This document discusses various drugs of abuse including opioids, cannabis, GHB, hallucinogens, nicotine, alcohol, benzodiazepines, ketamine, cocaine, amphetamines, and ecstasy. It covers the molecular targets, effects, tolerance, dependence, withdrawal symptoms, and treatments for addiction and withdrawal for each class of drug. The classification of substance use disorder by DSM-5 is also mentioned.

1. Dr M.KARTHIGA

2.  INTRODUCTION
 TOLERANCE
 CLASSIFICATION
 TREATMENT OF VARIOUS DRUG
ABUSE

3.  American Psychiatric Association 's
Diagnostic and Statistical Manual of
Mental Disorders (DSM) 5 (2013)
 SUBSTANCE DEPENDENCE
DISORDER-a cluster of symptoms
indicating that individual persists with
use of the substance despite significant
substance related problems

4. Taking the opioid in larger
amounts and for longer than
intended
Stopping or reducing important
social, occupational, or
recreational activities
Wanting to cut down or quit but
not being able to do it
Recurrent usein physically
hazardous situations
Spending a lot of time obtaining Consistent use despite
acknowledgment of persistent or
recurrent physical or psychological
difficulties
Craving or a strong desire to use Tolerance
Repeatedly unable to carry out
major obligations at work, school,
or home
Withdrawal
Continued use despite persistent
or recurring social or interpersonal
problems
2-3 (mild) : 4-5 (mod.) ;
>6 (severe)

5.  REINFORCEMENT - Capacity of drugs to produce
effects that make the user wish to take them again
 mesolimbic dopaminergic pathway  increase
dopamine level
 Starts from ventral tegmental area (VTA)
projecting into nucleus accumbens ,amygdala,
prefrontal cortex
 Serotonin,glutamate,NE,endogenous opiods and
GABA
 Cocaine Amphetamines,opioids and
barbituratesalcohol,inhalantsLSD,marijuana
DiazepamAnabolic steroids

7.  Reduction in response to the drug after repeated
administrations
 Innate tolerance-sensitivity to a drug that is
observed the first time that the drug administered
 Acquired tolerance
1. Pharmacokinetic tolerance Changes in the
distribution or metabolism of a drug after
repeated administrations such that a given drug
produces a lower blood concentration than the
same dose did on initial exposure

8.  Pharmacodynamic tolerance Adaptive changes that
have taken place within systems affected by the
drug so that response to a given concentration of the
drug is reduced
 Learned tolerance - Reduction in the effects of a
drug owing to compensatory mechanisms that are
acquired by past
 Acute tolerance - Rapid tolerance developing with
repeated use on a single occasion such as in a
“binge”

9.  Reverse tolerance= Sensitization - Increase in
response with repetition of the same dose of the
drug
 Cross tolerance - When repeated use of a drug in a
given category confers tolerance not only to that
drug but also to other drugs in the same structural
and mechanistic category Barbiturates ⇔ BDZs
Amphetamine ⇔ Cocaine
 Detoxification- t/t gradual decrease in dose
weaning

11. PHYSICAL DEPENDENCE PSYCHOLOGICAL
DEPENDENCE
A state that develops as a result of
the adaptation produced by a
resetting of homeostatic
mechanisms in response to
repeated use of drug Indicates
new balance in presence of drug
Need of continuous presence of
drug Withdrawal syndrome is
the actual evidence of physical
dependence
Motivational component: great
subjective need, compulsion, drive
to get the drug Will take drug
periodically Although physical
dependence for a drug may not
occur, “drug-seeking behavior” is
present

12.  Abrupt termination of drug in a physically
dependent person
 depends on category of drug
 Withdrawal of stimulantsedation
 Two origins –
 Removal of the drug of dependence –
 CNS hyperarousal owing to readaptation to the
absence of the drug of dependence

13.  Drugs activating GPCR-
Opioids,Cannabinoids,Gamma Hydroxy Butyric
Acid, LSD, Mescaline
 Drugs binding ionotrophic receptors – Nicotine,
Alcohol, BZD,Ketamine,Phencyclidine
 Drugs binding to transporters of biogenic amines –
Cocaine, Amphetamine ,Ecstasy

14. DRUGS MOLECULAR
TARGET/ACTION
ACTION ON DA
OPIODS μ- OR/AGONIST DISINHIBITION
CANNABINOIDS CB1 /AGONIST DISINHIBITION
GHB GABA b/WEAK
AGONIST
DISINHIBITION
LSD/MESCALINE 5-HT2A/PARTIAL
AGONIST

15. DRUGS MOLECULAR
TARGET/ACTION
EFFECT ON DA
NICOTINE nACh/AGONIST EXCITEMENT/DIS
INHIBITION
ALCOHOL GABA-A,5-HT3,
nACh, NMDA
“
BZD GABA-A/POSITIVE
MODULATOR
DISINHIBITION
KETAMINE/PHEN
CYCLIDINE
NMDA/ANTAGONI
ST

16. DRUG TARGET ACTION EFFECT ON
DA
COCAINE DAT,SERT,
NET
INHIBITOR BLOCKS DA
UPTAKE
AMPHETAMI
NE
VMAT,DAT,SE
RT,NET
REVERSE
TRANSPORT
“
ECSTASY SERT>DAT,
NET
REVERSE
TRANSPORT
“

17.  Pain euphoria
 Heroin
 Smoked/snorted/needle
 Oxycodone
 Heroinrapid onset
 Euphoriasedation and tranquillitywears off 3-5
hours
 Oscillating between high and sickness of early
withdrawal

18.  Analgesia
 - Altered mood
 - Euphoria
 - Dysphoria
 - Miosis
 - Sedation
 - Nausea , vomiting
 - Respiratory depression
 - Constipation

19. EFFECTS
 Tolerance
 Behavioural disorders
 Inc. bacterial infections
 SPEEDBALL- cocaine and heroin
 WITHDRAWAL SYNDROME- within 6- 12 hrs/72-
84 hrs
 Heroin brief and intense
 Methadone-slower and lasts longer

21. DETOXIFICATION
 Methadone therapy – 20-30mg
 Clonidine-α 2 agonistofflabel
 Lofexidine
 Autonomic withdrawal symptoms controlled
 Activation of endogenous opioid system
 acupuncture and transcutaneous electrical
stimulation

22.  Rx of opioid addiction
 Methadone substitution therapy
 Partial agonist maintenance
 - Buprenorphine
 - Buprenorphine + naloxone
 Antagonist treatment – naltrexone
 Extended release depot

23.  Cannabis sativa and indica
 Ganja,, Bhang, Hashish or Marijuana
 Δ tetrahydrocannabinol
 Smoked/oral ingestion
 +alcohol= green dragon
 Used as anti emetic,muscle relaxant ,anticonvulsant
and dec. IOP

24.  CB1 –Hippocampus,mesolimbic DA,
cerebellum,substantia nigra
 Anandamide ,Dronabinol and Nabilone
 Inc .appetite in AIDS patients
 Rimonabant CB1 antagonist t/t of obesity and
smoking cessation
 CB2 lymphoid system,suppress immune system

25.  Stimulation sedation
 Euphoria Feeling of well-being Relaxation
Grandiosity
 Sedationunnatural posture,impairment of
memory,simple learning tasks and motor in
coordination
 Tachycardia,bronchodilatation,Blood shot
appearance of conjunctiva
 Amotivational Syndrome

26.  Tolerance develops and disappears rapidly
 Withdrawal syndrome – mild
 Restlessness
 Irritability
 Agitation
 Insomnia
 Rx - Antidepressants

27.  GHB – liquid ecstasy - club drug
 1 st introduced as a general anesthetic
 Endogenous - during GABA metabolism
 Binds – GABAB receptor
 Available in salt form
 Euphoria ,Feeling of wellbeing , a feeling of social
closeness

28.  Psychedelic
 5-HT2A mediated disruption of thalamic gating
with sensory overload of cortex
 Hallucinogens –dec excitatory threshold of retina
 Hyperarousal – dec excitatory threshold of RAS

29.  Altered sensory perception - Shape and color
distortion - Distorted time perceptions,olfactory
perception
 somatic symptoms- nausea, blurred vision, dizziness
 Paranoid delusions l/t suicide
 Depersonalisation and dreamy state
 Bad trips/good trips
 Minimal tolerance/ No dependence/addiction d/t Bad
trip and Flashbacks

30. TREATMENT
 Reassurance
 Diazepam 20mg if agitation
 Antipsychotics-CI

31.  Nicotiana tabacum
 nAchR – selective agonist
 Release of DA in Nucleus Accumbens
 ά4β2- containing channels important for reward
 Smoking/Oral ingestion
 Euphoria and arousal
 Improves attention, learning, problem solving, and
reaction time
 Toxic dose - respiratory paralysis and severe
hypotension

32.  Mild tolerance
 Best feeling after a day of abstinence
 Strong dependence

33.  NICOTINE SUBSTITUITION THERAPY –
suppress withdrawal syndrome and improves
abstinence
 Gum/ Transdermal patch/Nasal spray,Inhaler
 SR preparation of bupropion
 Rimonabant
 Varenicline – partial agonist of ά4β2 nACh
 Higher affinityblocks access to N

34.  Action on many receptors - GABAA,5-HT3, nACh,
NMDA
 CNS depressant
 Inc in blood levelsedationcoma,death

35.  LIVER
 - Alcoholic fatty liver
 - Cirrhosis
 - Liver failure
 Neurotoxicity
 - depression
 - Peripheral neuropathy
 - Gait disturbance
 - Wernicke-Korsakoff syndrome

36.  CVS
 Cardiomyopathy and Heart Failure
 Arrhythmias
 Hypertension
 Coronary Heart Disease
 FETAL ALCOHOL SYNDROME

37.  Acute tolerance soon after administration of
alcohol
 Chronic tolerance due to altered metabolism
 Cross tolerance with BZDs
 Potentiates sedative actions
 Withdrawal syndrome is common and sometimes
severe

38.  Craving,sleep disturbances
 Tremor,irritability
 Sweating
 Nausea and vomiting
 Tachycardia
 Hypertension
 Seizures
 Visual hallucination

39.  Delirium tremens
 48-96 hrs
 Severe agitation,confusion
 Fever,profuse sweating
 Dilated pupils,tachycardia
 Nausea,diarrhoea

40.  Hydration,electrolytes ,vitamins
 Thiamine therapy
DETOXIFICATION
 Oxazepam 15-30 mg every 6-8 hrs
 Anticonvulsants – carbamazepine
 Relapse prevention,anticraving medication and cognitive
behavioural therapy

41. Gabapentin-improves sleep
 Depot Naltrexone -30 days

42.  Sedatives and anti anxiety drug
 Action on GABAA receptors
 Disinhibition DA neurons –reward
 Street lore – diazepam + methadone
 Combination abuse
 Tolerance for sedation

43. Resembles anxiety syndrome for which it was treated
 Anxiety, agitation
 Insomnia
 Dizziness
 Paresthesia,strange sensations
 Muscle cramps,myoclonic jerks
 High dosesseizures ,delirium

44.  Gradual reduction of dose
 Long acting BZD or non BZD -Buspirone
 Carbamazepine, phenobarbitone
 Withdrawal symptoms Rx by
phenobarbitone,Diazepam,Chlordiazepoxide
 Specific antagonist – flumazenil
 Outpatient long term rehab program

45.  Club drugs/Angel dust/Special K
 Disassociative anesthesia
 Blockade of NMDA receptor
 Powder forms – snorted ,smoked, ingested
 emotional withdrawal,concrete thinking
 High dose- hallucinations,assaultive behaviour

46.  Stupor ,coma
 Muscular rigidity,rhabdomyolysis and hyperthermia
 Enlarged non reactive pupil
TREATMENT
 Acidification of urine
 Psychotic state- diazepam
 Antipsychotic with Ach activity avoided

47.  alkaloid found in the leaves of Erythroxylon coca
 Free base/crack
 Smoked/nasal use/iv use
 blocks the uptake of dopamine,
 noradrenaline and serotonin
 Reinforcement –d/t inhibit DAT
 inc DA

48.  Psychostimulation
 - Increase arousal ,performance
 - Sense of self confidence, Alertness
 - Euphoria,craving
 Chronic abuse – involuntary motor
activity,paranoia,
 Binge use-Addiction
 Combination abuse

49. TOXICITY
 Cardiac arrhythmia,MI
 Myocarditis , aortic dissection
 Seizures
 Death from trauma
 Premature labour,abruptio placentae
 Orgasmic drive
 Chronicpsychiatric disorders

50. Withdrawal symptoms
 - Depression , Dysphoria
 - Craving, fatigue
 - Sleepiness Bradycardia
 Tolerance seen
 Benzoylecgonine – urinary metabolite – detecting
cocaine use

51.  Antidepressants-withdrawal syndrome
 No detoxification
 Enhancing GABAergic inhibition –prevent relapse
 Topiramate
 Baclofen,GABAb agonist
 Modafinil

52.  indirect-acting sympathomimetic
 Inc. presynaptic release of DA,NE and 5HT
 Dextroamphetamine,methylphenidate,methamphet
amine
 One of the CLUB DRUGS

53.  intravenous administration , pill, smoked
 Increase arousal
 Bruxism
 Skin flushing
 Reduce sleep
 Euphoria
 Hallucination
 Hypertensive crisis, stroke
 Neurotoxic on long term use

54.  Party drug or club drug
 Psychodelic
 Altered sense of time,pleasant sensation
 Tachycardia,dry mouth, jaw clenching
 Higher dose- visual hallucination,agitation,panic
attacks

55.  Available in tablet forms – 100mg
 Acute effect
 - Feeling of energy
 - Altered sense of time
 - Enhanced perception
 - Tachycardia
 - Dry mouth
 - Higher dose – visual hallucinations, hyperthermia,
 panic attacks
 - Long term - neurotoxicity