Drugs, Brain and Behaviour (9) - Opioids

Opiates

Naturally occurring alkaloids derived from the Opium Poppy (Papaver Somniferum)

Opioids

Broad class of drugs including natural, semi-synthetic, and synthetic substances that act on opioid receptors (e.g. morphine and codeine).

Uses of Opioids

• Analgesia (without removing other sensations).

• Cough suppression

• Diarrhoea

Morphine

A natural opiate that produces analgesia, euphoria, and a dream-like state. Named after Morpheus. Has a half life of 4 hours.

Codeine

A weaker natural opiate used for mild pain and cough suppression.

Narcosis

A dream-like, sedated state produced by opioids.

Opium

Dried sap of the opium poppy containing psychoactive alkaloids. Used for thousands of years for pain relief, cough suppression, and recreation (e.g. Laudanum). Largely concentrated in regions such as Afghanistan.

Hypodermic Syringe

Enabled injection of morphine, increasing addiction rates. → Morphine addiction (“Soldier’s disease”)

Opium Wars

Conflicts driven by opium trade leading to widespread addiction in China.

Pain Opioid Types (depending on Severity)

• Mild–moderate: Codeine and propoxyphene.

• Moderate–severe: Pethidine (meperidine).

• Severe pain opioids: Morphine, heroin (diamorphine), hydromorphone, and fentanyl.

Heroin

Diacetylmorphine. A semi-synthetic opioid derived from morphine → Heroin 5× more potent. Illegal in many countries but used medically in some (e.g., UK).

Effect of Acetyl Groups in Heroin

Increase lipid solubility and speed of brain entry

Heroin Metabolism in the brain

Converted back into morphine in the brain.

Prescription Opioid Misuse

Major contributor to modern opioid addiction.

Routes of Opioid Administration

• Oral

• Intravenous injection: Produces a rapid “rush” due to fast brain entry.

• Smoking

• Snorting

Desired effects of opioids

• Analgesia

• Euphoria

• Relaxation

• Reduced anxiety

• Sedation

Side effects of Opioids

• Nausea

• Vomiting

• Constipation (Reduced gastrointestinal motility)

• Respiratory depression (Slowed breathing and the main cause of opioid overdose death)

Overdose Reversal Drug

Naloxone - Short-acting antagonist

Tolerance

Reduced drug effect with repeated use requiring higher doses. For Opiods this develops for all effects but NOT constipation.

What Risks are associated with increased Tolerance?

Increased dosing raises overdose risk.

Withdrawal

Opposite effects occurring when drug (e.g. opioid) use stops. For Opioids:

• Pain sensitivity

• Anxiety

• Diarrhoea

• Sweating

• Agitation

Not usually life-threatening but highly unpleasant.

Sensitisation & Opioids

Increased (behavioural) response from the same dose (despite depressant effects of opioids)

Dopamine system and Opioids

Opioid use leads to sensitisation of DA system particularly in the VTA.

Behavioural Effects of Sensitisation

Increased locomotion and reward.

Measurement of Opioid Reward

Self-administration and conditioned place preference.

Dependence

Physical adaptation leading to withdrawal symptoms when drug use stops.

Addiction

Compulsive drug use with craving and relapse.

How Risky is opioid use?

• Hospital Use: Low addiction risk due to controlled dosing and context.

• Prescription opioids: Can cause dependence even without strong euphoria.

Main Harm linked to administration route and lifestyle rather than drug alone.

Causes of opioid-related death

• Overdose

• Infections

• Contaminated drugs.

But only Approximately 1–2% of users annually.

Methadone

Long-acting opioid used in substitution therapy → Prevents withdrawal without producing a strong rush.

Naltrexone

Long-acting opioid antagonist used to block opioid effects.

Harm reduction

Strategies aimed at reducing death and disease without abstinence (e.g. Needle exchange, naloxone distribution, supervised injection sites).

Benefits of Harm Reduction

• Reduced overdose deaths

• increased treatment engagement.

Opioid Receptors

Receptors in the brain and body that mediate opioid effects. Variation of opioid effects depends on receptor subtype and brain location.

Key danger of Opioids

• Low therapeutic index

• High overdose risk

Repeated Opioid Use Effects

• Tolerance

• Withdrawal Symptoms

• Sensitisation of reward systems.

Addiction mechanism of Opioids

Interaction with opioid receptors and dopamine reward pathways.