Dr. VANDANA M.THORAT MBBS. MD.

PhD
PROFESSOR
DEPT OF PHARMACOLOGY
KRISHNA INSTITUTE OF MEDICAL SCIENCES
DEEMED TO BE UNIVERSITY KARAD
 DRUG DEPENDENCE & ADDICTION
 Repeated administration of certain drugs may induce
a habit and dependence.
 Drugs capable of altering mood and feelings are
liable to repetitive use to derive euphoria, recreation,
withdrawal from reality, social adjustment etc
 Many of these drugs also induce adaptive
physiological changes
 Which result in escalation of the dose needed to
produce the same effect.
 If the habit forming agent is not made available -
develops withdrawal symptoms
 Characterized by psychic/physical disturbances like
headache, restlessness, tachycardia, palpitation,
anxiety and emotional upset and/or convulsions and
vasomotor collapse.
 Many terminology viz ‘dependence', ' physical
dependence', 'psychological dependence',
'addiction', ' habituation, 'drug abuse' has been
used over the past to describe the above
phenomena.
 Drug Dependence (WHO)
 “a state, psychic and sometimes also physical,
resulting from the interaction between a living
organism and a drug, characterized by
behavioral and other responses that always
include a compulsion to take the drug on a
continuous or periodic basis in order to
experience its psychic effects and sometimes to
avoid the discomfort of its absence”.
 Tolerance may or may not be present
 A person may be dependent on more than one
drug
Drug dependence - three types
I. Drugs that cause severe psychic as well as
physical dependence
 Opioids or Morphine type -
 Morphine and its congeners like codeine, heroin,
dihydromorphinone,
 Synthetic morphine substitutes - pethidine ,
methadone, pentazocine & diphenoxylate
 Alcohol-Barbiturate type
Ethyl alcohol, barbiturates, paraldehyde, chloral
hydrate, meprobamate, benzodiazepines
 Nicotine (tobacco).
II. Drugs that cause definite psychic but mild or
questionable physical dependence
 Opioid antagonist type
Nalorphine
 Amphetamine type
Amphetamine, methamphetamine & phenmetrazine.
Piperidines like methylphenidate and pipradol.
III. Drugs that cause only psychic dependence -
 Cocaine, LSD, psilocybin, mescaline, cannabis
(marihuana, hashish, charas), caffeine (coffee, tea)

IV. Volatile substances -

 Glue, nail varnish, petrol, paint solvents, hair spray
etc.
 A. Psychological
 B. Physical; and
 C. Combined -
 A. Psychological Dependence - A condition in
which a drug produces “a feeling of satisfaction and a
psychic drive that require periodic or continuous
administration of the drug to produce pleasure or to
avoid discomfort”, is called psychic dependence.
 B. In case of physical dependence, the body
“achieves” an adaptive state that manifests itself by
intense physical disturbances when the drug is
withdrawn (withdrawal syndrome).
Drugs of Abuse Based on Dependence
Agents having only, mild psychological dependence
Coffee, Tea, Cigarette smoking.( Up to 10 cigarettes )
Agents with moderate to severe psychological
dependence - Marijuana, Hashish, LSD, Cocaine,
Amphetamine, Nicotine, Inhalants.
Agents having moderate to severe psychological
dependence with mild physical dependence
Benzodiazepines, Alcohol (moderate).
Agents having severe psychological and physical
dependence - Opioids, Barbiturates, Alcohol (heavy).
Drug Addiction
 The term ‘addiction’ used to denote the phenomenon
involving both psychic and physical dependence on
drugs, is currently designated as drug abuse.
 Drug addiction - A person is said to have
developed 'drug addiction ' when he/ she believes
that optimal state of well being is achieved only
through the actions of the drug.
 This was earlier termed 'psychological dependence'.
However, to avoid confusion, the widely understood
term 'drug addiction' is used now.
Its characteristics include
 An overpowering desire (compulsion) to
continue taking the drug in spite of knowing its
harmful effects.
 A tendency to increase the dose; and
 A high tendency to withdrawal symptoms.
 These drugs act on CNS
 These drugs produce sense of well-being in the user -
euphoria - e.g. opioids, barbiturates, alcohol and
cocaine
 1.User’s personality, factors play imp role
 2. Availability of the drug
A potential addict may start and continue taking a
dependence inducing drug -
 Following its medicinal use
 To achieve a sense of relief from stresses and tension
 To satisfy curiosity about drug effects
 To achieve a sense of belonging, to be ‘accepted’ by
others in the group.
 To express hostility or independence.
 To have euphoric, new, thrilling or even dangerous
experiences.
 To gain an improved understanding or creativity
 To escape from reality and to have a dreamy state.
Reinforcement
 ability of the drug to produce effects that the user
enjoys and which make him/her wish to take it
again – drug seeking behavior
 Strong reinforcers – Opioids , Cocaine
 Weak reinforcers – Benzodiazepines
 Drugs which produce craving - powerful
reinforcers - masterful drugs.
 Drugs that cause serious disability of functioning
normally by inducing psychic/physical dependence
are called Hard Drugs e.g. cocaine and heroin.
 Drug Habituation
 Less intensive involvement with the drug
 Its withdrawal produces only mild discomfort.
 Dependence is absent.
 Consumption of tea, coffee, tobacco, social drinking
are regarded habituating but not addicting
 It is difficult to delineate when 'desire' turns
into 'craving'.
 It is better to avoid using the term 'habituation’ as a
distinct phenomenon.
 Drug Abuse
 Term which refers t0 use of a drug by self
medication
 Manner and amount of drug use deviates from the
approved medical and social patterns in a given
culture at a given time.
 The term conveys social disapproval of the manner
and purpose of drug use
 For regulatory agencies drug abuse refers to any
use of an illicit drug – highly addictive and illegal
substances
The two major patterns of drug abuse
 Continuous use - The drug is taken regularly &
the subject wishes to continuously remain under
the influence of the drug, e.g. opioids, alcohol,
sedatives.
 Occasional use - The drug is taken off-and-on to
obtain pleasure or high, recreation (as in rave
parties) or enhancement of sexual experience, e.g.
cocaine, amphetamines, psychedelics, binge
drinking (a pattern of excessive alcohol drinking),
cannabis, solvents (inhalation). etc
 Neuropharmacology of Reward And
Reinforcement
 Activate “Reward – Reinforcing Pathway” called as the
Mesolimbic Dopaminergic Pathway - (Pleasure
centre and Pleasure Neurotransmitter)
 Opioids – (μ), (κ), (δ) Receptors.
 Cannabinoids – CB1 receptors DA
 Cocaine (Dopamine Transporters)
 Barbiturates, BDZs (Cl channel of GABA receptors)
 Nicotine ( Na channel linked to Nicotinic Receptor)
 Ethanol ( Ca channel linked to NMDA receptor )
 TREATMENT OF DEPENDENCE
 Ultimate goal - “Drug Free Status” as early as possible
and “Prevent The Relapse”
 Drug Free Status - Pharmacotherapy
 Prevention of Relapse - Rehabilitation and Psychosocial
Intervention.
 Pharmacological approaches to treat drug
dependence and withdrawal include
 1. Substitution by similar drug.
 2. Aversive Therapy.
 3. Use of Proper antagonist to prevent relapse.
 4. Craving reducing drugs.
 5. Rehabilitation and Psychosocial interventions.
 Detoxification- done by slow withdrawal of drug
or substituting a cross dependent drug so that
neuroadaptive mechanisms can become normal
without withdrawal.
 Medication - manage withdrawal symptoms,
prevent relapse, or treat any co-occurring mental
health condition such as depression or anxiety.
 Behavioral counseling - Individual, group,
and/or family therapy .
 Long-term follow-up - prevent relapse -
attending regular in-person support groups or
online meetings
 Cocaine
 Highly addictive – CNS stimulant
 Alertness , attention and energy
 Coca plant , which is native to South America.
 Other names - Coke, Snow, Rock, Blow, Crack
 Different forms - most common is a fine, white
powder / solid rock crystal.
 Most cocaine users - snort the white powder into
their nose/ Some rub it onto their gums / dissolve it
in water and inject it with a needle.
 Others heat up the rock crystal and breathe the
smoke
 Tolerance - It is less marked
 Psychological Dependence with increased drug
seeking behavior
 No Physical Dependence
 A/E –
 Tachycardia, Hypertension, Cardiac Arrythmia.
 Mydriasis
 Pyrexia , Nausea and Vomiting
 Rhabdomyolysis (long term use)
 Neurological and Limb defects (Cocaine Babies)
 Lethal dose - 96mg/kg. But the exact dose for each
person will vary based on their tolerance to the
drug, the drug’s purity, the person’s age, and
their health
 Treatment - Counseling and other types of therapy -
 Management of Toxicity
 Use i.v. Diazepam with Propanolol or CCB to control
Hypertension, cardiac Arrhythmias and Convulsions.
 Psychotic manifestations -Haloperidol.
 DA agonist like Amantadine can be used to treat
withdrawal symptoms.
 CANNABINOIDS
 Active Principle - Extract of Hemp Plant (Cannbis
Sativa and Cannabis Indica)
 Tetrahydrocannabinol (THC)
 Dried Leaves - Bhang
 Dried Leaves and Flowering Tops- Marijuana
 Exudates of flower tops and Leaves - Charas
 Hashish - THC content of Hashish - double that
of Marijuana.
 Half Iife - 18 hrs – 3 days
 THC - lipophilic - sequestered - fats & adipose tissue
 It initially causes CNS stimulation then sedation
 Stimulatory Phase - Euphoria, Increased
talkativeness, Increased appetite, feeling of confidence
and well being.
 Sedative Phase - feeling of Passing the time slowly,
retention of unnatural posture, impairment of short
term memory, simple learning tasks and motor
incordination.
 Peripheral effects – tachycardia, Vasodilation,
Reduction of IOP, Bronchodilation.
Psychological dependence is mild
No physical dependence.
Withdrawal effects are mild like anxiety, irritability,
decreased appetite, stomach pain, insomnia.
Plasma testosterone and sperm count decreases
Lethal dose – very large – 4 gm for 70 kg
Treatment - Symptomatic , BZDs
 Ethyl Alcohol
 CNS Depressant.
 Euphoria due to depression of inhibitory centers .
 Causes both psychological and physical dependence
 Pharmacokinetic as well as cellular tolerance
Acute Alcohol Intoxication
Early gastric lavage
Patent airway, respiratory assistance
I V fluids & electrolytes
IV Glucose infusion
Thiamine 100 mg in 500 ml glucose
 Nicotine Dependence
 Produces Psychic Dependence.
 Withdrawal symptoms - Headache, Insomnia, Anxiety,
Restlessness and Constipation.
 Clonidine - reduces withdrawal effects and craving for
smoking and antagonizes insomnia.
 Clonidine >> Nicotine Chewing Gum
 Nicotine Transdermal Patches – limited success since
do not suppress craving
 Bupropion - atypical antidepressant - smoking
cessation
 Varenicline - very effective, recently approved,
synthetic - decrease release of DA
 Opioids
 High degree of dependence and abuse liability
 Mainly pharmacodynamic & partly pkt tolerance
 Tolerance develops to most of actions except
constipating and miotic actions
 High cross tolerance
 Withdrawal s/s – lacrimation, sweating, anxiety,
fear, tremors, diarrhoea, colic, palpitation , rise in
BP , rapid wt loss
 Cessation leads to life threatening withdrawal
symptoms
Acute Morphine Poisoning
 Lethal dose - 250 mg. Increased in addicts.
 Coma, respiratory depression, pinpoint pupil,
hypotension, convulsions, pulmonary edema.
 Treatment -
 Naloxone - 0.4-0.8 mg i.v. every 2-3 min till
respiration improves or picks up.
 Gastric lavage with potassium permangnate.
 Positive pressure ventilation
 i.v. fluids & vasoconstrictors if required.
Treatment of Dependence
 Substitution with Methadone – 10 – 40 mg /day
orally over long period to produce high degree
tolerance – so pleasurable effects not perceived
 Minimizes withdrawal symptoms
 Gradually methadone tapered off
 Opioid Antagonist – Naltrexone- Orally - can be
started after complete withdrawal of methadone to
block euphoria & to prevents relapse.
 Clonidine - reduces severity of withdrawal s/s
 Rehabilitation
 Barbiturates
 Chronic administration – both psychological &
physical Dependence – abuse liability
 Withdrawal s/s – excitement, hallucinations,
delirium , convulsions and death
 Tolerance– pharmacokinetic & pharmacodynamic
– adaptation of neuronal tissue
 Gradual withdrawal – up to 3 wks
 Withdrawal symptoms - Diphenhydramine
 Seizures - during withdrawal - Diazepam or CBZ
Acute Barbiturate poisoning-
 Lethal Dose -2.0 -10.0 gms- the usual lethal blood
level ranges from 40 to 80 mcg/ml
 Mostly suicidal sometimes accidental
 Rx – Gastric lavage
 Supportive measures
 Forced alkaline diuresis with mannitol or
frusemide
 Haemodialysis and haemoperfusion
 No specific antidote is available
Benzodiazepines
 Dependence liability – low & Less Hangover
 Withdrawal s/s – mild – anxiety ,insomnia ,
restlessness , malaise ,loss of appetite , bad dreams
 Tolerance – develops gradually
 If an intermediate / short acting BZD is abused - long
acting BZD can be substituted - subsequently
withdrawn by tapering doses
 BZD Overdose - Flumazenil - Not used orally ( as
bioavailability 16 % )
 Given 0.3 – 1 mg i.v – action starts in sec & last for 1-2
hr
October 14, 2021
 LSD (Lysergic acid diethylamide)
 Hallucinogen - users see or hear things that do not
exist
 Effects – altered - thoughts, feelings, and awareness of
one's surroundings
 Dilated pupils, increased blood pressure &body temp.
 Effects start within half an hour and last for up to 12
hrs.
 Used mainly as a recreational drug or for spiritual
reasons
 Panic attacks or feelings of extreme anxiety
 Dependence & addiction liability – low
 No documented fatalities attributed directly to an
LSD overdose
 Treatment
Reassurance
Safe environment is beneficial.
Agitation-
Benzodiazepines as lorazepam or diazepam.
PREVENTION OF DEPENDANCE /ADDICTION
 Promotion of Health –Through personal and
cultural practices.
 Focus on people and encouragement of social
interaction
 Local involvement of young people and respect
for cultural values
 Encouragement of positive alternatives
 Long-term perspective - Don't be discouraged if
results aren't immediate
 Community development - Education, health and
social services, housing, sanitation etc