Drug addiction and deaddiction

1. DRUG ADDICTION AND
DEADDICTION
DR. MANDEEP SARMA BASISTHA
PGT, DEPT. OF PHARMACOLOGY
GAUHATI MEDICAL COLLEGE
HOSPITAL

2. Introduction
• The Hindu mythology says
that during Amrit
Manthan one of the “14
Jewels” that the ocean
delivered was Varuni- the
Goddess of wine.
• 5000 B.C.: The Sumerian
people used the “joy
plant”, which is believed
to be opium.
Amrit Manthan
Sumerian Civilization

3. Introduction
• Smoking of Cannabis is known in
India since 2000 B.C.
• The Code of Hammurabi (1792-1750
BC) the oldest known form of legal
code, had guidelines and regulatory
provisions for preventing alcohol
abuse. King Hammurabi
(1792-1750 BC)
Code of Hammurabi

4. Why is it important?
DRUG USE IS ONE OF THE-
• Top 20 Risk Factors To Health Worldwide
• HIV/AIDS, Hepatitis
• Suicide – Psychiatric Disorders
• Tuberculosis
• Cardiovascular Diseases
• Overdose Deaths
• 30% Of HIV Infection Is Due To Injecting Drug Users
• When Criminal Activities Related To Drugs Are Included-
The Cost Of Drug Dependence can Amount To
2% Of The GDP.

5. Problem statement
• According to World Drug Report 2012 about 230 million
people, or 5 per cent of the world’s adult population, are
estimated to have used an illicit drug at least once in 2010.
• 10-13 per cent of drug users continue to be problem users.
• The prevalence of HIV (20 per cent), hepatitis C (46.7 per
cent) and hepatitis B (14.6 per cent) among injecting drug
users continues to add to the global burden of disease.

7. Problem statement
• India is located close to the major illicit opium growing
areas of the world, with- “Golden Crescent” on the
Northwest and “Golden Triangle” on the North–East.
• Licit substances (alcohol and tobacco) are the most
commonly used substances.
• Among illicit substances, cannabis and opiates are
most frequently used.

8. “Golden Crescent” and “Golden Triangle”

9. Drug dependence-
WHO has defined drug dependence as
“A state, psychic and sometimes also physical, resulting
from the interaction between a living organism and a drug,
characterized by behavioural 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.

10. USE
ABUSE
ADDICTION
DEPENDENCE

11. People Take Drugs in The First Place
To Feel Good
To have novel:
feelings
sensations
experiences
AND
to share them
To Feel Better
To lessen:
anxiety
worries
fears
depression
hopelessness

12. Drugs of Abuse
Engage Motivation and
Pleasure Pathways
of the Brain
People
Abuse Drugs

13. Addiction Involves Multiple Factors

14. Biological Factors Contribute to
Addiction--Comorbidity
Prevalence of Drug Disorders
Percent
Prevalence of
Nicotine Addiction
0
20
40
60
80
Percent
0
5
10
15
20
25
30
35
40

15. National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
Age
0.0%0.0%
0.2%0.2%
0.4%0.4%
0.6%0.6%
0.8%0.8%
1.0%1.0%
1.2%1.2%
1.4%1.4%
1.6%1.6%
1.8%1.8%
55 1010 1515 2121 2525 3030 3535 4040 4545 5050 5555 6060 6565
%ineachagegroupwho
developfirst-timedependence
CANNABIS
ALCOHOL
TOBACCO
Addiction Is A Developmental Disease
that starts in adolescence and childhood
Age at tobacco, alcohol, and cannabis dependence per DSM IV

17. Addiction Reward & well-being
Motivation
Movement
Dopamine

18. But Dopamine is only Part of the Story
• Scientific research has shown that other
neurotransmitter systems are also affected:
–Serotonin
• Regulates mood, sleep, etc.
–Glutamate
• Regulates learning and memory, etc.

20. All Abused Substances Enhance Dopamine (neurotransmitter) Activity
(particularly related to pleasure, motor, and cognitive function)

21. CLASSIFICATION OF DRUGS
OF ABUSE
• Drugs that activate GPCR
• Drugs that bind to ionotropic receptor and
ion channels
• Drugs that bind to transporter of biogenic
amines

22. Drugs that activate GPCR
Drugs Molecular
Target
Action Effect On DA
Neurons
Opiods μ- OR (Gio) Agonist Disinhibition
Cannabinoids CB1R (Gio) Agonist Disinhibition
Gamma-
hydroxybutyric
acid(GHB)
GABABR (Gio) Weak Agonist Disinhibition
LSD,
Mescaline,
Psilocybin
5-HT2AR (Gq) Partial Agonist

23. Drugs That Bind To Ionotropic
Receptor And Ion Channels
Drugs Molecular target Action Effect on DA
neurons
Nicotine nACh (α2β2) Agonist Excitement
Alcohol GABAA ,5-HT3,
nACh, NMDA,
Kir 3 channels
Excitement,
Disinhibition?
Benzodiazepin
es
GABAA Positive
modulator
Disinhibition
Phencyclidine,
Ketamine
NMDA Antagonists -

24. Drugs That Bind To Transporter
Of Biogenic Amines
Drugs Molecular
Target
Action Effect On DA
Neurons
Cocaine DAT, SERT,
NET
Inhibitor Blocks DA
uptake
Amphetamine DAT, SERT,
NET, VMAT
Reverses
transport
Blocks DA
uptake, synaptic
depletion
Ecstasy SERT > DAT,
NET
Reverses
transport
Blocks DA
uptake, synaptic
depletion

25. Drugs that Activate Gio-
Coupled Receptors
- Opioids
- Cannabis
- GHB
- LSD

26. – God's own medicine
Endogenous and exogenous agonists at- μ R, κ R, δ R.
In VTA
μ R κ R
on GABA D(-) on Dopamine
neurons neurons
INHIBITORY INHIBITORY
μ R agonists- Euphoria κ R agonists- Dysphoria

27. HEROIN
MORPHINE
CODEINE
OXYCODONE
MEPERIDINE
MOST COMMON OPOIDS ABUSED-
μ OPIOIDS

28. Features of opioid action
- Analgesia
- Altered mood
- Euphoria
- Dysphoria
- Miosis
- Sedation
- Nausea , vomiting
- Respiratory depression
- Constipation

29. Tolerance – OPIOIDS
High degree of tolerance
- Euphoria
- Sedation
- Nausea , vomiting
- Mental clouding

30. Physical dependence and withdrawal
syndrome - OPIOIDS
Symptoms Signs
Restlessness Mydriasis
Irritability Sweating, Lacrimation,
Rhinorrhea, Diarrhea
Insomnia Gooseflesh( piloerection)
Anxiety Tachycardia, ↑BP
Dysphoric Mood, Craving Yawning ,Fever

31. OPIOID WITHDRAWAL SYMPTOMS-
6-12 hr
• Craving for drug, Lethargy, Weakness
12 hr
• Yawning, Lacrimation, Rhinorrhoea, Tremor,
Anorexia
48 hr
• Fever, Tachycardia, Intestinal cramp, ↑B.P
7-10 days
• Restlessness, Insomnia, Weakness, Leg and back
pain.

32. TREATMENT OF TOXICITY
(OVERDOSE)
• OPIOID ANTAGONIST –
- I.V. NALOXONE : 2mg followed by repeat
injection in 5-10 min causes reversal of overdose.
But since naloxone has short half life, repeated
doses are needed every 1-2 hr.
- ORAL NALTREXONE ( For maintenance )
- I.V. NALMEFENE

33. TREATMENT OF DEPENDENCE
Detoxification
(treatment of
withdrawal syndrome)
1. Substitution Of Long Acting
Opioid Agonism- Methadone
2. Substitution Of Partial Agonist-
Buprenorphine
3. Substitution By α2 Agonists-
Clonidine , Lofexidine.
4. Clonidine
+Naltrexone+benzodiazepine+
NSAIDS
Maintenance therapy
1. Methadone
2. Buprenorphine
3. Opioid Antagonists-
Naltrexone

34. METHADONE :
Orally once daily.
1 mg will substitute 4 mg of morphine & 2 mg of
heroin.
Once the patient is stabilized on methadone, its dose is
gradually reduced by 20% daily & drug can be
completely stopped from 6th to 10th day.
CLONIDINE:
0.3- 1.2 mg/day and is tapered off in 10-14 days.

35. CANNABINOIDS
ganja- marijuana-hashish-
charas- BABA

36. CANNABINOIDS –ganja- marijuana-
hashish- charas
Delta 9-tetrahydrocannabinol (THC)
CB1 receptor action
Presynaptic inhibition of GABA neurons in the VTA
Disinhibition of DA neurons

37. Actions - cannabis
• Euphoria
• Feeling of well-being
• Relaxation
• Grandiosity
• Long term effects
- Panic, Anxiety
- Altered perception of passage of time
- Visual hallucination
- Diminished coordination
- Memory impairment
- Dysphoria
- Depersonalization
- Frank psychosis
- Depression
- Amotivational syndrome

38. Tolerance ,dependence, withdrawal
• Tolerance develops rapidly
• Withdrawal syndrome – mild
Restlessness
Irritability
Agitation
Insomnia
Nausea
Cramping
Rx of cannabis addiction
No specific treatment
CB-1 receptor blocker - Rimonabant

39. GAMMA-HYDROXYBUTYRIC ACID (GHB)
liquid ecstasy - club drug - date rape drug
• Endogenous - during GABA metabolism
. Binding site – GABAB receptor
. INDICATED IN – NARCOLEPSY
Before causing sedation and coma , GHB causes-
• Euphoria
• Enhanced Sensory Perceptions
• A Feeling Of Social Closeness
• Amnesia

40. LSD, MESCALINE &
PSILOCYBIN
 Molecular target- 5-HT2AR – Gq receptor. This
receptor couples to G proteins of the Gq type and generates
IP3, leading to a release of intracellular Calcium.
• Increase Glutamate release in the cortex
• Hallucinogens
• Effects-
- Altered sensory perception
- Shape and color distortion
- Distorted time perceptions
- Flash backs
- Bad trip
- Somatic symptoms- nausea, blurred vision, dizziness

41. LSD, MESCALINE &
PSILOCYBIN
• No dependence
• No addiction
• Tachyphylaxis
• Animal studies - no rewarding properties
- no DA increase
• Ritanserin - 5-HT2R antagonist – in animal studies
TREATMENT-
 Symptomatic treatment with anxiolytic, antidepressant,
antipsychotic along with supportive psychotherapy.

42. DRUGS THAT MEDIATE THEIR EFFECTS
VIA IONOTROPIC RECEPTORS
NICOTINE
ALCOHOL
BENZODIAZEPINES
PCP,KETAMINE

43. NICOTINE

44. • Nicotiana tabacum
• nAchR – selective agonist
• nAchR – expressed in VTA
• Nicotine causes release of DA in NA and PFC
• ά4β2- containing channels important for reward
• Most common route – smoking
• Oral ingestion

45. ACTION
• Some degree of euphoria and arousal
• Improve attention, learning, problem solving, and
reaction time
• Toxic dose - respiratory paralysis and severe
hypotension
MILD WITHDRAWAL SYMPTOMS
- Irritability
- Anxiety
- Restlessness
- Impatience

46. Rx Of Nicotine Addiction
• Nicotine substitution
- Gum
- Transdermal patch
- Nasal spray
All these do not achieve peak nicotine level – but
suppress the withdrawal

47. Two partial agonists of
α4β2 nAChRs
Plant-extract
Cytisine And its synthetic derivative - Varenicline
Both work by occupying nAChRs on dopamine neurons.
Varenicline may impair the capacity to drive and has been
associated with suicidal ideation.
Bupropion is approved for nicotine cessation therapy. It is
best when combined with behavioral therapies.
Cannabinoid (CB-1) receptor antagonist - Rimonabant -
increase abstinence.

48. ALCOHOL-ETHANOL
• Complex pharmacology
• Action on many receptors
- GABAA, 5-HT3, Glycine R, Kir3/ GIRK channels, NMDA
- Inhibition of Equilibrative Nucleoside Transporter 1-
Accumulation Of Adenosine
Stimulation Of Adenosine A2 R
Increased cAMP Response Element Binding Protein
Signalling
• Available in various concentration
• Mainly act as CNS depressant

49. CHRONIC ALCOHOL ABUSE = ALCOHOLISM
LIVER
- Alcoholic fatty liver
- Alcoholic hepatitis
- Cirrhosis
- Liver failure
Neurotoxicity
- Depression
- Peripheral neuropathy
- Gait disturbance
- Wernicke-Korsakoff syndrome
CVS
Cardiomyopathy and Heart
Failure
Arrhythmias
Hypertension
Coronary Heart Disease
FETAL ALCOHOL SYNDROME

50. Alcohol withdrawal syndrome
• Craving
• Tremor
• Sweating
• Nausea and vomiting
• Tachycardia
• Hypertension
• Seizures
• Visual hallucination
• Delirium tremens
8 hr
• Tremulousness, anxiety,
irritability, nausea,
vomiting.
24 hr
• Hyperexcitability, insomnia,
convulsion
2-5 days
• Tremor, Hallucination,
disorientation, Delirium
Tremens.

51. TREATMENT OF ALCOHOL ABUSE
ALCOHOL WITHDRAWAL ( INCLUDING DELIRIUM TREMENS ):
DETOXIFICATION
BENZODIAZEPINES- CHLORDIAZEPOXIDE, DIAZEPAM
OTHERS- CARBAMAZEPINE
ALCOHOL DEPENDENCE:
1. TREATMENT OF WITHDRAWAL- DETOXIFICATION
2. MAINTENANCE ( TO PREVENT RELAPSE AND MAINTENANCE OF
ABSTINENCE):
A. AVERSIVE DRUGS- DISULFIRUM
B. ANTICRAVING AGENTS- NALTREXONE, ACAMPROSATE,
TOPIRAMATE

52. BENZODIAZEPINES(BZDs)
• Action on GABAA receptors
• Increase frequency of single channel opening
• Disinhibition DA neurons –reward
• Short acting BZDs – more commonly abused

53. BENZODIAZEPINE WITHDRAWAL
DEPENDENCE IS COMMON
Anxiety Agitation
Insomnia
Phonophobia
Photophoobia
Dizziness
Paresthesia
Muscle Cramps
Seizure

54. Rx of BZDs ADDICTION
• Gradual reduction of dose
• Long acting BZD can be used for substitution
• ANTICONVULSANTS - Carbamazepine
Phenobarbitone
• Withdrawal symptoms Rx by PHENOBARBITONE
• Specific antagonist – flumazenil

55. KETAMINE & PHENCYCLIDINE (PCP)
• Club drugs
• Angel dust
• HOG
• Special K
Blockade of NMDA receptor
EFFECTS-
. Increase BP
. Impaired Memory Function
. Visual Alteration
Powder forms – snorted ,smoked, ingested
Dependence not seen
Chronic exposure – schizophrenia like state

56. INHALANTS
Ketones , Nitrates, Alipathic And Aromatic Hydrocarbons
Inhaled By- SNIFFING, HUFFING BAGGING
MOA- Altered function of ionotropic receptors, and ion channel
throughout the CNS.
Nitrous Oxide- NMDA R
Amyl Nitrite- Smooth Muscle Relaxation, Erection
Fuel Additives- Increased GABAA R
Toluene- Increase Excitability Of VTA
EFFECTS-
1. Euphoria
2. Chronic Exposure To Aromatic Hydrocarbons- Toxiciy To Many
Organs. White Matter Lesions In CNS.

57. DRUGS THAT BIND TO
TRANSPORTERS OF BIOGENIC
AMINES
- COCAINE
- AMPHETAMINE
- ECSTASY

58. COCAINE
• Alkaloid found in the leaves of Erythroxylon coca
• Local anesthetic
• Recreational Drug
• Orally, intranasally or smoking (free bashing)
• Common form – CRACK cocaine
• RUSH
• RUNS (Binges)
• CRASHES (Interruption Of Use)
• ‘SPEED BALL’

59.  PNS inhibits voltage-gated Na+ channels blocking
initiation and conduction of action potentials.
 CNS blocks the uptake of dopamine, noradrenaline, and
serotonin.
 The block of the dopamine transporter (DAT), by increasing dopamine
concentrations in the nucleus accumbens REWARDS
 Blockage of the norepinephrine transporter (NET) The
activation of the sympathetic nervous system
Acute Increase In Arterial Pressure,
Tachycardia
Ventricular Arrhythmias.
 Users typically lose their appetite, are hyperactive, and
sleep little.

60. INCREASE RISK OF
– Intracranial Haemorrhage,
– Ischaemic Stroke
– MI
– Seizures
OVERDOSE Hyperthermia, Coma, Death
WITHDRAWAL SYNDROME – is not as strong as that observed
with opioids. Tolerance may develop. In some users a
reverse tolerance is observed.
 DEPENDENCE
• Mild Physical
• Strong Psychic

61. TREATMENT –
 Cocaine overdose - IV Thiopentone/IV Diazepam (for
seizure & anxiety); IV Propranolol for sympathomimetic
effects.
 Chronic cases - Bromocriptine (a dopaminergic agonists) &
Amantidine (an antiparkinson drug) with psychotherapy is
used.

62. AMPHETAMINES
• Release of dopamine,
noradrenaline and serotonin.
• Students & Sportspersons are
the commonest users.
• Tolerance develops to Central
and Cardiovascular effects.
• "club drugs“
EFFECTS:
Increase Arousal
Euphoria
Abnormal Movements
Precipitate Psychotic
Episodes.
Neurotoxic
Alertness
Agitation
Confusion
Bruxism (Tooth Grinding)
Skin Flushing

63. INTOXICATION &
COMPLICATION-
• Tachycardia
• Hypertension,
• Seizure
• Hyperpyrexia,
• Tremor
• Pupillary Dilatation
• Tetany
• Acute intoxication may
mimics ‘Paranoid
Schizophrenia’.
• Tactile Hallucination
WITHDRAWAL SYNDROME-
• Depression(may be
suicidal),
• Apathy, fatigue,
• Hypersomnia etc.
TREATMENT-
Symptomatic treatment
• Antipyretic
• Antihypertensive
• Acidification Of Urine
With Vitamin-C.

64. MDMA = ecstasy
• Methylene dioxy
methamphetamine
• Party drug or club drug
• Preferential affinity for
the serotonin transporter
(SERT)
• Available in tablet forms –
100mg
Acute effect
- Feeling of energy
- Altered sense of time
- Enhanced perception
- Tachycardia
- Dry mouth, Dehydration
- Higher dose – visual
hallucinations,
hyperthermia, panic
attacks
- SEROTONIN SYNDROME
- Long term - neurotoxicity

65. STEROIDS ( anabolic – androgenic )
Commonly used anabolic steroids are: nandrolone phenyl
propionate , nandrolone decanoate , methanolone
acetate, oxandrolone .
Taken : Orally or injected, typically in cycles of weeks or
months.
Abused to enhance performance and to increase physical
appearance.
Adverse effects: hepatotoxicity,virilization in female
athlete,decreased spermatogenesis and testicular size ,
gynaecomastia.
High dose – hallucination, delusion, manic episodes

66. • No single treatment is appropriate for all
individuals.
• Treatment needs to be readily available.
• Treatment must attend to multiple needs of
the individual, not just drug use.
• Multiple courses of treatment may be
required for success.
• Remaining in treatment for an adequate
period of time is critical for treatment
effectiveness.
Treatment Can Work!
Principles of Treatment

67. Treating a Biobehavioral Disorder Must Go
Beyond Just Fixing the Chemistry
Pharmacological
Treatments
(Medications)
We Need to Treat the
Whole Person!
In Social Context
Behavioral Therapies
Social ServicesMedical Services

68. Drug treatment and care services
• Early screening, counselling and brief intervention
• Health care, including HIV and Hepatitis prevention
• Social assistance
• Families involvement
• Both psychosocial and pharmacologically assisted
drug dependence treatment services
• Mental health care, identification and treatment of
co-morbid psychiatric disorders
• Self-help techniques- Narcotics Anonymous

69. We Need to Keep Our Eye on
the Real Targets!
In Treating Addiction…

70. Where Do We Need
to Go From Here?
We Need to…
Advance the SCIENCE
Erase the STIGMA
and…
Erase the STIGMA
and…

71. The
Addiction
Ends
Here…!