lecture 16 - substance misuse and dependance Flashcards
give the definition for dependance and addiction
Dependence is when the body develops a phsycial need towards the drug
Addiction is the altered behaviour as result of an over whelming psychological need for a substance
what are the componets associated with substance misuse?
Behavioural aspects
Physical aspects
Psychological and associative aspects
Socioeconomic/Environmental aspects
what is substance misuse?
“A behavioural pattern of drug use, characterised by
overwhelming involvement with the use of a drug (compulsive use)
the securing of its supply (compulsive drug-seeking),
a high tendency to relapse after withdrawal”
What are the two theroies of dependance?
negative reinforcement models
phsycial depednance (withdrawal) theory
- relates mosty opiates, barbiturates, alcohol
–based largely on increased tolerance and physical dependence
Positive Reinforcement Models Positive incentive (reward) theory –relates mostly to cocaine, amphetamine, nicotine –based largely on reward and reinforcement
what are probelems associated with the negative model?
Amphetamine, Cocaine, Nicotine form strong dependency but have relatively little withdrawal effect.
Alcohol and Barbiturates have greater withdrawal but cause less dependence than heroin.
how does speed of effect of drug have an imapct?
Heroin is biochemically converted to morphine in body. Why isn’t morphine a greater cause of dependence? Because heroin enters the brain faster than morphine
Speed -> greater cause:effect relationship developed
what is the fastest absorption route of cocaine into the bloodstream?
IV> SMOKED> INTRANASAL> ORAL
give examples of drugs and activites/ pleasures in whcih dependay is mediated through the dopamien neotransmitter action
amphetamine
cocaine
opioids (morphine, heroin)
MDMA (ecstasy)
ethanol (alcohol)
PCP (angel dust)
Nicotine (smoking)
Food, Gambling, Internet,
Video Games, and sex, too
all directly or ultimately produce their effects via dopamine release in specific neural pathways in the brain
what are the key dependence/reward pathways in the brain that operate via dopamine neurotransmission?
Dopamine signaling from the ventral tegmental area (VTA) to the nucleus accumbens (NA) is increased by drug action.
Glutamate projections from the NA cause the prefrontal cortex to ‘remember’ the environment and behaviours which led to the reward
Excess signalling of glutamate neurons in the prefrontal cortex stimulates the NA, triggering drug-seeking behaviours at the expense normal behaviours
what are drugs of msiuse ?
- Stimulants (cocaine, nicotine)
- Depressants (tranquilizers, alcohol)
- Opioids (heroin and methadone)
- Marijuana/cannabis (about 10% of users develop clear dependence, for others it can result in reduced drive, memory problems, increased risk of mental illness etc.)
how do stimualnt drusg act in a differnet way in the brain?
Cocaine inhibits the dopamine reuptake transporter.
Amphetamines reverse the same transporter
Nicotine (smoking) stimulates acetylcholine receptor neurons but these in turn stimulate dopaminergic neurons.
Net effect: chronic dopamine flood into synapses… and stimulation of dopamine receptors on target neurons.
Importantly: unlike most drug-receptor interactions, those directly involving the dopamine system sensitize over time (contrast with tolerance). Sensitization leads to greater desire for next fix plus increased association with environmental cues that can trigger next fix/relapse
what is the action of depressants: babiturates and benzodiazepines?
Barbiturates heavily prescribed in 60s/70s as sedative-hypnotic-anxiolytic drugs: caused dependency E.g., Amobarbital (‘Downers’)
Phased out in favour of Benzodiazepines e.g., Diazepam (‘Jellies’), but these also cause dependence.
Patient failure to adhere to prescribed doses can cause dependence: increased 79% from 1992 to 2002 in US.
CNS develops tolerance to benzodiazepine sedation over a few months – leads to withdrawal (particularly short-acting/high potency forms). Patient escalates dose beyond prescribed amount.
what are Alcohol and barbiturate depressant actions mediated by ?
hyperexcitability of the inhibitory GABA receptors
Be aware that both indirectly trigger the Dopaminergic system and so adhere to the idea that this is a fundamental process in dependency
how do opiodis act as drugs of misuse?
Receptors for endogenous opioids:
Mu receptor prefers β-endorphin
Delta receptor prefers enkephalins
Kappa receptor prefers dynorphins
Mu receptor acted on by morphine, heroin and methadone
Morphine blocks cAMP secondary messenger production, neurons try to redress cAMP balance.
When morphine absence, too much cAMP generated…. This ‘sensitization’ induces withdrawal symptoms
what is cannibis/ mariguana mode of action?
Pharmacologically active components are:
Tetrahydrocannibinol (THC: main psychoactive component)
Cannabidiol (CBD: relaxant/anti-inflammatory action)
Cannabinol (CBN: small psychoactive effect)
These act on Cannabinoid Receptors CB1 and CB2 which are located throughout the brain and peripherally and bind the endogenous signalling molecules ‘anandamide’ and ‘2-Arachidonoylglycerol’.
Again, action via dopamine release.
Effects on coordination, pleasure/pain, memory, hunger, and higher order cognition/judgement
