HALLUCINOGENIC DRUGS, SYNTHETIC DRUGS

Intoxication can be difficult to diagnose due to polydrug abuse. Synthetic drugs are produced based on products such as opioids (fentanyl, meperidine), cocaine, or amphetamines.

ECSTASY, AMPHETAMINES

Psychostimulant effects:

Ecstasy or amphetamines act:

• as hallucinogens,
• or produce effects comparable to those of cocaine (as a stimulant).

Physical-chemical properties:

• Ecstasy is an amphetamine derivative of the methylenedioxy-methamphetamine group or MDMA.
• MDMA belongs to the group of entactogens (tactus – rhythm, en – within, gene – production). MDMA was synthesized and manufactured in the year 1914.
• The effect is felt after 15 to 60 minutes and lasts from 4 to 8 hours (MDMA).

Mechanism of toxicity:

Molecules attach to specific receptors on serotonin and act as indirect agonists at the level of presynaptic alpha2 receptors (serotonin syndrome). A decrease in efficiency is observed during repeated intake.

Serotonin, also called 5-hydroxytryptamine (5-HT), is a molecule that derives from tryptophan, an amino acid. Initially, it was identified as a factor released from blood platelets that cause a contraction of blood vessels, but it is also one of the main neuromodulators of the central nervous system.

Serotonin is produced starting from tryptophan, an amino acid that enters the brain from the blood circulation, among others. Some neurons of the "raphe nuclei", located in the brainstem, convert tryptophan into 5-hydroxytryptophan (5-HTP) thanks to an enzyme, tryptophan hydroxylase. 5-hydroxytryptophan is further converted into serotonin by another enzyme, L-amino acid decarboxylase (AADC).

Serotonin is found in the brain (where it plays the role of a neurotransmitter or neuromediator) and in the digestive system. It is involved in the regulation of functions such as thermoregulation, feeding and sexual behaviors, sleep-wake cycle, pain, anxiety or motor control. Recently, CNRS scientific researchers have discovered that maternal serotonin plays a significant role in the development of the embryo. Moreover, according to a recent study, a serotonin imbalance explains 50% of the cases of death from breastfeeding.

Indirect sympathomimetic action:

• The lethal dose for MDMA is 200 mg.
• Pure MDMA is rare, it is generally mixed (caffeine, strychnine, LSD, ketamine, chloroquine, etc).
• There are a large number of amphetamine derivatives and numerous commercialized molecules (Isoméride®, Pondéral®, Anorex®, Moderatan®, Ordinator®).

Symptoms:

Very similar to those of cocaine intoxication:

• Tachycardia, arterial hypertension, rhythm disturbances;
• Hyperthermia above 40 degrees;
• Restlessness, aggressiveness, tremors;
• Decrease in auditory and visual capacities, decrease in pain sensitivity, seizures, coma;
• Nystagmus (eye movement left-right, tic), reactive mydriasis (dilation of the pupil);
• Hyperventilation (excessive breathing), vomiting;
• Muscular hypertonia, rhabdomyolysis (The term rhabdomyolysis describes the destruction of striated or voluntary muscle as seen during the Bywaters' syndrome (muscle crush syndrome), among others).

Main complications:

• cardiac: of the type of paroxysmal ventricular rhythm disturbances;
• metabolic: hyperthermia (exacerbated by dancing for many hours) and dehydration.

Besides the reduction of sensations (thirst, pain), the consumer might dance until physical exhaustion.

A cardiac arrest and an acute respiratory distress syndrome (ARDS) are possible.

Treatment:

• Peripheral venous route for rehydration.
• Hypnovel®, Valium® (10 mg at repeated intervals if needed) for their sedative effect.
• Rivotril® in case of convulsions.
• Dantrolene® in case of refractory hyperthermia, consider external cooling.
• Avlocardyl® (contraindicated by some authors) or Vérapamil® in case of supraventricular arrhythmias.
• Adalate®, Loxen® if there is arterial hypertension.
• Xylocaïne® in case of ventricular arrhythmias.

Serotonin antagonists exist: méthysergide, cyproheptadine.

HYDROXYBUTYRATE GAMMA (GHB)

Physical-chemical properties:

• A powerful depressant of the central nervous system, GHB is an endogenous component of the brains of mammals where it is synthesized starting from gamma-amino-butyric acid (GABA).
• GHB increases dopamine levels in the brain and affects endorphins.
• First synthesized in 1961 by H. Laborit.
• It has been used as a general anesthetic in the treatment of insomnia and narcolepsy, in the treatment of alcoholism or alcohol withdrawal syndrome.
• Known under the name "Liquid Ecstasy", "Liquid X" or "Liquid E" due to its "socializing" effect that reminds us of the empathetic effect of Ecstasy and because it comes in liquid form.

Symptoms:

• Respiratory depression proportional to the dose, an effect increased by alcohol.
• With 10 mg/kg, amnesia and hypotonia.
• Between 20 and 30 mg/kg, drowsiness, intoxication, and euphoria.
• Between 50 and 70 mg/kg, coma, bradycardia [(from Greek bradus = slow and kardia = heart) Bradycardia is characterized by a heart rate much lower than normal.], bradypnea [(from Greek bradus = slow and pnein = to breathe) Bradypnea presents slow breathing («normal» breathing is 12 to 20 breaths per minute in an adult, and 30 breaths per minute in a newborn). It may be caused by cold or CO2 concentration.], Cheyne-Stokes respirations, mixed and vomiting.

Other frequently reported effects are:

• Cephalgia (headache);
• Confusion, distress, hallucinations;
• Ataxia (from Greek ataxiā, meaning disorder) – is a neuromuscular pathology involving the lack of coordination of voluntary movements;
• Tremors, convulsions;
• Hypertension or orthostatic hypotension (pressure drop when getting up from a lying position).

GHB, like all drugs obtained on the black market, may contain numerous impurities.

COCAINE, CRACK

Physical-chemical properties

• Odorless, colorless crystalline powder with a bitter taste. Used as a stimulant.
• Cocaine is absorbed through the nasal route; also, it can be mixed with a drink, smoked, or injected. It is generally "cut" with caffeine, strychnine, amphetamines, lidocaine, or heroin.
• It is a local anesthetic and a powerful vasoconstrictor (alpha-adrenergic effect).
• Its use in France is marginal but steadily increasing.
• Crack is a crystallized form of cocaine that can lead to addiction from the first use.

Mechanism of toxicity:

There is a slowing of the spread of the nerve impulse (local anesthetic effect), a blockade of the presynaptic uptake of catecholamines, responsible for an increase in sympathetic tone and a reduction in transmission at the level of the central nervous system (neuropsychiatric disturbances and convulsions).

Cocaine interferes with the neuronal reuptake of norepinephrine and dopamine, as well as with the metabolism of serotonin.

Poisoning:

• May be a result of:
  • A suicidal intent;
  • The purity (unusual) of the product.
• The clinical signs of poisoning are very similar to those observed in the case of amphetamines:
  • Headache, confusion, mydriasis, convulsions, coma;
  • Core temperature increase up to 42 degrees, rhabdomyolysis;
  • Tachycardia, arterial hypertension, ventricular rhythm disturbance. We may observe chest angina (chest pain due to lack of oxygen) to myocardial infarction (increase in O2 demand and circulatory failure) but also intestinal, renal or pulmonary infarction.
  • Tachypnea, bronchospasm, acute respiratory distress syndrome, pneumothorax, and pneumomediastinum.
• Consider the diagnosis in the case of cerebrovascular accident (stroke) or myocardial infarction in young subjects.
• Contraindication - propranolol (increases the risk of coronary spasm).

Treatment:

• There is no consensus on the modalities of therapeutic management;
• Oxygen therapy up to tracheal intubation;
• Benzodiazepine in case of seizures;
• Beta-blockers, injectable Tildiem® if there is tachycardia;
• Xylocaïne® Loxen®, if blood pressure does not decrease, this due to alpha receptor stimulation. An alpha-type Régitine® (phentolamine) can be used.
• The interest of thrombolysis in myocardial infarction has not been established;
• Hypotension in the depressive phase of intoxication can be ensured by a supplement and an inotropic vasopressor (dopamine).

MORPHINE AND DERIVATES

Natural substances - Opium, morphine, codeine

Synthetic substances - Heroin, hydromorphone, hydrocodone, methadone, fentanyl, nalbuphine, propoxyphene, pentazocine.

Overdose:

• Central nervous system depression;
• Respiratory depression;
• Miosis (constriction of the pupils).

The use of naloxone can be beneficial in cases of diagnostic suspicion. (Naloxone is the principal antagonist of morphine receptors. It is the standard treatment for heroin overdoses.) It should be noted that its duration of action is shorter than that of the toxins.

Heroin withdrawal

It lasts about 12 hours after the last intake and usually disappears after 48 to 72 hours.

Associated symptoms:

• Vomiting, diarrhea;
• Shaking, crying, insomnia, mydriasis;
• Fever, sweating.

A possible treatment is the intake of methadone (200 mg per hour) administered based on the symptoms.

LSD (LYSERGIC DIETHYLAMIDE ACID)

Associated symptoms:

• Tremors, confusion, disorientation;
• Mydriasis,
• Tachycardia,
• Tachypnea.

What should be done?

• Place yourself in a calm environment;
• Benzodiazepine if there are concerns;
• Droperidol if needed.

PSILOCYBIN

Drug extracted from a type of mushroom.

Associated symptoms:

• Visual hallucinations;
• Mydriasis;
• Tachycardia;
• Distress;
• Confusion;
• Vomiting;
• Diarrhea.

What should be done?

• Benzodiazepine;
• Anti-emetics;
• Place in a calm environment.

MESCALINE

Drug extracted from a type of cactus in North America.

Associated symptoms:

• Trembling, distress;
• Abdominal spasms (cramps);
• Vomiting;
• Visual hallucinations;
• In high doses an immediate drop in blood pressure, a respiratory depression.

What should be done?

• Place yourself in a calm environment;
• Benzodiazepine;
• Tracheal intubation if there is respiratory depression;
• “Compensation” if there are blood pressure disturbances.