someplace back there

Smiling in the pictures you would take

Doing crystal meth, will lift you up until you break

It won't stop, I won't come down

I keep stock with the tick-tock rhythm, I bump for the drop

And then I bumped up, I took the hit that I was given

Then I bumped again, then I bumped again

I said...

 

How do I get back there, to the place where I fell asleep inside you

How do I get myself back to the place where you said...

 

I want something else, to get me through this

Semi-charmed kinda life, baby, baby

I want something else, I'm not listening when you say good-bye

 

 

I believe in the sand beneath my toes

The beach gives a feeling, an earthy feeling

I believe in the faith that grows

And the four right chords can make me cry

When I'm with you I feel like I could die

And that would be alright, alright

 

 

And when the plane came in, she said she was crashing

The velvet it rips in the city, we tripped on the urge to feel alive

Now I'm struggling to survive, those days you were wearing that velvet dress

You're the priestess, I must confess

Those little red panties they pass the test

Slide up around the belly, face down on the mattress

 

One

And you hold me, and we're broken

Still it's all that I wanna do, just a little now

Feel myself, heading off the ground

I'm scared, I'm not coming down

No, no

And I won't run for my life

She's got her jaws now, locked down in a smile

But nothing is alright, alright

 

And I want something else, to get me through this life

Baby, I want something else

Not listening when you say...

Good-bye, good-bye, good-bye, good-bye

 

Doo doo doo, doo doo-doo doo...

 

The sky was gold, it was rose (Doo doo doo, doo doo-doo doo...)

I was taking sips of it through my nose (Doo doo doo, doo doo-doo doo...)

And I wish I could get back there (Doo doo doo, doo doo-doo doo...)

Someplace back there, in the place we used to start (Doo doo doo, doo doo-doo doo...)

 

 

I want something else (Doo doo doo, doo doo-doo doo...)

Lyrics as written by Stephan Jenkins.

____________________________________________________________

Semi Charmed Life is the happiest sounding song you'll ever hear about doing methamphetamine and drug addiction.

 

 

 

 

The beat goes on...

The US Federal government has moved to control five new synthetic cannabinoids as Schedule I controlled  substances.

Synthetic cannabinoid herbal incense

Image by Kevin G. Shanks (2015)

These newer alphabet soup synthetic cannabinoids include:

4-CN-CUMYL-BUTINACA
1-(4-cyanobutyl)-N-(1-methyl-1-phenylethyl)-1H-indazole-3-carboxamide

5F-AB-PINACA
N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(5-fluoropentyl)-1H-indazole-3-carboxamide

4-CN-CUMYL-BUT7AICA
1-(4-cyanobutyl)-N-(1-methyl-1-phenylethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide

MMB-CHMICA
Methyl(1-(cyclohexylmethyl)-1H-indole-3-carbonyl)-L-valinate

NM2201
Napthalen-1-yl 1-(5-fluoropentyl)-1H-indole-3-carboxylate

Chemical Structures of Newly Controlled Cannabinoids

Drawn by Kevin G. Shanks (2018)

With the inclusion of these five substances, the Federal government has now scheduled 38 synthetic cannabinoids since 2011. In case you want to learn more about synthetic cannabinoids, I wrote a 2.5 minute primer on them quite a while ago. It's a quick read and is still more than applicable -  you can find it here.

Also, there are many posts about these substances on this blog. Please read some of them as these are substances of extreme toxicological importance. These substances are cheap. They are used for convenience and to evade drug tests for THC. They are easy to get ahold of. Yet, they are complete pharmacological and toxicological unknowns. As I usually say, when people consume products containing synthetic cannabinoids, they are ingesting substances of unknown identification with unknown pharmacological and toxicology properties in unknown dosages in unknown combinations. It's a recipe for disaster.


And the beat goes on...

Stay safe.


References

United States DEA (2018) Notice of Intent: Schedules of Controlled Substances: Temporary Placement of NM2201, 5F-AB-PINACA, 4-CN-CUMYL-BUTINACA, MMB-CHMICA, and 5F-CUMYL-P7AICA Into Schedule I.
Federal Register, Volume 83, Number 103
https://www.deadiversion.usdoj.gov/fed_regs/rules/2018/fr0530.htm

CDC Warning - Vitamin K Dependent Antagonist Coagulopathy Associated With Synthetic Cannabinoid Use

Looks like the issue has spread - which isn't all that surprising. But is frightening.

The Center for Disease Control (CDC) issued a warning regarding the surge in severe bleeding cases associated with synthetic cannabinoid use from Illinois. From March 10 to April 5, 2018, ninety-four (94) people have presented to the hospital with severe bleeding symptoms after exposure to herbal incense/potpourri synthetic cannabinoid products. Eighty nine (89) of the cases are in Illinois, with the remaining five (5) originating in Indiana, Maryland, Missouri, and Wisconsin. There has been positive analytical confirmation of Brodifacoum in at least eighteen (18) individuals, with two (2) fatalities. Brodifacoum has been identified as a constituent in three (3) synthetic cannabinoid products.

Read here and here for previous my updates on this issue as well as a quick explainer as to what Brodifacoum actually is.

If you are on Twitter, check out Dr. Steve Aks (@ERtox) and Cook County Medical Examiner's Office (@CookCountyME) for updates.

Be safe.


References

Outbreak Alert: Potential Life-Threatening Vitamin K Dependent Antagonist Coagulopathy Associated With Synthetic Cannabinoid Use
https://content.govdelivery.com/accounts/USCDC/bulletins/1e6dac3
Accessed: April 7, 2018

Tainted Synthetic Pot Eyed As Cause Of Another Illinois Death As Store Owner Accused Of Selling Substance Held Without Bail
http://www.chicagotribune.com/news/local/breaking/ct-met-fake-pot-poison-cook-county-20180406-story.html
Accessed: April 7, 2018

Bleeding and Coagulopathy Associated with Synthetic Cannabinoid Products
https://dosemakespoison.blogspot.com/2018/03/bleeding-and-coagulopathy-associated.html

Update of an Outbreak of Severe Bleeding Cases / Synthetic Cannabinoid Use
http://dosemakespoison.blogspot.com/2018/04/update-of-outbreak-of-severe-bleeding.html

Update of an Outbreak of Severe Bleeding Cases / Synthetic Cannabinoid Use

As I wrote about the other day, there was a mass outbreak of severe bleeding cases associated with synthetic cannabinoid use in Illinois during March. As of March 29, there were 22 reports of vitamin K dependent severe coagulopathy.

Five days later and there have been 56 affected individuals. Symptoms include coughing up blood, blood in the urine, severe bloody nose, and/or bleeding gums. Nine people have tested positive for the vitamin K antagonist Brodifacoum (see my last post for explanation of its effects). Two people have died.

Three people have been arrested in Chicago in connection to selling some herbal incense/potpourri products that (according to police) have detectable amounts of Brodifacoum.

Dump your product if you have any.

Stay safe out there.


References

Bleeding and Coagulopathy Associated with Synthetic Cannabinoid Products
https://dosemakespoison.blogspot.com/2018/03/bleeding-and-coagulopathy-associated.html

Second Death of An Individual Who Used Synthetic Cannabinoids
http://www.dph.illinois.gov/news/second-death-individual-who-used-synthetic-cannabinoids
Accessed April 3, 2018.

3 Chicago Store Clerks Charged With Selling Synthetic Pot Laced With Rat Poison
http://abcnews.go.com/US/chicago-store-clerks-charged-selling-synthetic-pot-laced/story?id=54197525
Accessed April 3, 2018.

Bleeding and Coagulopathy Associated With Synthetic Cannabinoid Products

There have been warnings out of Chicago over the last couple days regarding users of synthetic cannabinoid products experiencing abnormal bleeding issues especially from the eyes and ears. As of today (Thursday, March 29), there have been 22 reports in the Chicago area since March 7. Vitamin K dependent severe coagulopathy has been observed in several cases which is consistent with exposure to a 4-hydroxycoumarin rodenticide (superwarfarin) such as brodifacoum.

 

Chemical Structure of Brodifacoum

Drawn by Kevin G. Shanks (2018)

A substance such as Brodifacoum inhibits the action of the vitamin K epoxide reductase enzyme. This enzyme inhibition interferes with the recycling of vitamin K epoxide to vitamin K and ultimately results in a steady decrease in blood vitamin K, which is a problem, because vitamin K is a vital part of the synthesis of prothrombin (coagulation factor II). Prothrombin is involved in the blood coagulation cascade, also known as blood clotting.

Low vitamin K means severely impacted blood clotting which can result in profuse bleeding.

Another effect of Brodifacoum is the increase in permeability of blood capillaries, leading to internal hemorrhaging, or when blood leaks from vessels. An individual can bleed internally progressively with time.

Brodifacoum is a highly lipophilic substance and has an extremely slow elimination pathway from the body. Biological half-life of the substance is 20-130 days. LD50 values for mammals are substantially less than 1.0 mg/kg. It is a potent substance with a long duration of action that can result in devastating effects in humans (and animals) - afterall, it's primary (only) use is to kill warfarin-resistant rodents (hence the class name superwarfarins).

Other superwarfarins include Bromadiolone, Coumatetralyl, Difenacoum, Flocoumafen, and Tioclomarol.

This is not the typical media hysteria/hyperbole that we all have grown accustomed to over the years with reporting on drugs. While no specific products have yet been implicated, my advice is that if you are a synthetic cannabinoid user (or know a user) in the Illinois area (including bordering states), discard your supply. Immediately.

Be safe.



References

Outbreak: severe coagulopathy associated with synthetic cannabinoids (K2/Spice)
http://myemail.constantcontact.com/Outbreak--Severe-coagulopathy-associated-with-Synthetic-Cannabinoids---K2-Spice--.html?soid=1100929526407&aid=_6hDV-Frs5Q; Accessed March 29, 2018.

Synthetic pot warning issued after 22 people in Illinois report bleeding from eyes, ears
http://www.chicagotribune.com/news/local/breaking/ct-met-fake-weed-synthetic-cannabis-warning-20180329-story.html; Accessed March 29, 2018.

Illinois health officials warn of synthetic pot after 17 people report of severe bleeding.
http://wgntv.com/2018/03/29/illinois-heath-officials-warn-of-synthetic-pot-after-17-people-report-severe-bleeding/; Accessed March 29, 2018.

IDPH issues warning about synthetic cannabinoids.
http://dph.illinois.gov/news/idph-issues-warning-about-synthetic-cannabinoids; Accessed March 28, 2018.

High Impact Research from JAT

One of my papers from 2014 is listed among the "highly cited articles" in the Journal of Analytical Toxicology. It involves the analytical detection of the synthetic cannabinoid 5F-PB-22 in postmortem toxicology and presentation of four deaths that were associated with its use. You can read it, along with other papers, for free at the link below. Have fun reading!

High-Impact Research from JAT

Forensic Toxicology Valentines

Happy Valentine's Day!

Here are a few Valentine's wishes.

Roses are CO red.
Violets are cyanotic blue.
Let's hope you're neither already dead,
Nor hypoxic too.

Postmortem blood is red.
And sometimes blue,
And oftentimes green.
And maybe black too.

Decomposed liver is brown.
Decomposed liver is too.
Decomposed kidney is also brown.
Why is everything brown?

Postmortem blood is red.
It may also be blue,
Though it can be black.
It smells horrible, too.

MDMA and cannabis are Schedule I.
LSD is too.
Do they belong?
Let me ask you.

NERD and Rihanna - Lemon

NERD and Rihanna’s song Lemon came across my Spotify list last night. The song came out a few months ago but this was my first time ever hearing it.

"Bath salt...bitin’ speakers in the face..."

Yes, the infamous 2012 Causeway Cannibal bath salts attack is referenced here - the attack that was not ever shown to be “bath salt” related, not to mention even drug related at all.

Here’s a link to the song. It's got a nice beat. Enjoy!

Kratom Redux

Kratom is back in the news. 

Long story short...

During the summer of 2016, the DEA moved to place kratom (mitragynine/7-hydroxymitragynine) into Schedule I of the Controlled Substances Act. Almost immediately there was a massive outcry from advocates of the plant, as well as members of Congress, toxicologists, and physicians. I initially wrote about this here. In an unprecedented move, the DEA rescinded their Notice of Intent in Fall 2016. In the Withdrawal, the DEA stated that they would accept public comment on the scheduling of these substances until December 1, 2016 as well as request a scientific/medical evaluation of the substances from the Food and Drug Administration (FDA). During the approximate 2 month comment period, the DEA received around 20,000+ comments, with near 100% having positive comments on the plant.

The FDA has now released their report on Kratom. If you want to read the 164 page document, you can find it here.

I'm not going to go into much here, because other folks have covered it comprehensively.

Nick Wing, a senior reporter with the Huffington Post, covered the FDA report and methodically looked at the case reports where Kratom was associated with cause of death that were covered in the FDA report. You can find his article here.

Dr. David Kroll at Forbes covered it as well and his excellent work can be found here.

Kratom researchers in academia from across the USA and Canada also penned a letter to the DEA and the White House's newly established Opioid Commission. The letter can be found here.

I highly recommend reading the links as they are all spot on.

When the DEA initially moved to schedule Kratom in summer 2016, I said the move was misguided. And farcical. And that the DEA hadn't thought it completely through. 

And after reading the FDA's report, I still believe that.

Random Observations on the Opioid Epidemic

Stop treating substance use, dependence, and addiction as a crime.

Listen to doctors and nurses. Listen to medical professionals. Listen to toxicologists.

The answer is not always, "Make it illegal!" or "It needs to be a controlled substance."

Stop throwing drug users in jail. Get those folks who are dependent or addicted the treatment they need.

Increase access to medical treatment for drug dependence/addiction.

Expand methadone and buprenorphine maintenance treatment.

Think about the harm reduction potential of safe injection sites and clean needle programs.

Don't conflate the medical use of pharmaceutical opioids with the misuse of pharmaceutical opioids.

Recognize the need for compassionate pain management.

Legalize medical and recreational cannabis.

Naloxone should be available over the counter everywhere.

Call for Abstracts and Speakers - MATT 2018

This will be one of the rare times you'll see a work affiliated post on this blog.

I'm chairing the scientific program for the Midwest Association of Toxicology and Therapeutic Drug Monitoring (MATT) meeting. The 2018 meeting will be held in Indianapolis, IN on April 12-13th.

The meeting announcement can be found here. There will be more information coming very soon.

If you have a toxicology topic of interest to present (either poster or oral presentation), please contact me at kshanks@axisfortox.com.

In the News: Tom Petty

The Los Angeles County, California Medical Examiner/Coroner's Office released Tom Petty's official cause and manner of death yesterday.

The cause of death was "multisystem organ failure due to resuscitated cardiopulmonary arrest due to mixed drug toxicity (fentanyl, oxycodone, temazepam, alprazolam, citalopram, acetylfentanyl, and despropionylfentanyl).

Other conditions listed included coronary artery atherosclerosis and emphysema.

Manner of death was accident.

Tom Petty's family released a statement on social media and his personal website. The statement can be read here.

_______________________________

What were the substances found in his system?

Several central nervous system depressants or related substances and an antidepressant.

Fentanyl is an synthetic opioid typically prescribed as the pharmaceutical medications Duragesic (transdermal), Actiq (oral transmucosal), or Fentora (buccal). Historically, it has been used to treat breakthrough pain and is used in pre-operation procedures as an analgesic and anesthetic. Fentanyl is a mu opioid receptor agonist that is considered to be approximately 100-200 times as potent as morphine as an analgesic. It is metabolized to norfentanyl. The substance is also illicitly manufactured in clandestine laboratories and has been found as a very common adulterant in street heroin and counterfeit tablets over the last few years. Fentanyl is a Schedule II controlled substance in the USA.

Oxycodone is a semisynthetic opioid that is derived from thebaine. Trade names of the  pharmaceutical medication include OxyContin, OxyIR, Roxicodone, Percocet, or Endocet. It is typically used for the relief of moderate to severe pain. It functions as a mu opioid receptor agonist. Oxycodone is metabolized to oxymorphone and noroxycodone. Oxycodone is a Schedule II controlled substance in the USA.

Temazepam is a benzodiazepine routinely prescribed as the brand name Restoril. Chemically, it is a 3-hydroxyl derivative of diazepam (trade name Valium). It is used for the treatment of short term insomnia. It functions as a GABAA receptor agonist. Temazepam is metabolized to the oxazepam. Temazepam is also a metabolite of diazepam. Temazepam is a Schedule IV controlled substance in the USA.

Alprazolam is a potent benzodiazepine prescribed as the brand name Xanax. It is typically used to treat anxiety and panic disorders. Much like temazepam (and other benzodiazepines), it functions as a GABAA receptor agonist. Alprazolam is metabolized to alpha-hydroxyalprazolam. Alprazolam is a Schedule IV controlled substance in the USA.

Citalopram is a drug prescribed as an antidepressant under the brand name Celexa. It functions as a selective serotonin reuptake inhibitor (SSRI) and is approved for treatment of major depressive disorder and is prescribed off-label for a multitude of other conditions including anxiety and panic disorders and obsessive-compulsive disorder. From a chemistry standpoint, citalopram is sold as a racemic mixture of the R and S enantiomers, with the S enantiomer having an antidepressant effect. A medication named Lexapro is sold as only the S enantiomer otherwise known as escitalopram. Citalopram is metabolized to desmethylcitalopram and didesmethylcitalopram. Citalopram is not a controlled substance, but is only available via prescription.

Acetylfentanyl is a synthetic fentanyl derivative that is considered to be about fifteen times more potent than morphine as an analgesic. It is not available as a prescription medication and is a true designer/research chemical substance. It functions as a mu opioid receptor agonist, much like fentanyl and oxycodone. Chemically, acetylfentanyl differs from fentanyl by a replacement of the propionyl group with an acetyl group. Acetylfentanyl has been found in the USA since 2013 and has been detected in street heroin and counterfeit pharmaceutical tablets. It was made a Schedule I controlled substance in the USA in 2015.

Despropionylfentanyl is also known as 4-ANPP. It is a very minor metabolite of fentanyl and is a precursor in the illicit (non-pharmaceutical) synthesis of illicitly manufactured fentanyl and related fentanyl analogs. The substance itself has very little pharmacological activity, but its presence in the human body can be used to aid in determining the source of fentanyl used, e.g. consumption of pharmaceutical fentanyl vs. ingestion of illicitly manufactured fentanyl.

My thoughts?

I won't give many thoughts because I am not privy to the case specifics. I do not know all the details. The only people that know the details are those who investigated his death and formulated the final autopsy report and cause of death certification. Any general comments I make are speculative in nature, but are based on my knowledge and experience in the field.

From a general forensic toxicology standpoint, the real takeaway is that this is a dangerous combination of substances to use concurrently. He was consuming two powerful opioid and two potent benzodiazepines which when used together can create synergistic effects and exaggerated central nervous system depression. Add that situation to an already compromised cardiovascular and respiratory system, and it's a recipe for disaster.  For my own information, I would love to see the full toxicology report with quantitative measures of drug, etc. How much fentanyl was present? How much temazepam and alprazolam were detected? Not that any of that really matters though.

With the detection of acetylfentanyl and despropionylfentanyl, it seems as if Tom Petty was supplementing his pharmaceutical medications with illicitly manufactured substances. Acetylfentanyl is not a pharmaceutical medication anywhere in the world and is only found as a designer opioid/analog meant to skirt the controlled substances act in the USA. Fentanyl does not metabolize to acetylfentanyl. As despropionylfentanyl is a precursor/intermediate used in the illicit (non-pharmaceutical) synthesis of fentanyl, it generally used as a marker for exposure to illicitly manufactured fentanyl. The presence of this substance has also been associated with the use of various fentanyl analogs including acetylfentanyl, acrylfentanyl, and furanylfentanyl. No one knows if the use of illicit opioid was intentional or not. Remember the situation surrounding Prince's death. Multiple pills were found in his residence that looked like pharmaceutical hydrocodone/acetaminophen but turned out to be counterfeit tablets containing fentanyl and the opioid research chemical U-47700.

As a conclusion, I'll say, please do not mix depressant drugs. Do not mix opioids with benzodiazepines. Do not mix either of them with ethanol. Stay safe, folks.

Addendum:

I just saw that the great Dr. David Kroll wrote an article on this matter over at Forbes. Go read his work here. He is one of the best writers on these sorts of topics.

Always confirm presumptive results. Always.

Baltimore police raided a grocery store at the beginning of December 2017 and seized 13.2 pounds of what they suspected was morphine and 16.5 pounds of what they suspected was fentanyl. Two individuals faced distribution of fentanyl and other related drug charges and then were held in jail without bail. Other items seized were vials, containers, tubes, capsules, and plastic bags.

Turns out that the drugs were neither morphine nor fentanyl. As reported by the Baltimore Sun, charges have been dropped in the case as the substances were not identified by the crime laboratory as morphine or fentanyl or illicit drugs or controlled substances. The story seems to still be developing and as reported, the police say they will provide more information Thursday (1/4/2018) as to the substance's identity.

Thoughts?

Now, I'm not sure in this case if presumptive field tests were used, but this is a good reminder to always confirm presumptive results prior to making any medical or legal decision. Field tests, color tests, reagent tests, point of care device tests, dipstick tests, laboratory immunoassay tests, and other similar tests are considered presumptive in nature. They are prone to false positive results (and false negative results too). Care must be taken in interpreting a presumptive test and if any important decision is to be made using the result, the result must be confirmed via an alternate more specific confirmatory method such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), which is not prone to false positives (or negatives).

Also, as to what the substance was? Maybe one of the many fentanyl analogs or designer opioids available in the wild these days? That's complete speculation, but if it was an analog, I wouldn't expect the police to drop charges. Maybe flour or sugar? Or some baking powder? This was a corner shop/grocery store after all. Who knows what the substance was. I guess we'll find out when the police let us know.

Stay tuned on this one.

In case you want to read about false positive results for amphetamines by a presumptive immunoassay test, read this (a little ditty...about immunoassays).


References

http://www.baltimoresun.com/news/maryland/crime/bs-md-ci-store-raid-folo-20171206-story.html

http://www.baltimoresun.com/news/maryland/crime/bs-md-ci-fentanyl-charges-dropped-20180103-story.html