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Your Brain on Weed: Is Cannabis a Neuroprotectant or a Neurotoxin?

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It has long been argued that you shouldn’t smoke weed because it will make you dumb and lazy. There is a reason why people call it “dope.” However, when we look at some of the most progressive, intelligent, and eloquent thinkers and artists of our time, we find that they admit tingly consume cannabis, sometimes in great quantities. So, what is the real story? Is cannabis good or bad for your brain? This argument is hard to put to rest, and science is nowhere near coming to a consensus on the matter.

Currently, it would be impractical and unethical to attempt a controlled experiment to determine the answer, and epidemiological data is unconvincing as it is impossible to adjust for so many factors that can contribute to intelligence and cognitive decline. However, this does not mean that we cannot have a scientific discussion on the matter. Several neurodegenerative diseases are well studied in the context of cannabis use, for which we can explore the issue using solid experimental and mechanical evidence.

Neurodegenerative diseases are progressing debilitating conditions that involve the loss of nerve cells in the brain and peripheral nervous systems. The societal burden of such diseases has significantly increased over the last few decades due to increased populations, longer life spans, and more abundant environmental pollutants. These neurodegenerative diseases include Alzheimer’s Dementia, Huntington’s, Parkinson’s, Multiple Sclerosis, and many others. Although each disease has different symptoms, causes, and prognoses, all are caused by the degeneration of nerve cells, primarily in the brain and spinal cord. These diseases offer us the unique opportunity to look at how cannabis affects the human brain as they progress over a relatively short period, and thus the effects of cannabis use can be studied and elucidated from anecdotal and clinical evidence. This article will explore knowledge about the contemporary roles of cannabis in affecting each disease, and summarize that information to help answer whether cannabis is a neuroprotectant or a neurotoxin.

(Weed | Ben Greenfield)

How does cannabis affect Parkinson’s Disease (PD)?

Parkinson’s Disease is a neurogenerative disease that primarily affects older adults, but occasionally in younger individuals. It is one of the most prominent neurodegenerative diseases and Alzheimer’s, affecting about 5% of people over 85 years old. In June 2020, a meta-review was published in the Journal Life. It is the largest, most current, and in-depth look at how cannabis and other drugs affect Parkinson’s patients, reviewing over 300 scientific studies and publications. This seminal work in the field indicates that marijuana helps treat the symptoms of Parkinson’s Disease and may also help reverse and prevent it.

Parkinson’s is a disease that results from the accumulation of misfolded proteins, leading to the toxic action on their own or indirectly through the loss of biological function in nerve cells. These misfolded proteins often result in what is called amyloid fibrils or plaques, as well as leading to neuro-fibrillary tangles, and intranuclear inclusions. In short, a disruption to the normal growth and function of nerve cells in the brain and body.

Another one of the prominent issues is neuroinflammation, an immune response. Early signs of the disease include reduced motor function, shaking, rigidity, and slowness. Later symptoms include dementia as well as cognitive and behavioral changes.

(THC and CBD | Google Image)

Because one of the actions of the mechanisms of this disease in neuroinflammation, compounds that affect the body’s immune response and inflammation circuits enter potentially relevant places to start looking for therapeutics, it is well established that the endocannabinoid system of the body controls inflammation. We find CB2 type receptors throughout the various components of the body’s immune system. The endocannabinoid system is responsive to both endocannabinoids, which refers to those produced by the body and endocannabinoids, those from nature, particularly the phytocannabinoids THC and CBD found in the Cannabis sativa plant.

The CB2 receptors are strongly influenced by Cannabidiol (CBD) and have long been used by PD patients in self-treatment, with about 44% of patients using it. It has been shown that the endocannabinoid system plays a vital role in not only the function but also the development of the central nervous system in mammals. Furthermore, from many of the studies on PD, it was shown that these cannabinoids have anti-inflammatory, antioxidant, and pro neurogenic properties.

Indeed, Parkinson’s patients who use cannabis describe improvements in mood, memory, fatigue, obesity, sleep, pain, tremor, and rigidity. Several studies have concluded that PD patients using cannabis have reported lower levels of disability after the intake phytocannabinoids. CBD shows the most promise, with clinical studies indicating a decrease in psychotic symptoms and an increase in well-being and functioning. Furthermore, CBD and the terpene β-caryophyllene helped to decrease the presence of the neurotoxin MPP+ by triggering the activation of nerve growth factor (NGF) while also leading to a decrease of oxidative/nitrosative stress on nerve endings.

(Marijuana | Google Image)

But it is not only CBD that affects these receptors. There are many terpenes and flavonoids founds in plants such as Cannabis sativa that are agonists or antagonists for these receptors, modulating the immune and nervous systems. Overall, these compounds have “been shown to reduce chronic activation of the neuroinflammatory response, mitochondrial dysfunction, and keep calcium homeostasis. It results in the decrease of oxidative stress, which prevents the proapoptotic cascade, promoting neurotrophic support.

Furthermore, ∆ 9 -THC seems to be a direct neuroprotectant by up regulating the expression of the genes which encode for CB1 receptors. Another study found that ∆ 9 -THC has neuroprotective effects by also restoring mitochondrial potential and reducing glutamate levels, both of which imitate apoptosis (or death) of brain cells in Parkinson’s patients.

In summary, cannabis is an effective neuroprotectant in PD patients. Many studies (both in humans and animals) include the phytocannabinoids found in the plants. And in clinical trials, it binds to CB1 receptors to inhibit neurotoxins and bind to CB2 receptors to decrease neuroinflammation and nerve cell apoptosis.

(THC | Google Image)

Cannabis and Multiple Sclerosis (MS)

Multiple Sclerosis is a potentially disabling disease of the brain and nervous system. As the disease progresses, the immune system attacks the sheathing of the neurons, impairing communication between parts of the body. Over time, scar tissue builds up on the neurons, and the disease becomes irreversible. Symptoms of the disease vary greatly between individuals; but include spacisity, chronic pain of extremities, acute paroxysmal phenomenon (seizures), tremors, emotional dysfunction, anorexia/weight loss, weakness, bladder disfunction, difficulty in walking or balance, and memory loss.

The disease’s mechanisms are still being understood, but it is thought that inflammation could play a major role in the disease. As an immune-related disease linked to inflammation, it would logically follow that the body’s endocannabinoid system could play a significant role in the development and progression of the disease and provide a way to treat it. CB1 receptors are responsive to the cannabinoid THC and have been shown to play a role in controlling spacisity involved in MS’s recent studies.

The CB-2 receptors react to cannabidiol, or CBD, and have been shown to help reduce inflammation and modulate the immune system. As such, patients with MS commonly self-medicate using cannabis to relieve their symptoms and reduce their dependency on opioids or other pharmaceutical medications.

A 1997 study published in the Journal of European Neurology, over 70% of MS patients claimed that cannabis helped with the pain, spacisity, and tremors. Another study in the same year recruited a total of 160 patients with MS to trial the prescription drug Sativex, which contains a 1:1 THC to CBD cannabinoid ratio. The study found that spacisity caused by neurodegeneration was greatly reduced in the group receiving the Sativex compared with the placebo and that there were no significant adverse effects on cognition.

Although the science is not as conclusive in the case of MS as it was in PD, it still indicates that phytocannabinoids play a strong role in the modulation of immune responses. And it has neuroprotective properties as indicated by the relief of symptoms associated with nerve degeneration on both the central and peripheral nervous systems.

(CB1 and CB2 | Medium)

Cannabis and Alzheimer’s Dementia (AD)

Alzheimer’s disease is the most common and severe subtype of dementia, making up approximately 60-80% of all cases, and is characterized by the formation of protein-based plaques within the brain. Similar to PD, the disease is characterized by a buildup of plaque formed by β-amyloid peptides (Aβ for short) and tangling of a protein found in neurons known as Tau. For many years, it was also assumed that cannabis use would be a risk factor for dementia and Alzheimer’s Disease but, in the studies published thus far, no correlation between the two has been found. Some studies have found precisely the opposite. In a 1999 study published in the American Journal of Epidemiology, the cognitive decline of 1,318 participants was tracked over 15 years. Participants were given a Mini-Mental State Examination three times separately over the study period, and the results were compared according to age, sex, educational level, and cannabis use. When it came to cannabis use, both light and heavy cannabis users showed less cognitive decline than non-users.

By 2009, many new studies had been completed, which were reviewed by the Cochrane Collaboration. The review noted that there is increasing evidence to prove that the body’s endocannabinoid system plays a major role in regulating neurodegenerative processes, including excessive glutamate production, oxidative stress, and neuroinflammation (as in the Parkinson’s studies).

According to 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, inflammation) and could prevent or slow the disease. This conclusion was further strengthened by work on mouse brains, published in the Journal of Alzheimer’s Disease in 2016. That study found that in mice treated with Sativex (a medication with 1:1 ratio of THC to CBD), the Aβ plaques and tangled Tau proteins generally associated with the disease were prevented from forming. Additionally, 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. The study concluded that the cannabis-based drug Sativex was effective in preventing the disease’s development and progression, 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 CB2 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. It could be done using non-psychoactive doses of cannabinoids, which have already been proved safe by the FDA.

(The Endocannabinoid system | cbdschool.com)

So, is cannabis a neuroprotectant or a neurotoxin?

Despite what your well-meaning parents may have told you about ‘dope,’ most of the studies of cannabis and neurodegeneration shows that the phytocannabinoids found in the plant act to protect human health. And in some cases, reverse the effects of aging and neurodegeneration. The endocannabinoid system plays a significant role in developing central and peripheral nervous systems and modulates the impact of the immune system. Phytocannabinoids help to reduce neuroinflammation, oxidation and glutamate release, and the development of amyloid plaques while also decreasing nerve cell apoptosis. This is not to discount the short-term adverse cognitive effects of consuming cannabis, which can include confusion, disorientation, time dilation, and short-term memory loss.

In conclusion, on the long-term, cannabis has the opposite effect, by slowing down the mechanisms which led to neurogenerative diseases, and possible typical factors involved with aging.

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Chad Scott is a freelance science writer who specializes in the field of cannabis. He spent over a decade living in Thailand. He was diagnosed with Acute Myeloid Leukemia while living in Thailand in 2016. Upon diagnosis, Chad immediately began chemotherapy at a rural hospital in the country. He continued to use cannabis oil throughout his chemotherapy treatments for almost 1 year, and never again experienced any nausea or vomiting, and was able to sleep and eat normally. From his personal experiences, he has become an advocate for medical cannabis and believes that all cancer patients should have the right to access this natural medicine if they so choose.
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