General/Cannabis Flashcards
why are these certain drugs abused?
to induce euphoria
hijack the endogenous reward system
main centres of the brain involved in the use of these drugs
nucleus accumbens (ventral striatum) ventral tegmental area
pathway of why these drugs are abused
mesolimbic dopamine system- central reward pathway
rewarding stimulus
to VTA
to NAcc
triggers dopamine release reward
what are the routes of administration?
Intra-nasal
Oral
Inhalation
Intra-venous
which is the fastest route of administration to get to the brain and why?
Inhalation- small airways and alveoli. rapid absorption.
snort- mucous membranes of nasal sinuses. slow adsorption
eat- gastrointestinal tract. very slow absorption.
inject- veins. rapid absorption, but needs to go back to the heart to be pumped into the brain, hence takes longer than inhalation.
classification for drugs of abuse:
plus examples
Narcotics/Painkillers – opiate like drugs e.g. heroin
Depressants – ‘downers’
e.g. alcohol, benzodiazepines (valium), barbiturates
Stimulants – ‘uppers’
e.g. cocaine, amphetamine (‘speed’), caffeine
metamphetamine (‘crystal meth’)
Miscellaneous – e.g. Cannabis, Ecstasy (MDMA)
what is cannabis?
comes from a plant
made up of approx. 400 compounds, 60 cannabinoids
Most potent of these are delta 9 THC and cannabidiol
what is significance of dosing of cannabis?
60’s + 70’s: ‘Reefer’ – 10mg THC
21st Century: ‘Skunkweed/Netherweed’
- 150mg THC - 300mg THC (+ hashish oil)
**the more THC you have the more negative effects experienced, and the less cannabidiol (protective nature) the less positive effects
pharmacokinetics:
- ROA
Oral – 5-15% delayed onset/slow absorption first pass metabolism OR Inhalation – 25-35%
where does cannabis accumulate and why?
very lipid soluble
therefore easily diffuses into tissues
if cannabis conc is high in the blood for a long time:
slowly accumulates in poorly perfused fatty tissues.
Subsequently, intensive accumulation occurs in less vascularised tissues and finally in body fat, the major long-term storage site, resulting in concentration ratios between fat and plasma of up to 104 : 1. The exact composition of the material
accumulated in fat is unknown, among them being unaltered THC and its hydroxy metabolites. A substantial proportion of the deposit in fat seems to consist of fatty acid conjugates of 11-OH-THC.
metabolism of cannabis?
phase 1: Liver - 11-hydroxy-THC
11-hydroxy is a phase 1 metabolite and is v potent
another issue is the enterohepatic recycling, since its so lipid soluble t just enters the gut again
fat and the brain
the brain has a lot of adipose tissue. Brain 60% lipid content – structural i.e. not available to be metabolised for energy. Poor correlation between plasma cannabinoid concentration and degree of intoxication
how long after smoking a cannabis cigarette will the effects persist in the body?
30 days
pharmacodynamics:
receptors for cannabis?
CB1 receptors- hippocampus/cerebellum/cerebral cortex/basal ganglia
CB2 receptors-
immune cells
CBR are depressants
reduce not as much adenylate cyclase produced
how does the euphoria occur with cannabis?
normally GABA released which is a natural suppressant for the release of dopamine.
cannabis binds to the CB1 receptors and slowing the activity of GABA neurones so now the reward endogenous pathway fires at a higher rate. Lots more dopamine
