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

Toxicology of Designer Drugs (Lecture 1, Introduction to Forensic Toxicology)

I'm teaching a toxicology of designer drugs course at IUPUI this fall via the Forensic and Investigative Sciences Program.

The outline of topics for the first lecture included:

Introduction to Forensic Toxicology

    • The Realms of Forensic Toxicology
      • Human Performance
      • Postmortem
      • Drug Facilitated Crimes
      • Urine Drug Testing
    • The Role of the Forensic Toxicologist
      • Analyze specimens
      • Analytical instrumentation
      • Develop and validate testing methods
      • Case review and release
      • Results interpretation
      • Education
      • Expert and fact witness courtroom testimony
      • Research, publish, and present
    • Autopsy and Toxicology Specimens
      • Blood
      • Urine
      • Vitreous Humor
      • Tissues
      • Bile
      • Gastric contents
      • Alternative matrices
    • Toxicological Terms
      • Pharmacokinetics
        1. Dose
        2. Dosing interval
        3. CMax
        4. TMax
        5. CMin
        6. Volume of distribution
        7. Concentration
        8. Elimination half life
        9. Elimination rate constant
        10. Bioavailability
      • Pharmacodynamics
        1. Onset vs. Duration of action
        2. Receptor agonism
        3. Receptor antagonism
        4. Receptor inverse agonism
        5. Catecholamines / Neurotransmitters
          • Serotonin
          • Norepinephrine
          • Dopamine
          • Histamine
          • Acetylcholine
          • GABA

Tuesday, September 19, 2017

Visited Purdue University Today

I visited Dr. Susie Swithers' Drugs and Behavior class at Purdue University today and introduced the students to forensic toxicology. Had some good interactions with the students. I have fun with things like this - love outreach and education.

While you're reading this, why not peruse Purdue's Psychological Sciences website and learn something new?

Forensic Toxicology Job Listings

Some good job opportunities are out there for forensic toxicology!

The following are good references and sites for job postings:

Society of Forensic Toxicologists - Job Listings

American Academy of Forensic Sciences - Job Postings

Midwestern Association of Forensic Scientists - Employment

Southwestern Association of Forensic Scientists - Employment

Northeastern Association of Forensic Scientists - Employment

Tuesday, September 12, 2017

Three more fentanyl analogs to be placed into Schedule I

The DEA announced today a notice of intent to place three more fentanyl analogs into Schedule I of the Controlled Substances Act. These compounds are Methoxyacetylfentanyl, Ortho-Fluorofentanyl, and Tetrahydrofuranfentanyl. 

According to the Federal Register, the first detection of Ortho-Fluorofentanyl in drug seizure evidence was in April 2016 and the first detection of Tetrahydrofuranfentanyl was in March 2017. Methoxyacetylfentanyl was first identified in solid dose evidence in April 2017. There have been multiple confirmed fatalities associated with each of these substances.

These three compounds make a total of nine (9) fentanyl analogs controlled by the DEA since 2015. Others controlled in this time period are Acetylfentanyl (2015), Betahydroxthiofentanyl and Butyrylfentanyl, and Furanylfentanyl (2016), and 4-Fluorisobutyrylfentanyl and Acrylfentanyl(2017).


References

United States DEA (2017) Notice of Intent. Schedules of Controlled Substances: Temporary Placement of Orthofluorofentanyl, Tetrahydrofuranylfentanyl, and Methoxyacetylfentanyl
 into Schedule I. Federal Register. Volume 82, Number 175.
https://www.gpo.gov/fdsys/pkg/FR-2017-09-12/pdf/2017-19283.pdf

Monday, September 11, 2017

Synthetic cannabinoid FUB-AMB to be placed into Schedule I

The DEA announced today a notice of intent to place the synthetic cannabinoid FUB-AMB into Schedule I of the Controlled Substances Act.

The chemical formula of FUB-AMB is C21H22FN3O3 and molecular weight is 383.42 g/mol. Alternative alphabet soup names for this substances include AMB-FUBINACA and MMB-FUBINACA. FUB-AMB emerged as a substance in herbal incense and smokable potpourri blends in the USA sometime between 2014-2016. FUB-AMB is structurally related to the Pfizer developed synthetic cannabinoid AB-FUBINACA. In 2016, Banister et al. reported on the pharmacology of FUB-AMB and structurally related compounds. They determined FUB-AMB to be a potent synthetic cannabinoid receptor agonist. In the study, FUB-AMB's half maximal effective concentration or EC50 at CB1 equaled 2.0 nM and 18 nM at CB2.

Image taken by Kevin G. Shanks (2017)


A "mass casualty event" in Brooklyn, New York occurred on July 12, 2016, when thirty three (33) people reported adverse effects after smoking an herbal incense product. Eighteen (18) of the 33 people were hospitalized. Adams et al. reported on this outbreak of illnesses in The New England Journal of Medicine on January 2017. Common reported effects included blank stares, slow responses, "zombielike" groaning, slow mechanical movements of the arms and legs, and lethargy. Blood, serum, and urine specimens were obtained from eight (8) of the people who were admitted to the hospital. The authors also analyzed a package of the product purported to be at the center of the mass illnesses - AK-47 24 Karat Gold. FUB-AMB was detected in the product. An FUB-AMB metabolite was detected in the blood or serum of all patients tested.

This act makes 33 synthetic cannabinoids scheduled at the federal level since 2011.

One more synthetic cannabinoid scheduled, one more to take its place.

The beat goes on...


References

United States DEA (2017) Notice of Intent. Schedules of Controlled Substances: Temporary Placement of FUB-AMB into Schedule I. Federal Register. Volume 82, Number 174.
https://www.deadiversion.usdoj.gov/fed_regs/rules/2017/fr0911.htm

S.D. Banister et al. (2016) Pharmacology of Valinate and tert-Leucinate Synthetic Cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and Their Analogues. ACS Chemical Neuroscience. 7: 1241-1254.
http://pubs.acs.org/doi/abs/10.1021/acschemneuro.6b00137

A.J. Adams et al. (2017) Zombie Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York. The New England Journal of Medicine. 376: 235-242.
http://www.nejm.org/doi/10.1056/NEJMoa1610300