Treatment 3

Repeated drug exposure causes adapation in the brains reward pathways

• Neural rewards show daminished activation of reward pathways

• longer term memories of use can reactivate cravings and trigger a relapase

treating withdrawl

• bupernoprhine is a partial agonist at the mu-opioid receptor and is used to treat withdrawls from opiods

• Clonidine at an a2-andernic againonist, produces cellular effects similar to opiod receptor activation, and dampens many of the physical signs and symptoms of opiod withdrawl

• Alchol faclitates (GABA) receptor function, benzodiapines (or other medications that moduclate gabba systems) are now used routinly to prvent the life threating side effects of alchol withdrawl

Blockade of the drug targets as part of tratment

• prevents the drug from reaching the target in the brain

• the blockade needs to also not cause activation

• Naltrexone is a good example

  • blocks opiods ablity to have many effects

  • BUT it also blocks natral opiods which can lead to depressed moods

  • it works for alchol and nictotine as well given their withdrawls are related to endogenous opiods

• We don’t have a good opp like Naltrexone for stimulants like cocaine or meth

  • We would need a molecule that would stop cocaine or meth from binding to dopamine transporter but it would allow it to function properly for dopamine

  • this is hard to devlop

• Some work has been done that could block coacaine from crossing blood brain barrier

  • Use ummunilogical approcahes to change the permeablity of the blood brain barrier

  • worked in animals but the timeline of use is diff for people

  • specific to cocaine

Blood brain barrier

• Interaction with the endothelium neurons ang glia

• permeablity changes

• Many transport mehanism

• both active and passive

• immuno-messergers result in changes in permeablity

Blockade of drug targets as part of treatment