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.