DRUGS OF

ABUSE
Don D. Cua, M.D., FPSECP
Our Lady of Fatima University
College of Medicine
Department of Pharmacology
 Course
Objectives:
Define the term drugs of abuse
Describe the major actions of commonly
abused drugs
Describe the major signs and symptoms
of overdose with and withdrawal from
drugs of abuse
Identify the most likely causes of death
from commonly abused drugs
Know how to manage drug abuse
 Definitions of
terms:
Abuse - any use of a drug for
non-medical purposes, almost
always, for altering
consciousness
Misuse-Use of a drug for the
wrong indication or wrong
dosage
 Definitions of
terms:
Psychologic dependence(ADDICTION)
- compulsive drug seeking behavior for
personal satisfaction like
heavy cigarette smoking

Physiologic dependence
- is present when withdrawal of the drug produce
signs and symptoms that are
frequently the opposite of those
sought by the user ( eg. alcohol or
coffee withdrawal)
 Definitions of
terms:
TOLERANCE decreased response to a
drug, necessitating larger doses to achieve
the same effect
Metabolic tolerance - disposition of a drug
Behavioral tolerance ability to compensate for
the effects of a drug
Functional tolerance changes in receptor or
effector system involved in drug actions
 DEPENDENCE- state characterized by signs
and symptoms, the opposite of those produced
by the drug when it is withdrawn from chronic
use or when the dose is abruptly lowered
ADDICTION disease of maladaptive learning;
compulsive, relapsing drug use despite
negative consequences (craving) (wanting
without liking). Addiction is a recalcitrant,
chronic, and stubbornly relapsing disease that
is very difficult to treat.
Withdrawal state of being deprived
Designer drug synthetic derivative of a
drug; slightly modified structure
 Controlled substance - a drug
deemed to have abuse liability
(schedules of controlled substances)
Relapse to fail or slip back into a
former state or way of acting
 Reasons for relapse:
Re-exposure to the
addictive drug
Stress
A context that recalls prior
drug use (people,
places, drug paraphernalia)
paraphernalia
 (Lame) Excuses for drug
abuse
Curiosity
Peer pressure
Reward
Poverty/Born to Privilege
Anxiety
 The Different DRUGS of ABUSE
Opiates & opioids - opium, heroin, morphine, oxycodone,
meperidine
Depressants & other sedatives - barbiturates, alcohol,
bromide, benzodiazepines
Stimulants - caffeine, nicotine, cocaine, amphetamine

Hallucinogens - LSD, mescaline, psilocybin, phencyclidine,

ketamine

Cannabinoids marijuana
*Inhalants
- anesthetics - chloroform, ether, halothane, nitrous
oxides
- industrial solvents - hydrocarbons
- aerosol propellants - fluorocarbons
- organic nitrites - amyl nitrites, butyl nitrites
*Steroids
SCHEDULE OR POTENTIAL FOR COMMENTS SAMPLE
CLASS ABUSE

CLASS I High All non-research use Narcotics = heroin

illegal; lack of accepted Hallucinogens
safety as a drug = LSD, MDA, STP, DMT, DET, mescaline,
bufotenine, ibogaine, psilocybin, PCP
Marijuana
Methaqualone

CLASS II High Abuse may lead to Opioids = opium and opium Alkaloids
psycho-physical = morphine, hydromorphone,
dependence. No oxymorphone, oxycodone
telephone prescription.
No refill Synthetic derivatives:
= meperidine (Demerol), methadone
levorphanol, fentanyl (Sublimaze)
Stimulants
= cocoa leaves, cocaine, amphetamine,
methamphetamine, nethylphenidate,
lisdexamfetamine, dextroamphetamine
Depressants
= Barbiturates
Amobarbital, pentobarbital
Secobarbital, gluthetiminde
Cannabinoids
- Nabilone
CLASS III Less than I and II Moderate or low potential for Opioids:
physical dependence with high Buprenorphine,
potential for psychological codeine
dependence. Prescription must
be rewritten after 6 months. dihydrocodeine
hydrocodeine
Can be given up to 5 refills opium (paregoric)
Stimulants:
benzphetamine
phendimetrazine
Depressants:
barbiturates in Class
II in suppository form
Butarbital, ketamine,
thiopental
Cannabinoids:
Dronabinol
Anabolic steroids:
Fluoxymesterone,
methyltestosterone,
nandrolone
decanoate/phenproate,
oxandrolone,
stanozolol
CLASS IV Less than that of Limited potential for Opioids:
dependence. Butorphanol,
Class III Prescription must be
rewritten after 6 Difenoxin
months. Given up to Pentazocine
5 refills.
Propoxyphne
Stimulants:
Lesser penalty for
illegal use than that in Diethylpropion
Mazindol
Class III
Phentermine
(Ionamin)
Fenfluramine
Pemoline,
Sibutramine
Depressants
Benzodiazepines
Chloral hydrate
Meprobamate
Zolpidem
Paraldehyde, Zaleplon

Phenobarbital
CLASS V Less than that Limited Opioids
of Class IV dependence is Codeine
possible. A 200mg/100ml
non-opioid. Diphenoxylate
(Lomotil)
May be Dihydrocodeine
dispensed w/o a Pregabalin
prescription
unless
additional state
regulations
apply
Pharmacology of
DRUG ABUSE
 Stimulation of the
Ventral Tegmental Area (VTA)
mesolimbic dopamine system(prime target)
(tip of the brainstem)
release of
dopamine
nucleus accumbens
(amygdala, the hippocampus, prefrontal cortex)

increase the level of DOPAMINE
reinforcement
(feelings of euphoria and
reward)
 Basic Pharmacology of Drug Abuse
3 distinct cellular mechanisms:
1. G10 protein-coupled receptors (GPCRs)-
the action of these drugs is preferentially on
the-aminobutyric acid (GABA) neurons that
act as local inhibitory interneurons.
2. Ionotropic receptors on ion channels
combined effect on dopamine and GABA neurons.
(enhance the release of dopamine)
3. Dopamine transporters interfere with
monoamine transporter; block reuptake of dopamine
or stimulate non-vesicular release of dopamine,
causing an accumulation of extracellular dopamine.
 1. G10 protein-coupled receptors
(GPCRs)- drugs that act on GABA
neurons
Opiods
Cannabinoids
Y-Hydroxybutyric (GHB) acid
Hallucinogens
 2. Ionotropic receptors on ion channels
combined effect on dopamine and
GABA neurons (enhance the release of
dopamine)
Nicotine
Alcohol
Benzodiazepine
Dissociative Anesthetics
Inhalants
3. Dopamine transporters
Drugs that bind to TRANSPORTERS of
biogenic amine
interfere with monoamine
Cocaine
transporter;
block reuptake of dopamine or stimulate
Amphetamines
non-vesicular release of dopamine, causing
Ecstasy
an accumulation of extracellular dopamine
 1. G10 protein-coupled receptors
(GPCRs)- drugs that act on GABA
neurons
Opiods
Cannabinoids
Y-Hydroxybutyric (GHB) acid
Hallucinogens
Opium flower, plant
Opium plant
OPIUM
Morphine
Heroin
Heroin user
 MECHANISM OF
ACTION
G protein coupled receptors
,,
couple to inhibitory G proteins
( they all inhibit adenyl cyclase) but with
opposing effects
- receptor inhibit GABA neurons, leading
to disinhibition
of dopamine receptor (euphoria),
k inhibit dopamine neuron.
(dysphoria)
MOST ABUSED: Morphine, Heroin
(diacetylmorphine),Codeine,
Oxycodone, Meperidine ( among health
professionals)
 Withdrawal
symptoms
= begins 8 - 10 hrs after the last
dose
= resemble increase sympathetic
activity
Early: lacrimation, rhinorrhea, yawning,
sweating, hypertension
Later: restless sleep, weakness, chills,
gooseflesh( cold turkey),
nausea/vomiting, muscle aches ,
involuntary movements ( kicking the
habit )
hyperpnea ( increase respiratory rate )
hyperthermia ( increase temp )
Complications:
- Overdose TREATMENT: Naloxone
- Hepatitis
- AIDS
- Bacterial infection
- at injection site: osteomyelitis, sepsis,
systemic abscess ,
meningitis
- Parkinsonism (spasticity )
MPTP( 1-methyl -4 phenyltetrahydropyridine)
deprivation of
dopamine in striatal cell cell
death
(noted in users of fake Meperidine due a highly
toxic neurotoxin)
- homicide
 Treatment of Opioid
Abuse
1. Pharmacologic approach chronic users
Principles of detoxification:
A. substitute a longer-acting, orally active,
pharmacologically equivalent drug such as:
- Methadone - saturates opioid receptors and prevents
the desired sudden onset of effects; OD
- Clonidine - centrally-acting sympatholytic agent that
reduces central sympathetic outflow ( recidivism)
- L-acetylmethadol - analog of methadone; 3x/week
- Buprenorphine 2-10mg OD, SL PARTIAL OPIOID RECEPTOR
AGONIST
B. stabilize the patient
C. gradually withdraw the substituted drug
- naloxone - used to eventually extinguish the habit;
100-150mg/d, 3x/week
2. Psychosocial approach - realization
Marijuana(CANNABINOID
S)
 Marijuana
(active substance: tetrahydrocannabinol or THC)
Cost: $20/gm
Causes: disinhibition of dopamine neurons
mainly by presynaptic inhibition of GABA neurons at
VTA
Results in euphoria, relaxation, well being,
grandiosity, altered perception of passage of time
Uses: appetite, IOP, relief of muscle
spasm,
attenuation of nausea (Dronabinol-agonist),
relief of chronic pain (Nabilone),
anticonvulsant (levonantradol)
Treatment: stopping the drug results to clarity of
thinking
 Marijuana
Route: smoking, IV
oral slow, highly variable, longer
duration of action
Tolerance seen among heavy, long-
term users
Hazards of use: lower serum
testosterone level,
airway narrowing; amotivational
syndrome
 Cannabis
Intoxication
= increase pulse rate, reddish conjunctiva,
hypotension,
antiemetic, muscle weakness,
unsteadiness,
increased deep tendon reflexes, impaired
psychotic test
= withdrawal symptom noted after a very
high dose

= decrease testosterone?,
bronchoconstriction?
(bronchitis, obstruction, metaplasia),
altered immunity?,
fetal effects?, angina may be
 -Hydroxybutyric
acid
( liquid
b receptorsecstasy;
General anesthetic
GABA sole mediator date
of GHB action
rape drug)
Cause: euphoria, enhanced sensory perception,
feeling of social closeness, amnesia
For narcolepsy
anticraving compound since at higher doses,
it hyperpolarizes dopamine neurons

Cost: $ 20-35/pill
 Hallucinogens
Tolerance develops rapidly
Reasons for abuse: perception
distortion
(how one looks at the
world)
new insights on personal
problems
 Hallucinogens
:
non-addictive
Lysergic acid, diethylamide
does not induce dependence
(LSD) but
The main molecular
cause
target tachyphylaxis
is 5-HT 2A receptor---couples to G proteins of the Gq type and
generates inositol trisphosphate (IP3 ), leading to a release of
intracellular calcium.
mescaline & psilocybin
Sources: cactus buttons or magical mushrooms
- deliriants = atropa belladona & datura stramonium
- also in morning glory seeds = monoethyl amide
Cause: alter consciousness; psychosis-like
manifestations: depersonalization, hallucination,
distorted time perception; somatic symptoms:
dizziness, nausea, paresthesia, blurred vision
MOA: glutamate release in the cortex, by enhancing
excitatory afferent input via presynaptic serotonin
receptors from the thalamus
 LSD
Ergot alkaloids; resemblance to 3
neurotransmitters
(NE, dopamine, serotonin)
MOA: activates serotonin (5HT2A) receptors at the
prefrontal cortex alters serotonin turnover
( 5-hydroxyindoleacetic acid)
enhances glutamatergic transmission,
resulting to the hyper arousal of CNS
(enhanced perception)
Psychoactive effects from 30mins to 6-12hrs.
20-30mcg
Neurotoxic and can cause uterine contractions
 2. Ionotropic receptors on ion channels
combined effect on dopamine and
GABA neurons (enhance the release of
dopamine)
Nicotine
Alcohol
Benzodiazepine
Dissociative Anesthetics
Inhalants
 Nicotine
Cause: enhance cognitive performance
Smoking, chewing, snuff. Chronic use is addictive.
Withdrawal is mild compared with opoid withdrawal---
irritability and sleep problems are most common.
MOA: selective agonist of the nicotinic acetylcholine
receptor
(nAChR) activated by Acetylcholine in VTA
alpha42-containing channels at VTA nAChRs
(loss is associated with Alzheimers dementia)
Treatment: nicotine (transdermal slows PK and PD)-
elimination
BUPROPION (antidepressant) + behavioral therapies
CYTISINE (plant extract) , VARENICLINE(synthetic)
- 2 partial agonists of 42containing nAChR
-prevent nicotine from exerting its action
NOTE: Varenicline-impair the capacity to drive---suicidal
ideation
 Alcohol

(ethanol)
MOA: COMPLEX --Alters the function of several
receptors and cellular functions, including GABA a
receptors, Kir3/GIRK channels, adenosine reuptake,
glycine receptor, NMDA receptor and 5HT3 receptors.
Causes: Slows reaction time and impair judgment and
coordination
Limit is 0.08% or 80mg/dl
Withdrawal syndrome: hand tremors, nausea and
vomiting, excessive sweating, agitation, anxiety,
visual, tactile and auditory hallucinations (12-24 hrs.
after cessation); delirium tremens hallucination,
disoriented, autonomic instability (48-72 hrs. after
cessation)
 Treatment of Alcohol
abuse:
Supportive; psychosocial approach
Use of benzodiazepines (oxazepam,
lorazepam; chlordiazepoxide)
After detoxification:
Naltrexone 50 mg OD
Acamprosate 1-2 tabs (333mg) 3x
a day
Disulfiram inhibits aldehyde
dehydrogenase
 Benzodiazepines
Sedative-hypnotic, anxiolytic
Withdrawal occurs within days: irritability, insomnia,
phonophobia, photophobia, depression, muscle cramps,
seizures
MOA: positive modulators of GABA receptors on
dopamine neurons of the VTA, mediated by 1subunit of
GABA receptors.
- > 40mg/d physiologic dependence-very common
- 15-30mg/d therapeutic dose dependence
- withdrawal leads to weight loss, changes in perception,
paresthesias, headache
Cost: $ 0.50 / 5mg tab.
Treatment: Detoxification (decrements of 15% -25% to
5%-10% of dose); antidote
Benzodiazepines
 CLUB DRUGS
General anesthetics
Sold in the names of angel dust, HOG and
SPECIAL K
They owe their effects to their use-dependent, noncompetitive
antagonism of the NMDA receptor. The effects of these substances
became apparent when patients undergoing surgery reported
unpleasant vivid dreams and hallucinations after anesthesia.
Club drugs also include GHB, ecstasy and amphetamines
Liquid, capsule, pill; snorted, ingested, injected,
smoked. Psychedelic effects last for about 1 hour and also
include increased blood pressure, impaired memory function,
and visual alterations.
Do not cause dependence and addiction but chronic
exposure leads to long-lasting psychosis resembling
schizophrenia
 Ketamine
- a dissociative anesthesia
- replaced PCP for human use
- effects: BP, impaired memory function,
visual alterations; unpleasant out-of-
body
and near-death experiences
- Toxicity of hallucinogen
panic reaction - bad trip
- Treatment: sedation with barbiturates or
benzodiazepine
"talking down"
 Phencyclidine (PCP,
angel dust)
Used as dissociative anesthetic
(separating bodily functions from the
mind without causing loss of
consciousness); detachment,
disorientation, distortion of body
image;
loss of proprioception
Withdrawn for use in humans
Replaced by ketamine
Smoked, snorted, oral or IV
 PCP Toxicity:
Toxicity
Psychologic consequence: panic
reactions,
errors of judgment best managed
by barbiturates or benzodiazepines
Antidote: physostigmine
acidification of urine (NH4Cl, vit C ,
cranberry juice),
diazepam
 Inhalants
KINDS: anesthetics :
Nitrous oxide, chloroform,
Ether, halothane
Industrial solvents
Hydrocarbons (toluene)
Aerosol propellants : fluorocarbons
Organic nitrites : amyl nitrites,
isobutyl
nitrites
 Inhalants:
Anesthetics
1. Nitrous oxide
= taken as 35% mixed w/ oxygen
= inhalation of 100% may cause asphyxia or death
= effects :difficulty in concentrating, dreaminess,
euphoria, numbness, tingling, unsteadiness,
visual/auditory disturbance
2. Ether & Chloroform
= effects: exhiliration initially followed by loss of

consciousness
= highly flammable
 Inhalants: Industrial
solvents
gasoline, paint thinner, glue,
rubber cement, acrylic paint
spray, shoe polish, degreasers
Toxicity: damage to liver, kidney,
peripheral nerve, brain, bone
marrow, lungs
Inhalant user
 Inhalants:
Hydrocarbons
toxic ingredients - toluene, heptane, hexane, benzene,
trichloroethylene, methylethylketone
motives for abuse - peer influence, low cost, readily
available, convenient packing, quick intoxication of
short duration (5-15 min.), mood enhancement
principal users - boys, early teens,
low socio-economic status, problematic people
= develops psychologic dependence
manner of abuse:
huffing: cloth is soaked w/ solvent & fumes are inhaled
bagging: aerosol propellants are inhaled from plastic bag
= effect : initially euphoria w/ relaxed & a drunk feeling,
followed later on by disorientation, slow passage of time
& hallucination
 Inhalants: Organic
nitrates
Amyl nitrates
- used medically for angina
- contained in fragile ampules covered by cloth which
easily can be broken (w/ popping sound) & inhaled
- called "poppers (not addictive)
Isobutyl nitrates
- bottled
- "locker room", "rush
Effects : giddiness (lightheadedness), dizziness, rapid
heart rate, decreased BP, flushing of skin, "speeding",
decreased inhibition, increased strength of erection
thus prolonging sexual intercourse
Toxicity: hazard to patients w/ cardiovascular disease
Inhalant hazards
3. Dopamine transporters
Drugs that bind to TRANSPORTERS of
biogenic amine
interfere with monoamine
Cocaine
transporter;
block reuptake of dopamine or stimulate
Amphetamines
non-vesicular release of dopamine, causing
Ecstasy
an accumulation of extracellular dopamine
 Cocaine
Alkaloid found in Erythroxylon coca from ANDES, highly
additive.
Sigmund Freudfor depression and alcohol
dependence

MOA: blocks the reuptake of dopamine, noradrenaline and

serotonin through their respective transporters
blocks DAT (dopamine transporter)
increase dopamine in nucleus accumbens--- rewarding
effect
Cause: loss of appetite, hyperactive, sleep little
Cause of death: intracranial hemorrhage, ischemic strokes,
MI, seizures
Overdose: hyperthermia, coma, death
Sniff, snort, smoke or IV
Treatment: antipsychotic or antidepressants
cocaine $ 166.70 / gm
CNS site of action of
cocaine
Cocaine
Cocaine powder
Sniffing cocaine
Snorting cocaine
Amphetamines
Anorexiants
Derivatives
Methamphetamine (shabu,
speed, ice)
Phenmetrazine
Methylphenidate (Ritalin)
Methylenedioxymethamphetami
ne (MDMA, ecstasy)
Amphetamines
Synthetic, indirect-acting
sympathomimetic drugs causing the
release of endogenous biogenic
amines such as dopamine and
noradrenaline
MOA: interferes with the vesicular
monoamine transporter (VMAT),
depleting synaptic vesicles of their
neurotransmitter content levels
of Dopamine
Metamphetamine various form
 Site of action of
metamphetamine

Since amphetamine(Amph) is a substrate of the DAT, it competitively

inhibits DA transport. In addition, once in the cell, amphetamine
interferes with the vesicular monoamine transporter (VMAT) and impedes
the filling of synaptic vesicles. As a consequence, vesicles are
depleted and cytoplasmic DA increases. This leads to a reversal of DAT
direction, strongly increasing non-vesicular release of DA, and further
increasing extracellular DA concentrations.
Amphetamines
Effects: arousal and reduce
sleep because of elevated
catecholamine levels; euphoria,
agitation and confusion
Neurotoxic
Pill, smoked, injected IV
Toxicity: hypertension,
vasoconstriction stroke
 Amphetamine
abuse:
abuse
run, rush; orgasm-like reaction
followed by a feeling of mental alertness
and marked euphoria (4g/d) paranoid-
schizophrenia-like state; delusions of
bugs crawling under the skin
(discrete excoriations)
necrotizing arteritis (IV) fatal brain
hemorrhages
withdrawal: ravenous appetite,
exhaustion, mental depression,
dysphoria, insomnia, general irritability
Overdose Treatment: haloperidol
Smokeable form of
metamphetamine
 Ecstasy
Derivative of methylene-
dioxymethamphetamine (MDMA); cost: $20-
$35/pill
Effects: foster feelings of intimacy and empathy
without impairing intellectual capacities
(prototypical designer drug)
MOA: cause release of biogenic amines by
reversing the action of their respective
transporter
(serotonin transporter or SERT)
Leads to long term cognitive impairment
Treatment: no single effective treatment;
substitution treatment
Ecstasy
 Miscellaneous Drugs
Caffeine - users of >600mg/d (6
cups)
= increase cAMP by blocking the
catabolic enzyme
phosphodiesterase but increasing
effects of catecholamine
neurotransmitters
= or interaction with receptors
for adenosine
 sports during
the 1940s and by the late 1980s
- Use was widespread in adolescents in
gymnasiums
and physical fitness centers
(40-240 mg/d methyltestosterone)
Effects:
increased muscle mass and strength
increases in aggression
changes in libido and sexual functions
mood changes with occasional psychotic
features
Cognitive impairment, including
distractability,
forgetfulness, and confusion,
aggression and paranoia
Withdrawal syndrome fatigue, depressed
mood, and a craving
 Clinical findings:
hypertrophied muscles
acne, oily skin
hirsutism in females
gynecomastia in males
needle punctures
edema and jaundice may develop in
heavy users
Common lab abnormalities include:
elevated hemoglobin and hematocrit,
elevated LDL,
and depressed HDL, elevated liver
function test
and depressed LH.
COMPLICATIONS OF
STEROIDS
 Treatment:
1. Mental health professionals
2. Peer counseling by former body
builders
and group support
3. Nutritional counseling
4. Consultation with a fitness
expert
5. Abusers need to avoid
gymnasiums until recovery is
firmly established
 Non-addictive drug
use:
- alters perception without causing
sensation
of reward and euphoria
- enhanced perception
- cause psychosis-like symptoms
- target: thalamocortical structures
 Approaches to
addiction:
addiction
Naltrexone- opioid and alcohol addiction
Baclofen high affinity GABA B receptor
agonist,
decrease craving
Rimonabant inverse agonist of the CB1
receptor (act as antagonist to
cannabinoids)
It was developed for smoking cessation and
to facilitate weight loss.
HONG KONG (3rd UPDATE) - A Hong
Kong court on Thursday sentenced
Ilocos Sur Rep. Ronald Singson to
one year and six months in prison
for illegal drug possession.
Singson had earlier pleaded guilty
to drug trafficking.
District Court Judge Joseph Yau
described the prison term as a
serious fall from grace for Singson,
a politician and music promoter,
who was caught with drugs at Hong
Kong's international airport last
year.
Earlier this year, the colorful 42-
 There is such a thing as personal
responsibility, however dire
ones circumstances are.
There is such a thing as making choices too
however narrow the range of them are.
Lest we forget, drugs kill.
Conrado de Quiros
Philippine Daily Inquirer
Feb. 23, 2011
In summary..
Define the term drugs of abuse
Describe the major actions of
commonly abused drugs
Describe the major signs and
symptoms of overdose with and
withdrawal from drugs of abuse
Identify the most likely causes of
death from commonly abused drugs
Know how to manage drug abuse
Thanks!