Journal of Analytical Toxicology 2014;38:563 –568 doi:10.1093/jat/bku067
Special Issue
XLR-11 and UR-144 in Washington State and State of Alaska Driving Cases Asa Louis*, Brianna L. Peterson and Fiona J. Couper Toxicology Laboratory Division, Washington State Patrol, 2203 Airport Way South, Suite 360, Seattle, WA 98134, USA *Author to whom correspondence should be addressed. Email: [email protected]
The case reports for 18 driving cases positive for the synthetic cannabinoid substances XLR-11 and/or UR-144 are discussed. Eleven of these cases had drug recognition expert evaluations performed. Slurred speech, lack of convergence and body and eyelid tremors were the most consistently noted interview characteristic. Pulse and blood pressure of the subjects were within the expected range. Most of the drivers contacted demonstrated poor driving; however, their performance on the standardized field sobriety tests yielded inconsistent diagnostic information. All cases were negative for other commonly detected drugs that affect the central nervous system, although one case was additionally positive for other synthetic cannabinoids. Of the studied cases, six were positive for only UR-144, whereas eight contained only XLR-11. Four cases were found to have both.
Introduction Synthetic cannabinoids, generically known as ‘Spice’, are comprised of a large number of compounds that are designed to mimic the effects of D9-tetrahydrocannabinol (THC), acting as CB1 and CB2 agonists. The first reported identification in the USA of one member of this class occurred in November 2008. In March 2011, the US Drug Enforcement Administration temporarily placed five such compounds into the Controlled Substance Act as Schedule I drugs (JWH-018, JWH-073, JWH-200, CP-47,497 and cannabicyclohexanol) (1, 2). Subsequently, three additional synthetic cannabinoid compounds were placed in this category in May 2013 (UR-144, XLR-11 and APINACA/AKB48) (3). In January 2014, four additional Spice substances were filed with notice of intent to be temporarily scheduled: PB-22, QUPIC, AB-FUBINACA and ADB-PINACA (4). As a consequence of scheduling on the Federal level, most States and Territories have enacted additional legislation regarding the sale, possession, manufacture and delivery of these and similar compounds (5, 6). While a literature search yields numerous reports that discuss the clinical symptoms, few have noted the driving behavior of subjects under the influence of Spice. This paper presents a summary of some of the driving behaviors and post contact observations, as reported by Washington State and State of Alaska law enforcement personnel, with blood samples that were submitted to the Washington State Patrol Toxicology Laboratory Division (WSPTLD) for testing. Samples that were found to contain the synthetic cannabinoids UR-144 and XLR-11 spanned from June 2012 through September 2013.
Method Cases in which Washington State or State of Alaska law enforcement personnel believe a drivers’ ability to safely operate a motor
vehicle is impaired are referred to the WSPTLD. The laboratory’s function is to aid in determining if there are substances in the driver’s blood that could explain the observed behavior. Cases are screened for volatile compounds via gas chromatography flame ionisation detector (GC-FID), and then presumptively tested for common central nervous system active drugs (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, methadone, phencyclidine and tricyclic antidepressants) via EMIT. Depending upon the case history, additional screening or confirmation may be performed via gas chromatography nitrogen phosphorus detector (GC-NPD), GC– MS and/or LC–MS-MS. In cases involving suspected Spice usage, the laboratory refers these to NMS Labs in Willow Grove, PA, USA. Following analysis using LC – MS-MS, their reporting limit is 0.1 mg/L, though no quantitative values were published (7). This study includes cases that meet three criteria: positive findings for UR-144 and/or XLR-11, no other drugs detected and sufficient detail in the arresting officer/drug recognition expert (DRE) observations of the subject’s behavior and physical tests in the submitted report.
Results Between June 2012 and September 2013, 32 suspected impaired driving cases were positive for UR-144/XLR-11. Of these cases, we report 18 that were found to contain no other drugs other than synthetic cannabinoids, specifically UR-144 and/or XLR-11. One included case also was found to have other Spice products AM-2201, JWH-018 and JWH-022. The population of this study has a mean age of 25 years (range 17 – 42, median 23.0) and all were male. A review of all 32 cases yielded only two female drivers where UR-144/XLR-11 was detected. A summary of the demographics and main signs and symptoms of the 18 reported cases is presented in Tables I and II.
Subject 1 A 22-year-old male reported to police for erratic driving was observed traveling over the yellow divider line for 15 – 20 ft. The vehicle returned over to the skip line, and then over the divider line for another 15– 20 ft, speeding up and nearly colliding with a motorcycle. Upon contact, the subject had slurred speech and lacked the coordination needed to find paperwork and exit the vehicle. Additional interview observations included bloodshot watery eyes, dilated pupils and droopy eyelids. The results of the standardized field sobriety tests (SFSTs) showed no clues of horizontal gaze nystagmus (HGN), five of eight clues on the walk and turn (WAT) and three of four clues on the one leg stand (OLS). During the OLS, the subject showed 4 – 6 inch sways with body and leg tremors. During the Romberg balance test, the investigator noted body sways and eyelid flutters. The
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subject was found to have Spice and a pipe in his possession and admitted to smoking 2 h prior to the stop. Blood was obtained 1 h and 10 min after contact and was found to contain UR-144.
Subject 2 A 22-year-old male was stopped by police for severe lane travel and driving on the shoulder. Upon contact, the subject had
slow, slurred and repetitive speech and had difficulty standing. He was also noted to be driving in the opposite direction of his intended destination. DRE interview observations included bloodshot eyes, dilated pupils, droopy eyelids and lack of convergence (LOC). The SFSTs reported no clues of HGN, two of eight clues on the WAT and one of four clues on the OLS. During the OLS, the subject showed body and leg tremors. He was found to have Spice and a pipe in his possession. He admitted to smoking 1.5 h prior to the stop. Blood was obtained 1 h and 50 min after contact and was found to contain UR-144.
Table I Summary of 18 Suspected Impaired Driving Subjects Subject Age (years)
Drug(s) detected
Last dosea (h)
Drug paraphernalia
Reason for initial police contact
1 2 3 4 5 6 7 8
22 22 25 42 29 30 22 23
2:00 1:30 0:15 10:00
Yes Yes Yes Yes Yes Yes No Yes
Speed, lane travel Lane travel Unconscious, accident Lane travel Erratic Speed, lane travel Lane travel Lane travel
9 10 11
30 25 27
UR-144 UR-144 UR-144 UR-144 UR-144 UR-144, XLR-11 UR-144, XLR-11 UR-144, XLR-11, AM-2201, JWH-018, JWH-022 UR-144, XLR-11 UR-144 XLR-11
2:00
Yes Yes Yes
12
27
XLR-11
72:00
No
13 14 15 16 17 18
30 17 22 19 22 23
XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11
2:00 0:00 24:00 4:00 2:30 1:00
Yes Yes Yes No No Yes
Accident Lane travel Speed, lane travel, accident Speed, lane travel, driving on curb, accident Moving violation Lane travel Unconscious, accident
Subject 3 A 25-year-old male was observed by police to stop on the highway for 30 s causing a potential hazard to other drivers, and then he abruptly accelerated away. The vehicle was then subsequently involved in a collision with a median divider. Upon contact, the driver was exhibiting seizure like behavior and was transported to hospital. His passenger, a 20-year-old female, admitted that they started smoking 15 min prior to the accident and were smoking while driving, and that the male was driving ‘crazy’. At the hospital, the male showed six clues of HGN and was visibly shaking while seated. His eyes were bloodshot and watery, and his speech was slurred and choppy. He also stated that he had blacked out. No other SFSTs were performed due to immobilization. Blood was obtained 1 h after contact and found to contain UR-144.
Subject 4 A 42-year-old male commercial vehicle operator was reported to police for erratic driving. Police observed lane travel, with the vehicle crossing the fog line three times. Upon contact, the subject
Driving on curb Wrong way driver
a
Self-reported time of last dose.
Table II Summary of Physical Observations of 18 Suspected Impaired Driving Subjectsa Subject Drug(s) detected
Coordination Eyesb
Speech
HGN
LOC
Tremorsc WAT
OLS
FTN
Internal clock (s)
Time of blood draw (h)
1 2 3 4
UR-144 UR-144 UR-144 UR-144
Poor Poor Shaking Poor
B, W, Dt B, Dt B, W B, W
Normal Slurred Slurred Slurred
– Yes – Yes
Yes Yes Yes No
5 clues 2 clues – 2 clues
3 clues 1 clue – 1 clue
– Normal – Normal
– 40 – 11
1:10 1:50 1:00 1:00
5 6 7 8
Poor Poor Normal Poor
B, Dr B, W Dt B, W
Slurred Slurred Raspy Slurred
No No Yes –
Yes Yes Yes No
3 5 0 2
2 0 2 2
Normal 5 clues Pad –
24 45 28 –
4:55 1:50 1:05 1:00
9 10
UR-144 UR-144, XLR-11 UR-144, XLR-11 UR-144, XLR-11, AM-2201, JWH-018, JWH-022 UR-144, XLR-11 UR-144
No No 6 clues 4 clues, then no clues No 2 clues 6 clues 4 clues
Normal Swaying
B B, W
No 4 clues
Yes Yes
Yes Yes
0 clues 3 clues
1 clue 2 clues
3 clues, Pad Normal
25 28
1:40 1:35
11 12 13 14 15 16 17 18
XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11
– Poor – Poor Poor Poor Slow Poor
B, Dt B, Dt B, C B, W, Dt B, W, Dt B, W, Dr B, Dr B
Normal Raspy, Slurred Slurred Slurred Normal Normal Slurred Slurred Mumbled Normal
No No 6 clues No 4 clues 6 clues 6 clues No
– Yes – – – Yes No Yes
No Yes No No No Yes Yes Yes
– 4 clues 4 clues 1 clue 3 clues 1 clue 2 clues 2 clues
– 1 clue 2 clues 0 clues 3 clues 1 clue 1 clue 2 clues
2 clues – – – 5 clues 5 clues, pad 3 clues
– 21 – 35 – 44 35 30
1:50 2:45 4:45 1:25 1:30 2:45 1:30 1:45
clues clues clues clues
‘2’, not performed. a HGN, horizontal gaze nystagmus; LOC, lack of convergence; WAT, walk and turn test; OLS, one leg stand test; FTN, finger-to-nose test. b B, bloodshot; W, watery; Dt, dilated pupils; C, constricted pupils; Dr, droopy eyelids. c Tremors, the presence of body and eyelid tremors.
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clues clues clues clues
had bloodshot watery eyes and droopy eyelids. He also had slurred speech and poor coordination. The officer noted poor field sobriety test with four clues of HGN. The DRE evaluation noted no HGN only 30 min later, no LOC, but a significantly accelerated internal clock (estimated 30 s in 11). The subject admitted to inhaling Spice 10 h prior to the stop. Blood was obtained 1 h after contact and contained UR-144.
Subject 5 A 29-year-old male was contacted for erratic driving. Upon contact, the subject had slurred speech and bloodshot eyes with droopy eyelids and poor coordination. Significant DRE findings noted three clues on the WAT and eyelid tremors. A container of Spice was found in the car, although the subject denied usage. The blood was obtained 4 h and 55 min after initial contact and was found to contain UR-144.
Subject 6 A 30-year-old male driver was reported to be driving 30 miles/ h below the posted speed limit and exhibiting severe lane travel, nearly colliding with several other vehicles. Contact was made after the driver had stopped. Initial contact noted slow, lethargic movements with unsteady gait. His eyes were bloodshot and watery with dilated pupils. Speech was also slow and slurred. The DRE noted two clues of HGN, five clues on the WAT and three clues on the OLS. The subject’s internal clock was also slow, estimating the passage of 45 s as 30. Body and leg tremors were also present. The driver had three packs of Spice in his possession. A blood sample was obtained 1 h and 50 min after contact. The blood was found to contain UR-144 and XLR-11.
Subject 7 A 22-year-old male was contacted after crossing into oncoming traffic and nearly colliding with the officer. The subject’s pupils were dilated and both eyelid and body tremors were observed. All clues of HGN were present, as well as LOC and rebound dilation. The WAT was satisfactorily executed, though the OLS showed two clues. The subject used the pad of his finger four times of six during the finger-to-nose (FTN) test. The subject admitted to using both Spice and marijuana; however, no THC or carboxy-THC was found. One hour and 5 min had passed from the time of contact to DRE completion. The blood obtained was found to contain UR-144 and XLR-11.
Subject 8 A 23-year-old male was stopped after being observed crossing over the center line and having his eyes closed while driving by the officer. During the investigation, the subject had bloodshot watery eyes and poor dexterity when handling paperwork. Slurred speech was also noted. Through the use of the SFSTs, the officer concluded impairment; however, no indicators were included in the submitted paperwork. The subject admitted to recently consuming marijuana and Spice, with Spice packaging found on the person. Processing time took 1 h, with the blood analysis ultimately yielding positive results for UR-144, XLR-11, AM-2201, JWH-018 and JWH-022.
Subject 9 A 30-year-old male was contacted after striking multiple vehicles. The officer noted bloodshot eyes and slow reactions. SFSTs were unremarkable other than the estimation of 30 s in 20 and severe leg and arm tremors. A DRE evaluation was conducted 90 min later. The DRE observed LOC and use of the pad of the finger during the FTN test, but no body or eyelid tremors. The subject had admitted to smoking Spice while driving and there was residual material found in his vehicle. Analysis revealed that UR-144 and XLR-11 from the blood sample obtained 1 h and 40 min after contact.
Subject 10 A 25-year-old male was contacted after reports of a suspected drunk driver. The stop occurred after the subject vehicle crossed over the fog line. Upon contact, the driver had difficulties pushing the button to lower the window. Investigation revealed bloodshot watery eyes, drooling and raspy, slurred and incoherent speech. The subject had poor balance and swayed and shook while standing. SFSTs could not be completed. The DRE noted the same physical symptoms, and an additional four clues on the HGN and three on the WAT. Eyelid tremors were also present. Spice was seen in plain view, and the subject admitted consumption. Blood was obtained 1 h and 35 min post contact. Blood analysis revealed UR-144.
Subject 11 A 27-year-old male was stopped after driving with inconsistent speed and being involved in a collision with the median barrier multiple times. The DRE noted slurred, incoherent speech, drool and dilated pupils. A pipe and packages of new and spent Spice were found on the subject. The subject was otherwise unresponsive, and no physical tests were conducted. The blood was obtained 1 h and 50 min after initial contact. Blood analysis revealed XLR-11.
Subject 12 A 27-year-old male was contacted after severe lane travel and striking a raised curb six times, going off the road and finally stopping after high centering the car on a raised curb. Multiple civilian witnesses and the officer noted slurred speech, disorientation, erratic and abnormal behavior. Physical tests demonstrated no HGN, bloodshot eyes and LOC with eyelid tremors. The WAT revealed four clues. Body tremors were present during the Romberg balance test, with an estimation of 30 s in 21 and 3 inch body sways. Pulse was noted to vary, slow, fast, and then slow again over the evaluation period. Paraphernalia found included a smoking pipe and a baggie of green matter, and the subject admitted to smoking 72 h prior. Blood was obtained 2 h and 45 min after law enforcement contact, and XLR-11 was detected in the sample.
Subject 13 A 30-year-old male was contacted after failing to stop at a stop sign. The investigator noted constricted pupils and bloodshot eyes. HGN testing noted four clues and vertical gaze nystagmus, XLR-11 and UR-144 in Driving Cases 565
four clues on the WAT and two clues on the OLS. A pipe and green material were found in the car, and the driver admitted to smoking 2 h prior to driving. XLR-11 was detected in the blood obtained 4 h and 45 min after the stop.
obtained 1 h and 45 min after contact. XLR-11 was detected in the blood obtained.
Discussion
Subject 17 A 22-year-old male was stopped by civilian and fire department personnel for driving on the curb. Police noted the driver to have bloodshot eyes and droopy eyelids with slow coordination. The DRE evaluation noted all clues present on the HGN test and two clues on the WAT. One clue was observed on the OLS, with body and leg tremors present. The subject used the pad of the finger on the FTN test five times. The subject admitted to smoking Spice 1 h prior to contact. Blood was obtained 90 min post contact and contained XLR-11.
The two compounds studied are structurally related, XLR-11 being the fluorinated analog of UR-144 ((1-pentyl-1H-indol3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone) (Fig. 1). Synthetic cannabinoid compounds are designed to mimic the agonistic effects attributed to THC in the human system. It has been reported that the toxicity of synthetic cannabinoid, however, may be greater than THC due to higher potency, unregulated and varied dose preparation and purity on the vegetable matter and stronger activity on the cannabinoid receptors (3, 8 –11). It has also been reported that some synthetic cannabinoids remain detectable for up to 102-day post drug use (12) and may have toxicity symptoms present for up to 14 h (13). Authors have also reported that there have been significant toxicological findings attributed to Spice exposure that have not been seen with typical recreational marijuana usage. These include acute nephrotoxicity (14 –16) adverse psychoactive responses—severe anxiety, psychosis and hallucination (2, 11, 17 – 19), withdrawal symptoms of tachycardia and myocardial infarction (2, 18, 20 – 22), respiratory depression (23), seizures (19, 22) and suicide ideation and death (13, 24 –26). With the driving cases studied, there were some behaviors consistent with cannabis usage. Typical DRE observations for cannabinoid impairment (27, 28) include the presence of LOC, normal to dilated pupils, increased heart rate and blood pressure, normal body temperature and no HGN or vertical gaze nystagmus. Consistent with these indicators, 8 of the 11 subjects in this study who were tested displayed LOC. The ratio of subjects displaying dilated pupils is lower with only 6 of the 18 showing this indicator. Pulse and blood pressure measures were consistent with markers for the cannabimimetic compounds, with all subjects observed to have these elevated, though within normal ranges, although Subject 12 had a pulse rate that varied greatly over the interview period. The body temperature of most of the subjects was considered normal (within +18 of 98.6 8F), though all appeared near the lower end of the range except Subject 9 who had a reported temperature of 99.4 F. Body and eyelid tremors are often seen in individuals dosed with THC, and this was also the case with drivers in this study (12 of 17 drivers who consented to testing). It is noted that many of the drivers exhibited slurred speech (11 of 18 overall), more so with those under the influence of only UR-144 (5 of 6) than only XLR-11 (4 of 8). Some behaviors were also typical of individuals under the influence of cannabinoids—drowsiness and impaired short-term memory (several individuals had to be reminded to follow the stimulus with just their eyes during the HGN evaluation).
Subject 18 A 23-year-old male was stopped by police officers after driving 20 miles in the opposing direction of traffic. The DRE noted bloodshot eyes, LOC, eyelid tremors, no HGN and two clues each on the WAT and OLS. There were three misses on the FTN, but no other findings. The subject admitted to smoking Spice twice in the last day, most recently 1 h prior to driving. Blood was
Figure 1. Chemical structure of UR-144 (left) and XLR-11.
Subject 14 A 17-year-old male was reported to police as driving with severe lane travel, nearly striking another vehicle and nearly driving into a ditch. Personal contact notes indicate dilated pupils and bloodshot watery eyes. Field tests yielded no significant findings. Inventory of the vehicle included Spice and a glass pipe. The subject admitted to smoking while driving. Blood obtains 1.5 h after the initial contact confirmed for XLR-11.
Subject 15 A 22-year-old male was found unconscious in his vehicle in a busy intersection after nearly striking other vehicles and pedestrians. The subject appeared groggy, and his speech was thick and slurred. The subject’s movements were slow and uncoordinated. There were four clues on the HGN, three clues on the WAT and three clues on the OLS. Spice packages were found in the vehicle and on his lap, although the subject denied using in the past day. A blood sample was taken 1.5 h after contact and was found positive for XLR-11.
Subject 16 A 19-year-old male was contacted for traffic violations. A DRE evaluation noted bloodshot watery eyes, droopy eyelids, LOC and all clues on the HGN. Body tremors were seen, but not from the eyelids. Rebound dilation was also noted. There were five misses on the FTN. The subject’s internal clock was slow with the estimation of 30 s as 44. The subject admitted to smoking Spice and marijuana 4 h earlier, with blood results indicating the presence of XLR-11, but no THC or marijuana metabolites. The blood was obtained 2 h and 45 min after initial contact.
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Inability to maintain vigilance to mundane tasks (23, 29, 30) may contribute to some of the driving behaviors reported, including loss of lane position control and improper speed. Of possibly greater interest, particularly for field investigators, are the behaviors that are not consistent with cannabis intoxication, most notably the presence of HGN. Individuals under the influence of THC typically do not exhibit HGN (27, 28). Of the 18 reports collected, half of the drivers exhibited this symptom, eight of which exhibited four or more clues. Of special interest, Subject 4 exhibited four indicators at first contact then showed none only half an hour later during the follow-up DRE examination. The FTN test, which is used to assess one’s proprioceptive abilities, is typically a helpful aid to determine the presence of cannabis. In this study, 7 of the 12 subjects demonstrated deficiencies, of which one had used the pad of the finger instead of the tip, but otherwise satisfactorily completed the task. There also appears to be little correlation with time of last (albeit self reported) dose and symptomology. Subject 4 showed extreme symptoms of an individual with very recent exposure to a strong cannabimimetic agent: slurred speech, bloodshot watery eyes, shaking, psychosis, loss of consciousness and poor driving ability and exhibiting signs of intoxication that are not typical for cannabis—specifically HGN. Contrasting this, Subject 14 who was also contacted for poor driving very shortly after exposure—both admitted to smoking while driving—demonstrated poor coordination, but no slurred speech and no indications by the SFSTs. Likewise, there seems to be little correlation regarding cases where there is greater elapsed time: Subject 4 reported 10 h since last dosing exhibited slurred speech, poor coordination, four indicators on the HGN test, LOC and body tremors; Subject 22 displayed similar symptoms 24 h post dosing. The uncontrolled and inconsistent application of active ingredient of unknown purity onto a varied delivery substrate of unknown origin (31) makes it is difficult, if not impossible to draw conclusions of dose response. Additionally, without concentrations for UR-144 or XLR-11, the difficulty to draw a dose – response relationship is compounded. With the 18 cases in this review, it can be noted that the effects of these Spice compounds can be powerful impairing agents that may have long-lasting effects, potentially up to 3 days. Symptoms are similar to those expected for those under the influence of cannabis but other indicators not normally seen, such as HGN, may confound the field diagnosis. Different individuals may also exhibit different signs and degrees of intensity of the various indicators. Most of the studied group exhibited bloodshot eyes, poor coordination with slurred speech and did poorly on the WAT. Other tests that usually are reliable indicators were less consistent. Proprioceptive tests and body and eyelid tremors are inconsistent, as were challenges to the internal clock. Personal communications (S. Beck, 10 March 2014) with one DRE bears this out: ‘From what our DRE program has reviewed in the past it was hard to pin down effects of Spice as the results are kind of all over the place’. The presence of paraphernalia may be a strong indicator that the individual is under the influence of a Spice product. As noted by previous authors, as compounds become scheduled, new ones will arise (32, 33). The first case presented to this laboratory was in June 2012. Over the following 16 months, until September 2013, there was a relatively steady flow of cases presented in which UR-144/XLR-11 was eventually detected. These two compounds were temporarily placed into Schedule
I status in May 2013, and presumably, suppliers used a new formulation to replace what stock had already been prepared. From September 2013 to February 2014, no new cases of UR-144/ XLR-11 have been presented to this laboratory.
Conclusion Based on the limited number of cases presented to the WSPTLD, Spice, particularly XLR-11 and UR-144, has the potential to strongly and negatively impact a driver’s ability to operate a motor vehicle safely. These reports indicate significant lane travel, inappropriate speed, collision and severe inattention. Although XLR-11 and UR-144 are classified as cannabimimetic compounds, they do not consistently manifest the classical cannabis indicators, as dictated by the DRE classification system, particularly the presence of HGN. Additional information through controlled clinical testing with known and measured dosing may allow the determination of dose response, as well as the duration of effects.
Conflict of Interest statement None declared.
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23. Jinwala, F.N., Gupta, M. (2012) Synthetic cannabis and respiratory depression. Journal of Child and Adolescent Psychopharmacology, 22, 459–462. 24. Favretto, D., Pascali, J.P., Tagliaro, F. (2013) New challenges and innovation in forensic toxicology: focus on the “New Psychoactive Substances”. Journal of Chromatography A, 26, 84– 95. 25. Thomas, S., Bliss, S., Malik, M. (2012) Suicidal ideation and self-harm following K2 use. Journal of the Oklahoma State Medical Association, 105, 430–433. 26. Fattore, L., Fratta, W. (2011) Beyond THC: the new generation of cannabinoid designer drugs. Frontiers in Behavioral Neuroscience, 5, 60. 27. Washington State Patrol. (2013) Drug recognition and classification training. “The Drug Recognition Expert School” Administrative Guide. http://www.wsp.wa.gov/breathtest/docs/webdms/DRE_ Forms/Manuals/dre7/Instructor%20Guide%20(DRE%207-Day)% 20-%20May%202013%20(230MB).pdf (accessed June 17, 2014). 28. Couper, F.J., Logan, B.K. (2004) National Highway Traffic Safety Administration. Drugs and Human Performance Fact Sheets. http:// www.nhtsa.gov/people/injury/research/job185drugs/ (accessed March 14, 2014). 29. Musshoff, F., Madea, B., Kernbach-Wighton, G., Bicker, W., Kneisel, S., Hutter, M. et al. (2014) Driving under the influence of synthetic cannabinoids (“Spice”): a case series. International Journal of Legal Medicine, 128, 59–64. 30. University of Washington Alcohol and Drug Abuse Institute. (2013) Spice and K2 (Synthetic Marijuana). http://adai.washington.edu/ marijuana/factsheets/spice.pdf (accessed March 14, 2014). 31. Presley, B.C., Jansen-Varnum, S.A., Logan, B.K. (2013) Analysis of synthetic cannabinoids in botanical material: a review of analytical methods and findings. Forensic Science Review, 25, 28 –46. 32. Johnson, L.A., Johnson, R.L., Portier, R.B. (2013) Current “legal highs”. Journal of Emergency Medicine, 44, 1108–1115. 33. Shanks, K.G., Behonick, G.S., Dahn, T., Terrell, A. (2013) Identification of novel third-generation synthetic cannabinoids in products by ultra-performance liquid chromatography and time-of-flight mass spectrometry. Journal of Analytical Toxicology, 37, 517–525.
Special Issue
XLR-11 and UR-144 in Washington State and State of Alaska Driving Cases Asa Louis*, Brianna L. Peterson and Fiona J. Couper Toxicology Laboratory Division, Washington State Patrol, 2203 Airport Way South, Suite 360, Seattle, WA 98134, USA *Author to whom correspondence should be addressed. Email: [email protected]
The case reports for 18 driving cases positive for the synthetic cannabinoid substances XLR-11 and/or UR-144 are discussed. Eleven of these cases had drug recognition expert evaluations performed. Slurred speech, lack of convergence and body and eyelid tremors were the most consistently noted interview characteristic. Pulse and blood pressure of the subjects were within the expected range. Most of the drivers contacted demonstrated poor driving; however, their performance on the standardized field sobriety tests yielded inconsistent diagnostic information. All cases were negative for other commonly detected drugs that affect the central nervous system, although one case was additionally positive for other synthetic cannabinoids. Of the studied cases, six were positive for only UR-144, whereas eight contained only XLR-11. Four cases were found to have both.
Introduction Synthetic cannabinoids, generically known as ‘Spice’, are comprised of a large number of compounds that are designed to mimic the effects of D9-tetrahydrocannabinol (THC), acting as CB1 and CB2 agonists. The first reported identification in the USA of one member of this class occurred in November 2008. In March 2011, the US Drug Enforcement Administration temporarily placed five such compounds into the Controlled Substance Act as Schedule I drugs (JWH-018, JWH-073, JWH-200, CP-47,497 and cannabicyclohexanol) (1, 2). Subsequently, three additional synthetic cannabinoid compounds were placed in this category in May 2013 (UR-144, XLR-11 and APINACA/AKB48) (3). In January 2014, four additional Spice substances were filed with notice of intent to be temporarily scheduled: PB-22, QUPIC, AB-FUBINACA and ADB-PINACA (4). As a consequence of scheduling on the Federal level, most States and Territories have enacted additional legislation regarding the sale, possession, manufacture and delivery of these and similar compounds (5, 6). While a literature search yields numerous reports that discuss the clinical symptoms, few have noted the driving behavior of subjects under the influence of Spice. This paper presents a summary of some of the driving behaviors and post contact observations, as reported by Washington State and State of Alaska law enforcement personnel, with blood samples that were submitted to the Washington State Patrol Toxicology Laboratory Division (WSPTLD) for testing. Samples that were found to contain the synthetic cannabinoids UR-144 and XLR-11 spanned from June 2012 through September 2013.
Method Cases in which Washington State or State of Alaska law enforcement personnel believe a drivers’ ability to safely operate a motor
vehicle is impaired are referred to the WSPTLD. The laboratory’s function is to aid in determining if there are substances in the driver’s blood that could explain the observed behavior. Cases are screened for volatile compounds via gas chromatography flame ionisation detector (GC-FID), and then presumptively tested for common central nervous system active drugs (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates, methadone, phencyclidine and tricyclic antidepressants) via EMIT. Depending upon the case history, additional screening or confirmation may be performed via gas chromatography nitrogen phosphorus detector (GC-NPD), GC– MS and/or LC–MS-MS. In cases involving suspected Spice usage, the laboratory refers these to NMS Labs in Willow Grove, PA, USA. Following analysis using LC – MS-MS, their reporting limit is 0.1 mg/L, though no quantitative values were published (7). This study includes cases that meet three criteria: positive findings for UR-144 and/or XLR-11, no other drugs detected and sufficient detail in the arresting officer/drug recognition expert (DRE) observations of the subject’s behavior and physical tests in the submitted report.
Results Between June 2012 and September 2013, 32 suspected impaired driving cases were positive for UR-144/XLR-11. Of these cases, we report 18 that were found to contain no other drugs other than synthetic cannabinoids, specifically UR-144 and/or XLR-11. One included case also was found to have other Spice products AM-2201, JWH-018 and JWH-022. The population of this study has a mean age of 25 years (range 17 – 42, median 23.0) and all were male. A review of all 32 cases yielded only two female drivers where UR-144/XLR-11 was detected. A summary of the demographics and main signs and symptoms of the 18 reported cases is presented in Tables I and II.
Subject 1 A 22-year-old male reported to police for erratic driving was observed traveling over the yellow divider line for 15 – 20 ft. The vehicle returned over to the skip line, and then over the divider line for another 15– 20 ft, speeding up and nearly colliding with a motorcycle. Upon contact, the subject had slurred speech and lacked the coordination needed to find paperwork and exit the vehicle. Additional interview observations included bloodshot watery eyes, dilated pupils and droopy eyelids. The results of the standardized field sobriety tests (SFSTs) showed no clues of horizontal gaze nystagmus (HGN), five of eight clues on the walk and turn (WAT) and three of four clues on the one leg stand (OLS). During the OLS, the subject showed 4 – 6 inch sways with body and leg tremors. During the Romberg balance test, the investigator noted body sways and eyelid flutters. The
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subject was found to have Spice and a pipe in his possession and admitted to smoking 2 h prior to the stop. Blood was obtained 1 h and 10 min after contact and was found to contain UR-144.
Subject 2 A 22-year-old male was stopped by police for severe lane travel and driving on the shoulder. Upon contact, the subject had
slow, slurred and repetitive speech and had difficulty standing. He was also noted to be driving in the opposite direction of his intended destination. DRE interview observations included bloodshot eyes, dilated pupils, droopy eyelids and lack of convergence (LOC). The SFSTs reported no clues of HGN, two of eight clues on the WAT and one of four clues on the OLS. During the OLS, the subject showed body and leg tremors. He was found to have Spice and a pipe in his possession. He admitted to smoking 1.5 h prior to the stop. Blood was obtained 1 h and 50 min after contact and was found to contain UR-144.
Table I Summary of 18 Suspected Impaired Driving Subjects Subject Age (years)
Drug(s) detected
Last dosea (h)
Drug paraphernalia
Reason for initial police contact
1 2 3 4 5 6 7 8
22 22 25 42 29 30 22 23
2:00 1:30 0:15 10:00
Yes Yes Yes Yes Yes Yes No Yes
Speed, lane travel Lane travel Unconscious, accident Lane travel Erratic Speed, lane travel Lane travel Lane travel
9 10 11
30 25 27
UR-144 UR-144 UR-144 UR-144 UR-144 UR-144, XLR-11 UR-144, XLR-11 UR-144, XLR-11, AM-2201, JWH-018, JWH-022 UR-144, XLR-11 UR-144 XLR-11
2:00
Yes Yes Yes
12
27
XLR-11
72:00
No
13 14 15 16 17 18
30 17 22 19 22 23
XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11
2:00 0:00 24:00 4:00 2:30 1:00
Yes Yes Yes No No Yes
Accident Lane travel Speed, lane travel, accident Speed, lane travel, driving on curb, accident Moving violation Lane travel Unconscious, accident
Subject 3 A 25-year-old male was observed by police to stop on the highway for 30 s causing a potential hazard to other drivers, and then he abruptly accelerated away. The vehicle was then subsequently involved in a collision with a median divider. Upon contact, the driver was exhibiting seizure like behavior and was transported to hospital. His passenger, a 20-year-old female, admitted that they started smoking 15 min prior to the accident and were smoking while driving, and that the male was driving ‘crazy’. At the hospital, the male showed six clues of HGN and was visibly shaking while seated. His eyes were bloodshot and watery, and his speech was slurred and choppy. He also stated that he had blacked out. No other SFSTs were performed due to immobilization. Blood was obtained 1 h after contact and found to contain UR-144.
Subject 4 A 42-year-old male commercial vehicle operator was reported to police for erratic driving. Police observed lane travel, with the vehicle crossing the fog line three times. Upon contact, the subject
Driving on curb Wrong way driver
a
Self-reported time of last dose.
Table II Summary of Physical Observations of 18 Suspected Impaired Driving Subjectsa Subject Drug(s) detected
Coordination Eyesb
Speech
HGN
LOC
Tremorsc WAT
OLS
FTN
Internal clock (s)
Time of blood draw (h)
1 2 3 4
UR-144 UR-144 UR-144 UR-144
Poor Poor Shaking Poor
B, W, Dt B, Dt B, W B, W
Normal Slurred Slurred Slurred
– Yes – Yes
Yes Yes Yes No
5 clues 2 clues – 2 clues
3 clues 1 clue – 1 clue
– Normal – Normal
– 40 – 11
1:10 1:50 1:00 1:00
5 6 7 8
Poor Poor Normal Poor
B, Dr B, W Dt B, W
Slurred Slurred Raspy Slurred
No No Yes –
Yes Yes Yes No
3 5 0 2
2 0 2 2
Normal 5 clues Pad –
24 45 28 –
4:55 1:50 1:05 1:00
9 10
UR-144 UR-144, XLR-11 UR-144, XLR-11 UR-144, XLR-11, AM-2201, JWH-018, JWH-022 UR-144, XLR-11 UR-144
No No 6 clues 4 clues, then no clues No 2 clues 6 clues 4 clues
Normal Swaying
B B, W
No 4 clues
Yes Yes
Yes Yes
0 clues 3 clues
1 clue 2 clues
3 clues, Pad Normal
25 28
1:40 1:35
11 12 13 14 15 16 17 18
XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11 XLR-11
– Poor – Poor Poor Poor Slow Poor
B, Dt B, Dt B, C B, W, Dt B, W, Dt B, W, Dr B, Dr B
Normal Raspy, Slurred Slurred Slurred Normal Normal Slurred Slurred Mumbled Normal
No No 6 clues No 4 clues 6 clues 6 clues No
– Yes – – – Yes No Yes
No Yes No No No Yes Yes Yes
– 4 clues 4 clues 1 clue 3 clues 1 clue 2 clues 2 clues
– 1 clue 2 clues 0 clues 3 clues 1 clue 1 clue 2 clues
2 clues – – – 5 clues 5 clues, pad 3 clues
– 21 – 35 – 44 35 30
1:50 2:45 4:45 1:25 1:30 2:45 1:30 1:45
clues clues clues clues
‘2’, not performed. a HGN, horizontal gaze nystagmus; LOC, lack of convergence; WAT, walk and turn test; OLS, one leg stand test; FTN, finger-to-nose test. b B, bloodshot; W, watery; Dt, dilated pupils; C, constricted pupils; Dr, droopy eyelids. c Tremors, the presence of body and eyelid tremors.
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clues clues clues clues
had bloodshot watery eyes and droopy eyelids. He also had slurred speech and poor coordination. The officer noted poor field sobriety test with four clues of HGN. The DRE evaluation noted no HGN only 30 min later, no LOC, but a significantly accelerated internal clock (estimated 30 s in 11). The subject admitted to inhaling Spice 10 h prior to the stop. Blood was obtained 1 h after contact and contained UR-144.
Subject 5 A 29-year-old male was contacted for erratic driving. Upon contact, the subject had slurred speech and bloodshot eyes with droopy eyelids and poor coordination. Significant DRE findings noted three clues on the WAT and eyelid tremors. A container of Spice was found in the car, although the subject denied usage. The blood was obtained 4 h and 55 min after initial contact and was found to contain UR-144.
Subject 6 A 30-year-old male driver was reported to be driving 30 miles/ h below the posted speed limit and exhibiting severe lane travel, nearly colliding with several other vehicles. Contact was made after the driver had stopped. Initial contact noted slow, lethargic movements with unsteady gait. His eyes were bloodshot and watery with dilated pupils. Speech was also slow and slurred. The DRE noted two clues of HGN, five clues on the WAT and three clues on the OLS. The subject’s internal clock was also slow, estimating the passage of 45 s as 30. Body and leg tremors were also present. The driver had three packs of Spice in his possession. A blood sample was obtained 1 h and 50 min after contact. The blood was found to contain UR-144 and XLR-11.
Subject 7 A 22-year-old male was contacted after crossing into oncoming traffic and nearly colliding with the officer. The subject’s pupils were dilated and both eyelid and body tremors were observed. All clues of HGN were present, as well as LOC and rebound dilation. The WAT was satisfactorily executed, though the OLS showed two clues. The subject used the pad of his finger four times of six during the finger-to-nose (FTN) test. The subject admitted to using both Spice and marijuana; however, no THC or carboxy-THC was found. One hour and 5 min had passed from the time of contact to DRE completion. The blood obtained was found to contain UR-144 and XLR-11.
Subject 8 A 23-year-old male was stopped after being observed crossing over the center line and having his eyes closed while driving by the officer. During the investigation, the subject had bloodshot watery eyes and poor dexterity when handling paperwork. Slurred speech was also noted. Through the use of the SFSTs, the officer concluded impairment; however, no indicators were included in the submitted paperwork. The subject admitted to recently consuming marijuana and Spice, with Spice packaging found on the person. Processing time took 1 h, with the blood analysis ultimately yielding positive results for UR-144, XLR-11, AM-2201, JWH-018 and JWH-022.
Subject 9 A 30-year-old male was contacted after striking multiple vehicles. The officer noted bloodshot eyes and slow reactions. SFSTs were unremarkable other than the estimation of 30 s in 20 and severe leg and arm tremors. A DRE evaluation was conducted 90 min later. The DRE observed LOC and use of the pad of the finger during the FTN test, but no body or eyelid tremors. The subject had admitted to smoking Spice while driving and there was residual material found in his vehicle. Analysis revealed that UR-144 and XLR-11 from the blood sample obtained 1 h and 40 min after contact.
Subject 10 A 25-year-old male was contacted after reports of a suspected drunk driver. The stop occurred after the subject vehicle crossed over the fog line. Upon contact, the driver had difficulties pushing the button to lower the window. Investigation revealed bloodshot watery eyes, drooling and raspy, slurred and incoherent speech. The subject had poor balance and swayed and shook while standing. SFSTs could not be completed. The DRE noted the same physical symptoms, and an additional four clues on the HGN and three on the WAT. Eyelid tremors were also present. Spice was seen in plain view, and the subject admitted consumption. Blood was obtained 1 h and 35 min post contact. Blood analysis revealed UR-144.
Subject 11 A 27-year-old male was stopped after driving with inconsistent speed and being involved in a collision with the median barrier multiple times. The DRE noted slurred, incoherent speech, drool and dilated pupils. A pipe and packages of new and spent Spice were found on the subject. The subject was otherwise unresponsive, and no physical tests were conducted. The blood was obtained 1 h and 50 min after initial contact. Blood analysis revealed XLR-11.
Subject 12 A 27-year-old male was contacted after severe lane travel and striking a raised curb six times, going off the road and finally stopping after high centering the car on a raised curb. Multiple civilian witnesses and the officer noted slurred speech, disorientation, erratic and abnormal behavior. Physical tests demonstrated no HGN, bloodshot eyes and LOC with eyelid tremors. The WAT revealed four clues. Body tremors were present during the Romberg balance test, with an estimation of 30 s in 21 and 3 inch body sways. Pulse was noted to vary, slow, fast, and then slow again over the evaluation period. Paraphernalia found included a smoking pipe and a baggie of green matter, and the subject admitted to smoking 72 h prior. Blood was obtained 2 h and 45 min after law enforcement contact, and XLR-11 was detected in the sample.
Subject 13 A 30-year-old male was contacted after failing to stop at a stop sign. The investigator noted constricted pupils and bloodshot eyes. HGN testing noted four clues and vertical gaze nystagmus, XLR-11 and UR-144 in Driving Cases 565
four clues on the WAT and two clues on the OLS. A pipe and green material were found in the car, and the driver admitted to smoking 2 h prior to driving. XLR-11 was detected in the blood obtained 4 h and 45 min after the stop.
obtained 1 h and 45 min after contact. XLR-11 was detected in the blood obtained.
Discussion
Subject 17 A 22-year-old male was stopped by civilian and fire department personnel for driving on the curb. Police noted the driver to have bloodshot eyes and droopy eyelids with slow coordination. The DRE evaluation noted all clues present on the HGN test and two clues on the WAT. One clue was observed on the OLS, with body and leg tremors present. The subject used the pad of the finger on the FTN test five times. The subject admitted to smoking Spice 1 h prior to contact. Blood was obtained 90 min post contact and contained XLR-11.
The two compounds studied are structurally related, XLR-11 being the fluorinated analog of UR-144 ((1-pentyl-1H-indol3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone) (Fig. 1). Synthetic cannabinoid compounds are designed to mimic the agonistic effects attributed to THC in the human system. It has been reported that the toxicity of synthetic cannabinoid, however, may be greater than THC due to higher potency, unregulated and varied dose preparation and purity on the vegetable matter and stronger activity on the cannabinoid receptors (3, 8 –11). It has also been reported that some synthetic cannabinoids remain detectable for up to 102-day post drug use (12) and may have toxicity symptoms present for up to 14 h (13). Authors have also reported that there have been significant toxicological findings attributed to Spice exposure that have not been seen with typical recreational marijuana usage. These include acute nephrotoxicity (14 –16) adverse psychoactive responses—severe anxiety, psychosis and hallucination (2, 11, 17 – 19), withdrawal symptoms of tachycardia and myocardial infarction (2, 18, 20 – 22), respiratory depression (23), seizures (19, 22) and suicide ideation and death (13, 24 –26). With the driving cases studied, there were some behaviors consistent with cannabis usage. Typical DRE observations for cannabinoid impairment (27, 28) include the presence of LOC, normal to dilated pupils, increased heart rate and blood pressure, normal body temperature and no HGN or vertical gaze nystagmus. Consistent with these indicators, 8 of the 11 subjects in this study who were tested displayed LOC. The ratio of subjects displaying dilated pupils is lower with only 6 of the 18 showing this indicator. Pulse and blood pressure measures were consistent with markers for the cannabimimetic compounds, with all subjects observed to have these elevated, though within normal ranges, although Subject 12 had a pulse rate that varied greatly over the interview period. The body temperature of most of the subjects was considered normal (within +18 of 98.6 8F), though all appeared near the lower end of the range except Subject 9 who had a reported temperature of 99.4 F. Body and eyelid tremors are often seen in individuals dosed with THC, and this was also the case with drivers in this study (12 of 17 drivers who consented to testing). It is noted that many of the drivers exhibited slurred speech (11 of 18 overall), more so with those under the influence of only UR-144 (5 of 6) than only XLR-11 (4 of 8). Some behaviors were also typical of individuals under the influence of cannabinoids—drowsiness and impaired short-term memory (several individuals had to be reminded to follow the stimulus with just their eyes during the HGN evaluation).
Subject 18 A 23-year-old male was stopped by police officers after driving 20 miles in the opposing direction of traffic. The DRE noted bloodshot eyes, LOC, eyelid tremors, no HGN and two clues each on the WAT and OLS. There were three misses on the FTN, but no other findings. The subject admitted to smoking Spice twice in the last day, most recently 1 h prior to driving. Blood was
Figure 1. Chemical structure of UR-144 (left) and XLR-11.
Subject 14 A 17-year-old male was reported to police as driving with severe lane travel, nearly striking another vehicle and nearly driving into a ditch. Personal contact notes indicate dilated pupils and bloodshot watery eyes. Field tests yielded no significant findings. Inventory of the vehicle included Spice and a glass pipe. The subject admitted to smoking while driving. Blood obtains 1.5 h after the initial contact confirmed for XLR-11.
Subject 15 A 22-year-old male was found unconscious in his vehicle in a busy intersection after nearly striking other vehicles and pedestrians. The subject appeared groggy, and his speech was thick and slurred. The subject’s movements were slow and uncoordinated. There were four clues on the HGN, three clues on the WAT and three clues on the OLS. Spice packages were found in the vehicle and on his lap, although the subject denied using in the past day. A blood sample was taken 1.5 h after contact and was found positive for XLR-11.
Subject 16 A 19-year-old male was contacted for traffic violations. A DRE evaluation noted bloodshot watery eyes, droopy eyelids, LOC and all clues on the HGN. Body tremors were seen, but not from the eyelids. Rebound dilation was also noted. There were five misses on the FTN. The subject’s internal clock was slow with the estimation of 30 s as 44. The subject admitted to smoking Spice and marijuana 4 h earlier, with blood results indicating the presence of XLR-11, but no THC or marijuana metabolites. The blood was obtained 2 h and 45 min after initial contact.
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Inability to maintain vigilance to mundane tasks (23, 29, 30) may contribute to some of the driving behaviors reported, including loss of lane position control and improper speed. Of possibly greater interest, particularly for field investigators, are the behaviors that are not consistent with cannabis intoxication, most notably the presence of HGN. Individuals under the influence of THC typically do not exhibit HGN (27, 28). Of the 18 reports collected, half of the drivers exhibited this symptom, eight of which exhibited four or more clues. Of special interest, Subject 4 exhibited four indicators at first contact then showed none only half an hour later during the follow-up DRE examination. The FTN test, which is used to assess one’s proprioceptive abilities, is typically a helpful aid to determine the presence of cannabis. In this study, 7 of the 12 subjects demonstrated deficiencies, of which one had used the pad of the finger instead of the tip, but otherwise satisfactorily completed the task. There also appears to be little correlation with time of last (albeit self reported) dose and symptomology. Subject 4 showed extreme symptoms of an individual with very recent exposure to a strong cannabimimetic agent: slurred speech, bloodshot watery eyes, shaking, psychosis, loss of consciousness and poor driving ability and exhibiting signs of intoxication that are not typical for cannabis—specifically HGN. Contrasting this, Subject 14 who was also contacted for poor driving very shortly after exposure—both admitted to smoking while driving—demonstrated poor coordination, but no slurred speech and no indications by the SFSTs. Likewise, there seems to be little correlation regarding cases where there is greater elapsed time: Subject 4 reported 10 h since last dosing exhibited slurred speech, poor coordination, four indicators on the HGN test, LOC and body tremors; Subject 22 displayed similar symptoms 24 h post dosing. The uncontrolled and inconsistent application of active ingredient of unknown purity onto a varied delivery substrate of unknown origin (31) makes it is difficult, if not impossible to draw conclusions of dose response. Additionally, without concentrations for UR-144 or XLR-11, the difficulty to draw a dose – response relationship is compounded. With the 18 cases in this review, it can be noted that the effects of these Spice compounds can be powerful impairing agents that may have long-lasting effects, potentially up to 3 days. Symptoms are similar to those expected for those under the influence of cannabis but other indicators not normally seen, such as HGN, may confound the field diagnosis. Different individuals may also exhibit different signs and degrees of intensity of the various indicators. Most of the studied group exhibited bloodshot eyes, poor coordination with slurred speech and did poorly on the WAT. Other tests that usually are reliable indicators were less consistent. Proprioceptive tests and body and eyelid tremors are inconsistent, as were challenges to the internal clock. Personal communications (S. Beck, 10 March 2014) with one DRE bears this out: ‘From what our DRE program has reviewed in the past it was hard to pin down effects of Spice as the results are kind of all over the place’. The presence of paraphernalia may be a strong indicator that the individual is under the influence of a Spice product. As noted by previous authors, as compounds become scheduled, new ones will arise (32, 33). The first case presented to this laboratory was in June 2012. Over the following 16 months, until September 2013, there was a relatively steady flow of cases presented in which UR-144/XLR-11 was eventually detected. These two compounds were temporarily placed into Schedule
I status in May 2013, and presumably, suppliers used a new formulation to replace what stock had already been prepared. From September 2013 to February 2014, no new cases of UR-144/ XLR-11 have been presented to this laboratory.
Conclusion Based on the limited number of cases presented to the WSPTLD, Spice, particularly XLR-11 and UR-144, has the potential to strongly and negatively impact a driver’s ability to operate a motor vehicle safely. These reports indicate significant lane travel, inappropriate speed, collision and severe inattention. Although XLR-11 and UR-144 are classified as cannabimimetic compounds, they do not consistently manifest the classical cannabis indicators, as dictated by the DRE classification system, particularly the presence of HGN. Additional information through controlled clinical testing with known and measured dosing may allow the determination of dose response, as well as the duration of effects.
Conflict of Interest statement None declared.
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