Drugs and Behaviour

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Drugs and Behaviour

• Dr Claire Gibson (cg95_at_le.ac.uk)
• School of Psychology

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Overview

• Definitions
• Routes of administration
• Drug effectiveness dose response, therapeutic
  index, tolerance
• What is a placebo?
• How do drugs act?
• Behavioural effects and mechanism(s) of action
• Cannabis
• Monoamine-related drugs
• Dissociative anaesthetics

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Definitions

• Drug
• Psychopharmacology
• Drugs have effects and sites of action

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Pharmacokinetics

• Absorption
• Distribution
• Metabolism
• Excretion

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Administration

• Route of administration determines (in part)
  amount of drug that reaches the brain and the
  speed at which it starts to act

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Routes of administration
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Routes of administration

• Ingestion
• Tablets, capsules, syrups,
• Depends on absorption by gut
• Inhalation
• Smoking, nasal absorption
• Takes advantage of rich blood supply of nose and
  lungs
• Peripheral injection
• Subcutaneous, intramuscular, intravenous
• Central injection
• Epidural, intracerebroventricular (icv)

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Absorption

• Absorption
• Dependent upon various factors
• including drug solubility, gastrointestinal
  motility and pH

Bioavailability
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Absorption
Plasma cocaine concentration (mg/ml)
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Distribution

• Must enter blood stream
• Gastrointestinal motility, pH
• Blood flow
• Diffusibility
• Solubility
• To get to brain must pass through blood-brain
  barrier (BBB)

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Blood-brain barrier (BBB)
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Metabolism and excretion

• Metabolism
• The liver
• First-pass metabolism
• Excretion
• The kidneys
• Drug testing

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Drug effectiveness
high
Dose response curve
Effect of drug
low
low
Dose of drug
high
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Drug effectiveness
Dose-response curve for the analgesic effect of
morphine
high
Dose-response curve for the depressive effect of
morphine on respiration
Margin of safety
Effect of drug
low
low
Dose of drug
high
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• Repeated administration
• Tolerance
• Sensitization
• Placebo
• Innocuous
• Any effect?

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How drugs act
Precursor
Enzyme
Neurotransmitter (NT)
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How drugs act

• Drug serves as a precursor
• Drug inactivates synthetic enzyme
• Drug prevents storage of NT
• Drug stimulates release of NT
• Drug inhibits release of NT
• Drug stimulates postsynaptic receptors
• Drug blocks postsynaptic receptors
• Drug inhibits synthesis/release of NT
• Drug increases synthesis/release of NT
• Drug blocks reuptake
• Drug inactivates acetycholinesterase
• Agonist
• Antagonist

Precursor
Enzyme
Neurotransmitter (NT)
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Drugs and receptors

• Direct agonist/antagonist
• Indirect agonist/antagonist

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Mind-altering drugs of abuse

• Classification difficult
• Dose important
• Psychotomimetic psychosis-mimicking
• Psychotogenic psychosis-generating
• Hallucinogenic
• Neurotransmitter mimics

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Mind-altering drugs of abuse

• True hallucinogens produce their effects without
  causing changes in the level of consciousness
• Share an ability to profoundly alter mood state
  and perceptual-motor functioning
• NOT common mechanism

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Hallucinogens

• Term is mis-leading?
• Psychedelics
• Dissociatives
• Deliriants

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Psychedelics

• mind expanding
• Enhance/amplify thought processes of brain
• E.g. LSD (acid), MDMA (ecstasy), magic
  mushrooms, cannabis
• High levels dissociative state

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Dissociatives

• Reduce or block signals to the conscious mind
• anesthesia
• e.g. PCP (angel dust), ketamine, nitrous oxide,
  muscimol
• Also act as CNS depressants
• death

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Deliriants

• Acetylcholine receptor antagonists
• true hallucinogens
• Plants such as deadly nightshade, mandrake,
  henbane, and datura, high doses of pharmaceutical
  drugs
• Side effects
• toxic

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Mind-altering drugs of abuse

• Cannabis
• Monoamine-related drugs
• Dissociative anaesthetics

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Cannabis

• Natural substance derived from hemp plant,
  Cannabis sativa
• Reported use as recreational drug for over 4000
  years
• However, since 4th century BC also employed as a
  therapeutic drug
• Today most commonly used street drug world wide

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Cannabinoids

• Cannabis plant contains over 60 compounds
• Cannabinoids
• Marijuana
• Hashish
• Active component
• delta-9 tetrahydrocannibinol (THC)
• street potency of cannabis i.e. THC content
• 1974 0.35
• 1990 3.54

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Effects of cannabis

• 1 initial period of euphoria and relaxation
  followed by depressant period.
• Euphoria, altered time perception, dissociation
  of ideas, paranoia, motor impairments and
  occasional hallucinations.
• Alterations in various cognitive and behavioural
  abilities

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Biological effects of cannabis

• Cannabinoid (CB) receptors CB1 and CB2
• Widespread distribution
• Highest in cerebral cortex, hippocampus,
  hypothalamus and amygdala
• Endogenous cannabinoids?

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Endocannabinoids

• Endogenous cannabinoids endocannabinoids
• i.e. anandamide, 2-arachidonoyl-glycerol, noladin
  ether
• Act at presynaptic CB receptors and decrease
  release of transmitters
• Physiological effects poorly understood

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Cannabis therapeutic uses

• Treatment of nausea and vomiting
• Appetite stimulation
• Analgesia
• Anticonvulsants

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Cannabis use and psychosis

• Theories
• Cannabis use cannabis psychosis
• May precipitate an episode of schizophrenia
• May exacerbate symptoms of schizophrenia
• Cannabis is harmless

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Monoamine-related drugs

• Similar molecular structure to monoamine
  neurotransmitters
• e.g. MDMA, LCD

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MDMA

• 3,4-methylenedioxymethamphetamine
• Ecstasy
• Amphetamine analogue
• Hallucinogen not stimulant
• ve effects (love drug)
• euphoria, tingling, increased sociability
• -ve effects
• neuronal damage, fatigue, insomnia, sweating,
  blurred vision, loss of motor coordination,
  anxiety, dehydration, psychosis

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Actions of MDMA

• Stimulate 5-HT release
• Increase synaptic concn. of dopamine
• Neurotoxic reaction
• Even limited use of MDMA may cause permanent
  neuronal damage to 5-HT neurones

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LSD

• Synthetic drug, related to a number of compounds
  in ergot fungus
• First synthesised in 1940s
• Very potent

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LSD

• ve effects
• Alterations in hearing and vision
• Hallucinations
• Subjective sense of time prolongation
• -ve effects
• bad trip
• Dysphoria
• Anxiety
• Depression
• Flashbacks
• Tolerance develops quickly

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Actions of LSD

• Affects 5-HT function
• May affect glutamate transmission
• May increase dopamine transmission

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Dissociative anaesthetics

• Induce profound anaesthesia
• e.g. Phencyclidine (PCP), ketamine
• PCP
• Synthesised in 1950s
• Ketamine
• date rape drug

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PCP

• angel dust
• Smoked, swallowed, sniffed or injected
• Low level of abuse
• Dose-dependent effects

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PCP - effects

• Dose
• Low
• Moderate
• High

• Effects
• drunken state or floaty euphoria, distorted
  body image
• Analgesia, anaesthesia, confusion, excitement,
  intoxication, impaired communication
• Definite psychosis, convulsions

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PCP mechanism of action

• Novel PCP binding site found
• High densities in hippocampus and motor cortex
• Discovered PCP binding site within NMDA receptor
  channel
• PCP NMDA receptor antagonist
• Also
• dopamine agonist in nucleus accumbens, prefrontal
  cortex and basal ganglia
• enhances 5-HT activity
• blocks muscarinic and nicotinic acetylcholine
  receptors

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PCP and psychosis

• PCP exacerbates symptoms of psychotic patients
• Heavy PCP users report schizophrenia- like
  psychotic episodes
• Part of evidence for glutamatergic involvement in
  schizophrenia

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Hallucinogens and risks

• Not necessarily addictive (still damaging)
• Social addiction
• e.g. Cannabis, Ecstasy
• Some psychological addiction if experience
  pleasant
• e.g. LSD, Magic mushrooms

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Study guide

• How does a drug reach its target?
• How does the blood-brain barrier limit the access
  of drugs to the brain?
• How do drugs effect synaptic transmission? Give
  examples.
• Which are the hallucinogenic drugs?
• What behavioural changes do they induce?
• What neurotransmitter systems underlie their
  activity?