Addiction

The Biochemical Phenomenon of Opioid Addiction

As previously mentioned, natural opioids are produced in the pituitary gland and interact with neurons in the ventral tegmental area of the brain. These neurons normally produce gamma aminobutyric acid (GABA) molecules that interact with neighboring dopamine producing neurons. Then, GABA inhibits these dopamine producing neurons from producing and releasing dopamine. However, when opioids bind with the opioid receptors on those GABA producing neurons, GABA production is stopped. This allows dopamine to be released. Therefore, the more opioid molecules that opioid receptors interact with, the more likely it is for GABA production to be inhibited and allow for a greater release of dopamine. Large doses of synthetic opioids, such as fentanyl or oxycodone, are extremely effective in inhibiting GABA production. When these synthetic opioids are taken in large doses over a long period of time, the opioid receptors begin working in overdrive and lead to GABA being continually suppressed. Due to this, GABA producing neurons must find a way to maintain GABA production. An example of this is carrying out the downregulation of opioid receptor genes, such as OPRM1. Downregulation of this gene will cause transcription and translation to be interfered with, and prevent the production of opioid receptors. Over time, this would lead to fewer OPRM1 receptors on GABA producing neurons. There is some evidence that OPRM1 receptor proteins are still made, but that cellular processes interfere with those receptors being integrated into the neuron cell membrane. There is other evidence that suggests the receptor proteins are made and integrated into the neuron cell membrane, but they are inhibited from the inside of the GABA producing neurons so that they can’t transmit a signal as effectively to halt GABA production.

Chronic Opioid Use

With chronic opioid use, the fewer fully functioning opioid receptor proteins on GABA producing neurons makes it harder to suppress GABA. Thus, making it harder to achieve dopamine responses. Therefore, due to this reduced capacity of opioid receptors, individuals with opioid use disorder have to take larger doses of synthetic opioids to achieve the same effects. Furthermore, when synthetic opioid use is stopped completely, you are only left with damaged OPRM1 receptor proteins that are unable to get a signal from our natural opioids for dopamine production.