Week 12: Cannabinoids & Psychedelics Flashcards
Main psychoactive substance of cannabis
9-tetrahydrocannabinol (9-THC)
Marijuana absorption rate through inhalation
- Peak = almost instantaneous
- Lungs –> absorbed through bloodstream
- Duration = 4 hrs
Marijuana absorption rate through mouth
- Peak = ~30-mins to 2 hrs
- ~30% absorbed/metabolized
- Slow absorption = slower effects
- Duration = 8 hrs
Endocannabinoids
- Endogenous (derived internally) NTs that activate cannabinoid receptors
PRIMARY ENDOCANNABINOIDS
- Anadamide
- 2-archidonoyl-glycerol (@-AG)
Retrograde NTs
Postsynaptic cell produces & releases into synapse
- Binds to presynaptic
CB1 receptor targets
MOSTLY CNS
- Motor activity
- Thinking
- Motor coordination
- Appetite
- Short term memory
- Pain perception
- Immune cells
CB2 receptor targets
MOSTLY PNS
- Gut
- Kidneys
- Pancreas
- Skeletal muscle
- Bone
- Eye
- Tumours
- Reproductive system
- Immune system
- Skin
- Cardiovascular system
- Liver
Cannabinoid receptor agonists
- Mimic actions of endocannabinoids/THC
- Evoke same reduction in inhibitory currents caused by depolarization-induced suppression of inhibition
- Depolarization-induced suppression of inhibition could be prevented by cannabinoid receptor antagonists
Cannabinoid receptors are ______ receptors
G-protein-coupled
CB1 receptor activity
- Activated by AEA and 2-AG
- Inhibits: cAMP accumulation, voltage-gated Ca+ channels, K+ channels, NT release in presynaptic excitatory & inhibitory synapses
CB1 receptors are largely _______
Pre-synaptic
CB1 receptor activation leads to _____ dopamine concentrations in the ____ ______
Increased; nucleus accumbens
- High CB1 agonist = increase dopamine in nucleus accumbens
- Decrease CB1 antagonist = decrease glutamate in nucleus accumbens
Reduced ___ ___ occurs in CB1 receptor knock-out mice
Reduced food
Behavioural effects of cannabinoids
- Mild memory deficits
- Lower activity in hippocampus and DLPFC (dorsolateral)
- Impair motor coordination and muscle tone
Long-term cannabis use
- Lower hippocampus and DLPFC activity (linked to memory)
- Decrease concentrations of acetylcholine and GABA in hippocampus
- Glutamate neurons from the hippocampus release less glutamate in structures
Subjective effects
- Buzz, high, stoned
- Fater passage of time
- Suspiciousness and paranoia (changes in PFC = less synaptic density/efficiency)
- Apathy, lethargy
- Effortful task seem less effortful
Cannabis and drug-discrimination procedures
- Only 9-THC produced 9-THC appropriate responding
Exposure to cannabinoids is known to result in ____ _____
CB1R downregulation = lower lvls of CB1 expression)
Medical uses of cannabis
- Autoimmune disease, cancer, epilepsy, glaucoma, neuropathic pain, unhealthy weight loss
Psychedelic drugs
- Induce reality-altering experience, consisting of hallucinations, sensory distortions, delusions
Hallucinogens
- LSD, psilocybin, mescaline, and dimethyltryptamine
- True: Perception of images/sounds that aren’t real
- Pseudo-hallucinations: Altered perception of things that are real
Absorption of LSD
- Normally orally (ex. paper holds acid & absorbed into mouth)
- Peak after ~60 mins
- Cells in liver metabolize LSD –> 2-oxo-3-hydroxy-LSD
- Last 6-12 hrs
- Half-life of 3 hrs
LSD pharmacodyanmics
- Activates both 5-HT1A and 5-HT2A receptors in visual cortex = modify visual processes
- Increased glutamate release through 5-HT2A activation
Brain activity w/ LSD
- Visual cortex became more active w/ rest of brain
- Blood flow to visual regions increased (believed to be correlated w/ hallucinations)
Default mode network (DMN)
Network interacting brain regions that is active when a person isn’t focused on the outside world
