Drug Dependence Drug Dependence and Drug Abuseand Drug Abuse

TypeType ExamplesExamples Dependence Dependence liabilityliability

Narcotic analgesicsNarcotic analgesics MorphineMorphine Very strongVery strong

   DiamorphineDiamorphine Very strongVery strong

General CNS depressantsGeneral CNS depressants EthanolEthanol StrongStrong

   BarbituratesBarbiturates StrongStrong

   MethaqualoneMethaqualone ModerateModerate

   GlutethimideGlutethimide ModerateModerate

   AnaestheticsAnaesthetics ModerateModerate

   SolventsSolvents StrongStrong

Anxiolytic drugsAnxiolytic drugs BenzodiazepinesBenzodiazepines ModerateModerate

Psychomotor stimulantsPsychomotor stimulants AmphetaminesAmphetamines StrongStrong

   CocaineCocaine Very strongVery strong

   CaffeineCaffeine WeakWeak

   NicotineNicotine Very strongVery strong

Psychotomimetic agentsPsychotomimetic agents LSDLSD Weak or absentWeak or absent

   MescalineMescaline Weak or absentWeak or absent

   PhencyclidinePhencyclidine ModerateModerate

   CannabisCannabis Weak or absentWeak or absent

Drug dependenceDrug dependence

Dependence is defined as a compulsive Dependence is defined as a compulsive craving that develops as a result of craving that develops as a result of repeated administration of the drug. repeated administration of the drug.

Dependence occurs with a wide range of Dependence occurs with a wide range of psychotropic drugs, acting by many psychotropic drugs, acting by many different mechanisms. different mechanisms.

The common feature of dependence-The common feature of dependence-producing drugs is that they have a positive producing drugs is that they have a positive reinforcing action ('reward') associated with reinforcing action ('reward') associated with activation of the mesolimbic dopaminergic activation of the mesolimbic dopaminergic pathway. pathway.

dependence is often associated with (i) dependence is often associated with (i) tolerance to the drug, which can arise by tolerance to the drug, which can arise by various biochemical mechanisms; (ii) a various biochemical mechanisms; (ii) a physical abstinence syndrome, which varies physical abstinence syndrome, which varies in type and intensity for different classes of in type and intensity for different classes of drug; (iii) psychological dependence drug; (iii) psychological dependence (craving), which may be associated with the (craving), which may be associated with the tolerance-producing biochemical changes. tolerance-producing biochemical changes.

Psychological dependence, which usually Psychological dependence, which usually outlasts the physical withdrawal syndrome, is outlasts the physical withdrawal syndrome, is the major factor leading to relapse among the major factor leading to relapse among treated addicts. treated addicts.

Though genetic factors contribute to drug-Though genetic factors contribute to drug-seeking behaviour, no specific genes have seeking behaviour, no specific genes have yet been identified. yet been identified.

Pharmacological approaches to treating drug dependencePharmacological approaches to treating drug dependence

MechanismMechanism ExamplesExamples

Substitution, to alleviate Substitution, to alleviate withdrawal symptomswithdrawal symptoms

Methadone, used short-term to blunt opiate Methadone, used short-term to blunt opiate withdrawalwithdrawal

   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 Immunisation against cocaine to produce circulating antibody (not yet proven)circulating antibody (not yet proven)

Aversive therapiesAversive therapies Disulfiram to induce unpleasant response to Disulfiram to induce unpleasant response to ethanolethanol

Modification of cravingModification of craving Bupropion (antidepressant)Bupropion (antidepressant)

  Naltrexone (blocks opiate receptors-also of value Naltrexone (blocks opiate receptors-also of value in treating other addictions)in 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 nicotinic At a cellular level, nicotine acts on nicotinic acetylcholine receptors, mainly of the α4β2 acetylcholine receptors, mainly of the α4β2 subtype, to cause neuronal excitation. Its central subtype, to cause neuronal excitation. Its central effects are blocked by receptor antagonists such effects are blocked by receptor antagonists such as as mecamylamine. mecamylamine.

At the behavioural level, nicotine produces a At the behavioural level, nicotine produces a mixture of inhibitory and excitatory effects. mixture of inhibitory and excitatory effects.

Nicotine shows reinforcing properties, associated Nicotine shows reinforcing properties, associated with increased activity in the mesolimbic with increased activity in the mesolimbic dopaminergic pathway, and self-administration can dopaminergic pathway, and self-administration can be elicited in animal studies. be elicited in animal studies.

Pharmacology of nicotinePharmacology of nicotine

Electroencephalography changes show an Electroencephalography changes show an arousal response, and subjects report arousal response, and subjects report increased alertness, accompanied by a increased alertness, accompanied by a reduction of anxiety and tension. reduction of anxiety and tension.

Peripheral effects of nicotine result Peripheral effects of nicotine result mainly from ganglionic stimulation: mainly from ganglionic stimulation: tachycardia, increased blood pressure tachycardia, increased blood pressure and increase gastrointestinal motility. and increase gastrointestinal motility. Tolerance develops rapidly to these Tolerance develops rapidly to these effects. effects.

Nicotine is metabolised, mainly in the Nicotine is metabolised, mainly in the liver, within 1-2 hours. Its inactive liver, within 1-2 hours. Its inactive metabolite, cotinine, has a long metabolite, cotinine, has a long plasma half-life and can be used as a plasma half-life and can be used as a measure of smoking habits. measure of smoking habits.

Nicotine replacement therapy Nicotine replacement therapy (chewing gum or skin patch (chewing gum or skin patch preparations) improves the chances preparations) improves the chances of giving up smoking, but only when of giving up smoking, but only when combined with active counselling. combined with active counselling.

NicotineNicotine

NicotineNicotine

Effects of ethanolEffects of ethanol

Ethanol acts as a general CNS Ethanol acts as a general CNS depressant, similar to volatile depressant, similar to volatile anaesthetic agents, producing the anaesthetic agents, producing the familiar effects of acute intoxication. familiar effects of acute intoxication.

Several cellular mechanisms are Several cellular mechanisms are postulated: inhibition of calcium postulated: inhibition of calcium channel opening, enhancement of channel opening, enhancement of GABA action and inhibitory action at GABA action and inhibitory action at NMDA-type glutamate receptors. NMDA-type glutamate receptors.

Effective plasma concentrations: Effective plasma concentrations: threshold effects: about 40 mg/100 ml threshold effects: about 40 mg/100 ml

(5 mmol/l) (5 mmol/l) severe intoxication: about 150 mg/100 severe intoxication: about 150 mg/100

ml ml death from respiratory failure: about death from respiratory failure: about

500 mg/100 ml. 500 mg/100 ml. Main peripheral effects are self-limiting Main peripheral effects are self-limiting

diuresis (reduced antidiuretic hormone diuresis (reduced antidiuretic hormone secretion), cutaneous vasodilatation and secretion), cutaneous vasodilatation and delayed labor (reduced oxytocin delayed labor (reduced oxytocin secretion). secretion).

Neurological degeneration occurs in Neurological degeneration occurs in heavy drinkers, causing dementia and heavy drinkers, causing dementia and peripheral neuropathies. peripheral neuropathies.

Effects of ethanolEffects of ethanol Long-term ethanol consumption causes liver Long-term ethanol consumption causes liver

disease, progressing to cirrhosis and liver failure. disease, progressing to cirrhosis and liver failure. Moderate ethanol consumption has a protective Moderate ethanol consumption has a protective

effect against ischemic heart disease. effect against ischemic heart disease. Excessive consumption in pregnancy causes Excessive consumption in pregnancy causes

impaired fetal development, associated with small impaired fetal development, associated with small size, abnormal facial development and other size, abnormal facial development and other physical abnormalities, and mental retardation. physical abnormalities, and mental retardation.

Tolerance, physical dependence and psychological Tolerance, physical dependence and psychological dependence all occur with ethanol. dependence all occur with ethanol.

Drugs used to treat alcohol dependence include Drugs used to treat alcohol dependence include disulfiram (aldehyde dehydrogenase inhibitor), disulfiram (aldehyde dehydrogenase inhibitor), naltrexone (opiate antagonist) and acamprosate naltrexone (opiate antagonist) and acamprosate (NMDA-receptor antagonist). (NMDA-receptor antagonist).

Metabolism of ethanol.

Fetal Alcohol SyndromeFetal Alcohol Syndrome

Fetal Alcohol Syndrome Fetal Alcohol Syndrome

CannabisCannabis Main active constituent is Δ9-tetrahydro cannabinol Main active constituent is Δ9-tetrahydro cannabinol

(THC), though pharmacologically active metabolites (THC), though pharmacologically active metabolites may be important. may be important.

Actions on CNS include both depressant and Actions on CNS include both depressant and psychotomimetic effects. psychotomimetic effects.

Subjectively, subjects experience euphoria and a Subjectively, subjects experience euphoria and a feeling of relaxation, with sharpened sensory feeling of relaxation, with sharpened sensory awareness. awareness.

THC also shows analgesic and antiemetic activity, THC also shows analgesic and antiemetic activity, Peripheral actions include vasodilatation, reduction of Peripheral actions include vasodilatation, reduction of

intraocular pressure and bronchodilatation. intraocular pressure and bronchodilatation. Cannabinoid receptors belong to the G-protein-Cannabinoid receptors belong to the G-protein-

coupled receptor family, linked to inhibition of coupled receptor family, linked to inhibition of adenylate cyclase and effects on calcium and adenylate cyclase and effects on calcium and potassium channel function, causing inhibition of potassium channel function, causing inhibition of synaptic transmission.synaptic transmission.

CannabisCannabis

Anandamide, an arachidonic acid derivative, is an Anandamide, an arachidonic acid derivative, is an endogenous ligand for the CNS cannabinoid endogenous ligand for the CNS cannabinoid receptor; its function has not yet been receptor; its function has not yet been ascertained. ascertained.

Cannabinoids are less liable than opiates, nicotine Cannabinoids are less liable than opiates, nicotine or alcohol to cause dependence but may have or alcohol to cause dependence but may have long-term psychological effects. long-term psychological effects.

Nabilone, a THC analogue, has been developed Nabilone, a THC analogue, has been developed for its antiemetic property. for its antiemetic property.

Though cannabinoids are not available for clinical Though cannabinoids are not available for clinical use, trials are in progress for symptomatic use, trials are in progress for symptomatic treatment of multiple sclerosis and AIDS. treatment of multiple sclerosis and AIDS.

MarijuanaMarijuana

MarijuanaMarijuana

HallucinogensHallucinogens

LSDLSD

CocaineCocaine

CocaineCocaine