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
what is the role of ACC
anterior cingulate cortex
- Involved with performance monitoring with behavioural adjustment in order to avoid losses
- Hypoactivity in cannabis users
Role of ACC - In changing environments we constantly need to adapt our behaviour by detecting and focusing on the goal-relevant information and selecting the most appropriate behaviour. For example, consider the ability to drive a car while simultaneously engaging in a discussion with a passenger. If we enter a narrow mountain road and a heavy storm breaks out, we might feel the need to discontinue our conversation in order to better focus our cognitive resources on safe driving.
pharmacodynamics- food intake
Positive effect on orexigenic neurones in lateral hypothalamus
- Presynaptic inhibition of GABA increases MCH neuronal activity
- Increased orexin
production
ALSO has immunosuppressant effects
central effects of cannabis summarised
Psychosis, Schizophrenia!!
Food intake – Hypothalamus
Memory loss – Limbic regions (Amnestic effects/↓ BDNF)
Psychomotor performance – Cerebral cortex
peripheral effects of cannabis summarised
Immunosuppressant
Tachycardia/vasodilation
(Conjunctivae!)
Medulla – Low CB1 receptor expression
Medulla – Low CB1 receptor expression
Why is this important?
cardio-respiratory control decreases
leads to cardio-resp failure
when do you get increase in regulation of CB receptors
- regulation of CB receptors;
Multiple sclerosis/pain/stroke – regulatory
Fertility/obesity - pathology
Endocannabinoids and CB1 receptors are up-regulated in the liver and adipose tissue in various forms of experimental as well as in human obesity. An up-regulation of CB1 receptors has been also reported in adipose tissue of genetically obese compared with lean mice, and elevated endocannabinoid levels have been detected in adipose tissue of obese compared with lean patients.
what is dronabinol used for?
Dronabinol is used to treat nausea and vomiting caused by chemotherapy in people who have already taken other medications to treat this type of nausea and vomiting without good results. Dronabinol is also used to treat loss of appetite and weight loss in people who have acquired immunodeficiency syndrome (AIDS).
what is savitex used for?
Sativex is indicated as treatment for symptom improvement in adult patients with moderate to severe
drugs that increase CB receptor stimulation
‘Autoprotection’
dronabinol
nabilone
savitex
