The Fentanyl Crisis

Opioid Overdose Crisis

• Approximately 70,000 individuals die annually from opioid overdoses
• Oxycodone was a major culprit in the early 2000s, particularly the drug OxyContin
• Fentanyl surpassed OxyContin and heroin around 2013 and became central to the opioid epidemic

Causes of the Fentanyl Crisis

• Greedy pharmaceutical companies contribute to the crisis
• Healthcare providers inappropriately prescribe opioids
• There's an influx of illegal fentanyl from China, Mexico, and India
• Fentanyl get's disguised as legitimate medications like Xanax or Adderall and trafficked in the U.S. and other countries
• The strength of fentanyl is 50 times that of heroin and 100 times that of morphine
• A dose of just two milligrams of fentanyl can be fatal
• Dependence and accidental overdoses from fentanyl are rapidly increasing

Legitimate Uses of Fentanyl

• Opiates are natural components of the sap of the opium poppy
• Opiates include morphine and codeine
• Opioids is an umbrella term for natural and synthetic components that bind to opioid receptors in the body
• Opioids include natural opiates, semi-synthetic opioids like heroin, and synthetic opioids like fentanyl
• The body creates its own opioids, called endogenous opioids, that bind to opioid receptors
• Endorphins are endogenous opioids

How Pain is Processed

• A pain signal travels from a sensory neuron in the affected area to the spinal cord
• The sensory neuron synapses with a secondary neuron in the spinal cord
• The secondary neuron carries the signal to the thalamus in the brain
• The thalamus directs the signal to the primary somatosensory cortex, where the pain is perceived
• The thalamus also sends a signal to the amygdala, which processes negative emotions associated with the pain
• The brain has a descending pathway that reduces pain through endogenous opioids
• The thalamus sends a signal to the periaqueductal gray in the midbrain
• The signal travels down the brainstem to the spinal cord, where it modulates pain signals by secreting endogenous opioids

Neurotransmitters and Opioids

• Neurons communicate through neurotransmitters, including glutamate and GABA
• Glutamate is an excitatory neurotransmitter
• GABA is an inhibitory neurotransmitter
• Glutamate stimulates a signal while GABA inhibits a signal
• Opioids can modulate synaptic signals through opioid receptors

Opioid Receptors

• The Mu receptor is most studied and preferred by fentanyl
• Fentanyl will bind to any of the three receptors (Mu, Delta, and Kappa)
• Opioid receptors are found throughout the body in varying densities
• Mu receptors are primarily in the digestive system, which explains constipation issues with opioid use
• In the nervous system, Mu receptors are in the substantia gelatinosa of the spinal cord and in the brainstem
• The hypothalamus is also affected
• Mu receptors in the cerebral cortex are associated with pain processing

Addiction and the Mesolimbic Pathway

• The mesolimbic pathway involves the ventral tegmental area (VTA) in the midbrain communicating with the nucleus accumbens
• The VTA secretes GABA to the nucleus accumbens
• The nucleus accumbens secretes dopamine
• Opioids bind to Mu receptors in the VTA, stopping GABA secretion, resulting in high dopamine release
• This dopamine release leads to the euphoric and pleasurable feelings associated with opioid use
• Over time, more of the substance is needed to produce the same effect, which is the basis of addiction

Dangers of Fentanyl

• Fentanyl is 100 times more powerful than morphine, and possibly 400 times more
• There are synthetic opioids stronger than fentanyl being sold illegally
• Fentanyl is used in specific medical circumstances to treat severe pain, such as cancer pain
• Anesthesiologists use fentanyl for surgeries and epidurals
• Overdoses are easy to occur due to the drug's potency

Respiratory Depression and Overdose

• Opioids affect the respiratory system in the brainstem and hypothalamus
• The body monitors carbon dioxide levels and triggers breathing reflexes
• Opioid overdose saturates the system and impairs the body's ability to compensate
• Respiratory depression causes death, because the person is unable to breathe

Naloxone (Narcan) as a Treatment

• Naloxone (Narcan) can reverse an opioid overdose
• Naloxone binds to opioid receptors, preventing fentanyl and other opioids from accessing them
• Naloxone allows the person to breathe again, but causes immediate withdrawal

Withdrawal Symptoms

• Opioid withdrawal is extremely uncomfortable
• Nerve pain increases because the body is accustomed to the absence of pain signals due to opioid use
• Neurons become highly sensitive, so even light touch can be painful
• Withdrawal symptoms are intensified in response to naxolone or narcan