Opioids/Benzodiazepines Poisoning 

Few reports describe the use of either benzodiazepines or opioids as incapacitating agents. In August 2002, Alexander Stone authored a brief report in Science titled, "Chemical weapons, US Research on Sedatives in Combat Sets Off Alarms." In this report, Stone highlights the Department of Defense's Joint Non-Lethal Weapons Program and how the funding for studies of nonlethal weapons has jumped from $14 million in 1997 to $36 million in 2001.^[1] The Institute of Emerging Defense Technologies at Pennsylvania State University is reportedly conducting research on the use of drugs as nonlethal agents and has reportedly urged the Marine Corps to give immediate consideration to weaponizing sedatives such as diazepam.

In October 2002, the Russian Military reportedly used "a fentanyl derivative" to neutralize terrorists holding hostages at the Moscow Dubrovka Theater Center. The Russian Health Minister declared that the "gas" used in that event "cannot by itself be called lethal." Despite that announcement, 127 of the hostages died following the use of that gas in the theater.

In 2005, the 3^rd European Symposium on Non-Lethal Weapons met in Stadthalle Ettlingen, Germany. At this meeting, an abstract was submitted by Hess and colleagues from the Institute for Clinical and Experimental Medicine and the Military Medical Academy, Czech Republic. In this abstract, they referred to their work using numerous potential pharmacological non-lethal weapons.^[2]

According to the abstract by Hess et al, a major drawback of opioid use is the development of respiratory depression, particularly if administered at higher doses inducing immobilization. In experiments with rabbits, they reportedly tested a combination of alfentanil or remifentanil together with a specific opioid antagonist (naloxone) seeking to identify the optimal agonist/antagonist ratio while maintaining immobilization and markedly reducing respiratory depression. Inhaled administration of opioids was reported to be associated with a very rapid onset of effect. The ultrapotent opioid etorphine, when combined with dimethylsulfoxide, was capable of crossing normal skin and inducing immobilization within 3-8 minutes.^[2]

Little has been published regarding the use of aerosolized opioids or benzodiazepines as incapacitating agents. The primary action of benzodiazepines is agonist activity at the γ -aminobutyric acid (GABA)–associated benzodiazepine receptors. This activity produces central nervous system depression, which may initially manifest as slurred speech, ataxia, nystagmus, and incoordination. As toxicity increases, the patient may become comatose and develop respiratory depression with airway compromise. In a 1994 article published in Epilepsia by Xi et al, aerosolized diazepam was reported to arrest seizure activity within seconds.^[3] In Science, Stone reported that diazepam was being given immediate consideration as a weaponized sedative.^[1]

Opioids possess agonist activity at the opioid receptor. The 3 current major classes of opioid receptors are m, k, and d; each has multiple subtypes with differing pharmacologic activity. Numerous opioid agonists also exist; each has varying affinity for each receptor. Fentanyl and its derivatives (ie, sufentanil, alfentanil, remifentanil, carfentanil) are the only opioids that have been described as potential aerosolized opioid agents. In Anesthesiology, Hung et al reported a rapid absorption rate following inhaled liposome-encapsulated fentanyl.^[4] In Annals of Emergency Medicine, Wax et al provide a comprehensive review of these agents in relation to the Moscow theater event.^[5] Alfentanil, remifentanil, fentanyl, and carfentanil are 75, 220, 300, and 10,000 times more potent than morphine, respectively.

Frequency

United States

No reports describe the use of aerosolized opioids or benzodiazepines as incapacitating agents in the US population.

International

Only 1 report describes the intentional use of an aerosolized opioid as an incapacitating agent. In the Moscow Dubrovka Theater incident, 50 Chechen rebels stormed the theater and took 800 hostages on October 23, 2002. On October 26, 2002, a gas was introduced into the theater through the ventilation system just before a rescue attempt by Russian Special Forces. Reportedly, 127 (16%) of the 800 hostages in the theater died. Subsequent reports indicated that all had died from complications associated with the gas. The Russian Health Minister announced 4 days after the events that "a fentanyl derivative was used to neutralize the terrorists." This was collaborated by reports that both Moscow and Western Embassy physicians noted signs and symptoms consistent with opiate intoxication. Laboratory confirmation of fentanyl use was not possible in these cases, but blood and urine specimens analyzed from 2 German survivors showed traces of halothane.

Mortality/Morbidity

The mortality and morbidity associated with the use of aerosolized benzodiazepines or opioids as incapacitating agents is unknown. Following the reported use of an aerosolized fentanyl derivative during the 2002 raid on Chechen rebels who had taken hostages in the Moscow Dubrovka Theater Center, 127 (16%) of the 800 hostages in the theater died, and 650 of the survivors required hospitalization. Whether these complications were the result of the use of an aerosolized fentanyl derivative or due to other complications is unclear.