Hallucinogens (Psychedelics, Psychotomimetics)
Hallucinogens are substances that induce changes in thought, perception, and mood, without causing major disturbances in the autonomic nervous system. Perceptual alterations can take the form of illusions, synaesthesias, or hallucinations. An illusion is the result of misinterpretation of an actual experi-ence, while synaesthesias are sensory misperceptions (e.g. hearing colour or seeing sounds). Both require external stimuli for their institution. Hallucinations differ from them in this important respect, since they are perceptual alterations without any external stimulation whatsoever. Hallucinations may be visual, auditory, olfactory, gustatory, or tactile in nature. Most hallucinogens induce visual or auditory hallucinations; a few cause tactile or olfactory manifestations. While a number of therapeutic drugs can cause hallucinations in overdose, they are not classified as hallucinogens. A true hallucinogen is a drug that induces hallucinations in small doses (sometimes, as in the case of LSD, in microgram doses). Most genuine hallucinogens cause vivid visual hallucinations, while the other types of hallucinations are relatively uncommon. Table 34.15 lists common hallucinogens, some of which will be discussed in detail in this section, while the others have been discussed in appropriate sections elsewhere.
· Lysergic acid diethylamide (LSD) is the synthetic diethylamide 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 certainother grains ( Fig 34.18).
Today, most LSD is synthesised entirely in the laboratory, and typically sold to addicts as liquid-impregnated blotting paper (Fig 34.19) or sugar cubes, tiny tablets (“microdots”), gelatin squares (“window panes”), liquid, or powder. LSD is said to be the most powerful of all hallucinogens, and is active in doses of 50 to 100 mg. 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 34.20) 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.
The LSD is almost always ingested. Other less common routes of intake include intranasal, sublingual, smoking, conjuctival instillation, and very rarely injection.
The 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-HT1A receptors, which are coupled to adenylcyclase. LSD is also an agonist at 5-HT2A, 2C receptors, which are not located presynaptically on seroton-ergic 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 ctivation of D1 (dopamine) receptors may contribute to the neurochemical effects of LSD.
The 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 mcg. Doses over 0.2 mg/kg are potentially lethal.
––Muscle weakness, ataxia.
––Euphoria or dysphoria.
––Vivid hallucinations, synaesthesias.
––Bizarre perceptual changes: People’s faces and 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.
· Prolonged psychotic reactions which are mainly schizo-phrenic in nature.
· Severe depression.
· Flashback phenomena: The person relives 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:
–– Pareidolias: images of faces on floor and walls, floating faces hovering in space.
–– Aeropsia: visualisation of air in the form of numerous vibrating pinpoint-sized dots (“mole-cules”).
■■Radioimmunoassay of serum or urine (limit of detection 0.1ng/ml).
■■ HPTLC (high performance thin layer chromatography) candetect 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.
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.
Phencyclidine (PCP), a phenylcyclohexylamine compound, is easily synthesised from piperazine, cyclohexanone, and potas-sium cyanide. It is commonly referred to by addicts as “angel dust” or “PCP”.
Phencyclidine was developed in the 1950s as a potential general anaesthetic by Parke-Davis under the brand name Sernyl. It was termed a “dissociative anaesthetic” because unlike conventional anaesthetics which induced a state of relaxed sleep, PCP induced a state of catatonia with flat facies, open mouth, fixed staring, rigid posturing, and waxy flexibility. Patients seemed dissociated from the environment without classical coma. However, a significant proportion of patients showed severe adverse reactions during emergence, including agitation and hallucinations. Some suffered from psychosis for up to 10 days. PCP was therefore quickly withdrawn. Today, ketamine a less potent PCP derivative is quite popular as an anaesthetic.
Phencyclidine (PCP) is abused by
smoking, insufflation, ingestion, or rarely IV injection. It is commonly sold
on the street as tablets (about 5 mg), capsules, powder, aqueous or alcoholic
solution, or as “rock salt” crystal. It is often mixed with parsley, mint,
oregano,or marijuana. Sometimes “crack” is
dipped in PCP and smoked (“tragic magic”), or cannabis is dipped in PCP (“love
Phencyclidine antagonises the action of glutamate at the NMDA (N-methyl-d-aspartate) receptor. It binds within the ion channel (PCP binding site) to block Ca++ influx which results from glutamate binding. Unlike the other types of glutamate receptor channels, NMDA channels are permeable to both Ca++ and Na+. Following NMDA receptor activation, NMDA-mediated Ca++ flux may lead to stimulation of calmodulin-dependant kinases with activation of postsynaptic second-messenger pathways. Opening the NMDA channel facilitates access of PCP to its receptor, accelerating the rate at which PCP-induced blockade of NMDA receptor-mediated neurotransmission takes place.
At doses much higher than at which it exerts its unique behav-ioural effects by blocking NMDA receptor-mediated neurotrans-mission, PCP also blocks presynaptic monoamine reuptake, thus directly increasing synaptic levels of dopamine and noradrenaline. At even higher doses, PCP blocks neuronal Na+ and K+ channels, as well as muscarinic cholinergic receptors. This may explain the occurrence of convulsions in PCP overdose.
The volume of distribution of phencyclidine is 6.2 L/kg. Plasma protein binding is about 65%. Since it is highly lipid soluble, it accumulates in brain and adipose tissue. Metabolism of the latter causes release of PCP which contributes to the recurrence of symptoms. PCP can be detected in urine up to 20 to 30 days (usually 2 weeks).
· Level of consciouness ranges from fully alert to coma-tose. The coma is usually preceded as well as followed (upon recovery) by agitation and psychosis.
· Confusion, disorientation, amnesia.
· Catatonia with unusual posturing, mutism, and staring.
· Myoclonic and dystonic movements, choreoathetoid, opisthotonus, torticollis.
· Acute toxic psychosis with bizarre behaviour, agitation, and violence.
· Cholinergic (sweating, miosis, salivation, bronchos-pasm), or anticholingeric (mydriasis, tachycardia, urinary retention) signs may be present.
· Hallucinations (auditory and visual).
· Blank stare
· Dysconjugate gaze
· Nystagmus (horizontal, vertical, or rotatory)
· Blurred vision
· Miosis (occasionally mydriasis).
· Sinus tachycardia
· Acute renal failure.
■■ Approximately 100 mg or more.
■■ Lethal blood level: 0.1 mg/100 ml.
Serum PCP levels usually do not correlate well with clinical picture. Therefore, a qualitative test is adequate in most cases.
· Elevated muscle enzymes
· EEG: Diffuse slowing with theta and delta waves.
The need for syrup of ipecac or gastric lavage should be assessed carefully. Often such measures may exacerbate agitation and violence.
· Activated charcoal is highly beneficial and can be admin-istered at a dose of 1 gm/kg every 4 hours for several doses.
· A single dose of a suitable cathartic such as sorbitol can be given (unless there are specific contraindications).
· Some authors recommend urinary acidification to enhance excretion of PCP (which is a weak base). But only 10% of the drug is excreted in the urine, while the remaining 90% is metabolised in the liver. Hence the practical utility of urinary acidification is negligible.
· Haemodialysis and haemoperfusion are not beneficial.
· As of now there is no antidote for PCP, though efforts are on to develop PCP-specific antigen binding fragmens (Fab) which can prove to be very useful.
· Agitated patients should be restrained, at first physi-cally and later pharmaceutically. Hypoglycaemia, if present, must be treated with 50% dextrose in water.
· Subsequently if agitation persists, administer titrated doses of diazepam 5 to 10 mg IV, every 10 minutes, until the patient is calmed. Phenothiazines should be avoided since they can worsen dystonic reactions, hypotension, hyperthermia, and lower the seizure threshold.
· Specific antihypertensive therapy should be instituted in patients with very high blood pressure.
· Myoglobinuria should be treated with IV infusion of 1 litre of 5% dextrose in water (containing 25 gm of mannitol and 100 mEq of sodium bicarbonate), at a rate of 250 ml/hour. Monitor the patient for hypokalaemia. If renal failure has occurred, haemodialysis should be undertaken.
Hallucinogen abuse has been traditionally a Western phenom-enon, and drugs of abuse such as LSD and phencyclidine have always been popular only in countries such as the USA, UK, Australia, and parts of Europe. The popularity of such drugs has been fuelled by their, glamourous representation in films and rock music. The 1960s saw an explosion of hallucinogen use almost in the form of an epidemic, and though it declined steeply in the 1970s and 1980s, there has been an alarming resurgence over the last decade.
The dangers of hallucinogen use do not have as much to do with acute toxicity, as with long-term psychological damage. The inevitable fallout is violent crime manifesting as assaulta-tive behaviour, homicides, and suicides. Several horrific crimes have been committed by drug-crazed individuals acting out their bizarre fantasies.
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