Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance ...

1
Endres GW, 5 Kennedy PD, 5 Fernández D, 1,3 Prud’homme J, 2 Nelson LS, 1,3 Hoffman RS, 1,3 Su MK, 1-3 Neubauer L, 5 Paon AL, 4 Moran JH 4 1 Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York, USA 2 New York City Department of Health and Mental Hygiene, New York, New York, USA 3 New York City Poison Control Center, New York, New York, USA 4 PinPoint Tesng, LLC, Lile Rock, Arkansas, USA 5 Cayman Chemical, Ann Arbor, Michigan, USA The “K2” Epidemic: Preliminary Results of a Health Department’s Synthec Cannabinoid Receptor Agonist (SCRA) Surveillance Project Table 1. Clinical signs with confirmed MAB-CHMINACA or AB-CHMINACA SCRA CNS Depression Delirium Agitaon Seizure MAB-CHMINACA AB-CHMINACA Represents a paent with the reported sign/symptom indicated Figure 3. SCRAs detected in “K2” products (16616) (15434) (14038) (11565) (16966) O N O N F FUB-PB-22 (14949) (15488) NM2201 (15334) Figure 1. “K2” Packets N N O NH O NH 2 AB-CHMINACA metabolite M1A (16387) OH N N O NH O OH AB-CHMINACA metabolite M2 (16389) N N O NH O OH AB-CHMINACA metabolite M3A (16391) OH AB-CHMINACA metabolite M4 (16393) O N OH N N N O NH O NH 2 OH MAB-CHMINACA metabolite M1 (17812) N N O NH O OH MAB-CHMINACA metabolite M2 (17813) HO N N O NH O OH MAB-CHMINACA metabolite M3 (17814) OH N N O NH O MAB-CHMINACA metabolite M10 (CRM) (18187) O N N O NH O NH 2 MAB-CHMINACA metabolite M11 (CRM) (18188) OH HO XLR11 Degradant (14055) N O F N O UR-144 Degradant (11928) N O OH O UR-144 Degradant N-pentanoic acid metabolite (9001453) N O OH UR-144 N-(5-hydroxypentyl) metabolite (11775) N O OH O UR-144 N-pentanoic acid metabolite (11773) N N O NH O NH 2 AB-PINACA N-(5-hydroxypentyl) metabolite (15050) OH N N O NH O NH 2 AB-PINACA N-(4-hydroxypentyl) metabolite (15049) OH N O OH F 5-fluoro PB-22 3-carboxyindole metabolite (common to NM2201) (14381) Figure 2. Parent SCRAs, metabolites, and degradants detected in blood and urine specimen Table 2: Results table of selected examples NY CASE NO. CLINICAL SAMPLE NO. LINKED TO FORENSIC SAMPLE NO. DESCRIPTION FORENSIC RESULT MATRIX SYNTHETIC CANNABINOID LC-MS/MS CONFIRMATION RESULTS (NG/ML) 010 NYC 2015-C025 F021 Kick Plant Feeder AB-CHMINACA blood AB-CHMINACA metabolite M1A (2.1), AB-CHMINACA metabolite M2 (8.1) 2015-C026 urine AB-CHMINACA metabolite M1A (20.7), AB-CHMINACA metabolite M3A (22.4) 011 NYC 2015-C027 F022 Sofa King Amazing AB-CHMINACA blood MAB-CHMINACA (2.1), AB-CHMINACA metabolite M1A (2.0), AB-CHMINACA metabolite M2 (10.1), MAB-CHMINACA metabolite M1 (9.1), MAB-CHMINACA metabolite M11 (4.7), UR-144 N-pentanoic acid metabolite (2.8) 2015-C028 urine AB-CHMINACA metabolite M1A (8.3), MAB-CHMINACA metabolite M1 (41.3), MAB-CHMINACA metabolite M3 (37.6), MAB-CHMINACA metabolite M11 (107.4) 012 NYC 2015-C029 F023 DAFUQ AB-CHMINACA blood AB-CHMINACA metabolite M1A (3.9), AB-CHMINACA metabolite M2 (27.0) 2015-C032 urine AB-CHMINACA metabolite M1A (16.5) 014 NYC 2015-C035 F025 & F026 Green Giant, Xtreme Aroma Therapy FUB-PB-22 (F025) & NM2201 (F026) blood FUB-PB-22, AB-CHMINACA metabolite M1A (4.3), AB-CHMINACA metabolite M2 (29.8), AB-CHMINACA M3A metabolite (4.5), MAB-CHMINACA metabolite M1 (1.4), MAB-CHMINACA metabolite M11 (0.57) 2015-C036 urine AB-CHMINACA metabolite M1A (65.5), AB-CHMINACA metabolite M3A (74.9), 5-fluoro PB-22 carboxyindole metabolite (15.9) 015 NYC 2015-C037 F027 Train Wrecked MDMB-FUBINACA blood none detected 2015-C039 urine none detected 016 NYC 2015-C040 F028 Blue Mixx Cigarillos Negave blood AB-PINACA (0.06), PB-22 (0.01), XLR11 Degradant (0.31), AB-CHMINACA metabolite M1A (5.4), AB-CHMINACA metabolite M2 (71.7), AB-CHMINACA metabolite M3A (4.9), UR-144-N-(5-hydroxypentyl) metabolite (0.6), UR-144 N-pentanoic acid metabolite (4.2) 2015-C042 urine AB-CHMINACA metabolite M1A (24.2), AB-CHMINACA metabolite M4 017 NYC 2015-C043 F029 & F030 Ice Dragon MAB-CHMINACA (F029) blood MAB-CHMINACA (11.4), XLR11 Degradant (0.11), AB-CHMINACA metabolite M1A (2.3), AB-CHMINACA metabolite M2 (11.6), MAB-CHMINACA metabolite M11 (8.6) 2015-C044 urine AB-CHMINACA metabolite M1A (15.7), AB-CHMINACA metabolite M3A (11.9), MAB-CHMINACA metabolite M1 (40.2), MAB-CHMINACA metabolite M3 (37.9) BACKGROUND: • SCRAs are popular novel drugs of abuse • Despite their banning, use has skyrocketed in the US • In 2015, there was a rise in the number of emergency visits associated with suspected SCRA use 1 • The clinical presentations of these patients vary HYPOTHESIS: • We hypothesize that the clinical effects of a specific SCRA are predictable based on the SCRA METHODS: • ED patients reporting “K2” use with SCRA toxicity were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015 • Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included • Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion • Specimens were stored and shipped at -20°C to an independent laboratory for analysis • The products were analyzed by GC-MS • The biological samples were analyzed by LC-MS-ToF and LC-MS/MS • This ongoing public health surveillance investigation was approved by the NYC Department of Health and Mental Hygiene RESULTS: • In this preliminary report, six products and seven biological results from 10 patients were available for analysis • SCRAs found in products (Figure 3) included: NM2201 (N=1), MAB-CHMINACA (N=2), XLR11 (N=2), AMB (N=1), AB-CHMINACA (N=1), and MDMB-FUBINACA (N=1), with some products having more than one SCRA identified RESULTS CONTINUED: • SCRAs found in biological specimens included: MAB-CHMINACA, MAB-CHMINACA metabolites, and AMB-CHMINACA metabolites • Not all SCRAs found in products could be identified in corresponding patient biological specimens • Some SCRAs found in biological specimens were not found in corresponding products • In patients with confirmed MAB-CHMINACA alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1) • CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-CHMINACA alone (Table 1) DISCUSSION: • Preliminary data from this health department investigation identified multiple SCRAs in products and biological specimens • Clinical effects varied from sedation to agitation in patients with the same SCRAs • This variability may result from dose-dependent effects, individual host factors, or co-exposures LIMITATIONS: • Not all suspected SCRAs or their metabolites can easily be identified in biological specimens • It is unclear if the products carried by patients were the exact products used • Some of the clinical effects may be due to coingestions that were unreported by the patients or bystanders and not found on clinical evaluation CONCLUSIONS: • SCRAs identified in packaged materials were primarily analogs of the most recent amino acid-based (‘INACA’) subclass • Metabolites of forensically identified SCRAs were detected and confirmed in 17 of the 32 samples • The toxicity associated with a specific SCRA is unpredictable based on this preliminary data

Transcript of Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance ...

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Endres GW,5 Kennedy PD,5 Fernández D,1,3 Prud’homme J,2 Nelson LS,1,3 Hoffman RS,1,3 Su MK,1-3 Neubauer L,5 Patton AL,4 Moran JH41Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York, USA2New York City Department of Health and Mental Hygiene, New York, New York, USA3New York City Poison Control Center, New York, New York, USA4PinPoint Testing, LLC, Little Rock, Arkansas, USA5Cayman Chemical, Ann Arbor, Michigan, USA

The “K2” Epidemic: Preliminary Results of a Health Department’sSynthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Table 1. Clinical signs with confirmed MAB-CHMINACA or AB-CHMINACA

SCRA CNS Depression Delirium Agitation Seizure

MAB-CHMINACA

AB-CHMINACA

Represents a patient with the reported sign/symptom indicated

Figure 3. SCRAs detected in “K2” products

(16616)

(15434)

(14038)

(11565)

(16966)

O N

O

N

F

FUB-PB-22(14949) (15488)

NM2201(15334)

The “K2” Epidemic: Preliminary Results of a Health Department’s Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Fernández D,1,3 Prud’homme J,2 Nelson LS, 1,3 Hoffman RS,1,3 Moran JH,4 Endres GW,5 Patton AL,4 Su MK1-3

1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York USA 2New York City Department of Health and Mental Hygiene , New York, NY, USA

3New York City Poison Control Center, New York, NY, USA 4PinPoint Testing, LLC, Little Rock, Arkansas, USA

5Cayman Chemical, Ann Arbor, Michigan, USA

Background: •  SCRAs are popular novel drugs of abuse. •  Despite their banning, use has skyrocketed in the US. •  In 2015, there was a rise in the number of emergency

visits associated with suspected SCRA use.1 •  The clinical presentations of these patients vary. Hypothesis: •  We hypothesize that the clinical effects of a specific

SCRA are predictable based on the SCRA. Methods: •  ED patients reporting “K2” use with SCRA toxicity

were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015.

•  Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included.

•  Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion.

•  Specimens were stored and shipped at -20°C to an independent laboratory for analysis. •  The products were analyzed by GC-MS. •  The biological samples were analyzed by LC-MS-ToF

and LC-MS/MS. •  This ongoing public health surveillance investigation

was approved by the NYC Department of Health and Mental Hygiene.

Results: •  In this preliminary report, 6 product and 7 biological

results from 10 patients were available for analysis. •  SCRAs found in products (Figure. 1) included:

NM2201 (N=1), MAB-Chminaca (N=2), XLR11 (N=2), AMB (N=1), AB-Chminaca (N=1), and MDMB-Fubinaca (N=1), with some products having more than one SCRA identified.

Figure 1. Suspected SCRA-containing Products

Table 1. Clinical Signs with Confirmed MAB-Chiminaca or AB-Chiminaca.

Results (continued): •  SCRAs found in biological specimens included: MAB-

Chminaca, MAB-Chminaca metabolites, and AB-Chminaca metabolites.

•  Not all SCRAs found in products could be identified in corresponding patient biological specimens.

•  Some SCRAs found in biological specimens were not found in corresponding products.

•  In patients with confirmed MAB-Chminaca alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1).

•  CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-Chminaca alone (Table 1).

Discussion: •  Preliminary data from this health department

investigation identified multiple SCRAs in products and biological specimens.

•  Clinical effects varied from sedation to agitation in patients with the same SCRAs.

•  This variability may result from dose-dependent effects, individual host factors, or co-exposures.

Limitations: •  Not all suspected SCRAs or their metabolites can

easily be identified in biological specimens. •  It is unclear if the products carried by patients were

the exact products used. •  Some of the clinical effects may be due to co-

ingestions that were unreported by the patients or bystanders and not found on clinical evaluation.

Conclusion: •  The toxicity associated with a specific SCRA is

unpredictable based on this preliminary data.

SCRA CNSDepression

Delirium Agita5on Seizure

MAB-Chminaca

✓✓✓ ✓

AB-Chminaca

✓ ✓ ✓

✓ Represents a patient with the reported sign/symptom indicated.

References: 1. Kunins H. 2015 Advisory #36: Increase in Synthetic Cannabinoid Related Adverse Events and Emergency Department Visits, New York City. Sept. 17, 2015.

The “K2” Epidemic: Preliminary Results of a Health Department’s Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Fernández D,1,3 Prud’homme J,2 Nelson LS, 1,3 Hoffman RS,1,3 Moran JH,4 Endres GW,5 Patton AL,4 Su MK1-3

1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York USA 2New York City Department of Health and Mental Hygiene , New York, NY, USA

3New York City Poison Control Center, New York, NY, USA 4PinPoint Testing, LLC, Little Rock, Arkansas, USA

5Cayman Chemical, Ann Arbor, Michigan, USA

Background: •  SCRAs are popular novel drugs of abuse. •  Despite their banning, use has skyrocketed in the US. •  In 2015, there was a rise in the number of emergency

visits associated with suspected SCRA use.1 •  The clinical presentations of these patients vary. Hypothesis: •  We hypothesize that the clinical effects of a specific

SCRA are predictable based on the SCRA. Methods: •  ED patients reporting “K2” use with SCRA toxicity

were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015.

•  Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included.

•  Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion.

•  Specimens were stored and shipped at -20°C to an independent laboratory for analysis. •  The products were analyzed by GC-MS. •  The biological samples were analyzed by LC-MS-ToF

and LC-MS/MS. •  This ongoing public health surveillance investigation

was approved by the NYC Department of Health and Mental Hygiene.

Results: •  In this preliminary report, 6 product and 7 biological

results from 10 patients were available for analysis. •  SCRAs found in products (Figure. 1) included:

NM2201 (N=1), MAB-Chminaca (N=2), XLR11 (N=2), AMB (N=1), AB-Chminaca (N=1), and MDMB-Fubinaca (N=1), with some products having more than one SCRA identified.

Figure 1. Suspected SCRA-containing Products

Table 1. Clinical Signs with Confirmed MAB-Chiminaca or AB-Chiminaca.

Results (continued): •  SCRAs found in biological specimens included: MAB-

Chminaca, MAB-Chminaca metabolites, and AB-Chminaca metabolites.

•  Not all SCRAs found in products could be identified in corresponding patient biological specimens.

•  Some SCRAs found in biological specimens were not found in corresponding products.

•  In patients with confirmed MAB-Chminaca alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1).

•  CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-Chminaca alone (Table 1).

Discussion: •  Preliminary data from this health department

investigation identified multiple SCRAs in products and biological specimens.

•  Clinical effects varied from sedation to agitation in patients with the same SCRAs.

•  This variability may result from dose-dependent effects, individual host factors, or co-exposures.

Limitations: •  Not all suspected SCRAs or their metabolites can

easily be identified in biological specimens. •  It is unclear if the products carried by patients were

the exact products used. •  Some of the clinical effects may be due to co-

ingestions that were unreported by the patients or bystanders and not found on clinical evaluation.

Conclusion: •  The toxicity associated with a specific SCRA is

unpredictable based on this preliminary data.

SCRA CNSDepression

Delirium Agita5on Seizure

MAB-Chminaca

✓✓✓ ✓

AB-Chminaca

✓ ✓ ✓

✓ Represents a patient with the reported sign/symptom indicated.

References: 1. Kunins H. 2015 Advisory #36: Increase in Synthetic Cannabinoid Related Adverse Events and Emergency Department Visits, New York City. Sept. 17, 2015.

The “K2” Epidemic: Preliminary Results of a Health Department’s Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Fernández D,1,3 Prud’homme J,2 Nelson LS, 1,3 Hoffman RS,1,3 Moran JH,4 Endres GW,5 Patton AL,4 Su MK1-3

1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York USA 2New York City Department of Health and Mental Hygiene , New York, NY, USA

3New York City Poison Control Center, New York, NY, USA 4PinPoint Testing, LLC, Little Rock, Arkansas, USA

5Cayman Chemical, Ann Arbor, Michigan, USA

Background: •  SCRAs are popular novel drugs of abuse. •  Despite their banning, use has skyrocketed in the US. •  In 2015, there was a rise in the number of emergency

visits associated with suspected SCRA use.1 •  The clinical presentations of these patients vary. Hypothesis: •  We hypothesize that the clinical effects of a specific

SCRA are predictable based on the SCRA. Methods: •  ED patients reporting “K2” use with SCRA toxicity

were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015.

•  Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included.

•  Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion.

•  Specimens were stored and shipped at -20°C to an independent laboratory for analysis. •  The products were analyzed by GC-MS. •  The biological samples were analyzed by LC-MS-ToF

and LC-MS/MS. •  This ongoing public health surveillance investigation

was approved by the NYC Department of Health and Mental Hygiene.

Results: •  In this preliminary report, 6 product and 7 biological

results from 10 patients were available for analysis. •  SCRAs found in products (Figure. 1) included:

NM2201 (N=1), MAB-Chminaca (N=2), XLR11 (N=2), AMB (N=1), AB-Chminaca (N=1), and MDMB-Fubinaca (N=1), with some products having more than one SCRA identified.

Figure 1. Suspected SCRA-containing Products

Table 1. Clinical Signs with Confirmed MAB-Chiminaca or AB-Chiminaca.

Results (continued): •  SCRAs found in biological specimens included: MAB-

Chminaca, MAB-Chminaca metabolites, and AB-Chminaca metabolites.

•  Not all SCRAs found in products could be identified in corresponding patient biological specimens.

•  Some SCRAs found in biological specimens were not found in corresponding products.

•  In patients with confirmed MAB-Chminaca alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1).

•  CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-Chminaca alone (Table 1).

Discussion: •  Preliminary data from this health department

investigation identified multiple SCRAs in products and biological specimens.

•  Clinical effects varied from sedation to agitation in patients with the same SCRAs.

•  This variability may result from dose-dependent effects, individual host factors, or co-exposures.

Limitations: •  Not all suspected SCRAs or their metabolites can

easily be identified in biological specimens. •  It is unclear if the products carried by patients were

the exact products used. •  Some of the clinical effects may be due to co-

ingestions that were unreported by the patients or bystanders and not found on clinical evaluation.

Conclusion: •  The toxicity associated with a specific SCRA is

unpredictable based on this preliminary data.

SCRA CNSDepression

Delirium Agita5on Seizure

MAB-Chminaca

✓✓✓ ✓

AB-Chminaca

✓ ✓ ✓

✓ Represents a patient with the reported sign/symptom indicated.

References: 1. Kunins H. 2015 Advisory #36: Increase in Synthetic Cannabinoid Related Adverse Events and Emergency Department Visits, New York City. Sept. 17, 2015.

The “K2” Epidemic: Preliminary Results of a Health Department’s Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Fernández D,1,3 Prud’homme J,2 Nelson LS, 1,3 Hoffman RS,1,3 Moran JH,4 Endres GW,5 Patton AL,4 Su MK1-3

1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York USA 2New York City Department of Health and Mental Hygiene , New York, NY, USA

3New York City Poison Control Center, New York, NY, USA 4PinPoint Testing, LLC, Little Rock, Arkansas, USA

5Cayman Chemical, Ann Arbor, Michigan, USA

Background: •  SCRAs are popular novel drugs of abuse. •  Despite their banning, use has skyrocketed in the US. •  In 2015, there was a rise in the number of emergency

visits associated with suspected SCRA use.1 •  The clinical presentations of these patients vary. Hypothesis: •  We hypothesize that the clinical effects of a specific

SCRA are predictable based on the SCRA. Methods: •  ED patients reporting “K2” use with SCRA toxicity

were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015.

•  Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included.

•  Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion.

•  Specimens were stored and shipped at -20°C to an independent laboratory for analysis. •  The products were analyzed by GC-MS. •  The biological samples were analyzed by LC-MS-ToF

and LC-MS/MS. •  This ongoing public health surveillance investigation

was approved by the NYC Department of Health and Mental Hygiene.

Results: •  In this preliminary report, 6 product and 7 biological

results from 10 patients were available for analysis. •  SCRAs found in products (Figure. 1) included:

NM2201 (N=1), MAB-Chminaca (N=2), XLR11 (N=2), AMB (N=1), AB-Chminaca (N=1), and MDMB-Fubinaca (N=1), with some products having more than one SCRA identified.

Figure 1. Suspected SCRA-containing Products

Table 1. Clinical Signs with Confirmed MAB-Chiminaca or AB-Chiminaca.

Results (continued): •  SCRAs found in biological specimens included: MAB-

Chminaca, MAB-Chminaca metabolites, and AB-Chminaca metabolites.

•  Not all SCRAs found in products could be identified in corresponding patient biological specimens.

•  Some SCRAs found in biological specimens were not found in corresponding products.

•  In patients with confirmed MAB-Chminaca alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1).

•  CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-Chminaca alone (Table 1).

Discussion: •  Preliminary data from this health department

investigation identified multiple SCRAs in products and biological specimens.

•  Clinical effects varied from sedation to agitation in patients with the same SCRAs.

•  This variability may result from dose-dependent effects, individual host factors, or co-exposures.

Limitations: •  Not all suspected SCRAs or their metabolites can

easily be identified in biological specimens. •  It is unclear if the products carried by patients were

the exact products used. •  Some of the clinical effects may be due to co-

ingestions that were unreported by the patients or bystanders and not found on clinical evaluation.

Conclusion: •  The toxicity associated with a specific SCRA is

unpredictable based on this preliminary data.

SCRA CNSDepression

Delirium Agita5on Seizure

MAB-Chminaca

✓✓✓ ✓

AB-Chminaca

✓ ✓ ✓

✓ Represents a patient with the reported sign/symptom indicated.

References: 1. Kunins H. 2015 Advisory #36: Increase in Synthetic Cannabinoid Related Adverse Events and Emergency Department Visits, New York City. Sept. 17, 2015.

The “K2” Epidemic: Preliminary Results of a Health Department’s Synthetic Cannabinoid Receptor Agonist (SCRA) Surveillance Project

Fernández D,1,3 Prud’homme J,2 Nelson LS, 1,3 Hoffman RS,1,3 Moran JH,4 Endres GW,5 Patton AL,4 Su MK1-3

1Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, New York USA 2New York City Department of Health and Mental Hygiene , New York, NY, USA

3New York City Poison Control Center, New York, NY, USA 4PinPoint Testing, LLC, Little Rock, Arkansas, USA

5Cayman Chemical, Ann Arbor, Michigan, USA

Background: •  SCRAs are popular novel drugs of abuse. •  Despite their banning, use has skyrocketed in the US. •  In 2015, there was a rise in the number of emergency

visits associated with suspected SCRA use.1 •  The clinical presentations of these patients vary. Hypothesis: •  We hypothesize that the clinical effects of a specific

SCRA are predictable based on the SCRA. Methods: •  ED patients reporting “K2” use with SCRA toxicity

were identified via New York City Poison Control Center (NYC PCC) calls from May to November 2015.

•  Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features reported were included.

•  Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion.

•  Specimens were stored and shipped at -20°C to an independent laboratory for analysis. •  The products were analyzed by GC-MS. •  The biological samples were analyzed by LC-MS-ToF

and LC-MS/MS. •  This ongoing public health surveillance investigation

was approved by the NYC Department of Health and Mental Hygiene.

Results: •  In this preliminary report, 6 product and 7 biological

results from 10 patients were available for analysis. •  SCRAs found in products (Figure. 1) included:

NM2201 (N=1), MAB-Chminaca (N=2), XLR11 (N=2), AMB (N=1), AB-Chminaca (N=1), and MDMB-Fubinaca (N=1), with some products having more than one SCRA identified.

Figure 1. Suspected SCRA-containing Products

Table 1. Clinical Signs with Confirmed MAB-Chiminaca or AB-Chiminaca.

Results (continued): •  SCRAs found in biological specimens included: MAB-

Chminaca, MAB-Chminaca metabolites, and AB-Chminaca metabolites.

•  Not all SCRAs found in products could be identified in corresponding patient biological specimens.

•  Some SCRAs found in biological specimens were not found in corresponding products.

•  In patients with confirmed MAB-Chminaca alone in biological specimens (N=4), one had agitation and three presented with central nervous system (CNS) depression (Table 1).

•  CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of AB-Chminaca alone (Table 1).

Discussion: •  Preliminary data from this health department

investigation identified multiple SCRAs in products and biological specimens.

•  Clinical effects varied from sedation to agitation in patients with the same SCRAs.

•  This variability may result from dose-dependent effects, individual host factors, or co-exposures.

Limitations: •  Not all suspected SCRAs or their metabolites can

easily be identified in biological specimens. •  It is unclear if the products carried by patients were

the exact products used. •  Some of the clinical effects may be due to co-

ingestions that were unreported by the patients or bystanders and not found on clinical evaluation.

Conclusion: •  The toxicity associated with a specific SCRA is

unpredictable based on this preliminary data.

SCRA CNSDepression

Delirium Agita5on Seizure

MAB-Chminaca

✓✓✓ ✓

AB-Chminaca

✓ ✓ ✓

✓ Represents a patient with the reported sign/symptom indicated.

References: 1. Kunins H. 2015 Advisory #36: Increase in Synthetic Cannabinoid Related Adverse Events and Emergency Department Visits, New York City. Sept. 17, 2015.

Figure 1. “K2” Packets

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

NN

ONH

O

NH2

NN

ONH

O

NH2

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

OH

MAB-CHMINACA metabolite M1(17812)

NN

ONH

O

OH

MAB-CHMINACA metabolite M2(17813)

NN

ONH

O

OH

MAB-CHMINACA metabolite M3(17814)

OH

NN

ONH

O

MAB-CHMINACA metabolite M10 (CRM)(18187)

NN

ONH

O

NH2

MAB-CHMINACA metabolite M11 (CRM)(18188)

OH

HOO

AB-CHMINACA metabolite M1A(16387)

OHN

N

ONH

O

OH

AB-CHMINACA metabolite M2(16389)

NN

ONH

O

OH

AB-CHMINACA metabolite M3A(16391)

OH

AB-CHMINACA metabolite M4(16393)

O N

OH

N

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

N

OOH

F

NN

ONH

O

NH2

AB-PINACA N-(5-hydroxypentyl)metabolite(15050)

Figure 2. Parent SCRA and metabolite(s) and degradants detected in blood and urine specimen

5-fluoro PB-22 3-carboxyindolemetabolite (common to NM2201)(14381)

N

O

OH

N

O

N

O

OH

O

N

O

OHO

XLR11 Degradant(14055)

UR-144 Degradant(11928)

UR-144 Degradant N-pentanoic acid metabolite(9001453)

UR-144 N-pentanoic acid metabolite(11773)

UR-144 N-(5-hydroxypentyl) metabolite(11775)

OH

NN

ONH

O

NH2

AB-PINACA N-(4-hydroxypentyl)metabolite(15049)

OH

NO F

Figure 2. Parent SCRAs, metabolites, and degradants detected in blood and urine specimen

Table 2: Results table of selected examples

NY CASE NO. CLINICALSAMPLE NO.

LINKED TO FORENSIC SAMPLE NO. DESCRIPTION FORENSIC RESULT MATRIX SYNTHETIC CANNABINOID LC-MS/MS

CONFIRMATION RESULTS (NG/ML)

010 NYC 2015-C025 F021 Kick Plant Feeder AB-CHMINACA blood AB-CHMINACA metabolite M1A (2.1), AB-CHMINACA metabolite M2 (8.1)

2015-C026 urine AB-CHMINACA metabolite M1A (20.7), AB-CHMINACA metabolite M3A (22.4)

011 NYC 2015-C027 F022 Sofa King Amazing AB-CHMINACA blood MAB-CHMINACA (2.1), AB-CHMINACA metabolite M1A (2.0), AB-CHMINACA metabolite M2 (10.1), MAB-CHMINACA metabolite M1 (9.1), MAB-CHMINACA metabolite M11 (4.7), UR-144 N-pentanoic acid metabolite (2.8)

2015-C028 urine AB-CHMINACA metabolite M1A (8.3), MAB-CHMINACA metabolite M1 (41.3), MAB-CHMINACA metabolite M3 (37.6), MAB-CHMINACA metabolite M11 (107.4)

012 NYC 2015-C029 F023 DAFUQ AB-CHMINACA blood AB-CHMINACA metabolite M1A (3.9), AB-CHMINACA metabolite M2 (27.0)

2015-C032 urine AB-CHMINACA metabolite M1A (16.5)

014 NYC 2015-C035 F025 & F026 Green Giant, Xtreme Aroma Therapy

FUB-PB-22 (F025) & NM2201 (F026) blood FUB-PB-22, AB-CHMINACA metabolite M1A (4.3), AB-CHMINACA metabolite M2 (29.8), AB-CHMINACA M3A metabolite (4.5),

MAB-CHMINACA metabolite M1 (1.4), MAB-CHMINACA metabolite M11 (0.57)

2015-C036 urine AB-CHMINACA metabolite M1A (65.5), AB-CHMINACA metabolite M3A (74.9), 5-fluoro PB-22 carboxyindole metabolite (15.9)

015 NYC 2015-C037 F027 Train Wrecked MDMB-FUBINACA blood none detected

2015-C039 urine none detected

016 NYC 2015-C040 F028 Blue Mixx Cigarillos Negative blood AB-PINACA (0.06), PB-22 (0.01), XLR11 Degradant (0.31), AB-CHMINACA metabolite M1A (5.4), AB-CHMINACA metabolite M2 (71.7), AB-CHMINACA metabolite M3A (4.9), UR-144-N-(5-hydroxypentyl) metabolite (0.6), UR-144 N-pentanoic acid metabolite (4.2)

2015-C042 urine AB-CHMINACA metabolite M1A (24.2), AB-CHMINACA metabolite M4

017 NYC 2015-C043 F029 & F030 Ice Dragon MAB-CHMINACA (F029) blood MAB-CHMINACA (11.4), XLR11 Degradant (0.11), AB-CHMINACA metabolite M1A (2.3), AB-CHMINACA metabolite M2 (11.6),

MAB-CHMINACA metabolite M11 (8.6)

2015-C044 urine AB-CHMINACA metabolite M1A (15.7), AB-CHMINACA metabolite M3A (11.9), MAB-CHMINACA metabolite M1 (40.2), MAB-CHMINACA metabolite M3 (37.9)

BACKGROUND:• SCRAs are popular novel drugs of abuse• Despite their banning, use has skyrocketed in the US• In 2015, there was a rise in the number of emergency visits associated with suspected SCRA use1

• The clinical presentations of these patients vary

HYPOTHESIS:• We hypothesize that the clinical effects of a specific SCRA are predictable based on the SCRA

METHODS:• ED patients reporting “K2” use with SCRA toxicity were identified via New York City Poison Control Center (NYC PCC) calls

from May to November 2015• Subjects in possession of suspected SCRA product(s) who had blood and urine specimens obtained and clinical features

reported were included• Blood, urine, and product samples were linked along with clinical effects in a de-identified fashion• Specimens were stored and shipped at -20°C to an independent laboratory for analysis• The products were analyzed by GC-MS• The biological samples were analyzed by LC-MS-ToF and LC-MS/MS• This ongoing public health surveillance investigation was approved by the NYC Department of Health and

Mental Hygiene

RESULTS:• In this preliminary report, six products and seven biological results from 10 patients were available for analysis• SCRAs found in products (Figure 3) included: NM2201 (N=1), MAB-CHMINACA (N=2), XLR11 (N=2), AMB (N=1),

AB-CHMINACA (N=1), and MDMB-FUBINACA (N=1), with some products having more than one SCRA identified

RESULTS CONTINUED: • SCRAs found in biological specimens included: MAB-CHMINACA, MAB-CHMINACA metabolites, and

AMB-CHMINACA metabolites• Not all SCRAs found in products could be identified in corresponding patient biological specimens• Some SCRAs found in biological specimens were not found in corresponding products• In patients with confirmed MAB-CHMINACA alone in biological specimens (N=4), one had agitation and three presented with

central nervous system (CNS) depression (Table 1)• CNS depression (N=1), delirium (N=1), and seizure (N=1) were reported in patients with biological confirmation of

AB-CHMINACA alone (Table 1)

DISCUSSION:• Preliminary data from this health department investigation identified multiple SCRAs in products and biological specimens• Clinical effects varied from sedation to agitation in patients with the same SCRAs• This variability may result from dose-dependent effects, individual host factors, or co-exposures

LIMITATIONS:• Not all suspected SCRAs or their metabolites can easily be identified in biological specimens• It is unclear if the products carried by patients were the exact products used• Some of the clinical effects may be due to coingestions that were unreported by the patients or bystanders and not found on

clinical evaluation

CONCLUSIONS:• SCRAs identified in packaged materials were primarily analogs of the most recent amino acid-based (‘INACA’) subclass• Metabolites of forensically identified SCRAs were detected and confirmed in 17 of the 32 samples• The toxicity associated with a specific SCRA is unpredictable based on this preliminary data