Glutamate antagonists: the answer for opioid dependence?

In 3400 BC, the Sumerians first cultivated the opium poppy plant. Since its discovery, opiates have been used medicinally to relieve pain, and more recently, to suppress coughing in patients with a “dry cough”. However, as with most pharmaceuticals, negative side effects exist to the continuous use of opiates: tolerance and dependence. The physical and psychological dependence that results from opiate use adversely impacts society. These factors make it dangerous for physicians to loosely prescribe opiates to patients (although this does not mean it doesn’t happen).
For many years, dopamine has been the focus for scientists when researching the effects of addictive drugs, though more recently, this focus has transitioned to include glutamate’s (another excitatory neurotransmitter) role in drug addiction. Glutamate exaggerates the withdrawal symptoms of opioid dependence by binding its receptors, specifically ionotropic receptors.
Learning point: There are two functionally different types of receptors that bind neurotransmitters: ionotropic and metabotropic. Ionotropic receptors are channels themselves and open in response to a neurotransmitter (i.e. glutamate). This causes an influx of ions (ionotropic) that either excites or inhibits the cell, depending on the ion moving through the channel. Metabotropic receptors are much slower than ionotropic receptors and act more indirectly in the cell. A series of proteins and second messengers interact with each other to signal a cascade of events in response to a neurotransmitter binding a metabotropic receptor.
Accumulating evidence shows that antagonists of ionotropic receptors (iGluRs) can attenuate the withdrawal symptoms of opioid dependence. One specific antagonist of interest to scientists is called MK-801. It is a glutamate antagonist that acts on NMDA receptors and protects against excitotoxicity (excessive stimulation of the neuron). Researchers are hopeful that MK-801 could suppress the psychotropic effects of prescription opiates. This is of great importance to researchers as it offers a potential way to decrease the negative side effects of opiate use. What a difference it would make if taking prescription opiates did not lead to dependence and moreover, illegal activity. Illegal activity? It is not uncommon for patients to sell their prescription drugs, such as morphine or codeine, to dependent users for a little extra cash. This is because those who are addicted to prescription opiates crave the drug due to its psychotropic effects and the withdrawal symptoms the person feels in the absence of the drug.
The ability to prescribe opiate analgesics (pain relievers) without the addictive effects (or any of the unnecessary side effects for that matter) is ideal. The illicit sale of opiates would significantly go down if this were possible. Of course, there would always be a black market sale of opiates, but at least users would not be able to obtain the drug so easily. Furthermore, the number of users addicted to opiates would drop considerably as the only people who would be addicted to opiates would be those who acquired opiates via the black market.
It is of upmost importance that scientists continue to investigate the use of glutamate antagonists as a means to subdue the negative effects associated with opiate use. It would be in the best interest of everybody to continue research in this arena. Patients would be safer, doctors would be relieved of the pressure to prescribe opiates, the community would become safer, and the stigma of prescription opiates would eventually be diminished.