DOA 1 - General/Cannabis Flashcards
Using general pharmacodynamics, explain why drugs are normally abused?
Dopaminergic neurones from the
• VTA (ventral tegmental area)
are STIMULATED to release DA (reward) into the
• NAcc (nucleus accumbens [ventral striatum])
General methods of administration of drugs and the speed of absorption?
• Intranasal
- mucous membranes of nasal sinuses = SLOW absorption
• Oral
- GI tract = VERY SLOW absorption
• Inhalation
- small airways & alveoli = RAPID absorption
• Intravenous
- veins = RAPID absorption
Which is the fastest route of administration to the BRAIN and why?
INHALATION
As pulmonary circuit is VERY SHORT
whereas
via. IV must do the systemic circuit before accessing the brain
Explain the 4 broad classifications of drugs
• Narcotics/painkillers
- opiate-like drugs
- e.g. heroin
• Depressants
- e.g. alcohol, benzodiazepines (valine), barbiturates
• Stimulants
- e.g. cocaine, amphetamine, caffeine, metamphetamine, nicotine
• Miscellaneous
- have effects from MULTIPLE classes of drugs
- e.g. cannabis, ecstasy (MDMA)
In regards to routes of administation for drugs, what is the order for onset of euphoria?
Oral < Intranasal < IV < Inhalation
Explain the different parts of cannabis and what is used for?
Cannabis/marijuana = the PLANT
Hashish (the resin) = is the TRICHOMES
• glandular hairs that contain the HIGHEST [THC]
Hash oil = SOLVENT EXTRACT
Cannabis contains over 400 compounds - what makes up for >60 of it?
CANNABINOIDS
• Delta9-THC is the MOST POTENT type
• Positive aspects from smoking weed are from cannabidiol
- believe balance between these two (cannabidiol vs. delta9-THC is needed)
Explain the dosing issues seen with cannabis in recent years
Doses in 60’s & 70s was
• ~10mg THC
Now the doses are
• ~150-300mg THC
Potency has increased over the years SO if delta9-THC has increased do has cannabidiol
• the -ve effects are therefore MORE pronounced than +ve effects (as more delta9-THC)
Explain the pharmacokinetics associated with the ROA of cannabis, oral and inhalation
ORAL - 5-15% THC delivered
• DELAYED onset (as slow absorption)
• First pass metabolism
INHALATION - 25-35% THC delivered
• fastest route to brain as pulmonary circuit is very short
General pharmacokinetics associated with cannabis?
Cannabis SLOWLY accumulates in the body as it is VERY LIPID SOLUBLE
• builds up as FA CONJUGATES in fatty tissue
• takes 30 days for the effects to cease on the body
Explain the pharmacokinetics associated with cannabis in terms of metabolism?
Liver CONVERTS THC
• to 11-OH-THC (more potent - PHASE 1 METABOLITE)
GIT excretes 65% of it
• much of the THC undergoes ENTEROHEPATIC RECYCLING due to lipid solubility (as part of BILE)
Urine excretes 25% of it
Explain the relationship between [plasma] of cannabis and degree of intoxication
POOR correlation between plasma [cannabinoid] & degree of intoxication
• THC is MORE [ ] in the brain matter than blood as it is very lipid soluble
• This leads to the poor correlation seen
Explain the receptors associated with cannabis usage
Brain
• CB1R - hippocampus, cerebellum, cortex & basal ganglia
Peripheral
• CB2R - immune cells
The CB Receptor is an INHIBITORY GPCR
• linked to adenylate cyclase
What is the body’s version of THC?
Endogenous Anandamide
Receptors associated with cannabis?
CBR = cannabinoid receptors
• depressants
2 main classes
• CB1
• CB2
Using pharmacodynamics, explain how people feel sense of euphoria when using cannabis?
Stimulation of CB1 receptor INHIBITS the release of GABA
• DISINHIBITON
This increases the release of dopamine by INHIBITING the inhibition of release of DA (via. VTA) to the NAcc
Using pharmacodynamics, explain why some people that use cannabis can lead to psychosis & schizophrenia?
One target of cannabis is ACC
• Anterior Cingulate Cortex
ACC is invovled in performance monitoring with behavioural adjustment
i.e. driving & talking with friend BUT starts to rain so stop talking to focus on road
Cannabis causes HYPOACTIVITY in the ACC
Using pharmacodynamics, explain the relationship of cannabis with food intake
Cannabis tends to affect the OUTPUT SYSTEMS (rather than the neurones that receive the signals)
[ONENOTE!!]
Has 2 primary actions on the LATERAL HYPOTHALAMUS
• Pre-synaptic inhibition of GABA = increases MCH (melanin concentrating hormone) neuronal activity
• Increases OREXIN production
BOTH of these act to INCREASE HUNGER
MCH - has a stimulatory effect on hunger
Orexin - has a stimulatory effect on hunger
Using pharmacodynamics, explain the relationship between cannabis and immunosuppresant?
Outside the brain, cannabis main effect is on the IS (as peripherally affects the immune cells)
Cannabis acts to DEPRESS the IS by AGONISING CB2 receptors on the following: • macrophages • mast cell • B-cell • T-cell • NK cells
Generally, explain the main CENTRAL effect of cannabis use?
- Psychosis, schizophrenia
- Food intake - Hypothalamus
• Memory loss
- Limbic regions (amnestic effects, decreased BDNF [brain derived neurotrophic factor)
- BDNF is the main thing in the hippocampus that drives memory formation
• Psychomotor performance - cerebral cortex
Generally explain the main PERIPHERAL effect of cannabis use
- Immunosuppresant
- Tachycardia/vasodilation
- via. TRPV1 receptors (NOT CBRs)
- leads to RED EYES as conjunctiva vasoDILATE
Why is it impossible to OD on cannabis?
Medulla has LOW CB1 receptor expression
• SO means the cardio-respiratory centre is NOT affected much
In regards to health & disease, explain how upregulation of CBRs can affect the body
In
MS/pain/stroke patients
• HELPS as regulates pain (remember it is a depressant!)
Fertility/obesity
• it is PATHOLOGICAL and may contribute to obesity (as present on adipose tissue) & infertility (inhibits the gonadotrophins for e.g.)
Drugs that be used for autoprotection purposes in term sof cannabis use as medical applications?
Delta9-THC drugs:
• Dronabinol
• Nabilone
(anti-emetics in cancer)
Delta9-THC + CBD drugs:
• Sativex
(treats MS pain)
ALL THESE ARE AGONISTS (stimulate the CBR)
Drugs that can be used for autoimpairment purposes in terms of cannabis use as medical applicaitons?
Rimonabant
• anti-obesity drugs (off-market)
• blocks feeling of hunger
• become off-marker as was linked to suicide (feeding pathway heavily linked to reward pathway)
This is an ANTAGONIST (inhibits the CBR)
Fatty acid amide hydrolase?
What produces the ENDOGENOUS ANANDAMIDE
So along with blocking the receptors can also block this
• Fatty acid amide hydrolase inhibitor
