CBD Oil for Sundowning: A Scientific Approach

Introduction

All of us probably know the awe-striking relation between dementia and Alzheimer’s disease: the two of them almost always accompany each other. Alzheimer’s disease is the most common cause of dementia in people. Dementia is the leading cause of memory loss in the people and maybe affecting someone due to degenerative brain diseases such as Alzheimer’s disease or due to physical brain injuries that cause pathological disproportions in the brain that lead to damage in the regions of the brain involved in the formation and reconsolidation of memories.

Sundowning – A Characteristic of Dementias

The term ‘sundowning’ is a time-dependent situation occurring most commonly in people suffering from different types of dementia such as dementia due to Alzheimer’s disease. Sundowning refers to a state of extreme confusion, that most commonly occurs in the afternoon or late in the day spanning into the night. The people affected by this odd situation are also known as suffering from what doctors often refer to as the ‘sundown syndrome’. The time-dependent nature of this odd situation becomes extremely confused with the state of his or her mind. The state of confusion, accompanied by anxiety and nervousness is sometimes so extreme that the person may start experiencing personal neglect: a situation where he or she may lose the identity of his or her body. As is evident from the word ‘sundown’, the symptoms have onset when the sun starts going down, in other words in the late afternoon or the evening, spanning into the night. 

The humans and the body of other animals and plants are aware of the time of the day in their surroundings due to the existence of an inner body clock, that synchronizes various functions of the body with the time of the day the person is in. The processes occurring at a very specific part of the day or night tend to repeat themselves the next day, and in this way, the body of that organism is able to adapt itself according to the surroundings which greatly helps the organism in achieving homeostasis. These rhythmical changes in the body of that organism are caused due to the existence of circadian rhythms. The circadian rhythms affect every action of our bodies ranging from eating to having a sleep. Everything is efficiently coordinated with the time of the day through the nervous system and hormonal secretions from the small gland located under the hypothalamus known as the pineal gland. Anything that disturbs or causes interference with the normal synchronization of the body with its surroundings have very drastic results, often manifested in the form of routine disturbances and extreme confusion, along with anxiety and nervousness that lasts throughout the day. 

The scientists still do not know the exact mechanism of why sundown syndrome occurs in the first place. Although this syndrome is found to be common in the persons suffering from dementia due to various causes, there are many cases where people are affected by this disorder merely due to the natural course of aging. This all provides the evidence that sundown syndrome is linked to the vital memory circuits of the brain, which may undergo simultaneous degradation with the normal course of body aging. We know that dementia is caused due to neurodegenerative diseases such as Alzheimer’s disease or due to physical disruption of vital neuronal circuits in the brain that are involved in the formation and reconsolidation of memories. The person having dementia often forgets about trivial things, so there is a huge chance of the body’s inner clock being directly affected by dementia. Dementia may also disrupt the coordination between the nervous and endocrine systems of the body, affecting particularly many neuronal circuits that are involved in controlling emotions and the behavior of any person. Once these vital neuronal circuits are affected, the emotional behavior of the person affected by this disorder becomes hugely unpredictable, often the person is found to be irritable easily and there is an overall confusion along with anxiety affecting the person at particular situations, during particular times of the day such as in the late afternoon or the evening. All of these symptoms together translate into the ‘sundown syndrome’. 

Sundowning and Alzheimer’s – The Relation

We know that Alzheimer’s disease is a neurodegenerative disease occurring primarily due to the age-related or pathologic degradation of the neurological circuits of the brain in the areas that are related to the formation and reconsolidation of memories. Alzheimer’s Disease is a disorder caused due to the gradual degeneration and the resultant death of cerebral cortical cells. These are the cells that are involved in the vital transmission of neuronal signals in the process of forming new memories and reconsolidating the old ones, which are stored probably in the idle areas of the brain like the hippocampus. The overall effect of the death of these cells is visible in the form of dementia in the patient. The most common symptom of AD is memory loss, which may be so severe that personal neglect occurs in some of the patients. This disease may also lead to impaired cognitive abilities of a person, due to the severely damaged skill of forming new memories. Acquired cognitive disabilities caused by this disease have a diverse effect on the social life, overall behavior, and day to day activity of the patients. The neurodegenerative nature of Alzheimer’s disease implicates that the disease worsens over time and as the person ages. This shows us that the visible symptoms of the disease, the most common one being dementia, also deteriorates as the disease worsens. Deteriorating dementia means that the symptoms will gradually lead to personal neglect, to an extent that will manifest the symptoms of sundowning.

Sundowning in the patients affected by the Alzheimer’s disease is more common in the older patients. Although Alzheimer’s disease is not a normal part of aging in any person, the majority of the patients with this disease are 65 years or older. This does not mean that this disease cannot affect people of young age, almost every young person is at the same risk of having Alzheimer's like that of an old person. In the early stages of this disease, the memory loss is mild, but with late-stage Alzheimer's, the patient loses cognitive ability to carry on a conversation and respond to the specific stimuli in their surroundings. On average, a patient having Alzheimer's disease lives anywhere from 4 to 8 years after the initial diagnosis of the disease. But these numbers are not at all strict, and the patient lifespan can vary as long as 20 years depending on other factors such as nutrition and treatment of the disease. 

The sundowning syndrome in Alzheimer’s disease has an opposite effect to that of the disease itself. The symptoms of sundowning are more striking in the initial stages of the disease. But, as the disease progresses and there is a greater degeneration, the sundowning symptoms decrease day by day. It is a common notice that the sundowning symptoms can found in as many as 66 out of 100 people suffering from Alzheimer’s disease or other kinds of dementia. The onset of sundowning symptoms is not defined strictly, as it can occur at any stage of the disease. The most common trend found is that it is maximum in the middle stages of dementia, and tends to lessen as the disease progresses in the later stages.

As sundowning is the result of dementia, sundowning almost always occurs in Alzheimer’s disease, due to the prevalence of dementia in this disease. The utter confusion at particular times of the day in the patient is exhaustive and unsettling not only for the patient but is of great concern for the caregiver. The people and the places that the patient was familiar with before the disease seem to be unfamiliar to the patient, thereby triggering anger or confusion in the patient. This is due to the loss of memory that comes packed with this disease.

Stress, due to the state of confusion for the patient suffering from Alzheimer’s disease is another prime cause for the patient to go through the sundowning process. The utter state of confusion that shrouds the patient always is unsettling, which causes stress in the patient. 

The Effect of Cannabidiol

CBD, due to its promising effects on the persons suffering from dementia, offers bright prospects in the field of providing treatment for this disease, and indirectly providing relief from the sundowning symptoms in the patients suffering from dementia due to Alzheimer’s that trigger sundowning. The effect of cannabinoids such as CBD on the central nervous system on various vital brain circuits in the nervous system has found bright prospects in the treatment of various forms of dementia including Alzheimer’s. In this regard, a study was conducted and the results were published on PubMed. The study consisted of a total of 21 cases in which cannabinoids particularly CBD obtained from Cannabis plants were used as a therapeutic measure against Alzheimer’s disease. 

The results of the study were primarily focused on the neuroprotective abilities of the CBD oil on a type of cell in the major areas of the brain known as the PC12 neuronal cells. PC12 cells are closely related to the phenotype of sympathetic autonomic ganglion neurons upon differentiation with nerve growth factor (NGF). These cells have stem cell like properties and can be divided indefinitely to produce alike cells. The effects were studied not only in vivo but also in vitro in the lab. The in vitro studies conducted to examine the effect of CBD on a patient with Alzheimer’s through affecting the endocannabinoid system of the CNS were carried out on the PC12 neuronal cells. The results were largely in the favour of CBD affecting the endocannabinoid system and enhancing the neuroprotective properties of the system. CBD activated the Peroxisome Proliferator-Activated Receptor through an intrinsic pathway in the central nervous system. When this pathway was activated, it protected the neuronal PC12 cells from degradation due to oxidation and neurotoxicity. 

The in vivo studies pursued a more proactive approach toward the healing and anti-inflammatory properties of CBD. The anti-inflammatory effects of CBD are more pronounced in the central nervous system, through discouraging inflammation in the central areas of the brain that are concerned with memory formation and cognitive abilities.

The in vivo studies were limited to using non-human sources for analyzing the results because the study involved administering CBD right into the area of the brain involved with memory formation and processing. This included the administration of CBD to the right dorsal hippocampus of a mouse, supplemented with a component human alpha beta peptide, a chemical found in the human central nervous system. The human alpha beta peptide simulated similar effects of the chemical, as it would insert on the human nervous tissue.

The results of this study were different from the in vitro effects. The studies showed that CBD actively inhibited the expression of the glial fibrillary acidic protein (GFAP) due to its effect on the mRNA encoding GFAP.  CBD interfered with the transcription of the messenger RNA that is involved in the production of GFAP protein through translation. The CBD administered to the mouse also actively inhibited the expression of several inflammation-causing factors such as interleukin 1-beta protein. Interleukin 1 beta protein is an important mediator of inflammation in humans, causing leukocytes such as eosinophils to invade the tissue causing inflammation. The healing properties of phytocannabinoids such as cannabidiol (CBD) for Alzheimer’s disease and their effect in controlling and preventing further degeneration from happening in the central nervous system to prevent dementia were well pronounced.

The results of these studies, as a whole, provided strong evidence in the favour of CBD being an effective drug to check the progression of Alzheimer’s disease. The anti-inflammatory properties enhanced the neuroprotective abilities of the endocannabinoid system, thereby enhancing the natural defenses of the body against not only the foreign agents but also the simultaneous body changes that might affect the central nervous system through degenerative changes due to aging. CBD activated the peroxisome proliferator-activated receptor through the beta-catenin pathway to protect PC12 cells from neurotoxicity and oxidation stress that leads ultimately to cell death, thereby indirectly increasing the rate of cell survival along with reducing ROS production. 

Apart from the anti-inflammatory effects, CBD also participated in protecting the body, the central nervous system in particular, from different kinds of oxidative stress. Our body is under constant danger from different kinds of free radicals that are continuously formed in our bodies due to ionizing radiation. These free radicals are also formed as a by-product of different chemical reactions that occur in our bodies. These free radicals can be a potent initiator of tumor production in our bodies, particularly in the central nervous system. If the brain areas involved in the formation of memories is affected, the symptoms might point to Alzheimer’s disease. 

Cannabidiol had potent effects to reduce free radical production in the body. CBD also indirectly reduced lipid peroxidation in the areas of the central nervous system. Lipid peroxidation is found to be the main culprit behind the uncontrolled tumor production through dangerous free radicals. Decreased lipid peroxidation inhibited the hyperphosphorylation of the tau protein. The unphosphorylated tau protein inhibits acetylcholestrinase (the enzyme responsible for the breakdown of acetylcholine at neuromuscular junctions). All of this leads to an increased rate of neurogenesis in the hippocampus, which is a vital part of the brain involved in the formation of long-term memories. Discrepancies in this area of the brain mostly lead to various types of dementia. CBD indirectly promotes the health of the hippocampus, thereby reducing the risk of dementia in the later life of a person.

Sundowning and Insomnia

Another risk factor involving sundown syndrome is the exposure of the patient to light patterns. We know that the internal clocks of our bodies, or better known as circadian rhythms, are responsible for the timing of specific tasks in our bodies. Ranging from sleeping to appetite patterns, everything is dictated through this system controlled by a very specific set of hormones that are secreted from the neurohormonal cells situated in the pineal glands in our brain. Rapidly changing or inconsistent light patterns trigger the sundown symptoms just like the photosensitive seizures due to epilepsy. The circadian rhythms of our body are disturbed in this disease because specific neuronal cells that undergo cell death in Alzheimer’s disease appear to have a large effect on the inner clock of our bodies that controls vital body patterns. 

When the vital body functions are disturbed out of their pattern due to the exhausting sundown symptoms, the patient who undergoes these symptoms has to suffer through severe insomnia, because the sleep cycle of the patient is disturbed due to those symptoms. Insomnia that is the resultant of these symptoms then gives birth to many psychic disorders in the patient.

The prospects of CBD in treating insomnia due to various diseases are very bright. CBD can help a person fall into sleep relatively easily than using sedatives to induce sleep in a person. Particularly, in patients suffering from Alzheimer’s disease and the sundowning symptoms, there is an increased pattern of disturbed sleeping because of the disturbance in the circadian rhythms of our bodies. Studies have shown that CBD is very effective in treating various types of dementia that can lead to sundowning symptoms and insomnia. 

CBD helps dementia patients by promoting the neuroprotective properties of the nervous system. It enhances the health of the cells that are located in the areas of the brain that are concerned with the formation and reconsolidation of memories. As long as dementia exists in the patient, the treatment of sundowning symptoms is very difficult, as the patient tends to forget the state of his or her own body. We have studied how CBD helps patients suffering from Alzheimer’s disease. Similar is the case for dementia due to other causes. CBD promotes the health of PC12 neuronal cells, which serve to be the main cells of the brain in the areas concerned with memory formation and reconsolidation later on. The prospects of CBD to treat dementia in people through exerting its effects on the PC12 neuronal cells provides a rather safe but efficient approach towards treating various types of dementia in people so that studies are widely being conducted all over the world in order to investigate the role of CBD in treating dementia. The studies have returned largely positive results so far, and somehow the neurologists have started suggesting CBD in the therapeutic prescriptions to the patients suffering from Alzheimer’s disease. 

Sundowning with Parkinson’s Disease (PD)

Parkinson’s disease is a neurologic disorder which is caused due to a decrease in a substance called dopamine, which is released from a part of the brain called the substantia nigra, located in the central areas of the brain concerned with the adaptive control of vital body functions like fine muscle control, voluntary and predictive movements and behavioral changes including sleep-wake cycles.  This disease is characterized by the presence of stiffness, shaking, and difficulty in walking and balance throughout the whole body. The disease is progressive: it worsens over time and as it worsens, it leads to extreme difficulty in walking and talking. The exact cause of cell death in the areas that produce dopamine in the brain is still not understood to the scientists and continues to be the hotspot of Parkinsonism research.

Parkinson’s disease patients usually develop a special kind of dementia known as the Parkinson’s Disease Dementia (PDD) at least a year after the diagnosis of the disease. This is because initially, Parkinsonism affects the parts of the brain involved in controlling the vital motor functions throughout the body. However, if left untreated, the disease may also progress to the brain areas that are involved in the mental processes such as the cognitive abilities, thinking, and the areas that are concerned with the formation and reconsolidation of the memories in the body. The key brain changes linked to Parkinson’s disease and Parkinson’s disease dementia are pathologic in nature. At least a year after the initial diagnosis of Parkinson’s disease, some abnormal and microscopic bodies are found to be deposited in the areas of the brain related to memory reconsolidation. These abnormal microscopic deposits consist chiefly of alpha-synuclein, a protein found widely in the brain with a normal function. The function of alpha-synuclein is not completely understood yet to the scientists. These abnormal microscopic deposits are called “Lewy bodies”. Lewy bodies are then responsible for causing the notorious Lewy Body Dementia in the patients. The symptoms and manifestations of this dementia are almost similar to other kinds of dementia such as Alzheimer’s disease.

Insomnia in Parkinson’s and the Use of CBD

Insomnia and sleep pattern disturbances are one of the most common non-motor symptoms of Parkinson’s disease. These secondary symptoms are caused due to the degradation of the neuronal circuits that are involved in memory formation. The Lewy bodies formed in the vital brain areas are responsible for dementia. As the disease progresses, the sleep disturbances gradually increase in frequency. The insomnia is probably due to the changes in the brain that cause the disease. Some of the drugs used for treating the symptoms of Parkinsonism are found to be the culprit in disturbing the sleep patterns. The impaired cognitive abilities in the patient, along with abnormal changes in memory and the reconsolidation of the old memories, behavioral changes such as repeated delusions and recurring irritability, disturbances in concentration, and going for a careful judgment are the areas where Parkinsonism shows its change. The patient might have some trouble interpreting visual information, with misalignment of certain visual signals. There might be muffled speech. The behavioral changes in the patients suffering from Parkinsonism include visual hallucinations and increased fear associated with those hallucinations, delusions, and especially paranoid ideas along with depression. Sleep disturbances are the most common ones, including excessive daytime drowsiness and rapid eye movement (REM) sleep disorder that is the characteristic of the sundowning symptoms in these people.

The extreme disturbances in the sleep patterns of patients suffering from Parkinson’s disease, and the formation of Lewy bodies in the central nervous system of the patient suffering from this disease, is responsible for causing sundowning symptoms. There is an increased nocturnal disturbance in the patient, with the patient sometimes not being able to sleep for the whole night. This sleep disturbance then causes sundown symptoms the very next day, thus haunting the patient with a never-ending vicious cycle that grows worse day by day. Hence, the patients suffering from this disease also have to suffer from inevitable insomnia, which dramatically degrades the lifestyle of the patient but also is full of trouble for the caregivers. 

The treatment of symptoms in those with Parkinson’s dementia is very difficult because the drugs which are used as the symptomatic treatment can sometimes aggravate hallucinations and confusion in those with Parkinson’s dementia or Lewy body dementia. This confusion and unsettling state can further cause uncomfortable sundowning symptoms in those patients. Another prospect that appears to be promising but is contraindicative in the patients suffering from Parkinson’s disease dementia (PDD) is deep brain stimulation (DBS). The contraindicative nature of this treatment hampers its safe use. However, a small study conducted by University College London scientists showed that deep brain stimulation (DBS) was comparatively much safer and well-tolerated than it was originally thought. 

Cannabis extracts, particularly CBD, has found to be useful in Parkinsonism and resulting in dementia due to Parkinsonism. So, it has indirectly all the requirements for treating the sundowning symptoms in these patients. The pain-reducing properties of CBD help reduce pain due to the motor symptoms of Parkinson’s disease, so it can improve the lifestyle of the patients suffering from this chronic disorder. The dose-related improvement due to the administration of CBD in dystonia was observed in all patients, and the collective effect of CBD ranged from relieving pain to getting rid of tremors throughout the body.

Psychosis and CBD

Another complication that might occur in Parkinson’s disease is psychosis, and the symptoms of psychosis gradually aggravate over time. Psychosis in Parkinson’s disease patients is the major trigger for the sundowning symptoms because of the resultant stress the patient has to go through. The psychotic symptoms in PD aggravate over time so that it is very important to get rid of these symptoms to avoid sundowning symptoms in the patients. A small study conducted in 2009 found CBD to have particularly canceling effects on the symptoms of psychosis, thereby improving the sleep and general lifestyle of the patients having Parkinson’s disease. A study conducted at the University of Louisville, Kentucky shows that CBD acts as an inverse agonist on the CPR6 receptors that are found in the brainstem and are responsible for controlling movement, emotions, and learning - all of which are affected by Parkinsonism. This means that CBD responds to these receptors, and can act as a therapeutic agent in relieving the symptoms of this disease. Studies also show a promising effect of CBD in treating psychosis and resulting in insomnia due to Parkinsonism’s Disease Dementia (PDD). A research was conducted in order to investigate the usefulness of administering oral doses of CBD to patients having Parkinsonism. The study found out that aside from relieving the psychotic symptoms that degrade the cognitive abilities in the PD patients, CBD also relieved the tremors and muscle instability due to the motor abnormalities in the patients suffering from PD.

Using CBD as a treatment for sundowning in dementia due to Parkinson’s disease is a relatively new concept, but has gathered much fame in recent times due to its safe and efficient nature. Cannabidiol (CBD) is not psychoactive like THC so that it does not give the ‘high’ effect that is due to THC in Cannabis. Moreover, using CBD to treat Parkinsonism and resulting dementia due to this disease (PDD) is also a relatively safe approach, as it is free from the side effects of the anti-psychotic drugs that are conventionally used to treat psychic disorders in the patients suffering from PD and AD. 

REFERENCES

1. Bliwise, Donald L. et al. "Disruptive Nocturnal Behavior In Parkinson's Disease And Alzheimer's Disease". Journal Of Geriatric Psychiatry And Neurology, vol 8, no. 2, 1995, pp. 107-110. SAGE Publications, doi:10.1177/089198879500800206. Accessed 6 Sept 2020.
2. "Sundowning | Alzheimer Society Of Canada". Alzheimer.Ca, 2020, https://alzheimer.ca/en/Home/Living-with-dementia/Understanding-behaviour/Sundowning.
3. Sundowning: Causes, Symptoms, and Treatment https://www.webmd.com/alzheimers/guide/manage-sundowning
4. https://www.flickr.com/photos/170378439@N03/46886846045