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Research Team Finds How CBD, a Component in Marijuana, Works Within Cells

The findings published in the Journal of Biological Chemistry could provide a new basis for developing CBD-based treatments for pediatric epilepsy

Newswise — STONY BROOK, N.Y., February 11, 2015 – A team of Stony Brook University researchers have identified fatty acid binding proteins (FABPs) as intracellular transporters for two ingredients in marijuana, THC and CBD (cannabidiol). The finding, published early online in the Journal of Biological Chemistry, is significant because it helps explain how CBD works within the cells. Recent clinical findings have shown that CBD may help reduce seizures and could be a potential new medicine to treat pediatric treatment-resistant epilepsy.

CBD differs from THC in that it is not psychoactive and does not bind to cannabinoid receptors. Some children who are resistant to conventional antiepileptic drugs have been reported to show improvement with oral CBD treatment. The Stony Brook research team found that three brain FABPs carry THC and CBD from the cell membrane to the interior of the cell. This action enabled them to conduct experiments inhibiting FABPs and thereby reducing anandamide breakdown inside the cells.

“Anandamide, an endocannabinoid, has been shown to have neuroprotective effects against seizures in basic research studies and this may turn out to be a key mechanism of seizure control,” explained Dale Deutsch, PhD, Professor of Biochemistry and Cell Biology and a faculty member of the Institute of Chemical Biology and Drug Discovery at Stony Brook University. “Therefore by CBD inhibiting FABPs, we could potentially raise the levels of anandamide in the brain’s synapses.”

The findings in the paper, titled “Fatty Acid Binding Proteins are Intracellular Carriers for THC and CBD,” stem from the team’s research that spans five years and includes their discoveries that showed anandamide levels were raised in rodent brains using novel drugs targeted to FABPs. In 2013, they received a $3.8 million grant from the National Institute on Drug Abuse, part of the National Institutes of Health (NIH), to target endocannabinoid transporters to develop drugs for pain and inflammation.

The current research involving FABPs as transporters of CBD involves the work of faculty and students from several Stony Brook Departments. The team includes four Professors – Dr. Deutsch, Martin Kaczocha (Anesthesiology), Iwao Ojima (Chemistry and the Institute of Chemical Biology and Drug Discovery), and Stella Tsirka (Pharmacological Sciences). The team also features a post-doctoral fellow (Jeremy Miyauchi in Pharmacological Sciences), a researcher who recently received his PhD (William Berger in Chemistry), a graduate student Matthew Elmes, a research technician Liqun Wang, and undergraduate students Brian Ralph, Kwan-Knok Leung, and Joseph Sweeney, all from the Department of Biochemistry and Cell Biology.

More States Move Forward With CBD-Only Measures, But Will They Help Patients

Lawmakers in Alabama and Utah recently approved legislation seeking to authorize the physician-supervised use of varieties of cannabis and/or extracts high in the non-psychotropic cannabinoid cannabidiol (CBD). Both measures, which I previously summarized as ‘largely unworkable,‘ have now been signed into law.

In recent days, lawmakers in three additional states — Kentucky, Mississippi, and Wisconsin — have similarly signed off on CBD-explicit legislation. These measures are now awaiting signatures from each states’ respective Governors.

Similar to Alabama’s SB 174 (aka ‘Carley’s Law), which only permits the use of CBD by prescription during the course of an FDA-approved clinical trial, the pending Kentucky and Wisconsin bills may also be classified as ‘research-centric’ measures. Kentucky’s SB 124 permits physicians “practicing at a hospital or associated clinic affiliated with a Kentucky public university” to “dispense” cannabidiol during the course of an FDA-approved clinical trial. Wisconsin’s AB 726 similarly limits those who may legally dispense CBD to only include those physicians who have obtained an FDA-issued investigational drug permit to prescribe it. In Tennessee, lawmakers are also close to finalizing similar language (included in HB 2461 and SB 2531) that seeks to allow university clinical researchers to “manufacture” and “dispense” high-CBD cannabis oil “as part of a clinical research study on the treatment of intractable seizures.” (By contrast, separate, broader medical cannabis measures seeking to authorize the use of the whole plant failed this year in all three states.)

As I’ve previously written here and here, it is unlikely that specific changes in state law will stimulate these type of proposed clinical trials from taking place in these states any time soon. Because CBD is acknowledged by federal regulators to be classified as a schedule I prohibited substance, multiple federal agencies — including the FDA, DEA, NIDA (US National Institute of Drug Abuse), and PHS (Public Health Service) must all sign off on any clinical investigation of the cannabinoid — a process that typically takes several years. A keyword search of FDA-approved clinical trials using the terms “cannabidiol” and “United States” yields fewer than ten ongoing human trials involving CBD — less than half of which are assessing its potential therapeutic application. (Two additional safety trials assessing the use of GW Pharmaceutical’s patented high-CBD formulation Epidiolex in children with severe epilepsy are also ongoing.)

Unlike the above-mentioned measures, Mississippi’s HB 1231, does not seek to encourage state-sponsored clinical trials. Rather, the measure exempts specific high-CBD formulated oils “that contain more than fifteen percent cannabidiol [and] … no more than one-half of one percent of tetrahydrocannabinol” from the state’s definition of a schedule I prohibited substance. However, like Utah’s HB 105 (aka ‘Charlee’s Law), Mississippi’s pending law does not provide guidance as to where patients could legally obtain such extracts. Though such high-CBD products are presently available in a limited number of medical cannabis states (such as in California and Colorado), these extracts are typically only available to in-state residents who possess authorization from a physician licensed to practice in that state. (Although Colorado state law also allows for a recreational cannabis market, which may be legally accessed by out-of-state residents, at present time such high-CBD concentrates are seldom available at retail outlets.)

Additional cannabidiol-specific measures also remain pending in Florida and South Carolina, among other states. NORML will report on these measures as they progress and we will continue to express caution in regards to their practical utility for those patients who require immediate access to whole-plant cannabis and its variety of naturally-occurring compounds.

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