Many drugs -human beings consume

-they choose to, and not because

they are advised by doctors.
Society in general disapproves,
Because there is a social cost
Use is banned in many countries.
3 most commonly used non-
therapeutic drugs are caffeine,
nicotine and ethanol-legally and
freely available.
Many other drugs are widely used
Psychotropic drugs-Those
affect brain
Used by Physician-Psychiatric
diseases-can be misused or
abused
Non-prescription psychotropic
drugs- legal or illegal
Psychopharmacology explains
how these drugs affect brain
They dominates the
lifestyle of the individual
and damages his or her
quality of life
Habit itself causes actual
harm to the individual or
the community. [HIV,
 Addiction[Substance abuse]
= Physiologic+ Psychologic
dependence
Psychologic =Compulsive drug
seeking, craving
Physiologic = symptoms and signs
opposite to drug
Tolerance-PK, PD
DIAGNOSTIC and STATISTICAL
Reinforcement:Tendency of a pleasure-
producing drug to lead to repeated self
administration
Withdrawal-Drug is suddenly stopped—
develop a withdrawal syndrome characterized
by craving, dysphoria, signs of sympathetic
overactivity.
Rebound -Drug (usually for a medically
sanctioned use)- suddenly stopped— their
symptoms come back in an exaggerated
fashion.
Eg. BZDP for panic attacks suddenly stop
panic attack[Rebound panic attack].
Detoxification: Tapering of a drug
that has caused dependence and
would cause withdrawal if stopped
suddenly.
Detoxification accomplished slowly
withdrawing the drug itself or by
substitution of a cross-dependent
drug that has a similar
pharmacological mechanism of
action.
Prevents withdrawal symptoms.
 Mesolimbic Dopamine Pathway and the Psychopharmacology
of Reward[Reinforcement]
•Pleasure center
•Pleasure
Natural High Neurotransmitter. [DA]
ntellectual accomplishments
Athletic accomplishments
Enjoying a symphony
Experiencing an orgasm
Less intense
Natural High Drug induced high
Brain’s own!!!
 •Brain’s own!!!
•Endorphins[Morph
ine!]
•Marijuana
(anandamide),
•Nicotine
•(acetylcholine)
•Cocaine and
• amphetamine
(dopamine itself)
•Alcohol, opiates,
•Stimulants,
•Marijuana,
•Benzodiazepines,
•Hallucinogens
•‘HIGH ON’ DEMAND
•Unfortunately at a
PRICE
Drug-induced reward
Feeding of dopamine to
postsynaptic limbic (D2) sites
-furiously crave more drug to
replenish dopamine
Drug stopped
Individual becomes preoccupied
with finding more drug and thus
beginning a vicious circle.
Few receptors High risk for
Low initial response to a drugultimate abuse

High initial response Aversion to drug

Many receptors
Stimulants: Cocaine and Amphetamine
 •Cocaine powerful
Cocaine inhibitor -dopamine
transporter.
•Blocking this
transporter acutely
causes dopamine to
accumulate,
•Produces euphoria,
•Reduces fatigue,

•Cocaine has similar but

less important actions at
the NE and 5HT
transporters.

Local anesthetic
Freud and tongue Ca
•Repeated intoxication with
cocaine
• Sensitization or
"reverse
tolerance.“
•Cocaine releases more and
more dopamine.

•Doses of cocaine that

previously only
induced euphoria

•Now create an acute

paranoid psychosis
virtually
indistinguishable from
•The clinical
effects of
amphetamine
Derivatives are
similar to those
of cocaine
•Euphoria - less
intense
•Last longer
than that due
to cocaine
The hallucinogens are a group of agents
that produce intoxication, sometimes
called
a "trip,“
With changes in sensory experiences,
including visual illusions and
hallucinations,
Enhanced awareness of external stimuli
Enhanced awareness of internal
thoughts and stimuli.
These hallucinations are produced with
a clear level of consciousness and a lack
of confusion
Psychedelic is the term for the
subjective experience, due to
Heightened sensory awareness, that
one's mind is being expanded or
that one is in unison with mankind or
the universe and having some sort of a
religious experience.
Psychotomimetic means that the
experience mimics a state of psychosis
•Hallucinogens such as Lysergic acid
diethylamide (LSD),Mescaline,
Psyloscibin, and 3,4-
methylenedioxymethamphetamine
(MDMA)
Phenylcyclidine (PCP) developed as an
anesthetic
Not used- psychotomimetic hallucinatory
experience.
Its structurally related and mechanism-related
analogue
Ketamine –Used
Phenylcyclidine causes intense
Analgesia, amnesia, delirium, stimulant as well
as depressant effects,
Staggering gait, slurred speech, and a unique
form of nystagmus (i.e., vertical nystagmus).
Catatonia (excitement alternating with stupor
and catalepsy),
Hallucinations, delusions, paranoia,
Cannabis preparations are smoked
THC delta-9-tetrahydrocannabinol
(THC)
Interact with brain's cannabinoid
receptors
Triggers dopamine release from the
mesolimbic reward system
Cannabinoid receptors,
CB1 - brain
CB2 - immune system
Anandamide –endo genous
ne-Cigarette smoking is a nicotine delivery sy

•Nicotine acts directly

on nicotinic cholinergic
receptors,
• which are located in
part on mesolimbic
dopamine neurons
 Reinforcing actions of nicotine similar cocaine and
Amphetamine-But SUBTLE

Nicotine shuts down receptor shortly

after binding to it

Neither it nor Ach can stimulate for a while

[longer and much more intense euphoria with cocaine]
Pleasure of nicotine is a desirable but
small boost in the sensation of
pleasure ("minirush"), → decline until
the smoker takes the next puff or
smokes
the next cigarette.

Somewhat self-regulating –
Behavioral effects less severe thancocaine
Over time,
up-
regulation
Of
receptors
 Nicotine and DA release

No Nicotine and No DA release

CRAVING
Cigarette smoking is a pulsatile
nicotine delivery system

withdrawal from nicotine is

characterized
by craving and agitation,
Nicotine →nAChRs- The inactive
α4β2 metabolite, cotinine,
Produces inhibitory has a long plasma
and excitatory effects half-life -used as a
measure of smoking
Shows reinforcing habits
properties
Tolerance, physical
Peripheral effects → dependence and
Ganglionic stimulation: psychological
tachycardia,↑ BP,and dependence (craving),
↓GI motility. and is highly
Tolerance develops addictive.
rapidly Long-term cessation
Metabolised, mainly in succeed -20% of cases
the liver, within 1-2 The life expectancy of
hours.
Cancer, particularly of the lung and
upper respiratory tract but also of
the oesophagus, pancreas and
bladder
CAD and other forms of PVD
Chronic bronchitis
Harmful effects in pregnancy-Birth
wt., physical and mental
development↓[7yrs]
Parkinson's disease is
Motivation
Psychological help
Transdermal patch
Nicotine gum
Bupropion
“Brain's own morphine-like molecules."

Opiate drugs act on a variety of receptors,

 Piloerection ("goose
bumps") associated
with opiate
Pain relievers,
withdrawal,
-Codeine or Morphine,
Symptoms
Drugs of abuse,
subjectively so
-Heroin,
horrible
Euphoria, -reinforcing
Opiate abuser will
property.
often stop at
Withdrawal syndrome nothing in order to
Dysphoria, craving for obtain another dose
another dose of of opiate to relieve
opiate, irritability, and symptoms of
signs of autonomic withdrawal.
hyperactivity, such as What may have
tachycardia, tremor, begun as a
 Alcohol acts by enhancing inhibitory
neurotransmission at GABA-A receptors
Reducing excitatory neurotransmission
at the (NMDA) subtype of glutamate
receptors
So alcohol enhances inhibition and
reduces
excitation,
 Alcohol

•Enhancie GABA inhibition

Decreases the •Reduces glutamate
actions excitation,
of the •Enhances euphoric effects
excitatory NMDA •by releasing
receptor complex •Opiates and
—that is, it
Naltrexone Blocks opiate receptors
Decreases craving -increases
abstinence rates.
If one drinks when taking
Naltrexone, the opiates released do
not lead to pleasure, so why bother
drinking?
Some patients may also say, why
bother taking Naltrexone?
 •Acamprosate, a derivative of the
amino acid taurine,
•Interacts with the NMDA receptor
•Substitute s for this effect of alcohol
during abstinence
•Thus, when alcohol is withdrawn and
the mesolimbic D2 receptors are
whining for dopamine because of too
much glutamate,
•Alcamprosate substitution reduces
neuronal hyperexcitability of alcohol
withdrawal,
Reduced withdrawal distress and
craving.
Treatment alcohol abuse and
dependence 12-step programs
 Benzodiazepine

Modulators of
GABA-A

•Benzodiazepine -drug-naive patient,

•Acute benzodiazepine effect,
•Opening the Cl- channel maximally-
Enhancing inhibitory
neurotransmission
Anxiolytic actions.
Psychopharmacological mechanism
of euphoria,
•Chronic administration of
a benzodiazepine
•Tolerance and dependence
•Cl- channel to open less
than before
•But still enough to give an
anxiolytic Euphoric and
drug-reinforcing effect.
•Less than before
•Brain gets used to too
much
benzodiazepine at its
receptors
 BZDP-SUDDEN WITHDRAWAL
BZDP-ACUTE ADMN. [REVERSE OF BENZODIAZEPINE INTOXICATION]

Euphoria Dysphoria and

Tranquility and lack of depression
anxiety Anxiety and agitation
Sedation and sleep Insomnia
Muscle relaxation Muscle tension
Anticonvulsant effects. Seizures
•These actions continue until
benzodiazepine is replaced
•Alternatively BZDP can be tapered
•So that the receptors have time to
readapt
withdrawal symptoms are
prevented.
Has the clinical condition benefitted?
If ‘Yes” is he stable?
Has the pt. limited the use within
prescribed limits?
BZDP tapering programme