What causes drug addiction?

[Philosophy Explorer]

I count alcohol as a drug for this thread.

I know that the more you do drugs (including alcohol), the more likely you can get addicted. And I know this involves the brain. The question at hand is what changes occur in the brain and can the effects be reversed?

PhilX

[Blaggard]

The cause is simple the cure not. Counting alcohol is not really very revealing; coffee is physically addictive, as is chocolate, you need to get to the cause not the symptoms.

GABAA receptors become inured to the drug of your choice, they become unable to function efficiently without that stimulus. The pathway and etiology is very clear, what is not so clear is how to cure addiction.

Target for benzodiazepines

The ionotropic GABAA receptor protein complex is also the molecular target of the benzodiazepine class of tranquilizer drugs. Benzodiazepines do not bind to the same receptor site on the protein complex as the endogenous ligand GABA (whose binding site is located between α- and β-subunits), but bind to distinct benzodiazepine binding sites situated at the interface between the α- and γ-subunits of α- and γ-subunit containing GABAA receptors (see figure to the right).[6][7] While the majority of GABAA receptors (those containing α1-, α2-, α3-, or α5-subunits) are benzodiazepine sensitive there exists a minority of GABAA receptors (α4- or α6-subunit containing) which are insensitive to classical 1,4-benzodiazepines,[8] but instead are sensitive to other classes of GABAergic drugs such as neurosteroids and ethanol. In addition peripheral benzodiazepine receptors exist which are not associated with GABAA receptors. As a result the IUPHAR has recommended that the terms "BZ receptor", "GABA/BZ receptor" and "omega receptor" no longer be used and that the term "benzodiazepine receptor" be replaced with "benzodiazepine site".[9]

In order for GABAA receptors to be sensitive to the action of benzodiazepines they need to contain an α and a γ subunit, between which the benzodiazepine binds. Once bound, the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for the GABAA receptor, increasing the frequency of opening of the associated chloride ion channel and hyperpolarising the membrane. This potentiates the inhibitory effect of the available GABA leading to sedative and anxiolytic effects.

Different benzodiazepines have different affinities for GABAA receptors made up of different collection of subunits, and this means that their pharmacological profile varies with subtype selectivity. For instance, benzodiazepine receptor ligands with high activity at the α1 and/or α5 tend to be more associated with sedation, ataxia and amnesia, whereas those with higher activity at GABAA receptors containing α2 and/or α3 subunits generally have greater anxiolytic activity.[10] Anticonvulsant effects can be produced by agonists acting at any of the GABAA subtypes, but current research in this area is focused mainly on producing α2-selective agonists as anticonvulsants which lack the side effects of older drugs such as sedation and amnesia.

The binding site for benzodiazepines is distinct from the binding site for barbiturates and GABA on the GABAA receptor, and also produces different effects on binding,[11] with the benzodiazepines causing bursts of chloride channel opening to occur more often, while the barbiturates cause the duration of bursts of chloride channel opening to become longer.[12] Since these are separate modulatory effects, they can both take place at the same time, and so the combination of benzodiazepines with barbiturates is strongly synergistic, and can be dangerous if dosage is not strictly controlled.

Also note that some GABAA agonists such as muscimol and gaboxadol do bind to the same site on the GABAA receptor complex as GABA itself, and consequently produce effects which are similar but not identical to those of positive allosteric modulators like benzodiazepines.

http://en.wikipedia.org/wiki/GABAA_receptor

The effects can of course be reversed, but once the receptors in your brain are keyed to a particular antagonist drug, it is very hard to reprogram your receptors to let it go.

Anyone who has drunk 6 cups of very strong coffee all their life who goes cold turkey on strong caffeine doses will tell you this, an opiate abuser will tell you this.

[Melchior]

I count alcohol as a drug for this thread.

I know that the more you do drugs (including alcohol), the more likely you can get addicted. And I know this involves the brain. The question at hand is what changes occur in the brain and can the effects be reversed?

PhilX

Plenty of info on google.

[HexHammer]

I count alcohol as a drug for this thread.

I know that the more you do drugs (including alcohol), the more likely you can get addicted. And I know this involves the brain. The question at hand is what changes occur in the brain and can the effects be reversed?

PhilX

Plenty of info on google.

Best answer yet!

[Skip]

The causes of addiction are a complex of chemistry and biology, the molecular mechanism varying with the drug, of course. http://www.drugabuse.gov/publications/t ... -addiction It is by no means restricted to humans, or even great apes: dogs, pigs and elephants have been documented alcoholics.

Some effects are reversible; many are permanent; some fatal. Brain deterioration cannot be reversed, but in a young person, many functions can be taken over by remaining sound tissue. Again, there is a wide variation, according to the drug, the person's metabolism, duration of drug use, and - very significantly - the age at which they began using and the age at which they cease.
There are stories of successful recovery, but I'm not at all convinced that there is a cure. One can stop using a particular drug, but the danger of relapse, either to that same habit or a closely-related substitute, becomes a life-long problem for most (if not all) addicts.

You'll probably find a correlation of a high rate of chemical dependency with dysfunctional societies (as in a state of wide economic disparity), stressful situations (like fighting an unwinnable, unjustifiable war) and long, dark winters. Whatever factors make people crazy also make people turn to self-medication.

[hammock]

The question at hand is what changes occur in the brain and can the effects be reversed?

Watch out, the last half of that is a back door creaking googly-google for something OnTopic to slip through into this general science forum. Better lock that sumbetch next time. In the Cave: Philosophy and Addiction

"...I am often asked how I got and stayed sober for those first 19 years; it was because of philosophy, which engendered in me a commitment to living an examined life, and gave me the tools and concepts to do so...."