The document discusses drug dependence and abuse, providing definitions and examples. It summarizes that dependence involves compulsive drug craving and can occur after repeated drug use, while addiction involves compulsive, uncontrolled behavior to obtain drugs despite negative consequences. It then categorizes examples of commonly abused drugs based on their dependence liability and mechanisms of action, including opioids, cannabis, benzodiazepines, cocaine, amphetamines, nicotine, and alcohol. Treatment approaches aim to alleviate withdrawal symptoms through substitution or block drug effects and cravings.
2. Terminolgies
Dependence
Previously known as ‘’Physical dependence’’ , defined as a
compulsive craving that develops as a result of repeated
administration of the drug.
Addiction.
Is ‘’Psychological dependence”
Occurs when the physical dependence is long gone
Addictive drugs directly increase dopamine, generate a strong
but inappropriate learning signal
Behavior becomes compulsive; that is, decisions are no longer
planned and under control, but automatic,which is the
hallmark of addiction
characterized by a high motivation to obtain and use a drug
despite negative consequences
3. Type Examples Dependence liability
Narcotic analgesics Morphine Very strong
Diamorphine Very strong
General CNS depressants Ethanol Strong
Barbiturates Strong
Methaqualone Moderate
Glutethimide Moderate
Anaesthetics Moderate
Solvents Strong
Anxiolytic drugs Benzodiazepines Moderate
Psychomotor stimulants Amphetamines Strong
Cocaine Very strong
Caffeine Weak
Nicotine Very strong
Psychotomimetic agents LSD Weak or absent
Mescaline Weak or absent
Phencyclidine Moderate
Cannabis Weak or absent
4. Drug dependence
Dependence occurs with a wide range of psychotropic drugs,
acting by many different mechanisms.
The common feature of dependence-producing drugs is that
they have a positive reinforcing action ('reward') associated
with activation of the mesolimbic dopaminergic pathway.
5. CONT..
Dependence is often associated with
Tolerance to the drug, which can arise by various
biochemical mechanisms;
Physical abstinence syndrome, which varies in type and
intensity for different classes of drug;
Psychological dependence (craving), which may be
associated with the tolerance-producing biochemical
changes.
6. CONT..
Psychological dependence, which usually outlasts the physical
withdrawal syndrome, is the major factor leading to relapse
among treated addicts.
Though genetic factors contribute to drug-seeking behaviour,
no specific genes have yet been identified
7. Positive reinforcement model
The rewarding effects of the drug such as euphoria,
increased alertness, anxiety reduction work as the
positive reinforcement to maintain drug use
Animal studies also support this hypothesis. Rats self
administer drugs after they have learnt to obtain the
drug
Animals can go to extremes and kill themselves with
overdose but researchers limit their study for few hours
Withdrawal symptoms work as negative reinforcement
8. CONT..
Drugs of abuse such as cocaine and marijuana hijack
brain’s reward system called Dopaminergic mesolimbic
system
They block the reuptake of dopamine (pleasure
neurotransmitter) from the synapses
Desensitizes the body’s natural production of it making
it difficult to experience pleasure
Theory challenged, Transgenic mice without cocaine
molecular target, DAT still selfadminstered cocaine
9. DRUGS OF ABUSE
All drugs of abuse increase dopamine
Classified according to molecular targets
Targets on Gio protein-coupled receptors
Opioids
cannabinoids,
gamma-hydroxybutyric acid (GHB), and
Hallucinogens
Targets on Ion channel receptors
Nicotine
Alcohol
Benzodiazepines
Dissociative anesthetics
11. Opioids
A large family of endogenous and exogenous agonists at three
G protein-coupled receptors: the μ-, κ-, and δ-opioid
receptors.
Mophine , codeine , Oxycodone and heroin act on μ receptors
on GABAernic neurons to cause euphoria,
Action by k receptor agonists on dopaminergic neurons cause
dysphoria.
Meperidine abused by health professionals
Elicit high tolerance and dependence.
Patients on opioid analgesic rarely develop addiction
compared to recreational users
12. CONT..
withdrawal syndrome may be very severe (except for
codeine) and includes;
intense dysphoria, nausea or vomiting,
muscle aches, lacrimation,
rhinorrhea, mydriasis,
piloerection, sweating, diarrhea
13. Tx of Opioid abuse and
addiction
naloxone
The opioid antagonist reverses the effects of a dose of
morphine or heroin within minutes. This may be life-saving in
the case of a massive overdose.
In the treatment of opioid addiction, a long-acting opioid
methadone, buprenorphine, morphine sulphate is often
substituted for the shorter-acting, more rewarding, opioid like
heroin
methadone is given orally once daily.
Using a partial agonist (buprenorphine) and the much longer
half-life (methadone, morphine sulphate, and buprenorphine)
may also have some beneficial effects
14. Cannabis
Main active constituent is Δ9-tetrahydro cannabinol (THC)
Actions on CNS include both depressant and
psychotomimetic effects.
experience euphoria and a feeling of relaxation, with
sharpened sensory awareness.
THC also shows analgesic and antiemetic activity,
Peripheral actions include vasodilatation, reduction of
intraocular pressure and bronchodilatation.
Cannabinoid receptors belong to the G-protein-coupled
receptor family, linked to inhibition of adenylate cyclase
and effects on calcium and potassium channel function,
causing inhibition of synaptic transmission.
15. Cannabis
Anandamide, an arachidonic acid derivative, is an endogenous
ligand for the CNS cannabinoid receptor; its function has not
yet been ascertained.
Cannabinoids are less liable than opiates, nicotine or alcohol
to cause dependence but may have long-term psychological
effects.
Nabilone, a THC analogue, has been developed for its
antiemetic property.
Though cannabinoids are not available for clinical use, trials
are in progress for symptomatic treatment of multiple
sclerosis and AIDS.
16. DRUGS THAT MEDIATE THEIR
EFFECTS VIA IONOTROPIC
RECEPTORS
Benzodiazepines
Commonly prescribed as anxiolytics and sleep medications.
Abused for their euphoriant effects, but most often abuse
occurs concomitant with other drugs, eg, to attenuate anxiety
during withdrawal from opioids.
Benzodiazepines are positive modulators of the GABA-A
receptor, increasing both single-channel conductance
The rewarding effects of benzodiazepines are mediated by α1-
containing GABA-A receptors expressed on VTA neurons
17. CONT..
Withdrawal from benzodiazepines occurs within days of
stopping the medication.
Symptoms include irritability, insomnia, phonophobia and
photophobia, depression
muscle cramps, and even seizures.
Typically, these symptoms taper off within 1–2 weeks.
Barbiturates
Preceded benzodiazepines as the most commonly abused
sedative-hypnotics (after ethanol)
Rarely prescribed to outpatients
Withdrawal symptoms similar to BZDPs
18. CONT..
Cocaine
blocks the uptake of dopamine, noradrenaline, and
serotonin through their respective transporters.
Blocking of the dopamine transporter (DAT), by
increasing dopamine concentrations in the nucleus
accumbens, has been implicated in the rewarding
effects of cocaine.
rewarding effects of cocaine are abolished in mutant
mice with a cocaine-insensitive DAT.
Although a withdrawal syndrome is reported, it is not as
strong as that observed with opioids.
19. CONT..
Cravings are very strong and underlie the very high
addiction liability of cocaine.
management of intoxication remains supportive.
Amphetamines
group of synthetic, indirect-acting sympathomimetic
drugs that cause the release of endogenous biogenic
amines, such as dopamine and Amphetamine,
methamphetamine.
exert their effects by reversing the action of biogenic
amine transporters at the plasma membrane
20. CONT..
Amphetamines are typically taken initially in pill form by
abusers, but can also be smoked or injected. Heavy users
often
progress rapidly to intravenous administration.
Within hours after oral ingestion, amphetamines increase
alertness and cause euphoria,agitation, and confusion.
Cheese??
Effects on heart rate may be minimal with some
compounds (eg, methamphetamine), but with increasing
dosage these agents often lead to tachycardia and
dysrhythmias.
Hypertensive crisis and vasoconstriction may lead to stroke
21. CONT..
With chronic use, amphetamine tolerance may develop,
leading to dose escalation. Withdrawal consists of
dysphoria, drowsiness (in some cases, insomnia), and
general irritability
22. CONT
ECSTASY (MDMA)
Ecstasy is the name of a class of drugs that includes a
large variety of derivatives of the amphetamine-related
compound methylenedioxymethamphetamine (MDMA)
The main effect of ecstasy appears to be to foster
feelings of intimacy and empathy without impairing
intellectual capacities
MDMA causes release of biogenic amines by reversing
the action of their respective transporters.
It has a preferential affinity for the serotonin
transporter(SERT)
23. CONT..
With repetitive administration, serotonin depletion may
become permanent,
Withdrawal is marked by a mood “offset” characterized
by depression lasting up to several weeks.
There have also been reports of increased aggression
during periods of abstinence in chronic MDMA users
24. nicotine
At a cellular level, nicotine acts on nicotinic acetylcholine
receptors, mainly of the α4β2 subtype, to cause neuronal
excitation. Its central effects are blocked by receptor
antagonists such as mecamylamine.
At the behavioural level, nicotine produces a mixture of
inhibitory and excitatory effects.
Nicotine shows reinforcing properties, associated with
increased activity in the mesolimbic dopaminergic pathway,
and self-administration can be elicited in animal studies.
25. nicotine
Electroencephalography changes show an arousal
response, and subjects report increased alertness,
accompanied by a reduction of anxiety and tension.
Peripheral effects of nicotine result mainly from
ganglionic stimulation: tachycardia, increased blood
pressure and increase gastrointestinal motility.
Tolerance develops rapidly to these effects.
26. CONT..
Nicotine is metabolised, mainly in the liver, within 1-2
hours. Its inactive metabolite, cotinine, has a long
plasma half-life and can be used as a measure of
smoking habits.
Nicotine replacement therapy (chewing gum or skin
patch preparations) improves the chances of giving up
smoking, but only when combined with active
counselling.
27. Effects of ethanol
Ethanol acts as a general CNS depressant, similar to
volatile anaesthetic agents, producing the familiar
effects of acute intoxication.
Several cellular mechanisms are postulated: inhibition
of calcium channel opening, enhancement of GABA
action and inhibitory action at NMDA-type glutamate
receptors.
28. CONT..
Effective plasma concentrations:
threshold effects: about 40 mg/100 ml (5 mmol/l)
severe intoxication: about 150 mg/100 ml
death from respiratory failure: about 500 mg/100 ml.
Main peripheral effects are self-limiting diuresis (reduced
antidiuretic hormone secretion), cutaneous vasodilatation and
delayed labor (reduced oxytocin secretion).
Neurological degeneration occurs in heavy drinkers, causing
dementia and peripheral neuropathies.
29. CONT..
Long-term ethanol consumption causes liver disease,
progressing to cirrhosis and liver failure.
Moderate ethanol consumption has a protective effect against
ischemic heart disease.
Excessive consumption in pregnancy causes impaired fetal
development, associated with small size, abnormal facial
development and other physical abnormalities, and mental
retardation.
Tolerance, physical dependence and psychological
dependence all occur with ethanol.
Drugs used to treat alcohol dependence include disulfiram
(aldehyde dehydrogenase inhibitor), naltrexone (opiate
antagonist) and acamprosate (NMDA-receptor antagonist).
33. NONADDICTIVE DRUGS OF
ABUSE
Some drugs of abuse do not lead to addiction.(LSD,
MESCALINE, & PSILOCYBIN)
These substances alter perception without causing
sensations of reward and euphoria such as the
hallucinogens and the dissociative anesthetics.
Unlike addictive drugs, which primarily target the
mesolimbic dopamine system, these agents primarily
target cortical and thalamic circuits.
Lysergic acid diethylamide (LSD)
Targets 5HT2A receptors in the prefrontal cortex and
enhance glutamate transmission in pyramidal neurons.
34. CONT..
Phencyclidine (PCP) and ketamine
Produce a feeling of separation of mind and body (
dissociative anesthetics) , stupor and coma at higher
doses.
The principal mechanism of action is a use-dependent
inhibition of glutamate receptors of the NMDA type
Dextromethorphan
can also elicit a dissociative state.
mediated by nonselective action on serotonin reuptake,
and opioid, acetylcholine, and NMDA receptors
35. Pharmacological approaches to treating drug dependence
Mechanism Examples
Substitution, to alleviate
withdrawal symptoms
Methadone, used short-term to blunt opiate withdrawal
Benzodiazepines, to blunt alcohol withdrawal
Long-term substitution Methadone substitution for opiate addiction
Nicotine patches or chewing gum
Blocking response Naltrexone to block opiate effects
Mecamylamine to block nicotine effects
Immunisation against cocaine to produce circulating
antibody (not yet proven)
Aversive therapies Disulfiram to induce unpleasant response to ethanol
Modification of craving Bupropion (antidepressant)
Naltrexone (blocks opiate receptors-also of value in
treating other addictions)
Clonidine (α-adrenoceptor agonist)
Acamprosate (NMDA-receptor antagonist)
