Lecture 25- Opiates and Weed Flashcards
Major medical use- Opiates
Pain relief
- Pain control without loss of consciousness
- NSAIDs (ex. ibuprofen) not as effective as opioids, sometimes not enough for severe pain
- Heroin is Schedule 1 drug… some opioids that are just as addictive or potentially worse are acceptable to use
Major medical use- Opiates
End-Stage Cancer
- tolerance not as concerning
- administration w low-dose Naltrexone
Major medical use- Opiates
Other ways opiates can help medically
- diarrhea- severe
- cough (dextromethorphan)- sold over the coutner in cough syrups
- Opiod use disorder- methadone and buprenorphine
Is heroin/opiod analgesics lethal?
- relatively safe- organs not damaged, destroyed, or threatened by even a lifetime of narcotic addiction
- concern is related to rise in use of opioids in the last decade
What makes heroin/opioid analgesics dangerous?
- Small therapeutic window (small ratio between effective dose and lethal dose)
- Toxic substances often used to dilute
- Often taken with other misused drugs- synergistic actions can contribute to the overdose deaths
- unstable levels of tolerance
What is the point of replacement therapy?
- to use different opiod with different PK to help cravings/withdrawal
- these will not get the person high
Replacement Therapy
Methadone
- a tool-not the answer
- doses are individualized
- Methadone clinics in China-ppl w opioid use disorder cdan go to a clinic daily to get methadone
What does methadone increase?
abstinence rates
What does methadone decrease?
- Crime rates
- HIV rates
- mortality
Replacement therapy
Buprenorphine (Suboxone)
- Some of the best qualities of both Methadone and Naloxone
- partial agonist/antagonist
- lowers withdrawal and craving effects
- only produces partial opioid effect
Heroin at receptor
full agonist
Buprenorphine (Suboxone) at receptor
- partial agonist (blocks the receptor but does not work/fit 100%)
Naloxone (Narcan) at receptor level
- antagonist
- fits into receptor but does not produce an effect- prevents an effect from occuring
- overall, reverses effects of opioids
Cannabis Sativa plant info
- translates to “intoxicant” in Portuguese
- Marijuana- leafy portion
- Hashish- dust/resin for protecting the plant
Marijuana Earliest uses
- Stone age (10,000 years ago): pots and household items made from cannabis fibers
- Shen Nung (mythical Emperor, 2800 BC)- used for sedation, analgesia, illness, evil spirits, psychoactive effects (purportedly used medically)
Early use internationally
India
- weed spread to surrounding countries including india
- India used for religious uses- included as a sacred plant in one of oldest Hinduism books
Early use internationally
Middle east and North Africa
- Hashish identified around 900 AD
- speed up childbirth
Early use internationally
Western civilization (1800s)
- Medical applications
- Rheumatism, pain, rabies, convulsions, cholera, neuralgia, gout rheumnatism, hysteria, depression, insanity, stomach pain, discomfort, restlessness, coughs, asthma
Early use internationally
Mental Illness
- Dr. Jacques Moreau believed marijuana could be used for mental illness
- “The Hashish Club” in France- descriptions of effects written by Theophile Gautier
Marijuana Tax Act of 1937
- Government an media trying to advertise and suggest that marijuana use led to people doing awful things like murdering family members
- “Reefer Madness”-movie in 1930s anti-marijuana
LaGuardia Committee Report
- Multidisciplinary experts started to investigate if the terrible effects of weed use were actually true
- Found marijuant not to particularly harmful w/ no association to aggresssion, violence, and belligerence, contrary to media depictions
- Did note: mental confusion, excited delirium, laughter, and anxiety
US National Academy of Science
- Found that weed can be used as pain treatment, nausea, vomiting, and appetite stimulation
What are some reasons people use weed?
- To relax
- pain relief
- for fun
- to be social
- to be creative
- to improve sex
- to sleep
- etc.
Percieved risk and marijuana use
- As perceived risk has decreased, past year use has increased
Absoprtion- what ways do people take in weed?
- ingested in liquid/food form in India centuries ago- slow PK
- leaves can be chewed
- smoking (most common), quickest absorption is through lungs (smoked or vaped)
What ways do people smoke weed?
- joint: cigarette form
- blunt: emptied out cigar w some tobacco effects
- vapor: water pipes/bongs/electronic devices
Absorption- time
- peak effect is in around 30 minutes
- Effects last around 2-4 hours
Factors that influence marijuana absorption
- cannabis potency
- time smoke is in lungs
- only around 20% of active ingredient in joint is absorbed
Weed- ADMET- Distribution
- Highly lipid-soluble (lipid-philic)
- Gets trapped (deposited) in various fatty tissues throughout the body, making it detectable for long time periods
- Certain compounds still detectable even if blood levels are 0!!
Weed- ADMET- Metabolism
- by liver and other organs
- into less active products
Weed- ADMET- Elimination
- slowly through feces/urine (1/2 live is around 1 week)
- some metabolites detected up to 30 days following single use- in urine for several weeks following chronic use
chemical makeup
How many unique compounds are in weed?
> 400 individual unique compounds in the plant
chemical makeup
Cannabinoids
- > 60 compounds in weed grouped as cannabinoids
- Delta-9-tetrahydrocannabinol (THC) is primary psychoactive compound
- Other cannabinboids (cannabidiol and cannabinol) can produce effects but are not psychoactive on their own
THC isolation
- delta-9-tetrahydrocannabinol isolated in 1964 in Israel by Drs. Gaoni and Mechoulam
Chemical makeup
Potency
- highly variable
- Highest in Sinsemilla (seedless)- around 10-30% thc
- lower in US grown- 8-10% now (but around 2% in 1980)
- concentration has risen over decades
Chemical makeup
Hash oil (processed)
- more potent than marijuana foliage
- upwards of 60% but typically around 20%
Cannabinoid receptor type 1 (CB1)
- mainly found in CNS (hippocampus, cerebellum, and cerebrum)
- metabotropic
Cannabinoid receptor type 2
- CB2
- mainly found in periphery/immune system (spleen, tonsillar, and immune cells)
Endocannabinoids
- Endogenous cannabinoids: anandamide (“bliss”), 2-arachidonoyl-glycerol (2-AG)
- fatty acids
- synthesized postsynaptically
- cannabinoid receptors are found presynaptically
- retrograde transmission
