Cannabis - Neurochemistry
- psychoactive component of the plant are buds (weed) and resin (hash)
- Tetrahydrocannabinol (THC) acts on specific cannabis receptors of the naturally occuring endocannabinoid system
What is special about Cannabis?
It has it’s own neurotransmitter system know as the endocannabinoid system
Endocannabinoid System
regulates appetite, pain sensation, mood and memory via endocannabinoids
Cannabis - Effects
- makes user feel relaxed, more sociable & talkative
- may distort time & space
- sometimes causes paranoia
Cannabis - Benefits
- useful against MS, spasms, pain, tremor, glaucoma, anorexia (or cancer patients)
Cannabis - Harms
- mostly associated with smoking which always causes harm
- 10% of users dependent
- Withdrawal: mood changes, decreased appetite, insomnia, loss of motivation and lack of enjoyment
Cannabis - Routes of use
- Spraying - medical use, least harmful
- Eating - slow onset (up to 4hrs) thus easy to OD
- Inhaling - healthier than smoking, allows deeper breaths which leads to more intoxication
- Smoking - most harmful, same risk as tobacco
Cannabis - Skunk
- increased THC levels, less cannabidiol (CBD)
Cannabis - Legalize it or nah?
Pro: less harmful than alcohol, anxiolytic, useful medication
Con: addiction, withdrawal, existing correlation between regular use and memory impairment
Article - Pharmacology of Cannabis - Kinetics (Smoking)
THC rapidly absorbed, enters bloodstream & reaches brain within minutes
Article - Pharmacology of Cannabis - Kinetics (Oral)
- has to pass metabolism in liver first (only 25-30% effectiveness of same dose smoked)
- onset delayed, longer duration due to continued absorption from the gut
- once absorbed rapidly distributed to other tissues
- very lipid -> accumulates in fatty tissues -> peak concentration reached in 4-5 days, full elimination up to 30 days
Article - Pharmacology of Cannabis - Metabolism
- metabolized in liver (11-hydroxy-THC)
- partly excreted in urine, mainly reabsorbed in gut room
Article - Pharmacology of Cannabis - Dynamics/Neurochemistry
- interacts with endogenous cannabinoid receptors CB1 (neuronal) and CB2 (spleen, immune cells)
- CB1: distributed across cerebral cortex, limbic areas, basal ganglia, cerebellum, thalamus, brainstem
- THC releases dopamine from nucleus accumbens & prefrontal cortex
What is psilocybin?
- main psychoactive component in shrooms, part of tryptamine/indolamine hallucinogens, structurally related to serotonin
- 45 times less potent than LSD
Psilocybin - Dynamics/Neurochemistry
- psilocybin & psilocin work as agonists on 5-HT (especially 5-HT2A -> responsible for hallucinogenic effects) receptors
- Psilocin: primarily on 5-HT2A where it mimics effect of serotonin
- Psilocin: indirectly increases dopamine in the basal ganglia
Psilocybin - Kinetics
- dephosphorylated to Psilocin in intestinal mucosa, max. plasma levels achieved after 85-105 minutes
- Psilocin distributed to all tissues, excreted within 6hrs
- highest levels of psilocin detected in neocortex, hippocampus, and extrapyramidal motor system and reticular formation
Psilocybin - Effects
In animals:
- high doses led to atypical behavior (backward walking)
In humans:
- psychedelic effects occur at 15mg+
Doses:
1. drowsiness, emphasize preexisting mood
2. altered state of consciousness
3. change in perception (body image, time, visuals), impaired attention, anxiety or ecstatic (varies greatly)
Psilocybin - Risks
- very low toxicity
- high risk if no experience
- set & setting important
- prolonged psychosis (48hrs) but rare, associated with personality predisposition
What are psychedelics?
- “mind manifesting”
- LSD, khat, ibogaine, ayahuasca, Psilocybin
- drugs with hallucinogenic, perception-altering effects
How do Psychedelics work? (Neurochemistry)
- primarily target/stimulate a subtype of the 5-HT (serotonin) receptor
empathogenic
produces sensations of care, love, and empathy
“Default mode”
- moderates “housekeeping” functions = memory, self-reflective thought, sense of self
- Psilocybin disrupts this mode thus disrupting sense of self
Set
What you bring to it, state of mind, previous experience, expectations
Setting
Environment where drug is consumed, familiar or novel, friends or strangers, indoors or outdoors
