Mechanisms of Opioid

Addiction
Aisha Shahzad
Review: What is Pain?
● Pain is defined as any sensory or emotional
experience associated with a stimulus that has
the potential to cause tissue damage.
● The sensory response to these harmful stimuli
are collectively called Nociception
○ During this process, specific nociceptors work to trigger
action potentials that will aid in multiple pain pathways:
■ Spinothalamic - Spinal cord → Thalamus →
https://masteringpaininstitute.com/how-pain-works/
Somatosensory Cortex
■ Trigeminal - Sensation concerning face and brain
■ Among many others!
How do Opioids Treat Pain?
Within the Spinothalamic Pain Pathway:

● Pain processing is directionally bilateral:

■ Ascending Pathway
● Site of injury → Spinothalamic Tract →
Thalamus → SMS Cortex
■ Descending Pathway
● Midbrain → Medulla → Release of
Serotonin/Noradrenaline → Inhibition of
Substance P → Stimulate Enkephalin
○ This causes an analgesic effect
● Opioids are known to bind to enkephalins and https://www.spinal-research.org/collaborative-research-neuropathic-pain

therefore prolong serotonin and noradrenaline

release at the site of injury.
○ Enkephalins are present in many areas of the brain!
What is Addiction?
● Biological… and Psychological?
○ Addiction is defined as intense drug craving and compulsive use.
● In the DSM 5, categorized as a mental illness and brain disease.
● In the absence of pain, opioids are still capable of triggering the
release of neurotransmitters.
● When opioids interact with mu opioid receptors, cells in the VTA
produce dopamine.
○ Normally, the prefrontal cortex advises against decisions that
overload this reward system, such as eating too much junk food.
■ This feature is notably compromised in individuals who are
addicted to opioid use.
● Repeated exposure to opioids therefore operates such that the
brain works abnormally in absence of the drug, and functions
normally in its presence.
Mechanisms of Opioid Addiction
● Dependence - The compulsion to continue use of a substance in order to
avoid symptoms of withdrawal.
● Tolerance - The compulsion of needing higher doses of opioids to achieve
the same effect.
○ Opium receptors in the brain become desensitized to the drug over time
● Withdrawal - Must take place after tolerance does, occurs after a few
weeks of heavy dosing.
○ Symptoms include:
■ Jitters
■ Anxiety
■ Muscle Cramps
■ Diarrhea
Locus Coeruleus and Symptoms of Withdrawal
● The Locus Coeruleus (LC) is the site of
noradrenaline synthesis.
○ Distribution of this neurotransmitter allows for stable
blood pressure, even breathing, and general alertness.
■ When opioid molecules bind to mu receptors in the
LC, they inhibit noradrenaline, resulting in lethargy,
slowed respiration, and low blood pressure.
■ Repeated exposure to opioids results in the LC
producing more NA to compensate
● Therefore, when opioids are present, they are
able to retain NA levels throughout the body
● During withdrawal, NA levels are much higher
than normal, resulting in jitters and anxiety,
Lucemyra Treatment for Withdrawal
● Lofexidine Hydrochloride
○ An oral pill and was recently approved by the FDA.
○ Groundbreaking in that it is the first treatment for
opioid abuse that is not an opioid in itself.
○ A 14 day treatment that aids in relieving the
symptoms of Opioid use withdrawal.
■ It does this by reducing the release noradrenaline from
the LC, resulting in less feelings of anxiousness, etc.
■ In theory, the lack of withdrawal symptoms will lead
those afflicted to no longer feel a dependency on the
drug.
● In addition, patients will become more susceptible
to lower levels of opioid use following treatment
with Lucemyra.
Cognitive Deficit Model
● The Prefrontal Cortex
○ The PFC is responsible for higher level cognition and reasoning. It limits our desires by
sending inhibitory signals to the VTA dopamine neurotransmitters in the mesolimbic
reward system.
● The Cognitive Deficit Model
○ Theorizes that individuals who develop addictive disorders have abnormalities in the PFC.
■ As a result, the afflicted have a reduced ability to use better judgement or to
restrain themselves from further abuse.
■ This model is consistent with the fact that addiction is common amongst those
diagnosed with asocial personality disorder
● Which is characterized by deficits in the prefrontal cortex.
Some Final Thoughts…
● Opioids are very helpful when used correctly - they revolutionized
modern medicine and post surgical pain.
○ They are only harmful when abused and so should be carefully
regulated by a professional!
● Stigma - Those addicted to opioids are not inherently bad or addictive,
○ Addiction is a mental illness and anyone can be afflicted by it!
● Although some demographics are more susceptible than others,
addiction can happen to anyone in any form.
○ The only accountability an individual afflicted with addiction has is seeking
professional guidance.
■ Seeking treatment is essential to return to a healthy, sustainable lifestyle!
Thank You!
Any Questions?