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:

Cyclopentylfentanyl
Isobutyrylfentanyl
Ocfentanil
Parachloroisobutyrylfentanyl
Parafluorobutyrylfentanyl
Paramethoxybutyrylfentanyl
Valerylfentanyl

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: https://www.britannica.com/topic/Hydra-Greek-mythology

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.

 
References

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) https://www.deadiversion.usdoj.gov/fed_regs/rules/2017/fr1213_2.htm

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.
Conclusion
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

References
Bosnian war criminal dies after swallowing poison in court. CNN. November 30, 2017. http://www.cnn.com/2017/11/29/europe/slobodan-praljak-hague-sentencing/index.html
Slobodan Praljak died after taking cyanide in court. Al Jazeera. December 2, 2017. http://www.aljazeera.com/news/2017/12/slobodan-praljak-died-cyanide-court-171202171937067.html
https://www.om.nl/actueel/nieuwsberichten/@101280/voorlopige/. 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. https://www.theguardian.com/science/blog/2017/jan/13/poisoned-shot-and-beaten-why-cyanide-may-have-failed-to-kill-rasputin
The Holocaust: A Learning Site for Students, United States Holocaust Memorial Museum. https://www.ushmm.org/outreach/en/article.php?ModuleId=10007714
Candy Man’s legacy still haunting today. Chron. October 30, 2003. http://www.chron.com/neighborhood/article/Candy-Man-s-legacy-still-haunting-today-9774087.php
Jones plotted cyanide deaths years before Jonestown. CNN. November 12, 2008. http://www.cnn.com/2008/US/11/12/jonestown.cyanide/index.html
How the Tylenol murders of 1982 changed the way we consume medication. PBS. September 24, 2014. https://www.pbs.org/newshour/health/tylenol-murders-1982
Bitter Pill: A Wife on Trial. CBS News: 48 Hours, 2001. https://www.cbsnews.com/news/bitter-pill-a-wife-on-trial/
Michael Marin, former Wall Street trader, took cyanide after arson conviction, says autopsy. CBS News.  July 27, 2012. https://www.cbsnews.com/news/michael-marin-former-wall-street-trader-took-cyanide-after-arson-conviction-says-autopsy/
Woodstock man at the center  of “S-Town” podcast . Tuscaloosa News. March 28, 2017. http://www.tuscaloosanews.com/news/20170328/woodstock-man-at-center-of-s-town-podcast
Methods of Execution. Death Penalty Information Center. https://deathpenaltyinfo.org/methods-execution

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.

 https://www.crowdrise.com/k-and-h-run-the-drumstick-dash/fundraiser/kevinshanks#the-story

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...


Or...

 
Or...

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 again...no 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!


References

Candy suspected in death of boy, 5 - 1970
http://www.nytimes.com/1970/11/07/archives/candy-suspected-in-death-of-boy-5.html

Candy Man's legacy still haunting today - 2003
http://www.chron.com/neighborhood/article/Candy-Man-s-legacy-still-haunting-today-9774087.php


 

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.

Marijuana.
Cocaine.
Beer.
Crystal meth.
Glue.
Ecstasy.
Pills.
China White (aka heroin).
Caffeine.

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.

Peace.

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

Saturday, September 23, 2017

Toxicology of Designer Drugs (Lecture 3, Fentanyl, Fentanyl Analogs, and Designer Opioids)

The third installment of Toxicology of Designer Drugs focused on the emergence of fentanyl, fentanyl analogs, and other designer opioids in modern street heroin.

The outline of topics for this lecture included:

Fentanyl, Fentanyl Analogs, and Designer Opioids

    • Sliding scale of harm
      • Water
      • SSRI antidepressants
      • Benzodiazepines
      • Tricyclic antidepressants
      • Barbiturates
      • Opiates / Opioids
    • Opioid Deaths in the USA (Pre-2014/2015)
      • 2000 - 2014 data
      • Opioid analgesic deaths continue to rise
      • Surge in deaths, two trends
      • Double trouble: heroin and fentanyl
    • Heroin
      • History
      • Chemistry
      • Pharmacology
      • Metabolism
      • Forms of the product
      • NFLIS data, 2001 - 2016
    • Fentanyl
      • History
      • Chemistry
      • Pharmacology
      • Metabolism
      • Forms of the product (licit vs. illicit)
      • Death of Prince
      • NFLIS data, 2001 - 2015
      • NFLIS data, 2013 - 2015
      • NFLIS data, 2016
      • NY Times report on trends in US overdose deaths, 2017
    • Fentanyl Analogs
      • What are they? Where do they come from?
      • How many compounds exist?
      • DEA scheduling actions, 2015 - 2017
      • DEA Emerging Threats Reports, 2017
      • Overdoses, hospitalizations, and reported deaths in media
      • Analyte Specific Looks
        1. 3-methylfentanyl (cis/trans)
        2. Acetylfentanyl
        3. Furanylfentanyl
        4. Acrylfentanyl
        5. Carfentanil
    • Designer Opioids
      • Opioid research chemicals
        1. U47700
          • Death of Prince
        2. AH7921
        3. MT-45
    • Analytical Methods
      • Method development
      • Method validation
      • Organic extraction
      • Instrumental analysis via LC-MS/MS
    • Prevalence
      • What drugs have been detected?
      • How prevalent are they?
      • What locations are they found?
      • Special look at Carfentanil detections
    • Postmortem Case Studies
      • Case 1 (Information Withheld)
      • Case 2 (Information Withheld)
      • Case 3 (Information Withheld)
      • Case 4 (Information Withheld)
      • Case 5 (Information Withheld)
      • Case 6 (Information Withheld)
      • Case 7 (Information Withheld)
      • Case 8 (Information Withheld)
    • Testing for Fentanyl Analogs and Designer Opioids vs. A Fishing Expedition
    • Conclusions

Toxicology of Designer Drugs (Lecture 2, A Brief History of Designer Drugs)

Here is the next installment of my Toxicology of Designer Drugs class - this lecture focused on a high level look at the timeline of designer drugs in the USA.

A Brief History of Designer Drugs
    • 1960s and 1970s
      • LSD
      • Mescaline
      • DOM (STP)
      • PCP / TCP / PCE
    • 1980s
      • Fentanyl derivatives (China White)
      • MDMA
      • MPPP / MPTP
      • Methamphetamine / Methcathinone / 4-methylaminorex
    • 1990s
      • Anabolic steroids
      • Research chemicals
      • The 2C family and PiHKAL / TiHKAL
    • 2000s and 2010s
      • Cathinones and designer stimulants
      • Synthetic cannabinoids
      • Analogs of sildenafil / herbal supplements
      • Designer opioids / fentanyl analogs
      • Benzodiazepine derivatives
      • NBOMes
      • Methoxetamine
      • Nootropics