Lysergic Acid Diethylamide (LSD) - Hallucinogen(Psychedelic Drug)

LYSERGIC ACID DIETHYLAMIDE (LSD)

Source

·              Lysergic acid diethylamide (LSD)* is the synthetic dieth-ylamide derivative of ergot alkaloids, and was originally synthesised exclusively from these alkaloids produced by the fungus Claviceps purpurea, which is a contaminant of rye and certain other grains.

·     Today, most LSD is synthesised entirely in the laboratory, and typically sold to addicts as liquid-impregnated blotting paper (Fig 20.1) or sugar cubes, tiny tablets (“microdots”), gelatin squares (“window panes”), liquid, or powder.

·     LSD is said to be the most powerful of all hallucino-gens, and is active in doses of 50 to 100 mcg. It occurs as a water-soluble, colourless, tasteless, and odourless powder.

·     Drugs related to LSD (lysergamides) also occur naturally in plants such as “Morning glory” (Rivea corymbosa) (Fig 20.2) and “Hawaiian baby woodrose” (Ipomoea violacea). Seeds of morning glory contain lysergic acid hydroxyethylamide, which is 1/10th as powerful as LSD. At least 200 to 300 seeds have to be pulverised—intact seed coat resists digestion—and ingested, for inducing hallucinogenic effects.

Mode of Intake

·              Lysergic acid diethylamide (LSD) is almost always ingested. Other less common routes of intake include intranasal, sublin-gual, smoking, conjuctival instillation, and very rarely injection

Mode of Action

·              LSD is structurally related to serotonin (5-hydroxy- tryptamine) and is an agonist at the 5-HT₁  receptor. Serotonin modulates many psychological and physiological processes including mood, personality, affect, appetite, sexual desire, motor function, temperature regulation, pain  perception, and sleep induction.

·              LSD inhibits central raphe neurons of brainstem through stimulation of 5-HT_1A receptors, which are coupled to adenylcyclase.

·              LSD is also an agonist at 5-HT receptors, which are not located presynaptically on serotonergic cell bodies but on certain subpopulations of neurons in postsynaptic regions. The majority of 5-HT₂ receptors in the brain are located in the cerebral cortex. Animal experiments have shown that LSD is anatomically distributed maximally in the visual and auditory cortex, and the limbic cortex (besides the pituitary, pineal, and hypothalamic areas), which parallels the finding of high concentration of 5-HT₂ receptors in human cerebral cortex.

·              Recent studies also suggest that activation of D₁ (dopamine) receptors may contribute to the neurochemical effects of LSD. 

Toxicokinetics

·              LSD has a half-life of 2.5 hours, while the duration of effects lasts for up to 8 hours. But psychotropic effects can occur for several days, and urine-screen is usually positive for 100 to 120 hours.

·     The route of metabolism is hepatic hydroxylation.

·     The usual dose of abuse is 100 to 300 micrograms. Doses over 0.2 mg/kg are potentially lethal.

Clinical (Toxic) Features

Acute Poisoning

a. Physical

·              Mydriasis, hippus*.

·              Vertigo.

·              Tachycardia, hypertension.

·              Sweating, piloerection.

·              Hyperthermia.

·              Tachypnoea.

·              Muscle weakness, ataxia.

·              Hyperactivity. ix. Coma.

b. Psychological

·              Euphoria or dysphoria.

·              Vivid hallucinations, synaesthesias.

·              Bizarre perceptual changes: People’s facesand body parts appear distorted, objects undu-late, sounds may be magnified and distorted, colours seem brighter with halos around objects. Occasionally there is depersonalisation, and the hallucinating person may feel as if he is observing an event instead of being involved in it.

Chronic Poisoning

·              Prolonged psychotic reactions which are mainly schizo-phrenic in nature.

·              Severe depression.

·              Flashback phenomena: The person re-lives the LSDexperience periodically in the absence of drug intake for months or years.

·              Post-hallucinogen perception disorder: A persistentperceptual disorder often described by the person as if he is residing in a bubble under water in a “purple haze” with trailing of lights and images. Associated anxiety, panic, and depression are common. The following unusual phenomena have also been reported:

o     Pareidolias—images of faces on floor and walls, floating faces hovering in space.

o     Aeropsia—visualisation of air in the form of numerous vibrating pinpoint-sized dots (“mole-cules”).

Diagnosis

·      Radioimmunoassay of serum or urine (limit of detection 0.1ng/ml).

·      HPTLC (high performance thin layer chromatography) can detect LSD in urine in concentrations less than 1 mcg/litre.

·      HPLC (high pressure/performance liquid chromatography) of serum and urine.

·              GC-MS (gas chromatography-mass spectrometry) can confirm positive LSD urine levels to a lower limit of 5 pg/ml.

Treatment

·      Avoid gut decontamination as LSD is ingested in micro-quantities and rapidly absorbed, rendering decontamina-tion procedures totally redundant.

·      Do not use restraints in agitated patients; it will only exac-erbate the condition.

·      Because of the short half-life and few serious medical reactions, elimination enhancement procedures such as haemodialysis, haemoperfusion, etc., are not warranted.

·      Treat acute panic attacks with quiet environment, reas-surance, supportive care, and administration of diazepam (5–10 mg IV) or haloperidol (in severe cases).

·      Treat acute psychotic reactions with cautious administration of neuroleptics such as haloperidol. Avoid phenothiazines which can cause hypotension, sedation, extrapyramidal reactions, lowered seizure threshold, and potentiation of anticholinergic effects.

·      Treat flashbacks with psychotherapy, anti-anxiety agents, and neuroleptics.

·      Treat post-hallucinogen perception disorder with long-lasting benzodiazepines such as clonazepam, and to a lesser extent anticonvulsants such as valproic acid and carbamazepine. This approach must be combined with behavioural therapy. The patient must be instructed not to consume alcohol, cannabis, caffeine, and other drugs which can intensify the disorder.