13. Drugs of abuse 1 (cannabis) Flashcards
why do people abuse drugs?
for the reward pathway (mesolimbic dopamine system)
what is the reward pathway?
the reward pathway is a collection of dopaminergic neurones that originate in the ventral tegmental area (where cell bodies are) and project down to the ventral striatum (the nucleus accumbens)
dopamine release in this area causes the feeling of reward
what different stimuli induce reward?
- food
- exercise
what are the different routes of administration?
- snort (intranasal): drug enters nasal sinus –> venous drainage –> lung –> heart –> brain
o Mucous membranes of the nasal sinuses will slow absorption - eat or drink (oral): stomach –> small intestine –> portal system –> liver –> heart –> brain
o There is very slow absorption due to the GI tract - smoke (inhalational): lungs (right next to the heart) –> heart –> brain
o Rapid absorption (seconds) - inject (intravenous): vein –> heart –> brain
o Rapid absorption (seconds)
how are drugs classified?
- narcotics/painkillers - opiate like drugs (e.g. heroin)
- depressants - ‘downers’ (e.g. alcohol)
- stimulants - ‘uppers’ (e.g. cocaine, caffeine)
- miscellaneous (e.g. cannabis, ecstasy)
why is inhalation the fastest route of drug administration to impact the brain?
- lungs are right next to the heart
- the alveoli are not much of a barrier to diffusion
what produces the high effect when smoking cannabis?
cannabinoids which make up 15% of compounds in the cannabis sativa plant
where in the plant are cannabinoids more concentrated?
the glandular hairs of the plant (trichomes)
where does the version of cannabis ‘hashish/resin’ come from?
the trichomes
where does the version of cannabis ‘hash oil’ come from?
solvent extraction
what is the most potent cannabinoid?
Δ9-tetrahydrocannabinol (Δ9-THC)
what is the effect of cannabidiol on THC?
protective effect from the negative effects of THC
how has the dosing of cannabis changed over the years?
- potency has increased
- attempts to concentrate THC to increase effects (10mg in 60s to 150mg nowadays)
what are the routes of administration of cannabis?
- oral: 5-15% of dose enters bloodstream
- inhalation: 25-35% of dose enters bloodstream (50% loss automatically because only 50% gets far enough down into the lungs to diffuse into the bloodstream and lots is breathed out)
describe the pharmacokinetics of cannabis
- cannabis is very lipid soluble
- it accumulates in poorly perfused fatty tissues
- most of the cannabis goes to very well perfused tissues however adipose tissue receives a bit of CO so very lipid soluble drugs can diffuse into fat
what happens to chronic cannabis smokers?
- build up in the fatty tissue (concentration ratios between fat and plasma up to 10^4:1)
- slow leakage back into the blood
what are the cannabis metabolites?
- 11-hydroxy-THC (more potent than Δ9-THC) is a metabolite formed in the liver
what happens to cannabis metabolites in the body?
- a large amount is secreted by bile (enterohepatic recycling)
- bile duct –> SI –> potential reabsorption
what does the recycling of cannabis metabolites mean?
there is a very poor correlation between plasma cannabinoid concentration and degree of intoxication (worse in chronic users)
what is the main concern with chronic users?
the brain is a fatty tissue so chronic use leads to accumulation in the brain
after smoking a cannabis cigarette how long do the effects persist in the body?
30 days
what are the pharmacodynamics of cannabis?
- the body produces cannabis-like substances –> endogenous anandamide which behaves like cannabis
- the targets for anandamide are cannabinoid receptors (Gi-protein coupled):
- -> CB1 receptors: mostly in brain
- -> CB2 receptors: mostly on immune cells in the periphery
how does cannabis/anandamide act on receptors?
binds to receptors –> G-protein is negatively coupled to adenylate cyclase –> downregulates adenylate cyclase (depressant at cellular level)
how is euphoria induced by cannabis?
- stimulation of the CB1 receptor switches off and blocks GABA transmission (GABA suppresses reward pathway)
- there are lots of CB1 receptors on GABA neurones
- cannabis binds –> reduces firing rate of GABAnergic neurones (depressant) –> dopaminergic neurone firing increases –> euphoria
