Mixed findings regarding quality of evidence supporting benefit of medical marijuana
June 23, 2015
Science Daily/JAMA - Journal of the American Medical Association
In an analysis of the findings of nearly 80 randomized trials that included about 6,500 participants, there was moderate-quality evidence to support the use of cannabinoids (chemical compounds that are the active principles in cannabis or marijuana) for the treatment of chronic pain and lower-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, sleep disorders, and Tourette syndrome, according to a study in the June 23/30 issue of JAMA.
Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms. In the United States, 23 states and Washington, D.C., have introduced laws to permit the medical use of cannabis; many other countries have similar laws. Despite the wide us of cannabis and cannabinoid drugs for medical purposes, their efficacy for specific indications is not clear, according to background information in the article.
Penny F. Whiting, Ph.D., of the University of Bristol, Bristol, United Kingdom, and colleagues evaluated the evidence for the benefits and adverse events (AEs) of medical cannabinoids by searching various databases for randomized clinical trials of cannabinoids for a variety of indications. The researchers identified 79 trials (6,462 participants) that met criteria for inclusion in the review and meta-analysis.
The researchers found that most studies suggested that cannabinoids were associated with improvements in symptoms, but these associations did not reach statistical significance in all studies. There was moderate-quality evidence to suggest that cannabinoids may be beneficial for the treatment of chronic neuropathic or cancer pain and spasticity due to multiple sclerosis (sustained muscle contractions or sudden involuntary movements). There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome; and very low-quality evidence for an improvement in anxiety. There was low-quality evidence for no effect on psychosis and very low-level evidence for no effect on depression.
There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. There was no clear evidence for a difference in association (either beneficial or harmful) based on type of cannabinoids or mode of administration. Only 2 studies evaluated cannabis. There was no evidence that the effects of cannabis differed from other cannabinoids.
"Further large, robust, randomized clinical trials are needed to confirm the effects of cannabinoids, particularly on weight gain in patients with HIV/AIDS, depression, sleep disorders, anxiety disorders, psychosis, glaucoma, and Tourette syndrome are required. Further studies evaluating cannabis itself are also required because there is very little evidence on the effects and AEs of cannabis," the authors write.
Editorial: Medical Marijuana
"If the states' initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized," write Deepak Cyril D'Souza, M.B.B.S., M.D., and Mohini Ranganathan, M.D., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.
"Conversely, if the goal is to make marijuana available for medical purposes, then it is unclear why the approval process should be different from that used for other medications. Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, double-blind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety. The federal government and states should support medical marijuana research. Since medical marijuana is not a life-saving intervention, it may be prudent to wait before widely adopting its use until high-quality evidence is available to guide the development of a rational approval process."
https://www.sciencedaily.com/releases/2015/06/150623113152.htm
Scientists discover potential new way to treat anxiety
August 4, 2013
Science Daily/Vanderbilt University Medical Center
Chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects, Vanderbilt University scientists will report next week.
Endocannabinoids are natural signaling molecules that activate cannabinoid receptors in the brain, the same receptors turned on by the active ingredient in marijuana.
These receptors are also found in the gastrointestinal system and elsewhere in the body, and there is evidence that they play a role in wide range of physiological and pathological processes, in addition to modulating stress and anxiety.
If the "substrate-selective" COX-2 inhibitors developed at Vanderbilt also work in humans without side effects, they could represent a new approach to treating mood and anxiety disorders, the researchers conclude in a paper to be posted online Sunday in the journal Nature Neuroscience.
Clinical trials of some of these potential drugs could begin in the next several years, said Lawrence Marnett, Ph.D., director of the Vanderbilt Institute of Chemical Biology and the paper's co-senior author with Sachin Patel, M.D., Ph.D.
The Vanderbilt scientists are pursuing other potential applications of activating endocannabinoids by substrate-selective COX-2 inhibition, including relieving pain, treating movement disorders, and possibly preventing colon cancer.
"The door is really wide open," said Patel, assistant professor of Psychiatry and of Molecular Physiology & Biophysics. "We've just scratched the surface."
Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) relieve pain and inflammation by blocking either or both of the cyclooxygenase (COX) enzymes, which produce pro-inflammatory prostaglandins.
It has been known for several years that COX-2 inhibition also activates endocannabinoids.
Because the "substrate selective" inhibitors developed at Vanderbilt increase endocannabinoid levels in the mouse without blocking prostaglandin production, "we think (they) will not have the gastrointestinal and possibly cardiovascular side effects that other NSAIDs do," said Marnett, University Professor and Mary Geddes Stahlman Professor of Cancer Research.
"We thought we knew everything there was to know about (COX-2 inhibitors) until about five years ago when we discovered the substrate selective inhibition," he added. The approach used by the Vanderbilt team "is a really powerful way to help design the next generation of drugs."
https://www.sciencedaily.com/releases/2013/08/130804144523.htm
How the brain suppresses pain during times of stress
March 6, 2013
Science Daily/National University of Ireland, Galway
New findings about how the brain functions to suppress pain have been published in the leading journal in the field Pain, by National University of Ireland Galway (NUI Galway) researchers. For the first time, it has been shown that suppression of pain during times of fear involves complex interplay between marijuana-like chemicals and other neurotransmitters in a brain region called the amygdala.
The work was carried out by Dr David Finn and his research team in Pharmacology and Therapeutics, Centre for Pain Research and Galway Neuroscience Centre at the National Centre for Biomedical Engineering Science, NUI Galway. The research builds on previous breakthrough findings from Dr Finn's research group on the role of marijuana-like chemicals in the brain's hippocampus in pain suppression during fear.
Pain is both a sensory and an emotional experience and is subject to modulation by a number of factors including fear and stress. During exposure to a high-stress environment or stimulus, pain transmission and perception can be potently suppressed. This important survival response can help us cope with or escape from potentially life-threatening situations. One brain region that is integral to the processing and expression of both emotional responses and pain is the amygdala.
Working with Dr Finn, first author Dr Kieran Rea was able to confirm the amygdala as a key brain region in the suppression of pain behaviour by fear (so-called fear-induced analgesia). Fear-induced analgesia was associated with increases in levels of marijuana-like substances known as endocannabinoids in the amygdala.
Furthermore, fear-induced analgesia was prevented by injecting a drug that blocked the receptor at which these endocannabinoids act into the amygdala. Further experimentation revealed that these effects involved an interaction between endocannabinoids and the classical neurotransmitters GABA (Gamma-amino butyric acid) and glutamate. An increased understanding of the biological mechanisms involved in fear-induced analgesia is important from a fundamental physiological perspective and may also advance the search for new therapeutic approaches to the treatment of pain.
Dr David Finn, Leader of the Galway Neuroscience Centre, Co-Director of the Centre for Pain Research at NUI Galway and study leader says: "The body can suppress pain when under extreme stress, in part through the action of marijuana-like substances produced in the brain. This research provides information on the complex interactions between multiple neurotransmitter systems including endocannabinoids, GABA and glutamate in times of stress and pain. This research which was funded by a grant from Science Foundation Ireland, advances our fundamental understanding of the neurobiology of pain and may facilitate the identification of new therapeutic targets for the treatment of pain and anxiety disorders."
https://www.sciencedaily.com/releases/2013/03/130306134014.htm