HMA - Recreational Drugs and CNS Acting Drugs

Liking

pleasurable or hedonic experience produced by a drug or reward; “I enjoy this.”

Wanting

motivation drive to obtain or consume a drug or reward; “I need this.”

Reward learning

learning that a particular cue, context, or behaviour predicts a reward outcome; “This cue means the drug is available.”

Ventral tegmental area (VTA)

dopamine source and reward prediction; contains dopamine neurons that project to the nucleus accumbens and other regions.

Nucleus accumbens (Ventral striatum)

converts reward to motivation; receives dopamine from the VTA and helps translate reward signals into motivated behaviour and drug-seeking.

Amygdala

emotional learning; associates drugs and drug-related cues with emotional significance, contributing to craving when those cues are encountered.

Hippocampus

context and memory; forms memories linking drug use to places, people and situations, allowing environmental cues to trigger craving.

Prefrontal cortex

executive control; Involved in decision-making, impulse control and inhibition of behaviour, which can be impaired by chronic drug use.

Reward prediction error

dopamine firing increases when a reward is better than expected, decreases when it is worse than expected, and becomes associated with cues that predict the reward.

Neuroplasticity

brain's ability to change its structure and function in response to experience, associated with stronger drug-related memories and associations, leading to greater response to drug cues + craving.

Tolerance

diminished response to a drug after repeated use, meaning higher doses are required to achieve the same response; often due to increased drug metabolism, receptor desensitisation, or adaptation of enzyme levels.

Dependence

state in which an organism only functions normally in the presence of the drug, meaning removal of drug causes a physical disturbance, manifesting as withdrawal symptoms.

Sensitisation

increased response to a drug after repeated exposure, particularly due to its motivational or behavioural effects.

Addiction (substance use disorder)

chronic disorder characterised by compulsive drug seeking and use despite harmful consequences, with impaired control over drug use.

Incentive-sensitisation theory of addiction

repeated drug use causes sensitisation of brain reward/motivation systems, making drug-related cues increasingly powerful at triggering “wanting” and craving, even when the pleasurable “liking” of the drug does not increase.

Voluntary drug use

goal-directed; drug is taken for rewarding affects as VTA dopamine acts on the ventral striatum; PFC can still exert control over behaviour.

Compulsive drug use

habit-based; repeated use causes neuroplasticity, shifting use from goal-directed reward seeking behaviour to automatic, habitual behaviour involving the dorsal striatum, with less PFC control.

Pharmacodynamic, metabolic, learned

What are the 3 types of tolerance?

Pharmacodynamic tolerance

the body’s response to a drug decreases, usually due to down-regulation of receptors.

Pharmacokinetic (metabolic) tolerance

the body breaks down or eliminates the drug more rapidly, reducing drug concentration often due to increased activity of drug-metabolising enzymes.

Behavioural (learned) tolerance

person learns to compensate for the drug’s effects through behaviour, reducing observable impairment.

Adenylate cyclase inhibition

activation of μ opioid receptor activation triggers inhibition of adenylate cyclase, leading to reduced production of intracellular signalling molecule, cAMP.

Potassium hyperpolarisation

activation of μ opioid receptors activates K⁺ channels, increasing outward K⁺ flow to hyperpolarise the membrane, thus reducing excitability.

Calcium inhibition

activation of μ opioid receptors closes voltage-gated Ca²⁺ channels, thus reducing vesicular release of neurotransmitters into the synaptic cleft.

Adenylate cyclase inhibition, potassium hyperpolarisation, calcium inhibition

List the 3 outcomes of activation Gi/o-coupled opioid receptors (mainly μ) that lead to reduced neuronal excitability.

Methodone

long-acting full μ-opioid receptor agonist with high oral availability that prevents withdrawal symptoms and reduces cravings while producing reduced euphoric and other effects than short-acting opioids.

Buprenorphine

partial μ-opioid receptor agonist that reduces withdrawal and cravings, with a lower risk of overdose than full agonists. Also a competitive antagonist to full agonist opioids.

Naloxone

short-acting opioid receptor antagonist that rapidly reverses opioid effects, particularly respiratory depression in overdose, BUT can precipitate severe withdrawal.

Naltrexone

long-acting opioid receptor antagonist used after detoxification to prevent opioids and alcohol from producing their usual rewarding effects, helping prevent relapse.

GABA-A enhancement

alcohol enhances GABA-A receptor activity, increasing Cl⁻ influx and hyperpolarising neurons, thereby reducing neuronal excitability.

NMDA inhibition

alcohol inhibits NMDA-type glutamate receptors, reducing excitatory neurotransmission and neuronal activity.

Opioid system activation

alcohol increases endogenous opioid peptide activity, which can further enhance dopamine release and contribute to its rewarding effects.

GABA-A enhancement, NMDA inhibition, opioid system activation

List the 3 outcomes of alcohol that lead to reduced neuronal excitability.

Delirium tremens

severe form of alcohol withdrawal occurring 2-3 days after alcohol use characterised by severe confusion, hallucinations, and autonomic hyperactivity.

Aversion therapy (disulfiram)

blocks aldehyde dehydrogenase needed for ethanol metabolism, resulting in the accumulation of acetaldehyde causing flushing, tachycardia, or distress to discourage alcohol consumption.

Clonidine

α₂-adrenergic agonist decreasing adrenergic neurotransmission to reduces autonomic withdrawal symptoms (inc. nausea, sweating, tachycardia), BUT does not treat opioid cravings directly.

Acamprosate

weak NMDA receptor antagonist to normalise disregulated neurotransmission, reducing cravings.

Benzodiazepines (oxazepam)

enhance GABA-A receptor activity to reduce the CNS hyperexcitability for short-term treatment of severe alcohol withdrawal.

Synapses, neurotransmitters, neuronal excitability

List 3 aspects of neuronal circuitry that are reorganised with persistent drug use, leading to dependence.

Synaptic plasticity

long-term changes in strength or efficiency of communication between neurons in response to repeated drug exposure.

Altered neurotransmitter release

changes in the amount of timing of neurotransmitter released from a neuron, altering signalling in brain reward and motivation circuits.

Altered intrinsic neuronal excitability

changes in how easily a neuron generates an action potential in response to input, making it more or less responsive.

Morphological changes

creation of new synapses or elimination of existing ones, physically changing neural circuits involved in reward, learning, and drug seeking.

Ligand-gated ion channels

neurotransmitter binds directly to the receptor → ion channel opens/closes causing a rapid change in membrane potential, e.g. nicotine receptor. Acts in milliseconds.

G protein-coupled receptors

ligand activates GPCR → G protein activates intracellular signalling pathways (e.g. cAMP, IP₃/DAG) leading to changes ion channels, enzymes or cell activity, e.g. muscarinic receptor. Acts in seconds.

Kinase-linked receptors

ligand binds receptor → activates an associated kinase to phosphorylate proteins causing changes cellular function and gene expression, e.g. cytokine receptor. Acts in hours.

Nuclear receptors

lipid-soluble ligand enters cell → binds intracellular/nuclear receptor causing regulation of gene transcription, e.g. oestrogen receptor. Acts in hours.

Synthesis and storage (1)

neurotransmitter is produced in the neuron and stored in synaptic vesicles in the presynaptic terminal.

Neurotransmitter release (2)

depolarisation reaches the presynaptic terminal causing voltage-gated Ca²⁺ channels open into the presynaptic terminal. Ca²⁺ triggers vesicles to fuse with the membrane → neurotransmitter is released by exocytosis.

Receptor binding (3)

neurotransmitter crosses the synaptic cleft and binds to postsynaptic receptors.

Termination (4)

neurotransmitter is removed by reuptake into neurons/glia, enzymatic breakdown or diffusion.

Blood-brain barrier (BBB)

selective barrier formed mainly by tight junctions between brain capillary endothelial cells, limiting movement of substances from blood into brain tissue.

Paracellular aqueous pathway

movement of small water-soluble molecules between through endothelial cell tight junctions; very limited for most substances.

Transcellular lipophilic pathway

lipid-soluble molecules diffuse directly through endothelial cell membranes; an important route for many CNS drugs.

Arachnoid mater

middle layer of the meninges surrounding the brain and spinal cord; helps protect the CNS and encloses the subarachnoid space, which contains CSF and blood vessels.

Choroid plexus

specialized tissue in the brain ventricles that produces CSF and forms the blood–CSF barrier, controlling movement of substances between blood and CSF.

Circumventricular organs (CVOs)

specialized brain regions with fenestrated/leaky capillaries, allowing blood-borne substances and hormones to interact with neural tissue; they therefore have a reduced or absent BBB.

Anxiolytic drugs

treatments used to reduce the mental and physical symptoms of anxiety, often alongside behavioural management strategies.

Benzodiazepine

bind to GABA-A receptor to increase the frequency of Cl⁻ channel opening leading to increased GABA inhibition of CNS excitability and anxiety.

Sedation, amnesia, dependence

List 3 key adverse effects of benzodiazepine.

Antidepressants

prescription medicines used to treat depression, anxiety, and other health conditions by increasing synaptic concentrations of serotonin and/or noradrenaline.

Major depressive disorder (MDD)

mental health condition causing ongoing sadness, a loss of interest in activities, and low energy that lasts for two weeks or more and affects daily life.

Restoring neuronal connections

What is the proposed theory for why many antidepressants take 4-6 weeks to begin acting?

Tricyclic antidepressants (TCAs)

antidepressant block reuptake of serotonin and noradrenaline into the presynaptic terminal, increasing their synaptic concentrations, e.g. amitriptyline, imipramine.

Anxiolytic benzodiazepines

What are alprazolam and lorazepam?

Tricyclic antidepressants

What are amitriptyline and imipramine?

Dry mouth, constipation, drowsiness, postural hypotension, overdose

What are 5 adverse affects of tricyclic antidepressants.

Selective serotonin reuptake inhibitors (SSRIs)

antidepressants selectively blocking serotonin reuptake to increase in synaptic concentration, e.g. fluoxetine, paroxetine.

Selective serotonin reuptake inhibitors

What are fluoxetine and paroxetine?

Nausea, diarrhoea, sexual dysfunction, insomnia

List 4 adverse affects of selective serotonin reuptake inhibitors.

Serotonin, dopamine, noradrenaline, adrenaline, acetylcholine

What are the 5 biogenic amines?

Opioids

What illicit drug has these effects? Euphoria, analgesia, relaxation, sedation.

Opioids

What illicit drug has these adverse effects? Respiratory depression, constipation, nausea/vomiting, dependence.

Alcohol

What illicit drug has these effects? Euphoria, relaxation, disinhibition, impaired judgement and coordination.

Alcohol

What illicit drug has these adverse effects? CNS depression, impaired memory, nausea/vomiting, dehydration, respiratory depression at high doses, dependence.

Cannabis

What illicit drug has these effects? Euphoria, relaxation, altered perception, increased appetite.

Cannabis

What illicit drug has these adverse effects? Impaired memory and coordination, anxiety/paranoia, tachycardia, impaired judgement.

Benzodiazepines

What illicit drug has these effects? Anxiolysis, sedation.

Benzodiazepines

What illicit drug has these adverse effects? Drowsiness, impaired coordination and memory, confusion, dependence, risk of respiratory depression.

Stimulants

What illicit drug has these effects? Increased alertness, energy and concentration, euphoria.

Stimulants

What illicit drug has these adverse effects? Tachycardia, anxiety, insomnia, hyperthermia, possible psychosis.

Opioids

What illicit drug has these withdrawal effects? 5-12 days of craving, restlessness, fever, GIT upset, dysphoria. Persistent insomnia and drug craving.

Alcohol

What illicit drug has these withdrawal effects? Craving, nausea, sweating, tachycardia, seizures, and delirium tremens.

Cannabis

What illicit drug has these withdrawal effects? Irritability, anxiety, insomnia, reduced appetite, low mood and cravings.

Benzodiazepines

What illicit drug has these withdrawal effects? Anxiety, insomnia, sweating and irritability, seizures, delirium and psychosis.

Stimulants

What illicit drug has these withdrawal effects? Fatigue, depressed mood, irritability, poor concentration and strong cravings; severe depression/suicidal thoughts can occur.

Opioid overdose

potentially fatal toxicity characterised by marked CNS and respiratory depression, typically with reduced consciousness, slow/shallow breathing and pinpoint pupils.

Breathing support, naloxone

Key treatments for opioid overdose.

Serotonin syndrome

potentially life-threatening condition caused by drug use leading to hyperthermia, seizures, rhabdomyolysis, or organ failure.

Stop serotonergic drugs, cooling and IV fluids, benzodiazepines

Key treatments for serotonin syndrome.

Benzodiazepine withdrawal

withdrawal syndrome which may cause seizures or delirium in severe cases.

Benzodiazepine tapering with diazepine, monitoring

Key treatments for benzodiazepine withdrawal.

Stimulant psychosis

psychotic state caused by acute or chronic stimulant use, involving paranoia, hallucinations, and impaired judgement, causing potentially dangerous behaviour.

Antipsychotics

Key treatment for stimulant psychosis.