Table I.
SC Receptor Agonists’ Case Histories with Clinical Symptoms, Autopsy Findings and Primary and Additional Drug Concentrations
| Drug | History | Clinical symptoms/Autopsy findings | Drug results (ng/mL, unless specified) | Reference |
|---|---|---|---|---|
| 5F-Cumyl-PEGACLONE | 37 y/o M found dead in apartment. Hx of mental health disorders and excessive cannabis use. | Brain and lung edema; bilateral cortical kidney bleeding, massive subacute stasis in liver and subcapsular hemorrhages and acute tubular kidney necrosis, TSS = 3 for 5F-Cumyl-PEGACLONE | Blood (central): 0.07 Blood (femoral): 0.45 9-OH-risperidone 18, trimipramine 250, +cinnarizine, +diphenhydramine Brain: 0.03 ng/g Urine: +5F-Cumyl-PEGACLONE metabolites (unspecified) |
(30) |
| 48 y/o F found dead at home. Hx of narcotic drugs and ‘spice’ use | Brain and pulmonary edema, acute blood stasis in liver and kidneys. COD acute heroin toxicity with contributory role of 5F-Cumyl-PEGACLONE (TSS = 1) | Blood (central): 0.21 Blood (femoral): 0.23 Morphine 297, 6-AM 20, codeine 21, oxazepam 450, alprazolam 10 and paroxetine <10 Urine: +5F-Cumyl-PEGACLONE metabolites (unspecified), 6-AM 12.3, dihydromorphine 29.7, noscapine 16, papaverine 27, +buprenorphine, +norbuprenorphine, +4F-MDMB-BINACA metabolites (unspecified), +AB-FUBINACA/FUB-AMB metabolites (unspecified) |
(30) | |
| 36 y/o M found near jail cell | Macroscopic organ examination unremarkable except for enlarged liver and spleen, TSS = 2 for 5F-Cumyl-PEGACLONE due to possible contributory role of pregabalin and temazepam | Blood (central): 0.22 Blood (femoral): 0.12 Pregabalin 6,000, temazepam 230, oxazepam 12, alprazolam 16, lorazepam <5 Urine: +5F-Cumyl-PEGACLONE metabolites (unspecified) |
(30) | |
| 33 y/o M found dead in apartment. Hx of ‘spice’ use | Asphyxiation signs: conjunctival petechiae and over-inflation/edema of lungs. Brain edema, massive blood stasis in heart and circulatory system, enlarged liver, TSS = 3 for 5F-Cumyl-PEGACLONE. COD: asphyxia due to SC induced vomiting and aspiration of partially digested gastric content | Blood (central): 0.35 Blood (femoral): 0.09 BZE 107, EME 11, +cocaine, +THC-COOH Urine: +5F-Cumyl-PEGACLONE metabolites (unspecified) |
(30) | |
| 5F-MDMB-PICA and 5Cl-ADAMANTYL-PINACA (5Cl-APINACA) | 67 y/o F went to ED 1.5–2 h after drinking yellow fluid from ‘winter melon tea’ bottle with upward eye rolling and brief limb jerking ∼45 min after ingestion. Drowsy with GCS = 6 by EMS | HR 111 bpm, RR 21/min, BP 125/52, Temp 36.3°C, SpO2 95% on 4 L/min nasal cannula. GCS = 15 ∼4.5 h after ingestion. Episodic hypotension during 87 h hospital stay | Urine: +5F-MDMB-PICA 3,3-dimethylbutanoic acid Seized drug: +5F-MDMB-PICA, +5CL-ADAMANTYL-PINACA |
(31) |
| 79 y/o F in bed, vomited 1×, became unconscious 1.5–2 h after drinking yellow fluid from ‘winter melon tea’ bottle. GCS = 7 by EMS. Transferred to ED | HR 67 bpm, RR 20/min, BP 113/71, Temp 37.0°C, SpO2 100% on room air. GCS = 15 ∼4 h after ingestion | Urine: +5F-MDMB-PICA 3,3-dimethylbutanoic acid Seized drug: +5 F-MDMB-PICA, +5CL-ADAMANTYL-PINACA |
(31) | |
| 5F-MDMB-PINACA (5F-ADB) | 47 y/o M with past hx of heroin and benzodiazepine use admitted to hospital for numbness and auditory hallucinations. Cardiovascular collapse on Day 2. Developed hypoxic ischemic encephalopathy and rhabdomyolysis. Developed pneumonia and died 11 days after admission | Macroscopic and microscopic examination of brain and lungs confirmed COD hypoxic ischemic encephalopathy and pneumonia following SC use | Antemortem urine (Day 4): +5F-MDMB-PINACA 3,3-dimethylbutanoic acid +7-amino-nitrazepam, +gabapentin |
(32) |
| 38 y/o M with hx of drug use arrived home looking pale. Went to bed and snored. Discovered cold and unresponsive 3 h later. Transferred to ED and pronounced dead | Enlarged heart, left ventricular hypertrophy, significant coronary atherosclerosis but no infarct. COD mixed drug toxicity with coronary artery disease | Blood and Urine: +5F-MDMB-PINACA 3,3-dimethylbutanoic acid +7-amino-nitrazepam, +amphetamine, +chloroquine, +codeine, +methadone, +methamphetamine, +nitrazepam, +nordiazepam |
(32) | |
| 8 patients (23–45 y/o; 7 M and 1 F) admitted to ED after IV heroin. Packets at scenes labeled ‘Santa Muerte’ (4), ‘50 Cal’ (4) and ‘Nick’ (1). All recovered following ED admission | 7 of 8 patients admitted to ED with classical opioid toxidrome, including CNS depression and pinpoint pupils. Following naloxone administration, patients exhibited severe agitation, combative behavior and anticholinergic and sympathomimetic toxidrome. Treated with benzodiazepines (8) and physostigmine (3) | Serum (N = 3): + +Cocaine (1), +heroin (3), +6-AM (3), +fentanyl (3), +THC (1), +alprazolam (1) Seized Drugs (N = 8): + +Heroin, +fentanyl |
(33) | |
| 49 y/o M with serious injury after jumping from second floor after drinking alcohol and smoking a herbal mixture. Died 6 days later | TSS = 3. COD polytrauma with leading craniocerebral injury | PM Blood: 0.2 Fentanyl 5.5, quetiapine 11.6, 7-OH-quetiapine 8.2, oxycodone 12.7, noroxycodone 2.7, oxymorphone 2.2 |
(34) | |
| 26 y/o M driving erratically | Unmotivated statements, changing moods, nonsensical statements, glassy eyes, sluggish, slow pupil response | Plasma: 0.19 +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA, 5OH-MDMB-PINACA 3,3-dimethylbutanoic acid, 4COOH-MDMB-PINACA, and others |
(34) | |
| 17 y/o F collapsed with foam on mouth and loss of consciousness after smoking a herbal mixture | N/A | Plasma: 0.11 | (34) | |
| 32 y/o M admitted to ED ∼15 h after taking what he believed to be ketamine | Dizziness, perception of rotating objects, incoordination, spasmodic rigidity, impaired gait, blepharospasm. Symptoms resolved ∼6 h and was discharged | Plasma: + | (35) | |
| 45 y/o M drove car into oncoming traffic and swerved into guard rail | Driver asleep with car running and lodged in guard rail, gear in reverse. Responsive to verbal stimuli, indicated ‘high’. Bilateral horizontal and vertical nystagmus, WAT unable to maintain heel-to-toe, lost count, raised arms; OLS put foot down, hands for balance; Arrested for operating vehicle while intoxicated | Blood: 26.4 +5F-MDMB-PINACA 3,3-dimethylbutanoic acid |
(36) | |
| 5F-MDMB-PINACA (5F-ADB) and 5F-MMB-PICA | 17 y/o M (n = 3) transported to ED after smoking ‘spice’ together | Psychomotor agitation, confusion, anxiety, psychosis, tachycardia, amnesia, temporary loss of consciousness | Urine: +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA | (37) |
| 14 y/o F transferred to ED after smoking ‘cherry bomb formula 6A’ and suffering seizure | Hypoactive, altered consciousness and headache | Urine: +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA, +5F-MMB-PICA 3-methylbutanoic acid Seized drug: +5F-MDMB-PINACA, +5F-MMB-PICA |
(37) | |
| 21 y/o M transferred to ED due psychomotor agitation and attempted suicide after smoking ‘spice’ | Agitation, altered language, bradypsychia, mydriasis and vomiting | Urine: +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA Herbal blend: +5F-MDMB-PINACA |
(37) | |
| 5F-MDMB-PINACA (5F-ADB) and MMB-FUBINACA (FUB-AMB) | 18 y/o M dead in bed after smoking three cigarettes containing ‘fake weed’ | Brain edema, acute respiratory distress syndrome, pulmonary edema, acute venous stasis in liver and spleen. COD acute respiratory failure due to acute intoxication with 5F-MDMB-PINACA and MMB-FUBINACA | Blood: 3.7 5F-MDMB-PINACA Seized drug: +5 F-MDMB-PINACA, +MMB-FUBINACA |
(38) |
| AB-CHMINACA | 29 y/o M discovered in cardiac arrest in office with three packages containing ‘leaves’ found nearby | Heavy lungs with severe alveolar effusions, air bubbles and hemorrhage, systemic hypoxia. COD AB-CHMINACA induced pulmonary edema resulting in systemic hypoxia | Blood: 7.6 ± 0.6 +AB-CHMINACA 3-methylbutanoic acid 56 ± 4, AB-CHMINACA 3-carboxyindazole 2.3 ± 0.1 +5F-MMB-PINACA (5F-AMB), +FUB-PB-22, +AB-FUBINACA. Seized Drug Packet 1: + AB-CHMINACA, +5F-MMB-PICA Seized Drug Packet 2: +5F-AB-PINACA Seized Drug Packet 3: +4-methyl-N-ethylpentedone |
(39) |
| AB-FUBINACA | 8 y/o M with known seizure disorder administered CBD oil purchased from online retailer. After 9 days seizure-free patient had >14 tonic-clonic episodes in 24 h | Intermittent agitation, delirium, depressed mental state, tachycardia, mydriasis. Returned to baseline and discharged in 2 days | Seized drug: + +CBD |
(40) |
| AB-FUBINACA and ADB-FUBINACA | 24 y/o M admitted to ED with acute confusion, agitation, visual hallucinations and palpitations after ingesting ‘2 drops’ of e-cigarette fluid ‘VapoFi’ mixed with fluid from unlabeled bottle believed to be ‘liquid cannabis’ | HR 169 bpm, RR 20/min, BP 163/93, Temp 36.3°C, SpO2 98% on room air. GCS 14/15. Supraventricular tachycardia, sinus tachycardia with multiple ventricular beats. Discharged after 22 h | ‘AB-FUBINACA’ Serum: 5.6 ‘ADB-FUBINACA’ Serum: 15.6 Seized drug: +AB-FUBINACA, +ADB-FUBINACA |
(41) |
| ADB-FUBINACA | 17 y/o M inhaled two puffs of ‘weed’ with friend. Both immediately began shivering uncontrollably and vomited. Assisted to home of friend to rest. Discovered unresponsive and cold to touch 6 h later. Transferred to ED and pronounced dead | At autopsy, internal macroscopic and microscopic examination of organs unremarkable. No injury or natural disease noted. COD: ADB-FUBINACA toxicity | Blood: 56 | (32) |
| 25 y/o M presented to ED with left severe hemiparesia, left hypesthesia, dysarthria and visual neglect after smoking ‘Freeze’ prior evening | Acute ischemic infarction of right middle cerebral artery, right cerebral edema | Urine: + +MDMB-CHMICA Seized drug: + |
(42) | |
| 38 y/o M inmate sent to medical center after 7-day hospitalization for abnormal behavior. Ovoid packets in GI tract (CT scan). 2 packages removed from the rectum, 2 by esophagogastroduodenoscopy and 22 by surgery on Days 7–8. 2 additional packages found in the rectum on Day 16 | HR 47 bpm, RR 12/min, BP 139/53, SpO2 95% on room air. Lethargic, unable to answer questions, shortness of breath, blank stare. Sinus bradycardia, hypoglycemia, hypotension, hypopnea, seizures following intubation. Intermittent hypertension, seizure activity and toxic encephalopathy until Day 16. After final two packets, mental status returned to baseline within 1 week. Discharged without neurological sequelae after 1 month |
Serum: 34 (Day 6); 17 (Day 8); +Diphenhydramine, +metoclopramide, +cocaine, +scopolamine, +midazolam Seized drug: + |
(43) | |
| AM-2201 | 18 y/o M stabbed F victim ∼20 times and injured 2 M witnesses after smoking ‘Mr. Green’ | Uncommunicative, calmly detached, sluggish motor movements, pupils slow to react to light, staggered gait and uncoordinated 1.5 h after incident. Psychiatric evaluation revealed abnormal personality and psychotic disorders tempore criminis, cannabis and ‘legal high’ addiction, and immature personality disorder. Psychiatric legal opinion: while performing charged acts individual totally or partially unable to appreciate nature and quality of acts and not in control of conduct due to mental defect | Blood: 0.48 THC-COOH 23 Seized drug: + |
(44) |
| MMB-FUBINACA (FUB-AMB) and PB-22 | 50 y/o M transferred to ED for altered mental status and chest pain after smoking ‘Scooby Snax Limited Edition Blueberry Potpourri’ | HR 52 bpm, RR 16/min, BP 87/52, Temp 36.7°C, SpO2 100% on 2 L nasal cannula. Somnolent, agitated with stimulation, combative. Intubated. Inferior wall myocardial infarction. Normal ECG and troponins on follow-up visits | Seized drug: +MMB-FUBINACA, +PB-22 | (45) |
| AMB-PINACA (MMB-PINACA) and ADB-PINACA | 29 y/o M transported by EMS for agitation and depressed consciousness after reported OD of heroin | Intubated; HR 75 bpm, RR 14 min, BP 152/0 (palpated), Temp 32.9°C, SpO2 100% on 100% inhaled O2, GCS 3T, ECG—Osborne waves and prolonged QRS (124 ms); discharged after 15 h | Serum: +AMB-PINACA, +ADB-PINACA |
(46) |
| 33 y/o M acting ‘bizarrely’, became unresponsive after tonic-clonic seizure after reported OD of heroin | EMS intubated. At ED HR 85 bpm, RR 14, BP 174/127, Temp 33.7°C, SpO2 100% on 100% inhaled O2, GCS 3T; normal ECG, EEG ‘mild bilateral cerebral dysfunction’; discharged after 24 h | Serum: +AMB-PINACA, +ADB-PINACA |
(46) | |
| 4-Cyano-Cumyl-BINACA | 29 y/o M transferred to ED by EMS after fall at home. 3-day hx of somnolence, weakness and vomiting | HR 105 bpm, BP 180/100, RR 22/min, Temp 39°C, SpO2 99% on room air. Altered mental state, combative, GCS 11. Nonoliguric kidney failure on Day 4. Mental status improved after dialysis on Days 5 and 6. Left AMA on Day 10 | Serum: 35.5 | (47) |
| Cumyl-PINACA | 36 y/o F customs inspector developed dry mouth, blurred vision, dizziness, balance disorder, weakness, numbness and palpitations 0.5 h after exposure to unknown viscous and sticky substance at the airport. Transferred to ED 6 h later | HR 105 bpm, BP 130/88; blurred vision, numbness, mydriasis, ataxia, somnolence, lethargy and confusion. 2 days post event reported amnesia and slowed perception | Blood: + Seized drug: + |
(48) |
| 22 y/o M customs inspector developed dizziness and weakness 0.5 h after exposure to unknown viscous and sticky substance at the airport. Transferred to ED 6 h later | HR 110 bpm, BP 145/95; Confused and mydriasis. Reported amnesia and slowed perception of time for 2 days | Blood: + Seized drug: + |
(48) | |
| 36 y/o M customs inspector developed blurred vision, dizziness, balance disorder, weakness and lethargy 0.5 h after exposure to unknown viscous and sticky substance at the airport. Transferred to ED 6 h later | HR 110 bpm, BP 130/80; somnolent and confused; mydriasis, ataxia; reported amnesia and slowed perception of time for 2 days | Blood: + Seized drug: + |
(48) | |
| JWH-122 | 18 y/o M with hx of extensive daily cannabis use admitted to addiction treatment unit with visual hallucinations after use of a ‘cannabis-like’ product | HR 88 bpm, RR 19/min, BP 130/80; mild hallucinations, blunted affect, anxiety and tension. Visual hallucinations and disturbances recurred following extensive cannabis intake for 4 years | Seized drug: + | (49) |
| MDMB-CHMICA | 9 patients presenting to ED. 23–62 y/o; 8 M and 1 F | Elevated plasma creatinine (6), dilated pupils (5), seizure (5), tachycardia (5), deep unconsciousness (5), respiratory depression (4), elevated blood and/or plasma lactate (4), agitation (3), delirium (3) and vomiting (3) | Serum: <1.3–86.4 (median = 18.6, mean = 24.5) +Diphenidine (1), +methylnaphthidate (1), +buprenorphine (2), +pregabalin (1), +5F-adamantyl-PINACA (1), +flubromazepam (1), +MMB-FUBINACA (1), +THJ-018 (1) |
(50) |
| 21 y/o M prison inmate presented to ED with hypercapnia | Bradycardia, 13 GCS. Administered naloxone, remained hypercapnic. ABG returned to normal 24 h post presentation | Blood: + +Mirtazapine/metabolites, +propranolol/metabolites (both prescribed) | (51) | |
| 23 y/o M prison inmate presented to ED after collapse and seizure | Administered naloxone and diazepam. Transferred to ED 70 min later. GCS 3, pulse 105 bpm, hypercapnic. Discharged ∼24 h after admission | Blood: + +Quetiapine/metabolite (prescribed), +promethazine/metabolite, +cocaine, +BZE, +levamisole |
(51) | |
| 43 y/o M prison inmate presented to ED after collapse and seizure | Administered naloxone and diazepam. At ED, GCS 3, pulse 114 bpm. 3 h post first episode, suffered tonic-clonic seizure. Released 24 h post admission | Blood: + +Olanzapine/metabolite (prescribed) |
(51) | |
| 5F-MDMB-PINACA (5F-ADB) and JWH-122 | 31 y/o M found dead in apartment. Postmortem interval ∼ 3 days. | ‘Tender’ coronary arteries, cerebral and pulmonary edema, cyanosis of internal organs | Blood: 0.57 JWH-122 12, diphenhydramine <10, doxylamine 83 Urine: 232 +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA, +JWH-122 metabolites (unspecified), doxylamine >500 |
(34) |
| MMB-FUBINACA (FUB-AMB) and EMB-FUBINACA (5 F-ADB) | 27 y/o M found dead in bed, hx of alcohol and ‘legal high’ use. COD: acute respiratory failure due to cardiotoxic effects of MMB-FUBINACA and EMB-FUBINACA | Congestion of internal organs; pulmonary edema, left-sided pleural adhesions | ‘MMB-FUBINACA’ Blood: ND Urine: 4.7 Urine (hydrolyzed): 8.2 ‘EMB-FUBINACA’ Blood: ND Urine: 0.2 Urine (hydrolyzed): 0.1 Blood: +Ethanol, +lorazepam, +haloperidol, +lidocaine |
(52) |
| MMB-FUBINACA (FUB-AMB) and 5F-MDMB-PINACA (5F-ADB) | 43 y/o F found dead in apartment following consumption of a herbal mixture. Estimated postmortem interval 3 days | Cerebral and pulmonary edema, hyperemia internal organs | Blood: 0.03 +5F-MDMB-PINACA 3,3-dimethylbutanoic acid, 5OH-MDMB-PINACA, 5OH-MDMB-PINACA 3,3-dimethylbutanoic acid, 4COOH-MDMB-PINACA and others, mirtazapine 7.5, +mirtazapine metabolites, lidocaine 43, 3-MeO-PCP 97 |
(34) |
| 5F-MMB-PINACA (5F-AMB) | 19 y/o M acting incoherently after sniffing/smoking unknown substance | BP 120/80; slow movements, slurred speech, disoriented, lethargic, hyporeflexia, uncoordinated, teeth grinding, fearful, loss of focus/memory, dry mucus membranes and tinnitus | Seized drug: + | (53) |
| NM-2201 | 25 y/o M presented to ED with agitation, double incontinence and incoordination in movement and speech 5 days after smoking ‘Black Mamba’ | Admission: GCS = 14, hyperactive agitation, left-sided incoordination, aphasia, generalized hypertonia, hyperreflexia, left-sided hemiparesis. Day 4: GCS 10, no visual tracking, elevated temp 38.7°C, diaphoresis, tachycardia, hypertension and agitation | Seized drug: + | (54) |
| O-2545 | 16 y/o M lost consciousness after smoking cannabis and ‘Bonsai’ | GCS E1M1V1, dilated pupils, unresponsive to light, tachycardia. Intubated due to persistent lack of consciousness and transferred to ICU. Discharged after overnight stay | Serum: + Urine: +THC-COOH |
(55) |
| UR-144 | 19 y/o F presented to ED in status epilepticus after using ‘space’ | Seizure activity 3 h, HR 138–150 bpm, RR 28/min, BP 90/60, Temp 37.1°C, severe biventricular failure; stress cardiomyopathy. Discharged on hospital Day 10 | Urine: + +UR-144 metabolites (unspecified) |
(56) |
| 27 y/o M with hx of polysubstance use became unresponsive within 1 h of inhaling ‘K2’. Transported to ED | HR 98 bpm, BP 144/84, Temp 36.2°C; Hypoxic on arrival, SpO2 100% on FiO2 0.5; Worsening bilateral alveolar infiltrates and diffuse alveolar hemorrhage on Day 2. Discharged 10 days post admission | Blood: +UR-144 5-hydroxypentyl (by ELISA) | (57) |
6-AM = 6-monoacetylmorphine, ABG = arterial blood gas, AMA = against medical advice; BP = blood pressure, BZE = benzoylecgonine, CBD = cannabidiol, CNS = central nervous system, CT = computed tomography, ECG = electrocardiogram, EEG = electroencephalogram, EME = ecgonine methyl ester, EMS = emergency medical services, F = female, GI = gastrointestinal, GCS = Glasgow Coma Score, HR = heart rate, hx = history, M = male, N/A = not available, OLS = one leg stand, PM = postmortem, RR = respiratory rate, SpO2 = oxygen saturation, Temp = temperature, THC-COOH = 11-nor-carboxy-delta-9-tetrahydrocannabinol, WAT = walk-and-turn, OD = overdose, ND = none detected, ICU = intensive care unit, ELISA = enzyme linked immunosorbent assay.