Define drug dependence?
What does it arise from?
State where drug use becomes compulsive, taking precedence over other needs
Arises from drug abuse
Define drug abuse?
Use of illicit substances (or illicit use of legal substances) characterised by recurrent and clinically significant adverse consequences
Describe the relationship between drug abuse and drug dependence?
Drug dependence arises from drug abuse
Describe the common reasons for drug abuse?
Rewarding effects of psychoactive drugs (positive reinforcement)
Habituation or adaptation
List some commonly abused drugs?
Which circuits are thought to be involved in drug abuse and addiction?
Reward/ salience areas
Inhibitory control areas
What is the key to the positive reinforcement provided by drugs of dependence and abuse?
Increase in dopamine in nucleus accumbens
What are the key NTs modulating dopaminergic transmission?
Ach, serotonin, NA
To which drug class does amphetmaine belong?
Describe the effect of amphetamine on NTs?
Releases Da, 5-HT and NA in CNS
Which variables alter the effects of amphetamine?
Describe the effects of amphetamine?
Increased locomotor activity
Improved physical and mental performance (fatigue postponed, confidence, faster performance but less accuracy)
Describe the effects of amphetamine overdose?
Anxiety, nervousness and physical tension
Tremors, confusion, dizziness, time passes quickly
Hyperthermia, tachycardia, increased BP, vascular collapse
Amphetamine psychosis - hallucinations
Why does amphetamine dependence occur?
When is depedence more likely to occur?
Related to dopaminergic actions in nuclear accumbens
More likely to occur in those starting at a 'lower basleine' (i.e. depressives, lonely)
Describe the effect of amphetamine on appetite?
Why does this occur?
Thought to be an effect of 5-HT
What is MDMA?
Describe the effects of MDMA on NTs?
Release DA and 5-HT
Describe the effects of MDMA?
Stimulant and hallucinogenic effects
Describe the adverse effects of MDMA?
Increased HR and BP
Disrupted thermoregulation (chills, sweating)
Potential degeneration of 5-HT and DA neurons
What is LSD?
Which drug class does is belong to?
Lysergic acid diethylamide
Describe the effects of LSD?
Visual, auditory and tactile hallucinations (sesnory modalitites confused)
Thought processes disturbed but aware
Describe the adverse effects of LSD?
Dependence not really an issue (aversive rather than reinforcing)
Describe the action of LSD in the body?
Agonist at 5-HT2 receptors
Describe the effects of caffeine?
Increases alertness, well-being
Delays onset of sleep
Stimulates mental activity
To which drug class does caffeine belong?
What is its action?
Adenosine antagonist, PDE inhibitor
Describe the effect of dependence in caffeine?
No strong reinforcing effect in animals
Social aspect in humans
What is D9-THC?
Active ingredient in cannabis
To which drug class does D9-THC belong?
Describe the effects of D9-THC?
Very subjective; influenced by characteristics of drug and individual
Sharpened sensory awareness, increased intensity of sounds and sights
Relaxation, feeling of well-being
Describe the effect of dependence with D9-THC use?
Some evidence of physical and psychological dependence in heavy users
Where does D9-THC act in the body?
Describe its effect?
Cannabinoid receptors (GPCRs) > inhibits adenylate cyclase > inhibition of transmission
Two receptor subtypes: CB1 and CB2
Describe the effects of ethanol?
Behavioural effects: subjective; increased confidence, euphoria, agression, mood swings
Motor effects: loss of coordination, slurred speech
Tissue effects: cardiovascular protection, liver damage, neurodegeneration, foetal impairment
To which class of drugs does does ethanol belong?
Describe its action?
Can inhibit Ca channel opening, enhance GABA action, inhibit glutamate receptors
Describe the effects of tolerance and dependence with ethanol use?
Marked tolerance, due to pharmacokinetic effects of enhanced clearance
Physical dependence, rather than psychological (well defined abstinence syndrome)
Describe the three generations of antidepressant drugs?
1st: tricyclic antidepressants, MAO inhibitors
2nd: SSRIs, SSNRIs
3rd: novel monoaminergic drugs, non-monoaminergic drugs
Describe the pharmacological action of tricyclic antidepressants?
Describe their selectivity?
Inhinit neuronal uptake of NA and serotonin
Anatgonise a-adrenoceptors, MuscR, HA receptors and serotonin receptors
Poor selectivity (based around somehow interfering with uptake of NA and serotonin
Give three examples of tricyclic antidepressants?
Describe the onset of clinical effects of tricyclic antidepressants?
Takes weeks to develop
Describe the therapeutic window of tricyclic antidepressants?
Limited efficacy, side effects become a problem
Describe the half lives of tricyclic antidepressants?
What impact does this have on dosage?
Gradual accumulation possible, so slowly developing side effects
Start dose low to avoid side effects, then increase
Describe the pharmacological action of monoamine oxidase inhibitors?
Increase levels of 5-HT, NA and DA
Describe the pharmacological effect of SSRIs?
Selective for blocking 5-HT uptake
Describe the side effects of SSRIs?
Loss of libido