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Basic Neurosciences · Paper A

Recreational drug use

The idea

Every recreational drug is a hand on one or more transmitter faders, and the symptom it causes is what that fader does when pushed too far or let go. Cocaine and amphetamine push dopamine, so they give euphoria and then a paranoid psychosis that looks like schizophrenia'sA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more → positive symptoms. MDMA floods serotonin, so it gives warmth and empathy and then hyperthermia and hyponatraemia. Ketamine blocks the NMDA glutamate channel, so it gives dissociationA disconnection between a person's thoughts, feelings, memories, or sense of identity, often as a response to stress.Read more → and reproduces both positive and negative symptoms in the laboratory. Opioids act on mu receptors in reward circuits and in the brainstem, so they give euphoria and stop breathing. Cannabis works as a partial agonistA drug that activates a receptor but produces a smaller effect than a full agonist, even at a high dose.Read more → at CB1, so its psychosis risk rises with dose and potencyHow small a dose of a drug is needed to produce a given effect.Read more →, and synthetic cannabinoids, being full agonistsA drug or chemical that activates a receptor to produce an effect.Read more →, are worse. The safety claims that matter most sit on the opioid fader: toleranceNeeding a larger dose of a drug over time to get the same effect.Read more → re-trims it within weeks, abstinence resets it, and the old dose after prison or detox is an overdose.

How it works

The syllabus asks for the link between each drug's action on transmission and the mental symptoms it produces, and the link runs through the same handful of receptors and transporters every time. Stimulants raise synaptic dopamine and noradrenaline: cocaine blocks the dopamine transporter (and the noradrenaline and serotonin transporters) so released dopamine lingers, while amphetamines enter the terminal, displace dopamine from vesicles and reverse the transporter, forcing release. Both act on the mesolimbic reward pathway (taught on the reward pathway card), which is why they are reinforcing; both, at sustained high dose, produce the persecutory delusionsA fixed false belief, held with total conviction, that is not shared by the person's culture and is not changed by evidence against it.Read more →, hallucinationsSeeing, hearing, or otherwise sensing things that are not really there.Read more → and stereotyped behaviour that Connell described in his 1958 monograph on amphetamine psychosis and that antipsychotics, which lower the same fader, relieve. MDMA reverses the serotonin transporter and releases serotonin in bulk, with smaller effects on dopamine and noradrenaline: the empathy and the rise in body temperature are serotonergicRelating to serotonin, a brain chemical involved in mood.Read more →, and the hyponatraemia comes from vasopressin release combined with drinking to stay cool. Ketamine is a non-competitive antagonistA drug that blocks a receptor, stopping it from being activated.Read more → at the NMDA glutamate receptor. Krystal and colleagues (1994, Archives of General Psychiatry) showed that a sub-anaesthetic dose in healthy volunteers produces dissociationA disconnection between a person's thoughts, feelings, memories, or sense of identity, often as a response to stress.Read more →, perceptual change and negative-symptom-like withdrawal, which is why NMDA hypofunction became a second model of schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more → beside dopamine excess. Opioids are mu-receptor agonistsA drug or chemical that activates a receptor to produce an effect.Read more →: in the ventral tegmental areaA midbrain structure that is a key source of the brain's dopamine reward pathways.Read more → they silence the GABAThe brain's main calming (inhibitory) chemical messenger, boosted by benzodiazepines and alcohol.Read more → interneurons that restrain dopamine cells, so dopamine rises; in the brainstem they depress the respiratory drive, and that second action kills. Tetrahydrocannabinol is a partial agonistA drug that activates a receptor but produces a smaller effect than a full agonist, even at a high dose.Read more → at presynaptic CB1 receptors, which normally dampen transmitter release; the risk of psychosis tracks dose and potencyHow small a dose of a drug is needed to produce a given effect.Read more →, and synthetic cannabinoids, full agonists at the same receptor, produce more severe agitation, seizures and psychosis. Classical hallucinogens (LSD, psilocybin) act at the 5-HT2AA serotonin receptor subtype that many antipsychotic drugs block, thought to help their antidepressant and antipsychotic effect.Read more → receptor and distort perception while insightA person's awareness and understanding that they are unwell and need help.Read more → usually survives. Nitrous oxide blocks NMDA receptorsA glutamate receptor in the brain involved in learning and memory, and a target of drugs like ketamine and memantine.Read more → and, with heavy use, inactivates vitamin B12 and damages the spinal cord. GHB and its precursor GBL act at GABA-B receptors, with a withdrawal that, like alcohol's, can be fatal.

How to spot it

  • An emergency department note records pinpoint pupils, six breaths a minute and a response to intramuscular naloxone that fades after forty minutes, in a man released from prison nine days earlier.
  • "He thinks the neighbours have put cameras in the light fittings": a sister describing a week of persecutory beliefs in a brother who has been using crack daily, whose beliefs fade within days on the ward.
  • A hostel worker reports that a resident became rigid, febrile and confused within an hour of taking a pill at a party and had started sertraline the previous week.
  • The finding that does not fit a stimulant story: pupils constricted rather than dilated, which sends you to the opioid fader.
  • A urine screen positive for ketamine in a young man with months of urinary frequency, pain on passing urine and sterile cultures.
  • A community team letter describes a man with schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more → whose relapses follow each return to high-potencyHow small a dose of a drug is needed to produce a given effect.Read more → cannabis, and whose psychiatrist has been asked whether services should still see him.
  • A twenty-year-old presents with numb feet and an unsteady gait after months of nitrous oxide canisters at weekends.

Tell it apart

  • Cocaine vs amphetamine — cocaine blocks reuptake and lasts under an hour; amphetamine forces release and lasts hours; the psychosis is the same in kind.
  • Stimulant psychosis vs schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more → — the drug-induced picture clears within days to a few weeks of abstinence; psychosis that persists beyond that suggests a primary illness the drug unmasked.
  • Opioid intoxication vs stimulant intoxication — pinpoint pupils, slowed breathing and drowsiness versus dilated pupils, tachycardia and agitation.
  • Opioid withdrawal vs GHB, alcohol or benzodiazepine withdrawal — opioid withdrawal is miserable (dilated pupils, yawning, rhinorrhoea, diarrhoea, piloerection) but not in itself life-threatening; GHB, alcohol and benzodiazepine withdrawal can cause seizures and delirium and can kill.
  • MDMA hyperthermia vs serotonin syndromeA dangerous reaction from too much serotonin activity, causing agitation, high temperature, and muscle overactivity.Read more → — both are serotonergicRelating to serotonin, a brain chemical involved in mood.Read more → and overlap; serotonin syndrome is the label when clonusRhythmic, involuntary muscle contractions, often tested at the ankle.Read more →, hyperreflexiaOveractive or overresponsive reflexes.Read more → and autonomic instability appear, and the risk rises sharply with an MAOIMonoamine oxidase inhibitor, an older antidepressant with strict food and drug interaction rules.Read more → or SSRISelective serotonin reuptake inhibitor, a common type of antidepressant.Read more → on board.
  • Cannabis vs synthetic cannabinoid — partial agonistA drug that activates a receptor but produces a smaller effect than a full agonist, even at a high dose.Read more → versus full agonistA drug or chemical that activates a receptor to produce an effect.Read more → at CB1: the synthetic product brings seizures, collapse and severe psychosis that plant cannabis rarely does.
  • Ketamine vs phencyclidine — both block NMDA channels; ketamine is shorter-acting and now common; phencyclidine is longer-acting and more violent in presentation, and rare in the United Kingdom.
  • Hallucinogen intoxication vs psychosis — under LSD or psilocybin the person usually knows the perceptions are drug-induced; a psychotic person does not.
  • Naloxone reversal vs recovery — naloxone acts for shorter than most opioids, methadone especially, so re-sedation after apparent recovery is expected and the person needs observation.

Watch for

  • ⚠️ Missing the loss-of-tolerance window, after release from prison or completion of detoxification, the old heroin dose can be fatal, because toleranceNeeding a larger dose of a drug over time to get the same effect.Read more → has fallen while the habit remembers the dose. Merrall and colleagues (2010, Addiction) confirmed the excess of drug-related deaths in the first two weeks after prison release across a meta-analysisA study that statistically combines the results of several separate studies into one overall estimate.Read more → of cohorts, and Strang and colleagues (2003, BMJ) documented overdose deaths after inpatient detoxification. The 2017 UK clinical guidelines on drug misuse and dependence (the Orange Book) recommend take-home naloxone and an explicit warning about lost tolerance at discharge from prison or detoxification.
  • ⚠️ Treating naloxone as the end of the emergency: it reverses mu-receptor effects within minutes but wears off before heroin does and long before methadone does, so repeat dosing and observation are needed, and any opioid overdose is an ambulance call.
  • ⚠️ Overlooking what was taken alongside the opioid: benzodiazepines, alcohol, gabapentinoids and high-potencyHow small a dose of a drug is needed to produce a given effect.Read more → synthetic opioids (fentanyl and, increasingly in the United Kingdom supply since 2023, nitazenes) multiply respiratory depression and account for a growing share of deaths.
  • Advising a person on MDMA to drink freely, water without sodium, plus vasopressin release, produces the hyponatraemia that has killed young people at clubs; the advice is sipping, cooling and rest.
  • Assuming cannabis carries no dependence, DSM-5 (2013) includes a cannabis withdrawal syndrome (irritability, insomnia, reduced appetite, restlessness), and ICD-11 recognises cannabis dependence.
  • Dismissing the psychosis risk as an old scare: in the EU-GEI case-control studyA study that starts with people who already have an outcome and looks backward to compare their past exposures with people who do not.Read more → (Di Forti and colleagues, 2019, Lancet Psychiatry, 901 cases and 1,237 controls), daily use carried adjusted odds of first-episode psychosis about three times those of never-users, and daily use of high-potencyHow small a dose of a drug is needed to produce a given effect.Read more → cannabis about five times, with about one in eight first-episode cases across the eleven sites, and about three in ten in London, attributable to high-potency use.

Use it again

  • Name the fader before the drug, dopamine up means stimulant, serotonin up means MDMA or a serotonergicRelating to serotonin, a brain chemical involved in mood.Read more → mix, NMDA down means ketamine or nitrous oxide, opioid means pinpoint pupils and slow breathing, CB1 means cannabis or a synthetic.
  • Read the pupils and the breathing first on any intoxication stem; they separate opioid from stimulant before anything else does.
  • Predict the withdrawal from the fader, releasing a pushed dopamine fader gives a crash of anhedoniaThe loss of the ability to feel pleasure from things that used to be enjoyable.Read more → and hypersomnia; releasing the opioid fader gives the flu-like syndrome; releasing GABAThe brain's main calming (inhibitory) chemical messenger, boosted by benzodiazepines and alcohol.Read more →-B (GHB) or GABA-A (alcohol, benzodiazepines) gives the dangerous one.
  • On any opioid stem, ask what toleranceNeeding a larger dose of a drug over time to get the same effect.Read more → is doing: weeks of use raise it, weeks of abstinence remove it, and naloxone is shorter-acting than the drug it reverses.
  • On a psychosis-with-cannabis stem, the answer hinges on dose and potencyHow small a dose of a drug is needed to produce a given effect.Read more → (Di Forti 2019) and on treating both conditions together (CG120), never on excluding the person from care.

In detail

In this lesson

  1. Hook — the ninth day out
  2. Plain definition — drugs sorted by the transmitter they move
  3. The critical caveat — tolerance is the fact the picture must be told
  4. First principles — the mixing desk
  5. Structured walk-through — reading an intoxicated patient off the desk
  6. Look-alikes & differentials — pairs the desk separates
  7. Diagnosis — history, pupils, breathing, and a screen
  8. Management — the rules that follow from the faders
  9. Exam pearl — the fortnight
  10. In one line — the trim

In this lesson

  1. Hook — the ninth day out
  2. Plain definition — drugs sorted by the transmitter they move
  3. The critical caveat — tolerance is the fact the picture must be told
  4. First principles — the mixing desk
  5. Structured walk-through — reading an intoxicated patient off the desk
  6. Look-alikes & differentials — pairs the desk separates
  7. Diagnosis — history, pupils, breathing, and a screen
  8. Management — the rules that follow from the faders
  9. Exam pearl — the fortnight
  10. In one line — the trim

Hook — the ninth day out

A man is found unresponsive in a hostel nine days after leaving prison. His pupils are pinpoint and he is breathing six times a minute. He took the dose he always took. The paramedic's naloxone brings him round within minutes, and forty minutes later he is drifting again. Nothing about his dose changed. What changed was inside him, and if you understand that one fact you understand the most important safety claim in this topic.

Plain definition — drugs sorted by the transmitter they move

Recreational drugs are substances taken for their psychoactive effect outside medical use, and the syllabus asks you to link each one's effect on neurotransmission to the mental symptoms it produces. Six systems cover almost all of them: dopamine (stimulants), serotonin (MDMA and the classical hallucinogens), glutamate at the (ketamine, nitrous oxide), (alcohol, benzodiazepines, GHB), the mu-opioid receptor (heroin, methadone, fentanyl), and the cannabinoid CB1 receptor (cannabis and its synthetic imitations). The reward pathway they share and the GABA-A receptor each have a card of their own; here the question is what each drug does to its own system and what follows.

The critical caveat — tolerance is the fact the picture must be told

Nothing in a drug's receptor pharmacology tells you that the same dose becomes lethal after a gap, yet that is the claim that decides most safety stems. Opioid builds within weeks of regular use and falls within weeks of abstinence. A person leaving prison or completing detoxification has lost the tolerance and kept the memory of the dose. Merrall and colleagues (2010, Addiction) pooled the cohorts and confirmed the excess of drug-related deaths in the first two weeks after release; Strang and colleagues (2003, BMJ) showed the same danger after inpatient detoxification. The 2017 UK clinical guidelines on drug misuse and dependence (the Orange Book) answer it by recommending take-home naloxone and a spoken warning at discharge from prison or detoxification, and you should be able to give both.

First principles — the mixing desk

Picture a sound engineer's desk with six faders, one per transmitter system, each resting at its trim. A recreational drug is a hand on a fader, and the sound is the symptom. Cocaine pushes dopamine up by blocking the transporter that would clear it (a reuptake block, so the effect lasts under an hour); amphetamines push it up by forcing release from the terminal (so the effect lasts hours). At moderate gain the sound is euphoria and alertness; at sustained high gain it is the persecutory , and stereotypies that Connell described in 1958 as amphetamine psychosis, and that antipsychotics, which pull the same fader down, relieve. Let the fader go and the crash follows: hypersomnia, hunger, , low mood.

MDMA pushes the serotonin fader by reversing the serotonin transporter (with smaller pushes on dopamine and noradrenaline). The empathy and warmth are the pleasant sound; hyperthermia, and when an or is already on the desk, are the dangerous ones; the hyponatraemia that has killed young people comes from vasopressin release plus water drunk to stay cool. Ketamine pulls the NMDA fader down, and Krystal and colleagues showed in 1994 that a sub-anaesthetic dose reproduces , perceptual change and negative-symptom-like withdrawal in healthy volunteers, the basis of the glutamate model of . Chronic ketamine use damages the bladder (ulcerative cystitis with frequency and pain on passing urine).

The opioid fader is wired to two speakers, and the desk is only trustworthy if you remember both: mu silence the interneurons that restrain dopamine cells in the , which is the reward, and they depress the brainstem respiratory drive, which is the death. Add the trim: weeks of use move it (), weeks of silence reset it (loss of tolerance), and the familiar push is now an overdose. The CB1 fader is pushed part-way by tetrahydrocannabinol, a at presynaptic receptors that normally dampen release, and fully by synthetic cannabinoids, which is why the synthetic product brings seizures, collapse and severe psychosis.

Structured walk-through — reading an intoxicated patient off the desk

Suppose a young woman is brought in agitated. Read the pupils and the breathing before anything else: dilated pupils with tachycardia point to the dopamine fader (stimulant), constricted pupils with slow breathing to the opioid fader, and the two are never confused if you look. If she is hot, rigid and confused with a history of a pill and an antidepressant, the serotonin fader is the story, and is the label when and appear. If she is detached, staring and analgesic, the NMDA fader is down. If she has seizures and collapse after a smoked herbal product, think synthetic cannabinoid rather than cannabis.

Then predict the withdrawal by imagining the fader released. Dopamine released gives the crash. Opioid released gives dilated pupils, yawning, lacrimation, rhinorrhoea, piloerection and diarrhoea, wretched but not in itself dangerous. released, whether from alcohol, benzodiazepines or GHB, gives the withdrawal that seizes and can kill, and GHB dependence can need round-the-clock dosing to hold off. Finally, ask what the fader has done to a mental illness already present. For example, in the EU-GEI study (Di Forti and colleagues, 2019), daily cannabis use carried adjusted odds of first-episode psychosis about three times those of never-users, and daily high- use about five times; NICE CG120 says treat the psychosis and the substance use together, and never turn the person away because of the drug.

Look-alikes & differentials — pairs the desk separates

  • Stimulant psychosis versus : the drug picture clears within days to weeks of abstinence.
  • MDMA hyperthermia versus : , and autonomic instability name the second.
  • Opioid overdose versus GHB overdose: both sedate and slow breathing; only the first answers naloxone.
  • Hallucinogen intoxication versus psychosis: is usually retained under LSD or psilocybin.
  • Cannabis versus synthetic cannabinoid: partial versus full , mild versus severe.
  • Ketamine cystitis versus urinary infection: sterile cultures and a drug history.

Diagnosis — history, pupils, breathing, and a screen

The diagnosis of intoxication or withdrawal is clinical, made from the history, the pupils, the vital signs and the mental state, with a urine drug screen as confirmation rather than the starting point (synthetic cannabinoids and many novel substances do not appear on routine screens). ICD-11 and DSM-5 (2013) both classify substance-induced psychotic disorders and withdrawal syndromes, and DSM-5 added a cannabis withdrawal syndrome. Ask every patient with psychosis about cannabis and frequency, and every opioid user about recent abstinence, prison, benzodiazepines, alcohol and gabapentinoids, because each of those multiplies the respiratory risk.

Management — the rules that follow from the faders

For opioid overdose: naloxone, repeated because it wears off before heroin and long before methadone, and an ambulance every time. For opioid dependence: methadone or buprenorphine as substitution under NICE TA114, psychosocial treatment including contingency management under CG51, and, as the Orange Book recommends, take-home naloxone with a spoken warning about lost at discharge from prison or detox. For psychosis with substance use: both treated, in the same service, under CG120. For stimulant psychosis: abstinence and short-term antipsychotic cover if needed, with review once the drug has cleared. For MDMA: cooling, cautious fluids, and treatment of if it declares. For GHB or alcohol withdrawal: medically supervised, because it can kill. Guidance checked on 6 September 2026.

Exam pearl — the fortnight

Explain, in one sentence that names , why the fortnight after prison release is the deadliest time for an opioid user, then say what two things should leave the prison gate with him. Tolerance fell while the remembered dose did not; naloxone and the warning go with him.

In one line — the trim

Each recreational drug is a hand on a transmitter fader, the symptom is the sound that fader makes when pushed, pulled or released, and the trim that weeks of use move and weeks of abstinence reset is the fact that turns a familiar opioid dose into a fatal one.

Try a question from this area

  • Question 1
  • Question 2
  • Question 3
  • Excluding a person with psychosis from mental health services because of substance use: NICE CG120 (2011) says treat both conditions and do not use the substance use as a reason to deny care.