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Article - The Mechanistic Classification of Addictive Drugs

ayjay

ayjay

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The consumption of a variety of natural and synthetic substances can lead to addiction, which is commonly defined by the loss of control and compulsive consumption despite negative consequences. Although addictive drugs have diverse molecular targets in the brain, they share the common initial effect of increasing the concentration of dopamine released from mesocorticolimbic projections.

In this article, we review recent research that has advanced our understanding of the molecular mechanisms underlying this increase of dopamine. Based on this research, we propose a new classification for addictive drugs that we believe may help in directing research towards more effective treatment of addiction ...
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More at http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0030437

I'm a bit iffy about the dopamine theory of addiction. My concern is that it ignores the recursive interaction between the dopamine system and higher cognitive function - instead defines all changes to dopamine system as drug effects.

Unfortunately - the neurochem in this article is outside my expertise to critique - any thoughts from the megabrains here?
 
The "dopamine hypothesis" of drug addiction is clearly far too simplistic.

Nicotinic acetylcholine receptors are clearly also involved, on the grounds that

(i) nicotine itself is more addictive than either heroin or cocaine, even though nicotine doesn't induce dopamine release

(ii) blocking alpha3beta4 nicotinic acetylcholine receptors with antagonists such as ibogaine or 18-methoxycoronaridine interferes with the addictive effects of a whole range of drugs acting by various mechanisms (opiates, cocaine, nicotine, methamphetamine etc)

(iii) early exposure to nicotine has been shown to predispose humans to becoming addicted to "hard drugs" later on in life, and the extent of this predisposition correlates with both the timing and extent of nicotine exposure (the earlier a kid starts smoking, and the more cigarettes they smoke, the more likely it is they will be addicted to heroin/cocaine/meth when they are an adult)

So blaming addiction purely on transient dopamine release is never going to fully explain it. Also i feel that any theory of addiction which focuses only on the neuropharmacology of particular drugs but ignores the psychological and sociological factors that also induce individuals to become addicted to drugs is going to be rather incomplete.
 
^thanks for that.

The dopamine theory interests me because it appears to be a strategy being used to validate the disease model of drug use (ie - "some people have a disease called 'addiction' which means that they cannot ever use <substance X> in a controlled fashion"). I think this model is fairly crap too. I'm glad that you take the trouble to include set/setting in your comment, mad scientist.
 
Well, I've only briefly browsed through those refs, but I think this might be useful (if you're feeling brave)

https://rikki.fi/tajkor/bl/Dopamine and drug addiction - the nucleus accumbens shell connection.pdf

It's a pretty hardcore paper, but basically I think it's saying that:

While other rewarding stimuli (such as food) cause an inital increase in activity in the shell of the nucleus accumbens, which then wanes as activity increases in the core of the nucleus accumbens and then later in the prefrontal cortex.

Drugs of abuse cause a far longer period of sensitisation of the shell. As if you're on a sort of 'hightened alert' for other rewarding stimuli.

Since there are alot of dopaminergic inputs into the prefrontal cortex, it could be argued that the prefrontal cortex acts as a way of 'incorporating rewarding stimuli with other behaviour'.

Also, individuals with prefrontal injury exhibit more compulsive and aggressive behaviour.

But certainly even if the nucleus accumbens is important in reward conditioning, how reward seeking influences other behaviour is a separate issue.
 
This is far from a rigorous theory, but I've been playing with the notion of the adrenaline rush as a significant factor in addiction.
We all know that dangerous sports, gambling, sex and other addictive activities involve the sense of danger, the fight-or-flight response, which releases adrenaline (and generally, subsequently, enkephalins/endorphins).
Smoking anything is considered a quick route to addiction. Even cannabis is reinforcing when smoked IMHO. Smoking something damages the lungs and is much more dangerous to the body than any other method of ingestion, at least immediately. So this causes the release of adrenaline as the body senses it is under stress and needs to kick into action.
This leads more credence to why smoking a drug is so much more addictive beyond the "rush factor" of it getting into the bloodstream faster, as cannabis produces no real rush like smoked amphetamines and crack.
It also lends credence to the addictive nature of tobacco, which, IMHO, CANNOT be explained by nicotine. I believe nicotine is minimally physically addictive and the psychological addiction is caused by several environmental factors such as the ease of obtaining cigarettes, visual cues, environments like bars, concerts, smoke breaks, etc. But, the adrenaline rush produced by smoking certainly could contribute.
And, of course, adrenaline is all tied into the DA system so DA agonists and agents that cause the release of NA and A from synaptic vesicles would be mimicking this effect. It obviously works both ways.
So thats some of my theory. I was thinking about this the other day, strange it turned up here as well.
 
^yes, but is this purely an effect of the nicotine, or connected to the user's expectations. In other words - what is the impact of 'set' on underlying neorochemistry?
 
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