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The Spice of Life? A Review of Synthetic Cannabinoids

Alicia Mattson, PharmD, BCPSPGY2 Emergency Medicine Pharmacy ResidentPharmacy Grand RoundsApril 12, 2016


Objectives• Describe the history of synthetic cannabinoids• Recall the effects patients get from synthetic

cannabinoids• Explain a treatment approach for a patient who

ingested a synthetic cannabinoid


Synthetic cannabinoids act on the same receptors as marijuana/cannabisTrue/False


History of Synthetic Cannabinoids• Used for years in pharmaceutical research

• Cannabinoid receptor research• Not designed to be a drug of abuse

• Illicit manufacturing began in early 2000s• JWH-018 and HU-210• First seen in Europe in 2004

• DEA first encountered in the US in 2008

DEA: Drug Enforcement Administration Kemp AM et al. Am J Med. 2016;129(3):240-44.e1


Pharmacology• Agonists at CB1 and CB2 receptors

• Higher affinity than THC• Full agonists

• Synthetic cannabinoids bind other receptors• Serotonin, nicotinic, potassium

Kemp AM et al. Am J Med. 2016;129(3):240-44.e1Pertwee RG. Int J Obes.2006;30:S13-18

Tyndall JA et al. Clin Toxicl. 2015;53(10):950-56

CB1 Primarily on central and peripheral neurons Mediate neurotransmitter release - glutamate, GABA

CB2 Primarily on immune cellModulate cytokine release


Production of Synthetic Cannabinoids• Powder made in bulk usually overseas• Packaged and shipped to the US labeled as

“fertilizer” or “industrial solvent”

http://www.businessinsider.com/what-is-synthetic-marijuana-2015-5


Production of Synthetic Cannabinoids• Wholesale buyers purchase and turn into liquid

by dissolving in acetone or alcohol• Liquid product can be sold• Sprayed onto dry plant matter and packaged

http://www.businessinsider.com/what-is-synthetic-marijuana-2015-5


Types of Synthetic CannabinoidsChemical Names

AM-2201 XLR11 JWH-022

UR-144 JWH-018 AM-1248

JWH-122 JWH-250 AB-PINACA

JWH-210 JWH081 ADB-PINACA

MAM-2201 JWH-073 AB-FUBINACA

AKB48 RCS-4 AB-CHIMINACA

JWH-203 PB-22 AM22015F-PB-22 5F-AKB48 MAB-CHMINACAJWH-019 STS-135 ADB-FUBINACAAM-649 AM-2233 THJ-2201RCS-8 JWH-200 CB-13

U.S. Drug Enforcement Administration, June 2014


Chemical Variations

JWH-018 AM-2201 UR-144


O

N

F

O

N

H3C

O

N

H3C

H3CH3C

H3C

H3C


Types of Synthetic CannabinoidsStreet Names

K2 Moon Rocks

Skunk Angry Birds

Bhang Bliss

Black Mamba Bombay Blue

Dr. Feel Good Fake Weed

Gansta Mojo

Killa Gorilla NinjaMr. Nice Guy Outer SpaceScooby Snax Sexy Monkey

Smacked Smoking SantaTomcat WANTED

Kemp AM et al. Am J Med. 2016;129(3):240-44.e1


Synthetic cannabinoids are legalTrue/False


Regulatory Issues• Marijuana listed as Schedule I per DEA • Synthetic Cannabinoids not initially scheduled

• Available to sell legally • 2011: 5 Synthetic cannabinoids temporarily

scheduled JWH-081 JWH-073JWH-200 CP-47, 497

CP-47, 497 C8



Synthetic Drug Abuse Prevention Act 2012-26 synthetic cannabinoids and cathinones

permanently became Schedule I substances-DEA can place temporarily schedule

substances for 36 months

S. 3190 (IS) – Synthetic Drug Abuse Prevention Act of 2012

Additional Temporary Scheduled SCs2014: 4 SCs scheduled 2015: 3 SCs scheduled

2016: 1 additional SC scheduled

Synthetic Cannabinoid Trends

NFLIS: National Forensic Laboratory Information System Schwartz et al. J Emerg Med.2015;48(5):573-80


Increasing Use of Synthetic Cannabinoids



Obtaining Synthetic Cannabinoids• Availability

• Internet• Convenience stores• Smoke shops/Head shops• Gas stations

• Marked “not for human consumption” • Marketed as incense and herbal blends• Cost is around $10/gram

Kemp AM et al. Am J Med. 2016;129(3):240-44.e1


Synthetic cannabinoids will not show up on a urine drug screen. True/False


Detection of Synthetic Cannabinoids • Current urine drug screen don’t commonly

contain assays for synthetic cannabinoids• Certain labs have assays to detect• Limitations

• Large number of synthetic cannabinoids on the market

• Continual change in available products• Time to availability once new chemical is

identified


Metabolism of Synthetic Cannabinoids



Synthetic cannabinoids have a specific toxidrome to look forTrue/False


Effects of Synthetic Cannabinoid Intoxication

Seizures, Altered mental status, psychosis, confusion, disorientation, aggression, somnolence, ischemic stroke

Tachycardia converting to bradycardia, hypertension, chest pain, myocardial ischemia

Respiratory depression, pneumonia

Acute kidney injury, rhabdomyolysis

Hyperglycemia, hypokalemia, nausea, vomiting, hyperthermia, DEATH


Colorado Outbreak • 2013 - patients smoking “black mamba”• 263 possible cases with 76 patients presenting

to 2 emergency rooms

• 7 patients required intubation• 1 additional patient admitted to the medical floor• “black mamba” = ADB-PINACA

Monte AA et al. N Engl J Med. 2014;370(4):389-90

Altered mental status (67.6%) Agitation (42.1%)

Seizures (14.4%) Initial tachycardia: 100bpmHR <50bpm (10%)


Georgia Outbreak• 2013 - patients smoking “crazy clown”• 22 patients

• 5 patients required intubation• 6 patients admitted to the MICU• “crazy clown” = ADB-PINACA

Confusion/disoriented (32%) Aggression (32%)Seizures (14%) Somnolence (32%)

Hyperglycemia (59%) Hypokalemia (41%)Acidosis (32%) Tachycardia (59%)

Schwartz MD et al. J Emerg Med.2015;48(5):573-80


Florida Outbreak


• 2014 - patients ingesting synthetic cannabinoids• 35 patients treated at University of Florida ED

• 5 patients (14.3%) required intubation• 2 additional patients admitted to the MICU and

3 to medical floors• SC in these patients: AB-CHMINAA

Altered mental status (61%) Hallucinations (6%)Seizures (40%) Tachycardia & Hypertension


Ischemic Stroke

Freeman MJ et al. Neurology. 2013;81:2090-93Takematsu M et al. Clin Toxicol. 2014;52:973-75

33yo Male, previously healthyCC: Right sided weakness and aphasiaSmoked two joints of “WTF” 10 minutes before symptoms onsetNIHSS: 5, BP: 163/63, CT scan negative Treatment: IV tPA, most symptoms resolved, 24h CT showed acute infarctionSynthetic Cannainoid: XLR-11

26yo Male with history of asthmaCC: dysarthria, expressive aphasia, right face and arm weaknessSmoked “spice” a few hours prior, no recent marijuana useBP: 158/88, sinus tach, CTA: L MCA infarctionTreatment: IV tPASynthetic Cannabinoid: JWH-018


Ischemic Stroke

Takematsu M et al. Clin Toxicol. 2014;52:973-75

19yo Woman, history of tobacco use, anxietyCC: aphasia, right hemiplegia, sensory lossSmoked “spice” BP: 143/73, sinus tach, CTA: embolic strokeTreatment: Supportive Synthetic Cannabinoid: JWH-018


Myocardial Infarction

McKeever RG et al. J Med Toxicol. 2015;11:129-31Schwartz MD et al. J Emerg Med.2015;48(5):573-80

16yo M, 24h substernal chest pain, nausea, vomiting, dyspneaPMH: ADHD [methylphenidate, aripiprazole]Reported K2 use prior to symptom onsetEKG: ST-elevations on II, III, AVF and V4-6Troponin: 1.47 ng/mL (8.29 peak), CKMB: 17.5 ng/mL (33.9 peak)Cardiac cath on day 4 showed normal coronaries

30yo M, combative, aggressive, cardiac arrest during EMS transportReported K2 use EKG: anterior ST-elevations Cardiac cath: 100% LADPMH: familial hypercholesterolemia, premature CAD, cocaine use

EKG Changes in Pediatric Patients

Clark BC et al. J Pediatr. 2015;167:757-61

AgeLast

use to onset

Symptoms EKG Findings Troponin(ng/mL) Treatment

15 Day of AMS NSR, LVH, ST flattening in lateral leads, T wave inversion 0.16 Observation

16 Day of AMS NSR, ST elevation, T wave inversion inferiorly - x1 Observation

17 Day of AMS, chest pain Sinus tach, ST elevation 0.39 Observation

17 Day of SOB, labored respirations

NSR, T wave inversion lead III, ST elevation in septal leads - x3 Observation

15 Day of Palpitations, dizzy/weak ST elevation leads II, III, aVF - x2 Observation

18 2-3 days Chest/back pain NSR, J point elevation -x1 Appendectomy

16 Day of Seizure Sinus arrhythmia, ST elevation lead I and aVL NA Observation

16 Day of Syncope, palpitations

Sinus arrhythmia, leftward axis, early repolarization, nonspecific

ST changesNA Observation


Acute Kidney Injury

Buser GL et al. Clin Toxicol. 2014;52:664-73

17yo male previously healthyCC: Nausea, vomiting, bilateral CVA tendernessSmoked “Clown Loyal” 30 minutes priorLabs: BUN 65, SCr 10.2UA: >100 RBC, trace proteinuria without casts, 1+ eosinophilsTreatment: IV furosemide, IV methylprednisolone 500mg daily x 3 days followed by prednisone 30 mg BID, tapered over 2 weeks Renal Biopsy: acute tubular injury with mild interstitial nephritis

15yo male previously healthyCC: abdominal pain, nausea, lower back pain x 3 daysReported marijuana and K2 use in the past monthsLabs: BUN 48, SCr 7.8, UA trace proteinTreatment: prednisone 60 mg, hemodyalisis x 2Renal Biopsy: acute tubular necrosis with peritubular capillaritis

AKI Cases from XLR-11Age Initial symptoms Last use

to onsetInitial

BUN/SCrPeak

BUN/SCr Treatment

18 Nausea, emesis, flank & abdominal pain <1 day 14/0.99 42/6.6 Fluid management

27 Flank painHematuria 14 days 24/4.3 29/4.7 Fluid management

Antihypertensives

19Nausea, emesis, myalgia, oliguria,

diaphoretic6.5 hours 24/3.1 28/4.9 Fluid management

19 Nausea, emesis, flank pain 14 days 32/2.6 32/2.6 Fluid management

18 Nausea, emesis, abdominal pain 7.5 hours 20/1.6 37/5.5 Fluid management

18 Nausea, emesis, abdominal pain 7.5 hours 48/6.3 65/9.6 Fluid management

diuresis

16Nausea, emesis, epigastric pain, headache, AMS

< 1 day 177/17.1 177/17.1 Fluid management

Buser GL et al. Clin Toxicol. 2014;52:664-73


Synthetic cannabinoid intoxication is treated only with supportive careTrue/False


Treatment of Synthetic Cannabinoid Intoxication• ABCs

• Often end up with compromised airway• Supportive

• Tachycardia: fluid resuscitate • Agitation/Aggression

• Liberal benzodiazepines• Antipsychotics: Haldol, quetiapine,

droperidol• Seizures: benzodiazepines • Replace electrolytes


Severe Complications• Myocardial infarction

• ACS treatment• Consider cardiac cath

• Acute Kidney Injury• Manage fluids and diurese as needed• Consider corticosteroids:

• Prednisone 60 mg daily• Ischemic Stroke

• IV tPA based on standard inclusion criteria

ACS: Acute Coronary SyndrometPA: Tissue Plasminogen Activator


Synthetic cannabinoids are not addictiveTrue/False


Addictive Potential • Increased binding affinity and full agonistic

effects on CB receptors may contribute to their addictive potential

• New Zealand treatment center• 47 patients with synthetic cannabinoid addiction• 93% smoked >2.5g/day, mean was 4.6g/day• Symptoms: agitation, irritability, mood swings• Treated with diazepam (5-25mg/day) and/or

quetiapine (25-475mg/day)

• Case reports in the United States

Macfarlane V, Christie G. Drug Alcohol Rev. 2015;34:147-53Nacca N, et al. J Addict Med.2013;7(4):296-98


Summary: Synthetic Cannabinoids• Certain chemical formulations are illegal• Not detected on a standard urine drug screens• Intoxications do not all present the same

• Seizure, delirium, AKI, ischemic stroke• MI, tachycardia/bradycardia, hypertension

• Treatment of intoxication is supportive and individualized based on effects

• Synthetic cannabinoids seem to have an addictive potential

AKI: acute kidney injuryMI: myocardial infarction


The Spice of Life? An Update on Synthetic Cannabinoids and Synthetic Cathinones

Alicia Mattson, PharmD, BCPSPGY2 Emergency Medicine Pharmacy [email protected] Grand RoundsApril 12, 2016

the spice of life? - mayo school of continuous ... alicia pgr 4 12... · the spice of life? a ......

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