Drug addiction

Question 1

What are the characteristics of drug addiction

Answer 1

1. Compulsion to seek and take the drug (despite harmful consequences and log-lasting changes to the brain)
2. Loss of control in limiting intake
3. Emergence of a negative emotional state (dysphoria, anxiety, irritability)

Question 2

How is drug addiction diagnosed?

Answer 2

DSM-5 criteria. Two or more symptoms from the diagnostic criteria including:

Question 3

State the stages of addiction (cycle)

Answer 3

• Initial Use and Reinforcement:
  o Positive Reinforcement
• Transition to Compulsive Use:
  o Tolerance and Dependence
  o Negative Reinforcement

Question 4

Symptoms of heroin/drug withdrawal

Answer 4

tremors
abdominal pain
joint pain

sweating, gooseflesh (cold turkey), irritability, aggression.

Question 5

The role of the HPA axis in drug addiction

Opioids and cocaine

Answer 5

Drug withdrawal is characterised by the hyperactivity of the HPA axis = increased stress levels.

connections between the reward centres and amygdala and hippocampus become stronger in addiction

connections between reward centres and the PFC become stronger (memories of substance gets stronger)

Descending inhibitory impulses become weaker (lose executive control of impulses)

*Drug taking behaviour becomes automatic

Question 6

molecular mechanism of tolerance (opioid)

Answer 6

opioids stimulate mu opioid receptor, leadingg to opening of potassium channel and hyperpolarisation.

Repeated administration of opioids results in the recruitment of G-receptor kinases (this phosphorylates the intracellular and extracellular domain of the mu-opioid receptor)

following phosphorylation there is a recruitment of beta-arrestin molecule. this causes desensitisation of opioid receptors.

Question 7

In the dependent state….

Answer 7

Reduced/suppressed activity of the pre-frontal cortex…associated with poor decision making

Reward system is depressed. stimulation can only occur with use of substance of abuse.

there is downregulated dopamine D2 receptors.

The PFC is suppressed

Question 8

describe the role of the frontal cortex in drug addiction

Answer 8

The neural pathways between the reward centre of the brain (primarily the nucleus accumbens, part of the ventral striatum) and areas involved in judgement (like the prefrontal cortex (PFC) are strengthened.

In addiction, the prefrontal cortex (PFC), responsible for executive functions such as decision-making and self-control, fails to regulate the orbitofrontal cortex (OFC).

Question 9

Briefly describe the self-administration paradigm commonly used in the addiction field to assess operant behavior

Answer 9

The self-administration paradigm in addiction research involves training animals to perform a task, such as lever pressing, to receive a drug, simulating voluntary drug intake.
It is crucial for assessing the reinforcing properties of substances, with behavior frequency indicating the drug’s reinforcement strength.
It can be adapted by introducing variables like delays, dosage changes, or environmental cues.
These modifications help study reinforcement and drug-induced compulsivity and the effects of interventions.
This paradigm provides valuable insights into the mechanisms of addiction and potential treatment strategies.

Question 10

What stages of drug addiction can be targeted for pharmacotherapy

Answer 10

Overdose
Withdrawal/Abstinence initiation
Relapse prevention
Sequelae

Question 11

neuroadapatations

Answer 11

Neuroadaptations:
With repeated exposure, the brain starts to adapt. Sensitivity of the reward circuits decreases, a phenomenon known as tolerance. The brain may produce less dopamine or reduce the number of dopamine receptors.

Question 12

Methadone use for opioid therapy

Answer 12

long acting mu opioid receptor agonist
half-life: 24-36h

methadone occupies opioid receptor for longer periods of time (preventing heroin binding)

Question 13

advantages of long-acting opioid agonist

Answer 13

methadone occupies opioid receptor for longer periods of time (preventing heroin binding)

Normalises the HPA axis activity (which is enhanced in withdrawal)

Question 14

Methadone MOA

Answer 14

stimulates the mesolimbic dopaimergic pathway by activating mu opioid receptors. This induces reward but to a lesser extent than heroin/morphine.

This helps to alleviate withdrawal symptoms

Question 15

State the benefits of methadone

Answer 15

Benefits:
Lifestyle stabilisation
Decrease in criminal behaviour
Employment
Decrease in injection drug use/shared needles (HIV)

Question 16

State the limitations of methadone

Answer 16

Limitations:
Still dependent on methadone
Use for a long period of time
Not great at preventing relapse (7 out 10 relapse after a month on detox)

Dependent individuals will often use heroin on top of methadone increasing risk of overdose
Improvement of quality of life is debatable

Question 17

Alternative to methadone

Answer 17

Buprenorphine - mu partial antagonist and kappa receptor antagonist

Question 18

Buprenorphine

Answer 18

Buprenorphine stimulates the mesolimbic dopaminergic system by activating mu opioid receptors, inducing reward to a lesser extent than morphine/methadone

stimulates the reward system

safer than methadone (doesn’t stimulate the reward pathway as much as methadone)

Question 19

Role of Kappa receptors

Answer 19

opioid receptors
induces dysphoria (stress)

inhibiting this suppresses stress and syrphoria

Question 20

state other treatments for dependence

Answer 20

Naltrexone (opioid antagonist) prevents euphoria to opioids

Question 21

Pharmacotherapies for alcohol withdrawal

Answer 21

Benzodiazepines for acute withdrawal symptoms
Disulfiram for alcohol release prevention
Naltrexone for relapse reduction, alcohol consumptions and craving

Question 22

Disulfiram MOA

Answer 22

Disulfiram inhibits aldehyde dehydrogenase and enzyme responsible for the metabolism of acetaldehyde to acetate.

Question 23

antabuse reaction

Answer 23

flushing, weakness, nausea, tachycardia, hypotension

Question 24

Smoking cessation: NRT

Answer 24

Nicotine replacement therapy (NRT)
NRT - slow release of nicotine over time. It doesn’t reach the brain as fast as smoking and the levels are lower/smaller than smoking

Question 25

Nicotine replacement therapy (NRT)

Answer 25

Stimulates the mesolimbic dopaminergic system by binding to a4b2 nAchRs

Question 26

Varenicline

Answer 26

Most effective smoking cessation

partial a4b2 nAChr agonist
full agonist for a7 nAChr

Question 27

Buproprion

Answer 27

Blocks monoamine reuptake
Nicotnic antagonist

increases dopamine in nucleus accembens

Question 28

compare NRT, Varenicline to Buproprion

Answer 28

NRT: reduces cigarette consumption but is not greatly effective at relapse prevention

Varenicline: most effect smoking cessation therapy. it relieves psychological and physiological withdrawal symptoms
however, not greatly effective at relapse prevention and increasing abstinence.

Buproprion: increases dopamine in nucleus accembens.
however it can induce seizures

Question 29

methadone vs oxytocin

Answer 29

oxytocin has pro-social effects

Question 30

Define drug addiction

Answer 30

A chronic, relapsing disorder characterized by compulsive drug seeking, continued use despite harmful consequences, and long-lasting changes in the brain.

Question 31

Define Addiction

Answer 31

Addiction is a chronic, relapsing disorder characterised by:
1. Compulsion to seek and take the drug (despite harmful consequences and log-lasting changes to the brain)
2. Loss of control in limiting intake
3. Emergence of a negative emotional state (dysphoria, anxiety, irritability)

Question 32

Define tolerance

Answer 32

Tolerance: Higher doses of a drug are required to achieve the same effect originally produced by a lower dose.
*A person’s reaction to a drug decreases such that larger doses are needed to achieve the same effect

Question 33

Define dependence

Answer 33

Dependence: an adaptive state that develops from repeated drug administration. Resulting in the emergence of physical and emotional withdrawal symptoms when drugs are stopped.

Question 34

How do Opioids and cocaine differ in terms of effects on the HPA axis?

Answer 34

Opioids suppress the HPA axis, reducing stress hormones and leading to calming effects, but cause a rebound increase during withdrawal. Cocaine, on the other hand, stimulates the HPA axis, boosting stress hormones and enhancing alertness and euphoria. Chronic use of each leads to HPA dysregulation, influencing addiction and stress responses differently.

Question 35

potential strategies for relapse prevention

Answer 35

Better addressing emotional withdrawal symptoms and enhancing social behaviour and relationships.

SSRIs have shown limited efficacy in treating depression associated with opioid abstinence.

Question 36

What brain system do drugs of abuse activate?

Answer 36

Mesolimbic dopamine system

Question 37

What happens to the PFC in the dependent state

Answer 37

Decreased activity

The PFC; responsible for executive functions such as decision making and self-control, fails to regulate the orbiofrontal cortex (OFC)

Question 38

Brains reward system

Answer 38

Nucleus accembens

Ventral tegmental area (VTA) –> to the nucleus accembens

Question 39

Opioids MOA

Answer 39

Opioids inhibit GABAergic interneurons (normally suppress dopamine release).
inhibiting these interneurons leads to an increase in dopamine release in the nucleus accembens = enhances reward and pleasure sensations.

Question 40

Intranasal oxytocin as a novel treatment for opioid addiction

Answer 40

Oxytocin, administered intranasally, is proposed as a treatment for opioid addiction due to its effects on enhancing social bonding and reducing stress responses, which are key components in the addiction cycle. It may modulate the reward and stress pathways in the brain, potentially reducing craving and withdrawal symptoms associated with opioid use.

Question 41

Limitations of Intranasal oxytocin as a novel treatment for opioid addiction

Answer 41

Critics argue that the efficacy of oxytocin in addiction treatment could be overstated. There are concerns about its varying effects across different individuals, potential side effects, and the complexity of its influence on emotional and social processing that might not translate uniformly into therapeutic benefits.

Question 42

E-cigarettes vs Nicotine Replacement for smoking cessation

Answer 42

E-cigarettes deliver nicotine in a manner that mimics the behavioural and sensory aspects of smoking, potentially making them more effective for some smokers in quitting compared to traditional nicotine replacement therapies (NRTs) like patches or gums, which do not address the behavioural component of smoking addiction.

Question 43

Limitations of E-cigarettes for smoking cessation

Answer 43

The debate around prescribing e-cigarettes for smoking cessation includes concerns about their safety profile, long-term health effects, and the risk of non-smokers starting to use nicotine through e-cigarettes. Furthermore, regulatory bodies are still assessing the best approaches to balance harm reduction with the prevention of new nicotine addictions.

Question 44

Role of Gut Microbiota in Drug Addiction

Answer 44

Research into the gut-brain axis suggests that gut microbiota may influence brain functions and behaviours relevant to addiction. The gut microbiota could affect the central nervous system by producing bioactive compounds, influencing inflammatory pathways, and altering the stress response systems that are integral to addiction behaviours.

Question 45

Limitations of Gut Microbiota in Drug Addiction

Answer 45

The concept that gut microbiota significantly impacts drug addiction is still under debate, with some considering it speculative at this stage. Research is ongoing, and therapeutic implications are yet to be firmly established. The complexity of microbiota interactions and their exact role in addiction make this a challenging area to harness for direct therapeutic interventions.