Pharm 13: Drugs of Abuse 1 (general/cannabis) Flashcards
Why are drugs abused ?
- all drugs can all cause euphoria
euphoria = rewarding feeling - mediated by
reward pathway
- dopaminergic pathway
organ in Ventral Tegmental Area (VTA) projects down (via axons) to ventral striatum
nucleus accumbens (NAcc) = area of the striatum –> dopamine release here –> causes euphoria
–> drugs hijack the central reward pathway
list different methods of administrating the main drugs of abuse
and compare rates of absorption (ROA)
- intranasal –> (ROA = slow)
- orally –> (ROA = very slow)
- inhalational –> (ROA = rapid- fastest–> rapid passive diffusion by alveolar gas exchange)
- intravenous –> (ROA =rapid )
What are the 4 main classification of drugs of abuse ?
give examples of each
- narcotics/ painkillers
- -> opiate like drugs
- -> e.g heroin/morphine - depressants
- -> downers
- -> decreases brain function
- -> e.g alcohol, benzodiazepines, barbiturates - stimulants
- -> uppers
- -> increases brain function
- -> cocaine, methamphetamine, caffeine - Misc.
- -> e.g Cannabis, ecstasy (MDMA)
describe the pharmacokinetics of cannabis
oral = 5-15% enters blood
–> delayed onset
inhalation = 25-35% enters blood
cannabis = lipid soluble / non lipid soluble
cannabis = very lipid soluble
chronic cannabis users have huge cannabis store in fat how is this?
- cannabis = very lipid soluble
- it slowly accumulates in poorly-perfused fatty tissues –> which is a major storage site
then it is slowly released into blood –> greater accumulation –> stronger effects
note:
10^4 : 1 (fatty tissue vs plasma)
How long after smoking a cannabis
cigarette will the effects persist in the body?
If non-smoker had 1 cannabis cigarette, effects persist for 30 days (still detectable)
–> because it takes 5 days to accumulate in fat
–> then slowly released from then on
what is a Endogenous cannabinoid-like substance =
Anandamide
where are the 2 different types of cannabinoid receptors located at?
Cannabinoid receptors:
o CB1 receptors = (mostly) in Hippocampus/cerebellum/cerebral cortex/basal ganglia
o CB2 receptors in Immune cell / WBC
How is the state of ‘euphoria’ reached?
Normally, GABA neurones supress DA-nergic neurones projecting from VTA
–> so GABA supresses reward pathway
o CB1 receptors are on GABA neurones –> cannabis binds
(causes disinhibition)
–> decreases firing rate of GABA neurones –> less suppression –> more reward path activity + DA release
Anterior Cingulate Cortex (ACC) is hyperactive/hypoactive in cannabis users
Anterior Cingulate Cortex (ACC) is hypoactive in cannabis users
–> can lead to psychosis + schizophrenia
What is Anterior Cingulate Cortex (ACC) responsible for?
involved with error detection, performance monitoring, and behavioural adjustment in order to avoid losses (e.g. concentrating on road when driving rather than conversation)
what effect does cannabis have on food intake
(increases food intake)
Positive effect on orexigenic neurones in Lateral Hypothalamus by:
a) –>Presynaptic inhibition of GABA –> increases MCH neuronal activity
b) –> Increased orexin production
How does taking cannabis affect the immune system?
CB2 receptor expression
o CBs impair functions of different immune cells
What are some peripheral effects of cannabis?
Peripheral effects:
o Immunosupressant
o Tachycardia/vasodilation (e.g. in conjunctivae –> (bloodshot eyes) – both involves TRPV1 receptor, NOT CB receptors
o Medulla has low CB1 expression –> important because it means small effect on CVS/respiratory system
