Brain imaging insight into cannabis as a pain killer

(Press-News.org) 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.'

### Notes to Editors

Dr Michael Lee says: 'Living with chronic pain involves more than just coping with the pain. It runs through your life, through your decisions and what you're motivated to do. Some people might have a known cause for the pain – MS, cancer or an injury – but many others may have no specific cause or diagnosis for their lower back or neck pain, abdominal pain, headaches or other symptoms. That can be very difficult to accept and it can be difficult to treat.

'It is impossible to recommend one single treatment, especially when there are so few therapies for intractable pain. It needs a combined approach that can involve painkillers, exercise and physiotherapy, counselling, even surgery.

'Drugs may be able to relieve the pain somewhat, or offer some comfort. But healthcare should be more than that. It should be about comfort, but also improving quality of life and enabling patients to do more. We need to learn more about pain drugs and their long-term effects. If we can identify how the brain responds to such drugs, we can be more confident about any benefits they may have. It is that which has motivated this study.'

The group initially recruited 15 men to the study. However, data from 2 volunteers was excluded when it became clear they had used cannabis before. One participant experienced THC-induced claustrophobia which meant he could not go in the MRI scanner. His symptoms passed in a number of hours. Women were not included in the study because hormones associated with the menstrual cycle may have influenced experiences of pain over the course of the 4–6 week study.

The paper 'Amygdala activity contributes to the dissociative effect of cannabis on pain perception' by Michael C. Lee, Markus Ploner, Katja Wiech, Ulrike Bingel, Vishvarani Wanigasekera, Jonathan Brooks, David K. Menon, Irene Tracey (DOI: 10.1016/j.pain.2012.09.017) will appear in PAIN®, Volume 154, Issue 1 (January 2013) published by Elsevier.

About PAIN® PAIN®, the official journal of the International Association for the Study of Pain® (IASP®), publishes 12 issues per year of original research on the nature, mechanisms, and treatment of pain. This peer-reviewed journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest and is cited in Current Contents and MEDLINE. It is ranked 1st out of the 28 journals in the Anesthesiology category according to the 2011 Journal Citation Reports published by Thomson Reuters. www.painjournalonline.com

About the International Association for the Study Of Pain® (IASP®) Founded in 1973, IASP® is the world's largest multidisciplinary organization focused specifically on pain research and treatment. It is the leading professional forum for science, practice, and education in the field of pain bringing together scientists, clinicians, health care providers, and policy makers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide. IASP currently has more than 7900 members from 130 countries and in 89 chapters. www.iasp-pain.org

The study was funded by the Medical Research Council and the National Institute for Health Research Oxford Biomedical Research Centre.

The NIHR Oxford Biomedical Research Centre is a partnership between the Oxford University Hospitals NHS Trust and the University of Oxford. Its main aim is to enable clinical research for patient benefit and foster innovation to improve healthcare. It is funded by the National Institute for Health Research (NIHR). The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world class facilities (both NHS and university), and conducting leading edge research focused on the needs of patients. www.oxfordbrc.nihr.ac.uk

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website. The views expressed in this news release are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK's top-ranked medical school.

From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.

A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions. END