Summary Of Exposure |
A) USES: Herbal mixtures, referred to as "Spice", "K2", and other names, have been found to contain cannabinoid receptor agonists (THC homologs). It is speculated that the THC homologs are mixed into a solvent and are sprayed onto plants and herbal blends as the vehicle for delivery. Although recently banned in the United States and in many countries in Europe, these products have been sold on the internet and in various specialty shops and are marketed as incense, but are smoked for their reported cannabis-like effects. On November 24, 2010, the United States Drug Enforcement Administration (DEA) has temporarily designated several synthetic THC homologs, including JWH-018, JWH-073, JWH-200, CP-47, 497 and cannabicyclohexanol, as Schedule I controlled substances.
B) TOXICOLOGY: THC homologs (synthetic cannabinoids) are cannabinoid receptor agonists that target the CB1 and CB2 marijuana receptors, but are not structurally related to marijuana. Although the herbal mixtures, containing these cannabinoid receptor agonists, are being smoked for their reported cannabis-like effects, these compounds may have up to 28 times greater potency than tetrahydrocannabinol (THC).
C) EPIDEMIOLOGY: Because of accessibility via the internet and undetectability during routine toxicology screens, use of these products is occurring more frequently.
D) WITH POISONING/EXPOSURE
1) MILD TO MODERATE TOXICITY: Mild to moderate intoxication can result in alterations in mood and perception, xerostomia, reddened conjunctiva, and an increase in pulse rate, similar to marijuana (THC). Hyperemesis, similar to marijuana, has been observed in a patient following excessive use. Other effects reported that may not follow the current pattern of exposure to THC compounds have included hypertension, agitation, tremors, paranoia, hallucinations and, rarely, hypokalemia. The onset of effects after inhalation is rapid and gradually resolves.
2) SEVERE TOXICITY: Severe agitation, hyperthermia, recurrent seizures, supraventricular tachycardia, rhabdomyolysis (infrequent) and psychosis have been reported. ST elevation MI has been reported in several adolescents, and can occur in patients with normal coronary arteries. Acute renal injury has been reported among teenagers after smoking a new synthetic cannabinoid referred to as XLR-11. Acute renal failure and significant rhabdomyolysis occurred in a young adult following an episode of persistent hyperemesis after using a synthetic cannabinoid product. The type and amount of THC homologs, contained within herbal products, can vary considerably. There is a possibility of severe overdose due to batch-to-batch variability within the same product. In addition, there is very little known regarding the herbal mixtures used as the delivery vehicle; the herbs themselves may also have additive psychoactive properties.
|
Vital Signs |
3.3.1) SUMMARY
A) WITH POISONING/EXPOSURE 1) Severe hyperthermia (temperature 106.1 degrees F) and rhabdomyolysis have been reported in a young adult following the use of K2; symptoms resolved over several days following aggressive IV hydration (Sweeney et al, 2016).
|
Heent |
3.4.3) EYES
A) WITH POISONING/EXPOSURE 1) CONJUNCTIVITIS: Significant reddening of the conjunctivae occurred in 2 individuals approximately 10 minutes after smoking a cigarette containing 0.3 g of "Spice diamond" (Auwarter et al, 2009).
2) BLURRED PERIPHERAL VISION was reported in an 18-year-old man approximately 30 minutes after smoking 1 oz of a dried herbal product, "K2 Summit". Analysis of the product determined that the product contained JWH-018, a cannabinoid receptor agonist (Cunning et al, 2010).
3) MYDRIASIS: According to a report from the National Poison Data System (NPDS), 9 "Spice" exposures were reported in a five-state region, serviced by the Rocky Mountain Poison and Drug Center in Colorado, from September 2009 to April 2010. Two cases (22.2%) developed mydriasis ( Banerji et al, 2010).
3.4.6) THROAT
A) WITH POISONING/EXPOSURE 1) XEROSTOMIA: Dry mouth was reported in 2 individuals approximately 10 minutes after smoking a cigarette containing 0.3 g of "Spice diamond" (Auwarter et al, 2009), and in 2 individuals who smoked cigarettes containing 100 to 150 mg of the herbal incense product "Smoke". This product was subsequently determined to contain the synthetic cannabinoid, JWH-018 (Teske et al, 2010).
|
Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) TACHYCARDIA 1) WITH POISONING/EXPOSURE a) Intoxication with "Spice" or "K2" products may produce tachycardia (Hermanns-Clausen et al, 2013; U.S. Drug Enforcement Administration, 2011; Schneir et al, 2010; Vearrier & Osterhoudt, 2010; Bebarta et al, 2010; Rosenbaum et al, 2010).
b) A significant increase in pulse rates occurred in 2 individuals 10 minutes after smoking a cigarette containing 0.3 g of "Spice diamond" (Auwarter et al, 2009), and in 2 individuals who smoked cigarettes containing 100 to 150 mg of the herbal incense product "Smoke". This product was subsequently determined to contain the synthetic cannabinoid, JWH-018 (Teske et al, 2010).
c) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network, tachycardia occurred in 173 (37.3%) cases and was one of the most common events observed. In this study, tachycardia and hypertension were the most common cardiovascular effects (Forrester et al, 2011).
d) According to a report from the National Poison Data System (NPDS), 9 "Spice" exposures were reported in a five-state region, serviced by the Rocky Mountain Poison and Drug Center in Colorado, from September 2009 to April 2010. Tachycardia was reported as the most frequent adverse effect, occurring in 6 cases (66.7%) ( Banerji et al, 2010).
e) CASE REPORT/SUPRAVENTRICULAR TACHYCARDIA: A 48-year-old man ingested ethanol and JWH-018 (confirmed by laboratory analysis) and developed recurrent seizures. Shortly after arrival to the ED, the patient was given lorazepam and intubated for airway protection. Ethanol was 3.8 mg/dL and creatinine phosphokinase was 2649 Units/L; a urine toxicology screen was negative for other drugs of abuse. Refractory supraventricular tachycardia developed during the first day of admission requiring electrical cardioversion; no further dysrhythmias occurred. The patient continued to do well and was discharged to home several days later (Lapoint et al, 2011).
f) CASE REPORT: A 17-year-old boy smoked an herbal mixture and a short time later was found to be severely somnolent. Upon admission to the ER, vital signs were normal with the exception of sinus tachycardia (160 beats/min). Other symptoms included mydriasis, anisocoria, retrograde amnesia, and mild somnolence. A head CT for suspected hemorrhage was negative and laboratory studies were normal with the exception of leukocytosis. The patient clinically improved within 12 hours. A blood serum sample obtained 4 hours after admission was positive for MAM-2201 (0.15 ng/mL) and UR-144 (0.24 ng/mL) and metabolites of JWH-122 and UR-144 were found in the urine. No other agents were detected (Hermanns-Clausen et al, 2013).
B) HYPERTENSIVE EPISODE 1) WITH POISONING/EXPOSURE a) Intoxication of "Spice" or "K2" products may produce hypertension (U.S. Drug Enforcement Administration, 2011; Vearrier & Osterhoudt, 2010; Bebarta et al, 2010).
b) According to a report from the National Poison Data System (NPDS), 9 "Spice" exposures were reported in a five-state region, serviced by the Rocky Mountain Poison and Drug Center in Colorado, from September 2009 to April 2010. Hypertension was reported in 2 cases (22.2%) ( Banerji et al, 2010).
c) INCIDENCE: In a retrospective study of synthetic cannabinoid exposure (n=464) reported to the Texas Poison Center Network, hypertension occurred in 45 (9.7%) cases and was one of the most common events observed. In this study, tachycardia and hypertension were the most common cardiovascular effects (Forrester et al, 2011).
C) HYPOTENSIVE EPISODE 1) WITH POISONING/EXPOSURE a) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network, hypotension was reported infrequently (n=10; 2.2%). Hypotension was mild and symptoms improved with IV fluids; vasopressors were not required (Forrester et al, 2011).
D) SUPRAVENTRICULAR TACHYCARDIA 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 48-year-old man with a long history of consuming cannabis on a monthly basis, ingested two thirds of a g of a spice blend (K2 Summit Blend) and after 45 minutes he felt slightly "high" and ingested another one third of a g of JWH-018 powder. He complained of nausea and feeling detached. His wife found him unresponsive and shaking violently; EMS witnessed a generalized tonic-clonic seizure. Upon arrival he was intubated due to copious foaming of the mouth and respiratory acidosis. Initial vital signs and ECG were normal. Fourteen hours after admission, the patient developed supraventricular tachycardia (heart rate: 186 to 214 beats/min) and hypotension (BP 59/43 mmHg). Electrical cardioversion (100 Joules) was successful. Following supportive care, the patient was extubated on day 2 and discharged on day 5 with no permanent sequelae (Tofighi & Lee, 2012).
E) MYOCARDIAL INFARCTION 1) WITH POISONING/EXPOSURE a) SUMMARY: ST elevated myocardial infarction was associated with recreational use of K2 (synthetic cannabis) in 3 male (all 16 years old) teenagers (Mir et al, 2011). 1) CASE ONE: A male athlete presented with a 3-day history of midsternal chest pain. Upon admission, an ECG revealed ST segment elevation in the inferolateral leads and a troponin level of 3 ng/mL (normal: less than 0.4 ng/mL). He reported smoking K2 one day prior to admission and had smoked marijuana 3 weeks earlier. Worsening chest pain was reported one day after admission with more pronounced ST segment elevations. His troponin level peaked at 25 ng/mL. An echocardiogram and coronary angiography were normal. A urine screen was positive for delta-9-THC only (Mir et al, 2011).
2) CASE TWO: The second teenager reported a one-week history of chest pain. His initial troponin level was 11.6 ng/mL with an ECG revealing ST-segment elevation in the inferolateral leads. He had smoked marijuana 2 weeks prior to admission and had smoked K2 3 days prior to presentation. Diagnostic studies (echocardiogram, coronary angiography) were normal. A urine screen for cannabis and cocaine were negative (Mir et al, 2011).
3) CASE THREE: The third teen was admitted with a 3 day history of chest pain described as retrosternal and episodic lasting up to 1 to 2 hours. An ECG revealed ST-elevation along with a troponin level of 7 ng/mL (peaked at 12 ng/mL). He reported occasional marijuana use and had used K2 one week prior to the development of chest pain. An echocardiogram was normal. A urine screen was positive for THC and testing for JWH-013 and JWH-073 were negative (Mir et al, 2011).
4) CASE REPORTS/ABD-PINACA: A cluster of 6 young adults and one teenager developed various symptoms, including anxiety, delirium, psychosis, and aggressive behavior, after smoking the same synthetic cannabinoid product (Crazy Clown) found to contain ADB-PINACA. Three of the 7 patients were severely agitated and combative and required sedation and intubation by EMS. Of these patients, a 30-year-old man had a witnessed cardiac arrest in route to the ED. Upon arrival his ECG showed an anterior ST-elevated myocardial infarction and he was found to have complete occlusion of his left anterior descending artery that was successfully treated with balloon angioplasty. Once alert he reported a history of premature coronary artery disease, familial hypercholesterolemia and past cocaine use. He did well and was released on hospital day 5 (Schwartz et al, 2015).
F) ISCHEMIC STROKE 1) WITH POISONING/EXPOSURE a) CASE REPORTS: Two healthy young women developed acute ischemic stroke (AIS) after first-time use of synthetic cannabis; thrombolytics were not given in either case due to late arrival. Diagnostic testing for vascular risk factors were also negative for both women. In the first case, a 22-year-old woman taking atomoxetine and an oral contraceptive containing estrogen developed palpitations, dyspnea and feelings of intense anxiety resulting in chest pain while smoking the spice product "K2". Several hours later she developed dysarthria and difficulty standing. Her exam included drowsiness, inattention, dysarthria, left face and body weakness. A head CT was negative but a MRI revealed a right middle cerebral artery AIS. In addition, a CT angiogram showed a proximal right M1 occlusion with distal reconstitution but no deep vein thrombosis. Urine toxicology screening was positive for tetra-hydrocannabinol, benzodiazepines and salicylates. On follow-up, ambulation was limited and she was unable to use her left arm. In the second case, a 26-year-old woman with a history of migraines with aura, tobacco smoking, a family history of superficial thrombophlebitis, and taking an estrogen-containing oral contraceptive, smoked "Peak Extreme" for migraine symptoms. The next morning she had left facial weakness and numbness and dysfluency. Her symptoms resolved with no changes in CT. Twenty-four hours later she had left-sided weakness and difficulty speaking. Her physical exam was consistent with her symptoms. A repeat CT showed evidence of a near occlusion of the right M1 segment and an extensive middle cerebral artery territory infarction was present on MRI imaging. She was started on warfarin. A toxicology screen was negative. Upon follow-up, her speech and comprehension had improved (Bernson-Leung et al, 2014).
|
Respiratory |
3.6.2) CLINICAL EFFECTS
A) DYSPNEA 1) WITH POISONING/EXPOSURE a) CASE REPORT/CHRONIC EXPOSURE: A 21-year-old previously healthy man developed significant dyspnea following a minor car accident in which he was restrained requiring rapid endotracheal intubation and intubation. A CT scan was negative for acute traumatic pulmonary contusion; however, extensive and diffuse airspace nodules in a peribronchovascular distribution were present (bilateral subacute lung infiltrates). An extensive workup for infection, malignancy, autoimmune or hematologic effects were negative. The patient and family reported recent (4 months prior to hospitalization) use of several synthetic cannabinoid products daily by inhalation using a pipe or bong; 4 spice products (AM-2201, JWH-122, JWH-210, AND JWH-018) were confirmed in the urine, blood and saliva of the patient. Unopened packages of the product were individually tested and each one was found to contain AM-2201. He gradually improved over 8 days with antibiotic and steroid therapy and he was successfully extubated (Alhadi et al, 2013).
B) DECREASED RESPIRATORY FUNCTION 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 19-year-old man, with a history of smoking K2 powder about twice per month for 6 months, was admitted to the ER after his family noticed an alteration in his mental status. Upon admission, he alternated between unresponsiveness to combativeness and abnormal speech. He required intubation for respiratory insufficiency (respiratory rate of 7 breaths/min). A toxicology screen was negative. The patient later reported occasional use of marijuana and a history of alcohol abuse for the past 3 years. Respiratory and CNS function improved uneventfully and he was discharged with outpatient information for substance abuse counseling (Jinwala & Gupta, 2012). 1) In another case, a 15-year-old boy went to a rave party and drank alcohol (60 mL of vodka) and a 680 mL can of Four Loko (a combination of alcohol, caffeine, taurine and guarana) and smoked an unknown amount of an herbal incense ("Silver K-2"). He returned home and was noted to have a sudden onset of difficulty breathing; his parents contacted emergency services. Prior to arrival in the ER, his breathing was shallow with a respiratory rate of 8 breaths/min. Upon admission, he was noted to have apneic spells and alterations in consciousness and required immediate intubation which was needed for 2 days. Chest x-ray, CT scan and laboratory testing were all within normal limits. A urine drug screen was negative. By day 4, the patient was clinically improved and was referred for outpatient substance abuse treatment (Jinwala & Gupta, 2012).
b) CASE REPORT/INFANT: A 10-month old developed an altered mental status several hours after ingesting "potpourri". Upon admission he was unresponsive and rigid. His vital signs were significant for a temperature of 90.4 degrees F. Laboratory studies were significant only for a serum BUN of 32 mg/dL and lactic acid of 3.6 mmol/L. A toxicology screen and ethanol concentration were negative. Endotracheal intubation was performed for apneic periods and oxygen desaturation. Active warming was needed once during admission for hypothermia. By day 2, he was successfully extubated and discharged to home on day 3 without sequelae. Analysis of the substance ingested and serum analysis confirmed the presence of MAB-CHMINACA, a synthetic cannabinoid (Hawkins et al, 2015). c) CASE REPORT/INFANT: A 10-month-old girl was found by her mother chewing on a "K2 cigarette". Upon admission, her physical exam and respiratory status were initially within normal limits and laboratory studies were unremarkable. However, about 90 minutes later she developed sedation and respiratory depression necessitating intubation. In addition, the patient was found to be positive for influenza A. Intubation was needed for 36 hours and she was easily extubated with no permanent sequelae. Blood and urine specimens were positive for AB-PINACA (42 ng/mL) and its metabolite AB-PINACA N-pentanoic acid (345 ng/mL) at the time of admission. A toxicology screen was negative for other agents (Thornton et al, 2015). |
Neurologic |
3.7.1) SUMMARY
A) WITH POISONING/EXPOSURE 1) Anxiety, agitation, confusion, tremors, and alterations in mood and perception have been reported following inhalational exposure to synthetic cannabinoids. Recurrent seizures were reported in one adult following ingestion of JWH-018.
3.7.2) CLINICAL EFFECTS
A) ANXIETY 1) WITH POISONING/EXPOSURE a) SUMMARY 1) Agitation has been reported in patients following inhalation of herbal incense products containing synthetic cannabinoids, including JWH-018 (Cohen et al, 2012; Vearrier & Osterhoudt, 2010; Bebarta et al, 2010; Rosenbaum et al, 2010). At times agitation can be so severe that it has lead to combative and violent behavior (Schwartz et al, 2015).
2) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network during 2010, agitation occurred in 86 (18.5.%) cases and was one of the most common events observed (Forrester et al, 2011).
3) According to a report from the National Poison Data System (NPDS), 9 "Spice" exposures were reported in a five-state region, serviced by the Rocky Mountain Poison and Drug Center in Colorado, from September 2009 to April 2010. Four cases (44.4%) reported agitation and irritability ( Banerji et al, 2010).
4) CASE REPORT: An 18 year-old boy developed agitation and diaphoresis after smoking "Spice." Upon admission he was uncooperative, restless, and aggressive. Based on a limited exam, he had sinus tachycardia and an elevated blood pressure with 3 to 4 mm pupils that were equal but sluggish. Lorazepam was given for agitation along with diphenhydramine 50 mg IV. Over the next few hours, he gradually improved and was discharged to home (Cohen et al, 2012).
5) CASE REPORTS: Two patients experienced increased anxiety after smoking "Spice", an herbal incense product, subsequently determined to contain 2 synthetic cannabinoids, JWH-018 and JWH-073. The first patient, a 22-year-old woman, also experienced palpitations, bilaterally injected conjunctiva, and lateral gaze nystagmus bilaterally. The second patient, a 20-year-old woman, in addition to anxiety, developed tachycardia and bilaterally injected conjunctiva. Both patients recovered spontaneously and were discharged (Schneir et al, 2010).
6) CASE REPORTS/ABD-PINACA: A cluster of 6 young adults and one teenager developed various symptoms, including anxiety, delirium, psychosis, and aggressive behavior, after smoking the same synthetic cannabinoid product (Crazy Clown) found to contain ADB-PINACA. Three of the 7 patients were severely agitated and combative and required sedation and intubation by EMS. One patient required intubation for 3 days, but everyone was successfully treated and released. A female patient who was alert and oriented with marked anxiety, but not aggressive, left against medical advise before being evaluated (Schwartz et al, 2015).
b) PATIENTS WITH PSYCHOTIC DISORDERS 1) CASE REPORTS: Four patients with a history of paranoid schizophrenia were hospitalized for intensive psychiatric care. While hospitalized, the patients smoked an unknown product (presumed to be a synthetic cannabinoid) with tobacco brought by a visitor and they developed new psychotic symptoms. After smoking the synthetic cannabinoid, each patient's clinical status changed rapidly and were not characteristic of their underlying chronic symptoms associated with schizophrenia. The first patient developed markedly elevated mood, began crawling around the room stating he was a cow, marked sedation and narrowed consciousness. His symptoms of toxicity resolved in approximately 6 hours without further drug therapy. In the second case, severe agitation, anxiety and paranoid delusions developed. He complained of chest pain with mild tachycardia (135 beats per minute). His neurologic status remained normal. Oral diazepam was increased and after 4 hours he was less anxious and agitated. Similar symptoms were reported in the third patient with the exception of high blood pressure (BP 170/120 mmHg). His oral lorazepam dose was increased to 2.5 mg 3 times a day. After 2 hours, his symptoms began to subside along with normalization of his vital signs. The last patient also became agitated with moderate anxiety. However, he had no changes in mood or alterations in consciousness. His symptoms gradually resolved over a 24-hour period (Celofiga et al, 2014).
B) SEIZURE 1) WITH POISONING/EXPOSURE a) SUMMARY 1) Seizures have been reported in a number of cases of exposure to "spice" products (Schwartz et al, 2015; Hermanns-Clausen et al, 2013; McQuade et al, 2013; Tofighi & Lee, 2012; Bebarta et al, 2012; Harris & Brown, 2013; Lapoint et al, 2011).
b) CASE REPORTS 1) CASE REPORTS/ABD-PINACA: A cluster of 6 young adults and one teenager developed various symptoms, including anxiety, delirium, psychosis, and aggressive behavior, after smoking a synthetic cannabinoid product (Crazy Clown) found to contain ADB-PINACA. Three of the 7 patients were severely agitated and combative and required sedation and intubation by EMS. Another patient developed disorientation and a delayed-onset of seizures in a healthy 24-year-old man, seven days after smoking two different synthetic cannabinoids (ie, Crazy Clown and 10X). He was treated with IV fluids and released. However, the following day his family reported that he was confused and disoriented. He was readmitted 2 days later and had severe agitation and a witnessed seizure requiring intubation. An EEG was normal and he was extubated the next day. On hospital day 7, the patient was ready for discharge, but appeared disoriented and had another seizure. A repeat EEG was again normal and he was discharged the following day (Schwartz et al, 2015).
2) CASE REPORT: A 20-year-old man with a history of poorly controlled type 1 diabetes developed a rapid onset of a tonic-clonic seizure lasting for approximately 2 to 3 minutes after smoking a spice product called "Black Mamba". He instructed his friends to inject him with 50 units of insulin to reportedly counteract the effects of the Spice product. Upon arrival he was awake with a Glasgow coma score of 14/15 and noted to be incontinent of urine. His blood glucose was 25.8 mmol/L upon arrival. He was observed in the ED for several hours and given 1 L of 0.9% NS with no further seizure-activity. His blood glucose was 9.3 mmol/L one hour after admission. At approximately 2 hours, the patient left against medical advice. Urinalysis collected at the time of admission detected metabolites of AM-2201; no other drugs were detected after an extensive analysis (McQuade et al, 2013).
3) CASE REPORT: A 48-year-old man with a long history of consuming cannabis on a monthly basis, ingested two-thirds of a g of a spice blend (K2 Summit Blend) and after 45 minutes he felt slightly "high" and ingested another one-third of a g of JWH-018 powder. He complained of nausea and feeling detached. His wife found him unresponsive and shaking violently; EMS witnessed a generalized tonic-clonic seizure. Upon arrival he was intubated due to copious foaming of the mouth and respiratory acidosis. Initial vital signs and ECG were normal. Fourteen hours after admission, the patient developed supraventricular tachycardia (heart rate: 186 to 214 beats/min) and hypotension (BP 59/43 mmHg). Electrical cardioversion (100 Joules) was successful. Following supportive care, the patient was extubated on day 2 and discharged on day 5 with no permanent sequelae (Tofighi & Lee, 2012).
4) CASE REPORT: A 25-year-old solider on active duty had a witnessed tonic-clonic seizure and was brought to the battalion aide station in a post-ictal state. He later reported smoking Spice approximately 3 hours prior to admission and had a history of smoking Spice and a pack of cigarettes daily. He was transported to a higher level of care, and a brain CT and toxicology screen were normal. Vital signs and laboratory studies were also normal. No additional seizures were reported (Bebarta et al, 2012).
5) CASE REPORT: A 19-year-old man with history of heavy cannabis use and a recent 2 month history of smoking K2 developed seizure-like activity, followed by foaming at the mouth and unconsciousness. This was followed by combativeness requiring 4-point restraints during transport; he appeared somnolent at the time of admission. He recovered uneventfully; his urine drug screen was positive for THC (184.7 ng/mL) only (Harris & Brown, 2013).
6) CASE REPORT: A 19-year-old man developed generalized seizures of 1 to 2 minutes while smoking an incense referred to as "Happy Tiger Incense" and was reportedly labelled as JWH-018 free. He was treated with midazolam prior to arrival to the ED. The patient was slightly confused upon arrival, but symptoms rapidly resolved with no further seizure activity. Laboratory studies were normal with a negative toxicology screen (except benzodiazepines). The patient was discharged after a brief observation period. Laboratory testing of the product was positive for JWH-018, JWH-081, JWH-250 and AM-2201 (Schneir & Baumbacher, 2012).
7) CASE REPORT: A 48-year-old man ingested ethanol and JWH-018 (confirmed by laboratory analysis) and developed a witnessed generalized seizure within 30 minutes of ingestion. The patient had another seizure during transport to the ED and another after arriving at the ED. Shortly after arrival, the patient was given lorazepam and intubated for airway protection. Ethanol was 3.8 mg/dL and creatinine phosphokinase was 2649 Units/L; a urine toxicology screen was negative for other drugs of abuse. Supraventricular tachycardia developed during the first day requiring electrical cardioversion; no further dysrhythmias occurred. The patient continued to do well and was discharged to home several days later (Lapoint et al, 2011).
8) CASE REPORT: A 48-year-old healthy man drank half a pint of vodka and smoked 3 g of spice and developed 2 episodes of generalized tonic clonic seizures the following morning while at work and another episode after arrival to the ED. Seizures resolved with lorazepam therapy. Laboratory studies were normal except for an increased creatine kinase concentration of 1200 units/L. A toxicology screen was negative for other agents; serum alcohol concentration was 140 mg/dL. A urine sample confirmed the presence of primarily JWH-018 (Pant et al, 2012).
9) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network during 2010, seizures developed in 17 (3.75%) cases. Severe agitation, hyperthermia, and seizures developed in 2 patients requiring sedation and intubation. In most patients, urine screening was negative. Only one patient who had a seizure had a positive urine drug screen for other agents (Forrester et al, 2011).
C) COMA 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 19-year-old man smoked a spice product ('Bonzai') twice, one evening and again the next morning, and developed tonic-clonic seizures after the second exposure. He became unresponsive and started vomiting repeatedly while lying prone. An EMS physician found him comatose with respiratory insufficiency requiring immediate intubation and mechanical ventilation. Shortly after admission, a bronchoscopy was performed and vomitus was found in the main bronchi. Several hours after removal of the vomitus, the patient was successfully extubated. The patient's clinical status improved and he was discharged on day 3. A blood serum sample collected 2 hours after admission was positive for JWH-122 (230 ng/mL), JWH-210 (7.8 ng/mL) and JWH-018 (0.39 ng/mL) (Hermanns-Clausen et al, 2013). Other agents found not related to this hospitalization included: citalopram (likely taken as a regular medication) and natural cannabinoids unlikely related to the clinical events reported during this admission.
b) CASE REPORT/INFANT: A 10-month old developed an altered mental status several hours after ingesting "potpourri". Upon admission he was unresponsive and rigid. His vital signs were significant for a temperature of 90.4 degrees F. Laboratory studies were significant only for a serum BUN of 32 mg/dL and lactic acid of 3.6 mmol/L. A toxicology screen and ethanol concentration were negative. Endotracheal intubation was performed for apneic periods and oxygen desaturation. Active warming was needed once during admission for hypothermia. By day 2, he was successfully extubated and discharged to home on day 3 without sequelae. Analysis of the substance ingested and serum analysis confirmed the presence of MAB-CHMINACA, a synthetic cannabinoid (Hawkins et al, 2015).
D) DROWSY 1) WITH POISONING/EXPOSURE a) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network during 2010, drowsiness developed in 86 (18.5%) cases and was one of the most common events observed (Forrester et al, 2011).
b) CASE REPORT/INFANT: A 10-month-old girl was found by her mother chewing on a "K2 cigarette". Upon admission, her physical exam and respiratory status were initially within normal limits and laboratory studies were unremarkable. However, about 90 minutes later she developed sedation and respiratory depression necessitating intubation. In addition, the patient was found to be positive for influenza A. Intubation was needed for 36 hours and she was easily extubated with no permanent sequelae. Blood and urine specimens were positive for AB-PINACA (42 ng/mL) and its metabolite AB-PINACA N-pentanoic acid (345 ng/mL) at the time of admission. A toxicology screen was negative for other agents (Thornton et al, 2015).
E) CATATONIA 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 36-year-old man, with a long history of schizophrenia and synthetic cannabinoid abuse, presented with illogical speech and paranoid ideations and a report of auditory hallucinations. He was admitted for psychiatric care and reported recent noncompliance with his outpatient medications and started smoking synthetic cannabis. His history was confirmed by a family member. The patient was restarted on clozapine and perphenazine. Twenty-four hours after admission the patient's speech was slower along with evidence of motor slowing and posturing. Lorazepam was added for a presumed diagnosis of catatonia. Despite temporary improvement in affect, 48 hours after hospitalization, he was withdrawn with increasing catatonia (ie, rigidity, inability to feed self) that worsened over the next several days. He required assistance with all activities of living; antipsychotics were discontinued. His clinical course was further complicated by aspiration pneumonia. Lorazepam was increased to 3 mg IM every 6 hours with no or minimal effect. On day 26, the patient received his first electroconvulsive therapy (ECT) and was noted to have immediate clinical improvement. Over the next 16 days, the patient had a total of 6 ECT treatments. After he recovered he reported an increase in smoking "K2" (2 to 3 times daily for 3 weeks) because it was less expensive than cannabis and continued to use it despite paranoia and increasing irritability until the day of admission. He denied any similar effects with prior use of smoking marijuana. He was discharged on day 46 with no residual symptoms of catatonia and maintained on clozapine 225 mg twice daily (Leibu et al, 2013).
b) CASE REPORT: A 16-year-old girl was transferred from an another hospital with altered mental status after smoking marijuana containing "K2". Upon arrival to the emergency department she was catatonic. Her vital signs were essentially normal with sinus tachycardia (heart rate 105 beats/min). Pupils were equal and reactive, but she was noted to have vertical nystagmus. The upper extremities had normal tone, while the lower extremities were slightly rigid and flexed. She was also unresponsive to verbal and painful stimuli. The remainder of her physical examination was normal. After 50 mg of IV diphenhydramine she began to slowly move her lips. Lorazepam was also given and the patient began to slowly speak. She was monitored overnight and her motor and verbal function improved and by the next morning she was ambulating and able to eat on her own and was discharged to home (Cohen et al, 2012).
F) CLOUDED CONSCIOUSNESS 1) WITH POISONING/EXPOSURE a) According to a report from the National Poison Data System (NPDS), 9 "Spice" exposures were reported in a five-state region, serviced by the Rocky Mountain Poison and Drug Center in Colorado, from September 2009 to April 2010. Three cases (33.3%) reported confusion ( Banerji et al, 2010).
b) CASE REPORT: A 16-year-old boy was admitted with altered mental status after smoking "Spice" about 5 hours prior to admission. He was admitted with agitation and was dysarthric with pressured speech. The patient appeared dystonic with some confusion. Vital signs were stable. His physical exam was normal with the exception of hypertonia of the upper and lower extremities and hyperreflexia with normal strength. Lorazepam was given. Urine and serum toxicology screens were negative. He gradually improved and was discharged to home within several hours (Cohen et al, 2012).
c) CASE REPORT: Chronic consumption of "Spice Gold" by a 20-year-old man, at a dose up to 3 g daily for 8 months, resulted in listlessness and an inability to think clearly (Zimmermann et al, 2009).
G) TREMOR 1) WITH POISONING/EXPOSURE a) Tremors have been reported in patients following exposure, via smoking, of "Spice" products that contain cannabinoid receptor agonists, including JWH-018 and JWH-073 (Cunning et al, 2010; Banerji et al, 2010).
H) MOOD DISORDER 1) WITH POISONING/EXPOSURE a) Alterations in mood and perception occurred in 2 individuals 10 minutes after smoking a cigarette containing 0.3 g of "Spice diamond" (Auwarter et al, 2009).
I) HALLUCINATIONS 1) WITH POISONING/EXPOSURE a) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network during 2010, hallucinations occurred in 50 (10.8%) cases and was one of the most common events observed (Forrester et al, 2011).
|
Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) NAUSEA AND VOMITING 1) WITH POISONING/EXPOSURE a) CASE REPORT: An 18-year-old man developed nausea, persistent vomiting with retching, tremors, and peripheral blurred vision approximately 30 minutes after smoking 1 oz of "K2 Summit", a dried herbal product, subsequently determined to contain JWH-018, a cannabinoid receptor agonist. With supportive therapy, the patient recovered. It is unclear whether the patient's symptoms were due to JWH-018 or an unidentified adulterant. Friends, who were also exposed to the same product, did not experience the same gastrointestinal effects (Cunning et al, 2010).
b) INCIDENCE: In a retrospective study of synthetic cannabinoid exposures (n=464) reported to the Texas Poison Center Network during 2010, vomiting occurred in 73 (15.%) cases and nausea developed in 46 (9.9%) cases and were two of the most common events observed (Forrester et al, 2011).
B) HYPEREMESIS 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 27-year-old man was admitted with persistent vomiting, paresthesia in the legs and the absence of urine for 2 days after ingesting a synthetic cannabinoid product the week before hospitalization. He was noted to be dehydrated with dry mucous membranes and unable to walk. Initial laboratory findings were as follows: creatinine 40,000 Units/L, serum myoglobin greater than 1000 ng/mL, lactic acid 2.9 mmol/L, phosphate 13.2 mg/dL (range, 2.4 to 4.6), hyponatremia and hypocalcemia. In addition, a CT scan showed extensive pneumomediastinum without evidence of airway or esophageal rupture. A urine drug screen was negative. Initial treatment included ondansetron and IV morphine for vomiting with minimal relief of symptoms. IV fluids and electrolyte repletion were also started. Despite significant rhabdomyolysis and acute renal failure, the patient did not require hemodialysis and gradually recovered with close monitoring of IV fluid and electrolyte repletion. All laboratory studies normalized by day 8 and the patient completely recovered (Argamany et al, 2016).
b) CASE REPORT: A 30-year-old man, with a history of long-term marijuana abuse, was admitted to the ER with repeated, cyclical, episodes of intractable nausea and vomiting following the use of synthetic cannabinoids ("Scooby Snacks" (laboratory analysis was positive for JWH-018, JWH-073, JWH-122, AM-2201 and AM-694)). Symptoms were not relieved by oral antiemetics. The patient reported that frequent, hot showers was temporarily effective in relieving symptoms. His usual pattern of use was to smoke synthetic marijuana daily and at times he was smoking hourly including use up to several times at night. During this admission, he was treated with IVFs and IV ondansetron and symptoms resolved. Upon follow-up 3 months later, the patient was abstinent from marijuana and synthetic cannabinoid products and had no further episodes of nausea and/or vomiting (Hopkins & Gilchrist, 2013).
C) ABDOMINAL DISTENSION 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 29-year-old man with a 5-year history of regular synthetic cannabinoid (Bonzai(TM)) use was admitted to the ED with abdominal distension, tenderness and nausea and vomiting. An abdominal x-ray showed a large amount of gas in the fundus. A nasogastric tube was inserted with 6 L of brownish black fluid returned. A CT of the abdomen showed a huge stomach, elongated towards the pelvis and accompanying hepatic portal venous gas. No perforations were detected. An emergent endoscopy was performed that showed severe mucosal edema and patchy ischemic areas around the stomach. The patient required hospital admission for ongoing endoscopic surveillance, nasogastric decompression, and broad spectrum antibiotic therapy for 7 days when the findings returned to normal. The exact mechanism for acute gastric dilation was not certain, but it was considered to be mediated by binding to cannabinoid binding 1 receptors (Sevinc et al, 2015).
|
Genitourinary |
3.10.2) CLINICAL EFFECTS
A) ACUTE RENAL IMPAIRMENT 1) WITH POISONING/EXPOSURE a) SUMMARY/CASE REPORTS: During 2012, the Centers for Disease Control and Prevention reported acute kidney injury (AKI) in teenagers and young adults following synthetic cannabinoid use in several states. Of the 16 patients that developed AKI, all required hospitalization. Symptoms included nausea and vomiting (all cases) and abdominal, flank or back pain in most patients (n=12). The peak serum creatinine ranged from 3.3 to 21 mg/dL and occurred 1 to 6 days after exposure. Of the 8 patients that underwent a renal biopsy, 6 had evidence of acute tubular injury and 3 had acute interstitial nephritis. Hemodialysis was needed for 5 patients and 4 patients received corticosteroid therapy; everyone recovered. No other source for AKI was found in these patients. Although no single product or brand was used by each individual, one product was detected in 5 of the 16 patients. XLR-11 (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl) methanone) is known as a novel fluorinated synthetic cannabinoid that became available during early 2012 (Centers for Disease Control and Prevention, 2013).
b) CASE SERIES: A cluster of acute kidney injury (AKI) has been associated with smoking synthetic cannabinoids in 9 young adult males. All patients required hospitalization. In the majority of cases (n=8), the initial symptoms included an acute onset of severe nausea, emesis, and back or abdominal pain. One patient developed gross hematuria and one developed uremic encephalopathy (BUN 177 mg/dL). Of those cases who could recall the onset of symptoms with the time of synthetic cannabinoid use, the average time was approximately 30 min and 24 hours (median: 8 to 12 hours) after smoking the product. Serum creatinine concentrations peaked 2 to 7 days after the onset of symptoms; median peak creatinine 7.9 mg/dL (range: 2.6 to 17.7 mg/dL). Renal ultrasound showed a nonspecific increase in cortical echogenicity without hydronephrosis in seven patients. Autoimmune and infectious diagnostic studies were negative and no other causes of AKI were identified. Most patients (n=7) recovered with supportive care one day after peak serum creatinine was reached. In two patients, one required corticosteroid therapy and one required hemodialysis. No permanent sequelae occurred (Buser et al, 2014).
c) CASE REPORT: A 27-year-old man was admitted with persistent vomiting, paresthesia in the legs and the absence of urine for 2 days after ingesting a synthetic cannabinoid product the week before hospitalization. He was noted to be dehydrated with dry mucous membranes and unable to walk. Initial laboratory findings were as follows: creatinine 40,000 Units/L, serum myoglobin greater than 1000 ng/mL, lactic acid of 2.9 mmol/L, phosphate of 13.2 mg/dL (range, 2.4 to 4.6), hyponatremia and hypocalcemia. In addition, a CT scan showed extensive pneumomediastinum without evidence of airway or esophageal rupture. A urine drug screen was negative. Initial treatment included ondansetron and IV morphine for vomiting with minimal relief of symptoms. IV fluids and electrolyte repletion were also started. Despite significant rhabdomyolysis and acute renal failure, the patient did not require hemodialysis and gradually recovered with close monitoring of IV fluid and electrolyte repletion. All laboratory studies normalized by day 8 and the patient completely recovered (Argamany et al, 2016).
d) CASE REPORT: A 26-year-old man with a history of chronic (2 to 3 times daily for one year) synthetic cannabinoid use developed a sudden onset of abdominal pain, nausea, vomiting and low back pain. On day 2, his serum creatinine and BUN peaked at 7.74 and 39 mg/dL, respectively. His symptoms and laboratory studies were consistent with acute kidney injury (AKI). Diagnostic studies were normal. By day 6, he was discharged with a serum creatinine of 3.09 mg/dL, and by day 23 it was 1.1 mg/dL. Following liquid chromatography screening, only XLR-11 and UR-144, newly described synthetic cannabinoids, were detected (Thornton et al, 2013).
|
Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) RHABDOMYOLYSIS 1) WITH POISONING/EXPOSURE a) CASE REPORT: A 27-year-old man was admitted with persistent vomiting, paresthesia in the legs and the absence of urine for 2 days after ingesting a synthetic cannabinoid product the week before hospitalization. He was noted to be dehydrated with dry mucous membranes and unable to walk. Initial laboratory findings were as follows: creatinine 40,000 Units/L, serum myoglobin greater than 1000 ng/mL, lactic acid of 2.9 mmol/L, phosphate of 13.2 mg/dL (range, 2.4 to 4.6), hyponatremia and hypocalcemia. In addition, a CT scan showed extensive pneumomediastinum without evidence of airway or esophageal rupture. A urine drug screen was negative. Initial treatment included ondansetron and IV morphine for vomiting with minimal relief of symptoms. IV fluids and electrolyte repletion were also started. Despite significant rhabdomyolysis and acute renal failure, the patient did not require hemodialysis and gradually recovered with close monitoring of IV fluid and electrolyte repletion. All laboratory studies normalized by day 8 and the patient completely recovered (Argamany et al, 2016).
b) CASE REPORT: A 27-year-old man, with a history of schizophrenia and noncompliance with his medications, was brought to an ED for extreme agitation and disruptive behavior. He was found eating grass at a local field. Witnesses reported that he had been smoking K2 (later reported to be "Mr. Big Shot"). Upon admission he was combative requiring IV sedation with midazolam and haloperidol. He was found to be hyperthermic (initial temperature 106.1 degrees F) and tachycardic (heart rate 173 beats/min). External cooling measures and aggressive IV hydration were started. Creatinine, lactate and creatinine phosphokinase were all elevated at the time of admission. A urine toxicology screen was negative for drugs of abuse. Once stabilized he was admitted to a telemetry unit for further management. His CPK (rose to 29,580) and liver enzymes continued to increase and he was transferred to the ICU where he received aggressive hydration with lactate ringers solution. CPK peaked (57,050) on day 2. By day 4, his laboratory studies were improving and he was moved to a general medicine floor. During his hospital stay he intermittently developed episodes of psychosis/agitation that were successfully treated with haloperidol and olanzapine. By day 10, he was transferred to a psychiatry unit for further management of his schizophrenia (Sweeney et al, 2016).
c) CASE REPORT: A 23-year-old man with no history of psychiatric illness developed severe rhabdomyolysis and acute psychosis after using a synthetic cannabinoid (SC) (ie, Mr. Nice Guy). He was admitted with severe agitation and an altered mental status. Prior to admission, he was observed banging his head on the ground and hitting himself. His initial creatine phosphokinase (CPK) was 44,300 International Units. A urine drug screen was positive for cannabinoids only. Treatment included aggressive IV fluid therapy and lorazepam. His CPK level gradually declined over a 9 day period with no renal injury reported. Due to ongoing episodes of paranoia, severe agitation and psychotic behavior, the patient was hospitalized for 15 days and gradually returned to a normal affect. He reported that he had sporadically begun to use SCs over the prior 6 months, and began using it daily 2 weeks prior to his hospital admission (Durand et al, 2015).
|