Cannabis: Non-addictive pathway to pain relief?

Medicinal properties of cannabis examined

January 12, 2017

Science Daily/Oregon Health & Science University

OHSU research suggests an avenue for developing treatments for chronic pain that harness the medicinal properties of cannabis while minimizing the threat of addiction.

The study, conducted in a rodent model, provides additional rationale for the development of therapeutics using cannabinoid receptors to treat chronic pain, which afflicts about 30 percent of the U.S. population. OHSU investigators studied the function of two forms of cell membrane receptors that bind cannabinoids that occur naturally within the body, called endocannabinoids.

"It may be an avenue where we can get better pain medications that are not addictive," said senior author Susan Ingram, Ph.D., an associate professor of neurosurgery in the OHSU School of Medicine.

Ingram and colleagues report the treatment of chronic pain has challenged the medical system, with medications that are ineffective or create serious side effects: "However, emerging data indicate that drugs that target the endocannabinoid system might produce analgesia with fewer side effects compared with opioids."

The body's endocannabinoid system comprises receptors, endocannabinoid molecules and enzymes that make and degrade the endocannabinoids located in the brain and throughout the central and peripheral nervous system. The research team focused on two cannabinoid receptors, known as CB1 and CB2, in the rostral ventromedial medulla -- a group of neurons located in the brainstem known to modulate pain. The study is the first to examine CB1 and CB2 receptor function at the membrane level in late adolescent and adult neurons.

The researchers observed that chronic inflammatory pain increased activity of CB2 receptors and decreased CB1 activity. Cannabis activates both CB1 and CB2 receptors equally. The study suggests that selective activation of CB2 receptors contributes to the medicinal benefit of cannabis while minimizing the propensity of the other cannabinoid receptor, CB1, to induce tolerance and withdrawal. Ingram said the next phase of the research will further explore this area of brain circuitry, which ultimately could lead to the development of a new class of pain medications.

Co-authors include lead author Ming-Hua Li, Ph.D., and Katherine L. Suchland, both with the Department of Neurological Surgery, OHSU School of Medicine.

The study was funded by grants from the National Institutes of Health (DA035316 and R56NS093894) and American Heart Association (13SDG14590005, MH.L.).

https://www.sciencedaily.com/releases/2017/01/170112130145.htm

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

Cannabis as painkiller

August 7, 2012

Science Daily/Deutsches Aerzteblatt International

Cannabis-based medications have been demonstrated to relieve pain. Cannabis medications can be used in patients whose symptoms are not adequately alleviated by conventional treatment. The indications are muscle spasms, nausea and vomiting as a result of chemotherapy, loss of appetite in HIV/Aids, and neuropathic pain.

This is the conclusion drawn by Franjo Grotenhermen and Kirsten Müller-Vahl in issue 29-30 of Deutsches Ärzteblatt International.

The clinical effect of the various cannabis-based medications rests primarily on activation of endogenous cannabinoid receptors. Consumption of therapeutic amounts by adults does not lead to irreversible cognitive impairment. The risk is much greater, however, in children and adolescents (particularly before puberty), even at therapeutic doses.

Over 100 controlled trials of the effects of cannabinoids in various indications have been carried out since 1975. The positive results have led to official licensing of cannabis-based medications in many countries. In Germany, a cannabis extract was approved in 2011 for treatment of spasticity in multiple sclerosis. In June 2012 the Federal Joint Committee (the highest decision-making body for the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany) pronounced that the cannabis extract showed a slight additional benefitfor this indication and granted a temporary license until 2015.

https://www.sciencedaily.com/releases/2012/08/120807101232.htm

Cannabis: A new frontier in therapeutics

February 15, 2015

Science Daily/McGill University Health Centre

While debate about recreational marijuana use continues, researchers are investigating the effectiveness of cannabis for treating pain, spasticity, and a host of other medical problems. In a symposium organized by the McGill University Health Centre (MUHC) as part of the 2015 American Association for the Advancement of Science Annual Meeting held this week in San Jose, California, experts from North America and the U.K. share their perspectives on the therapeutic potential of medical cannabis and explore the emerging science behind it.

"We need to advance our understanding of the role of cannabinoids in health and disease through research and education for patients, physicians and policy-makers," says Dr. Mark Ware, director of clinical research at the Alan Edwards Pain Management Unit at the MUHC, in Canada.

As a pain specialist Dr. Ware regularly sees patients with severe chronic pain at his clinic in Montreal, and for some of them, marijuana appears to be a credible option. "I don't think that every physician should prescribe medical cannabis, or that every patient can benefit but it's time to enhance our scientific knowledge base and have informed discussions with patients."

Increasing numbers of jurisdictions worldwide are allowing access to herbal cannabis, and a range of policy initiatives are emerging to regulate its production, distribution, and authorization. It is widely believed that there is little evidence to support the consideration of cannabis as a therapeutic agent. However, several medicines based on tetrahydrocannabinol (THC), the psychoactive ingredient of cannabis, have been approved as pharmaceutical drugs.

Leading British cannabis researcher Professor Roger Pertwee, who co-discovered the presence of tetrahydrocannabivarin (THCV) in cannabis in the 70's, recently published with collaborators some findings of potential therapeutic relevance in the British Journal of Pharmacology. "We observed that THCV, the non-psychoactive component of cannabis, produces anti-schizophrenic effects in a preclinical model of schizophrenia," says Pertwee, professor of Neuropharmacology at Aberdeen University. "This finding has revealed a new potential therapeutic use for this compound."

Neuropsychiatrist and Director of the Center for Medicinal Cannabis Research (CMCR) at the University of California, San Diego Dr. Igor Grant is interested in the short and long-term neuropsychiatric effects of marijuana use. The CMCR has overseen some of the most extensive research on the therapeutic effects of medical marijuana in the U.S. "Despite a commonly held view that cannabis use results in brain damage, meta analyses of extensive neurocognitive studies fail to demonstrate meaningful cognitive declines among recreational users," says Dr. Grant. "Bain imaging has produced variable results, with the best designed studies showing null findings."

Dr. Grant adds that while it is plausible to hypothesize that cannabis exposure in children and adolescents could impair brain development or predispose to mental illness, data from properly designed prospective studies is lacking.

https://www.sciencedaily.com/releases/2015/02/150215070209.htm

Herbal cannabis not recommended for rheumatology patients

March 3, 2014

Science Daily/Wiley

Patients with rheumatic conditions are in need of symptom relief and some are turning to herbal cannabis as a treatment option. However, the effectiveness and safety of medical marijuana to treat symptoms of rheumatic conditions such as rheumatoid arthritis, lupus, or fibromyalgia is not supported by medical evidence. A new article published in Arthritis Care & Research, a journal of the American College of Rheumatology (ACR), explores the risks associated with using herbal cannabis for medicinal purposes and advises healthcare providers to discourage rheumatology patients from using this drug as therapy.

The reason for the medical interest in herbal cannabis is that the human body has an extensive cannabinoid system comprising molecules and receptors that have effects on many functions including pain modulation. Medical cannabis is commonly used to self-treat severe pain associated with arthritis and musculoskeletal pain. In fact, previous research reports that 80% of marijuana users in a U.S. pain clinic are treating myofascial pain with the drug. In population studies in the U.K. and Australia, up to 33% of individuals report using marijuana to treat arthritis pain. As of June 2013, estimates from the office of Information Commissioner of Canada list "severe arthritis" as the reason the 65% of Canadians who are allowed to possess marijuana for medicinal purposes.

"With the public outcry for herbal cannabis therapy, governments around the world are considering its legalization for medicinal use," explains lead investigator Dr. Mary-Ann Fitzcharles, a researcher and rheumatologist at the McGill University Health Centre (MUHC) and the Research Institute of the MUHC in Quebec, Canada. "Physicians caring for patients who are self-medicating with marijuana need to understand the health implications of using this drug. Our study aims to provide health care professionals with that medical evidence related to medical marijuana use in patients with rheumatic conditions."

In the U.S. twenty states, including the District of Columbia (DC), have legalized cannabis for medical purposes. The present study examines the dosing, administration, efficacy and risks of herbal cannabis in pain management for patients with rheumatic conditions. The health issues with recreational marijuana use in this patient population are not covered.

Concentrations of tetrahydrocannabinol (THC) -- the substance found in Cannabis sativa that provides pain relief and alters brain function (psychoactive effect) -- vary in the plant material by up to 33% and absorption rates are between 2% and 56%, making the dosing of herbal cannabis unreliable. While cannabis may be ingested, most users prefer to inhale the compound for a quicker response. However, smoking a "joint" is not recommended by the medical community due to adverse effects on the respiratory system from hydrocarbons, tar and carbon monoxide.

Furthermore, there is no formal short-term or long-term study of the effectiveness of herbal cannabis in patients with rheumatic diseases. Studies that show good efficacy of cannabinoids for cancer and neuropathic pain may not be extended to rheumatic diseases because of the differing mechanism in the types of pain.

The study authors highlight that use of medical marijuana comes with inherent risks such as compromised cognitive and psychomotor function. Long-term use of cannabis may lead to mental illness, dependence, addiction and memory issues. In fact, a prior U.S. study of 8,000 adults who used cannabis in the previous year found that the odds of depression were 1.4 times higher in cannabis users compared to non-users.

"At this time, we cannot recommend herbal cannabis for arthritis pain management given the lack of efficacy data, potential harm from the drug, and availability of other therapies for managing pain," concludes Dr. Fitzcharles. "Physicians should discourage rheumatology patients from using medical marijuana as a therapy."

https://www.sciencedaily.com/releases/2014/03/140303083543.htm