Transcript - ISpatula

ADDICTION
Cannabinoid
Professor Suleiman Olimat
What is addiction?
(Latin) addictus---attached to something,
positive. Today alcoholism called a “brain
disease”or bad habit or sin. Leading
assumption of the text: Addiction is the
key, not the substance or behavior
Addiction defined by researchers as “a bad
habit,” “a brain disease,” “helplessness,”
“a problem of motivation”
Definitions
Addiction—pattern of compulsive use.
Has physical, psychological, social aspects.
Emphasis on process rather than outcome.
The Diagnostic and Statistical Manual of Mental
Disorders (DSM (
Changes to DSM in new edition: no longer dichotomy
between abuse and dependence
Addiction now the preferred term instead of
dependence.
Addiction now seen as a continuum.
Substance use disorder requires 2 of following:
tolerance
withdrawal problems
use more than intended
reduced involvement
inability to stop
excessive spending or effort
to obtain
continued use
The question is often asked: Why would anyone addict to
drugs?
Research has shown that people generally take
drugs to either feel good (i.e., sensation
seekers, or anyone wanting to experiment
with feeling high or feeling different) or to feel
better (i.e., self-medicators, or individuals who
take drugs in an attempt to cope with difficult
problems or situations, including stress,
trauma, and/or to lessen anxiety, fears,
depression, or hopelessness).
Why people taking Drugs?
Why Do People Take Drugs in The First Place?
They like what it does to their brains
To Feel Good
To Feel Better
Image courtesy: Vivian Felsen
From being an addict to being a poet.
Dependence
Physical Dependence: Withdrawal of
drug produces physical symptoms.
Body needs the drug for normal
physiological function
Psychological Dependence: Cravings
for a drug, overcome by the desire to
have a drug.
Cannabinoid
Structure of THC and
synthetic analogs
Lipophilic side chain
Most potent
analog: 100s
times more
potent than THC
Commonly used terms
• Cannabis is the preferred general term.
• Other terms: marijuana, ganga, mull, grass, hash,
pot, weed, dope
• Types of cannabis, in increasing strength
– Leaf << Head << Oil/resin
• Diverse methods of smoking
– joint = cigarette of cannabis, typically 0.5g
– cone: smoked via a water pipe (bong), typically
0.25g
– vaporisers (increased ammonia levels via this
method)
Why do people use cannabis?
• To experience euphoria or perceptual
distortions
• Because others do so
• To relieve mental symptoms
– negative symptoms of schizophrenia
– anxiety
• To relieve physical symptoms
– Eg. nausea, anorexia, cancer & HIV
The Cannabis High Described
Gives sensation of euphoria, relaxation, sexual
arousal.
1sttime users may experience nothing (experts say
they must learn to appreciate the effects)
-Marijuana tends to inhibit aggression and
accentuate caution as opposed to alcohol
-Marijuana causes time expansion (over estimation
of time elapsed)
-Workers say that smoking marijuana help them to
work harder
Typical effects of cannabis
• Mental effects
– Euphoria, relaxation and wellbeing
– Increased appetite (‘munchies’)
– Talkativeness, disinhibition
• Physical effects
– Vasodilator (systemic and portal)
– Bronchodilation (short-term effect only)
• Highly variable
– Many people dislike it and discontinue use
– Influenced by surroundings
Cannabinoid Receptors
G protein-coupled, with seven transmembrane regions
• CB1
Brain, fat cells, liver, duodenum, muscle
• CB2
lymphocytes>macrophages>cytokines
Mode of cannabis action
• Two specific cannabinoid receptors
– CB1 - brain and peripheral tissues
– CB2 - immune system
• Linked to G-proteins with diverse
downstream signalling pathways
• Euphoria results from stimulation of
mesolimbic dopaminergic neurons, like
other drugs of abuse
Cannabinoid CB1 and CB2 Receptors
Characteristics of CB1 and CB2 Receptors
•
•
•
•
•
•
Both densely distributed throughout the body
CB1 highly enriched in central nervous system
Located on axon terminals
Mediate retrograde signaling (Dendrite → Axon)
G-protein coupled
CB2 highly enriched in periphery
– Especially in immune system
• CB2 also in brain and CNS
– Fewer than CB1; ~ Same density as μ opioid
– Nonetheless, CB2s modulate neural signaling
CB1 and CB2
• Here is a picture of a synapse containing the endogenous cannabinoid
system. The CNS contains CB1 receptors and natural neurochemicals such as
anandamide and 2-AG.
• Presynaptic neuron (releasing glutamate or GABA)
• Postsynaptic neuron and receptors
• Glutamate acting on glutamate receptor proteins nested in postsynaptic
membrane
• Presynaptic CB1 receptor - many CB1 receptors appear to be presynaptic.
That is, in many cases this system acts to modulate the release of other
neurotransmitters eg.glutamate. That is, act to inhibit the release of other
neurochemicals.
• A new study published in the prestigious journal Nature has shown that
endogenous cannabinoid are synthesised postsynaptically, when the
postsynaptic cell receives a large influx of calcium ions, and then travel
backwards to act on presynaptic cannabinoid autoreceptors to inhibit the
release of neurotransmitters GABA or glutamate.
Neurotransmitter
Receptor
Influences nt release
Neurotransmitter
Receptor
Post-synaptic
release of
endog.
cannabinoid
Annandamide
(arachidonyl-ethanolamid)
2-Arachidonoyl - glycerol (2AG)
more abundant, less potent
Endocannabinoids
Both Δ9-THC, the
psychoactive
component of Cannabis
sativa, and anandamide,
an endogenous
neurotransmitter in our
brain, bind o the same
cannabinoid receptor
CB1 receptor summary
• Abundantly expressed throughout the brain
• Majority on axons and synaptic terminals
• CB1 activation inhibits synaptic transmission
Endocannabinoids: Bind CB1 > CB 2
Drugs Can be Chemical Imposters
(THC mimics a natural brain chemical)
Brain’s Chemical
Drug
Anandamide
THC
Effects on Reproduction
There is not evidence of long term reproductive problems from cannabis
use, yet hormonal changes do occur.
Males:
• Reduces level of testosterone (still within normal levels)
• Reduces sperm count (10 joints/day, effect disappears when use
stopped)
• Changes in shape and morphology of sperm
• Effects of THC can be estrogen-like producing breast development
(gynecomastia).
Females:
• Reduction in luteinizing hormone, necessary for egg implantation into the
uterus. (Not seen in regular users – implies tolerance).
• Reduction of prolactin levels (associated with increased release of
dopamine in the hypothalamus), effecting lactation.
Effects on Cognition
There is evidence that long term
use may lead to deficits in
learning memory and attention.
However, it is unknown how long
these deficits may persist after
abstinence from the drug.
Significant prior usage may reduce
the adverse cognitive effects of
acute marijuana exposure.
This has led to the hypothesis that
behavioral (“cognitive”) tolerance
develops in heavy marijuana
smokers.
Effects of Heavy Marijuana Use on Attention, Learning, &
Memory in Undergraduates
Researchers compared 65 "heavy users," (smoked a median
of 29 of the past 30 days), and 64 "light users," (smoked a
median of 1 of the past 30 days).
After 19-24 hours of abstinence from marijuana and other illicit
drugs and alcohol, the undergraduates were given several
standard tests measuring aspects of attention, memory, and
learning.
Heavy marijuana users made more errors and had more
difficulty sustaining attention, shifting attention to meet the
demands of changes in the environment, and in registering,
processing, and using information.
However, the question remains open as to whether this
impairment is due to a residue of drug in the brain, a
withdrawal effect from the drug, or a frank neurotoxic effect of
the drug?
A motivational Syndrome.
Recent studies have found that users of
moderate amounts of marijuana show no
personality disturbances, but heavy users were
characterized as suffering from apathy,
dullness, lethargy, and impairment of
judgment.
However, heavy users were defined as people
who smoked 17-200 marijuana cigarettes per
day!
Does marijuana lead to
?
There is evidence that cannabis use is correlated
with degradation in mental health, especially in those
with a predisposition to mental illness. However, it is
uncertain whether cannabis use is a cause,
contributing factor, associated social phenomenon,
or type of self-medication.
In North Africa and India, higher incidence of
psychiatric problems associated with THC are
reported.
Withdrawal Symptoms
Marijuana addiction is also linked to a
withdrawal syndrome that can make it
hard to quit. Symptoms include:
•
•
•
•
•
irritability,
sleeping difficulties,
craving,
anxiety, and
increased aggression.
Warning
Marijuana is illegal in most places
Marijuana is, in general, much less dangerous
than it is made out to be, and certainly less
harmful than legal drugs like tobacco and
alcohol.
It is impossible die from marijuana, unlike most
other illegal drugs and many legal ones.
Most of the supposed scientific evidence for brain
damage, infertility, etc. have been disproven.