1) The usual form in which this drug is consumed is as cigarettes referred to as reefers, joints, or numbers. Marijuana contains 1 to 3% THC(Nahas, 1984).
2) Hashish, which is usually 5 to 10 times more potent than the flowering tops, is a light brown to dark black resinous material which is usually smoked in a pipe. Hashish contains 3 to 6% THC (Nahas, 1984).

1) EDIBLE MARIJUANA: In recent years, edible marijuana has been available to consumers that use cannabis for medical purposes and in those states where it is legalized in the US. Common products include baked goods, beverages, candy and chocolate. In one study, 75 products were evaluated to determine the amount of cannabidiol and THC found in the various products. The results indicated that 17% of products were accurately labeled, 23% were under labeled and 60% were over labeled with respect to THC content. Potential adverse effects could occur in individuals that ingest products that contained more THC than labeled (Vandrey et al, 2015).
2) INADVERTENT EXPOSURE: Several individuals were inadvertently exposed to marijuana after eating brownies purchased from a sidewalk vendor in California. Typical symptoms lasted several hours and all patients recovered. The authors suggested that marijuana should be considered as a potential contaminant in food when investigating a possible foodborne outbreak (Centers for Disease Control and Prevention, 2009).

1) Although much less common, intravenous use of the oil has also been described, and associated with high mortality.

1) Marijuana purported to be "super grass" or products sold as the active ingredient THC, frequently turn out to contain the more dangerous and potent illicit drug phencyclidine.

1) CAPSULES: It comes in round, amber, soft gelatin capsules filled with sesame oil in which either 2.5, 5, or 10 mg of THC is dissolved.
2) ORAL SOLUTION: Syndros (R), an oral solution containing dronabinol, is available as a 5 mg/mL clear, pale yellow to brown solution supplied in a multi-dose clear, amber colored 30 mL glass bottle. The formulation also contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol (Prod Info SYNDROS(TM) oral solution, 2016).

1) PESTICIDE RESIDUE: A study was conducted to quantify the potential amount of pesticides and other chemicals cannabis consumers may be exposed to through inhaled cannabis smoke. Three different devices were studied and included hand-held glass pipe, unfiltered water pipe and a filtered water pipe. Various pesticides including diazinon, paclobutrazol, bifenthrin, and permethrin were recovered in smoke condensate. However, the total amount of pesticide residue varied significantly depending on the device used with the highest quantity found in the hand-held pipe (ranging between 60.3% and 69.5%), followed by the unfiltered water pipe (ranging between 42.2% and 59.95) and the least amount of residue in the filtered water pipe (ranging between 0.08% and 10.9%) (Sullivan et al, 2013).

a) An increase in heart rate and cardiac output may follow marijuana exposure, the response is dose-related (Shukla & Moore, 2004; DiGregorio & Sterling, 1987). The heart rate may increase as much as 20 to 50 beats per minute.
b) CASE REPORT: A 2-year-old girl with a family history of childhood seizures (a paternal aunt) presented with fluttering of her eyelids, shaking of her arms, ataxia, lethargy, tachycardia (HR 144 bpm), mydriasis and sluggish pupil reactivity after ingesting an unknown quantity of marijuana. A blood toxicology screen was positive for cannabinoids, specifically 11-nor-delta-9-THC-9-carboxylic acid, with a level of 67 ng/mL. Following supportive care, she recovered and was discharged home within 24 hours of admission (Bonkowsky et al, 2005).
c) CASE REPORT: A 35-year-old woman presented to the hospital with a one-month history of headaches and hypertension (a sitting BP of 179/119 mmHg). After taking amlodipine (10 mg once daily) tablets, her blood pressure improved to 159/107 mmHg. Approximately 20 to 30 minutes after smoking cannabis while in the hospital, she experienced palpitations, chest pain, and shortness of breath. Her blood pressure and pulse rate were 233/140 mmHg and 150 bpm, respectively. An ECG revealed a narrow complex tachycardia, confirmed as a typical atrial flutter with 2:1 atrioventricular block, after the intravenous use of adenosine. The cardiac rhythm degenerated into atrial fibrillation (a rate of 146 bpm). Following treatment with flecainide, sinus rhythm was restored. She recovered and was discharged home without further sequelae (Fisher et al, 2005).
d) CHRONIC USE: Chronic cannabis use has been associated with supraventricular cardiac dysrhythmias, which usually do not require treatment. However, there have been individual cases of lethal ventricular dysrhythmias reported in the literature (Reece, 2009).

a) A brugada-like ST segment abnormality was reported in a 19-year-old man who had a syncopal episode after deeply inhaling a marijuana cigarette. Examination and physiologic studies were negative for vasovagal mediated syncope. Urine and blood toxicology screening showed markedly elevated THC concentrations. Echocardiogram was normal; the ECG changes resolved and could not be reproduced with procainamide challenge. The authors suggested that the ST segment abnormalities are likely due to partial sodium channel agonist activity, and that these dysrhythmias are self-limiting and do not require further electrophysiologic evaluation (Daccarett et al, 2007).

a) A slight elevation in blood pressure occurs commonly and significant hypertension has been reported (Kosior et al, 2001; Kosior et al, 2000; Beaconsfield et al, 1972).
b) CASE REPORT: A 35-year-old woman presented to the hospital with a one month history of headaches and hypertension (a sitting BP of 179/119 mmHg). After taking amlodipine (10 mg once daily) tablets, her blood pressure improved to 159/107 mmHg. Approximately 20 to 30 minutes after smoking cannabis while in the hospital, she experienced palpitations, chest pain, and shortness of breath. Her blood pressure and pulse rate were 233/140 mmHg and 150 bpm, respectively. An ECG revealed a narrow complex tachycardia, confirmed as a typical atrial flutter with 2:1 atrioventricular block, after the intravenous use of adenosine. The cardiac rhythm degenerated into atrial fibrillation (a rate of 146 bpm). Following treatment with flecainide, sinus rhythm was restored. She recovered and was discharged home without further sequelae (Fisher et al, 2005).

a) CASE REPORT: A 21-year-old man without any risk factors developed an acute myocardial infarction after drinking a large amount of alcohol and smoking one marijuana cigarette the night prior to admission. ECG revealed ST segment elevation of 1 mm in leads II, III and aVF. During an angiography, two clots in his left anterior descending coronary artery were found; a large proximal clot and a distal 100% blockage. Additionally, he had a right dominant coronary circulation and a large area of anteroapical hypokinesis. Although the initial blood tests revealed no troponin or creatine kinase (CK) rise, CK levels 12 hours and 24 hours after admission were 547 Units/L and 1330 Units/L, respectively. A urine toxicologic screen was positive for cannabinoids but cocaine and other sympathomimetics were not detected. Following supportive care, he recovered and was discharged 5 days post-admission (Caldicott et al, 2005).
b) CHRONIC USE/CASE SERIES: In a larger study of adults with a history of chronic cannabis use, a significant association between chronic use and myocardial infarction was observed. A dose response effect, with adjusted hazard ratios of 2.5 and 4.2, was found for less than weekly and weekly use of cannabis, respectively (Reece, 2009).

a) Atrial fibrillation has been reported in several patients after smoking marijuana (Kosior et al, 2001; Kosior et al, 2000; Singh, 2000).

a) In another study, Mathew and Wilson (1993) found that the cerebral blood flow increase was not related to plasma levels of tetrahydrocannabinol.

a) In prospective studies of chronic marijuana smokers compared to tobacco smokers, inhalation of marijuana was associated with a 4 to 5-fold increase in blood carboxyhemoglobin level, a 3-fold increase in amount of tar inhaled, and an increased respiratory tract retention of tar (Wu et al, 1988; Tashkin et al, 1988).

a) Long-term smoking of marijuana has been associated with chronic respiratory symptoms such as sore throat, rhinitis, bronchitis, and deterioration of pulmonary function suggesting airway narrowing (Tashkin et al, 1980; Tilles et al, 1986; Wu et al, 1988; Bloom et al, 1987). Studies have also suggested that chronic exposure to cannabis smoke can stimulate inflammation of the airways as well as obstruction and hyperinflation. Emphysema-like changes have also been noted (Reece, 2009).

a) PARAQUAT CONTAMINATION: There has been a concern over paraquat contamination of marijuana possibly producing lung disease following inhalation of smoke. There is good evidence to show that the paraquat is destroyed by the burning cigarette which produces bipyridyl.
b) Marijuana alone can produce changes in pulmonary function.
c) A 1983 survey of confiscated marijuana found 3.6% of 910 specimens to contain detectable paraquat. States closer to Mexico had the highest rate of contamination (12.8% of 180 specimens). Combustion testing indicated that 0.2% of paraquat passes into smoke.

a) Marijuana use may potentiate seizures in patients with existing seizure disorders.
b) CASE REPORT: A 2-year-old girl with a family history of childhood seizures (a paternal aunt) presented with fluttering of her eyelids, shaking of her arms, ataxia, lethargy, tachycardia (HR 144 bpm), mydriasis and sluggish pupil reactivity after ingesting an unknown quantity of marijuana. The authors suggested that the ingestion of marijuana may have lowered seizure threshold in a predisposed child. A blood toxicology screen was positive for cannabinoids, specifically 11-nor-delta-9-THC-9-carboxylic acid, with a level of 67 ng/mL. Following supportive care, she recovered and was discharged home within 24 hours of admission (Bonkowsky et al, 2005).

a) REM rebound has occurred following withdrawal of large, but not small, doses.

a) NABILONE: Drowsiness was reported in 52% of patients (n=132) who received nabilone orally during placebo-controlled clinical trials (Prod Info CESAMET(TM) oral capsules, 2006).

a) Drowsiness and stupor occurs rapidly after accidental ingestion of marijuana by children.
b) Coma has been reported in children after ingestion of hashish or marijuana (Appelboam & Oades, 2006; Macnab et al, 1989; Lacroix et al, 1989). Recovery generally occurs within 6 to 12 hours (Macnab et al, 1989; Pettinger et al, 1988).

a) NABILONE: Euphoria was reported in 11% of patients (n=132) who received nabilone during placebo-controlled clinical trials (Prod Info CESAMET(TM) oral capsules, 2006).

a) Recent (short-term) memory loss has been shown to occur after THC exposure. Studies have been split as to whether the impairment continues after an exposure (Schwartz, 1991; Schwartz et al, 1989).
b) CASE REPORT: A 6-year-old child developed transient global amnesia, ataxia, and sinus tachycardia after ingesting cookies containing marijuana. A urine toxicologic screen was positive for cannabinoids. The child recovered, with his memory returning to normal, 14 hours postingestion (Shukla & Moore, 2004).

a) NABILONE: Vertigo was reported in 52% of patients (n=132) who received nabilone orally during placebo-controlled clinical trials (Prod Info CESAMET(TM) oral capsules, 2006).

a) NABILONE: Concentration difficulties were reported in 12% of patients (n=250) who received nabilone orally during controlled clinical trials (Prod Info CESAMET(TM) oral capsules, 2006).

a) Whether or not marijuana use affects human cognition remains controversial. Some studies have reported some degree of cognitive impairment from chronic marijuana use (Block & Ghoneim, 1993; Schwartz et al, 1989), while others have found that impairments were absent or negligible (Block & Ghoneim, 1993).
b) Cognitive impairments may depend on the frequency of chronic use (Block & Ghoneim, 1993).

a) Other studies have reported little or no residual impairment of cognitive performance several hours after inhalational marijuana use (Barnett et al, 1985) (Cone & Johnson, 1986) (Heishman et al, 1989)(Leirer et al, 1989). Cone et al (1988) found that subjects ingesting marijuana rather than smoking it experienced behavioral signs for up to 11.5 hours following ingestion, which may mimic residual effects.
b) ALCOHOL/MARIJUANA: Chait & Perry (1994) studied moderate doses of alcohol and marijuana, alone and in combination, on the performance of regular users and found little evidence that impairment persisted 10 hours later.

a) ANTICHOLINERGIC EFFECT: An 18 year-old man developed anticholinergic symptoms including dry mouth, excessive thirst and difficulty urinating after being enticed by his friends to try "bhang" (an oral form of cannabis found in India) for the first time. Following the ingestion he also complained of restlessness, anxiety, and abdominal pain. There was no evidence of psychosis or affective disorder and his physical exam (ie, dry mouth, urinary retention and tachycardia) was consistent with his symptoms. Treatment included lorazepam 2 mg intramuscularly. The patient became calmer, slightly drowsy and was able to void. He was discharged a short time later. On follow-up the next day, the patient was symptom free and 2 days later his urine test was positive for a trace amount of cannabis (Mangot, 2013).

a) NABILONE: Ataxia was reported in 14% of patients (n=132) who received nabilone orally during placebo-controlled clinical trials (Prod Info CESAMET(TM) oral capsules, 2006).

a) CASE REPORT: Ataxia and mild nystagmus was reported in a 4-year-old boy who appeared "drunk" with an otherwise normal neurologic exam. Three hours after observation, the patient had no signs of ataxia and was acting appropriately for age. The patient volunteered that he had smoked an "L" given to him by his mother (a recurring pattern), and described in detail the smoking of a marijuana cigarette. A urine screen for cannabinoids was positive. Follow-up with child protective services was performed (Blackstone & Callahan, 2008).
b) CASE REPORT: A 2-year-old girl with a family history of childhood seizures (a paternal aunt) presented with fluttering of her eyelids, shaking of her arms, ataxia, lethargy, tachycardia (HR 144 bpm), mydriasis and sluggish pupil reactivity after ingesting an unknown quantity of marijuana. A blood toxicology screen was positive for cannabinoids, specifically 11-nor-delta-9-THC-9-carboxylic acid, with a level of 67 ng/mL. Following supportive care, she recovered and was discharged home within 24 hours of admission (Bonkowsky et al, 2005).

a) CASE REPORT: A 2-year-old girl with a family history of childhood seizures (a paternal aunt) presented with fluttering of her eyelids, shaking of her arms, ataxia, lethargy, tachycardia (HR 144 bpm), mydriasis and sluggish pupil reactivity after ingesting an unknown quantity of marijuana. A blood toxicology screen was positive for cannabinoids, specifically 11-nor-delta-9-THC-9-carboxylic acid, with a level of 67 ng/mL. Following supportive care, she recovered and was discharged home within 24 hours of admission (Bonkowsky et al, 2005).

a) CANNABINOID HYPEREMESIS SYNDROME: Paradoxical, cyclic vomiting syndrome has been reported in individuals that chronically use marijuana (Wild & Wilson, 2012; Donnino et al, 2011). In three male adults, repeated episodes of vomiting occurred after smoking marijuana, with no obvious pathology found (ie, physical exam, laboratory studies and diagnostic studies were normal). Two patients reported frequent bathing to help alleviate symptoms. Each patient was encouraged to stop using marijuana with no recurrence of symptoms. Upon reuse, symptoms would recur almost immediately (Donnino et al, 2011). Although there is no clear mechanism, cannabinoid 1 (CB1) receptors found in the gastrointestinal mucosa are known to suppress peristalsis and gastric emptying in a dose-dependent manner.
b) CLINICAL FEATURES: Cannabinoid hyperemesis syndrome is frequently observed in men with chronic daily cannabis use (Williamson et al, 2014; Wallace et al, 2011). Similar episodes of hyperemesis have been reported in several cases of women that chronically used cannabis (Wild & Wilson, 2012; Schmid et al, 2011). It may be accompanied by compulsive hot water bathing/showering behaviors (lasting up to several hours or multiple times per day) to relieve symptoms. Many patients described a relief of cyclic vomiting and epigastric pain with exposure to hot water. Extensive diagnostic imaging (eg, abdominal x-rays, CT, esophagogastroduodenoscopy (EGD), barium swallow) and laboratory studies were normal. Symptomatic improvement usually occurred with the abstinence of cannabis, and intravenous hydration in some cases. Antiemetics (ie, metoclopramide, ondansetron) were not found to be useful in most cases (Williamson et al, 2014; Wallace et al, 2011).
c) CASE REPORT/PREGNANCY: Cannabinoid hyperemesis syndrome was reported in a 26-year-old woman with chronic daily cannabis use for 13 years who was 10 weeks pregnant at presentation. The patient had stopped daily cannabis use about 10 days prior to hospitalization when she had learned she was pregnant. Initially, the patient was treated with standard antiemetics with no relief. The patient reported symptomatic relief after frequent, hot showers; all antiemetics were stopped. She also reported that she had episodes of recurrent vomiting about twice per year over the past 3.5 years associated with daily cannabis use. The patient was discharged the following day. All symptoms resolved within 2 weeks. The patient remained abstinent and her pregnancy progressed without further complications (Schmid et al, 2011).

a) CASE REPORT: A 29-year-old man presented with a 1-day history of abdominal pain, nausea, and vomiting. Physical examination showed a distended and diffusely tender abdomen. Initial laboratory tests revealed an amylase level of 1,997 IU/mL (reference value 0 to 180 IU/mL), a WBC count of 17.2 x 10(9)/liter (reference value 4 to 11 x 10(9)/liter) and a C-reactive protein level of 132 mg/L (reference value 0 to 10 mg/L). An abdominal CT scan indicated an inflamed pancreas and an ERCP confirmed that there were no gallstones, biliary tree pathologies, or structural abnormalities of the pancreas. At this time, the patient admitted to an increase in cannabis use over the past few weeks prior to presentation of symptoms.

a) CHRONIC EXPOSURE: Studies have associated the long term use of cannabis in humans with significant bone loss. It appears to interfere with bone metabolism. Chronic use has also been associated with severe alveolar bone loss from the jaw, which is often found with erosive periodontitis (Reece, 2009).

a) DRONABINOL: No teratogenicity was noted in animal reproduction studies involving mice and pregnant rats administered dronabinol at up to 30 times and 5 to 20 times the maximum recommended human dose, respectively Maternal toxicity appeared dose-dependent. There are no well-controlled dronabinol studies in pregnant women (Prod Info SYNDROS(TM) oral solution, 2016).
b) NABILONE: Nabilone administration in pregnant rats at doses up to 12 mg/kg/day (approximately 16 times the human dose on a body surface area basis) and in pregnant rabbits at doses up to 3.3 mg/kg/day (approximately 9 times the human dose on a body surface area basis) did not appear to have teratogenic effects; however, dose-related developmental toxicity, including increases in embryolethality, fetal resorptions, decreased fetal weights, and pregnancy disruptions, occurred in both species (Prod Info CESAMET(TM) oral capsules, 2006).

a) Significant loss of maze learning in rats prenatally exposed to cannabis resin extract has been described. There has been conflicting evidence of developmental and other defects in offspring due to prenatal delta-9-tetrahydrocannabinol (THC) exposure. Adverse effects reported in some studies may be due to THC induced maternal toxicity, rather than direct adverse effects of THC on the embryo of fetus (Hutchings & Dow-Edwards, 1991).

a) RABBITS: In a rabbit study, marijuana was embryotoxic but not teratogenic (Rosenkrantz et al, 1986).
b) RATS: A study by Hutchings & Dow-Edwards (1991) incorporated pair-fed controls and fostering controls. Tetrahydrocannabinol (THC) administration from gestational day 8 through birth resulted in a significant dose-related increase in offspring mortality rates. Birth weights were also reduced in a dose-related fashion. The low dose group (15 mg/kg/day) quickly increased in weight in the postnatal period, while offspring born to dams in the high dose group (50 mg/kg/day) had a prolonged period of delayed growth. There were no apparent effects of THC treatment on offspring activity. Nipple attachment in the high dose group appeared delayed; however, it did not differ from the behavior of pups born to untreated control dams that had been fed similar amounts of food and water as the THC-exposed dams.
c) Decreased growth rates and abnormal behaviors have been inconsistently reported in other studies in which rats or mice were prenatally exposed to THC.
d) RATS: Extremely high doses of tetrahydrocannabinol (THC) administered to pregnant rats during various gestational periods have been associated with nonviable litters. Maternal toxicity manifested as suppressed weight gain during pregnancy. Lower doses (which also suppressed maternal weight gain) were associated with decreased pup birth weight but not with effects on litter size. At 21 days of age, the THC pups were similar in weight as the controls and did not significantly differ from controls in behavioral test performance (Abel, 1984).

a) RAT: Navarro et al (1994) exposed pregnant rats to hashish extract and measured motor behavior and dopaminergic activity in the adult offspring. Spontaneous locomotor activity was not affected; however, induced stereotypical behaviors were altered in males but not females. This sexual dimorphism paralleled findings of an increased D2 receptor density in males.

a) A study of pregnant sheep found that the acute maternal inhalation of marijuana smoke produced changes in the fetus on electroencephalography (EEG) (Szeto et al, 1991). Repeated exposure (3 to 4 times) to marijuana smoke, however, was not associated with EEG changes, suggesting the development of tolerance in the fetus. The inhalation of placebo smoke did not produce the EEG changes.

a) Shortly after smoking marijuana (eg, 1 hour), tetrahydrocannabinol (THC) levels in breast milk were much higher than those in the maternal plasma (Perez-Reyes & Wall, 1982). THC and metabolites were measurable in a stool sample from a nursing infant, indicating THC absorption and biotransformation.
b) Exposure of infants and children may occur through the ingestion of breast milk or dairy milk of animals that consumed large quantities of cannabis.

a) DRONABINOL: There is limited data on the presence of dronabinol in human milk (Prod Info SYNDROS(TM) oral solution, 2016).
b) NABILONE: No reports describing the use of nabilone during human lactation are available and the effects on the nursing infant from exposure to the drug in milk are unknown. It is not known if nabilone affects the quantity and composition of human milk. Because some cannabinoids are excreted into human milk, the use of nabilone is not recommended in women who choose to breastfeed their infants (Prod Info CESAMET(TM) oral capsules, 2006).

a) MOUTH CANCER: Marijuana smoking has been implicated as a possible cause of mouth cancer (Caplan, 1991).
b) HEAD AND NECK CARCINOMA: Donald (1986) reported six cases of head and neck carcinoma in regular marijuana users under age 40. Four of the six were also tobacco smokers and alcohol users, which the author speculated may have had a synergistic carcinogenic effect.
c) It is difficult to experimentally study the carcinogenic potential of marijuana in humans. Obtaining a study sample of persons who consistently use marijuana over a long period of time but are not exposed to other carcinogens (eg, tobacco smoke) and can be evaluated over many years is problematic.
d) An estimated exposure to 1 or 2 marijuana cigarettes per day is reportedly sufficient to increase one's risk of lung cancer (Wu, 1988). This estimate is based on a comparison of the constituents of marijuana and tobacco smoke and the probable delivery of these constituents according to smoking behavior.

a) Marijuana smoke residue has been rated as an equivocal tumorigenic agent based on in vitro study results (RTECS, 1996).
b) Experimental animal studies have shown that tar produced by burning marijuana is more carcinogenic than tar from tobacco smoke (Jaffe, 1990).
c) Lung cancer due to smoking is difficult to produce in experimental animals, and alternative methods are used to determine carcinogenic potential (Cohen, 1979). A substituted method of determining carcinogenicity is painting tar extracts on the skin of mice. Tar obtained from marijuana produced sebaceous gland metaplasia and other cellular changes which correlate with carcinogenicity (Cottrell et al, 1973).
d) Exposure of human and animal lung cell cultures to marijuana smoke has been associated with abnormalities in cellular growth which represented an early phase of malignant cell transformation (Leuchtenberger et al, 1973). The effect was similar to that evoked by tobacco smoke.

a) Pharmacodynamic models have predicted that a blood THC concentration between 7 and 29 ng/mL is necessary to produce 50% of the maximal subjective high effect (Cone & Huestis, 1993).

a) Urine THC analysis is especially vulnerable to adulterants. Addition of salt, Visine(R), soap, bleach, Drano(R), goldenseal, and vinegar may all produce false negatives. All but Visine(R) are detectable by pH, specific gravity, and cloudiness assessments, which should always be performed (Schwartz & Hawks, 1985; Mikkelsen & Ash, 1988).
b) Ingestion of 3000 mg of ascorbic acid, 1560 mg of golden seal root, and 750 mL of cranberry juice did not interfere with EMIT testing of urine for cannabinoids. Levels were reduced but still detectable (Schwartz & Bogema, 1988).
c) The addition of Visine (R) eye drops in concentrations of 20 to 100 mL per liter of urine resulted in false negative urine assays for cannabinoids using the EMIT and TDx assays. This effect was more evident when glass specimen containers were used. Studies with various components of Visine (R) showed the benzalkonium chloride to be primarily responsible, although the borate buffer had some effect (Pearson et al, 1989).
d) False negative results were seen in cannabinoid EMIT assays with the adulterants sodium hypochlorite, Joy (R) liquid dish detergent, and sodium chloride. The amount of sodium chloride needed to produce this effect (greater than 50 g/L) would preclude its practical use. When the same adulterants were tested with an RIA assay or the Abbott TDx assay, no false negatives were seen, but false positives occurred with the Joy (R) detergent (Warner, 1989).

a) PROTON PUMP INHIBITORS
b) COMMERCIAL BABY WASHES

a) However, THC metabolites are excreted at different times after smoking marijuana; assays to detect them can pinpoint the time of usage to recent (within the previous 24 hours of measurement) or past use (Manno et al, 1994).

a) An average of 16 days (up to 46 days) before the first negative and up to 77 days (average 27 days) before it was less than the cut off of 20 ng/mL for 10 consecutive days (Ellis et al, 1985).
b) A study of 13 chronic marijuana users demonstrated positive EMIT urine assays for 3 to 25 days after cessation of smoking. The excretion half-life for the delta-THC-7-oic acid metabolite ranged from 0.8 to 9.8 days (Johansson & Halldin, 1989).

a) Other studies have shown similar results (Cone & Johnson, 1986; Mason et al, 1983; Perez-Reyes et al, 1983).
b) Passive inhalation of smoke may produce detectable levels of the metabolites in the urine, but generally only under conditions in which the marijuana smoke is so concentrated in the atmosphere as to be irritating and noxious (Cone et al, 1987).
c) Sidestream smoke from 4 to 16 marijuana cigarettes for 1 hour/day for 6 days produced positive urine assays in 5 volunteers (Cone & Johnson, 1986).

a) Positive salivary levels of THC suggest marijuana smoking within a 12 hour period (Verebey et al, 1986).
b) One study indicated that salivary THC levels, as determined by GC-mass spectrometry, correlated well with a subjective index of intoxication and with heart rate (Menkes et al, 1991).

a) Hair analysis is still controversial; it can detect drug usage up to 90 days later and cut-off values are lower for hair than urine. However, THC is excreted into the urine for a long time following drug use and hair contains only tiny amounts of THC, making hair analysis more expensive and no more useful than urine for marijuana detection (DuPont & Baumgartner, 1995; Mieczkowski, 1995).
b) Cirimele et al (1995) have reported a method for testing hair for cannabinoids; they suggest using pubic hair for testing. Jurado et al (1995) have developed a method for measuring cannabinoids, opioids, and cocaine simultaneously in hair.

1) The assay detects major urinary metabolites of delta(9)-tetrahydrocannabinol, with a detection limit (sensitivity) of 50 ng/mL for 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid.
2) Also available is a qualitative EMIT urine assay, which has a detection limit of 200 ng/mL for 11-nor-delta(9)-carboxylic acid.
3) Two systems are available, an EMIT-st (single test) and EMIT (d.a.u) drugs of abuse in urine. The first has a sensitivity of 100 ng/mL, the second 20 ng/mL (DiGregorio & Sterling, 1987).

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) For mild and moderate toxicity, treatment consists primarily of supportive care. Most patients do not require any specific treatment, and especially with inhalational exposure, symptoms should resolve in a few hours.
b) Ingestions may have prolonged duration of symptoms, especially in small children. In severe overdoses, especially in the pediatric population, marked obtundation may result and may require intensive care evaluation and management (Wang et al, 2013) and airway support.
c) There have also been reports of atrial fibrillation and other cardiac dysrhythmias in patients after smoking marijuana that should receive supportive care.
d) ABSTINENCE SYNDROME: Abrupt discontinuation of chronic use can cause agitation, apprehension, tremor, insomnia, rhinorrhea, diarrhea and diaphoresis.

a) CHRONIC USE: Cannabinoid hyperemesis syndrome (CHS) has been described in some chronic cannabis users. Men (77%) are more likely to complain of this syndrome (Nicolson et al, 2012). Patients that do not remain abstinent, often have recurring visits to the ED for repeated episodes of vomiting (Hickey et al, 2013).
b) MECHANISM: The mechanism by which chronic marijuana users develop hyperemesis is unclear. It has been shown that cannabinoids affect central CB1 receptors and peripheral CB2 receptors. CB1 receptors have an effect on memory, cognition, nausea and vomiting; any alteration in CB1 function is thought to be responsible for the development of cannabinoid hyperemesis syndrome (Hickey et al, 2013).
c) DIAGNOSTIC FINDINGS: Extensive diagnostic imaging (eg, abdominal x-rays, CT, EGD) and laboratory studies were found to be within normal limits in these patients (Williamson et al, 2014; Wallace et al, 2011; Donnino et al, 2011), and are generally not necessary if a clear history of cyclical vomiting in the setting of chronic cannabis use can be obtained and the abdominal exam is not concerning.
d) TREATMENT: Symptomatic improvement usually occurs with the discontinuation of marijuana (Nicolson et al, 2012); vomiting usually stops within 1 to 3 days of abstinence (Williamson et al, 2014). Intravenous hydration has been used in some cases to replace fluids and manage dehydration (Donnino et al, 2011).
e) PHARMACOLOGIC AGENTS: Vomiting may be resistant to antiemetic (eg, ondansetron, metoclopramide) therapy (Williamson et al, 2014).
f) NABILONE: A young adult woman, with a history of chronic marijuana (smoked 1 g of cannabis daily for several years) use, developed tremors, decreased appetite, poor sleep and CHS 1 day after abrupt discontinuation of cannabis. Laboratory and diagnostic studies were essentially normal; mild hypokalemia (potassium 3.2 mmol/L) was the only positive finding. Initial treatment included metoclopramide, ondansetron, dimenhydrinate with minimal clinical improvement. Nabilone (1 mg twice daily) was then started and within 2 hours, symptoms were significantly improved and she was able to tolerate an oral diet. She was discharged 2 days later with no further symptoms and a 2 week prescription for nabilone (same dose) as well as a referral to an outpatient cannabis cessation program (Lam & Frost, 2014).
g) SUPPORTIVE MEASURES/HOT SHOWERS: Compulsive hot water bathing is often described by patients to temporarily improve symptoms. Patients have reported taking extremely hot showers for an hour or longer; this practice can be repeated multiple times per day (Nicolson et al, 2012; Williamson et al, 2014).
h) RELAPSE: Cyclic vomiting often reoccurs with the resumption or relapse of marijuana use (Nicolson et al, 2012; Donnino et al, 2011).

a) SUMMARY: Cannabis-induced psychotic symptoms (CIPS) may appear similar to schizophrenia. However, CIPS appears more frequently in males and involves more frequent expansive moods and ideation, derealization/depersonalization, visual hallucinations, and disturbances in the sensorium. Currently, there is very little information to assess the effectiveness of antipsychotics to treat CIPS. ARIPIPRAZOLE has been used as an off-label agent to treat patients with psychiatric disorders for the treatment of comorbid cannabis addiction (Rolland et al, 2013).
b) CASE REPORT: A 22-year-old man, with a 7 year history of daily cannabis use and denial of other substances besides tobacco use, sought help for his addiction. He was noted to have a blunted affect, odd beliefs and thinking and poor social interaction. His symptoms met 5 of 9 criteria for schizotypal personality disorder and his recent functional decline placed him at ultra-high risk for psychosis. The patient also reported paranoid ideations and feelings of alien control while smoking cannabis. The patient was started on aripiprazole 10 mg/day to treat his cannabis-induced psychotic symptoms. At 6 month follow-up, the patient reported immediate cessation of his psychotic symptoms, although his cannabis use had not changed. He also reported improved social contact. Aripiprazole was continued at the same dose (Rolland et al, 2013).

a) EXPERIMENTAL THERAPY/DEXMEDETOMIDINE

a) NABIXIMOLS (currently not available in the US; approved for use in the UK and other countries): A randomized, double-blind inpatient trial with 6 days of nabiximols or placebo treatment, 3 days of washout, and a 28-day follow-up period was conducted in 51 subjects seeking cannabis detoxification. Each patient had a history of cannabis dependence and high levels of use who experienced withdrawal symptoms during previous attempts to reduce or stop cannabis use. Nabiximols, an agonist replacement therapy, contains THC, cannabidiol and various terpenoids derived from the Cannabis sativa plant was administered twice daily on day 1 (8 buccal sprays, total of 21.6 mg THC and 20 mg CBD) followed by 8 sprays 5 times daily (86.4 mg of THC and 8 mg of CBD) on day 2 and 3, followed by a tapered dose of 6 sprays 4 times daily on day 4 (64.8 mg of THC and 60 mg of CBD) and 4 sprays 4 times daily on day 5 (10.8 mg of THC and 10 mg of CBD) and 2 sprays 4 times daily (5.4 mg THC and 5 mg of CBD) on day 6. Days 7,8, and 9 were the washout period. Nabiximols were able to significantly suppress withdrawal related irritability, cravings, and depression. Patients experienced minimal rebound or an increase in symptoms following the cessation of nabiximols on day 6. Based on the primary outcome measure (Cannabis Withdrawal Scale), nabiximols significantly reduced CWS scores (mean 66% decrease from baseline) compared to placebo (mean 52% increase) treatment. Despite clinical improvement of withdrawal symptoms, nabiximols did not alter long-term reductions (or absence) in cannabis use. Further research of nabiximols for the ongoing management of cannabis dependence and withdrawal treatment has been suggested (Allsop et al, 2014).

a) DRONABINOL: PROPHYLAXIS: CAPSULE: 5 mg/m(2) orally 1 to 3 hours prior to chemotherapy then every 2 to 4 hours; maximum of 4 to 6 doses/day. If needed, the dose may be increased by 2.5 mg/m(2) increments to a maximum of 15 mg/m(2) per dose. The incidence of disturbing psychiatric symptoms increases significantly at this maximum dose; therefore caution is advised (Prod Info MARINOL(R) oral capsules, 2006).
b) DRONABINOL: PROPHYLAXIS: ORAL SOLUTION: The recommended starting dose is 4.2 mg/m(2) administered 1 to 3 hours prior to chemotherapy and then every 2 to 4 hours after chemotherapy. Maximum dose: 12.6 mg/m(2) per dose for 4 to 6 doses/day. Food may delay absorption (Prod Info SYNDROS(TM) oral solution, 2016).
c) NABILONE: The usual dose is 1 to 2 mg twice daily. On the day of chemotherapy, 1 to 2 mg 1 to 3 hours prior to chemotherapy is recommended. The maximum recommended daily dose is 6 mg given in divided doses 3 times daily (Prod Info CESAMET(TM) oral capsules, 2006).

a) DRONABINOL

a) EDIBLE CANNABIS: RECOMMENDED DOSE: Since the legalization of recreational marijuana in some states (ie, Colorado) in the US, edible cannabis includes various candies, pills, drinks and baked goods infused with 100 mg or less of THC with a recommended starting dose of 10 mg (Hudak et al, 2015).

a) The onset of effects occurs within 6 to 12 minutes and continues for 172 to 240 minutes (Nahas, 1979) Ohlsson et al, 1980, Lemberger et al, 1972).
b) There is a nonlinear relationship between plasma THC levels and degree of intoxication (Agurell et al, 1986).
c) Roughly, absorption of less than 50 micrograms/kilogram of THC by smoking will result in a "low dose" effect, and absorption of greater than 250 micrograms/kilogram will produce "high dose" effects. Between these values the dose-effect is variable (Ishbell et al, 1967).
d) Conjunctival reddening was associated with plasma THC levels greater than 5 nanograms/milliliter (Hollister et al, 1981).
e) Heart rate is maximal at plasma levels of about 45 nanograms/milliliter (Hollister et al, 1981).

a) PASSIVE INHALATION
b) INGESTION

a) COMA - A 12-week-old female ferret presented in a comatose state following a bout of sneezing and ataxia. The ferret was unresponsive, hypothermic, hypotensive, and experiencing cardiac arrhythmias. Upon post-mortem examination, delta-9 THC, cannabidiol, and cannabinol were found in body tissues and fluids. The animal's owner admitted that ingestion of marijuana was probable (Smith, 1988).

a) REMOVE the patient from the source of exposure.

a) STABILIZE seriously ill patients with supportive care, which may include fluids for hypotension, warming for hypothermia, and treatment for tachycardia or cardiac arrhythmias.

a) Emesis is only recommended if the patient is asymptomatic and known to have ingested marijuana. Emesis is most useful within one hour of ingestion (Dumonceaux & Beasley, 1990).

a) Activated charcoal and cathartic may be useful for ingestions.

a) Retain samples of blood, urine, and stomach contents for analysis.

a) Recovery from acute intoxication may take several days; continue supportive care as necessary.

a) Diagnosis of allergic dermatitis is based upon intradermal skin testing and reaction to hyposensitization and environmental treatment. Systemic and topical corticosteroids and antihistamines provide temporary and partial relief from signs, but testing and hyposensitization is the recommended treatment (Evans, 1989).