Insecticide Misuse With Cannabinoids and Its Resulting Complications: A Case Report

Publication
Article

Peer Reviewed

Pharmacy Practice in Focus: Health SystemsJanuary 2024
Volume 13
Issue 1

The use of adulterated cannabinoids mixed with insecticides is becoming more common.

Abstract

Ingesting or inhaling insecticides may lead to an altered state of perception and/or consciousness, producing euphoria similar to that from methamphetamine use.1 This use of pyrethroids, a chemical component commonly found in household insecticides (eg, Raid Ant & Roach), can result in hyperexcitation. We present a case of pyrethroid toxicity associated with altered mental status (AMS) in a patient who smoked insecticide-laden marijuana. The patient became hyperexcitable, combative, and agitated within 4 hours of ingestion. Upon evaluation, the patient’s laboratory results were remarkable for leukocytosis, hyperlactatemia, mild transaminitis, and rhabdomyolysis. The patient received aggressive intravenous (IV) hydration and symptom management during hospitalization, which resulted in normalization of creatine kinase and improved mentation.

Insecticide being sprayed on plants -- Image credit: Delphotostock | stock.adobe.com

Image credit: Delphotostock | stock.adobe.com

Introduction

Modifying or combining compounds, such as dousing a burnable substance (eg, marijuana, tobacco, spice) with insecticide and smoking it, is a way for substance users to increase their high.1 Individuals utilizing this method may experience a faster onset of a euphoric altered state of cognizance, but they may also exhibit drooling and lethargic movements. The method has gained popularity due to its accessibility for purchase (ie, it is not a regulated substance) and cost, and because it is untraceable in routine, standardized drug panels.2 Investigators in a study from Kentucky reported that 1 in 6 individuals who use drugs endorsed the use of “wasp dope,” the drug trend combining insecticide-containing pyrethroids with illicit substances. Wasp dope is strongly associated with homelessness, lack of transportation, methamphetamine use, and injection drug use.1

Insecticides containing pyrethroids can cause toxic effects that interfere with the central nervous system. Pyrethroids are sodium channel blockers that delay the closure of sodium channels and prolong neuronal excitation, resulting in symptoms such as paresthesia and increased salivation.3,4 Although this class of chemicals is typically not harmful to humans, high-dose exposures can cause neurotoxicity. Despite its potential harm, the toxicity of pyrethroids has not been studied extensively.5,6 We offer a case report on a patient who presented to the emergency department (ED) with altered mental status following the use of insecticide-laden marijuana.

Patient Case

A 44-year-old man with a history of schizophrenia, bipolar disorder, posttraumatic stress disorder, and polysubstance use (methamphetamine IV and fentanyl inhalation) was voluntarily admitted to a mental health and substance use treatment center. While at the treatment center, the patient was witnessed by staff spraying marijuana with commercially available insecticide and then smoking the product. The staff noted that the insecticide was Raid (SC Johnson Professional), which contains synthetic pyrethroids. When questioned, the patient stated that he added Raid to his marijuana to create “DIY meth,” which he called “Shake ‘n Bake,” to mimic the euphoric effects of methamphetamines. He also discussed the use of fentanyl and methamphetamine the day prior.

The patient became agitated approximately 4 hours after smoking insecticide-laden marijuana. He was described by staff as restless, uncooperative, and grossly disorganized, “flopping around” and yelling incomprehensible words. The patient was treated with 20 mg of olanzapine oral, 6 mg of lorazepam intramuscular (IM), and 100 mg of diphenhydramine IM without satisfactory control of the agitation. The facility staff called for emergency medical services (EMS) to transport the patient to an acute care hospital for escalation of care. Upon EMS arrival, the patient was combative and had hit his mouth against a wall. He was awake and oriented to a person by name only.

On admission to the ED, the patient remained agitated, combative, and unable to answer questions. Vital signs were noted: height, 71 in; weight, 70 kg; temperature, 38.4 °C (101.2 °F); pulse, 62 beats per minute; blood pressure, 112/52 mm Hg; respiration, 21 breaths per minute; and 98% oxygen saturation as measured by pulse oximetry on room air. The patient received 5 mg of haloperidol IM, 5 mg of lorazepam IV, and 35 mg of ketamine IV within 1 hour of arriving at the ED. Laboratory workup was remarkable for mild leukocytosis (white blood cells, 13.6 x 109/L), hyperlactatemia (lactate, 1.7 mmol/L), mild transaminase level elevations (aspartate aminotransferase, 71 U/L; alanine aminotransferase, 87 U/L), and rhabdomyolysis (creatine kinase [CK], 11,960 U/L). Serum creatinine was 0.8 mg/dL. Urine drug screen was positive for amphetamines, benzodiazepines, tetrahydrocannabinol, and fentanyl; it was negative for opiates, barbiturates, cocaine, methadone, phencyclidine, propoxyphene, and 3,4-methylenedioxymethamphetamine. All other laboratory and radiology results were unremarkable. Poison Control Center was contacted and recommended supportive care, cooling, and sedation; however, no specific treatment for insecticide exposure was recommended. Cooling measures were implemented with ice packs, and the patient was administered 3 L of lactated Ringer solution IV prior to admission to the intensive care unit (ICU) for further management of encephalopathy and rhabdomyolysis.

The patient continued to receive aggressive IV hydration for rhabdomyolysis at an average rate of 3.3 mL/kg/h over 4 days. Serum CK levels declined over 5 days without laboratory evidence of kidney injury. Serum CK levels trended down with the following daily peak levels: 11,960 U/L at initial admission, 6439 U/L on day 2, 1066 U/L on day 3, 624 U/L on day 4, and 490 U/L on day 5. While in the ICU, the patient continued to exhibit AMS with agitation despite treatment with benzodiazepines. He was given a total of 32 mg of lorazepam IV over 5 days with an average 6 mg daily dose of lorazepam IV. The patient’s mental status slowly improved, but he remained mildly agitated upon being moved to a standard floor bed on hospital day 3. Despite improvement, the medical team wanted to monitor the patient for further improvement of his mental status, but on day 7, he left against medical advice.

Discussion

A patient presented with agitated delirium following acute ingestion of insecticide-laden marijuana. Although pyrethroids are generally considered safe for humans, an increase in overdose cases has raised concerns about pyrethroids’ toxic potential. The clinical presentation of pyrethroid toxicity is based on the type of pyrethroid and concentration.4 Type I pyrethroids hold the sodium channels open for a shorter duration than type II compounds do, resulting in paresthesia, fine tremors, and reflex hyperexcitability. At high concentrations, type II pyrethroids also target voltage-gated chloride channels but primarily manifest with salivation, myotonia, and seizures.4,7,8 Results of animal studies have shown repetitive motor disturbances with increasing tone and progression to writhing spasms and heightened stimulus response linked to the sympathoadrenal medullary system stimulation.9 Both type I and II pyrethroid toxicities are characterized by marked catecholamine release, particularly epinephrine and norepinephrine, which can create a sympathomimetic toxidrome–like presentation.10 Mild pyrethroid toxicity may initially present as nausea, vomiting, headache, dizziness, and paresthesia. In large ingestions, patients may experience coma, pulmonary edema, and hemorrhage.4

The patient described in this case presented with a similar agitated delirium, which developed several hours after ingestion of insecticide-laden marijuana. The active ingredients listed on the product labels of most Raid products include imiprothrin, which is a synthetic pyrethroid insecticide, and cypermethrin, a type II pyrethroid. Although the inherent toxic potential of pyrethroids is high with the median lethal dose ranging from 0.5 mg/kg to 250 mg/kg, this degree of AMS typically does not present unless more than 250 mL of insecticide is ingested.3,4 The pyrolytic effects of smoking pyrethroids can make them highly volatile, and inhalation can induce a rapid onset of the toxic effects.10 Furthermore, results of an experimental human volunteer trial on cypermethrin oral and dermal pharmacokinetics determined the urinary elimination time to be as long as 16.5 hours.11 The combination of heightened stimulus response, polysubstance use, and potentially long duration may have led to this patient’s prolonged agitated delirium.

Although there is limited information regarding the pharmacokinetics of inhaled pyrethroids, there are potential interactions due to cytochrome P450 (CYP) enzyme metabolism. Cannabis is a major inhibitor of CYP2C8, CYP2C9, and CYP3A4.12 Pyrethroids are metabolized by CYP enzymes, with studies identifying CYP2C8, CYP2C9, and CYP3A5 as potential mediators.13 This CYP enzyme inhibition may increase the toxic effects of pyrethroids and extend the sympathomimetic effects of amphetamines, resulting in the increased neuromuscular hyperactivity and agitation seen in this patient. There are also reports of acute kidney injury associated with atypical manifestations of toxicity.3 In animal studies, this nephrotoxicity has been linked to gene disruption and histopathological lesions.14 Acute tubular necrosis has also been seen with chronic exposure to pyrethroids in limited case reports.15 Although this patient’s imaging findings were insignificant, given the unknown extent of his polysubstance use and his prolonged agitated hyperactivity, these factors could have contributed to the patient’s rhabdomyolysis.

In patients with suspected pyrethroid toxicity, we recommend contacting a Poison Control Center and providing supportive care tailored to the patient’s presentation. In mild pyrethroid toxicity, where polysubstance use or sympathomimetic syndrome is more prevalent, sedation with benzodiazepines may be needed to manage agitation, withdrawal, and seizures. In severe toxicity, securing the patient’s airway may be necessary due to the increased risk of aspiration, seizures, and respiratory depression. In addition to supportive care, available antidotes should be considered to reverse the effects of the causal agent.

Currently, there is no proven antidote for pyrethroid toxicity. However, there may be potential for using sodium channel blockers to antagonize pyrethroids’ effects on prolonging the duration of sodium channel opening. Animal studies have shown that local anesthetics, such as lidocaine and tetracaine, exhibit activity against pyrethroid-modified sodium channels.16 Sodium channel blockers may be considered for severe, symptomatic cases of confirmed pyrethroid toxicity when other causes have been ruled out. More studies need to be conducted to determine the efficacy and safety of sodium channel blockers as antidotes for pyrethroid toxicity.

Conclusion

Underlying differentials in this case were broad, given the patient’s polysubstance use. Treatment with supportive care for agitation, rhabdomyolysis, and substance withdrawal was given based on his initial presentation. Once neurological and cardiorespiratory causes were ruled out, it was concluded that his presentation was likely due to a combination of ingesting insecticide-laden marijuana and polysubstance use. Given the emergence of household insecticide utilization with polysubstance use, this case highlights potential management considerations such as sedation for agitation and fluid resuscitation for rhabdomyolysis should a similar case present.

References

1. Young AM, Livingston M, Vickers-Smith R, Cooper HLF. Emergence of wasp dope in rural Appalachian Kentucky. Addiction. 2021;116(7):1901-1907. doi:10.1111/add.15291

2. WCHM. Drug laced with bug spray leads to spike in overdose calls in Indiana. WATE.com. March 24, 2018. Accessed November 20, 2023. https://www.wate.com/news/watercooler/drug-laced-with-bugspray-leads-to-spike-in-overdose-calls-in-indiana-2/

3. Cha YS, Kim H, Cho NH, et al. Pyrethroid poisoning: features and predictors of atypical presentations. Emerg Med J. 2014;31(11):899-903. doi:10.1136/emermed-2013-202908

4. Ramchandra AM, Chacko B, Victor PJ. Pyrethroid poisoning. Indian J Crit Care Med. 2019;23(suppl 4):S267-S271. doi:10.5005/jpjournals-10071-23304

5. Panwar M, Usha G, Kumath M. Status epilepticus: an association with pyrethroid poisoning. Indian J Crit Care Med. 2013;17(2):119-120. doi:10.4103/0972-5229.114825

6. Yang PY, Lin JL, Hall AH, Tsao TC, Chern MS. Acute ingestion poisoning with insecticide formulations containing the pyrethroid permethrin, xylene, and surfactant: a review of 48 cases. J Toxicol Clin Toxicol. 2002;40(2):107-113. doi:10.1081/clt-120004397

7. Bradberry SM, Cage SA, Proudfoot AT, Vale JA. Poisoning due to pyrethroids. Toxicol Rev. 2005;24(2):93-106. doi:10.2165/00139709-200524020-00003

8. Jacob MS, Iyyadurai R, Jose A, et al. Clinical presentation of type 1 and type 2 pyrethroid poisoning in humans. Clin Toxicol (Phila). 2022;60(4):464-471. doi:10.1080/15563650.2021.1994145

9. Cremer JE, Seville MP. Comparative effects of two pyrethroids, deltamethrin and cismethrin, on plasma catecholamines and on blood glucose and lactate. Toxicol Appl Pharmacol. 1982;66(1):124-133. doi:10.1016/0041-008x(82)90067-9

10. Ray DE, Forshaw PJ. Pyrethroid insecticides: poisoning syndromes, synergies, and therapy. J Toxicol Clin Toxicol. 2000;38(2):95-101. doi:10.1081/clt-100100922

11. Woollen BH, Marsh JR, Laird WJD, Lesser JE. The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration. Xenobiotica. 1992;22(8):983-991. doi:10.3109/00498259209049904

12. Foster BC, Abramovici H, Harris CS. Cannabis and cannabinoids: kinetics and interactions. Am J Med. 2019;132(11):1266-1270. doi:10.1016/j.amjmed.2019.05.017

13. Godin SJ, Crow JA, Scollon EJ, Hughes MF, DeVito MJ, Ross MK. Identification of rat and human cytochrome p450 isoforms and a rat serum esterase that metabolize the pyrethroid insecticides deltamethrin and esfenvalerate. Drug Metab Dispos. 2007;35(9):1664-1671. doi:10.1124/dmd.107.015388

14. Naz M, Rehman N, Nazam Ansari M, et al. Comparative study of subchronic toxicities of mosquito repellents (coils, mats and liquids) on vital organs in Swiss albino mice. Saudi Pharm J. 2019;27(3):348-353. doi:10.1016/j.jsps.2018.12.002

15. Bashir B, Sharma SG, Stein HD, Sirota RA, D’Agati VD. Acute kidney injury secondary to exposure to insecticides used for bedbug (Cimex lectularis) control. Am J Kidney Dis. 2013;62(5):974-977. doi:10.1053/j.ajkd.2013.04.020

16. Oortgiesen M, van Kleef RG, Vijverberg HP. Block of deltamethrin-modified sodium current in cultured mouse neuroblastoma cells: local anesthetics as potential antidotes. Brain Res. 1990;518(1-2):11-18. doi:10.1016/0006-8993(90)90947-a

About the Authors

Catherine Tran, PharmD, is a clinical pharmacist in the Department of Clinical Pharmacy at the University of California Irvine Medical Center in Orange, California.

Christine Vo, PharmD, is a clinical pharmacist in the Department of Clinical Pharmacy at the University of California Irvine Medical Center in Orange, California.

Stephen Lee, PharmD, BCPS, BCCCP, is an emergency medicine pharmacist in the Department of Clinical Pharmacy at the University of California Irvine Medical Center in Orange, California.

Jeffrey R. Suchard, MD, FACEP, FACMT, is a professor of clinical emergency medicine and clinical pharmacy, and director of medical toxicology in the Department of Emergency Medicine at the University of California Irvine Medical Center in Orange, California.

Disclaimer

The authors have nothing to disclose regarding financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this manuscript.

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