Drug abuse and dependence Flashcards
What professionals are required for the management of drug abuse and dependence?
Social scientists
Psychologists
Pharmacologists
Why is drug dependence important?
It is a global burden with high social cost
100 million people affected
What is substance dependence?
A state in which an organism functions normally only in the presence of a drug
Symptoms of psychological dependence
Craving
Compulsive seeking behaviour
Symptoms of physical dependence
Withdrawal upon cessation of drug use
Examples of harm caused by recreational drug use
Overdose
Direct physical damage
Inappropriate behaviour
Drift into criminal subculture
Self-neglect
Spread of disease
Exposure to unknown substance
Example of direct physical damage caused by drug use
Liver cirrhosis
Example of inappropriate behaviour caused by drug use
Driving while drunk
Why do drug abusers often show self-neglect?
They’re pleasure comes solely from a drug
So there is no need to find pleasure anywhere else
How do drug users get exposed to unknown substances?
Drugs are often laced with dangerous impurities
Characteristics of drug dependence
Psychological dependence - craving, compulsive drug-seeking behaviour
Physical dependence - tolerance associated with withdrawal syndrome
Tolerance - the need to increase dose to maintain the desired effect
What is the Misuse of Drugs Act?
Drugs are categorised A-C reflecting their addictive and harmful power
Their unauthorised possession is a criminal offence
Examples of class A drugs
Heroin
Cocaine
LSD
Examples of class B drugs
Amphetamine
Cannabis
Examples of class C drugs
Tranquilisers
Some pain killers
Length of criminal offence for each class of drug
Class A
Possession: 7 years
Dealing: up to life
Class B
Possession: 5 years
Dealing : 14 years
Class C
Possession: 2 years
Dealing: 14 years
What happened under prohibition in 1910-1930
Alcohol was banned
This lead to a rise in gang, crimes and cirrhosis
What did a rat study show about addiction?
Persistence in drug-seeking behaviour - forget to eat and only push the lever
Resistance to punishment - push the lever even when this is coupled with electrical shock
Where in the brain is the rewards system found?
Mesolimbic and mesocortical parts
Midbrain-forebrain bundle formed by dopaminergic neurons
What happens normally in the midbrain-forebrain bundle?
Dopaminergic neurons release dopamine from their synaptic terminus, leading to pleasure
A modulatory system controls this pathway through negative feedback
They do this through the release of dynorphins, pre-synaptic inhibitory modulators of dopaminergic neurons
What happens in the brain following drug addiction?
The pleasure system is constantly activated
Along with dopamine and dynorphin, Delta-fos-b (TF) is also released with the stimulation of pleasure center
The build up of delta-fosb transcription factors inhibit the dynorphin production and therefore causes the pleasure pathway to become overactivated
Why is the brain of an addict changed?
Plasticity of the brain
What mechanisms induce tolerance to a drug?
Increase in enzyme production of pathway that is inhibited
Downregulation of receptors
Receptor desensitisation
Classes of drugs abused for their central effects
Opioids
Stimulants
Anxiolytics
Depressants
Where is cocaine derived from?
Erythroxylon coca plant
Mechanism of action of cocaine
Inhibits reuptake of dopamine by neurons through dopamine transporter inhibition
Inhibits sodium channels
Mechanism of action of ethanol
Activates GABA-gated chloride channels
Enhances chloride influx
Causing hyperpolarization
Also inhibits NMDA receptors and voltage gated Ca2+ channels
How does ethanol stimulate the reward center?
Inhibition of the inhibitory input
Symptoms of ethanol abstinence
Tremors
Nausea
Sweating
Hallucinations
Aggressiveness
Unwanted effects of ethanol use
Motor incoordination
Feminisation of men due to reduced testosterone levels
Dementia
Liver disease
Fetal alcohol syndrome
Mechanism of action of nicotine
Desensitisation of central nicotinic acetylcholine receptors
Long term use = large increase in the number of nicotinic receptors in the CNS
How is tolerance observed in nicotine addiction?
Normally tolerance is correlated with a decrease in receptor density
Paradoxical increase in receptor number is likely because of the high proportion of receptors being in the desensitised state
What are three ways to treat alcoholism?
Opioid antagonists such as Naloxone
Aversion therapy
Behavioural aspects of the addiction
Describe aversion therapy
Disulfiram is used to make the alcohol taste badly
Inhibits one of the metabolic mechanisms using aldehyde dehydrogenase
Acetylaldehyde builds up as a response and causes a toxic bad feeling
Why do alcoholics most often die?
Vitamin B1 deficiency due to malnutrition
Which leads to encephalopathy and coma
Where are cannabinoids found?
Derived from cannabis sativa
Endocannabinoids are found naturally in the body
What are the two active component of cannabinoids?
Tetrahydrocannabinol
Cannabidiol
Components of the endocannabinoid system
Endogenous THC-like substances
At least two types of receptors
Enzymes that synthesize ECs
Systems that transport ECs into and out of cells
Enzymes that degrade ECs
What is the effect of the endocannabinoid system in the body?
Endocannabinoids are involved in many physiological functions and pathological states involving most of the systems of the body
Which receptors does THC interact with?
CB1
CB2
Which receptors does CBD interact with?
CB1
CB2
Weakly*
Where are CB1 receptors found?
Neurons
Where are CB2 receptors found?
Immune system
C-fibres
How are endocannabinoids made?
By demand
Through enzymatic cleavage of membrane lipid precursors
What is the effect of endocannabinoids on pre-synaptic neurons?
Endocannabinoids are made in the post-synaptic neuron and act on the pre-synaptic neuron to inhibit the release of the neurotransmitter
Which type of neurons do endocannabinoids act on?
GABAergic
Glutamatergic
How do endocannabinoids affect the inflammatory cells?
Autocrine mediators
Inhibits the production of inflammatory mediators via CB receptors
What is the main endogenous cannabinoid?
Anandamide
It is an arachidonic acid derivative
What type of receptors are CB receptors?
G-protein coupled
Gi
Main sites of function of CB1 receptors
Association regions of the cerebral cortex
Hippocampus
Cerebellum
Hypothalamus
Which cells primarily express CB2 receptors?
Leukocytes
Effects of the CB1 receptor
Higher brain function
Increases appetite
Inhibits nausea and vomiting
Modulate muscle contraction
Effects of the CB2 receptor
Inhibition of macrophages
Inhibition of T cell activation
Difference between THC and CBD
THC binds strongly to CB receptors
CBD has weak interactions, does not cause euphoria and reduces anxiety probably by activation of 5HT1A receptors
Medical uses of THC and CBD
Patients with multiple sclerosis-related muscle spasticity
Adults with vomiting or nausea caused by chemotherapy
Children and adults with rare, severe, untreated forms of epilepsy
Main unwanted effect of Cannabinoids
Increase schizophrenia rates in children
Diseases targeted by CB1 agonists
MS
PD
Cancer
Chemotherapy-induced nausea
Glaucoma
Diseases targeted by CB1 antagonists
Obesity
Alcoholism
Smoking
Diseases targeted by CB2 agonists
Inflammatory conditions
5 main categories of drugs
Cannabinoids - relaxation, euphoria
Opioids - euphoria
Hallucinogens - altered perception
Depressants - release of inhibition, sedation
Stimulants - increased alertness
Examples of depressants
Ethanol
Benzodiazepine
Examples of stimulants
Amphetamines
Cocaine
Nicotine
Examples of hallucinogens
LSD
Psilocybin
Why are opioids particulalry dangerous?
High addiction rates due to causing both euphoria and depressant action
