Topic 26: Cannabis Flashcards

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1
Q

What is Cannabis sativa?

A

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

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2
Q

What is the history of cannabis use?

A

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

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3
Q

What is the history of cannabis regulation in Canada?

A

regulation was highly sensationalized

in Canada marijuana was outlawed proactively in 1923

first seizure of cannabis by police in Canada was not until 1937

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4
Q

What is the contemporary recreational use for cannabis?

A

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

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5
Q

What is the contemporary medical use for cannabis?

A

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

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6
Q

What is the legality of cannabis worldwide?

A

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

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7
Q

What are the psychoactive effects of cannabis?

A

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

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8
Q

How is cannabis prepared?

A

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)

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9
Q

What is hashish?

A

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

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10
Q

What is the pharmacology of cannabis?

A

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

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11
Q

What is the distribution of cannabis?

A

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

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12
Q

What is the metabolism and excretion of cannabis?

A

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

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13
Q

What is a caveat to studying the psychoactive and physiological effects of cannabis in animal models?

A

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

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14
Q

Who was Jacque-Joseph Moreau?

A

father of psychopharmacology

introduced hashish to French literary society

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15
Q

What are the subjective effects of cannabis?

A

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

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16
Q

What are the physiological effects of cannabis?

A

dilation of small blood vessels in eyes and skin: characteristic red eyes, increased blood flow to the skin, sensation of warm

increased heart rate, decreased blood pressure: may be felt as a pounding heart beat, can cause orthostatic hypotension (dizzyness)/nausea on movement - reinforces tendency to remain sedentary

dry mouth - compulsion to drink

increased appetite - “munchies”

17
Q

What are the adverse effects of cannabis?

A

adverse subjective effects are seen occasionally, often in first-time users (more rare in chronic users)

anxiety or panic associated with feeling of paranoia

delirium or hallucinations extremely rare (but have been documented)

can precipitate psychosis in schizophrenia

hallucinations are a more common occurrence with administration of pure THC or synthetic cannabinoids

common occurrence with some illicit synthetic cannabinoid preparations (Spice, K2)

presence of adulterants can cause hallucinations (e.g., PCP)

headaches reported with increased doses

18
Q

What are the cognitive effects of cannabis?

A

intoxication can result in disordered thinking or speech and inability to remain focused on a topic

no effects on recall of information (previously encoded)

THC administration may impact explicit memory encoding/recall (short-term memory): dose-dependent effect

previous exposure may decrease cognitive effects: “cognitive”/behavioral tolerance

deficits seen in tasks requiring sustained attention

no decrease in simple reaction time measures BUT impairs ability to drive

interaction with alcohol: low dose cannabis use exacerbates the impairment due to alcohol

impairments may relate to attention deficits - impaired ability to attend to peripheral stimuli

19
Q

What are the cognitive effects of cannabis seen in animal models?

A

IV THC admin results in mixed effects on locomotion
low doses: mixed stimulant and depressant effects
high doses: more uniform motor depression, catalepsy (lack of voluntary movement)

administration results in deficits in various learning and memory tasks: radial arm maze, morris water maze, impairment seen with direct intrahippocampal injection of THC

20
Q

What are the therapeutic effects of cannabis?

A

decreases ocular pressure: useful adjunctive therapy for treatment of glaucoma

antiemetic: promoted as treatment for chemotherapy associated nausea

orexigenic: treatment for disease associated anorexia (cancer, HIV/AIDS)

anxiolytic: therapeutic potential for psychiatric illness

anticonvulsant and antipsychotic: especially strains high in CBD

anti-spastic: treatment for spinal injury/disease (MS, TBI, SCI)

analgesic: modulation of pain response

anti-oxidant and neuroprotective: various cannabinoids are antioxidant and neuroprotective against glutamatergic toxicity