Synthetic cannabis deaths sound alarms in Australia Compounds a chemistry graduate student could make are taking a toll worldwide 14 Jan. 2015 By Dennis Normile The deaths of Synthetic cannabinoids have caused a large number of emergency presentations to hospitals for adverse cardiovascular events including numerous deaths, particularly for the more potent analogs acting on the CB<sub>1</sub> receptor. While smoked cannabis use is often associated with significant change …
Synthetic cannabis deaths sound alarms in Australia
Compounds a chemistry graduate student could make are taking a toll worldwide
- 14 Jan. 2015
- By Dennis Normile
The deaths of two men—one yesterday and one today—and a rash of recent hospitalizations in Australia, all suspected to result from the use of synthetic cannabis, are focusing attention on a growing worldwide problem.
Drug users have been embracing products touted as producing a natural marijuanalike high. The effect is produced by synthetic compounds designed to mimic THC, the active ingredient in marijuana, which are sprayed onto plant material then often marketed as “Spice.” However, “synthetic cannabinoids certainly have the potential to be significantly more dangerous than the natural plant material that they supposedly mimic,” says David Caldicott, an emergency medical doctor at the Australian National University in Canberra.
The compounds were originally designed to study the neurobiology of cannabis in animals. They were never intended for human use. But “these drugs aren’t too difficult to synthesize,” says Richard Kevin, a psychopharmacology Ph.D. candidate at the University of Sydney in Australia who is studying the effects of the synthetic compounds on mice. He says a competent chemistry grad student could cook them up in a university lab. So a worldwide cottage industry has sprung up producing synthetic cannabis. But with no standards, no regulation, and no quality control, there is “a large variety of synthetic cannabinoids with largely unknown toxicity,” Kevin says. And “because they are simply sprayed onto whatever carrier plant material is chosen,” Caldicott says, “hot spots can occur where the concentration is higher than intended.”
Haphazard production has led to particularly toxic batches and clusters of poisoning. According to news reports , synthetic cannabis use killed 25 and sickened more than 700 in northern Russia alone last fall.
Kevin says one reason people use these products is to foil drug testing. Although the synthetic cannabis targets the same brain regions as THC, the molecular structures are different and escape detection by standard drug tests. Australian states have outlawed drugs that mimic cannabis. But proving cannabislike effects of any particular compound “can be tricky,” Kevin says. And to keep ahead of the law and drug testing, makers are constantly tweaking their recipes. “The rate of evolution of these drugs is such that many have never been seen before,” Caldicott says.
When buying synthetic cannabis, “you can’t know exactly what you’re getting, so you’re taking a big risk,” Kevin says. He says that although some synthetic cannabinoids appear to be relatively well tolerated, others have been linked to acute kidney injury, panic attacks, and seizures. His own studies with mice suggest “long-term memory impairment after heavy chronic dosing.”
“We need wittier and wiser responses to the problem of harm from drugs if these deaths are not to become a more frequent occurrence,” Caldicott says.
Cannabis as a cause of death: A review
Synthetic cannabinoids have caused a large number of emergency presentations to hospitals for adverse cardiovascular events including numerous deaths, particularly for the more potent analogs acting on the CB1 receptor. While smoked cannabis use is often associated with significant changes in heart rate and cardiac output, amongst other physiological changes, it has been rarely considered in the forensic literature as a significant contributory or causal factor in sudden unexpected death. A review of case reports of admissions to hospitals for cardiovascular events was undertaken together with a review of epidemiological studies, and case reports of sudden death attributed, at least in part, to use of this drug. These publications show that use of cannabis is not without its risks of occasional serious medical emergencies and sudden death, with reports of at least 35 persons presenting with significant cardiovascular emergencies who had recently smoked a cannabis preparation. At least 13 deaths from a cardiovascular mechanism have been reported from use of this drug which is very likely to be an under-estimate of the true incidence of its contribution to sudden death. In addition, many cases of stroke and vascular arteritis have also been reported with the latter often involving a limb amputation. While it is a drug with widespread usage among the community with relatively few deaths when faced with a circumstance of very recent use (within a few hours), a positive blood concentration of THC and a possible cardiac-related or cerebrovascular cause of death this drug should be considered, at least, a contributory cause of death in cases of sudden or unexpected death.
Keywords: Arrhythmias; Cardiovascular disease; Forensic; Heart disease; Myocardial infarction; Stroke.
Copyright © 2019 Elsevier B.V. All rights reserved.
Thomas G, Kloner RA, Rezkalla S. Thomas G, et al. Am J Cardiol. 2014 Jan 1;113(1):187-90. doi: 10.1016/j.amjcard.2013.09.042. Epub 2013 Oct 5. Am J Cardiol. 2014. PMID: 24176069 Review.
Richards JR, Bing ML, Moulin AK, Elder JW, Rominski RT, Summers PJ, Laurin EG. Richards JR, et al. Clin Toxicol (Phila). 2019 Oct;57(10):831-841. doi: 10.1080/15563650.2019.1601735. Epub 2019 Apr 9. Clin Toxicol (Phila). 2019. PMID: 30964363
Hartung B, Kauferstein S, Ritz-Timme S, Daldrup T. Hartung B, et al. Forensic Sci Int. 2014 Apr;237:e11-3. doi: 10.1016/j.forsciint.2014.02.001. Epub 2014 Feb 12. Forensic Sci Int. 2014. PMID: 24598271
Moustafa B, Testai FD. Moustafa B, et al. Curr Neurol Neurosci Rep. 2021 Apr 7;21(6):25. doi: 10.1007/s11910-021-01113-2. Curr Neurol Neurosci Rep. 2021. PMID: 33825077 Review.
Hackam DG. Hackam DG. Stroke. 2015 Mar;46(3):852-6. doi: 10.1161/STROKEAHA.115.008680. Stroke. 2015. PMID: 25700287 Review.
Bockmann EC, Brito R, Madeira LF, da Silva Sampaio L, de Melo Reis RA, França GR, Calaza KDC. Bockmann EC, et al. Cell Mol Neurobiol. 2022 Aug 4. doi: 10.1007/s10571-022-01263-y. Online ahead of print. Cell Mol Neurobiol. 2022. PMID: 35925507 Review.
Edinoff AN, Doppalapudi P, Fort JM. Edinoff AN, et al. Health Psychol Res. 2022 Apr 26;10(3):34617. doi: 10.52965/001c.34617. eCollection 2022. Health Psychol Res. 2022. PMID: 35774900 Free PMC article.
Weresa J, Pędzińska-Betiuk A, Mińczuk K, Malinowska B, Schlicker E. Weresa J, et al. Cells. 2022 Mar 28;11(7):1142. doi: 10.3390/cells11071142. Cells. 2022. PMID: 35406706 Free PMC article. Review.
Gahr M, Ziller J, Keller F, Muche R, Preuss UW, Schönfeldt-Lecuona C. Gahr M, et al. Eur J Public Health. 2022 Apr 1;32(2):239-245. doi: 10.1093/eurpub/ckab207. Eur J Public Health. 2022. PMID: 35043164 Free PMC article.
Murata T, Noritake K, Aki T, Uemura K. Murata T, et al. Toxicol Rep. 2021 Apr 30;8:980-987. doi: 10.1016/j.toxrep.2021.04.014. eCollection 2021. Toxicol Rep. 2021. PMID: 34026562 Free PMC article.