Drugs of Abuse: Cannabis Flashcards
Which areas of the brain does cannabis act on
Nucleus Accumbens
Ventral tegmental area
Identify the ‘reward’ pathways in the brain activated by drugs of abuse
A rewarding stimulus
Ventral tegmental area -> nucleus accumbens
Nucleus accumbens release dopamine (reward)
What are the routes of drugs of abuse administration
Intra-nasal - snort
Oral - eat
Inhalational - smoke
Intra-venous - inject
What is the rate of absorption for snorting and eating drugs of abuse and why
Snort - slow absorption - mucus membrane of nasal sinuses
eat - very slow absorption - GI tract
What is the rate of absorption for smoking and injecting drugs of abuse and why
Smoke - Rapid absorption as it can return to the left atria/ventricle rapidly to be projected to the brain
Inject - rapid absorption - Must return to the heart and be projected to the pulmonary system first before then being returned to the heart and subsequently brain
What are the types of drugs of abuse and give examples of each
Narcotics/painkillers - heroin
Depressants - alcohol, benzodiazepines, barbiturates
Stimulants - cocaine, amphetamine, caffeine, metamphetamine
Miscellaneous - cannabis, ecstasy
What is the dosing of cannabis
150mg THC 300mg THC (hashish oil)
Describe the oral route of administration for cannabis
5-15%
Delayed onset/slow absorption
First pass metabolism
Describe the inhalation route of administration for cannabis
25-35%
50% of a drug will be exhaled out while the remainder of the drug must travel deep into the lungs
Describe the pharmacokinetics of cannabis in fat
Slowly accumulates in poorly perfused/less vascularised fatty tissues
Fatty acid conjugates therefore build up in fatty tissue, resulting in concentration ratios between fat and plasma of up to 104 : 1. THC and its hydroxy metabolites (fatty acid conjugates of 11-OH-THC)
Describe the relationship between plasma cannabinoid concentration and degree of intoxication
Poor correlation between plasma cannabinoid concentration and degree
of intoxication
Plasma cannabinoid concentration does not give any indication of THC in fat, in the bile or in the gut
Describe the elimination of cannabis
In the liver, GIT and urine
Liver - 11-hydroxy-THC - more potent
GIT - 65%, bile + enterohepatic recycling
Urine - 25%
How long after smoking a cannabis cigarette will the effects persist in the body?
Can persist in the blood for 30 days
Half life of 7 days in tissue
Which receptors are involved in cannabis action
CB1 -hippocampus/cerebellum/cerebral cortex/basal ganglia
CB2 - immune cells
Describe the CB1 and CB2 receptors
G-protein (i/o) coupled receptors that are negatively coupled to adenylate cyclase
Identify the ‘reward’ pathways in the brain activated by cannabis
- CB1 stimulated by cannabis
- Slowing of activity of the GABA interneurone to VTA
- VTA -> NAcc at a higher rate
- Dopamine release
What are the pharmacodynamic effects of cannabis and the areas which are involved in these
Psychosis, schizophrenia Food intake (hypothalamus) Memory loss (limbic) Psychomotor performance (cerebral cortex)
What are the peripheral effects of cannabis
Immunosuppressant
Tachycardia/vasodilation -> conjunctivae
What are the effects of cannabis on food intake
Positive effect on orexigenic neurones in the lateral hypothalamus
- Presynaptic inhibition of GABA increases MCH neuronal activity
- Increased orexin
production
What are the immunosuppressant effects of cannabis
CB2 receptors are found on immune cells so cannabis causes depressing of activity B cells T cells NK cells M cells Macrophages
Explain why cannabis causes psychosis and schizophrenia
Hypoactivity of the anterior cingulate cortex (ACC)
What is the function of the anterior cingulate cortex (ACC)
Involved with performance monitoring with behavioural adjustment in order to avoid losses
Error Detection
When are CB1 receptors unregulated and where
Liver and adipose tissue
Multiple sclerosis/pain/stroke – regulatory (good)
Fertility/obesity - pathology (contributes to development)
What is the onset of cannabis -
Seconds to minutes
What is cannabis Sativex and what is it used for
Δ9-THC + CBD
Analgesic
Symptom improvement
MS
What is Donabinol and nabilone and what is it used for
-Δ9-THC
Stimulates appetite in AIDS patients and those who have undergone chemo
Prevents feelings of nausea
What is anandamide
endogenous cannabinoid with binds to the receptors
Describe the expression of CB1 receptors in the medulla and explain its relevance
Low CB1 receptor expression in the medulla.
The medulla is where the cardiorespiratory control resides. Cannabis is not capable of suppressing cardiorespiratory control
What is rimonabant used for
Blocks the effects of the cannabinoid
Anti-obesity
