Synthetic Cannabinoid Receptor Agonists (2020 – 2021)
by Kevin Shanks, M.S., D-ABFT-FT
Note: This is an excerpt of a presentation given to the LTG (London Toxicology Group) in June 2021.

Packages of SCRA products
Photograph by Kevin G. Shanks (2015)
Synthetic cannabinoid receptor agonists (SCRA) are laboratory synthesized chemicals which bind to cannabinoid receptors in the human body. There are thousands of these compounds in existence and there is no way to discuss all of them, but since 2009, many of these compounds have been sold as ingredients in smoking blends and herbal incense/potpourri in the United States. Over the last several years, the government has enacted various pieces of legislation controlling these compounds as Schedule I controlled substances and, currently, there are 43 SCRA considered to be controlled substances. The prevalence of specific synthetic cannabinoids vary over time and new compounds routinely emerge and disappear.

Chemical structures of 5 Common SCRA
Structures drawn by Kevin G. Shanks (2021)
According to data from the Center for Substance Abuse Research (CESAR) via quarterly Emerging Threats Reports (ETR), the prevalence of 5F-ADB and FUB-AMB have waned over the last couple of years, and the most prevalent compounds reported in 2020 were 5F-MDMB-PICA, followed by the MDMB-4en-PINACA and 4F-MDMB-BINACA. If you look at data from the National Forensic Laboratory Information System (NFLIS), compiled by the Drug Enforcement Administration (DEA) via non-biological evidence seizure, for 2020, the most common SCRAs were 5F-MDMB-PICA, MDMB-4en-PINACA, and 4F-MDMB-BINACA.

Detection of SCRA in Blood at Axis, 2018
Data compiled by Kevin G. Shanks (2021)

Detection of SCRA in Blood at Axis, 2019
Data compiled by Kevin G. Shanks (2021)

Detection of SCRA in Blood at Axis, 2020
Data compiled by Kevin G. Shanks (2021)
If we look at Axis Forensic Toxicology from the last few years, we can see that our data for postmortem toxicology mirrors what is reported by ETR and NFLIS. In 2018, 5F-ADB was the most prevalent SCRA (80.4% positivity in all sample tested for SCRA), while in 2019, 4F-MDMB-BINACA was the most prevalent compound (42.3% positivity). During 2020, the most prevalent compound reported in postmortem toxicology casework for synthetic cannabinoids testing was 5F-MDMB-PICA (60.0% positivity). During 2020, three compounds (5F-MDMB-PICA, 4F-MDMB-BINACA, and 5-ADB) accounted for 90+% of positive synthetic cannabinoid detections in blood samples tested.

Chemical structures of 3 Emerging SCRA
Structures drawn by Kevin G. Shanks (2021)
Recognizing this ever changing scope of testing, we must always look towards the future and we need to be aware of newly reported SCRA compounds. Some of these compounds include 4F-MDMB-BICA, ADB-BINACA, and ADB-HEXINACA. What more should we expect in the future? We should expect more of the same. The beat goes on and new compounds emerge. They become prevalent. They disappear. And then new compounds take the place of the old ones.

The Puzzle Pieces of an SCRA
Image drawn by Kevin G. Shanks (2021)
Axis Forensic Toxicology continues to adapt SCRA testing to provide a relevant scope of analysis and aid in the medical-legal investigation of death and poisoning. For more information, the current scope of testing offered by Axis Forensic Toxicology can be found in the online test catalog (Order Code 42130, Synthetic Cannabinoid Panel, Blood).
If you would like a full copy of this presentation, please contact [email protected].
References
- Synthetic Cannabinoid Receptor Agonists (2020 – 2021). K. Shanks. London Toxicology Group (LTG) Virtual Meeting. (2021).
- Synthetic Cannabinoids. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages 1979-1986. (2020).
- Synthetic Cannabinoid Receptor Agonists. Novel Psychoactive Substances: Classification, Pharmacology, and Toxicology. Paul Dargan and David Wood. Academic Press (Elsevier). 317-338. (2013).
- Axis Forensic Toxicology. Laboratory Data. Indianapolis, IN. (accessed July 2021).
- Published in Drug Classes
Drug Primer: Synthetic Cannabinoids
by Kevin Shanks, M.S., D-ABFT-FT
Synthetic cannabinoids are laboratory synthesized chemicals which bind to cannabinoid receptors in the human body. The JWH series of cannabinoids was developed by Dr. John Huffman at Clemson University. UR-144 is an Abbott Labs compound which was developed during investigational drug research. ADB-FUBINACA is a synthetic cannabinoid which was synthesized by Pfizer. Numerous synthetic cannabinoids, such as 4F-MDMB-BINACA and 5F-MDMB-PICA, exist, which have no formal history in academic or pharmaceutical industry research.
In the USA, since 2008-2009, synthetic cannabinoids have been sold as ingredients in herbal incense, potpourri, or smoking blends. Throughout the last decade, various waves of legislation have been passed by the Federal government classifying several synthetic cannabinoids as Schedule I controlled substances. There are currently 43 synthetic cannabinoid substances that are controlled at the Federal level in the USA. These substances have no recognized medicinal application. Each state has its own controlled substance laws and may vary according to their regional drug trends.

Chemical structures of 3 Synthetic Cannabinoids
Structure drawn by Kevin G. Shanks (2021)
Synthetic cannabinoids are cannabinoid receptor agonists. The cannabinoid receptor 1 (CB1) is found primarily in the central nervous system and is responsible for mediating the psychoactive effects of cannabis and related-substances. Cannabinoid receptor 2 (CB2) is located in the peripheral nervous system, the spleen, and the immune system, and is thought to be involved in pain perception mediation and immunosuppression. Unlike delta-9-tetahydrocannabinol (THC), which is a partial agonist of CB1 and CB2 receptors, the majority of synthetic cannabinoids are considered to be full agonists of the receptors.
Pharmacokinetics such as blood elimination half-life and volumes of distribution are not known for these compounds. Most synthetic cannabinoids are biotransformed to hydroxylated or carboxylic acid metabolites. Reported effects of synthetic cannabinoid use or exposure include poor coordination, sedation, slurred speech, nausea, vomiting, tachycardia, hypertension, hyperthermia, agitation, delusions, paranoia, hallucinations, psychosis, and acute kidney injury. Fatalities have occurred after the use of these substances.

Detection of Synthetic Cannabinoids in Blood at Axis Forensic Toxicology, 2020.
Data Compiled by Kevin G. Shanks (2020).
As the prevalence of specific synthetic cannabinoids vary over time, the modern forensic toxicology laboratory should have a relevant scope of analysis. Typically only parent drugs are monitored in blood specimens, but some compounds require a metabolite be monitored in lieu of the parent drug. Detection limits for both parent drug and metabolite vary in biological matrices, but are generally 0.1 – 2 ng/mL. During 2020, three compounds (5F-MDMB-PICA, 4F-MDMB-BINACA, and 5-ADB) accounted for 90+% of positive synthetic cannabinoid detections in blood samples tested.
There current scope of testing offered by Axis Forensic Toxicology can be found in the online test catalog (Order Code 42130, Synthetic Cannabinoid Panel, Blood), and these compounds are detected by the Comprehensive Panel with Analyte Assurance™ (70510).
Axis Forensic Toxicology prides itself on its expertise in the field of novel psychoactive substances. Here are citations for papers published by Axis on the topic of synthetic cannabinoids:
- “Three Cases of Fatal Acrylfentanyl Toxicity in the United States and a Review of the Literature”, D.C. Butler, K. Shanks, G. Behonick, D. Smith, S.E. Presnell, L.M. Tormos. J Anal Tox. 42, e6-e11 (2018).
- “Synthetic Cannabinoid Product Surveillance by LC/ToF in 2013-2015”. K. Shanks, G. Behonick. J Forensic Toxicol Pharmacol, 4:3 (2016)
- “Death After Use of the Synthetic Cannabinoid 5F-AMB”. K. Shanks, G. Behonick. For Sci Int, 262, e21-e24 (2016)
- “Death Associated with the Use of the Synthetic Cannabinoid ADB-FUBINACA”. K. Shanks, W. Clark, G. Behonick. J Anal Tox, 40:3, 24-242 (2016)
- “Case Reports of Synthetic Cannabinoid XLR-11 Associated Fatalities”. K. Shanks, D. Winston, J. Heidingsfelder, G. Behonick. For Sci Int, 252, e6-e9 (2015)
- “Four Postmortem Case Reports with Quantitative Detection of the Synthetic Cannabinoid, 5F-PB-22”. G. Behonick, K. Shanks, D. Firchau, G. Mathur, C. Lynch, M. Nashelsky, D. Jaskierny, C. Meroueh. J Anal Tox, 38, 559-562 (2014)
- “Identification of Novel Third Generation Synthetic Cannabinoids in Products by Ultra Performance Liquid Chromatography and Time of Flight Mass Spectrometry”. K. Shanks, T. Dahn, G. Behonick, A. Terrell. J Anal Tox, 37: 517-525 (2013)
- “Detection of Synthetic Cannabinoids and Synthetic Stimulants in First and Second Generation Legal Highs by Ultra Performance Liquid Chromatography with Time of Flight Mass Spectrometry (UPLC/ToF)”. K. Shanks, T. Dahn, G. Behonick, A. Terrell. J Anal Tox, 36: 360-371 (2012)
- “Detection of JWH-018 and JWH-073 by UPLC/MS/MS in postmortem whole blood casework”. K. Shanks, T. Dahn, A. Terrell. J Anal Tox, 36: 145-152 (2012)
If you would like a copy of these papers, please contact [email protected].
References
- Synthetic Cannabinoids. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages 1979-1986. (2020).
- Tetrahydrocannabinol. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages 2041-2045. (2020).
- Synthetic Cannabinoid Receptor Agonists. Novel Psychoactive Substances: Classification, Pharmacology, and Toxicology. Paul Dargan and David Wood. Academic Press (Elsevier). 317-338. 2013).
- Axis Forensic Toxicology. Laboratory Data. Indianapolis, IN. (accessed April 23, 2021).
- Published in Drug Classes
Axis Experts to Present at Fall National Medical Examiner and Toxicology Conferences
By Denise Purdie Andrews
The life blood of advancing the science of forensic toxicology lies in the academic peer reviewed contributions of the field’s rank-in-file members. A variety of forums exist for a laboratory to share its experiences for the greater good. These include published full length journal manuscripts, case reports, and technical notes; additionally, sharing our experiences with colleagues from around the United States and the world is made possible by our participation in various meetings and scientific gatherings. Most often, these take the form of short oral platform presentations, poster sessions and contributions as workshop faculty speakers. The opportunity to do these things is only possible by the diligence, skilled professional competence, and effort of the laboratory as a team. We also acknowledge the collaboration we enjoy with our coroner and medical examiner clients.

Axis Forensic Toxicology (2021)
https://axisfortox.com
We are pleased to announce that Axis Forensic Toxicology subject matter experts have had presentations accepted for national forensic toxicology and medical examiner conferences upcoming in the fall 2021.
Kevin Shanks, M.S., D-ABFT-FT will be presenting two poster presentations and one oral platform presentation on various topics including novel psychoactive substances (synthetic cannabinoids and metonitazene) at the Society of Forensic Toxicologists (SOFT) annual meeting in Nashville, TN in September 2021.
George Behonick, Ph.D., F-ABFT will be presenting a case report describing novel psychoactive substances (brorphine, flualprazolam, and metonitazene) in the setting of heroin and fentanyl at the National Association of Medical Examiners (NAME) annual meeting in West Palm Beach, FL in October 2021.
We hope you can attend these presentations.
Postmortem Toxicology in Kentucky: Looking Back at 2020
Kevin G. Shanks1, Dr. George S. Behonick1, and Dr. William Ralston2
1Axis Forensic Toxicology
2Kentucky Office of the Medical Examiner
The Ever-Changing Scope of Synthetic Cannabinoids in Toxicology Casework II (2016-2020)
Kevin G. Shanks1 and Dr. George S. Behonick1
1Axis Forensic Toxicology
Emergence of the Novel Opioid, Metonitazene, in Postmortem Toxicology and Detection by LC-QToF-MS
Kevin G. Shanks1*, Dr. George S. Behonick1, and Dr. Lisa K. Mannix2
1Axis Forensic Toxicology
2Butler County, Ohio Coroner’s Office
Case Report: Detection of Novel Psychoactive Drugs in the Context of Fentanyl and Heroin use
Dr. George S. Behonick1, Dr. Zhuo Wang2, Kevin G. Shanks1 and Merrilee Frey2
1Axis Forensic Toxicology
2Office of the Lake County Coroner, Crown Point, IN
If you would like a copy of these presentations, we can provide them after the conference dates. Please email us at [email protected].
The Society of Forensic Toxicologists (SOFT), founded in 1970, is a professional organization for forensic toxicologists and chemists. The Society’s peer reviewed scientific journal is the Journal of Analytical Toxicology.

Society of Forensic Toxicologists (2021)
http://www.soft-tox.org
The National Association of Medical Examiners (NAME), founded in 1966, is a professional organization for medical examiners, forensic pathologists, and medical-legal affiliates and administrators. The Association’s peer reviewed scientific journal is The American Journal of Forensic Medicine and Pathology.

National Association of Medical Examiners (2021)
https://name.memberclicks.net
- Published in Announcements
Kevin Shanks presents to London Toxicology Group
by Denise Purdie Andrews
Kevin Shanks will be giving a presentation on synthetic cannabinoids at the meeting of the LTG (London Toxicology Group) on June 18, 2021. He will be speaking alongside colleagues in the field of forensic toxicology from Cuyahoga County (Ohio) Medical Examiner’s Office, the University of Lincoln (United Kingdom), The Office of the Chief Medical Examiner (Alberta, Canada), and the Federal Bureau of Investigation (FBI).
The LTG, first established in 1979, aims to promote the advancement of the science of analytical toxicology for public benefit and education. The group is comprised of members from the United Kingdom, Ireland, and elsewhere.
The agenda for the meeting can be found here: Agenda
- Published in Announcements
From the Experts: Axis’ New Blog Debuts
by Denise Purdie Andrews
Axis Forensic Toxicology, your forensic toxicology partner, is excited to announce its new blog! This new feature of our website will provide an additional communication channel to bring you important information to help you be more productive and effective with your toxicology testing. We are committed to keeping you informed of the ever changing landscape of forensic toxicology. This information will be prepared by our experienced toxicologists and chemists as well as our client service professionals. Articles will include:
- Primers regarding drugs or drug classes
- Statistics and trends for various drugs drawn from our nationwide base of toxicology testing.
- Current event articles, including emerging threats
- Book reviews and links to other references
- Operational bulletins to assist with collection and submission of testing requests
We will begin publishing the blog in June and are committed to posting at least monthly. Our goal is to continue to serve you well, so please let us know if there are particularly topics of interest. We hope that you find this to be a helpful resource to your important work.
- Published in Announcements
The Realms of Forensic Toxicology
By Kevin Shanks, M.S., D-ABFT-FT
Toxicology is the study of the effects of substances on living organisms. Forensic toxicology is the use of toxicology in medical-legal investigations. Forensic toxicologists use analytical chemistry, pharmacology, and clinical chemistry to aid in these investigations of death, poisoning, intoxication, or substance use.

Image is by Simon Strandgaard Licensed with CC BY 2.0.
The field of forensic toxicology can be broken down into three main realms: postmortem toxicology, human performance toxicology, and forensic drug testing.
Postmortem toxicology is the analysis of biological specimens obtained at autopsy in order to identify the effect of drugs or poisons. These biological specimens may include blood, urine, vitreous humor, bile, gastric contents, and tissues such as liver, kidney, spleen, and brain. The toxicological analyses and toxicologist’s expertise aid in the certification of cause and manner of death, which is determined by the forensic pathologist, medical examiner, or coroner.
Human performance toxicology is the analysis of biological specimens obtained by a hospital or law enforcement agency in order to identify the effects of drugs on psychomotor performance. The typical biological specimen analyzed is whole blood, but may also include blood serum, blood plasma, or in some case, urine. The toxicological analyses and toxicologist’s opinion, in conjunction with observed witness reports and field tests administered by law enforcement officials, help in the determination if a person is under the influence of a substance during a specific incident, such as a motor vehicle stop or collision.
Forensic drug testing is the analysis of biological specimens obtained by a physician, hospital system, the criminal justice system, the public business sector (e.g. Department of Transportation, etc.) and private workplaces or businesses to identify substance use. The primary specimen used in forensic drug testing is urine, but other specimens analyzed include oral fluids, hair, and sweat. The presence or absence of substances detected in biological specimens along with the toxicologist’s scientific opinion, after review of case circumstances and context, allow for the decision to be made regarding potential substance use.
Common instrumentation used across all three realms of forensic toxicology includes immunoassay, gas chromatography with mass spectrometry (GC-MS), and liquid chromatography with mass spectrometry (LC-MS). Routine drugs monitored in all realms include amphetamine, methamphetamine, cocaine, heroin, fentanyl, prescription opioids, PCP, barbiturates, cannabis, and ethanol. The scope of analysis can change to include a more comprehensive scope (e.g. designer opioids, synthetic cannabinoids, novel psychoactive substances, etc.) according to the case circumstances and specifics.
To stay current with the scope of testing for all realms of toxicology offered by Axis Forensic Toxicology, please consult the online test catalog.
- Order Code 70530, Drugs of Abuse Panel, Blood
- Order Code 70510, Comprehensive Drug Panel, Blood
- Order Code 70080, Drugs of Abuse Panel, Urine
- Order Code 13810, Designer Opioids Panel, Blood
- Order Code 42130, Synthetic Cannabinoid Panel, Blood
- Order Code 13610, Psychoactive Substances Panel, Blood
References
Guidelines for the Interpretation of Analytical Toxicology Results. Disposition of Toxic Drugs and Chemicals in Man. Twelfth Edition. Randall C. Baselt. Biomedical Publications. Pages xxx-xlii. (2020).
Introduction to Forensic Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 1-12. (2008).
Postmortem Toxicology. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 191-218. (2008).
Postmortem Forensic Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 3-14. (2017).
Alcohol, Drugs, and Driving. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 299-322. (2008).
Human Performance Toxicology. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 15-30. (2017).
Workplace Drug Testing. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 135-152. (2008).
Forensic Drug Testing. Principles of Forensic Toxicology. Fourth Edition. Barry Levine. AACC, Inc. Pages 31-48. (2017).
Drug Facilitated Sexual Assault. Clarke’s Analytical Forensic Toxicology. Sue Jickells and Adam Negrusz. Pharmaceutical Press. Pages 287-298. (2008).
- Published in General