HALLuCINOGENs

Presented by
Sonakshi. M
4th pharm d
16Q1028
Presented to
Mr. Kumaraswami.
Asso. Professor.
Dept of pharmacy practice.
Saccp.
Contents.
 Defination.
 Classification.
 Source.
 Mode of intake.
 Mode of action.
 Toxicokinetics.
 Clinical features.
 Management.
 Hallucinogens are substances that induce
changes in thoughts perception and mood
without causing major disturbances in the
autonomic nervous system.

 It
is derived from the latin verb ‘alucinari’ to
wonder in mind or to dream.

 Hallucinations may be visual, auditory,

olfactory, gustatory or tactile in nature.
• Classification.
 Hallucinogens are commonly spilt into two categories:

 1) Classic hallucinogens.( such as LSD).

 other examples include psilocybin, mescaline
and DMT.

 2) Dissociative drugs ( such as PCP).

 other examples include ketamine,
dextromethorphan , and salvia.
Classic hallucinogen.
 LSD( 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 contaminated of rye and
certain other grains.

 Today , most LSD is synthesised entirely in the

laboratory and typically sold to addicts as lipid
impregnated blotting paper or sugar cubes, tiny
tablets, gelatin squares, powders.
 LSD is said to be the
most powerful of all
hallucinogens and active
in doses of 50 to 100
micrograms.
 It occurs as a water

soluble , colorless,
tasteless, and odourless
powder.
Mode of intake.
 The LSD is almost always ingested.

 Other less common routes of intake include

intranasal , sublingual , smoking, conjuctival
instillation , and very rarely injection.
Mode of action .
 TheLSD is structurally related to serotonin and is an agonist at the
5 HT receptor .

 Serotoninmodulates many psychological and physiological

processes including mood, personality , affect, appetite, sexual
desires, motor functions, temperature regulation , pain perception
and sleep induction.

 LSD inhibits central raphe neurons of brainstem through stimulation

of 5 HT receptor, which are coupled to adenylcyclase .

 Themajority of 5 HT2 receptors in the brain are located in the

cerebral cortex.

 Animal experiments have shown that LSDs is anatomically

distributed maximally in the visual and auditory cortex and limbic
cortex , which parallels the finding of high concentrations of 5 HT2
receptors in human cerebral cortex.
Toxicokinetics.
 The LSD has a half life of 2.5 hours, while duration of
effects lasts for up to 8 hours.

 Butpsychotropic 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.

Clinical features.
 1) Acute poisoning.

 A) Physical:
 mydriasis, hippus, vertigo, tachycardia,
hypertension, sweating, piloerection,
hyperthermia, tachypnoea, muscle weakness,
ataxia, hyperactivity, and coma.

 B) psychological :
 euphoria or dysphoria.
 Vivid hallucinations, synaesthesias.
 occasionally there is depersonalization.
 2) Chronic poisoning.
 A) prolonged psychotic reactions which are

mainly schizophrenic in nature.

 B) severe depression.
 C) flashback phenomena: the person relives

the LSD experience periodically in the

absence of drug intake for months or years .
 D) post hallucinogen perception disorder:
 pareidolias.
 aeropsia.
Diagnosis.
 Radioimmunoassay of serum or urine ( limit
of detection of 0.1 mg/ml).

 HPTLCcan detect LSD in urine in

concentrations less than 1 mcg/litre.

 HPTLC of serum and urine.

 GC- MS can confirm positive LSD urine levels

to a lower limit of 5 pg/ml.
Treatment.
 Avoidgut decontamination as LSD is an ingested in micro
quantities and rapidly absorbed , rendering decontamination
procedure totally redundant.

 Donot used restraints in agitated patients; it will only

exacerbate the condition.

 Because of short half life and few serious medical reactions,

elimination enhancement procedures such as haemodialysis,
haemoperfusion , etc are not warranted.

 Treatacute panic attacks with quiet environment , reasurance,

supportive care, and adminstration of diazepam ( 5 – 10 mg IV)
or haloperidol ( in severe conditions)
 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.

 Treatflashbacks with psychotherapy, anti

anxiety agents, and neuroleptics.
 Treatpost 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.

 Thepatient must be instructed not to

consume alcohol, cannabis, and other drugs
which can intensify the disorder.
Dissociatve drugs.
Phencyclidine ( PCP).

 It is commonly referred to by addicts as “ angel

dust” or “ PCP”.
 PCP 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.

 Today ketamine a less potent PCP derivative is

Source.
 Phencyclidine, a phenylcyclohexylamine, is
easily synthesised from piperazine,
cyclohexanone, and potassium cyanide.
Mode of intake.
 PCP is abused by smoking, insufflation ,
ingestion or rarely IV injection.

 Itis commonly sold on the street as tablets

(about 5 mg), capsule , powder , aqueous or
alcoholic solution, or as “rock salt” crystal.

 It
is often mixed with parsley, mint, oregeno, or
marijuana.

 Sometimes “crack” is dipped in PCP and smoked

( tragic magic or cannabis is dipped in PCP ).
Mode of action .
 Phencyclidine antagonises the action of
glutamate at the NMDA ( N- methyl-d-
aspartate) receptor.

 Itbinds within the ion channel to block ca++

and Na+.

 Unlike the other type of glutamate receptor

channels, NMDA channels are permeable to
both ca++ and Na+.
 At doses much higher than at which it exerts
its unique behavioural effects by blocking
NMDA receptor mediated neurotransmission.
 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.
 They may explain the occurrence of

convulsions in PCP overdose.

Toxicokinetics.
 The volume of distribution of phencyclidine is
6.2L/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.
Clinical features.
 1) CNS:
 a) Level of consciousness ranges from fully alert
to comatose. the coma is usually preceded as
well as followed by agitation and psychosis.
 b) confusion, disorientation, amnesia.
 c) catatonia with unusual posturing ,mutism and
staring.
 d) myoclonic and distonic movements .
 e)cholinergic ( sweating , miosis , salivation ,
bronchospasm) and anti cholinergic ( mydriasis,
tacycardia) signs may be present.
 f) hallucinations, convulsions, and hyperthermia.
 2) EYE.
 Bank stare.
 Dysconjugate gaze.
 Nystagmus.
 Blurred vision.
 Miosis.

 3) CVS.
 Sinus tachycardia.
 Hypertension.
 4) GIT:
 Vomiting.
 5) RS:

 Tachypnoea.
 6) Renal:

 myoglobinuria.
 Acute renal failure.
Usual fatal dose .
 Approximately 100 mg or more.

 Lethal blood level: 0.1 mg/ 100ml.

Diagnosis.
 Serum PCP levels usually do not correlate well with
clinical picture. Therefore , a qualitative test is
adequate in most cases.

 1) Laboratory findings.
 Leucocytosis.

 Hypoglycemia.

 Hyperkalaemia.

 Elevated muscle enzymes.

 2) ECG:
 Diffuse slowing with theta and delta waves.
Treatment .
 The need for syrup of ipecac or gastric lavage
should be assessed carefully.
 Activated charcoal is highly beneficial and can

be administered at a dose of 1gm/kg every 4

hours for several doses.
 A single dose of cathartic such as sorbitol can

be given.
 Haemodialysis and haemoperfusion are not

beneficial.
 Asof now there is no antidote for PCP, though efforts on to
develop PCP- specific antigen binding fragments which can
prove to be very useful.

 Agitatedpatients should be restrained, at first physically 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, every 10
minutes, untill patient is calmed.

 Phenothiazines should be avoided since they can worsen

dystonic reactions , hypotension, hyperthermia and lower the
seizure threshold.
 25gm of mannitol and 100mEq of soSpecific
antihypertensive therapy should be instituted
in patient with very high blood pressure.
 Myoglobinuria should be treated with IV

infusion of 1 litre of 5% dextrose in

(containing dium bicarbonate) , at a rate of
250ml/hour.
 Monitor the patient for hypokalaemia. If renal

failure has occurred , haemodialysis should

be undertaken.
Dimethyltryptamine.( DMT)
 N,N-Dimethyltryptamine is a hallucinogen
obtained from the seeds and leaves of certain
south American plants such as piptadenia
pergynia and virola calophylla, as well as in
the tropical legume mucuna pruriens.
 DMT is not absorbed from gastro intestinal

tract, and so is typically snorted,smoked,or

injected.
 This elicits a virtually instantaneous onset of

visual hallucinations, body dissociation,

extreme shifts in mood , and auditory
phenomena.
 Effects peak within 2 minutes after injection
and resolve in 20 to 30 minutes.
 This has earned it the name “businessman’s

trip”.
 Physical effects include mydriasis, raised

body temperature, tachycardia and

hypertension.
 Treatment involves “ taking the patient down”

in a quiet, dark room, and institution of

symptomatic measures.
 Phenothiazines should be avoided to

minimise the danger of convulsions.

Mescaline.
 Mescaline is the principal hallucinogenic
agent among several alkaloids present in
peyote, a small bluish green spineless cactus
that grows in dry and rocky areas of
Southwestern united states and northern
mexico.

 The scientific name of the cactus is

Lophophora williamsii.
Clinical features.
 Ingestion of 6 to 12 mescal buttons is
required to induce a hallucinatory experience.
Symptoms usually resolve in about 12 hours
after ingestion.
 1) phase of GI distress: (30 to 60 minutes) –

nausea, vomiting ,diarrhoea ( rare).

 2) phase of sympathomimetic effects: ( 1 to 2

hours)- mydriasis, tachycardia , hypertension,

sweating and tremor.
 3) phase od sensory manifestations: (4 to 6

hrs)- vivid visual hallucinations, emotional

lability, anxiety, panic reactions.
Treatment.
 Involves provision of a quiet dark
environment, and calm reassurance,.
 Diazepam may be given orally or

intravenously.
Inhalants
(glue sniffing;volatile substance abuse)
 Inhalants drugs are widely available and
frequently abused , especially by adolescents
from poor socio economic background.
 These substances are volatile hydrocarbons
which are used as solvents, propellants,
thinners, and fuels.
 The hydrocarbon is typically inhaled by pouring
into container for “sniffing”, a rag or sock for “
huffing”, or a plastic/paper bag for“ bagging”.
 Abusers often begin with “sniffing”(lower
concentrations) and progress subsequently to “
huffing” and “ bagging”( higher level of
exposure).
 Chronic users can maintain a prolonged high with
periodic inhalations every few hours. The most
commonly abused inhalants include toluene from
paints and glues; petrol ; butane from butane from
cigarette lighter fluids; butyl and isobutyl nitrite ; and
halogenated hydrocarbons from typewriter correction
fluids, propellants, and dry cleaning fluids.
 Inhalation of volatile substances produces intoxicating

effects rapidly. They are well absorbed through the

lungs and distributed quickly to the CNS.
 One or two huffs will begin to intoxicate the user

within second, and the effects usually last for several

hours.
Clinical features.
 1) Acute:
 a) CNS- excitation, agitation, hallucinations,

headache , vertigo, ataxia, convulsions,

lethargy, stupor, respiratory depression.
 b) CVS- arrhythmias and sudden death.
 c) other effects-

 methaemoglobinaemia.( butyl and isobutyl

nitrites).
 Carbon monxide poisoning.
 hepatitis.
 Metabolic acidosis , rhabdomyolysis, renal

failure, hypokalaemia.
 2) chronic:
 a) chronic painter syndrome – a

neurobehavioural syndrome due to solvent –

induced encephalopathy, characterised by
memory loss, anxiety, depression, sleep
disorders, and personality changes.
 b) cerebral dysfunction with chorea.
 c) peripheral neuropathy.
 d) abdominal pain, nausea, vomiting.
 e) cardiomyopathy.
 f) hepatotoxicity.
 g) pulmonary disorders; pulmonary

hypertension, acute respiratory distress.

Medicosocial and forensic issues.
 Hallucinogen abuse has been traditionally a
western phenomenon, and drugs of abuse
such as LSD and phencyclidine have always
popular only in countries such as the USA,
UK, Australia and parts of Europe.
 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 as been an alarming resurgence
over the last decade.
 The dangers of hallucinogen use do not have
much to do with acute toxicity, as with long
term psychological damage.
 The inevitable fallout is violent crime

manifesting as assaultative behaviour,

homicides, and suicides.
 Several horrific crimes have been committed

by drug- crazed individuals acting out their

bizzare fantasies.
 Volatile substance abuse is a uniquely

adolescent phenomenon, and is particularly

common among lower socio economic classes,
mainly because these substances are cheap,
easily available,and legal to possess.
 VSAis quiet common among street urchins of
major Indian cities, probably because these
expensive substances offer a rare exciting to
escape from the daily misery of poverty.

 Persons with adolescent conduct disorder and

adult antisocial personality disorder are
especially prone to VSA.
References.
 Modern medical toxicology; fourth edition by
VV Pillay.
 Page no: 284 – 288 and 572-576
Thank you.