This will be about what dependance is, the molecular mechanisms of it, as well as how drug qualities and delivery routes relate to addictivity. We will also go over common drugs of abuse and their mechanisms, which can help us learn about specific neurotransmitter roles
we will also talk about abuse potential and which drug classes are more harmful.
Dependance
Dependance is a complex term with 2 subtypes: physical and psychological
Physical dependance is when you take a drug regularly have go through withdrawl symptoms when you stop using the drug.
Psychological dependance is akin to what people usually think of when addiction is brought to mind. It is characterised by compulsive drug taking, where it becomes more importance than anything else, and the urge remains after withdrawals have stopped.
These 2 concepts are closely related to the idea of tolerance, where there is decrease in the effect of a drug for a specified dose over repeated use.
SAD
Repeated activition of the dopaminergic release pathways can lead to physical and psychological dependance. This can elevate to a substance use disorder. This is when a drug becomes hard to shrug off and starts to rule your life
ego inflation vs dissolution and its effects on dependance.
Ego inflation (seen in cocaine and such) has been shown to increase dependance where as ego-dissolution has been shown to decrease dependance
Role of dopamine in drug dependance
Most drugs which cause dependance increase dopamine in the brain. This implicated dopamine as a central player in dependance and addiction. Intense phasic firing of dopamine receptors is more likely to cause drug dependance.
This is due to the fact that it is the d1 receptors which are responsible for the euphoria, and they have a lower affinity for dopamine than the D2 receptors. This leads to D2 receptors mopping up dopamine and only when a certain threshold is passed do we start to get our euphoric feelings associated with d1 receptor activation. This is why the faster more intense spikes feel the best
Addictive qualities
There are things which can make a drug more or less addictive. These can be chemical elements or route of administration. Generally anything that will make the dopamine spike faster and higher will be more addictive.
Chemical qualities.
Chemical structures that are fast absorbed and release lots of dopamine quickly will be the most addictive
Route of administration
The route of administration matters, as injecting or smoking (inhaling) a drug increases the intensity and rapidity of the high much more than oral or intranasal usage.
Drugs of abuse
Drugs that increase dopamine more than serotonin are called stimulants and drugs that increase serotonin more than dopamine are called entactogens/empathogens
Noradrenaline and dopamine releasing agents (Amphetamines)
These are amphetamine and methamphetamine. These drugs enter vesicles and push out dopamine and noradrenaline into the synapse. Methamphetamine enters the brain faster than amphetamine and has a increased dependance risk as a result, thus showing the more rapid and intense the effect is the more addicting it is.
Cocaine
Cocaine is an NDRI (as well and a local anaesthetic). Its effects are longer lasting when taken intranasally which decreases addiction potential but smoking it is highly addictive. This is called crack cocaine.
Opioids
Opioids work through the µ opioid receptor, and produce a rush of euphoria and analgesia when given
Opioid tolerance ramps up quickly, with addicts being able to take 50-100x a therapeutic dose of opioids
you should not prescribe opioids for long, because there is an addiction risk.
Alcohol
This is a GABA PAM and it is a CNS depressant. you feel drunk (subjective intoxication) as the rate of change of BAC is positive but as it becomes 0 you feel sober. you still have impaired coordination. this is why you cant drive even though you feel sober
Alcohol is commonly in the 7 top causes of death.