Brain imaging insight into cannabis as a pain killer

December 20, 2012

Science Daily/University of Oxford

The pain relief offered by cannabis varies greatly between individuals, a brain imaging study carried out at the University of Oxford suggests.

The researchers found that an oral tablet of THC, the psychoactive ingredient in cannabis, tended to make the experience of pain more bearable, rather than actually reduce the intensity of the pain.

MRI brain imaging showed reduced activity in key areas of the brain that substantiated the pain relief the study participants experienced.

'We have revealed new information about the neural basis of cannabis-induced pain relief,' says Dr Michael Lee of Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB).

He adds: 'Our small-scale study, in a controlled setting, involved 12 healthy men and only one of many compounds that can be derived from cannabis. That's quite different from doing a study with patients. My view is the findings are of interest scientifically but it remains to see how they impact the debate about use of cannabis-based medicines. Understanding cannabis' effects on clinical outcomes, or the quality of life of those suffering chronic pain, would need research in patients over long time periods.'

The researchers report their findings in the journal Pain. The study was funded by the UK Medical Research Council and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre.

Long-term pain, often without clear cause, is a complex healthcare problem. Different approaches are often needed to help patient manage pain, and can include medications, physiotherapy and other forms of physical therapy, and psychological support. For a few patients, cannabis or cannabis-based medications remain effective when other drugs have failed to control pain, while others report very little effect of the drug on their pain but experience side-effects.

'We know little about cannabis and what aspects of pain it affects, or which people might see benefits over the side-effects or potential harms in the long term. We carried out this study to try and get at what is happening when someone experiences pain relief using cannabis,' says Dr Lee.

The Oxford research team carried out a series of MRI scans with each of the 12 volunteers at the FMRIB centre in Oxford.

Before a scan, participants were given either a 15mg tablet of THC or a placebo. THC, or delta-9-tetrahydrocannabinol, is the active psychotropic compound in cannabis -- the ingredient that's responsible for the high that drives recreational use of the drug.

To induce a certain level of pain, the volunteers also had a cream rubbed into the skin of one leg. This was either a dummy cream or a cream that contained 1% capsaicin, the ingredient of chillis that causes a hot, burning and painful sensation.

Each participant had four MRI tests to cover each combination of THC or placebo, and chilli pain-inducing cream or dummy cream.

'The participants were asked to report the intensity and unpleasantness of the pain: how much it burned and how much it bothered them,' says Dr Lee. 'We found that with THC, on average people didn't report any change in the burn, but the pain bothered them less.'

While this average effect was statistically significant, there was great variability among the participants in THC's effect on the pain they experienced. Only six out of the 12 reported a clear change in how much the pain bothered them, for example.

The brain imaging results substantiate the reports of the participants. The change in unpleasantness of pain was matched with a suppression of activity in the part of the brain called the anterior mid-cingulate cortex. This structure sits in a deep part of the brain and is involved in many functions, and has previously been implicated in the emotional aspects of pain.

There were also changes in activity of the right amygdala that correlated with the lessening in the unpleasantness of the pain with THC. It is already known that the right side of the amygdala can be 'primed' by pain.

Of most interest to the researchers, however, was the strength of the connection in individuals between their right amydala and a part of the cortex called the primary sensorimotor area. The strength of this connection in individual participants correlated well with THC's different effects on the pain that that volunteer experienced.

This is suggestive that there might be a way of predicting who would see benefits from taking cannabis for pain relief.

'We may in future be able to predict who will respond to cannabis, but we would need to do studies in patients with chronic pain over longer time periods,' says Dr Lee.

He adds: 'Cannabis does not seem to act like a conventional pain medicine. Some people respond really well, others not at all, or even poorly. Brain imaging shows little reduction in the brain regions that code for the sensation of pain, which is what we tend to see with drugs like opiates. Instead cannabis appears to mainly affect the emotional reaction to pain in a highly variable way.'

https://www.sciencedaily.com/releases/2012/12/121220195744.htm

Discovery of Mechanism that Processes 'THC' Type Brain Compound May Lead to New Medicines for Pain, Addiction

March 31, 2009

Science Daily/Stony Brook University Medical Center

Dale Deutsch, Ph.D., Professor of Biochemistry and Cell Biology at Stony Brook University and colleagues discovered a new molecular mechanism for the processing of endocannabinoids, brain compounds similar to THC, the active ingredient in marijuana, and essential in physiological processes such as pain, appetite, and memory.

Reported online this week in the Proceedings of the National Academy of Sciences (PNAS), the finding could pave the way for new medicines for pain, addiction, appetite control and other disorders.

Dr. Deutsch and colleagues in the Departments of Biochemistry and Cell Biology (Martin Kaczocha) and Neurobiology and Behavior (Sherrye Glaser, Ph.D.) are the first to successfully identify two known fatty acid binding proteins (FABPs) that carry the endocannabinoid anandamide (AEA), a neurotransmitter, from the cell membrane to interior of the cell where it is destroyed. This identification enabled the research team to inhibit FABPs in various laboratory experiments and thereby reduce AEA breakdown inside cells. In their study, “Identification of intracellular carriers for the endocannabinoid anandamide,” the researchers report that they decreased the breakdown of AEA in some instances by approximately 50 percent.

“Inhibiting FABPs could potentially raise the levels of AEA in the brain’s synapses,” says Dr. Deutsch. “Naturally occurring AEA levels have been shown to curb pain without the negative side effects, such as motor coordination problems, from molecules like THC. Therefore, it makes sense to target AEA for therapeutic purposes.”

He emphasizes that their groundbreaking discovery of the role of FABPs in transporting this class of neurotransmitters may prove to be a crucial step in developing novel drug targets for endocannabinoids by way of inhibiting FABPs. In support of the research, The State University of New York (SUNY) Stony Brook Office of Technology Licensing and Industry Relations (OTLIR) has filed U.S. Patent applications comprising the discovery.

The OTLIR manages all intellectual property matters for the SUNY Research Foundation. In actively marketing this unlicensed technology created by Dr. Deutsch, the Stony Brook OTLIR welcomes commercial entities interested in partnering with the University. The licensing agent for the project is Adam DeRosa of the OTLIR.

The breakdown of AEA requires two factors. First, there needs to be a mechanism for transporting AEA to the location where it is inactivated because AEA is a fatty compound and thus unable to move inside the watery cellular environment. Second, the cell must express an enzyme called FAAH, which controls the breakdown and inactivation of AEA. In the laboratory, the researchers coaxed a nonneuronal cell type (COS-7) to express FAAH. These FAAH-expressing COS-7 cells were able to break down AED efficiently, indicating that the intracellular AEA transport mechanism was already present and operation in these cells. The researchers identified these carriers as two separate FABPs.

Dr. Deutsch believes that because a transporter for the AEA class of neurotrasmitters had never been discovered until the Stony Brook findings, continued research may explain many unanswered questions about AEA. Future research may uncover more knowledge about AEA transport, as well as the entire role these neurotransmitters play in pain, inflammation, appetite control, addiction, and perhaps other physiological processes related to many human disorders.

The research was funded by the National Institute on Drug Abuse, part of the National Institutes of Health.

https://www.sciencedaily.com/releases/2009/03/090325190342.htm