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Substance Abuse in Adolescents
Yedidia Bentur, MD
Israel Poison Information CenterRambam Medical Center
Faculty of Medicine, Technion, Haifa, Israel
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“We live in a decadent age. Young people no longer respect their parents. They are rude and impatient. They frequent taverns and have no self-respect.”
Inscription on Egyptian tomb circa 3000 B.C.
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Anti Drug Authority, Israel 2001
12 – 18y, one use/year Substances
volatiles 7.4%
medications w/o indication 6.1% sedatives 4.8%, methylphenidate 2.9%
illegal drugs (w/o cannabis) 5.4% Ecstasy 2.7%
cannabis 5%, (USA 20% - 50%) marijuana 4%, hashish 3.3%
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Poison Information Center Data Adolescents, 2003
Israel USA
32 (0.16%) 14, 875 (0.6%)
Cannabis Amphetamines
MDMA Caffeine
Opioids Cannabis
LSD MDMA
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Volatile Substance Inhalant Abuse (VSIA)
Recreational use of volatile substances
Since 19th century, use since 1960s
Age: 14 - 22y (9 – 29y) Inexpensive, available, legal,
easy to conceal and handle,perceived erroneously as safe
Sudden death with negative autopsy findings
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Classification of inhalants Volatile solvents
adhesives (glue sniffing), thinners, lighters, correction fluid, dry cleaning, gasoline
Aerosols (propellants and solvents) spray paint, hair spray, deodorizers
Gases freons (air conditioning), halothane, N2O (whipped cream, laughing gas)
Nitrites sexual stimulants: amyl nitrite, butyl nitrite, cyclohexyl nitrite
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Inhalants
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Exposure
Dose inhaled depends on: concentration in preparation mode of inhalation (container, aerosol, cloth, plastic bag, etc.) duration number of exposures
Levels x100-1000 occupational thresholds
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Factors affecting clinical response
Dose
Genetic factors
Diet
Alcohol consumption
Smoking habits
Concomitant drugs
Physical activity
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Glue sniffing - toluene
Absorption 50%Tmax 15 – 30minDistribution to adipose tissuesMetabolism: liver, extensive (80%)
inhibited by ethanol P450 (CYP 1A1) and ALDH2 polymorphism oxidation to benzoic acid conjugation with glycine hippuric acid
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Toluene (2)
Excretion < 20% by inhalation, unchanged urinary hippuric acid (filtration + secretion)
Elimination biphasic; triphasic in workers terminal T½ 15-90h
Chronic abuse: induction of P450 hippuric acid, exhaled unchanged
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Mechanism of toxicity
Perivascular myelin loss,degeneration of white matter(cerebral cortex, cerebellum)
Hypoxemia (freons, plastic bag)AspirationHypoperfusion Sensitization of myocard to catecholamines Irritation (freons)Frostbites (freons)
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Clinical manifestations
Nausea, vomiting, bronchospasm
Confusion, psychomotor impairment, drunkenness, disinhibition, dizziness, headache, slurred speech, drowsiness, ataxia
Hallucinations, delusions, mydriasis HR, BP, respiration, coma, seizures
Death: anoxia, respiration, arrhythmias
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Distal renal tubular acidosis (toluene)
Hemolysis (nitrites)
Hepatitis (halogenated hydrocarbons)
Head trauma (freons – air conditioning)
Burns (concomitant smoking)
Clinical manifestations (2)
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Sequelae: neuropsychiatric, irreversible epilepsy, atrophy, polyneuropathy cognition, psychosis
Withdrawal tolerance, psychological addiction resembles alcohol withdrawal
Fetal solvent syndrome (glue and gasoline)
Clinical manifestations (3)
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Diagnosis
High index of suspicion – thorough history unexplained neuropsychiatric / C-V manifestations
ECG monitoring High anion gap metabolic acidosis (esp. toluene) Urinary hippuric acid:
used in occupational biomonitoring interference: dietary benzoic acid (prunes, cranberries, plums, Chinese preserves, black tea)
Toluene blood and urine levels: not useful
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Treatment
Removal
Supportive
Avoid catecholamines: arrhythmias
Tachyarrhythmias: propranolol IV, esmolol IV
No specific antidote
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Cannabissativa
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Cannabis
Cannabis sativa Known in Asia for > 5,000y 61 cannabinoids: 9- tetrahydrocannabinol (THC): psychoactive 8-THC, cannabidiol, cannabinol Smoked (joint, 20mg THC), eaten (cookies) “Gateway” drug Medicinal – dronabinol (Ronabin, 2.5mg)
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Marijuana (grass): leaves, flowers, stem (1-5% THC)
Hashish: dried and compressed resin (10% THC)
Hashish oil (30-50% THC)
Charas: resin; ~20% THC (India)
Bhang: leaves (India)
Dagga: (South Africa)
Kef
Common types of cannabis
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Toxicokinetics Bioavailability: oral 10-20%, lung 20-30% rapid
Onset 10-60min, Tmax 2-4h
Distribution to adipose tissues (brain)
Metabolism: hydroxylation 11-OH--THC (active) 11-nor-9 carboxy--THC (inactive)
T½ 20-30h, chronic user 5d (1-12d), duration 1-8h
Individual variability (experience, tolerance)
Toxic dose: psychoactive 3-15mg, lethal 30mg/kg
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Mechanism of toxicity
Cannabinoid receptors nervous system (CB1): of transmitter release immune cells (CB2): modulate cytokine release testis (CB1), LH, prolaction
Endocannabinoids: anandamide, 2-arachidonyl-glycerol
Stimulant
Sedative
Hallucinogen
Catecholamine (dopamine) release (abuse)
Inhibition of sympathetic reflexes
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Neurotoxicity of cannabis
Acute effects mood cognition behavior psychmotor
Chronic effects antimotivational psychosis dependence
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Clinical manifestations
Euphoria, sensory awareness, time – space distortion, palpitations, sedation
reaction time, incoordination, performance
Impaired memory, depersonalization, hallucinations, paranoid psychosis
Tachycardia, orthostatic hypotension, conjunctival injection, slurred speech, ataxia
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Chronic users: manic, schizophreniform, confusional psychosis acute & chronic respiratory toxicity Children (cookies): pallor, fine tremor, ataxia, hypotonia, coma, apnea, HR
Contaminants: pulmonary aspergillosis, paraquat Withdrawal: after 180mg/d, 2-3wks; lasting 48h restlessness, insomnia, anxiety, tremor, hot flushes
Clinical manifestations (2)
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Diagnosis
High index of suspicion – thorough history
HR, conjunctival injection, altered mood / cognition
Urine THC: after 1h days (acute), weeks (chronic) no correlation to severity false negatives: dilution, lemon juice, vinegar, bleach, salt, Visine false positives: NSAIDs passive smoking positive results
R/0 other drugs of abuse
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Treatment
Reassurance
Benzodiazepines
Sinus tachycardia: β blockers ( rarely needed)
Orthostatic hypotension: IV fluids
No specific antidote
Not life threatening
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Ecstasy
3,4-methylenedioxymethamphetamine - MDMA
(hallucinogenic amphetamine)
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אקסטזי
אקסטה
כדור
מיצובישי
עגול
120mg
X10-100 variability
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Toxicokinetics
Absorption, oral: rapid
Onset of action: 30-60 min
Peak action: 90 min
Duration of action: 4-6 h (could be >8 h)
Metabolism: liver, P450 and N-demethylation, some metabolites active
Urine excretion: 65% unchanged, 35% - metabolites
Elimination kinetics: non-linear
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Mechanism of action
Hallucinogenic and stimulant
Serotonin release followed by prolonged depletion (wks)
Permanent destruction of serotonergic nerve endings in every experimental model
Stimulate NorE release with dose stimulate - and -adrenergic receptors
SIADH
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Pattern of use
Usually at rave parties
Hours of dancing
Heavy water intake
Up to 10 tab / night
Repeated use → reinforcement
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Clinical manifestations
Toxic dose: variable
Can be delayed for hours
Unpredictable severity of effects
Severe poisoning and death - even after 1 tablet
Causes of death: cardiac arrhythmias, hyperthermia, hyponatremia
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Clinical manifestations (2)
“Positive”: mood, euphoria, talkative, intimacy
“Negative”: HR, anxiety, anorexia, bruxism, mydriasis
Next day:
myalgia, somnolence, depression, concentration
Repeated use: tolerance to the positive effects
Frequent use, dose: negative effects
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Clinical manifestations (3)
Nausea, vomiting
Chest pain, HR, BP, arrhythmias, MI (rare), ARDS
temp., dehydration, rhabdomyolysis, ARF, DIC
Seizures, brain hemorrhage / infarct / edema
Na, myoglobinuria, metabolic acidosis
Hepatitis
Serotonin syndrome
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Clinical manifestations (4)
Emotional instability, insomnia
Confusion, depression, suicidal thoughts
Flashbacks, hallucinations
Impaired cognition
Psychosis (paranoid), panick attack
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Diagnosis / Evaluation
High index of suspicion - thorough history
Unexplained neuropsychiatric / C-V manifestations
Na, K, blood gases, CPK, myoglobin
ECG & cardiac monitoring
R/O complications, other diagnosis
Urine assay: qualitative (usually), quantitative
Blood level: not clinically useful
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Differential diagnosis
Toxicological causes of agitation and seizures cocaine, amphetamines, TCA, MAO - I, isoniazid
Non-toxic causes alcohol withdrawal intracranial hemorrhage manic behavior, psychosis, seizure disorder metabolic disorder (e.g. hyperthyroidism) cardiovascular abnormalities
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Management
Do not delay treatment !
Sedation: benzodiazepines caution neuroleptics (e.g. haloperidol): seizures, temp., arrhythmias, dystonia
Supportive oxygenation, ventilation – as needed hypertension: nitroprusside seizures: benzodiazepines hyperthermia: sedation, cooling, hydration, dantrolene hyponatremia: water restriction? saline (0.9%? , 3%?)
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General warning signs
Changes in school behavior
Mood changes
Dropping out of usual activities
Changed physical appearance
New friends / loss of old friends
Missing items / money
Change in sleep patterns
Depression / anxiety
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Cannabis