How Cannabis and Alcohol Induce a Depressant Effect Flashcards
Identify potential drug targets for alcohol & cannabis and discuss the difficulties associated with predicting these drugs' effect on the brain Evaluate how the major toxic effects associated with alcohol & cannabis are produced and discuss the comparative toxicity of the two drugs
What is the drug target for cannabis? How does it function?
The cannabinoid receptor which is a G protein receptor negatively coupled (Gi/o) to adenylate cyclase. This receptor decreases activity activity within the cell, and this is a classic effect of depressants. THC is an agonist. The most common endogenous agonist is anandamide.
What are the drug targets of alcohol?
Alcohol does not have any specific drug target but it can induce weak effects on multiple targets. Alcohol can bind to one of the binding sites on the opioid receptor.
What are some of the effects of alcohol at some of its targets?
Is an agonist for GABA (inhibitory) receptor. Is an antagonist for NMDA (excitatory) receptor and for calcium channels (excitatory). It has weak affinity and efficacy for these targets, so need more alcohol to produce effects.
What are the effects of alcohol and cannabis and how do they produce them?
Most of the effects of alcohol and cannabis are produced in the brain which makes their mechanisms very hard to determine. Also, alcohol acts on many targets. Alcohol and cannabis have the common effect of inducing memory loss and impairing psychomotor performance.
How do cannabis and alcohol induce memory loss?
Cannabis activates cannabinoid receptors on the mitochondria within the dentate nucleus which leads to the impaired formation of memories. Alcohol’s mechanism of inducing memory loss is unknown because it has many targets.
How do cannabis and alcohol induce psychomotor performance?
Basal ganglia, cerebral cortex, cerebellum are involved in psychomotor performance. Cannabinoid receptors are all present in these areas but it’s unknown which area is most important. Alcohol’s target is almost impossible to determine.
What is the most serious toxic effect of alcohol? How does it happen?
Respiratory depression. Could lead to suffocation. The respiratory rhythm is generated in the medulla and it is unclear which target is responsible for the depression, most likely opioid.
How does alcohol induce liver damage? Describe the steps
Alcohol and aldehyde dehydrogenase use NAD+ as a cofactor leading to increased NADH. Impairs B-oxidation of fatty acids –> fatty liver.
In chronic alcohol intake, cytochrome P450 system upregulated and it leaks oxygen radicals. If the production exceeds cellular defence, mitochondria get damaged and inflamed due to oxidative stress.
Acetaldehyde build up leads to enzyme activity decrease and hepatocyte death
This all results in hepatitis. Fibroblasts replace lost hepatocytes with connective tissue and metabolic capacity decrease –> cirrhosis
What is psychosis and how does cannabis use lead to it?
Psychosis is the inability to display appropriate behaviour in a given context. We need to changeour behaviour to adapt to different environments to avoid loss. The anterior cingulate cortex has a role in this - but cannabis’ link is less well known. It’s thought to depress this region of the brain.
