Chapter 11 - Marijuana
Cannabis Sativa
hemp plant
source of fiber
marijuana - leafy top portion
hashish - dust of plant resin
used in other cultures and as a drug for centuries
not used as a drug in the US until the early 20th century
History
stone age - used for fiber
2800 BC - used medicinally in China
one of five sacred plants in India
10th & 11th century - spread to Middle East & North Africa
1800s - medical use explored in Great Britain & France
1960s - marijuana becomes popular in Europe
in the New World
hemp raised for fiber in Chile, Virginia, and New England by 1629
some medical use in the 1800s
little recreational use until the 1920s, coincident with Prohibition
smoking marijuana was introduced to the USA in the 1920s
Controlling Marijuana
1920s - lots of use in New Orleans
1927 - Louisiana outlawed possession and sale
1930 - 16 states prohibited marijuana
1937 - nearly all states prohibited marijuana
1937 - marijuana tax act
Committee Reports
1944 - LaGuardia Commission
marijuana use not particularly harmful
produces mental confusion, excitement, laughter, and anxiety
later reports in India, Britain, Canada, & US → similar conclusions
1968 - Baroness Wootton Report (Great Britain)
1972 -
Canadian Govt’s LeDain Commission
Marijuana: A Signal of Misunderstanding (US)
1982 - 9th Report to Congress
1984 - Drug Abuse & Drug Abuse Research
recommendations to approve use for treatment
1988 - Britain’s House of Lords
1999 - US National Academy of Sciences
pain relief, nausea/vomiting, appetite stimulation
2002 - Cannabis: our position for a Canadian Public Policy
amend laws to allow compassionate medical access
license individuals to sell and produce cannabis
amnesty for those convicted of possession under current/past legislation
Epidemiology
most widely used illicit drug
third-most-used recreational drug
Who Uses Marijuana?
most prevalent
young adults
teenagers
men more likely than women
use varies by ethnic group:
Native Americans > Blacks > Whites > Hispanics
fewer people than in the 70s
Marijuana Usage Laws by State
nearly half of states have legalized recreational marijuana use
only about 1 in 10 Americans say marijuana use should not be legal at all
Views on Legalization
can differ by race, ethnicity, age, partisanship
public opinion - uptick 70s-2020s favoring legalization and downturn on making illegal
Cannabis Dispensaries
more concentrated where laws allow medicinal & recreational use
A Gateway?
most marijuana users don’t become heroin addicts
high-school students
alcohol use → marijuana use
90% of crack users previously used marijuana
frequent marijuana users were 140 times more likely to use other illicit drugs
modern research supports a “common risk” model more than a true “gateway model”
Methods of Use
methods of use
eat
drink
chew
smoke
historically
marijuana & hashish were ingested in liquid and food form
people have also chewed marijuana leaves
most common in US today: smoking
very efficient for absorption
variety of methods
Active Ingredients
> 400 chemical compounds
> 60 cannabinoids are unique
delta-9-tetrahydrocannabinol
most effective
other cannabinoids
include cannabidiol and cannabinol
may be biologically active
may modify THC effects
Potency
lower THC content in American-grown marijuana
currently 5-6% THC
hashish shows similar variability
hash oil
concentrated marijuana extract
~20% THC
can contain up to 60%
Pharmacokinetics
absorption
depends most on mode of consumption
smoking
most rapid
onset in minutes
peak levels 30-60 min later
oral ingestion
slower
less efficient
onset in an hour
peak levels 2-3 hours
distribution, metabolism, excretion
concentrated in brain, lungs, kidney, and liver
crosses the placenta
plasma levels of THC decrease quickly
THC deposited in organ tissue, especially those with fatty material
metabolized slowly in liver and other organs
most metabolites excreted in 1 week
some detachable for > 30 days
THC Mechanisms of Action
slows activity of several neurotransmitters
ACH
I-glutamate
GABA
Noradrenalin
Dopamine
Serotonin
enhances activation of movement
facilitates release of serotonin
→ changes in dopamine system
Endogenous THC?
brain receptors: CB1 & CB2
CB1 receptors control memory, cognition, movement, & mood
CB2 receptors are in the immune system
endogenous chemicals acting on CB receptors
anandamide
2-arachiconoyl-glycerol (2-AG)
Tolerance & Dependence
tolerance
clearly present in animal studies
less obvious in humans; inconsistent findings
tolerance is more likely if high doses are taken over a longer time
dependence
some argue that there is no significant withdrawal syndrome
other identify withdrawal syndrome:
sleep disturbance, nausea, irritability, and restlessness
most likely to occur following sustained, heavy use
physical dependence due to social use is rare
most doubted it existed until 1970s
1970-80s
cessation of high, chronic use → withdrawal
~210 mg THC/day
symptoms
irritability, restlessness, decreased appetite, sleep problems, sweating, tremor, nausea, vomiting, & diarrhea
1999
withdrawal seen after 4 days of smoking 4 joints/day
3.1% THC content
mild
most with marijuana dependence abuse other drugs
Physiological Effects
acute effects
bloodshot eyes, sluggish pupils
increased heart rate, blood pressure
decreased movement
high doses: decreased REM sleep
longer-term effects
respiratory
reversible airway obstruction
marijuana delivers more tar and carcinogens than tobacco
no damaging effects on heart of immune system in healthy users
reproduction
decreased sperm & motility
nonovulatory menstrual cycles
risk of premature birth, lower birth weight, shorter baby body length
risk of childhood cancer & ADHD
Psychological Effects
behavioral
decreased movement
increased talkativeness
feelings of relaxation
impaired driving ability
cognitive effects
impaired short-term memory
decreased ability to concentrate
perception that time passes more slowly
emotional effects
improved mood
intensity of euphoria is dose-related
negative feelings are common
social/environmental effects
doesn’t enhance social skills
doesn’t cause increased aggression
probably doesn’t account for amotivational syndrome
Therapeutic Uses
brief therapeutic use history
Shen Nung
childbirth
1800s
mental illness, rheumatism, pain, rabies, cholera
1930s: in over-the-counter medicines
stomach pain, restlessness, coughing
currently, synthetic THC:
Dronabinol (Marinol)
Nabilone (Cesamet)
Sativex (oral spray)
synthetics do not give rapid effect of smoking marijuana
current medical uses
nausea & vomiting due to cancer therapy
Cachexia (weight loss, muscle loss, and inflammation even when eating is normal)
Glaucoma (but limited evidence it actually reduced intraocular pressure)
Therapeutic Uses - 2017 Report
2017 National Academies of Sciences report supports use of marijuana for:
substantial evidence of effectiveness
reducing chronic pain in adults
antiemetic for chemotherapy-induced nausea and vomiting
improving multiple sclerosis (MS) spasticity symptoms
moderate evidence of effectiveness
improving short-term sleep outcomes in various sleep disturbances
limited evidence of effectiveness for
increasing appetite and decreasing weight loss associated with HIV/AIDS
improving clinician-measured MS spasticity symptoms
improving symptoms of Tourette syndrome
improving anxiety symptoms in social anxiety disorders
improving symptoms of PTSD
report also indicated that conclusions fo rmedical use are often based on limited data
state laws that allow medical use could facilitate future research
regulatory barriers, including schedule I classification, impede research
May 2024: DEA issued notice of proposed rulemaking indicating FDA intends to transfer marijuana from Schedule I to Schedule III