Drug Abuse Notes

Lecture 29, 30 & 33

Drug Abuse

• Classes of drugs

  • Alcohol; Nicotine; Caffeine

  • Solvents/Inhalants (legal to have, but not to sell)

  • Anxiolytic/Sedatives/Hypnotics

  • Antidepressants

  • Anaesthetics

  • Opiates (narcotics)

  • Stimulants (cocaine, amphetamine, khat, methamphetamine (speed) & MDMA)

  • Cannabis (low doses=no hallucinations; high doses=hallucinations)

  • Hallucinogens (LSD, mescaline, psilocybin & phencyclidine)

• Dependence

  • Need to continue drug taking

    • Psychological (craving)

    • Physical (withdrawal syndrome)

      • Put into detox and clear body of drug, should get rid of this

      • But, fails quite often so PSYCHOLOGICAL must be main driving force

  • Important brain neurotransmitters

    • Dopamine

      • Cocaine, heroin, nicotine, alcohol etc.

      • Reward/euphoric

    • 5-Hydroxytryptamine (serotonin)

      • Elevation of mood (bit happy)

      • E.g. Ecstasy

• The ‘reward pathway’

  • Dopaminergic pathway (drugs over-activate this)

  • Ventral Tegmental Area (VTA) to nucleus accumbens

  • Enhanced dopamine levels at synaptic cleft

  • Natural rewards= food, water, sex, nurturing

  • Drugs acting on this pathway

    • Cocaine and amphetamine act on nucleus accumbens

    • Morphine acts on GABAergic inhibitory interneurone=disinhibition of VTA

    • Heroin acts on VTS

      • Long term

        • Rise in DA in nucleus accumbens=paraphernalia and process of drug taking

        • I.e. euphoria from seeing blood sucked back into needle

• Tolerance

  • General

    • (Not for all drugs e.g. cocaine)

    • More of drug required to induce same effect

      • Changes in metabolism

      • Changes in sensitivity of target site

  • Types

    • Dispositional (metabolic)

      • Ethanol, barbiturates

      • Liver gets bigger over weeks so drug more easily metabolised

    • Functional (cellular or pharmacodynamic)

      • Opioids, ethanol, benzodiazepines

    • Behavioural

      • Overcome effect of stimulant (alcoholics hiding fact they’re drunk)

    • Sensitisation

      • May occur with cocaine

  • Other things to know

    • Cross tolerance

      • Drugs acting in same way

      • Ethanol & benzodiazepines; Different opioids

    • Tolerance reversal

      • Abstinence e.g. detox or prison (tolerance falls when stop taking)

      • Overdose when subject takes same dose they took when tolerant

    • Polypharmacology

      • Opioid addicts rarely take on drug

      • Problem as don’t know interactions

      • Alcohol + Cocaine= Toxic metabolite

• Heroin

  • Why do people take it?

    • Buzz and euphoria

    • Remove from reality of situation

    • Many have other mental health problems

  • Treatment of heroin addiction

    • Methadone maintenance

      • Orally active, long t

      • Side effects: general state of activity

    • Stabilise (onto methadone) and maintain (not going through withdrawal)

    • Stabilise and withdraw (withdrawal from methadone not as bad as heroin)

    • Buprenorphine

      • + naloxone (antagonist)= Prevents effect of heroin in case of relapse

      • Give as sublingual tablet as naloxone not absorbed sublingual or in gut, so can’t crush up and inject/sell. No effect when injected

      • Most addicts prefer methadone (mental health problems)

    • Safely controlled heroin supply

      • Failure rate lower than first two (people not involved in crime)

• Stimulants

  • Cocaine

    • Weak base

    • Mechanism

      • Blockade of dopamine reuptake at nerve terminals

      • Get more DA in synaptic cleft

      • Potential for drug treatment

        • Antibodies for cocaine (those who are scared of relapse)

        • Stop cocaine binding to transporter but don’t inhibit DA reuptake

    • Crack

      • Crystals of cocaine (weak base) and bicarbonate

      • Insoluble in water (rocks)

      • Vaporises at 90C (salt melts at 190C- can’t do to powder, melts)

      • Smoked and absorbed from lungs (more rapid than snorting)

  • Amphetamine, methamphetamine

    • Mechanism of action

      • Indirectly acting sympathomimetic agents

        • Substrate for transporter; Blockade of DA reuptake; Inhibit enzymic degradation of MAO; Stimulate DA release

    • Amphetamine

      • Effects

        • Elevated mood; Alertness; Insomnia; Increased stamina; Anorexia; Aggression; Psychosis; Increased HR; Raised BP

      • Post drug

        • Depression; Dysphoria; Psychiatric disorders; Fatigue

    • Methamphetamine

      • Effects

        • Increased activity; Less need for sleep; Decreased appetite

        • General sense of well-being

        • Can last 6-8 hours

        • After initial rush, can be agitation and violent behaviour

  • Ecstasy (MDMA)

    • Mechanism of action

      • Causes 5-HT release

      • Inhibit 5-HT re-uptake- substrate for transporter

      • Comparison with Prozac

        • Effects of MDMA immediate

        • MDMA can cause degeneration of 5-HT containing nerves

      • Neurotoxicity of MDMA blocked by Prozac

    • MDMA

      • Effects

        • As amphetamine but no aggression; Perception disruption; High body temp; Thirst; Allergic reaction; 5-HT syndrome

      • Post drug

        • As with amphetamine but less CV effects

        • Anxiety, depression

    • Ecstasy and neuronal degeneration

      • 5-HT (serotonin)

        • Depletion of 5HT; Loss of 5HT transporter

      • Dopamine

• Cannabis

  • General

    • Effects

      • Sedation; Well-being; Perceptual changes; Amnesia; Lowered tem; Increased HR; Anti-emetic; Appetite stimulation; Analgesia

    • Withdrawal

      • No reported abstinence syndrome

      • Addictive behaviour patterns rare

      • Psychological addiction (amotivational syndromes)

  • Biochemistry

    • Structure

      • Active components are lipid soluble cannabinoids

      • Δ⁹-tetracyclocannabinol (THC)= extremely lipophilic

    • Receptors

      • CB1 and CB2 (Gi/Go-coupled)

      • None in brainstem (opioid receptors) so doesn’t depress...

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