11. Drug Dependence

• physical drug dependence:

  • anxiety/insomnia, cramps, tachycardia, piloerection, diarrhoea

  usually from opiates
• psychological drug dependence:

  • compulsive behaviour and anxiety

  increases likelihood to reuse drugs
• origins of drug dependence is the dopamine pathway - increases reward

  • different drugs have different levels of effect on the mesolimbic dopaminergic pathway and therefore different degrees of reward
• drug tolerance can be innate (fast metabolism decreases impact) or acquired

  • alcohol intake increases the enzymes that metabolise it, meaning more alcohol is needed for the same effect
  • pharmacodynamic e.g. opiate: activates Gi which inhibits cAMP, so body produces more cAMP and therefore more is needed to inhibit cAMP again
• opiates - heroin, morphine, pethidine

  • heroin is more lipophilic so crosses BBB faster, increasing addiction
  • rapid tolerance - not to all effects but to the reward pathway
  • can be cut with something caustic to cause histamine release like heroin does
• opiates inhibit adenylate cyclase which decreases cAMP

  • opiate receptors are on GABA interneurons that surround dopaminergic neurones
  • inhibiting the interneurons increases activation of dopamine pathway
• opiate treatment:

  • naloxone - blocks opiate receptors, short half life so must be continually administered
  • dependence is treated by psychotherapy and methadone - this is an opiate agonist with a longer half life that decreases the reward of heroin and morphine (low success rate)
• caffeine is a social drug - withdrawal includes lethargy, irritability and headache

  • acts as a phosphodiesterase inhibitor (enzyme that metabolises cAMP)
• cocaine is a stimulant that inhibits catecholamine reuptake, increasing dopamine at the synapse increasing reward

  • causes tissue necrosis as it causes vasoconstriction
  • withdrawal is eased with TCA due to cross pharmacology
• amphetamine is a dopamine releaser, overdose is treated with neuroleptics (schizophrenia treatments - dopamine antagonists)
• MDMA/ecstasy is a serotonin releaser that causes lesions of serotonin neurones - can cause psychiatric issues

  • can cause cardiac arrest
• cannabis activates cannabinoid receptors, low doses cause euphoria and sharpened sensory awareness, high doses are sedating and cause dream like state

  • lipid soluble so fast acting
• alcohol and benzodiazepines are sedatives that increases the effect of GABA - hyperpolarising the neurone