Saturday, January 20, 2018

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.


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.

Wednesday, January 3, 2018

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.


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).


Wednesday, December 13, 2017

More Opioids Scheduled in the USA...

The United States Federal government filed a Notice of Intent today to schedule the following seven fentanyl analog compounds:


Interestingly, Isobutyrylfentanyl was technically already covered as a controlled substance as the government had previously controlled Butyrylfentanyl (and its isomers) in March 2016. Also, Parafluorobutyrylfentanyl was technically covered as the government had previously controlled Parafluoroisobuyrylfentanyl (and its isomers) in March 2017. Maybe this is another sign by the Government that the Analogue Enforcement Act is neither effective nor efficient in its purpose?

Also published was a Final Order to control the opioid research chemical MT-45. It seems that the government skipped filing a Notice of Intent and went directly to Final Order on this one.

Heracles vs. the Hydra. Southern entrance to the Hofburg,Vienna, Austria.
Image from:

This brings the list up to 20 total fentanyl analogs and designer opioids scheduled by the Federal government since 2015.

2015: Acetylfentanyl

2016: AH-7921, Betahydroxythiofentanyl, Butyrylfentanyl, Furanylfentanyl, U47700

2017: Acrylfentanyl, Cyclopentylfentanyl, Cyclopropylfentanyl, Isobutyrylfentanyl, Methoxyacetylfentanyl, MT-45, Ocfentanil, Orthofluorofentanyl, Parachloroisobutyrylfentanyl, Parafluorobutyrylfentanyl, Parafluoroisobutyrylfentanyl, Paramethoxybutyrylfentanyl, Tetrahydrofuranylfentanyl, Valerylfentanyl

It is quite alarming to see that the number of compounds scheduled has rapidly increased each year since the initial scheduling of Acetylfentanyl in 2015. Also, don’t forget that the other major fentanyl derivative that has caused many intoxications and deaths in the USA, Carfentanil, is already Schedule II.

Novel psychoactive substances (NPS) are like the mythological Hydra. Sever one head, and two more sprout from the wound.


Schedules of Controlled Substances: Temporary Placement of Seven Fentanyl-Related Substances in Schedule I. 21 CFR Part 1308, Docket No. DEA-475, Federal Register Volume 82, Number 238 (December 13, 2017)

Schedules of Controlled Substances: Placement of MT-45 into Schedule I. 21 CFR Part 1308, Docket No. DEA-451, Federal Register Volume 82, Number 238 (December 13, 2017)                          

Sunday, December 10, 2017

Cyanide: A 2 Minute Primer

Slobodan Praljak, formerly a general in the Croatian Army and Croatian Defense Council, was convicted of crimes against humanity and violations of war/Geneva Convention during the Croat-Bosniak War (1992-1995). He received a 20-year prison sentence in 2013. At an appeals hearing in The Hague on November 29, 2017, and upon hearing that his conviction would be upheld, Praljak spoke, “Judges, Slobodan Praljak is not a war criminal. With disdain, I reject your verdict!” He then drank from a small bottle and said, “What I am drinking now is poison.” The judge stopped the hearing and medical professionals were summoned. He died a short while later.

Image of Slobodan Praljak in the act of drinking a vial of liquid during his appeals hearing at The Hague on November 29, 2017.
It has now been reported by Dutch officials that Slobodan Praljak committed suicide by drinking cyanide.
What is cyanide?
Cyanide, also known as hydrocyanic acid, has a molecular formula HCN and its molecular weight is 27.03 g/mol. HCN’s boiling point is 25.6°C (78.1°F). Hydrogen cyanide was first isolated from the pigment Prussian blue; hence another alternative name is prussic acid. In the 1800s, cyanide was given its modern name from the English word cyan, which means a shade of blue.  Hydrogen cyanide and its potassium and sodium salts have been used as fumigants, insecticides, metal polishes, and in gold/silver electroplating solutions. Cyanide vapor can be detected by a characteristic almond odor, but it is estimated that up to approximately 50% of the human population cannot detect this odor due to a recessive genetic trait. Cyanide can be found in trace levels in the human body as a result of normal metabolic processes, as well as from eating a diet high in cyanogenic foodstuffs (e.g. apples, apricots, bitter almonds, and cherries) and smoking cigarettes.

Chemical structure of Hydrogen Cyanide

Structure drawn by Kevin G. Shanks (2017)

What does cyanide do to the body?
Cyanide inhibits cellular respiration by binding to the iron atom in the cytochrome c oxidase enzyme, an enzyme involved in the last step of the mitochondrial electron transport chain. Normally, during this step, molecular oxygen is converted into water. This inhibition causes oxidative phosphorylation to halt and the Kreb’s cycle is disrupted. Adenosine triphosphate (ATP) cannot be produced by the mitochondria. Pyruvic acid, formed during glycolysis, accumulates and is modified anaerobically to lactic acid. Lactic acid buildup causes metabolic acidosis. Oxygen also builds up in tissue and alters the gradient for oxygen release from hemoglobin, which produces cellular hypoxia.
The onset of symptoms of cyanide poisoning is dependent on the route of exposure/administration. Hydrogen cyanide vapor is rapidly absorbed through inhalation. Potassium and sodium cyanide salts are more easily absorbed via oral ingestion, but are absorbed at lower rates and if ingested orally, they are converted to hydrogen cyanide via gastric acids. The lethal dose of hydrogen cyanide has been estimated to be 100 mg while sodium/potassium cyanide’s lethal dose has been estimated to be 200-300 mg.
Acute intoxication symptoms of cyanide poisoning are central nervous system stimulation, headache, dizziness, tachycardia, shortness of breath, rapid breathing, and vomiting. Other symptoms that may occur after initial intoxication include seizure, bradycardia, hypotension, coma, and cardiac arrest. Chronic administration of cyanide can lead to abnormalities of vitamin B12, folate, and thyroid function as well as severe longer-term neurological issues.
What does the body do to cyanide?
Cyanide is biotransformed to thiocyanate by the hepatic enzymes rhodanese and beta-mercaptopyruvate-cyanide sulfurtransferase. Thiocyanate is then excreted into the urine. Other metabolic pathways include trapping of cyanide by hydroxocobalamin via formation of vitamin B12, oxidation to formic acid and carbon dioxide, and pulmonary excretion of unchanged substance. The elimination half-life of cyanide in whole blood is reported as 0.7-2.1 hours. Volume of distribution is 0.4 L/kg.
Has it been used as a historical poison?
Because of its ease of use and toxicity, cyanide has appeared throughout history regularly as a poison, in warfare, suicides, and homicides. Some of the most well-known modern cases are:
It is rumored that cyanide played a role in Grigori Rasputin’s assassination in 1916. He was allegedly given cyanide-laced cakes and Madeira wine.
Hydrogen cyanide, as the pesticide Zyklon B, was used in gas chambers to murder people in the Nazi concentration camps during World War II.
In the 1940s, Erwin Rommel, Eva Braun, and Heinrich Himmler all committed suicide by cyanide liquid ingestion. The six children of Joseph Goebbels were murdered by being injected with morphine by Helmut Kunz, an SS dentist, and administered cyanide Ludwig Stumpfegger, Adolf Hitler’s personal doctor.
In 1974, Ronald Clark O’Bryan gave potassium cyanide laced Pixie Stix to his son, daughter, and three other children. The son ate the candy, while none of the other children did. The boy died. During the police investigation it was determined that the boy had a life insurance policy on him worth a very large amount of money. The father was convicted of murder in 1975 and was executed via lethal injection in 1984.
In 1978, in Jonestown, Guyana, 907 people died in a mass suicide event lead by Jim Jones. Cyanide, alongside diazepam, chloral hydrate, and promethazine, was consumed via a grape flavored beverage.
In 1982, seven people died from a series of drug tampering cases in Chicago, Illinois. Tylenol brand acetaminophen had been laced with potassium cyanide by an unknown person. Several more deaths occurred in copycat crimes. No one was ever convicted of these homicides.
In 1988, Stella Nickel was convicted of murdering her husband and another woman with cyanide-laced Excedrin tablets. She received a 90 year prison sentence.
Cyanide has also been used in capital punishment in the United States, with the last gas chamber execution via cyanide occurring in Arizona in 1999. It still remains an option for capital punishment in six states.
In 2012, Wall Street trader Michael Marin consumed a cyanide tablet while in the courtroom shortly after a guilty verdict for arson was rendered.
In 2015, John McLemore committed suicide using potassium cyanide. He was currently recording a narrative for the investigative journalism podcast S-Town.
Cyanide is a rapidly acting substance that causes death via disruption of cellular respiration and results in hypoxia and cardiac arrest. It is found as hydrogen cyanide or as potassium or sodium salts. It has been effectively used throughout history as an agent to murder people and has been implicated in suicides

Bosnian war criminal dies after swallowing poison in court. CNN. November 30, 2017.
Slobodan Praljak died after taking cyanide in court. Al Jazeera. December 2, 2017. Translated from Dutch to English via Google Translate. 12/03/2017.
Baselt, R. Cyanide. Disposition of Toxic Drugs and Chemicals in Man. Eleventh Edition. Biomedical Publications: Seal Beach, CA, 536-539 (2017).
Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. (2017).
Poisoned, shot, and beaten: why cyanide along may have failed to kill Rasputin. The Guardian. January 13, 2017.
The Holocaust: A Learning Site for Students, United States Holocaust Memorial Museum.
Candy Man’s legacy still haunting today. Chron. October 30, 2003.
Jones plotted cyanide deaths years before Jonestown. CNN. November 12, 2008.
How the Tylenol murders of 1982 changed the way we consume medication. PBS. September 24, 2014.
Bitter Pill: A Wife on Trial. CBS News: 48 Hours, 2001.
Michael Marin, former Wall Street trader, took cyanide after arson conviction, says autopsy. CBS News.  July 27, 2012.
Woodstock man at the center  of “S-Town” podcast . Tuscaloosa News. March 28, 2017.
Methods of Execution. Death Penalty Information Center.

Saturday, November 11, 2017

Running for Charity

The kid and I are running the Drumstick Dash in Indianapolis on 11/23. We are trying to raise money to help provide meals for the homeless in Indianapolis and all money raised goes to Wheeler Mission. We've raised $100 so far and would love to raise more to help. If you can can help, it's much appreciated (hit the link below) or since this is the kid's first race so drop a comment wishing him good luck. 

Here is a good informational source on homelessness in Marion county, Indiana for 2016 from the Indiana University Public Policy Institute.

Thursday, October 26, 2017

Tales of (Un)Poisoned Halloween Candy

It's Halloween time and stories are starting to emerge (again...groan) about drugs being given out in Halloween candy or candy being poisoned and handed out to the kiddos.

Headlines like this...



Let me just stop you right there and right now.

Folks are not giving out drugs in Halloween candy. They are not.

Drugs are expensive. No one is giving away that stuff. No one.

It's true that drugs can be made to look like candy. Especially marijuana/THC infused edibles. They can look like this...

Cute and tasty looking gummy bears! Though each of those bears contains 10 mg of THC, the main psychoactive substance found in cannabis/marijuana. Let me be quite clear one is giving these out for free. Edibles are damned expensive. And hard to come by in certain locales. No one is giving them out to random children for free.

And of course, Ecstasy tablets look like candy...

But Ecstasy is expensive. Drug dealers are not just going to give up tablets for free. It makes no sense to think this does happen.

These headlines pop up every year just before Halloween, but did you know that there has never been a single documented case where someone was randomly handing out drugs in Halloween candy or poisoned-laced loot.

None. Zero. Nil. Nada. Zilch.

It's an urban legend. A myth.

Now, let's not confuse this with homicide/murder during Halloween times and then blaming it on the "candy was poisoned" myth. 
In 1970, a 5 year old child in Michigan ate some Halloween candy and died a few days later. Toxicology showed the death was from a heroin overdose. The Halloween candy was analyzed by the lab and heroin was found. The police investigation concluded that the child found a family member's drug stash and consumed some of it. To cover up the death and the family member's involvement, family concocted a scheme to contaminate the Halloween candy with heroin after the boy's death.

In 1974, a Texas father gave potassium cyanide laced Pixie Stix to his son and daughter and three other children. The son ate the candy, while none of the other children did. The boy died. During the police investigation it was determined that the boy had a life insurance policy on him worth a very large amount of money. The father used the poisoned Halloween candy myth (the legend was around back then too) as cover for his plot to kill the boy and collect the life insurance. The father was convicted of murder in 1975 and was executed via lethal injection in 1984.

There have been countless other drugs in Halloween candy scares across the USA since the 1970s and upon investigation, each one has proven to be untrue.

So, please, go ahead and eat your Halloween candy loot this year without drug worries.

Happy Halloween!


Candy suspected in death of boy, 5 - 1970

Candy Man's legacy still haunting today - 2003


Monday, October 2, 2017

Girl on LSD

It is being reported that Tom Petty is in critical condition on life support after being found in cardiac arrest. Some outlets have reported he has passed. I have grown up listening to Petty's music - through high school and college and into adulthood. His music has been a huge part of my music listening life. So many good songs. So many good associations.

His most beautiful song? Wildflowers.

Best song to drive to? You Wreck Me and Runnin' Down A Dream. Preferably played back to back.

One of the first songs I knew all the words to? Free Fallin

Biggest song memory in junior high/high school? You Don't Know How It Feels

Song that makes me think about life? Learning to Fly

Coolest music video? Don't Come Around Here No More - I'm a sucker for Alice in Wonderland themes.

Song I can't help but sing no matter where I am? Mary Jane's Last Dance, always thought it was neat that it mentioned Indiana, then found out later it was originally titled Indiana Girl and thought that was even more awesome.

But the song I'll never forget is the one song that never made it to an album because it was deemed too controversial at the time by record execs, but was the B side on the 1994 single release of You Don't Know How It Feels...

Girl on LSD.

Such a great song from a drug and toxicology perspective.

Crystal meth.
China White (aka heroin).

Give it a listen. And while you're at it, smile and throw some good thoughts out there. The world needs some positivity these days.


Update: Tom Petty has passed on. The Rock Band In The Sky added one more member.