Topic 26: Cannabis Flashcards
What is Cannabis sativa?
species of flowering shrub indigenous to central Asia
3 subspecies: C. sativa sativa, C. sativa indicus, C. sativa ruderalis
long history of cultivation for production of hemp fiber and as an herbal/recreational drug
hemp fibre historically used for rope, cloth, and paper
hemp seeds cultivated for food and oil content
psychoactive effects due to presence of chemicals termed cannabinoids
What is the history of cannabis use?
cultivation for fibre documented from 8000 BCE: the first evidence of paper making was from hemp fibre
documented medical and religious use in China from 2700 BCE
recreational use of hashish became popular in the Middle East: introduced to Europe by Napoleonic soldiers returning from Egypt
production of fibre in North America was extensive until 1950’s
What is the history of cannabis regulation in Canada?
regulation was highly sensationalized
in Canada marijuana was outlawed proactively in 1923
first seizure of cannabis by police in Canada was not until 1937
What is the contemporary recreational use for cannabis?
easily the most popular illicit drug in North America: most common psychoactive drug after caffeine, alcohol, and nicotine
lifetime use ~50%
past-year use ~10%
highest rates of use among 15-24 year olds
law enforcement cost attributable to cannabis ~$500 million
What is the contemporary medical use for cannabis?
legal for medical use in Canada since 2001
regulated use suitable for end-of-life care for symptoms associated with terminal disease: chronic pain, anorexia, nausea, arthritis, seizures
multiple sclerosis, spinal cord injury/disease, cancer, HIV/AIDS, epilepsy
What is the legality of cannabis worldwide?
enforcement has been often compared to alcohol prohibition: similar arguments made for prohibition of alcohol and cannabis
Canada - partial legalization & regulation (Oct 2018)
USA - 10 states since 2012, controlled substance federally
What are the psychoactive effects of cannabis?
cannabis contains more than 85 psychoactive cannabinoids, of which two are most prominent
THC is the principal psychoactive component and is responsible for euphoric and antiemetic effects
cannabidiol is 2nd major cannabinoid and is responsible for relaxation and anxiolytic effects of cannabis
both are present as inactive carboxylated prodrugs that are converted by heating
How is cannabis prepared?
marijuana generally refers to the cannabinoid-rich flowering “buds”
cannabinoids are generally thought to be defensive chemical to discourage predation
cannabinoids are enriched in specialized structures on the flowering bodies known as trichomes
marijuana < 25% THC (w/w)
What is hashish?
hashish (hash, hash oil) is produced from trichromes (kief)
increased cannabinoid content Hash is a solid pressed cake of trichomes (50-90% THC)
hash oil is an alcohol extract of trichomes reduced to a viscous liquid
What is the pharmacology of cannabis?
cannabinoids are typically administrated by inhalation (smoking) or orally (e.g. baked goods)
inhalation: rapid entry to bloodstream, recovery of ~20% of THC content
oral administration: slow, prolonged, but variable uptake, much less efficient due to breakdown in GI, slow absorption, and first-pass metabolism
oral administration results in less absorption but prolonged elevation of THC in blood due to sustained absorption over time
What is the distribution of cannabis?
cannabinoids are lipid-soluble and cross the BBB
rapid uptake into blood paradoxically does not lead to rapid uptake into brain
onset of psychoactive effects is delayed by 5-30 minutes (longer for oral administration)
cannabinoids effects are attenuated primarily due to absorption into fat tissues: psychoactive effects last ~3 hours
What is the metabolism and excretion of cannabis?
THC is metabolized in the liver by cytochrome P450 enzymes
primarily metabolite is 11-hydroxy THC (11-OH-THC, psychoactive)
secondary inactive metabolite is 11-nor-9-carboxy THC (THC-COOH)
half-life of THC is very long: 20-30 hours: slow elimination is exacerbated by release from lipid stores
11-OH-THC and THC-COOH are excreted unmodified in feces (60% total excretion)
glucuronic acid esters of THC-COOH are also excreted in urine (~20% total excretion)
due to slow release from lipid store THC metabolites can be detected for weeks after a single dose
What is a caveat to studying the psychoactive and physiological effects of cannabis in animal models?
current research models (animal and human) typically involve administration of a single cannabinoid (THC or CBD)
availability and consistency of cannabis first argument of researchers
ethics limit administration methods (e.g. respiratory risks of smoking)
limits the generalizability of findings
in animal models administration is usually IV for practical reasons: IV administration of cannabinoids is effectively unheard of, limits the validity of findings
Who was Jacque-Joseph Moreau?
father of psychopharmacology
introduced hashish to French literary society
What are the subjective effects of cannabis?
low to moderate doses
initial light-headedness or dizzyness (“buzz”)
euphoria and exhilaration: disinhibition, increased laughter
calm, relaxed, dreamlike state (“stoned”): relaxation most common self-reported effect, drowsiness, promotes sedentary behavior, sensory reactions such as floating sensation, enhanced visual and auditory perception, visual illusions, slowing of the passage of time