Drug Addiction

Question 1

What are the main substances of abuse?

Answer 1

Alcohol, nicotine, opioid agonists, psychostimulants, THC, sedatives, hallucinogens, inhalants.

Question 2

What are endogenous opioids?

Answer 2

Come from 3 distinct protein families. Those opioids that come from the outside world (exogenous opioids) act on the same receptors as endogenous opioids.

Question 3

What are opioid receptors?

Answer 3

Distributed widely in the body, which is why drugs that act on these receptors produce a range of effects. Metenkephalin (composed of 5 amino acids) and morphine are similar - this allows them to act on the same receptor that are placed on the synaptic membrane.

Question 4

What are the types of opioid receptors?

Answer 4

4 main types of opioid receptor - MOR, KOR, DOR, & NOP. When opioid receptors are activated, cellular function tends to decrease, because calcium channels are blocked and potassium cells are opened.

Question 5

What are the main effects of opioid agonists?

Answer 5

Has effects on the brain, respiratory tract, brain, heart, and GI system (nausea/vomiting and constipation). Can have respiratory depression and die - this is why people die of opioid overdose. Drug has to have effect really rapidly to give an intense high - pass blood/brain barrier quick - inject, inhale, or snort to get quick effects. One of the most well-known effects is analgesia - powerful suppression of pain.

Question 6

How do drugs act on transporters?

Answer 6

The proteins that sit on the synaptic bottom to reuptake the transmitter into the synapse. The transporter for amines - dopamine, norepinephrine, and serotonin.

Question 7

How does cocaine act?

Answer 7

Cocaine binds to transports, which depends on whether the neuron is active or inactive. If not active, there is no consequence. If neuron is active - it releases an amine, which will be reuptaken into the synapse by the transporter. If take cocaine, the amine cannot be reuptaken, meaning more of the amine in the synapse (e.g. more dopamine). These amines are involved in many different processes, explaining the effect of cocaine. The effects of cocaine are impulse-dependent - depends on whether the neuron is active or not.

Question 8

How do amphetamines act?

Answer 8

Not only blocks the reuptake of dopamine, it also pushes dopamine outside at the level of the synapse = has a much more dramatic effect. Doesn’t matter if the neuron is active or not. So, more dopamine in the terminal, inverts the flow of dopamine.

Question 9

What are the main effects of psychostimulants?

Answer 9

First local anaesthetic discovered - can produce local anaesthesia. Opioids create a down effect, psychostimulants create an up effect.

Question 10

What is the mechanism of action of alcohol?

Answer 10

Depress neurons. Act on GABA a receptor - chloride channels which is negative, causes cell to become more negative (hyper polarised), difficult to excite the cell when GABA is present. GABA a acts on the same neurons as those associated with anxiety - compensate the excitatory mechanism with inhibitory mechanism. THC (cannabis) acts on CB1 and CB2 receptors. MDMA, ketamine (hallucinations) act on serotonergic mechanism.

Question 11

Are there shared substrates of drug reward and addiction?

Answer 11

Many agree that what drugs have in common is its action on the dopaminergic system. Projects from VTA to the prefrontal cortex, the striatum (in particular nACC) and the hippocampus. Dopaminergic circuit are connected. The focus of drugs has been on the projection from the VTA to the nucleus accumbens (nACC).

Question 12

How does the dopaminergic system work?

Answer 12

The dopaminergic system mediates the rewarding property of the drug. Berridge – there is a part of the brain (the dopaminergic system) that is responsible for the distribution of incentive salience. Increase incentive salience linked to the drug, leads to be attractive to and consume the drug. One process produces pleasure, the other pleasure produces incentive salience – liking and wanting are separate.

Question 13

What happens due to repeated activation of dopaminergic neurons?

Answer 13

Repeated activation of dopaminergic neurons produce neuroplastic adaptation – the neuron changes structurally. Results in long term changes in the functioning of the circuit, make neuron more sensitive (produce more dopamine). More dopamine = more wanting, want more of the drug (this is why Berridge splits wanting from liking).

Question 14

Is the dopaminergic system the core process for all types of drug reward?

Answer 14

The reinforcing effect of heroin does not depend on dopaminergic transmission – after training animals, they blocked dopaminergic receptors. Then looked at the consequence of heroin and cocaine self-administration. Cocaine administration progressively decreased. However, heroin self-administration initially goes down, but then goes back to normal. There is no robust evidence that reinforcing effect of alcohol and nicotine are mediated by dopaminergic transmission. Some evidence that when humans use cocaine dopamine levels go up, but evidence has found that heroin does not increase dopamine levels in the brain.

Question 15

Are there similar neuroplastic changes in cocaine and morphine?

Answer 15

Can see opposite changes - not the same. Found with cocaine there is an change in the PFC and NAc, with heroin there is opposite changes.

Question 16

What is the prevalence of substance use?

Answer 16

Over 96 million adults estimated to have tried illicit drugs at some point in their lives. More common in males. Most commonly used drug is cannabis, then cocaine, then MDMA, then amphetamines, and then opioids. Different drugs have different pattern of prevalence in different countries. No way to enforce quality of street drugs.

Question 17

What are substance use disorders?

Answer 17

11 criteria apply to all kinds of substance use disorders. Need 2/3 to qualify. If have 3/4 more severe type of disorder, more than 6 = very severe disorder. Criteria has to do with inability to control drug use. Drugs change in their ability to produce addiction - drug that has the greatest ability to produce addiction is nicotine (70% chase across lifetime), 20% for alcohol and cocaine, cannabis less then 10%. Chance of being addicted to medically prescribed drugs is about 3%, most of whom had already had a drug problem previously.

Question 18

What are risk factors for substance use disorders?

Answer 18

Substantial genetic contributions to addiction vulnerability supported by data. Younger age, male (more prone to female), caucasian more likely, being non-married, lower psychological functioning (facilitate loss of control of drug use), family history of drug problem, history of child abuse, psychosis diagnosis.

Question 19

What is the contribution of genetic and environmental risk in substance abuse?

Answer 19

Depending on dose of drug, there is a different contribution of genetics and environment. In the case of cocaine – almost 60% of variance is due to genetics, to heritability is high. In the case of heroin, less than 20% is due to genetics. Shared vs environmental factors of cocaine and heroin – when you remove genetics, shared environmental factors play a minor role, most are unique to the individual.

Question 20

Is there a chance of dual diagnosis?

Answer 20

Some type of psychological condition that increase by up to 7x to develop addiction.

Question 21

What did Nutt et al. 2010 find about the harm of drugs?

Answer 21

¥ Drug-specific mortality – intrinsic lethality of the drug expressed as ratio of lethal dose and standard dose (for adults)
¥ Drug-related mortality – the extent to which life is shortened by the use of the drug (excludes drug-specific mortality) – e.g. road traffic accidents, lung cancers, HIV, suicide
¥ Drug-specific damage – drug-specific damage to physical health – e.g. cirrhosis, seizures, strokes, cardiomyopathy, stomach ulcers
¥ Drug-related damage – drug-related damage to physical health, including consequences of, for example, sexual unwanted activities and self-harm, blood-borne viruses, emphysema, and damage from cutting agents.

Question 22

What is the margin of exposure for daily drug use?

Answer 22

MOE = ratio between the point on the dose-response curve, which characterises adverse effects in epidemiological/animal studies, and the estimated human intake of the same compound. The lower the MOE, the larger the risk for humans - how harmful it is.

Question 23

What are acute drug-inducted death?

Answer 23

Respiratory depression - heroin and other opiates, barbiturates, alcohol and psychostimulants. Tachyarrhythmias - psychostimulants. Cardiac arrest - cocaine and other psychostimulants. Myocardial infarction/Ischemic stroke - psychostimulants. Hypertension/Hemorrhagic stroke - psychostimulants.

Question 24

When was there a heroin death strike?

Answer 24

Deaths from heroin and methamphetamine climbed steeply between 2013 and 2014. Other drugs and alcohol saw lesser increases.

Question 25

What is drug-induced damage caused by alcohol?

Answer 25

Fatty liver, cirrhosis, liver cancer. Cancer of mouth, larynx, oesophagus, stomach, pancreas, breast etc. Ð Gastritis, duodenitis, gastric ulcer. Acute and chronic pancreatitis. Malnutrition, thiamine deficiency (Wernicke-Korsakoff syndrome). Neurological deficits Paracetamol – alcohol turns it into toxins that kill liver cells – most liver failure caused by paracetamol.

Question 26

What is drug-induced damage caused by psychostimulants?

Answer 26

Ð Tachyarrhythmias Ð Atherosclerosis Ð Ischemic heart disease, brain ischemia Ð Hyperytension.

Question 27

What is drug-induced damage caused by tobacco?

Answer 27

Ð Cancer of mouth, tongue, larynx, lungs, pancreas, etc. Ð Atherosclerosis Ð Chronic obstructive pulmonary disease.

Question 28

What are heroin arms?

Answer 28

Initially track marks may be almost invisible, but with repeated use veins will collapse, causing bruising to appear following the vein. Blisters caused by tetanus infection.

Question 29

What is psychological drug harm to others?

Answer 29

Dependence – the extent to which a drug creates a propensity or urge to continue to use despite adverse consequences (ICD 10 or DSM IV). Drug-specific impairment of mental functioning – e.g. amphetamine-induced psychosis, ketamine intoxication, mood disorders secondary to drug-user’s lifestyle or drug use. Notion that drugs fry your brain is not supported by evidence – does not disintegrate. Drugs are associated with certain kinds of psychiatric conditions – e.g. panic disorder, social phobia, specific phobia, and generalised anxiety disorder.

Question 30

Is there a relationship between cannabis and psychosis?

Answer 30

Yes there is a relationship, but nature of relationship is unclear. Have 2x as much chance of developing schizophrenia than those who don’t.

Question 31

What are clinical implications of cannabis and psychosis?

Answer 31

Cannabis use in adolescence leads to two-to-threefold increase in relative risk for schizophrenia or schizophreniform disorder in adulthood. The earlier the age of onset of cannabis use, the greater the risk for psychotic outcomes. Cannabis does not appear to represent a sufficient or a necessary cause for the development of psychosis but forms part of a casual constellation. A minority of individuals experience harmful outcome consequent to their use of cannabis. However, this minority is significant both from a clinical point of view and at a population level. It is estimated that about 8% of schizophrenia could be prevented by elimination of cannabis use in the population.

Question 32

What are limitations in studies into cannabis and psychosis?

Answer 32

Prospective studies relied on self-report measures of cannabis use only. Most findings are based on very small groups of individuals who experienced rare outcomes in adulthood. More prospective longitudinal research is required to estimate the long-term impact of cannabis use.

Question 33

What did Barkus and Murray, 2010 find about cannabis and psychosis?

Answer 33

Are those who are psychosis prone more likely to use cannabis or, regardless of underlying predisposition, can cannabis use cause or precipitate psychotic symptoms? Patients with established psychosis who continue to use cannabis have a worse prognosis than those who stop (e.g., Grech et al. 2005, Kovasznay et al. 1997, Linszen & van Amelsvoort 2007). Administration of Δ-9-THC, produces a transient psychosis-like state in healthy volunteers (D’Souza et al. 2004, Morrison et al. 2009) and can exacerbate psychotic symptoms in patients with schizophrenia, despite them being clinically stable and medicated at the time (D’Souza et al. 2005).

Question 34

What is social harm of drug harm to users?

Answer 34

Loss of tangibles: extent to loss of tangible things (e.g. income, housing, job, educational achievements, criminal record, imprisonment). Loss of relationships: extent to loss of relationship with family and friends. ¥ Crime: extent to which the use of a drug involves or leads to an increase in volume of acquisitive crime (beyond the use-of-drug act), directly or indirectly (at the population level, not the individual level) ¥ Environmental damage: extent to which the use and production of a drug causes environmental damage locally – e.g. toxic waste from amphetamine factories, discarded needles ¥ Family adversities: extent to which the use of a drug causes family adversities – e.g. family breakdown, economic wellbeing, emotional wellbeing, future prospects of children, child neglect ¥ International damage: extent to which the use of a drug in the UK contributes to damage internationally – e.g. deforestation, destabilisation of countries, international crime, new markets ¥ Economic costs: extent to which the use of a drug causes direct costs to the country (e.g. health care, police, prisons, social services, customs, insurance, crime) and indirect costs (e.g. loss of productivity, absenteeism) ¥ Community: extent to which the use of a drug creates decline in social cohesion and decline in the reputation of the community Straight link between binge drinking and domestic violence. Alcohol most dangerous drug.

Question 35

What is physical/psychological harm to others caused by drug harm?

Answer 35

Injury: extent to which the use of a drug increases the chance of injuries to others both directly and indirectly – e.g. violence (including domestic violence), traffic accident, fetal harm, drug waste, secondary transmission of blood-borne viruses.

Question 36

What are the key features and principles of harm reduction?

Answer 36

¥ That the primary goal is reducing harm rather than drug use per se; ¥ That there is acceptance that drugs are a part of society and will never be eliminated; ¥ That harm reduction should provide a comprehensive public health framework; ¥ That priority is placed on immediate (and achievable) goals; and That harm reduction is underpinned by values of pragmatism and humanism.