Psychiatry

1. Biological basis of Tobacco
addiction & Implications for
treatment
Dr.Abinayaa Arasu,
Junior Resident.

2. Why do people begin to abuse drug?
1.To feel good-feeling of pleasure,”high”
2.To feel better-Eg.relieves stress
3.To do better-improve performance
4.Curiosity & peer pressure
According to National Institute on Drug Abuse,”Addiction” is defined
as a chronic,relapsing disorder characterized by compulsive drug
seeking and use despite adverse consequences.
The term Addiction is replaced my “Drug Dependence” by the WHO.
Drug Dependence is a behavioural pattern in which the use of a
given psychoactive drug is given a sharply higher priority over other
behaviours which once had a significantly higher value.

3. Dependence Syndrome:
• A strong desire or a sense of compulsion to take the substance;
• Difficulties in controlling the substance-taking behavior in terms its
onset,termination,or levels of use;
• A physiological withdrawl state when substance use as ceased or been reduced,as
evidenced by:the characteristic withdrawl syndrome for the substance or use of the
same (or a closely related)substance with the intention of relieving or avoiding
withdrawl symptoms;
• Evidence of tolerance,such that increased doses of the psychoactive substance are
required in order to acheive the effects originally produced by lower doses(clear
examples of this are found in alcohol-and opiate-dependent individual who may take
daily doses sufficient to incapacitate or kill non-tolerant users);
• Progressive neglect of alternative pleasures or interests because of psychoactive
substance use,increased amount of time necessary to obtain or take the substance or
to recover from its effects;
• Persisting with substance use despite clear evidence of overtly harmful consequences
such as harm to the liver through excessive drinking,depressive mood states
consequent to periods of heavy substance use,or drug related impairment of cognitive
functioning;efforts should be made to determine that the user was actually, or could
be expected to be,aware of the nature and extent of the harm.

4. PFC
TRY IT AGAIN VS TOO RISKY?
Amygdala Signals Hippocampus
RECORDS MEMORY OF
EXPERIENCE
I AM GOING TO REMEMBER
THIS
Nacc Signals Amygdala
WEIGHS THE PLEASURE OF
EXPERIENCE
THIS IS WORTH REPEATING
Drug Ingested - Stimulates NAcc
EUPHORIA WOW!

5. Drug
Addiction
has both
aspects,

6. • Nicotine is an alkaloid derived from the leaves of
the tobacco plant Nicotiana tabacum.
• The WHO estimates that there are 1 billion
smokers worldwide and they smoke 6 trillion
cigarettes a year.
• Also estimates that tobacco kills more than 2
million people each year.
• Consumable products of tobacco,
 Smoking
(Cigarettes,Cigars,Beedis,Hookah,Chillum,Cheroot)
 Smokeless
(Chewing,Snuffing,Local application)
• About 4000 chemicals have been detected in
tobacco smoke while around 3000 in smokeless
tobacco.
• Heroin & Cocaine are the two most addictive
drugs,with nicotine in the third spot.

7. Neurobiology:
o Nicotine affects CNS by acting as an agonist at the
nicotinic subtype of acetylcholine receptors( 4β2-
nAchRs).
o 25% of inhaled nicotine reaches brain through blood
stream in 6-15 seconds .
o Half life is about 2 hours.
o Brain imaging studies show that nicotine acutely
increases activity in PFC, thalamus and visual
system consistent with activation of cortico-basal
ganglia-thalamic brain circuits.
o Nicotine acts upon the nAchRs of DA,Glut & GABA
neurons over VTA.
o It activates the mesolimbic dopamine system.
o Nicotine stimulates the release of dopamine in the
pleasure circuit and increases extracellular level of
dopamine in NAc.
o Other neurotransmitters, including norepinephrine,
epinephrine, serotonin,
GABA,Achglutamate,endorphins,and
vasopressin,ACTH & cortisol are released as well.

8. Neurotransmitter Behavioral effect
Dopamine Pleasure, appetite suppression
Norepinephrine Arousal, appetite suppression
Acetylcholine Arousal, cognitive enhancement
Glutamate Learning, memory enhancement
Serotonin Mood modulation, appetite suppression
Beta-endorphin Reduction of anxiety and tension
Gamma-amino-butyric acid (GABA) Reduction of anxiety and tension
Neurotransmitters and their behavioral effects:

9. Genetics of tobacco addiction:
• CYP2A6 is an enzyme responsible for the majority of inactivation of
nicotine in humans.Genetic variation in CYP2A6 gene may protect
individuals from becoming nicotine-dependent smokers.
• Dopamine transporter (DAT) gene (SLC6A3) encodes protein that
regulates the synthetic levels of dopamine in the brain and leads to
addictive behavior.
Conditioning behavior in nicotine addiction:
• Classical conditioning theory predicts that drug-related stimuli can
become associated with the rewarding aspects of using drug
paraphernalia(cigarette packets,pipes) & environment where drug
taking occurs.
• For smokers,just the sight of a cigarette packet can evoke the feeling of
wanting to smoke.
• These stimuli can evoke responses,such as craving and drug seeking.

10. Tolerance and Dependence:
• The basal level of nicotine maintained by the smoker throughout the smoking
day keeps a proportion of nAChRs in a desensitized state, while the
remaining are available for activation by nicotine boli, if appropriate
concentrations are achieved. This way smokers manipulate their plasma nicotine
profile to achieve balance desensitization versus activation.
• When a smoker is asleep, plasma level of nicotine decreases and the nicotine
receptors gradually recover their active function. In the morning, a smoker has a
greater number of active nAChR sites (up-regulation) contributing to withdrawal
symptoms and craving. It is, therefore, the first cigarette of the day is, most
satisfying, as overnight abstinence allows a substantial recovery from nAChRs
desensitization.
• Post-mortem findings in smokers brain show increased number of nAChR
binding sites than normal individuals.

11. Clinical Features:
 Improved attention
 Learning & Problem solving ability
 Lifts mood
 Reduces tension
 Decreases depressive feeling
Short term exposure ,
• Increases cerebral blood flow
• Relaxes skeletal muscle.

12. Adverse Effects:
 In low dose produces nausea,vomiting,weakness,abdominal
pain,diarrhea,dizziness,headache,tachycardia,hypertension,
tremors.
 Toxicity leads to
 Respiratory paralysis
 Decreased REM amount of sleep.
 Smoking during pregnancy has ,
 Risk of having LBW babies
 Newborn with persistent pulmonary hypertension.

13. Withdrawl Symptoms:
According to DSM V ,withdrawl symptoms can develop
within 2 hours of smoking the last cigarette,they generally
peak in the first 24-48 hours & can last for weeks or months.
The common symptoms include an intense craving for
tobacco,tension,irritability,difficulty in
concentrating,drowsiness,paradoxical trouble
sleeping,decreased heart rate and BP,increased appetite &
weight gain,increased muscle tension and decreased motor
performance.
A mild syndrome of tobacco withdrawl can appear when a
smoker switches from regular to low-nicotinic cigarettes.

14. MECHANISM OF PHARMACOTHERAPY FOR SMOKING-CESSATION:
1. Nicotine replacement therapy:
FDA approved NRT includes transdermal patch, gum, nasal spray, inhaler and lozenges
which relieves craving and withdrawal symptoms, which are relieved with relatively low
blood nicotine levels, and causes positive reinforcement for arousal and stress relieving.
2. Antidepressant agents
Bupropion increases dopamine and norepinephrine blood levels, similar to the effect of
nicotine on these neurotransmitters. Nortriptyline is a norepinephrine reuptake blocker
and as such simulates noradrenergic actions of nicotine in the brain.
3. Clonidine
It is an alpha2 -adrenergic receptor agonist and reduces sympathetic neural outflow
resulting into sedation, anxiolysis, potential hypotension, bradykinesia and dry mouth.
Calming and anxiolytic effect helps in smoking cessation, particularly in those who are
very anxious while quitting smoking

15. Varenicline
It is an analog of plant alkaloid, reported to have some benefit in smoking cessation.
Varenicline has high and selective activity at alpha4–beta2 receptor, producing lesser
response than that of nicotine (30–60%) but also blocks the effect of any nicotine
added to the system. Thus, varenicline maintains a moderate level of dopamine
release, which reduces craving and withdrawal symptoms during abstinence. It also
blocks the reinforcing effects of nicotine obtained from cigarette smoke in the case of
relapse.
NicVAX
It works by stimulating the immune system to make antibodies that bind to nicotine
molecules, making them too big to cross the blood–brain barrier and preventing them
from reaching nicotine receptors and triggering the pleasure sensation that smokers
and users of nicotine experience and become addicted to. Data from pre-clinical trials
suggest that the injectable vaccine would be effective not only in helping people quit
smoking but also in relapse prevention because the nicotine antibodies last a long
time.

16. THANK YOU