Drug Dependence andDrug Dependence and
Drug AbuseDrug Abuse
TypeType ExamplesExamples Dependence liabilityDependence liability
Narcotic analgesicsNarcotic analgesics MorphineMorphine Very strongVery strong
DiamorphineDiamorphine Very strongVery strong
General CNS depressantsGeneral CNS depressants EthanolEthanol StrongStrong
Anxiolytic drugsAnxiolytic drugs BenzodiazepinesBenzodiazepines ModerateModerate
Psychomotor stimulantsPsychomotor stimulants AmphetaminesAmphetamines StrongStrong
CocaineCocaine Very strongVery strong
NicotineNicotine Very strongVery strong
Psychotomimetic agentsPsychotomimetic agents LSDLSD Weak or absentWeak or absent
MescalineMescaline Weak or absentWeak or absent
CannabisCannabis Weak or absentWeak or absent
Drug dependenceDrug dependence
Dependence is defined as a compulsive cravingDependence is defined as a compulsive craving
that develops as a result of repeatedthat develops as a result of repeated
administration of the drug.administration of the drug.
Dependence occurs with a wide range ofDependence occurs with a wide range of
psychotropic drugs, acting by many differentpsychotropic drugs, acting by many different
The common feature of dependence-producingThe common feature of dependence-producing
drugs is that they have a positive reinforcingdrugs is that they have a positive reinforcing
action ('reward') associated with activation ofaction ('reward') associated with activation of
the mesolimbic dopaminergic pathway.the mesolimbic dopaminergic pathway.
dependence is often associated with (i)dependence is often associated with (i)
tolerance to the drug, which can arise by varioustolerance to the drug, which can arise by various
biochemical mechanisms; (ii) a physicalbiochemical mechanisms; (ii) a physical
abstinence syndrome, which varies in type andabstinence syndrome, which varies in type and
intensity for different classes of drug; (iii)intensity for different classes of drug; (iii)
psychological dependence (craving), which maypsychological dependence (craving), which may
be associated with the tolerance-producingbe associated with the tolerance-producing
biochemical changes.biochemical changes.
Psychological dependence, which usuallyPsychological dependence, which usually
outlasts the physical withdrawal syndrome, is theoutlasts the physical withdrawal syndrome, is the
major factor leading to relapse among treatedmajor factor leading to relapse among treated
Though genetic factors contribute to drug-Though genetic factors contribute to drug-
seeking behaviour, no specific genes have yetseeking behaviour, no specific genes have yet
been identified.been identified.
Pharmacological approaches to treating drug dependencePharmacological approaches to treating drug dependence
Substitution, to alleviateSubstitution, to alleviate
withdrawal symptomswithdrawal symptoms
Methadone, used short-term to blunt opiateMethadone, used short-term to blunt opiate
Benzodiazepines, to blunt alcohol withdrawalBenzodiazepines, to blunt alcohol withdrawal
Long-term substitutionLong-term substitution Methadone substitution for opiate addictionMethadone substitution for opiate addiction
Nicotine patches or chewing gumNicotine patches or chewing gum
Blocking responseBlocking response Naltrexone to block opiate effectsNaltrexone to block opiate effects
Mecamylamine to block nicotine effectsMecamylamine to block nicotine effects
Immunisation against cocaine to produce circulatingImmunisation against cocaine to produce circulating
antibody (not yet proven)antibody (not yet proven)
Aversive therapiesAversive therapies Disulfiram to induce unpleasant response to ethanolDisulfiram to induce unpleasant response to ethanol
Modification of cravingModification of craving Bupropion (antidepressant)Bupropion (antidepressant)
Naltrexone (blocks opiate receptors-also of value inNaltrexone (blocks opiate receptors-also of value in
treating other addictions)treating other addictions)
Clonidine (α-adrenoceptor agonist)Clonidine (α-adrenoceptor agonist)
Acamprosate (NMDA-receptor antagonist)Acamprosate (NMDA-receptor antagonist)
Pharmacology of nicotinePharmacology of nicotine
At a cellular level, nicotine acts on nicotinicAt a cellular level, nicotine acts on nicotinic
acetylcholine receptors, mainly of the α4β2 subtype,acetylcholine receptors, mainly of the α4β2 subtype,
to cause neuronal excitation. Its central effects areto cause neuronal excitation. Its central effects are
blocked by receptor antagonists such asblocked by receptor antagonists such as
At the behavioural level, nicotine produces a mixtureAt the behavioural level, nicotine produces a mixture
of inhibitory and excitatory effects.of inhibitory and excitatory effects.
Nicotine shows reinforcing properties, associated withNicotine shows reinforcing properties, associated with
increased activity in the mesolimbic dopaminergicincreased activity in the mesolimbic dopaminergic
pathway, and self-administration can be elicited inpathway, and self-administration can be elicited in
animal studies.animal studies.
Pharmacology of nicotinePharmacology of nicotine
Electroencephalography changes show anElectroencephalography changes show an
arousal response, and subjects reportarousal response, and subjects report
increased alertness, accompanied by aincreased alertness, accompanied by a
reduction of anxiety and tension.reduction of anxiety and tension.
Peripheral effects of nicotine result mainly fromPeripheral effects of nicotine result mainly from
ganglionic stimulation: tachycardia, increasedganglionic stimulation: tachycardia, increased
blood pressure and increase gastrointestinalblood pressure and increase gastrointestinal
motility. Tolerance develops rapidly to thesemotility. Tolerance develops rapidly to these
Nicotine is metabolised, mainly in the liver,Nicotine is metabolised, mainly in the liver,
within 1-2 hours. Its inactive metabolite,within 1-2 hours. Its inactive metabolite,
cotinine, has a long plasma half-life andcotinine, has a long plasma half-life and
can be used as a measure of smokingcan be used as a measure of smoking
Nicotine replacement therapy (chewingNicotine replacement therapy (chewing
gum or skin patch preparations) improvesgum or skin patch preparations) improves
the chances of giving up smoking, but onlythe chances of giving up smoking, but only
when combined with active counselling.when combined with active counselling.
Effects of ethanolEffects of ethanol
Ethanol acts as a general CNSEthanol acts as a general CNS
depressant, similar to volatile anaestheticdepressant, similar to volatile anaesthetic
agents, producing the familiar effects ofagents, producing the familiar effects of
acute intoxication.acute intoxication.
Several cellular mechanisms areSeveral cellular mechanisms are
postulated: inhibition of calcium channelpostulated: inhibition of calcium channel
opening, enhancement of GABA actionopening, enhancement of GABA action
and inhibitory action at NMDA-typeand inhibitory action at NMDA-type
glutamate receptors.glutamate receptors.
Effective plasma concentrations:Effective plasma concentrations:
threshold effects: about 40 mg/100 mlthreshold effects: about 40 mg/100 ml
(5 mmol/l)(5 mmol/l)
severe intoxication: about 150 mg/100severe intoxication: about 150 mg/100
death from respiratory failure: about 500death from respiratory failure: about 500
mg/100 ml.mg/100 ml.
Main peripheral effects are self-limitingMain peripheral effects are self-limiting
diuresis (reduced antidiuretic hormonediuresis (reduced antidiuretic hormone
secretion), cutaneous vasodilatation andsecretion), cutaneous vasodilatation and
delayed labor (reduced oxytocindelayed labor (reduced oxytocin
Neurological degeneration occurs inNeurological degeneration occurs in
heavy drinkers, causing dementia andheavy drinkers, causing dementia and
peripheral neuropathies.peripheral neuropathies.
Effects of ethanolEffects of ethanol
Long-term ethanol consumption causes liver disease,Long-term ethanol consumption causes liver disease,
progressing to cirrhosis and liver failure.progressing to cirrhosis and liver failure.
Moderate ethanol consumption has a protective effectModerate ethanol consumption has a protective effect
against ischemic heart disease.against ischemic heart disease.
Excessive consumption in pregnancy causes impairedExcessive consumption in pregnancy causes impaired
fetal development, associated with small size, abnormalfetal development, associated with small size, abnormal
facial development and other physical abnormalities, andfacial development and other physical abnormalities, and
mental retardation.mental retardation.
Tolerance, physical dependence and psychologicalTolerance, physical dependence and psychological
dependence all occur with ethanol.dependence all occur with ethanol.
Drugs used to treat alcohol dependence includeDrugs used to treat alcohol dependence include
disulfiram (aldehyde dehydrogenase inhibitor),disulfiram (aldehyde dehydrogenase inhibitor),
naltrexone (opiate antagonist) and acamprosate (NMDA-naltrexone (opiate antagonist) and acamprosate (NMDA-
receptor antagonist).receptor antagonist).
Main active constituent is Δ9-tetrahydro cannabinol (THC),Main active constituent is Δ9-tetrahydro cannabinol (THC),
though pharmacologically active metabolites may bethough pharmacologically active metabolites may be
Actions on CNS include both depressant andActions on CNS include both depressant and
psychotomimetic effects.psychotomimetic effects.
Subjectively, subjects experience euphoria and a feeling ofSubjectively, subjects experience euphoria and a feeling of
relaxation, with sharpened sensory awareness.relaxation, with sharpened sensory awareness.
THC also shows analgesic and antiemetic activity,THC also shows analgesic and antiemetic activity,
Peripheral actions include vasodilatation, reduction ofPeripheral actions include vasodilatation, reduction of
intraocular pressure and bronchodilatation.intraocular pressure and bronchodilatation.
Cannabinoid receptors belong to the G-protein-coupledCannabinoid receptors belong to the G-protein-coupled
receptor family, linked to inhibition of adenylate cyclase andreceptor family, linked to inhibition of adenylate cyclase and
effects on calcium and potassium channel function, causingeffects on calcium and potassium channel function, causing
inhibition of synaptic transmission.inhibition of synaptic transmission.
Anandamide, an arachidonic acid derivative, is anAnandamide, an arachidonic acid derivative, is an
endogenous ligand for the CNS cannabinoid receptor; itsendogenous ligand for the CNS cannabinoid receptor; its
function has not yet been ascertained.function has not yet been ascertained.
Cannabinoids are less liable than opiates, nicotine orCannabinoids are less liable than opiates, nicotine or
alcohol to cause dependence but may have long-termalcohol to cause dependence but may have long-term
psychological effects.psychological effects.
Nabilone, a THC analogue, has been developed for itsNabilone, a THC analogue, has been developed for its
antiemetic property.antiemetic property.
Though cannabinoids are not available for clinical use,Though cannabinoids are not available for clinical use,
trials are in progress for symptomatic treatment oftrials are in progress for symptomatic treatment of
multiple sclerosis and AIDS.multiple sclerosis and AIDS.