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See Inside Scientific American Mind Volume 24, Issue 5

Nasal Sprays Offer Therapy With a Sniff

Nasal sprays may open the door for new medications
Nasal passage illustration



Jim Kopp

Snorting chemicals has a bad rap. But as a method of drug delivery, it may be on the verge of a renaissance. Unlike medications taken orally, intravenously or otherwise, those sniffed up the nose gain direct access to the brain. Recent findings that intranasal administration is indeed safe and effective—and a revamped delivery system more elegant than a rolled-up twenty—have inspired a new appreciation of the sniff. Below we list a few of the drugs that researchers are experimenting with, including molecules of new shapes and sizes as well as novel uses of medications developed decades ago.

The secret to the nose's potential lies in the nerve fibers embedded in its tissue. The nasal cavity houses the endings of nerves that connect to the brain stem and olfactory bulb. Chemicals traveling through or alongside these fibers can bypass the intimidating blood brain barrier. Consisting of tight cellular junctions, this barrier prevents most molecules in the bloodstream from reaching the brain. The barrier keeps pathogens out; however, it also limits the types of medications used to treat brain disorders. Intranasal delivery thus opens the door to entire new classes of therapeutic molecules—or even therapeutic cells.

Oxytocin

  • What it is: Oxytocin is a hormone and neuromodulator associated with romantic and familial bonding and trust.
  • Intranasal effects: Early research suggests oxytocin therapy may reduce social deficits in individuals with autism spectrum disorder, social phobia and schizophrenia. For instance, in a study of 13 individuals with autism, intranasal oxytocin treatment was associated with increased sociability during a game of catch. Animal studies indicate that intranasal oxytocin may also ease symptoms of alcohol withdrawal in moderately dependent users and reduce food intake and enhance metabolism in the context of obesity.
  • Status: Efficacy studies have yielded inconsistent results. Researchers are currently investigating whether the genotypes of patients can explain the variability in how they respond to treatment.

Insulin

  • What it is: Secreted by the pancreas, insulin circulates throughout the body, facilitating the absorption of glucose (cellular energy) from the blood. Like cells in other parts of the body, neurons use the glucose that insulin provides as fuel.
  • Intranasal effects: Researchers are aggressively pursuing this medication to manage Alzheimer's disease and mild cognitive impairment. In a study of 33 patients with Alzheimer's, intranasal insulin therapy led to improvements of verbal memory. Theoretically, insulin could also treat a number of neurological and psychiatric disorders, such as schizophrenia, bipolar disorder and post-traumatic stress disorder.
  • Status: The first large-scale multicenter studies will commence this year. Pending results from these trials, intranasal insulin could be available to Alzheimer's patients as early as 2017.

Ketamine

  • What it is: Ketamine, a tranquilizer and illicit party drug, interacts with the brain's glutamate pathway, which mediates learning, memory and mood [see “Is Ketamine the Next Big Depression Drug?,” by Simone Grimm and Milan Scheidegger; Scientific American Mind, May/June 2013].
  • Intranasal effects: Research on intravenous ketamine suggests the drug may offer hope for patients not responding to conventional antidepressants. In a study of 26 individuals with treatment-resistant depression, a single dose of ketamine appeared to significantly reduce suicidal thoughts. Investigators are hopeful that intranasal delivery will provide equal—if not better—outcomes.
  • Status: Johnson & Johnson is currently testing the safety and efficacy of intranasal esketamine, a lab-created chemical twin, and hopes to bring the drug to market by 2017.

This article was originally published with the title "A Sniff of Therapy."

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