One of the more interesting, and seemingly paradoxical, effects of cannabis which has been intriguing researchers recently is its neuroprotective properties. Science (and most users would agree) that cannabis use can lead to short-term residual memory and cognitive impairments, however, the long term effects might be exactly the opposite, and some studies have shown that both THC and CBD can work as neuroprotectants and possibly even aid in neurogenesis (the growth of new brain cells). This has opened a new line of inquiry into the medicinal uses of cannabis, particularly in the treatment of dementia and Alzheimer's Disease.
Dementia is an aging-related disease which affects about 5.7 million Americans, and around 50 million people worldwide. The disease is defined as a measurable cognitive decline sufficient enough to impair functioning. It usually, but not always, affects those over 65 years old, and as our population is aging and living longer it is becoming more of a problem for individuals, their families, and society as a whole.
The risk factors for dementia include age, prior cognitive impairment, stroke, high blood pressure, heart disease, diabetes, alcohol/tobacco consumption, and anti-depressant use. Alzheimer's disease is the most common and more severe subtypes of dementia, making up approximately 60-80% of all cases, and is characterized by the formation of protein-based plaques within the brain. Currently, there are no FDA approved medications to treat Alzheimer's Dementia.
Cannabis and Cognitive Decline
For many years, it was also assumed that cannabis use would be a risk factor dementia and Alzheimer's Disease, but in studies, the published thus far no correlation between the two has been found. In fact, some studies have found exactly the opposite.
In a 1999 study published in the American Journal of Epidemiology, the cognitive decline of 1,318 participants aged under 65 was tracked over 15 years. Participants were given a Mini-Mental State Examination three sperate times over the study period and the results were compared according to age, sex, educational level, and cannabis use. Interestingly, the study found the strongest correlation between cognitive decline and education level (those with higher levels of education had less decline), and a slight difference between males and females. When it came to cannabis use, both light and heavy cannabis users showed less cognitive decline then non-users, however, the results were not statically significant. The study was one of the first to look at the long-term effects of cannabis use on cognition, paving the way for future studies.
By 2009, many more studies had been completed, which were reviewed by the Cochrane Collaboration. The review noted that there was increasing evidence that the body's endocannabinoid system played a major role in regulating neurodegenerative processes including excessive glutamate production, oxidative stress, and neuroinflammation. The study concluded that, while some research had shown evidence for the neuroprotective effects of cannabis, no studies could conclusively show that cannabis was effective at treating Alzheimer's dementia. This was because most of the evidence was not from randomized double-blind placebo-controlled trials, the so-called gold standard of medical science. It would be another decade until enough new studies could be completed to lend more credibility to the claims being made at the time.
How does Cannabis Effect Alzheimer's Dementia?
As discussed above, dementia is a loss of cognitive ability leading to decreased function and abilities. In Alzheimer's dementia, the disease is characterized by a build-up of plaque formed by β-amyloid peptides (Aβ for short) and tangling of a protein found in neurons known as Tau. Together, these give rise to a wide range of symptoms, including confusion, memory loss, agitation, irritability, anorexia, depression, and more. Not only is the disease extremely hard on the person suffering from it, but also on those attempting to care for them, and often secondary symptoms such as depression, anxiety, and decreased quality of life are obvious for the patient's caretakers.
As there are currently no drugs approved to specifically treat Alzheimer's, drugs for other conditions are used off-label to treat some of the symptoms of the disease. Although sometimes effective at muting symptoms, these drugs can do nothing to prevent or treat the root causes of the disease.
As recently as 2016, the American Journal of Psychiatry outlined the difficulty in treating the symptoms of Alzheimer's stating that adequate options for alleviating the symptoms of the disease were lacking and mostly involved the use of antipsychotics, sedatives, hypnotics, and anti-depressants which had never demonstrated nor been approved for such applications. Furthermore, all of these drugs have serious mental and physical side effects which increase the rates of mortality, and no studies have been completed to evaluate whether or not their benefits outweigh the risks.
Conversely, cannabis may offer treatment of the symptoms and causes of Alzheimer's, without the negative side-effects experienced with other medications. In a 2015 study published in the Journal of Alzheimer's Disease, medical cannabis oil was tested on ten Alzheimer's patients in addition to their current medications. Patients were evaluated for changes in behavior and psychological symptoms, as well as safety. The study found that cannabis oil was safe, with no patients experiencing negative side effects.
Furthermore, the study found that cannabis oil significantly reduced the occurrence of delusions, agitation/aggression, irritability, apathy, sleep issues, and caregiver distress. The conclusion of the study was that cannabis oil was both safe for use in Alzheimer's patients as an add-on to their current drug regiments and also was effective at reducing some of the symptoms of the disease which cause the most stress for the patients and their caregivers. The same study also noted that other research had shown that the THC based drug, Dronabinol had been effective at reducing anorexia in Alzheimer's patients. Although this paper did not explore the mechanisms for the observed benefits, it did mention that the body's endocannabinoid system is responsible for the regulation of psychomotor activities, mood, sleep, and eating behaviors, all of which are impaired in Alzheimer's patients, so endocannabinoids were a logical place to start looking for new solutions.
In the Cochrane Review mentioned above, the science behind the neuroprotective properties of cannabis was explained, and it was put forward that THC and CBD may actually interrupt the processes that lead to Alzheimer's (glutamate production, oxidation, inflation) and could prevent or slow the disease. This conclusion was further strengthened by work on mouse brains which was published in the Journal of Alzheimer's Disease in 2016. That study found that in mice treated with Sativex (a medication containing a 1:1 ratio of THC to CBD) the Aβ plaques and tangled Tau proteins normally associated with the disease were prevented from forming. Additionally, levels of GABA (a neurotransmitter that acts to block impulses in the brain that can lead to anxiety and agitation) was higher in the mice treated with the cannabinoids. This effect seemed to work on all the Alzheimer's mice, but interestingly not in the wild mice control group. The study concluded that the cannabis-based drug Sativex was effective in preventing the development and progression of the disease, but not reversing the damage in mice already affected by the disease.
Another study published the same year came to similar conclusions, finding that, in mice, the CB-2 type receptors (those triggered by CBD) were responsible for the clearance of the Aβ peptide, reducing memory loss and learning impairment.
Both studies mentioned that the endocannabinoid system was a better target for the development of new drugs to prevent Alzheimer's and other forms of dementia, and could be done so using non-psychoactive doses of cannabinoids which have already been proved safe by the FDA. Interestingly, a 2017 trial could not repeat these results when only THC was used in the absence of CBD, indicating the importance of both cannabinoids being administered concurrently.
Potentials for New Treatment Methods
It may be too early to start touting cannabis as the cure for dementia and Alzheimer's, but with 10% of the population over 65 and 25% of those over 80 being affected by Alzheimer's, new medications and treatments need to be found. Current evidence has shown that cannabis-based drugs are well-tolerated and safe for use in these patient cohorts, and may be beneficial when used alongside traditional treatments. There is currently a need for more rigorous trials to be completed and for comparisons of benefit to side-effect ratios between cannabis-based drugs and the off-label pharmaceuticals currently being utilized.
This sentiment was probably most well summarized in the Journal of British Journal of Pharmacology, as "manipulation of the cannabinoid system offers the potential to upregulate neuroprotective mechanisms while dampening neuroinflammation. Whether these properties will be beneficial in the treatment of AD [Alzheimer's Dementia] in the future is an exciting topic that undoubtedly warrants further investigation.”
Read further about Cannabis Health:
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- First Cannabis Medicines: Epidyolex and Sativex Approved for Use on NHS to Treat Epilepsy and Multiple Sclerosis
- One in Ten Women with Endometriosis Reported Using Cannabis to Ease Their Pain
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