10. drugs of abuse

made by ai

Which legal drugs of abuse are excluded from this lecture?

Alcohol, nicotine and caffeine.

What are the different origins of drugs of abuse?

Naturally occurring (cannabis, cocaine), semi-synthetic (heroin) and entirely synthetic (LSD).

How do drugs of abuse affect the CNS?

All affect CNS function; some are stimulants, some are depressants.

Are all drugs of abuse associated with addiction and dependence?

No, many are associated with addiction and dependence, but not all.

What are the main classes of illicit drugs?

Cannabinoids, cocaine, amphetamines, opioids, ecstasy/MDMA, hallucinogens/psychedelics and ketamine.

What are the main reasons people take illicit drugs?

Pleasure and euphoria, curiosity and experimentation, social influences and peer pressure, stress relief and coping, self-medication, enhancement of mood or confidence, performance enhancement, escapism, sensation seeking, dependence and addiction.

Which neurotransmitter has a key role in the reward pathway?

Dopamine (DA).

What pathway is important in drug reward and reinforcement?

The mesolimbic pathway.

What are examples of cannabinoids?

Phytocannabinoids (THC and CBD) and synthetic cannabinoids (e.g. Spice).

What is the main psychoactive component of cannabis and which receptors does it act on?

THC; acts primarily at CB₁ and CB₂ receptors (GPCRs).

Where are CB₁ receptors expressed?

Cortex, hippocampus, basal ganglia, cerebellum, amygdala and nucleus accumbens.

How does activation of presynaptic CB₁ receptors affect neurotransmitter release?

Inhibits neurotransmitter release by reducing Ca²⁺ influx and increasing K⁺ conductance.

How do cannabinoids contribute to abuse potential?

Cannabis indirectly increases DA signalling within the mesolimbic reward pathway.

What are the main effects of cannabinoids?

Euphoria, relaxation, altered sensory perception, increased appetite and reduced psychomotor performance.

How do cannabinoids affect cognitive function?

Affect attention, learning, short-term memory and executive function.

What happens with repeated cannabinoid use?

Tolerance, CB₁ receptor desensitisation and neuroadaptation.

What are the long-term effects of cannabinoid use?

Dependence, cognitive impairment and reduced educational and occupational performance.

What psychological effects are associated with high-potency cannabis and synthetic cannabinoids?

Increased anxiety, panic attacks and psychosis.

What type of drug is cocaine?

A potent psychostimulant.

How does cocaine increase dopamine signalling?

By inhibiting dopamine, noradrenaline and serotonin transporters.

What effect does cocaine have on extracellular dopamine concentrations?

Increases extracellular DA concentrations within the reward pathway.

What are the key sites of cocaine action?

Ventral tegmentum, nucleus accumbens, prefrontal cortex, amygdala and striatum.

What effects does enhanced DA signalling within the mesolimbic reward pathway produce?

Euphoria, reinforcement and a high potential for addiction.

What are the main effects of cocaine?

Increased alertness, energy, confidence, sociability and reduced fatigue.

What are the peripheral sympathetic effects of cocaine?

Tachycardia, hypertension, mydriasis and vasoconstriction.

What psychological effects can high doses of cocaine cause?

Anxiety, agitation, panic attacks, paranoia, hallucinations and psychosis.

What are the effects of repeated cocaine exposure?

Tolerance, craving and compulsive drug-seeking behaviour.

What are the long-term effects of cocaine use?

Dependence, depression, cognitive impairment, cardiovascular disease, myocardial infarction and stroke.

Why is cocaine cardiotoxic when combined with alcohol?

The combination is cardiotoxic.

What are examples of amphetamines?

Amphetamine and methamphetamine.

How do amphetamines affect neurotransmitter signalling?

Increase DA and NA signalling within the CNS.

How do amphetamines enter presynaptic terminals?

Via DA and NA transporters.

How do amphetamines increase monoamine release?

Reverse transporter function and promote release of monoamines from synaptic vesicles through interaction with VMAT2.

What are the main sites of amphetamine action?

Ventral tegmentum, nucleus accumbens, prefrontal cortex and striatum.

What does increased DA signalling within the mesolimbic reward pathway produce?

Euphoria, reinforcement and a high potential for addiction.

What are the main effects of amphetamines?

Increased alertness, energy, concentration, confidence and reduced fatigue.

What are the physiological effects of amphetamines?

Tachycardia, hypertension, mydriasis, sweating, vasoconstriction and appetite suppression.

What psychological effects can high doses of amphetamines produce?

Agitation, anxiety, paranoia, aggressive behaviour, hyperthermia and psychosis.

What are the effects of repeated amphetamine use?

Tolerance, craving and compulsive drug-seeking behaviour.

What are the long-term effects of amphetamine misuse?

Dependence, sleep disturbance, weight loss, depression, cognitive impairment and persistent psychiatric symptoms.

What does chronic methamphetamine exposure cause?

Dopaminergic neurotoxicity and severe patterns of addiction and relapse.

What are examples of opioids?

Heroin, fentanyl and oxycodone.

Which receptors do opioids activate?

μ-opioid receptors, which are Gi/o-coupled GPCRs.

How does activation of μ-opioid receptors affect neuronal activity?

Inhibits adenylyl cyclase, reduces Ca²⁺ influx and increases K⁺ efflux, resulting in neuronal inhibition.

How do opioids increase dopamine release in the nucleus accumbens?

In the VTA, opioids inhibit GABAergic interneurons, causing disinhibition of dopaminergic neurons and increased DA release.

What are the main sites of opioid action?

Ventral tegmentum, nucleus accumbens, brainstem respiratory centres, spinal cord and limbic system.

What are the main effects of opioids?

Analgesia, sedation, anxiolysis, miosis, reduced GI motility and respiratory depression.

How do opioids produce euphoria and addiction?

Enhanced DA signalling within the reward pathway produces euphoria and a high risk of addiction.

What does repeated opioid exposure produce?

Tolerance, physical dependence and compulsive drug-seeking behaviour.

What are the symptoms of opioid withdrawal?

Agitation, anxiety, muscle aches, sweating, diarrhoea, abdominal cramps and insomnia.

What are the long-term harms of opioid misuse?

Dependence, overdose, respiratory failure, infectious diseases (particularly with injection use) and increased mortality.

What are examples of hallucinogens?

LSD, psilocybin (magic mushrooms) and newer synthetic psychedelic compounds.

How do hallucinogens affect the CNS?

Alter perception, cognition, mood and sensory processing rather than producing strong physical dependence.

What is the main mechanism of action of hallucinogens?

Activation of 5-HT₂A receptors.

What are the main sites of hallucinogen action?

Prefrontal cortex, thalamus, limbic system and cortical association networks.

How does activation of 5-HT₂A receptors affect the brain?

Disrupts normal sensory integration and cortical information processing.

How does LSD affect communication between brain regions?

Produces changes in perception, thought patterns and consciousness.

What are the main psychological effects of hallucinogens?

Visual hallucinations, sensory distortions, altered perception of time and enhanced emotional responses.

What changes in perception can hallucinogens produce?

Intensified colours, altered sounds, feelings of insight and changes in self-awareness.

What are the physiological effects of hallucinogens?

Mydriasis, tachycardia, mild hypertension, sweating and tremor.

What are the adverse psychological effects of hallucinogens?

Anxiety, panic reactions, paranoia, confusion and bad trips.

What happens with repeated hallucinogen use?

Physical dependence is uncommon, but tolerance can occur through 5-HT₂A receptor desensitisation.

What are the rare but serious adverse effects of hallucinogens?

Persistent perceptual disturbances and exacerbation of psychiatric disorders.

What does MDMA stand for?

3,4-methylenedioxymethamphetamine.

How does MDMA primarily increase serotonin transmission?

Through reversal of the 5-HT transporter.

Which other neurotransmitters does MDMA promote release of?

Dopamine (DA) and noradrenaline (NA).

What are the major sites of MDMA action?

Raphe nuclei, prefrontal cortex, limbic system, hypothalamus and mesolimbic reward pathway.

What does massive 5-HT release produce?

Enhanced empathy, sociability, emotional warmth and mood elevation.

What are the main psychological effects of MDMA?

Euphoria, increased energy and sensory perception, emotional closeness and reduced social anxiety.

What are the physiological effects of MDMA?

Tachycardia, hypertension, mydriasis, sweating, jaw clenching and increased body temperature.

Why is hyperthermia important in MDMA toxicity?

Hyperthermia is a major cause of serious toxicity.

What are the adverse effects of MDMA?

Dehydration, anxiety, panic reactions, hyponatraemia and serotonin syndrome.

What are the effects of repeated MDMA use?

Tolerance, serotonin depletion, low mood, sleep disturbance, memory impairment and cognitive deficits.

What type of drug is ketamine?

A dissociative anaesthetic increasingly misused recreationally.

What is ketamine's main mechanism of action?

Non-competitive NMDA receptor antagonist, reducing excitatory glutamatergic neurotransmission.

Which other systems does ketamine interact with?

Dopaminergic, opioid, cholinergic and monoaminergic systems.

What are the main sites of ketamine action?

Cerebral cortex, thalamus, hippocampus, limbic system and mesolimbic reward pathway.

How does NMDA receptor blockade produce dissociative effects?

Disrupts normal sensory processing.

How does ketamine contribute to its reinforcing and abuse-producing properties?

Indirectly increases DA release within the nucleus accumbens.

What are the main effects of ketamine?

Euphoria, relaxation, analgesia, perceptual distortion, altered awareness and feelings of detachment.

What effects can higher doses of ketamine produce?

Profound dissociation, hallucinations, impaired coordination, slurred speech and loss of awareness (K-hole).

What are the physiological effects of ketamine?

Tachycardia, hypertension, dizziness and nystagmus.

What are the long-term effects of ketamine misuse?

Memory impairment, reduced cognitive function and persistent psychological symptoms.

What urinary effects can heavy ketamine use cause?

Urinary tract damage, bladder pain, haematuria and irreversible bladder dysfunction.

What was the famous NASA study in 1995 investigating?

The effects of drugs on web construction in European garden spiders.

How were drugs administered in the NASA spider study?

In sugar water or via drugged flies.

How did cannabis affect spider web construction?

Smaller webs; lost focus halfway through, leaving significant gaps.

How did amphetamine affect spider web construction?

Larger webs spun frantically but lacking internal structure.

How did sedatives affect spider web construction?

Spiders fell asleep or abandoned the task shortly after starting.

How did caffeine affect spider web construction?

Most chaotic, disorganised and fragmented webs, losing their sense of geometry.

Who evaluated the harms caused by recreational drugs in the UK?

Addiction and public health experts from the Independent Scientific Committee on Drugs (ISCD).

How many drugs were evaluated in the UK drug harms study?

20 legal and illegal drugs.

What criteria were used to rate the drugs?

16 criteria: 9 individual harms (e.g. mortality, dependence) and 7 societal harms (e.g. crime, economic cost).

What did the study find about empirical evidence and legal classifications?

Evidence regarding harm to users and society did not reflect legal controls and statutory classifications of substances.

What are the main pharmacological targets of illicit drugs?

CB₁, 5-HT₂A, μ-opioid and NMDA receptors, and monoamine transporters (e.g. SERT, DAT, NET).

How are the pleasurable effects of illicit drugs mediated?

Directly or indirectly by enhancing DA signalling between the VTA and nucleus accumbens (reward pathway).

How variable are the harms associated with illicit drug use?

Highly variable (some very low).

Which illicit drugs are being investigated for therapeutic effects?

MDMA for PTSD and psilocybin for treatment-resistant depression.

Recreational drugs or illicit drugs.

what are drugs of abuse also known as?

Recreational drugs or elicit drugs