Substance Abuse in Adolescents

Yedidia Bentur, MD

Israel Poison Information CenterRambam Medical Center

Faculty of Medicine, Technion, Haifa, Israel

“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.

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%

Poison Information Center Data Adolescents, 2003

Israel USA

32 (0.16%) 14, 875 (0.6%)

Cannabis Amphetamines

MDMA Caffeine

Opioids Cannabis

LSD MDMA

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

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

Inhalants

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

Factors affecting clinical response

Dose

Genetic factors

Diet

Alcohol consumption

Smoking habits

Concomitant drugs

Physical activity

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

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

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)

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

Distal renal tubular acidosis (toluene)

Hemolysis (nitrites)

Hepatitis (halogenated hydrocarbons)

Head trauma (freons – air conditioning)

Burns (concomitant smoking)

Clinical manifestations (2)

Normal

Inhalant abuse

Sequelae: neuropsychiatric, irreversible epilepsy, atrophy, polyneuropathy cognition, psychosis

Withdrawal tolerance, psychological addiction resembles alcohol withdrawal

Fetal solvent syndrome (glue and gasoline)

Clinical manifestations (3)

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

Treatment

Removal

Supportive

Avoid catecholamines: arrhythmias

Tachyarrhythmias: propranolol IV, esmolol IV

No specific antidote

Cannabissativa

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)

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

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

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

Neurotoxicity of cannabis

Acute effects mood cognition behavior psychmotor

Chronic effects antimotivational psychosis dependence

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

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)

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

Treatment

Reassurance

Benzodiazepines

Sinus tachycardia: β blockers ( rarely needed)

Orthostatic hypotension: IV fluids

No specific antidote

Not life threatening

Ecstasy

3,4-methylenedioxymethamphetamine - MDMA

(hallucinogenic amphetamine)

אקסטזי

אקסטה

כדור

מיצובישי

עגול

120mg

X10-100 variability

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

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

Pattern of use

Usually at rave parties

Hours of dancing

Heavy water intake

Up to 10 tab / night

Repeated use → reinforcement

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

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

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

Clinical manifestations (4)

Emotional instability, insomnia

Confusion, depression, suicidal thoughts

Flashbacks, hallucinations

Impaired cognition

Psychosis (paranoid), panick attack

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

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

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%?)

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

Cannabis