Reward / Drugs of Abuse / Legal Highs (Vince Wilson) Flashcards
What is Dependence Syndrome?
Strong desire or compulsion to take the substance
Difficulties in controlling use (amount, onset, termination)
Physical withdrawal state
Behaviour changes
Tolerance
Progressive neglect of other interests, increasing time spent obtaining and taking substance
Persistence with substance despite detrimental effects e.g. social, cognitive and physical.
What are the progressive steps of substance abuse?
Time set aside for getting and using substance
Time increases - drug seeking behaviour and time spent recovering
Social, occupational and recreational activities reduced
Development of tolerance - reduced intensity
Dependence - induced increase in drug use
Withdrawal - continued use despite recognition of problems
Withdrawal induced anhedonia and depression
What is the meso-limbic dopamine pathways association with reward pathways of the brain?
Many drugs of abuse increase dopamine release in the nucleus accumbens (NAC)
Opiates, nicotine, amphetamine, cocaine, ethanol, cannabis. ecstasy, barbiturates, caffeine.
Which drugs enhance serotonin function?
LSD (lysergic acid diethylamide)
Ecstasy
What does the graph of dopamine effect show about the ‘rush’?
The greater and faster dopamine levels peak in the brain, the greater the rush/euphoria
Formulation is a factor.
How does formulation effect the euphoria associated with drugs?
IV heroin ‘better’ than methadone by mouth
Inhaling cocaine better than chewing coca leaves
Smoking cigarettes better than chewing tobacco
What is Bromocriptine used for?
Stops breast milk production for medical reasons
Problems caused by having inappropriate levels of prolactin
Treating non cancerous tumours in the brain called prolactinomas
Treating Parkinson’s disease (increase dopamine levels)
What side effects are associated with Bromocriptine?
Impulse control disorders
Behaviours such as addictive gambling, excessive eating or spending, abnormally high sex drive or an increase in thoughts/feelings
Also Ropirinole
How do opiates work?
Heroin, morphine, methadone, codeine
Agonists at G protein coupled opioid receptors that lower neurotransmitter release in brain and periphery.
Analgesia, euphoria
Respiratory depression, dysphoria, sedation
What are the acute effects of opioids?
Euphoria, tranquility, miosis, drowsiness, itching, nausea
What are the chronic effects of opioids?
Constipation, anhedonia (no enjoyment), depression, insomnia, dependence
Nutritional status tends to be poor, danger of HIV / hepatitis from injecting
Significant tolerance
What are the withdrawal symptoms of opioid use?
Craving, restlessness, muscle and bone pain, vomiting, diarrhoea, insomnia
Cold flashes with goosebumps (cold turkey)
Kicking movements (kicking the habit)
Major withdrawal symptoms peak 48-72h after last dose and subside after about a week.
Sudden withdrawal from heavy users in poor health can be fatal (less dangerous than barbiturate or alcohol withdrawal).
What is cocaine?
Benzoylmethylecgonine / alkaloid extracted from the coca tree
Leaves chewed in Peru etc
How is cocaine taken?
Snorted, (hydrochloride can cause perforation of nasal septum), or smoked with tobacco.
What are the effects of cocaine?
Euphoria and excitement, increased capacity for work
How does cocaine cause effects?
Increased catecholamine neurotransmitter function by preventing re-uptake
DA most importnat for CNS behaviour
What happens in high doses of cocaine?
Overactvity of sympathetic system
Hypertension, tachycardia, hyperpyrexia, dilated pupils, palpitations
What is ‘crack’?
Free base that can be smoked
Very rapid dependence
Is cocaine addictive?
STRONG Psychological dependence; very little physical tolerance or physical dependence.
What is ‘speed’?
Amphetamine Phenyethylamine drugs (methamphetamine)
What are the effects of amphetamines?
Increased wakefulness, concentration Performance enhancing (some tolerance) Euphoria, increased libido, energy, self esteem and confidence, aggression, excessive feelings of power, obsession and paranoia.
How do amphetamines work?
Release monoamines from neuronal synaptic DA, NA, 5HT uptake transporters, causing increased synaptic NTs
What is amphetamine psychosis?
Chronic or high dose use can induce
Increases cardiovascular tone, raised BP, tachycardia
What is the active agent in cannabis?
THC mimics effect of small endogenous lipid messengers (anandamide).
How does cannabis work?
Inhibits a wide range of NT release in the brain and periphery via specific Gi protein coupled cannabinoid receptors.
What are the effects of taking cannabis?
Mild euphoric effect; dysphoric in high doses, especially in naive users. Context dependent
Very low acute toxicity but some concern re precipitation of psychosis in chronic users
Stimulates appetite through actions on feeding centres in hypothalamus
What treatment is known as agonist substitution?
Methadone treatment for opiate abuse
Long-acting synthetic opiate agonist administered orally for sustained period at dose sufficient to prevent opiate withdrawal.
What is the benefit of methadone treatment?
Blocks illicit opiate use and decreases opiate craving
Patient stabilises on adequate sustained doses and can hold jobs, avoid crime and violence and reduces exposure to HIV.
What are the formulations of nicotine replacement therapy?
Gum patches sprays etc
*Relatively ineffective in patient long term smoking cessation
What partial receptor agonists are used to help quit smoking?
Varenicline (Champix) - nicotinic Ach
What partial receptor agonists are used to help withdrawal from opioids?
Buprenorphine u opioid
What short term antagonist treatments are available in the treatment of substance abuse?
Naltrexone: therapy for opiate addiction, patients must be detoxified and opiate free for several days to prevent precipitating opiate abstinence syndrome.
Mecamylamine: nicotinic acetylcholine receptor antagonist that blocks the rewarding actions of nicotine and cue-induced craving
What is Acamprosate’s role in anti-craving treatment?
Use as adjunct in maintaining abstinence in alcohol dependent patients.
Reduces neuronal excitability that occurs during alcohol withdrawal.
