Lecture 25- Opiates and Weed

Question 1

Major medical use- Opiates

Pain relief

Answer 1

• 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

Question 2

Major medical use- Opiates

End-Stage Cancer

Answer 2

• tolerance not as concerning
• administration w low-dose Naltrexone

Question 3

Major medical use- Opiates

Other ways opiates can help medically

Answer 3

• diarrhea- severe
• cough (dextromethorphan)- sold over the coutner in cough syrups
• Opiod use disorder- methadone and buprenorphine

Question 4

Is heroin/opiod analgesics lethal?

Answer 4

• 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

Question 5

What makes heroin/opioid analgesics dangerous?

Answer 5

• 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

Question 6

What is the point of replacement therapy?

Answer 6

• to use different opiod with different PK to help cravings/withdrawal
• these will not get the person high

Question 7

Replacement Therapy

Methadone

Answer 7

• 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

Question 8

What does methadone increase?

Answer 8

abstinence rates

Question 9

What does methadone decrease?

Answer 9

• Crime rates
• HIV rates
• mortality

Question 10

Replacement therapy

Buprenorphine (Suboxone)

Answer 10

• Some of the best qualities of both Methadone and Naloxone
• partial agonist/antagonist
• lowers withdrawal and craving effects
• only produces partial opioid effect

Question 11

Heroin at receptor

Answer 11

full agonist

Question 12

Buprenorphine (Suboxone) at receptor

Answer 12

• partial agonist (blocks the receptor but does not work/fit 100%)

Question 13

Naloxone (Narcan) at receptor level

Answer 13

• antagonist
• fits into receptor but does not produce an effect- prevents an effect from occuring
• overall, reverses effects of opioids

Question 14

Cannabis Sativa plant info

Answer 14

• translates to “intoxicant” in Portuguese
• Marijuana- leafy portion
• Hashish- dust/resin for protecting the plant

Question 15

Marijuana Earliest uses

Answer 15

• 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)

Question 16

Early use internationally

India

Answer 16

• weed spread to surrounding countries including india
• India used for religious uses- included as a sacred plant in one of oldest Hinduism books

Question 17

Early use internationally

Middle east and North Africa

Answer 17

• Hashish identified around 900 AD
• speed up childbirth

Question 18

Early use internationally

Western civilization (1800s)

Answer 18

• Medical applications
• Rheumatism, pain, rabies, convulsions, cholera, neuralgia, gout rheumnatism, hysteria, depression, insanity, stomach pain, discomfort, restlessness, coughs, asthma

Question 19

Early use internationally

Mental Illness

Answer 19

• Dr. Jacques Moreau believed marijuana could be used for mental illness
• “The Hashish Club” in France- descriptions of effects written by Theophile Gautier

Question 20

Marijuana Tax Act of 1937

Answer 20

• 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

Question 21

LaGuardia Committee Report

Answer 21

• 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

Question 22

US National Academy of Science

Answer 22

• Found that weed can be used as pain treatment, nausea, vomiting, and appetite stimulation

Question 23

What are some reasons people use weed?

Answer 23

• To relax
• pain relief
• for fun
• to be social
• to be creative
• to improve sex
• to sleep
• etc.

Question 24

Percieved risk and marijuana use

Answer 24

• As perceived risk has decreased, past year use has increased

Question 25

Absoprtion- what ways do people take in weed?

Answer 25

• 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)

Question 26

What ways do people smoke weed?

Answer 26

• joint: cigarette form
• blunt: emptied out cigar w some tobacco effects
• vapor: water pipes/bongs/electronic devices

Question 27

Absorption- time

Answer 27

• peak effect is in around 30 minutes
• Effects last around 2-4 hours

Question 28

Factors that influence marijuana absorption

Answer 28

• cannabis potency
• time smoke is in lungs
• only around 20% of active ingredient in joint is absorbed

Question 29

Weed- ADMET- Distribution

Answer 29

• 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!!

Question 30

Weed- ADMET- Metabolism

Answer 30

• by liver and other organs
• into less active products

Question 31

Weed- ADMET- Elimination

Answer 31

• 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

Question 32

chemical makeup

How many unique compounds are in weed?

Answer 32

> 400 individual unique compounds in the plant

Question 33

chemical makeup

Cannabinoids

Answer 33

• > 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

Question 34

THC isolation

Answer 34

• delta-9-tetrahydrocannabinol isolated in 1964 in Israel by Drs. Gaoni and Mechoulam

Question 35

Chemical makeup

Potency

Answer 35

• 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

Question 36

Chemical makeup

Hash oil (processed)

Answer 36

• more potent than marijuana foliage
• upwards of 60% but typically around 20%

Question 37

Cannabinoid receptor type 1 (CB1)

Answer 37

• mainly found in CNS (hippocampus, cerebellum, and cerebrum)
• metabotropic

Question 38

Cannabinoid receptor type 2

Answer 38

• CB2
• mainly found in periphery/immune system (spleen, tonsillar, and immune cells)

Question 39

Endocannabinoids

Answer 39

• Endogenous cannabinoids: anandamide (“bliss”), 2-arachidonoyl-glycerol (2-AG)
• fatty acids
• synthesized postsynaptically
• cannabinoid receptors are found presynaptically
• retrograde transmission