Drug abuse 1 Flashcards
Why are they abused?
All these drugs cause euphoria: rewarding feeling: mediated by the reward pathway (dopaminergic). MESOLIMBIC DOPAMINE SYSTEM
Dopaminergic neurone projects from the ventral tegmental area. Nucleus Accumbens (ventral striatum) - dopamine is released into this area.
Rewarding stimulus activates the dopaminergic neurone in the VTA
What are the route of administration?
- ‘Snort’: intranasal
- ‘Eat’: oral
- ‘Smoke’: inhalation
- ‘Inject’ - intravenous
Describe the speed of absorption for all the different routes of administration.
Snort’ – Mucous membranes of nasal sinuses –> diffuses into the venous drainage. Slow absorption
‘Eat’ – Gastrointestinal tract
Very slow absorption
‘Smoke’ – Small airways and alveoli. Rapid absorption. This is the fastest route of administration to get to the brain. If you get deep enough in the lungs the alveoli have a very thin wall making it very easy for it to diffuse across into the venous system. From there the drug then has to travel less distance compared to a normal IV injection.
‘Inject’ – Veins
Rapid absorption
Order of ascending order for onset of euphoria
Oral < Intranasal < Intravenous < Inhalational
What are the classifications of drug abuse?
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 (has deppressent + hallucinogenic effects), Ecstasy (MDMA)
Describe cannabis
Cannabis/marijuana - cannabis compounds found in very high concentrations in the trichomes (glandular hairs)
Hash oil - solvent extract
> 400 compounds in the plant - >60 cannabinoids
Two major cannabinoids:
delta9-tetrahydrocannabinol (delta9-THC) - most potent cannabinoid (causes positive effects at low dose)
It is also is responsible for the negative effects of cannabis (feeling low) especially at high dose.
Cannabidiol - Don’t really know what it does
Describe the how the dosing has changed?Pharmacokinetics
60’s + 70’s: ‘Reefer’ – 10mg THC
21st Century: ‘Skunkweed/Netherweed’
- 150mg THC - 300mg THC (+ hashish oil)
Levels of THC has been increasing.
This is relevant and a concern because the dose relationship of THC is closely associated with negative symptoms. This is true for the positive effects as well but not to the same degree.
What are the two major routes of administration of cannabis?
Eaten or smoked
Oral – 5-15%
delayed onset/slow absorption
first pass metabolism –> then into the blood stream
Inhalation – 25-35% (usually only half the drug you inhale gets into the lungs. Then only a small portion get deep into the lungs)
You can have the same affects if you just adjust the dose.
Describe the pharmacokinetics of cannabinoids
FAT:
They are very lipid soluble –> they will accumulate in your fatty tissue very well.
Slowly accumulates in poorly perfused fatty tissues. Fatty tissue doesn’t have a good blood supply that’s why it is slow.
Chronic cannabis users can have a cannbanoid ratio of 10^4:1 fatty tissue vs plasma. As a result you get a slow leak back.
LIVER:
The metabolites of cannibanoids are even more potent: active metabolite produced
Liver - 11-hydroxy-THC
GIT:
The body will try to excrete the cannabinoid as bile - enterohepatic recycling. Because cannabinoids are so lipid soluble they will just get reabsorbed in the gut back into the blood stream.
As a result there is poor correlation between plasma cannabinoid concentration and degree of intoxication. Problem in chronic users of cannabis.
Where do cannabinoids target?
There are endogenous receptors: cannabinoid receptors (G-protein coupled). Remember cannabis is a depressor –> The receptor decreases adenlyate cyclase
CB1 receptors
Hippocampus/cerebellum/
cerebral cortex/basal ganglia
CB2 receptors
Immune cells
See slides for diagram - endogenous cannabinoid = anandamide
How does cannabis cause euphoria? (Pharmacodynamics)
GABA NT - inhibits the reward pathway. When you stimulate the CB1 receptor it suppresses (depresses the firing rate of) the GABA neurone. Remember cannabis is depressor. Therefore there is increased activation of these dopaminergic neurones
Process of dysinhibiton
What are the side effects of cannabis?
Psychosis, Schizophrenia
Hypoactivity in cannabis users - which may link psychosis and schizophrenia
The Anterior Cingulate Cortex (ACC):
Involved in error detection. E.g see slide. It says green but its written in red.
Involved with performance monitoring with behavioural adjustment in order to avoid losses. 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.
Describe the pharmacodynamics of cannabis related to food intake?
Cannabis has a positive effect on food intake. Three regions of the hypothalamus.
Arcuate nucleus - responds to peripheral signals. There are neurones that are anabolic (increase feeding) and neurones that are catabolic (inhibit feeding)
Ventromedial hypothalamus - inhibition of feeding.
Lateral hypothalamus - increases feeding.
Cannabis acts at the lateral hypothalamus to increase the feeding drive.
1) Pre-synaptic inhibition of GABA neurones increases MCH neuronal activity
2) Increase orexin production (orexin regulates appetite)
Together they promote feeding behaviour
Describe the pharmacodynamics of cannabis related to immunity?
Cannabis is an immunosuppressant - antiinflammatory
Depresses a bunch of immune cells
Summarise the pharmacodynamic effects of cannabis?
Psychosis, Schizophrenia!
Food intake – Hypothalamus
Memory loss – Limbic regions (Amnestic effects/↓ BDNF)
Psychomotor performance – Cerebral cortex
Summarise the peripheral effects of cannabis?
Immunosuppressant
Tachycardia/vasodilation
(Conjunctivae!)
Medulla (cardiorespiratory control centre) – Low CB1 receptor expression. This means its very difficult to overdose on cannabis. Whereas opiods and anaesthetics will suppress the medulla resulting in a shut down in cardiorespiratory system.
