Drug addiction Flashcards
What are the characteristics of drug addiction
- Compulsion to seek and take the drug (despite harmful consequences and log-lasting changes to the brain)
- Loss of control in limiting intake
- Emergence of a negative emotional state (dysphoria, anxiety, irritability)
How is drug addiction diagnosed?
DSM-5 criteria. Two or more symptoms from the diagnostic criteria including:
State the stages of addiction (cycle)
- Initial Use and Reinforcement:
o Positive Reinforcement - Transition to Compulsive Use:
o Tolerance and Dependence
o Negative Reinforcement
Symptoms of heroin/drug withdrawal
tremors
abdominal pain
joint pain
sweating, gooseflesh (cold turkey), irritability, aggression.
The role of the HPA axis in drug addiction
Opioids and cocaine
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
molecular mechanism of tolerance (opioid)
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.
In the dependent state….
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
describe the role of the frontal cortex in drug addiction
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).
Briefly describe the self-administration paradigm commonly used in the addiction field to assess operant behavior
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.
What stages of drug addiction can be targeted for pharmacotherapy
Overdose
Withdrawal/Abstinence initiation
Relapse prevention
Sequelae
neuroadapatations
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.
Methadone use for opioid therapy
long acting mu opioid receptor agonist
half-life: 24-36h
methadone occupies opioid receptor for longer periods of time (preventing heroin binding)
advantages of long-acting opioid agonist
methadone occupies opioid receptor for longer periods of time (preventing heroin binding)
Normalises the HPA axis activity (which is enhanced in withdrawal)
Methadone MOA
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
State the benefits of methadone
Benefits:
Lifestyle stabilisation
Decrease in criminal behaviour
Employment
Decrease in injection drug use/shared needles (HIV)
State the limitations of methadone
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
Alternative to methadone
Buprenorphine - mu partial antagonist and kappa receptor antagonist
Buprenorphine
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)
Role of Kappa receptors
opioid receptors
induces dysphoria (stress)
inhibiting this suppresses stress and syrphoria
state other treatments for dependence
Naltrexone (opioid antagonist) prevents euphoria to opioids
Pharmacotherapies for alcohol withdrawal
Benzodiazepines for acute withdrawal symptoms
Disulfiram for alcohol release prevention
Naltrexone for relapse reduction, alcohol consumptions and craving
Disulfiram MOA
Disulfiram inhibits aldehyde dehydrogenase and enzyme responsible for the metabolism of acetaldehyde to acetate.
antabuse reaction
flushing, weakness, nausea, tachycardia, hypotension
Smoking cessation: NRT
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
Nicotine replacement therapy (NRT)
Stimulates the mesolimbic dopaminergic system by binding to a4b2 nAchRs
Varenicline
Most effective smoking cessation
partial a4b2 nAChr agonist
full agonist for a7 nAChr
Buproprion
Blocks monoamine reuptake
Nicotnic antagonist
increases dopamine in nucleus accembens
compare NRT, Varenicline to Buproprion
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
methadone vs oxytocin
oxytocin has pro-social effects
Define drug addiction
A chronic, relapsing disorder characterized by compulsive drug seeking, continued use despite harmful consequences, and long-lasting changes in the brain.
Define Addiction
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)
Define tolerance
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
Define dependence
Dependence: an adaptive state that develops from repeated drug administration. Resulting in the emergence of physical and emotional withdrawal symptoms when drugs are stopped.
How do Opioids and cocaine differ in terms of effects on the HPA axis?
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.
potential strategies for relapse prevention
Better addressing emotional withdrawal symptoms and enhancing social behaviour and relationships.
SSRIs have shown limited efficacy in treating depression associated with opioid abstinence.
What brain system do drugs of abuse activate?
Mesolimbic dopamine system
What happens to the PFC in the dependent state
Decreased activity
The PFC; responsible for executive functions such as decision making and self-control, fails to regulate the orbiofrontal cortex (OFC)
Brains reward system
Nucleus accembens
Ventral tegmental area (VTA) –> to the nucleus accembens
Opioids MOA
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.
Intranasal oxytocin as a novel treatment for opioid addiction
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.
Limitations of Intranasal oxytocin as a novel treatment for opioid addiction
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.
E-cigarettes vs Nicotine Replacement for smoking cessation
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.
Limitations of E-cigarettes for smoking cessation
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.
Role of Gut Microbiota in Drug Addiction
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.
Limitations of Gut Microbiota in Drug Addiction
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.
