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Brain's Receptors Sensitive To Pot May 'Open Door' In Treating Drug Dependence, Brain Disorders

Science Daily, May 7, 2006

A team of Johns Hopkins researchers developed a new radiotracer—a radioactive substance that can be traced in the body—to visualize and quantify the brain’s cannabinoid receptors by positron emission tomography (PET), opening a door to the development of new medications to treat drug dependence, obesity, depression, schizophrenia, Parkinson’s disease and Tourette syndrome.

Discovery of the [11C]JHU75528 radioligand, a radioactive biochemical substance that is used to study the receptor systems of the brain, “opens an avenue for noninvasive study of central cannabinoid (CB1) receptors in the human and animal brain,” explained Andrew Horti, assistant professor of radiology at Johns Hopkins Medicine, Baltimore, Md. He explained that there is evidence that CB1 receptors play an essential role in many disorders including schizophrenia, depression and motor function disorders. “Quantitative imaging of the central CB1 using PET could provide a great opportunity for the development of cannabinergic medications and for studying the role of CB1 in these disorders,” added the co-author of “PET Imaging of Cerebral Cannabinoid CB1 Receptors with [11C]JHU75528.”

Cannabinoid receptors are proteins on the surface of brain cells; they are most dense in brain regions involved with thinking and memory, attention and control of movement. The effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. “Blocking CB1 receptors presents the possibility of developing new, emerging medications for treatment of obesity and drug dependence including alcoholism, tobacco and marijuana smoking,” said Horti.

The usefulness of in vivo (in the body) radioligands for studying cerebral receptors by PET depends on the image quality, and a good PET radiotracer must display a high level of specific receptor binding and low non-specific binding (binding with other proteins, cell membranes, etc.), said Horti. “If the non-specific binding is too high and specific binding is too low, the PET images become too ‘noisy’ for quantitative measurements,” he noted. “We developed a PET radiotracer with a unique combination of good CB1 binding affinity and relatively low non-specific binding in mice and baboon brains,” he added. “Previously developed PET radioligands for imaging of CB1 receptors were not suitable for quantitative imaging due to the high level of image ‘noise,’” he added.

“Even though PET methodology was developed 30 years ago, its application for studying cerebral receptors is limited due to the lack of suitable radioligands,” said Horti. “Development of [11C]JHU75528 will allow noninvasive research of CB1 receptor,” he added, indicating that Johns Hopkins researchers need to complete various safety studies and obtain Food and Drug Administration approval before [11C]JHU75528 can be used for PET imaging in people.

“This discovery would not have been possible without involvement of many highly qualified researchers, including the teams of Robert Dannals and Dean Wong and support of Richard Wahl, director of the nuclear medicine department,” said Horti.

Abstract: A.G. Horti, H. Fan, H.T. Ravert, J. Hilton, A. Kumar, M. Alexander, A. Rahmim, H. Kuwabara, D.F. Wong and R.F. Dannals; Radiology, Johns Hopkins Medicine, Baltimore, Md., “PET Imaging of Cerebral Cannabinoid CB1 Receptors With [11C]JHU75528, SNM’s 53rd Annual Meeting June 3–7, Scientific Paper 387.