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group_4_presentation_3_-_effects_of_marijuana_on_the_brain [2017/04/04 14:44] josephht created |
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| - | =======Alzheimer's Disease Powerpoint======= | ||
| - | {{:alzheimers_presentation_2_.pptx|}} | ||
| - | ======= Alzheimer's Disease ======= | ||
| - | {{youtube>large:Ey5AXGgywsY}} | ||
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| ===== INTRODUCTION ===== | ===== INTRODUCTION ===== | ||
| - | Alzheimer’s disease is a type of dementia specifically targeting areas of the brain responsible for memory, behaviour and language. Throughout the progression of this disease, neurons lose their ability to properly communicate, causing cell death in these regions. Alzheimer’s is a progressive disease where its symptoms accumulate very slowly, and worsen over time (da Silva, 2017). Beginning stages are typically very mild, however eventually individual’s lose the ability to engage in everyday tasks such as having meaningful conversation and responding to environmental cues. Though Alzheimer’s is not a normal side effect of aging, its greatest risk factor is age. However, approximately five percent of people between the ages of 40-50 develop early-onset Alzheimer’s (da Silva, 2017). | + | Marijuana comes from the hemp plant known as Cannabis Sativa (Deem, 2013). It is made up of a concoction of the dried, shredded leaves and flowers from this particular plant (Deem, 2013). Cannabis Sativa plants were initially native to Central and Southern Asia (Deem, 2013). However, today majority of its best-known varieties are grown in Colombia, Mexico, Brazil, and Africa (Deem, 2013). The dominant psychoactive chemical in marijuana, which is responsible for majority of the intoxicating, mind-altering effects that people experience, is delta-9-tetrahydrocannabinol (THC), seen in figure 1 (Deem, 2013). This chemical is found in its most abundant concentrations in resin, which is the byproduct of smoking marijuana. Resin can be smoked as well, however, it is considered to be the unhealthiest aspect of smoking marijuana due to its high concentrations of tar and carbon (Deem, 2013). Additionally, the plant contains over 500 other chemicals, including compounds chemically similar to THC, referred to as cannabinoids (Deem, 2013). |
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| + | When marijuana is smoked, THC, along with the other chemicals contained within marijuana, pass from the lungs and enter the bloodstream. Once in the bloodstream these chemicals are rapidly carried throughout the body to the brain. The parts of the brain most affected by THC are the hippocampus and cerebellum, as these contain high levels of cannabinoid 1 receptors (which is what THC binds to) (Bonsor & Gerbis, 2001). Once these chemicals reach the brain the effects of the drug are felt. People’s experiences vary from a sense of relaxation, laughter, and increased appetite, to anxiety, fear, or panic. But the latter effects are most common when an individual is inexperienced with the drug or intakes a high amount (Bonsor & Gerbis, 2001). Detectable amounts of THC can remain in the body for days after use, however, noticeable effects from inhaled marijuana generally last between one to three hours (Bonsor & Gerbis, 2001). Once these effects ware off a person will generally return to their typical sober state. The reason why marijuana is considered dangerous is because the ingested THC binds to cannabinoid receptors found in the brain which leads to neural changes, affecting diverse cognitive processes. However, there is currently a lot of debate around how much of these changes are permanent (Bonsor & Gerbis, 2001). | ||
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| + | <box 80% round | >{{:thc.gif|}} </box|Figure 1: The chemical structure of delta-9-tetrahydrocannabinol (THC). (Deem, 2013)> | ||
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| + | =====CANNABIS CONSUMPTION===== | ||
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| + | Marijuana can be consumed in various ways ranging from liquid tinctures to dermal patches and oral sprays. Firstly, liquid tinctures are extracts taken from the marijuana plant that are taken orally; as well as oral sprays which could also be administered orally (Cohen & Rudick, 2007). Dermal patches are effective due to the lipophilic property of marijuana, which allows it to be readily dissolved in a fat-soluble substance and penetrate the cell membrane (Rosenthal & Newhart, 2002). The most common way of consuming marijuana is through smoking, vaporizing and eating edibles. Marijuana is often consumed by packing the dried buds into rolling paper, cigars, pipes, or bongs. Also, many prefer to eat marijuana edibles such as, weed brownies and cookies. Other less common methods of consumption include, capsules and lozenges (Rosenthal & Newhart, 2002). | ||
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| + | =====CANNABIS USAGE===== | ||
| + | ====MEDICINAL==== | ||
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| + | Marijuana has three prominent usages, medicinal, spiritual and recreational. It is often quite difficult for scientists to study potential medicinal marijuana uses since it is difficult to obtain permission for human medical trials (Richard & Paul, nd). Furthermore, marijuana is currently classified as a schedule 2 substance by the federal government, making it even tougher to obtain permission (Hoffmann & Weber, 2010). In addition, far more studies regarding the potential harmful effects of marijuana have been conducted and only very minimal (6%) have been conducted studying its potential benefits (Gupta, 2013). Many studies focusing on the medicinal use of marijuana have shown varying results and despite little research on marijuana per se, it is important to note this does not imply that marijuana has no medicinal purposes. | ||
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| + | However, few case studies and research has led to promising results for potential medicinal uses of marijuana. Firstly, marijuana can be considered during chemotherapy to alleviate common side effects such as vomiting and nausea (Murnion, 2015). Individuals with HIV/AIDS may also use marijuana for similar reasons along with improving their appetite. Marijuana has also been somewhat effective in treating chronic pain and muscle spasms, including pain from neuropathy that may be caused due to fibromyalgia and rheumatoid arthritis (Murnion, 2015). Marijuana has also shown limited evidence in treating neurological problems such as, multiple sclerosis and epilepsy. In epilepsy specifically, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have shown to give patients relief from cases of spasticity (Murnion, 2015). In addition, some studies have shown marijuana has significantly improved tics in patients suffering from Tourette syndrome. Marijuana can also act as a supplementary means of treatment in individuals suffering from anorexia, arthritis, glaucoma and migraines (Richard & Paul, nd). | ||
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| + | Although minimal research has been conducted on cannabinoids and its use in treatment of cancer, cannabinoids have displayed anti-cancer effects in various laboratory experiments. There is ongoing research being conducted to explore different medicinal properties of marijuana. There has been extensive focus on marijuana’s effect on dementia, diabetes, epilepsy, glaucoma, and Tourette syndrome. Cannabinoids have been hypothesized to relieve some of the symptoms associated with Alzheimer’s Disease and may assist in slowing cell damage in diabetes mellitus type 1 (Caulkins, Kilmer, & Kleiman, 2016) | ||
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| + | ====SPIRITUAL==== | ||
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| + | Marijuana has had a long history of spiritual use and both historically and presently has been viewed as an entheogenic. To elaborate, marijuana has been used to reach a stage of enlightenment, connection, and nirvana. Despite its rich historical use, many religions have opposing stances on marijuana, but those in support have associated the psychoactive effects that marijuana may produce with an intense spiritual experience (Bello, 2007). | ||
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| + | ====RECREATIONAL==== | ||
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| + | The use of a psychoactive drug to alter one’s mind state, modify emotions, cognitions, and perceptions is often described as recreational usage. Marijuana has been long used as a recreational drug due its psychoactive effects (Bello, 2007). Today, people use marijuana for several activities and occasions, including but not limited to (Osborne & Fogel, 2008) : | ||
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| + | * Relaxing and Concentrating | ||
| + | * Making everyday activities more enjoyable | ||
| + | * Eating | ||
| + | * Listening to music | ||
| + | * Socializing | ||
| + | * Watching movies | ||
| + | * Playing sports | ||
| + | * Having Sex | ||
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| - | Alzheimer’s is the most common neurodegenerative disease. Individuals diagnosed with this disease live approximately eight years after symptoms become noticeable (Alzheimer's Association, 2011). This is a result of the progressive nerve cell death and tissue loss within the brain. Consequently, as an individual continues to age the size of the brain drastically shrinks, causing loss of function to almost all areas. | ||
| - | <box 65% round | > {{:brain_comparison.png|}} </box| Figure 1 - Brain size comparison between a healthy and advanced Alzheimer’s brain. (Alzheimer’s Association, 2011))> | ||
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| - | =====SIGNS & SYMPTOMS===== | ||
| - | Though there are many signs of early onset Alzheimer’s, five of the major symptoms include: | ||
| - | - **Memory loss**: I.e. forgetting important dates or repeatedly asking the same question | ||
| - | - **Difficulty with familiar tasks**: I.e. not being able to drive to familiar locations | ||
| - | - **Confusion with time or place**: I.e. losing track of dates/seasons | ||
| - | - **New issues with speaking or writing**: I.e. trouble following/ joining a conversation | ||
| - | - **Changes in mood and personality**: I.e. becoming confused, depressed and anxious | ||
| - | <box 90% round | > {{:ad.png|}} </box| Figure 2 - Common symptoms of Alzheimer’s. (Cephalicvein, 2016)> | ||
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| ===== EPIDEMIOLOGY ===== | ===== EPIDEMIOLOGY ===== | ||
| - | Key Points: | + | In 2012, 43% of Canadians reported that they had used marijuana at some time in their lives, and 12% reported using it in the past year (Statistics Canada, 2013). Marijuana use was more common among males than females (Statistics Canada, 2013). People aged 18 to 24 had the highest prevalence of past-year marijuana use, and tended to use it more frequently than did people of other ages (Statistics Canada, 2013). |
| - | * Worldwide, nearly 44 million people have Alzheimer’s or a related dementia. | + | |
| - | * Only 1-in-4 people with Alzheimer’s disease have been diagnosed. | + | |
| - | * Alzheimer’s and dementia is most common in Western Europe (North America is close behind). | + | |
| - | * Alzheimer’s is least prevalent in Sub-Saharan Africa. | + | |
| - | * Alzheimer’s and other dementias are the top cause for disabilities in later life. (Alzheimer’s Disease International, 2015) | + | |
| - | <box 70% round | > {{:epia.png|}} </box| Figure 3 - Projected growth of Dementia in the world in several areas. (Alzheimer's Disease International, 2015) > | + | |
| - | The incidence of AD is approximately 5–8 for per thousand person, which represents half of new dementia cases each year are AD (Bermejo-Pareja et al, 2008). One of the primary risk factor for AD, where there is a correlation of the incidence rate of every five years after the age of 65, the risk of acquiring AD approximately doubles (Di Carlo et al, 2002). Furthermore, there is also higher incidence rates in women compared to men of developing AD particularly in the population older than 85 (Andersen et al, 1999). | + | |
| - | In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group. (Hebert et al, 2003) Prevalence rates of AD is less in developed countries compared to developing countries (Ferri et al, 2006). AD accounts to 50-70% of all forms of dementia, making it the leading cause of this neurodegenerative disease (7). Furthermore, due to the rapid increase of dementia, individuals would also be at increased risk of AD. Another study estimated that in 2006, 0.40% of the world population were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050. (Brookmeyer et al, 2007) | + | |
| - | <box 70% round | > {{:deathsa.png|}} </box| Figure 4 - Deaths due to Alzheimer's in 2012 (Red indicating larger number of deaths compared to orange). (Wikipedia, 2013) > | + | |
| - | <box 70% round | > {{:resized.png|}} </box| Figure 5 - The prevalence and incidence rates in various areas compared to an age category. (Qiu, Kivipelto & Strauss, 2009) > | + | |
| + | In Canada, as in many other countries, marijuana is the most commonly used illicit drug (Statistics Canada, 2013). | ||
| + | <box 80% round | >{{:rsz_1231324reqwf.png|}} </box|Figure 2: Estimated prevalence (proportion) of cannabis dependence by age, sex and region, 2010. (Degenhard et al, 2013)> | ||
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| + | Throughout the world the prevalence was higher in males than females, resulting in an average male:female sex ratio of 1.8 (Degenhard et al, 2013). Prevalence peaks worldwide in the 20-24 years age group at between and then steadily decreasing after that age group thereafter (Degenhard et al, 2013). | ||
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| + | <box 50% round | >{{:rsz_1journalpone0076635g002.png|}} </box|Figure 3: Pooled regional prevalence of cannabis dependence, 2010. | ||
| + | Note. Prevalence estimates were standardised by population age and sex; AP-HI: Asia Pacific, High Income, As-C: Asia Central, AS-E: Asia East, AS-S: Asia South, A-SE: Asia Southeast, Aus: Australasia, Caribb: Caribbean, Eur-C: Europe Central, Eur-E: Europe Eastern, Eur-W: Europe Western, LA-An: Latin America, Andean, LA-C: Latin America, Central, LA-Sth: Latin America, Southern, LA-Trop: Latin America, Tropical, Nafr-ME: North Africa/Middle East, Nam-HI: North America, High Income, Oc: Oceania, SSA-C: Sub-Saharan Africa, Central, SSA-E: Sub-Saharan Africa, East, SSA-S: Sub-Saharan Africa Southern, SSA-W: Sub-Saharan Africa, West. (Degenhard et al, 2013)> | ||
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| + | Prevalence in high income regions was much higher than that in low to middle income regions and the global average (Degenhard et al, 2013). Cannabis dependence in Australasia is about 8 times higher than prevalence in Sub-Saharan Africa, West (Degenhard et al, 2013). | ||
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| + | <box 50% round | >{{:rsz_journalpone0076635g004.png|}}</box|Figure 4: Country-level DALYs per 100,000 population for cannabis dependence, age-standardised, for 2010. | ||
| + | Note. Low: shows countries with statistically lower DALY rates than global mean; Middle: Shows countries with DALY rates that are not statistically different to global mean; High: Shows countries with statistically higher DALY rates than global mean. (Degenhard et al, 2013)> | ||
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| + | Worldwide, DALYs are closely associated with high income countries having more effected years compared to those of low income countries (Degenhard et al, 2013). The statistical DALY rates are comparably higher than the global mean in higher income countries than lower income (Degenhard et al, 2013). | ||
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| - | ===== PATHOPHYSIOLOGY ===== | + | ===== SHORT-TERM EFFECTS ===== |
| - | The early onset of Alzheimer’s disease (AD) is marked by neuronal loss occurring within the entorhinal cortex of the brain, which is located under the cerebral cortex (Columbia University Medical Center, 2013). The major function of this region of the brain is to submit information to and from structures in the hippocampus. The hippocampus then accumulates this information and stores it as long-term memory. Any pathology in these areas of the brain would affect an individual’s memory, being as they are so closely associated with memory processing (Saylor, 2017). Additionally, pathology is also seen in the amygdala, a region accountable for emotional responses and behaviour to various stimuli (Saylor, 2017). During the moderate onset of AD, cortical and hippocampal atrophy continues, alongside the widening of cerebrospinal fluid-filled ventricles within the brain (Salcudean, 2010). This ventricle widening causes further damage to surrounding tissues in the brain. A patient affected by AD may experience an inability to accomplish daily tasks, increased anxiety and emotional outbursts, and language impairment among several other symptoms as their memory loss continues. The severe (late) stage of dementia is characterized by the presence of two major neuropathological trademarks including intracellular neurofibrillary tangles and extracellular amyloid plaques (Salcudean, 2010). At this point, irreversible neuronal loss is evident throughout the brain, causing extensive dysfunction and extreme atrophies to affected areas (see Figure 6). This individual would experience severe loss of autonomic functions and would require complete dependence on others for care. | + | The short-term effects of marijuana on the user can range from increasing relaxation and relieving disease related symptoms to more negative impacts, such as increased heart rate and increased risk of heart disease (Ameri, 1999). |
| - | <box 45% round | >{{:brain-w550.jpg|}} </box|Figure 6: Normal brain vs. Brain affected with Alzheimer's Disease. Atrophy of cerebral cortex, and hippocampus is shown, as well as enlarged ventricles (Whole Health Insider, 2013)> | + | Positive Effects: |
| + | Not all users of marijuana do it for the sole purpose of reaching the euphoric sensation of being “high.” Many use cannabis to experience increased relaxation, creativity and pain relief from symptoms associated with various diseases. Recreational users of marijuana enjoy the immediate effect of mild relaxation as well as the increased social enhancement that is involved with using the drug (Lee et al., 2007). Other users smoke cannabis to enhance their creativity, as marijuana is known to reduce inhibition. Whether the drug leads to actual increases in creativity or just an enhanced perception of one’s creativity is still up for debate, as studies show conflicting results (Jones et al., 2009). Yet, many other users of the drug do so in order to decrease chronic pain or the uncomfortable symptoms of different diseases. Cannabis in pharmacotherapy of diseases is still under extensive research, but much of it leans towards treating convulsions, depression, and asthma, among others abnormalities (Martin-Sanchez et al., 2009). Cannabinoids in the brain are associated with improvements in motor control in many patients suffering from Parkinson’s disease, showing its medical usage potential (Lotan et al., 2014). | ||
| + | Additionally, marijuana is known as a stimulant to appetite, leading to increases in food consumption (Foltin et al., 1988). It enhances the user’s taste and smell sensitivity to food, as well as increases the number of snacking occasions throughout the day. This is especially beneficial to cancer patients, as it helps minimize nausea that results from chemotherapy (Voth et al., 1997, Martin-Sanchez et al., 2009). | ||
| - | Amyloid precursor proteins (APP) are constantly released during normal metabolism in the brain. Little is understood about the functioning of these proteins, especially regarding its part in the pathogenesis of AD (Lin, 2001). APP can be cleaved by α-secretase proteases, which would result in normal functioning of the brain, and no buildup of extracellular amyloid plaque (Lichtenthaler, 2012) (See left hand side of Figure 7). However, if the APP molecule is cleaved by β-secretase and/or γ-secretase, amyloid-β peptide fragments are released into the extracellular space due to an abnormal cleavage of the protein by these enzymes (Salcudean, 2010). In small amounts, this procedure is not harmful and may even be desirable for normal synaptic functioning. More often than not, however, the over activity of these β- and γ-secretase enzymes cause a large, toxic amount of amyloid-β peptide fragments. In excessive amounts, these fragments aggregate and form plaque in the extracellular space (see right hand side of Figure 7). PSEN1 and PSEN2 (Presenilin 1 and 2 respectively) play a part in regulating APP processing through γ-secretase, but mutuations in these protein molecules increase γ-secretase activity, which can lead to even more plaque formation (Salcudean, 2010). A huge component of these plaques are found throughout the brains of patients affected by AD, showing that they may play a huge role in the loss of functioning of the brain in these individuals (Lin, 2001). | + | Negative Effects: |
| - | <box 45% round | > {{:screen_shot_2017-03-04_at_8.35.30_pm.png|}} </box| Figure 7: Normal cleavage vs Abnormal cleavage of the APP molecule by proteases (da Silva, 2015).> | + | Although marijuana may have some positive short-term impacts on the user, it may also bring about a range of harmful effects as well. The extent to which these effects are detrimental to the user depends on the age and tolerance of the person consuming the drug. Studies show that cannabis use, especially early onset use (before age 15), is associated with increased delinquent behaviour, future employment and financial issues, mental health problems and substance abuse (Fergusson et al., 1996). This may be due to a sensitive period of cognitive development at this age, during which the impact of cannabinoid receptors in the brain hinder normal development (Pope et al., 2003). Moreover, cannabis may be more toxic to the developing brain than it is to mature brains, causing a decrease in white matter in developing brains (see Figure 5) (Pope et al., 2003). These toxic changes occur when cannabinoid receptors interfere with normal functioning of neurotransmitters in different regions of the brain (Ameri, 1999). While many scientists may consider cannabis as a potential pharmacotherapy, research shows it may actually bring more harmful effects to the user than beneficial ones (Lotan et al., 2014). Some research even indicates that frequent marijuana use can lead to acute psychosis and manic episodes, especially in individuals with pre-existing psychotic disorders (Khan, 2009). This may be an explanation as to why some individuals experience lowered anxiety while others face anxiety-inducing effects post cannabis use. It is not uncommon for those facing heightened anxiety to hallucinate, feel paranoid, feel irrational panic or have a sudden fear of dying after smoking marijuana (Khan, 2009). In addition, frequent cannabis use can lead to even more negative consequences, including disruptions with short-term memory, lowered coordination, delayed reaction time, increased heart rate and sexual problems (Drug Free World, 2006). Thus, it is very important for an individual to do more research before making the decision to consume cannabis in any form. |
| - | Similarly, the brains of patients with AD seem to have an abundant amount of intracellular neurofibrillary tangles (Salcudean, 2010). Microtubules run along the length of axons, simulating tracks for motor proteins like kinesin and dynein to use in transporting their neuron signals to other areas of the brain. The Tau protein binds to this microtubule to stabilize it and prevent its depolymerization (Salcudean, 2010) (See Figure 8 a). In normal physiology of a healthy neuron, protein kinases phosphorylate tau, lifting them off the microtubule and allowing the passage of the motor proteins along the track. After this passage, the tau dephosphorylates and reattaches to the microtubule, stabilizing it once again (Salcudean, 2010). This procedure is much different in pathology of a diseased neuron. Hyperphosphorylation of tau proteins occur, which causes tau to aggregate with other taus, forming tangles in the brain (See Figure 8 b). Neuron signaling is not able to function as normal when this occurs, and it seems to have a choking affect on nerve cells, killing them in abundance (Ballatore, 2007). | + | <box 65% round | >{{:brain.png|}} </box|Figure 5: White matter in brains of marijuana users (right) and non-users (left). (Arnone, 2008)> |
| - | <box 45% round | > {{:screen_shot_2017-03-04_at_9.05.44_pm.png|}} </box| Figure 8: Healthy vs. Diseased neuron and formation of intracellular neurofibrillary tangles (Brunden, 2008).> | ||
| - | Thus, both these processes are seen in many patients that suffer from AD. However, there are some patients with AD that do not seem to have mutations in their APP, PSEN1 and PSEN2 genes. This insinuates that some forms of this dementia can be associated with alterations in other genes that have yet to be identified by scientific research (Mayo Foundation for Medical Education and Research, 2016). | ||
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| - | ===== DIAGNOSIS ===== | + | ===== LONG-TERM EFFECTS ===== |
| - | Alzheimer’s Disease can be categorized into three stages; Early, Mild-to-severe, and Advanced. The clinical diagnosis is most often made during the mild-to-severe stage. Nonetheless, definitive diagnosis of Alzheimer’s can only be made post-mortem by examining brain tissues (Dubois et al., 2014). | + | As a result of the chemical THC binding to cannabinoid 1 (CB1) receptors in the brain, observed long term morphological brain alterations connected to marijuana use are reported in CB1 receptor-enriched areas (Filbey et al, 2014). This includes regions such as the orbitofrontal cortex, amygdala, hippocampus, and cerebellum, a few of which are illustrated in figure # below (Filbey et al, 2014). Studies focusing on the physical brain effects from marijuana have found significant amounts of brain volume reductions in these CB1 enriched areas, particularly within the orbitofrontal cortex (Filbey et al, 2014). However, whether these reductions in brain volume lead to a cascade of downstream alterations in brain organization and function is still unknown. However, there is a high possibility that as a consequence of brain volume reductions, connectivity changes emerge as well (Filbey et al, 2014). These connectivity declines are currently a possible explanation for why someone who has used marijuana over long periods of time may appear cognitively slower. |
| - | Clinicians can diagnose the presence of Alzheimer’s disease with an adequate amount of certainty using several factors. These factors include the individual’s medical history, history from relatives, behaviour observations, presence of characteristic neurological and neuropsychological features, and the absence of alternate conditions (Dubois et al., 2014). This probable diagnosis of Alzheimer’s Disease can be made with approximately 90% confidence based on the stated criteria. Clinicians focus heavily on a combination of both brain imaging and clinical assessments for diagnosis, particularly focusing on declining mental ability (Dubois et al., 2014). In order to identify the presence of neurological features, a number of brain imaging techniques are used, such as, computed tomography (CT), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). These can not only be used to identify presence of neurological features characteristic of Alzheimer’s disease, but also exclude other pathology or subtypes of dementia that may be mistaken for Alzheimer’s Disease (McKhann et al., 2011) . Figure 9 shows a PET scan in which we can compare a healthy brain to a mild-to-moderate Alzheimer’s Disease brain. Not only is there a shrinkage in mass of the Alzheimer’s Disease brain, but glucose metabolism, indicated by the red probe, seems to be significantly decreased in the Alzheimer’s Disease brain relative to the healthy brain (Landau et al., 2014). In addition, assessment of the individual’s intellectual functioning can further help support a diagnosis. The Mini-Mental State Examination (MMSE) is the most common administered test to evaluate cognitive impairments such as problems with memory, attention and language. Further examinations are crucial to diagnose Alzheimer’s with sufficient certainty, including, interviews with family members and caregivers, who can provide important information about daily living abilities (McKhann et al., 2011). | + | <box 80% round | > {{:marijuana-brain_2_.jpg|}} </box|Figure ##: A few cannabinoid 1 (CB1) receptor sites within the brain. (Bonsor & Gerbis 2001) > |
| - | <box 40% round | > {{:picture1222.jpg|}} </box| Figure 9 - Healthy brain vs. Alzheimer's Disease brain in the mild-to-moderate stage (daSilva, 2015)> | + | A study done by Filbey et al used high-resolution MRI techniques to obtain brain images from a cohort of chronic cannabis users, in comparison to age- and sex-matched nonusing controls. Their obtained images revealed a significant decline in gray matter volume in the orbitofrontal cortex (OFC) in the marijuana users in comparison to the controls (Filbey et al, 2014). The OFC is the primary region in the reward network, and it is also enriched with CB1 receptors, which helps explain why it was mainly targeted in the chronic marijuana users. However, the cannabis group also showed higher levels of functional connectivity within the OFC compared with the control group, this can be seen in figure # below. These findings could help explain why marijuana users claim to experience feelings of creativity. |
| - | It is vital to also identify biomarkers that will help assess risk, diagnosis, and monitor the progression of the disease (Hansson et al., 2006). They can provide valuable indications of health and disease, and contain high sensitivity and specificity that defines their diagnostic utility (Humpel, 2011). Biomarkers can help distinguish between different types of dementias that may appear very similar to Alzheimer’s Disease. There are no specific biomarkers that can confirm Alzheimer’s Disease with 100% certainty. However, it is possible to use measurements of B-amyloid (1-42), total tau, and phosphorylated-tau—181 in the cerebrospinal fluid as biomarkers for Alzheimer’s Disease (Humpel, 2011). The combination of all three can significantly increase the diagnosis of Alzheimer’s Disease (Humpel, 2011). In patients with Alzheimer’s, due to aggregation of B-Amyloid (1-42) in the brain, B-amyloid (1-42) would essentially be reduced in the cerebrospinal fluid, whereas total tau and phosphorylated tau would be enhanced (Humpel, 2011). | + | <box 80% round | > {{:f2.medium.gif|}} </box|Figure ##: Brain imaging of activity level in marijuana users versus nonusing controls. (Filbey et al, 2014)> |
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| + | Additionally, the effects of cannabis may be beneficial to white matter by regulating mitochondrial activity and antioxidant processes, consequently protecting neurons on the molecular level (Filbey et al, 2014). These results suggest that OFC grey matter has higher vulnerability to the neurotoxic effects of cannabis use. In terms of cognition, marijuana use can cause functional impairment, however, the degree and/or duration of the impairment depends on the age when an individual initially began using and the duration of their use (Abuse, 2017). A large longitudinal study in New Zealand focused on the effects of marijuana as a result of age. Their findings revealed that persistent marijuana use beginning in adolescence was strongly associated with a loss of six to eight IQ points, as measured in mid-adulthood (Abuse, 2017). Significantly, those who partook in marijuana use heavily as teenagers but quit in adulthood, did not recover their lost IQ points (Abuse, 2017). Conversely, those who began using marijuana heavily in adulthood did not lose any IQ points (Abuse, 2017). These results suggest that marijuana has its strongest long-term impact on younger individuals, whose brains are still maturing and building new connections. Another study conducted by Zalesky et al expanded on the idea of cannabis use in adolescence and revealed that THC is hazardous to white matter of developing brains. However, he also suggests that the level of harm it elicits on white matter diminishes with age. | ||
| - | Candidate gene studies for Alzheimer’s Disease do not allow conclusive evidence for the presence of disease beyond a simple hypothesis. The Genome-wide association studies (GWAS) test many genetic markers to detect the presence of diseases related to Alzheimer’s Disease. This form of study is most often used in clinical trials rather than clinical diagnosis (Bertram & Tanzi, 2009). | ||
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| - | ===== CURRENT TREATMENTS ===== | ||
| - | Similar to the diagnosis of the disease, there has yet to be an effective cure for Alzheimer’s Disease. Although there are several treatments available that help treat the symptoms of the disease, they provide relatively few benefits. They have not shown to delay the onset of AD or halt the progression of the disease. Current treatments can be pharmaceutical, psychosocial and caregiving in nature (Yiannopoulou & Papageorgiou, 2013). | + | ===== MECHANISM OF ACTION ===== |
| - | Pharmaceutical treatments include acetylcholinesterase inhibitors and as well as a NMDA receptor antagonist. Donzepil, Rivastigmine, and Galantime are acetylcholinesterase inhibitors most often used in the mild-to-moderate stage of the disease (Lahiri, Greig, & Sambamurti, 2002). Alzheimer’s Disease is correlated with a decrease in the activity of cholinergic neurons, and these drugs inhibit the activity acetylcholinesterase (breakdown of acetylcholine), therefore increasing the concentration of acetylcholine in the brain. Approximately 20% of patients taking one of these three drugs may show common side effects associated with cholinergic excess such as, nausea and vomiting (Lahiri, Greig, & Sambamurti, 2002). Memantine is a NMDA receptor antagonist, which is predominantly used in the moderate-to-severe stages of the disease (Reisberg et al., 2003). In Alzheimer’s Disease the excitatory neurotransmitter Glutamate is overstimulated, ultimately causing cell death though a process known as excitotoxicity. Memantine acts on the glutamatergic system by inhibiting the overstimulation of glutamate. Common side effects of this drug include, hallucinations, confusion, fatigue, headache, and dizziness (Reisberg et al., 2003). | + | Marijuana’s active ingredient, delta-9-tetrahydrocannabinol (THC) targets the endocannabinoid system, which is one the communication systems within the brain and body. This system is part of the CNS and is highly integrated with the full function of the body. There are 2 main parts of the endocannabinoid system, the cannabinoid (CB) receptors and the cannabinoids which act on these receptors (neurotransmitters). The human body produces natural cannabinoids called anandamide and 2-AG (arachidonoyl glycerol). THC is an agonist of these neurotransmitters and competes with the natural cannabinoids produced by the body (Scholastic, 2011). |
| - | <box 75% round | > {{:treatments22.jpeg|}} </box| Figure 10 - Pharmaceutical Treatments Summarized (Lahiri, Grieg, & Sambamurti, 2002)> | + | Specifically there are 2 main CB receptors, CB1 receptors, which are abundant in the CNS and many parts of the brain, and the CB2 receptors whicher are found in tissues associated with immune function such as the spleen, leukocytes, and bone marrow. Particularly, CB1 receptors are the focus of the effects of marijuana on the brain (Scholastic, 2011). |
| - | In addition to pharmaceutical treatments, many Alzheimer’s patients will undergo psychosocial and caregiving treatments. Psychosocial treatments specifically target the cognition, emotion, behaviour, and stimulation-oriented aspects of the disease (Brodaty, Green, & Koschera, 2003). A common example of a psychosocial intervention is known as Reminiscence Therapy, in which patients are involved in a discussion of past experiences with photographs, music, and other familiar items. This type of intervention tends to show minor improvements in the cognition and mood of the patients (Sitzer, Twamley, & Jeste, 2006). Caregiving is essential to help patients who are incapable of carrying out common day-to-day activities. Both have received minimal scientific support but seem to be significant in helping patients adjust to the illness (Brodaty, Green, & Koschera, 2003). | + | {{:nida10-ins2_endocannabinoid-v1.jpg|}} |
| - | ---- | + | Most nervous communication systems, neurotransmitter pathways start from vesicles inside the presynaptic cleft, exiting the presynaptic cleft and binding to receptors on the postsynaptic cleft. In contrast, specifically CB1 receptors are located on the presynaptic cleft, while anandamide and 2-AG are produced at the postsynaptic site, further released to bind to the CB1 receptors located on the pre-synaptic cleft. This reverse mechanism gives rise to its ultimate function, controlling all physiological changes induced by the neurotransmitters that create synapses from presynaptic to postsynaptic neurons (Iverson, L., 2003). Cannabinoids alter neurotransmitter trafficking and concentrations by controlling the mechanisms occurring in the presynaptic cleft, having to do with the release of many transmitters. In essence, cannabinoids are known as “dimmer switches” particularly due to how they modulate the prolonged or transient reduction of neurotransmitters. Specific physiological changes observed are the reduction of calcium uptake of pre-synaptic neurons, which are the main triggers of releasing neurotransmitter filled vesicles, as well as an increase of potassium which minimizes depolarization, dampening synapse activation (Iverson, L., 2003). |
| - | ===== FUTURE TREATMENTS ===== | + | {{:cn-4-3-239_f2.jpg|}} |
| - | Researchers are continually looking at possible ways to delay and halt the progression of Alzheimer’s Disease. Current treatments only provide minimal relief to the symptoms of the disease and not the underlying disease itself. | + | |
| - | Some possible therapeutics include drugs that decrease the production of B-amyloid plaques and tau tangles, removing the toxic aggregates, or preventing the aggregation (Yiannopoulou & Papageorgiou, 2013). | + | When marijuana is smoked, or administered into the body in other ways, THC, being an agonist of these natural cannabinoids, has a great concentration and is able to bind to these CB1 receptors in the brain (Scholastic, 2011). They override the natural system and takeover completely, having various effects such as slowing down reaction time, decrease function of short-term memory, affected judgment or cause of anxiety. In addition, THC triggers areas of the brain that make you feel good, known as the “high” (Scholastic, 2011). |
| - | Figure 11 depicts therapeutics that target Tau aggregates through kinase inhibitors, which block the formation of the tau aggregates (Yiannopoulou & Papageorgiou, 2013). | + | {{:nida10-ins2_thc-brain-v1.jpg|}} |
| - | <box 40% round | > {{:picture122.jpg|}} </box| Figure 11 - Possible therapeutics targeting tau aggregates (daSilva, 2015)> | + | The binding of THC initiates a signal transduction which essentially has 4 targets: adenylate cyclase, calcium channels, potassium channels, kinases and ceramides (Vathi, S., 2013). Adenyl cyclase modulation leads to an increase or decrease in cAMP, in this a decrease, further causing a decrease in calcium from intracellular stores located in the pre-synaptic cleft. For potassium channels, cannabinoids act on the Kir and Ka channels, which allows greater influx of potassium in the presynaptic cleft, causing hyperpolarization, in other words, a decrease in depolarization occurs (Vathi, S., 2013). We also see these CB1 receptors associated with enzymes that hydrolyze shingomyelin to ceramide and phosphocholine. These act as second messengers with activate pathways such as Raf1 and ERK. We also see proliferation and differentiation activated such as the JNK and p38 MAPK pathways (Vathi, S., 2013). |
| - | Figure 12 shows four distinct ways amyloid specific antibodies may be able to degenerate the B-amyloid plaques (Yiannopoulou & Papageorgiou, 2013). | + | {{:gzm.jpg|}} |
| + | ---- | ||
| - | <box 40% round | > {{:picture133.jpg|}} </box| Figure 12 - Possible therapeutics targeting B-amyloid plaques (daSilva, 2015)> | + | ======= EFFECTS OF MARIJUANA ON THE BRAIN VIDEOS======= |
| - | In addition to future treatments, it is important to focus on advancing research and development in biomarkers that can help assess risk and monitor the underlying disease. | + | {{youtube>large:f_jCD3YkXwM}} |
| + | {{youtube>large:-SZzgfyXhJI}} | ||
| + | ---- | ||
| + | =======EFFECTS OF MARIJUANA ON THE BRAIN POWERPOINT======= | ||
| + | [[https://drive.google.com/file/d/0B2ajAdP9iGxrbnBwVkFEMWVGNkk/view?usp=sharing|Download Link]] | ||
| ---- | ---- | ||
| === References === | === References === | ||
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