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Introduction
Hallucinogens, also called psychedelics form a comprehensive class of drugs. Their major effects are set on brain. They bring about-
Visual & auditory hallucinations.

Altered perception of time, space, emotions and consciousness.

Overall, hallucinogens create delusion in brain. As a result, brain interpret some sensation, images and sounds which may seem real but they do not exist. 1
History & Development
During 15th & 16th century hallucinogens were considered sacred by Aztec of Mexico. They called hallucinogens ‘God’s Flesh’. In 19th century, different ‘Plains’ tribes in southwestern of USA practiced ‘Peyote Ritual’. Native American Church was formed in 1918 to protect ‘Peyotism’ when it was fused with Christian worships.

Scientific interest was gradually overtaken when the principal constituent of Peyote, called ‘Mescaline’ isolated in 1896. In 1943, a Swiss chemist ‘Albert Hoffman’ accidentally discovered LSD during a study on Schizophrenia. ‘Gordon Wasson’ a mycologist from USA found interest in Mexican mushrooms and eventually discovered ‘Psilocybin’, an active constituent. 2
Sources
Naturally occurring hallucinogens: Major source of hallucinogens. Drugs can be isolated from them or whole organisms can be used as drugs.
Examples- Psilocybin mushrooms, morning glory seeds, Peyote cactus.

Synthetic hallucinogens: They are synthesized chemically.

Examples- Phencyclidine (PCP), LSD, MDMA. 2
Types
Classic Hallucinogens: They induce visual ; auditory hallucinations which eventually results in altered perception of time, height etc.
Examples- LSD, DMT etc.

Dissociative Drugs: They induce ‘Derealization’ and ‘Depersonalization’.
Examples- PCP, Ketamine etc. 3
Major Health Effects
Hallucinogens produce-
Transitional behavior: Rapid ; intense mood swings that a person experiences multiple emotion at a time simultaneously.

Physiological effects: Including increased body temperate, heart rate ; blood pressure, overdose may produce seizure ; convulsion. 2
We will be focusing on three most potent hallucinogens. They are LSD, DMT ; PCP.

LSD (Lysergic Acid Diethylamide)
It is a synthetic hallucinogen which is first synthesized in 1938. Its d-isomer is extremely potent whereas l-isomer is inactive. Firstly, it was used as antipsychotic drugs but prohibited by FDA since people started to abuse it for recreational purposes.
center-140300Fig. LSD
Chemical Properties:
Molecular Formula- C20H25N3O
Molecular weight- 323.48
Route of exposure
Oral
Intravenous
Inhalation (less extent)
Mechanism of Action
Exact pathway of its mechanism is not elucidated. LSD exert its effect on activation of 5-HT (serotonin) receptors. LSD can be partial agonist or full agonist. Range of T
Metabolism
LSD is metabolized by hepatocytes via N-demethylation, N-deethylation and hydroxylation. A small fraction is eliminated in urine. It is highly protein bound (90%).

Range of Toxicity
Hallucinogenic Dose: 35 mcg
Recreational dose: 25-250 mcg
Minimal Lethal dose: 0.2- 1mg/kg body weight
Toxicity
In normal doses, LSD causes cognition alteration resulting in auditory ; visual hallucinations, mood swings, acute psychotic reactions within 30 minutes of oral ingestion. After one hour, a person experiences tension, lightheadedness, tachycardia, hypertension etc. Depersonalization and derealization occur from 2 to 12 hours. ‘Flashbacks’ with panic attacks can occur even after one year of exposure but it is very unusual.

Similar symptoms are seen in intravenous injection.

In toxic doses, people die from trauma not from altered perception. Prolonged seizure and convulsion occur rapidly.

LSD is a ‘Developmental Toxicant’. It shows teratogenic effect.

Drug interaction profile shows that if LSD is taken with other serotonergic drugs results in serotonin syndrome.

Management of Toxicity
Diagnosis
Plasma and urine LSD concentrations can be detected but the techniques are very rare. Creatinine kinase level and kidney function examinations are done with prolonged seizure patients. Neurologic examination and head CT help in patients with altered mental status.
Treatment
Both oral and parenteral exposures are treated in same ways. They are described below.

Mild to Moderate Toxicity
Anxiolytic drugs including benzodiazepines such as ‘lorazepam’ or ‘diazepam’ is used in anxiety.

Severe Toxicity
Activated charcoal is of little use because LSD is rapidly absorbed from GIT. Patients with severe anxiety should be sedated with benzodiazepines (lorazepam ; diazepam). ‘Fluid hydration’ is applied in ‘Rhabdomyolysis’.

People with severe anxiety can be treated with butyrophenones such as haloperidol.

Gastrointestinal decontamination is very limited. It is not recommended in recreational ingestion.

In recent ingestion, co-operative patients can be treated with activated charcoal though it is of little use. Gastric lavage, whole bowel irrigation has no role in severe toxicity.

Airway Management
Rare form of toxicity occurs when LSD is inhaled. These types of patients cannot be treated with intubation therapy as it is detected after a certain time.

Antidote
There is no official antidote is introduced for LSD toxicity.

Enhanced Elimination
It is highly excreted by fecal excretion and a small portion is eliminated in urine. As a result, Hemodialysis are of no use. Purgatives are useful within 30 minutes. 4
DMT (N,N-Dimethyltryptamine)
Discovered in late 20th century by two scientists. It is called ‘Spirit Molecule’. Different Amazonian tribes used it with tea (Ayahuasca). It is one of the most potent psychedelics. It is an alkaloid and isolated from two species of grasses Phalaris Arundinacea and Phalaris Aquatica. 5
center-136500Fig. DMT
Chemical Properties
Molecular Formula- C12H16N2
Molecular weight- 188.27
Route of Exposure
Oral with an MAOI
Intravenous
Intramuscular
Mechanism of Action
DMT exert its by binding with 5-HT 2A receptor. DMT also binds with alpha-1 receptor.

Metabolism
DMT is metabolized by monoamine oxidase enzyme via N-oxidation.

Range of Toxicity
Hallucinogenic dose: 5-15 mg
Toxic dose: 10-30 mg
Toxicity
Mild to Moderate Toxicity
Physical effects: Dilated pupil, tachycardia, mild hypertension etc.

Psychotropic effects: Sense of exhilaration, hallucinations including vivid bright colors, euphoria, distortion of sense of time etc.

Severe Toxicity
Physical effects: Muscular weakness, increased deep tendon reflexes, flushing etc.

Psychotropic effects: Mood alteration, powerful distortion, acute psychosis etc.

Management of Toxicity
Treatment
Acute seizure is treated with benzodiazepines. If seizure prolongs then propofol and barbiturates are given. Hyperthermia is rare but if occurs then patient is treated with sedative doses of benzodiazepines and rapid cooling with ice water or cool mist spray.

GIT decontamination cannot be done because patients are usually present late and uncooperative.

Airway Management
Endotracheal intubation is must performed for patients with persistent seizure.

Antidote
There is no official antidote for DMT toxicity.

Enhanced Elimination
No methods are used officially. 6
Phencyclidine (PCP)
PCP was used for medical purposes but its use was ended in 1950s. It is a synthetic hallucinogen. 5
center-78700
Fig. PCP
Route of Exposure
Orally
Intravenously
Mechanism of Action
PCP stimulates alpha adrenergic receptors. As a result, it inhibits the reuptake of catecholamines. It also stimulates opioid receptors and inhibit NMDA receptors.
Metabolism
PCP is primarily metabolized by the liver via oxidative hydroxylation.
Range of Toxicity
Hallucinogenic dose: 1-10 mg
Toxic dose: 20 mg or more.

Toxicity
Mild to Moderate Toxicity
Tachycardia, hallucinations, euphoria etc. It also causes mild to moderate agitation and acute mood swings.
Severe Toxicity
Psychosis, severe psychomotor agitation, hyperthermia etc. Death is followed by coma.

Reproductive Toxicity
PCP crosses placenta and causes neonatal irritability.

Management of Toxicity
Treatment
Mild to Moderate Toxicity
Benzodiazepines are used for agitation. Anti-psychotics are used in acute psychosis.

Severe Toxicity
High doses of benzodiazepines are used in hyperthermia and psychomotor agitation. For hyperthermia, control agitation and increase evaporative heat loss should be done by keeping the skin moist. Ice water immersion is performed in severe cases. Barbiturates and propofol are used in persistent seizure. Aggressive fluid resuscitation is done in multi organ failure, metabolic acidosis and rhabdomyolysis.

Gastric lavage cannot be done. Activated charcoal can be used in cooperative patients.

Airway Management
Endotracheal intubation is required if CNS depression develops.
Antidote
There is no official antidote for PCP toxicity.

Enhanced Elimination
Dialysis cannot be performed and are of no use. Urinary acidification may increase elimination of PCP but the risk of systemic acidosis may increase. As a result, it is not recommended. 7
Conclusion
From the study above, we have known about three most potent hallucinogens but here are more hallucinogens present. Though hallucinogens once used clinically, at present most of the hallucinogens are banned all over the world. Hallucinogens can trigger dormant schizophrenia genes and can worsen the situation of mentally ill patients. Hallucinogens causes long term mental disorders and addiction even if it is taken in very small amount. Finally, it is our duty to aware people about the danger and consequences of hallucinogens abuse for the nation’s welfare.

Bibliography
Psychology Today. (2018). Hallucinogens | Psychology Today. online Available at: https://www.psychologytoday.com/us/conditions/hallucinogens#treatments Accessed 10 Nov. 2018.

Psychology Today. (2018). Hallucinogens | Psychology Today. online Available at: https://www.psychologytoday.com/us/conditions/hallucinogens#treatments Accessed 10 Nov. 2018.

DrugAbuse.com. (2018). What Are Hallucinogens? – DrugAbuse.com. online Available at: https://drugabuse.com/library/what-are-hallucinogens/ Accessed 10 Nov. 2018.

Toxnet.nlm.nih.gov. (2018). LSD – National Library of Medicine HSDB Database. online Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@[email protected]+3920 Accessed 10 Nov. 2018.

Oceanbreezerecovery.org. (2018). The 12 Most Popular Psychedelic Drugs and Hallucinogens. online Available at: https://oceanbreezerecovery.org/blog/psychedelic-drugs/# Accessed 10 Nov. 2018.

Toxnet.nlm.nih.gov. (2018). TOXNET. online Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~8YJpS2:3 Accessed 10 Nov. 2018.

Toxnet.nlm.nih.gov. (2018). TOXNET. online Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~HlIV2l:3 Accessed 10 Nov. 2018.

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