Synthetic cannabinoid and cathinone use among us soldiers.
Subject: Marijuana (Military aspects)
Marijuana (Laws, regulations and rules)
Bath products (Laws, regulations and rules)
Bath products (Military aspects)
Authors: Berry-Caban, Cristobal S.
Kleinschmidt, Paul E.
Rao, Dinesh S.
Jenkins, Jamie
Pub Date: 10/01/2012
Publication: Name: U.S. Army Medical Department Journal Publisher: U.S. Army Medical Department Center & School Audience: Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 U.S. Army Medical Department Center & School ISSN: 1524-0436
Issue: Date: Oct-Dec, 2012
Topic: Event Code: 930 Government regulation; 940 Government regulation (cont); 980 Legal issues & crime Advertising Code: 94 Legal/Government Regulation Computer Subject: Government regulation
Product: Product Code: 7754001 Marijuana; 2844560 Bath Preparations NAICS Code: 32562 Toilet Preparation Manufacturing
Accession Number: 309980590
Full Text: New hallucinogenic drugs of abuse, known generically as "spice" and "bath salts," have become readily available in the United States. Spice refers to a variety of synthetic cannabinoids that act on the body in a way similar to delta-9-tetrahydrocannabinol (THC). Bath salts refer to a group of hallucinogens that contains various cathinone-like chemicals.

Synthetic cannabinoids have been an area of research since the 1960s for both academia and industry. (1) This is understandable because compounds that mimic the anti-inflammatory and analgesic properties of THC without the psychotropic effects could have significant academic and industrial application. (2) Not surprisingly, these synthetic cannabinoids found their way into the world of recreational drug use. Synthetic cannabinoids were initially available in Europe in 2004 under the brand name Spice. (3) Since then, the substance has continued to increase in popularity. Over time, "spice" came to refer generically to all herbal mixtures with synthetic cannabinoids. There are a number of products marketed with different brand names that are still referred to as spice products.

When spice blends first went on sale in the early 2000s, it was thought that they achieved an effect through a mixture of legal herbs. Subsequent laboratory analysis from Germany and Austria in 2008 showed this was not the case; in fact they contained added synthetic cannabinoids that act on the body in a way similar to cannabinoids found naturally in cannabis, such as THC. A large and complex variety of synthetic cannabinoids, most often cannabicyclohexanol, JWH-018, JWH-073, or HU-210, are used in an attempt to avoid the laws that make cannabis illegal, making synthetic cannabinoids designer drugs. (4)

Spice is used as an alternative to marijuana because of the similarity of their "high" effects. Depending on the synthetic compound in specific commercial brands, spice can be anywhere from 4 times to over 100 times more potent than THC. Furthermore, since their introduction, they have been undetectable by routine urine drug screens. This is a significant draw for abusers. Only recently have specific tests for these drugs become available. Significant adverse effects of spice have been documented, including seizure activity, agitation, hallucinations, myocarditis, and chest pain, as well as compulsive dosing to sustain effect. Redosing is common for both spice and bath salts.

Bath salts are distinguished by their packaging and locations for retail sale from the preparations that are traditionally used as bath or soaking preparations. The most common substances identified in these products are 3,4-methylenedioxypyrovalerone (MDPV), mephedrone, and derivatives of cathinone, all of which produce sympathomimetic effects. Bath salts pose significant health risks and can cause severe symptoms, including death. Since the main ingredients can be compounds similar to 3,4-methylenedioxy-N-methylamphetamine ("ecstasy"), other methamphetamines, Khat, or cocaine, there can be a wide variety of symptoms based on which compound predominates. These symptoms include severe paranoia, violent behavior, hallucinations, decreased need for sleep, lack of appetite, chest pain, and self-mutilation.

Both spice and bath salts are sold over the internet and in various retail locations under multiple brand names. Labels on packets of bath salts and spice state "not for human consumption" and inform consumers that the powder should not be smoked or used as snuff. Nonetheless, the drugs can be inhaled, ingested, smoked, or (in the case of bath salts) injected. Users may develop cardiac and circulatory disturbances, agitation, delirium, paranoia, and psychosis. There have been several cases in which users have attempted to inflict injury on themselves or others. The agitation and delirium may persist for days to weeks.

Similar to spice products, bath salts are sold online and in drug paraphernalia stores under a variety of names. Because these products are relatively new to the drug abuse scene, knowledge about their precise chemical composition and short-term and long-term effects is limited. In addition, because the main ingredients can mimic several different known hallucinogens and stimulants, it is difficult to predict the effect on the user from "brand to brand" or even from packet to packet.

Reports from users indicate the euphoric high of bath salts and spice typically lasts 2 to 4 hours with the letdown effects lasting several hours thereafter. Reported doses for bath salts range from 5 mg to 10 mg for the more lipophilic MDPV, and 100 mg to 250 mg for mephedrone. (5)

Since research on spice and bath salts is still developing, there are few published studies on how these synthetic drugs affect the user. However, case studies have been published that show the harmful side-effects of using spice and bath salts. These demonstrate that spice and bath salts differ in their clinical presentations. In these case studies the majority of the patients are young (18 to 25 years of age), healthy males. Analyzing case studies is the only current way to differentiate the clinical presentations of these designer drugs. For example, in 4 spice case reports, all patients were male, aged 19 to 25 years. (6,7) They all presented to the Emergency Department (ED) with symptoms of either unresponsiveness, paranoia, or seizure activity. All laboratory tests and drug screens proved unremarkable for the 4 patients, however 1 patient was tachycardic (122 bpm) and 3 patients were hypertensive. Also, one patient was combative and had to be restrained. Only upon interviewing the patients were the providers able to determine that the use of spice was the cause for the patients presenting symptoms. (7,8) In an examination of 2 bath salt cases, both patients were female, aged 22 and 27 years respectively. One presented to the ED with symptoms of hallucinations/delusions, while the other presented with suicidal ideation. Upon examination, both were observed as being anxious and frightened, but apart from that all other vital signs, laboratory tests, and drug screens were unremarkable. The hallucinations/delusions experienced by one patient were so severe that she called the police and told them that someone was trying to break into her home. When the police arrived, the patient had barricaded herself in her bedroom because she thought she was about to be killed. She also told police that there was a dead body in her hallway, which was also part of her hallucination. (8) Of these 6 cases examined, 2 were Soldiers stationed at Fort Bragg, North Carolina. (7)

Spice and bath salts use among active duty military is mostly anecdotal. However, there have been several high profile media reports. At the Naval Air Station, Pensacola, Florida, 28 Sailors were involved in incidents with spice over a 2-year period. (9) At Hill Air Force Base near Salt Lake City, Utah, the US Air Force discharged 7 Airmen in early 2010 for spice use, and another 11 Airmen were pending disciplinary action. (10) In October 2011, it was reported that 64 Sailors were found to have either been using or distributing spice, and they were being processed for separation from the military. (11)

Poison control centers in the United States fielded 304 calls for bath salt exposures and 2,906 calls for spice exposures in 2010. (12) In 2011, these increased to 6,138 closed human exposure calls for bath salts and 6,959 exposure calls for spice. While bath salt calls to poison control centers appear to be declining, the number of spice related calls continues to increase. (12) The distribution of these calls from January 2011 through May 2012 is presented in the Figure.

Although synthetic cannabinoids do not produce positive results in routine urine drug tests for cannabis, it is possible to detect the metabolites in human urine. The Department of Defense Forensic Toxicology Drug Testing Laboratories (FTDTL) currently tests urine samples for spice and bath salts upon request. A downside to FTDTL testing is the approximately 3 weeks required to receive results, and the tests are only for known synthetic stimulant metabolites. The FTDTL does not currently test for spice and bath salt substances in routine urine drug screening due to technological and resource constraints.

The synthetic cannabinoids contained in the various spice products have been made illegal in many European countries. (13) Responding to similar potential health concerns, on March 1, 2011, the US Drug Enforcement Agency published a final order placing 5 synthetic cannabinoids into Schedule I of the Controlled Substances Act (CSA) (21 USC [section]801). This action was based on a finding by the Administrator that the placement of these synthetic cannabinoids into Schedule I of the CSA was necessary to avoid an imminent hazard to the public safety. As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil, and administrative penalties, sanctions, and regulatory controls of Schedule I substances were imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cannabinoids. Prior to this announcement, several US states had already made them illegal under state law. (9)

[ILLUSTRATION OMITTED]

The Food and Drug Administration Safety and Innovation Act (S.3187, Title XI, Sec. 1152), enacted on July 9, 2012, permanently bans the chemical compounds marketed and sold as bath salts in the United States.

The branches of the US Armed Forces set their own laws against these substances. Per Army Regulation 600-85, (14) both spice and bath salts fall in the category of substances that could cause impairment or intoxication, and the regulation states that Army personnel are not to use such substances. Soldiers may face disciplinary action under the Uniform Code of Military Justice (UCMJ) * and/or administrative action for using these illicit substances.

Army Regulation 600-85 prohibits Soldiers from using substances:

These regulations are in place to protect Soldiers and to discourage them from jeopardizing their fitness and mental readiness. In addition to spice and bath salts, the following substances are also specifically prohibited by the UCMJ: hemp or products containing hemp oil; controlled substance analogues (designer drugs); chemical propellants or inhalants (huffing); dietary supplements that are banned by the US Food and Drug Administration; prescription or over-the-counter drugs and medications (if illicit or excessive use beyond what is normal, sufficient, or prescribed); and naturally occurring substances (to include but not limited to Salvia divinorium and jimson weed). (14(pp24-25))

Outside of the use prohibition in Army Regulation 600-85, the Army implements and enforces bans against the possession, distribution, and introduction of these products on an installation-by-installation basis. Until spice and bath salts were banned, (15,16) the promulgation of an installation General Order banning the possession, use, sale, distribution, or introduction of these products was the most common solution to the spice dilemma. Fort Bragg, North Carolina, has adopted this policy concerning Soldiers using spice and bath salts. Under the Fort Bragg policy, Soldiers can be punished for possession or transfer of the drugs; they do not have to be using the drug to face regulatory action. Violators of the policy face punishment under the UCMJ.

METHODS

The target population included all active duty Soldiers presenting to the emergency department at Womack Army Medical Center, Fort Bragg, North Carolina, that reported that they had taken spice, bath salts, or were suspected of having ingested these drugs between October 2010 and September 2011. Statistical analyses were conducted using IBM SPSS Statistics version 18 (IBM Corporation, Armonk, NY). All values were statistically analyzed using frequency distributions with calculations of means and standard deviations. Continuous variables were assessed for normality of distribution and compared using 2-tailed t tests. Categorical variables were compared using the [chi square] test. Statistical significance was established at a P value less than or equal to 0.05. This project was reviewed by the Womack Army Medical Center Institutional Review Board.

RESULTS

At the time of admission, 155 patients stated that they were using an illegal substance or were suspected by a provider of using an illegal substance including spice or bath salts (Table 1). The majority of patients were male (144, 92.3 %) and under 30 years of age (mean age=25.6; range=20-52). Of the patients that were suspected of using spice or bath salts, 12 (7.7%) tested positive for spice and 13 (8.3%) tested positive for bath salts (Table 2).

Rates of spice use were greatest among individuals aged 19 to 24 (75.0%). Comparatively, rates for bath salts use were also greatest among individuals aged 19 to 24 (69.2%). All patients that tested positive for bath salts or spice were male.

Of the 26 admitted patients, 19.2% had used bath salts and 11.5% had used spice. The majority of bath salt (46.2%) and spice patients (58.3%) were sent home and one bath salt patient was transferred to a different hospital.

COMMENT

Use of synthetic cannabinoids and synthetic stimulants/ hallucinogens within the Army is a problem that not only affects the individual Soldier, but also the Soldier's unit and the Army as a whole. While seeking help for substance abuse may have been taboo among military personnel in the past, great strides have been made to create a better atmosphere for seeking assistance. (17)

Soldiers who use spice and bath salts will sometimes present to the ED due to the dangerous side effects of these substances. There are many medical challenges that should be addressed concerning these patients. Users tend to be panicked, diaphoretic, tachycardic, and/or hyperthermic. The substances may also trigger depression, restlessness, suicidal ideation or action, paranoia, or hallucinations. In severe cases, security personnel may be required to control the patient prior to sedation. It is important to also note that these patients may require high doses of sedatives to achieve control. Healthcare professionals with a long history in medicine and prehospital care may see these users as the modern day equivalent of the LSD abusers during the 1960s.

Military installations face many challenges when treating patients who have used spice and bath salts. First, only 5 military hospitals have inpatient drug rehabilitation facilities:

* Walter Reed National Military Medical Center, Bethesda, Maryland

* Eisenhower Army Medical Center, Fort Gordon, Georgia

* Fort Belvoir Community Hospital, Virginia

* Naval Medical Center, San Diego, California

* Malcolm Grow Medical Center, Joint Base Andrews Naval Air Facility, Maryland

Furthermore, military treatment facilities do not routinely perform illegal drug testing unless requested by the Soldier's chain of command. In our study, patients in the Emergency Department who are suspected of synthetic drug use are tracked by the Womack Army Medical Center Department of Social Work and referred to the Department of Behavioral Health.

Unfortunately, there are no published guidelines for admission versus discharge. The provider should look for and consider potential complications from the sympathomimetic effects such as heat stroke, arrhythmias, and seizures. Also, providers should keep in mind that even patients without any critical physiologic abnormality can still be combative and agitated with active hallucinations, and may require sedation and observation. Physicians should also be aware of chronic issues like insomnia, short-term memory loss, and persistent cognitive changes that can affect these patients.

Upon discharge, patients are instructed to return to the ED if symptoms return or worsen. Also, patients are referred to the Army's Alcohol and Substance Abuse Program (ASAP), and are not allowed to drive, handle weapons, or perform tasks that require critical thinking until they are cleared on a follow-up visit.

It is obvious that opportunities to obtain these drugs of abuse are widespread, and unfortunately many Soldiers are apparently availing themselves of these opportunities. From past experiences with other substance abuse, it is likely that the number of Soldiers presenting to the emergency department represents a minority of the Soldiers using these substances. With the apparent increasing opportunity for use and the rising number of cases, the military must be proactive in curbing this trend to maintain combat readiness.

Training, pamphlets, guidebooks, and posters are offered through the ASAP to assist commanders, Families, and Soldiers in identifying substance abuse problems and risk factors within themselves and others. Classes that address stress factors common to Soldiers are provided throughout normal duty, as well as during and immediately after deployments.

Resources are abundant and can be found online, through family readiness groups, and within the chain of command. Military OneSource (http://www.militaryonesource.mil) and ASAP are starting points for confidential information and help. Military OneSource offers 12 free counseling sessions per person, per issue. These are confidential and not reported to the Soldier's chain of command unless he or she presents a danger to himself/herself, or others.

Little is known about the metabolism and toxicology of synthetic cannabinoid compounds. Furthermore, it cannot be assumed that the risks associated with the use of synthetic cannabinoids are comparable to those seen with THC. There is reason for concern that these drugs may have a greater potential to cause harm. Moreover, because of the lack of information on the synthetic cannabinoid and synthetic cathinone experience, dose intake, the interaction between other drug consumption, and prior psychiatric comorbidity, further studies to reliably assess these risks are warranted.

REFERENCES

(1.) Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow ... and back again? A review of herbal marijuana alternatives (K2, spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol. 2012;8(1):15-32.

(2.) Huffman JW. CB2 receptor ligands. Mini Rev Med Chem. 2005;5(7):641-649.

(3.) Dresen S, Ferreiros N, Putz M, Westphal F, Zimmermann R, Auwarter V. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom. 2010;45(10):1186-1194.

(4.) The European Monitoring Centre for Drugs and Drug Addiction. Understanding the 'Spice'phenomenon. 2009. Available at: http://www.emcdda.europa.eu/publications/thematic-papers/spice. Accessed April 5, 2012.

(5.) Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K. Withdrawal phenomena and dependence syndrome after the consumption of spice gold. Dtsch Arztebl Int. 2009;106(27):464.

(6.) Simmons J, Cookman L, Kang C, Skinner C. Three cases of "spice" exposure. Clin Toxicol (Phila). 2011;49(5):431-433.

(7.) Berry-Caban CS, Berry CE, Ee J, Ingram V, Kim E. Synthetic cannabinoid overdose in a 20-year-old male US soldier. Subst Abus. 2012. In press.

(8.) Antonowicz JL, Metzger AK, Ramanujam SL. Paranoid psychosis induced by consumption of methylenedioxypyrovalerone: two cases. Gen Hosp Psychiatry. 2011;33(6):640.e5-640.e6.

(9.) Flor A. Spice-I want a new drug. The Army Lawyer. July 2010:23-25. Available at: http://www.loc.gov/rr/frd/Mili tary_Law/pdf/07-2010.pdf. Accessed April 5, 2012.

(10.) Dougherty JM. 7 Hill airmen discharged for spice use. Deseret News. March 27, 2010. Available at: http://www. deseretnews.com/article/700020576/7-Hill-airmen-discharged-for-spice-use.html. Accessed April 5, 2012.

(11.) Basu S. Air Force gets new instruments to test for synthetic marijuana. US Med. 2012;48(5):1,6

(12.) American Association of Poison Control Centers. Bath salts data & synthetic marijuana data information pages [updated June 8, 2012]. Available at: http://www.aapcc.org/dnn/NewsandEvents/NewsMediaResources.aspx. Accessed June 11, 2012.

(13.) Moller I, Wintermeyer A, Bender K, et al. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test Anal. 2011;3(9):609-620.

(14.) Army Regulation 600-85: The Army Substance Abuse Program. Washington, DC: US Dept of the Army; February 2, 2009 [December 2, 2009].

(15.) Chemicals used in "bath salts" now under federal control and regulation; DEA will study whether to permanently control three substances [press release]. Washington, DC: US Drug Enforcement Administration; October 21, 2011. Available at: http://www.justice.gov/dea/pubs/pressrel/pr102111.html. Accessed April 5, 2012.

(16.) Chemicals used in "spice" and "K2" type products under federal control and regulation for additional 6 months; DEA continues studies to determine whether to permanently control five substances [press release]. Washington, DC: US Drug Enforcement Administration; February 29, 2012. Available at: http://www.justice.gov/dea/pubs/pressrel/pr022912.html. Accessed April 5, 2012.

(17.) McFarling L, D'Angelo M, Drain M, Gibbs DA, Olmsted KLR. Stigma as a barrier to substance abuse and mental health treatment. Mil Psychol. 2011;23(1):1-5.

Cristobal S. Berry-Caban, PhD

Paul E. Kleinschmidt, MD

Dinesh S. Rao, MD

Jamie Jenkins, BS

AUTHORS

Dr Berry-Caban is a Clinical Researcher in the Department of Clinical Investigation, Womack Army Medical Center, Fort Bragg, North Carolina.

Dr Kleinschmidt is the Education Director, Department of Emergency Medicine, Womack Army Medical Center, Fort Bragg, North Carolina.

Dr Rao is a General Medical Officer and Clinical Research Associate, Womack Army Medical Center, Fort Bragg, North Carolina.

Ms Jenkins is a Clinical Research Coordinator for the Henry M. Jackson Foundation, Womack Army Medical Center, Fort Bragg, North Carolina.
for the purpose of inducing excitement, intoxication, or
   stupefaction of the central nervous system. (14(p24))


Table 1. Patient demographics.

Gender      No.        Percentage
         (N = 155)

Male        144           92.3
Female       12            7.7

Age
19-24        84           54.2
25-29        54           34.8
30-39        12            7.7
>40           5            3.2

Mean Age = 25.59

Table 2. Distribution of patient test results.

Detected Drug       No.   Percentage
                 (N=155)

Alcohol            16        10.3
Bath Salts         13         8.3
Benzodiazepines    33        21.2
Cocaine            20        12.8
Spice              12         7.7
THC                26        16.7
Negative           36        23.0
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