Drugs of abuse 1 Flashcards
How do drugs produce euphoria?
Overide the mesolimbic dopaminergic system -ventral tegmental neurons project to the nucelus accumbens (ventral striatus)- release dopamine => associated with feeling of reward (help drive behaviour towards those feelings, like food,
What are the main routes of entry for drugs of abuse?
Snorting-mucous membranes of nasal sinuses-to veins-to heart-to brain- slow absorb
Eating-GI tract-to veins-to liver-heart-to brain- very slow absorbtion
Smoking-go straight to left side of heart-to brain-fastest
inject (intravenous)-venous system-to heart-then brain
How can drugs of abuse be classified ?
In pharma-classify via what they do
Narcotics/painkillers-opiates (heroin)
Depressants-downers-alcohol, benzodiazepam, barbituates
Stimulants-uppers-cocain, apmhetamine, caffeine, metapheramine
miscelaneous-ecstasy, cannabis
Describe whsere cannabis comes from? What are the main active component?
about 60 cannabinoids in the plant-most powerful-Delta9-THC and another common is cannabidiol
in 1970-10mg THC per cig
21st century-nearly 150mg THC => dose response effects seen (evidence shows only increased bad symptoms)
Cannabidiol seems to modulate the negative effects of THC-and in modern cannabis with very high THC-lower cannabidiol-more negative side effects
describe pharmacolokinetics of cannabis?
Oral-slow route and about 5-15% bioavailability (first pass metabolism)
Inhalation-faster-bioavailability-25-35%
cannabinoids are very lipid soluble-diffuse across membranes-pretty much follows perfusion-more in highly perfused tissue-like brain
adipose tissue very low perfusion-but very lipid-slow accumulation-if smoke cannabis often-accumulation in fatty tissue (10^4 in FA vs plasma)-and slowly leak back
brain also has a lot of fat (structural) and has these build ups
because of that-cannabis stays around for 30days -and can be detected in blood and have some effects
How is cannabis metabolised and extreted
Phase 1 metabolism-make more water soluble-make 11-hydroxy-THC (more potent than THC)
Conjugated and excreted-(but can only do so much)
65% of cannabis exits via GIT (bile)-but enterohepatic recycling (especially in lipid soluble drugs)-just recycles back into the blood
25% in urine
Bad correlation between plasma THC and degree of entoxication (because no indication of fat, enterohepatic recycling, liver function, how much stays in brain, etc)
What does cannabis actually do in the body (receptor target/location)?
Depressant action-inhbitory to most cells
CB1/2 receptors -Cannabinoid receptors-
CB1 - in brain-very common GCPR
CB2-immune cells/peripheral cells-Gi (negative Adenylyl cyclase)
endogenous thing that binds-anandemide
GABA neurons projecting to nucleus accumbens (reward)-suppresses the reward -need to be switch of to get reward
CB1 receptor on GABA neurons-negative inhibition of GABA-which allows endogenous reward pathway to fire
The psychotic symptoms-Anterior cingulate cortex is important (normally processes errors/monitoring/drives behaviour) => hypoactivity in cannabis users (supresses ability to change behaviour based on changing conditions)
High THC-more pshycotic effects than THC+cannabidiol
How does cannabis modulate food intake?
Pre-synaptic inhbition of GABA neurons increase the MCH neurons in lateral hypothalamus-that drives the eating-its like the output system-
MCH has positive effect on food seeking by reducing its inhbit by gaba
Orexin-unsure how it works but stimulated oxerin activation
Both of these are outputs that causes
(where the POMC/AgRP neurons would project to)
Does Cannabis have immunosupressant activities?
CB2 is present on nearly all immune cells
And cannabis has supressant effects-supresses the immune cells
Seems to reduce immune system, especially if chronic user
What are the summary of the effects of cannabis
Central-phsycosis-schizo
Food intake
Memory loss-limbic region-lower BDNF
Physomotor performance down
Peripheral-immunosupressant
Tachycardia/vasodilation
Medulla has low CB1 receptors-if depress cardio-resp control-die -but cannabis cant cause that because low CB1
What are the medical applications of cannaboids like drugs
Depressant effects are looked for
In MS/Pain/Stroke-elevation of CB1 receptors (seems protective)
In fertility/obesity-increase of CB1 seems to contribute to disease
Dronabinol/nabinole-just THC-used to stimulate appetite/anti emetics/
Sativex-THC and canabidiol-used as analgesic (neuropathic), in MS
Rimonabant-inhbitory action of CB1/2-anti obesity agent-decreases weight = but kinda cause suicide
trying to increase anandemide via amide hyrolase inhbitors -didnt go well at all
