Living the High Life

by Women's Brain Health Initiative:The relationship between cannabis and the brain is complex, and there remains much to learn about the interconnection between the two. The negative effects of cannabis have received much publicity for decades and one of the main messages communicated to the public has been that using cannabis can impair cognitive function. While this may be true in the context of recreational use of the plant, research now suggests that cannabis may have a positive impact on the brain – acting as a neuroprotectant and anti-inflammatory – and can perhaps even prevent, stop, or reverse brain disease.Cannabis & Cognitive FunctionAccording to Health Canada, the long-term effects of cannabis use on the brain can include harm to memory, concentration, IQ, and the ability to think and make decisions. Health Canada’s website explains that these effects appear to worsen for individuals who start using cannabis earlier on in life and for those who partake frequently and for a lengthy duration. Health Canada further warns that the long-term effects of cannabis on the brain may not be fully reversible when cannabis use ceases.However, new research suggests that cannabis may sometimes positively impact cognitive function. Preliminary results from the very first study of medical marijuana’s effect on cognitive performance were published in the 2016 issue of Frontiers in Pharmacology. The researchers found that “medical marijuana may not impair, and in many cases, may actually improve executive functioning in adults.”These results were based on 11 participants who, in general, performed better on certain cognitive tasks after receiving three months of medical marijuana treatment. Specifically, the participants experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and the Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy. It is possible that the improvement in cognitive function was related to alleviation of the primary physical or psychological symptoms that the medical marijuana was used to address (such as pain or anxiety).Dr. Staci Gruber, Director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital in Belmont, Massachusetts and the lead researcher involved in the study, provided several possible reasons why these findings appear to contradict the widely publicized negative effects of cannabis. As Dr. Gruber explained, the age of the participants, the differences in chemical composition of recreational versus medical marijuana, and the ways in which the products are used may account for the study’s findings.The researchers further noted that improvements in cognitive performance may also be related to patients’ reduced use of conventional medications, such as opiates, that can result in “cognitive fog.” As Dr. Gruber cautioned, though, while these results are intriguing, “it’s important to remember that these initial findings are preliminary and based on a small sample size. [The] study will continue for at least two years and [the researchers] will eventually have data on a much larger group of participants.”More recently, a study conducted by German and Israeli researchers, published in the May 2017 issue of Nature Medicine, examined the impact of delta-9-tetrahydrocannabinol (THC) – a major bioactive compound in cannabis – on memory performance and cognitive functioning in mice. The researchers administered a low dose of THC to young, mature, and aged mice over a period of four weeks. Thereafter, they tested learning capacity and memory performance in the animals – including, for instance, orientation skills and the recognition of other mice.The young mice treated with THC performed slightly worse on behavioural tests of memory and learning than the control group (i.e. those mice that received a placebo). As expected, the elderly mice that only received a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the elderly mice treated with THC closely resembled that of the young, untreated mice. In fact, the treatment completely reversed the loss of cognitive performance in the elderly mice.When the researchers examined the brains of the treated elderly mice for an explanation, they noticed that neurons in the hippocampus (a brain area critical for learning and memory) had sprouted more synaptic spines, the points of contact for communications between neurons. Surprisingly, the molecular signature of the elderly mice no longer corresponded to that of the untreated, elderly mice but was instead very similar to that of the young, untreated animals. As the researchers observed, it appeared as though the THC treatment “turned back the molecular clock.” While many experts have praised this study, they have cautioned against extrapolating the findings to humans. Further research is required in order to determine whether small doses of THC will affect human brains in a similar way.These positive findings about the impact of cannabis on cognitive function may be explained, at least in part, by dosage. Cannabinoids, and THC in particular, have what is called a “biphasic effect,” which means that low and high doses of the same substance can produce opposite effects in users. Finding the optimal dosage, without the negative side effects, is the first step to effective treatment. Since cannabis therapeutics is personalized medicine, the right treatment regimen depends upon the individual and the condition being treated.Cannabis & DementiaThere is also research that indicates the potential benefits of cannabinoids for older individuals who are at risk of developing dementia or who have already been diagnosed.Tackling Underlying Hallmarks of Alzheimer’s DiseaseOur bodies have what is called an endocannabinoid system that consists of a group of cannabinoid receptors in the brain, and throughout the central nervous system and the peripheral nervous system. Currently, there are two known receptors, CB1 and CB2. The brain naturally produces cannabinoids, which affect both of those receptors. When an individual uses a cannabis product, that product targets those same receptors and imitates the effects of the cannabinoids that are produced naturally in the body.The endocannabinoid system is associated with brain aging. For instance, scientists have found that the brains of mice age much faster when they do not have any functional CB1 receptors. Also, the quantity of cannabinoids that is produced naturally in the body is known to decrease with age and when this occurs, researchers have noticed rapid aging in the brain.The endocannabinoid system is associated with more than just brain aging and has been linked specifically with neurodegenerative diseases and dementia, including Alzheimer’s disease. Accordingly, researchers are studying the effects of targeting the endocannabinoid system as a potential therapeutic approach to treat Alzheimer’s disease. According to a 2015 review article by Ahmed et al., published in Clinical Pharmacology and Therapeutics, several studies have found that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles—all hallmarks of Alzheimer’s disease. An earlier review by Aso et al., published in the 2014 issue of Frontiers in Pharmacology, shared similar findings and specifically noted that beneficial effects were observed with the use of both natural and synthetic cannabinoids at non-psychoactive doses.Findings from a study by Currais et al., published in June 2016 in Aging and Mechanisms of Disease, suggest that cannabinoids may be able to remove existing amyloid beta from brain cells. This research was conducted on nerve cells altered to produce high levels of amyloid beta in a laboratory setting at the Salk Institute in California. Researchers found that high levels of amyloid beta were linked with cellular inflammation and higher rates of neuron death. When the human neurons were exposed to THC, it reduced the levels of amyloid beta and eliminated the inflammatory response, thereby allowing the nerve cells to survive.Helping with Alzheimer’s SymptomsCannabinoids may also help alleviate some of the neuropsychiatric symptoms commonly experienced with Alzheimer’s disease, especially in the mid-to-later stages of the illness. A 2015 review article published in CNS Drugs cited six studies that found that the synthetic cannabinoids dronabinol and nabilone had a significant positive impact on agitation and aggression. The researchers cautioned, however, that definitive conclusions could not be reached based on those studies alone due to the small sample sizes, short study duration, and the lack of placebo controls in some instances.Another small study, involving ten Alzheimer’s patients who received medical cannabis oil containing THC for a four-week period, found that participants experienced significant reductions in both behavioural and psychological symptoms, which included agitation, aggression, apathy, and delusions. The researchers, Shelef et al. from Tel-Aviv University and Bar-Ilan University in Israel, concluded that cannabis oil is a safe and promising treatment option for Alzheimer’s disease. (The results of this study were published in the November 2015 issue of the Journal of Alzheimer’s Disease.)Helping with PainPain is common among dementia patients even though they may lack the ability to express it. An article published in the last issue of Mind Over Matter magazine examined the topic of pain and shared pertinent information about how to recognize signs of pain in individuals with dementia, as well as emphasized the importance of treating pain when it is present. Importantly, cannabinoids are known to help alleviate pain.In 2017, the National Academies of Sciences, Engineering, and Medicine in the U.S. issued a rigorous review of the scientific research published since 1999 regarding the health impacts of cannabis and cannabis-derived products. With respect to chronic pain in adults, the researchers found that cannabis or cannabinoids helped patients experience “a significant reduction in pain symptoms.”While we now know that cannabis can help alleviate chronic pain, the question becomes how safe is it? Do the benefits outweigh the risks, if any? A team of Canadian researchers, led by Dr. Mark Ware from the Research Institute of the McGill University Health Centre in Montreal, examined these questions and published their findings in the December 2015 issue of The Journal of Pain. “We found that patients with chronic pain who used medical cannabis daily for one year did not have an increase in serious adverse effects compared to pain patients who did not use cannabis,” explained Dr. Ware. “Medical cannabis appeared to be reasonably safe for the participants in our study. In particular, we did not find any evidence of harmful effects on cognitive function.”Much More Research is NeededAs the date for legalization of non-medical cannabis quickly approaches in Canada, it is now more critical than ever to expand the research on cannabis, and there are many individuals and organizations working to draw attention to this urgent need.Dr. Lynda Balneaves, an associate professor at University of Manitoba’s College of Nursing, is a researcher pushing for more investment in cannabis research. In particular, she wants to see research expand on the potential risks and benefits of medical cannabis. Currently, research has been largely focused on the physiological and social harms of recreational use. “There is so much we don’t fully understand about cannabinoids and how best to use them for therapeutic effect,” she said. “For example, which cannabinoid or combination of cannabinoids work best for what conditions? What is the appropriate dosage? What delivery mechanism is best—smoking, vaping, tincture, pill, edibles, topical? These are important questions that need to be answered so that health professionals can make informed decisions about what to recommend to patients.”Dr. Mark Ware from Montreal, who is co-chair of the federal government’s Task Force on Cannabis Legalization and Regulation, also observes the pressing need for more research and education. He said, “Canada needs to be supporting connections between researchers studying plant sciences, pharmacology, clinical research and policy to better understand what the impact of legalization will be on individual health and on public health.”The Canadian Medical Association (CMA) agrees that cannabis research should be a priority. The CMA’s website indicates that the organization “will continue to urge that Health Canada support development of rigorous research on the effects, both positive and adverse, that the use of marijuana for medical purposes will have.”The Arthritis Society in Canada is another organization encouraging more cannabis research and has demonstrated its support by providing significant funding (the Society has committed to spending $720,000 between 2015 and 2019 on cannabis research, and in 2016 it also created the Medical Cannabis Strategic Operating Grant that provides at least $120,000 per year for medical cannabis research). Additionally, the Canadian Institutes of Health Research announced the “Catalyst” funding opportunity in May 2017. This program will provide a total of $1 million over a one-year period for “population health intervention research related to the legalization and regulation of non-medical cannabis in Canada.” Hopefully this is just the beginning of a rapid expansion of investment in cannabis research, by both the government and more private sector organizations.Source: MIND OVER MATTER - V5