New Pressurized Olfactory Device shows direct CNS effect of morphine

A simple new approach to nasal drug administration may allow morphine and other strong pain medications to be targeted directly to the central nervous system (CNS), reports an experimental study in the September issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

John D. Hoekman, Ph.D., and Rodney J.Y. Ho, Ph/D., of University of Washington, Seattle, developed and tested a new "pressurized olfactory device" (POD) in experimental animals. A similar technique used in humans might provide an effective, noninvasive technique for opioid drug administration, with the potential for excellent pain control with fewer side effects and a faster onset of action.

Drs. Hoekman and Ho designed the POD to deliver morphine (or other drugs) with pinpoint precision directly to the olfactory region of the nasal cavity. The olfactory region is small and difficult to reach—it makes up no more than ten percent of the surface area of the human nasal cavity, and can only be accessed through a one- to two-millimeter slit in the back of the nasal cavity. However, its location between the nose and the brain makes the olfactory region an attractive target for drugs targeting the CNS.

Experiments in rats showed significantly enhanced effects of morphine delivered through the POD. Unlike other methods of drug administration, the POD showed evidence of a direct "nose-to-CNS" transport mechanism.

With POD injection, 38 to 55 percent of the total morphine dose was directly transported to the CNS. This provided a greater pain-relieving effect, without increasing the morphine concentration in the blood.

Experiments also showed promising results with POD delivery of another powerful analgesic drug called fentanyl. Administered via the POD, fentanyl achieved a faster and more intense pain-relieving effect, compared to a simple nasal spray.

Opioid drugs such as morphine and fentanyl are widely used for pain control—for example, after surgery or for treatment of severe cancer pain. Although very effective, these drugs have some potential side effects and other disadvantages. For example, morphine can cause problems with constipation, while fentanyl may act too slowly for optimal treatment of "breakthrough" cancer pain.

It's not a new discovery that delivering drugs to the olfactory region can have a direct "nose-to-CNS" effect. However, this method of administration is infrequently used—largely because there's no simple and convenient way to administer medications directly to the olfactory region.

So far, the POD is just a preliminary concept—it has yet to be tested in humans. However, the promising results suggest that a similar device for direct "nose-to-CNS" drug delivery might provide a simple new approach to maximizing the response to morphine and fentanyl, while avoiding disadvantages like side effects and delays to pain relief.

"Intranasal delivery of drugs to the CNS bypasses the barrier of the systemic circulation as well as the blood-brain barrier," comments Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia & Analgesia.

'There may be benefits of administering opioids intranasally, but the rapid pain relief has to be balanced against the risks inherit with a rapid onset of respiratory depression."

Although the POD concept is relatively simple, it could lead to the development of new types of pain medications, Dr. Shafer believes. "This technology is particularly exciting with molecules such as small peptides and biologic agents, which are so rapidly destroyed in the blood that they are ineffective if given orally or intravenously. Intranasal delivery may create an opportunity for the introduction of entirely new classes of pain killers that could not be effectively administered by traditional methods."