Free Influence of Cannaboidson Epilepsy (adults) and other Neurological Problems Dissertation Example
Influence of Cannaboids on Epilepsy in Adults
Level: Masters and Discipline: Science
Course: Readings and Research in Biosciences
Date: January 2017
The writing and completion of this thesis would not have been completed with much success without the help of amazing and supportive colleagues, tutors, and my family. First, I am much thankful to the almighty God for sustaining me and giving me the strength through this research. Secondly, I appreciate the support I have received from my family, their unconditional love, care, and concern gave me the courage to believe in myself. I am also thankful and much indebted to my friends, who through their SMS, emails, and calls, kept me motivated when I felt like giving up. Indeed, to all my friends I owe you everything in this research, as you always gave me a reason to keep on moving. Lastly, I thank my awesome supervisor for pushing me hard, it only made me realize that I could do more than I ever imagined. Indeed, my professor was my best friend during this research as he kept on advising me on the areas that needed improvement.
This study aims at providing information on the perspective of using cannabis to treat epilepsy. All the necessary health issues surrounding this condition illustrated. Additionally, scientific evidence and clinical trials will be analyzed. Also, the mechanism proposal behind seizures and their anatomy and central nervous system examined. Besides, recent reports have raised interest in cannabis therapies. Cannabis has been used over an extended period to treat seizures. Recent anecdotal reports of mechanistic insights and animal models have an elevated focus on antiepileptic treatments. Further, through psychoanalysis, essential strategies towards choosing an active drug for seizures have been evaluated. The thesis shows that Cannabinoid prevents psychoactive impacts while endocannabinoid is a promising treatment for epileptic seizures. Cannabidiol has proved to have anticonvulsive effects on both animals, and human beings and their side effects are favorable. The first part of this paper is an introduction and history of epilepsy. Part two entails a review of the literature with their main recommendations. The absolute target of this examination is evaluating and generating understanding cannabis in epilepsy for future knowledge and medical work. However, any prospect study should equip matters not discussed in this paper left out in this paper.
Keywords: Cannabis, epilepsy, seizure.
Table of Contents
TOC o “1-3” h z u CHAPTER ONE: INTRODUCTION PAGEREF _Toc516665603 h 7Cannabis in epilepsy PAGEREF _Toc516665605 h 7Thesis statement PAGEREF _Toc516665606 h 9Background of the problem PAGEREF _Toc516665607 h 9Anatomy PAGEREF _Toc516665608 h 9Histology PAGEREF _Toc516665609 h 9Electrophysiology PAGEREF _Toc516665610 h 10The Neuron Synapse and Neurotransmitters PAGEREF _Toc516665611 h 10Excitability of Neurons and Epileptogenesis PAGEREF _Toc516665612 h 11Structural changes PAGEREF _Toc516665613 h 11Metabolic changes PAGEREF _Toc516665614 h 12Classification of seizures PAGEREF _Toc516665615 h 12Epilepsy syndrome PAGEREF _Toc516665616 h 13Lennox- Gastaut syndrome PAGEREF _Toc516665617 h 13Dravet syndrome PAGEREF _Toc516665618 h 14Epileptic Encephalopathy PAGEREF _Toc516665619 h 14Drug-resistant epilepsies PAGEREF _Toc516665620 h 14Justification of the problem PAGEREF _Toc516665621 h 15Deficiency in the evidence PAGEREF _Toc516665622 h 15Definition of Terms PAGEREF _Toc516665623 h 16Rationale of the study PAGEREF _Toc516665624 h 16Hypothesis PAGEREF _Toc516665625 h 17Summary PAGEREF _Toc516665626 h 17CHAPTER 2: LITERATURE REVIEW PAGEREF _Toc516665627 h 18Electroencephalography (EEG) PAGEREF _Toc516665628 h 22ECG PAGEREF _Toc516665629 h 23Accelerometers PAGEREF _Toc516665630 h 23Video detection systems PAGEREF _Toc516665631 h 24Mattress antenna PAGEREF _Toc516665632 h 24Audio baby alarm PAGEREF _Toc516665633 h 24Detection of a seizure using seizure helps dogs PAGEREF _Toc516665634 h 25Seizure alert dogs PAGEREF _Toc516665635 h 25Seizure response dog PAGEREF _Toc516665636 h 26Methods for seizure prediction PAGEREF _Toc516665637 h 28Phase synchronization PAGEREF _Toc516665638 h 29Entropy PAGEREF _Toc516665639 h 29Intelligent expert schemes PAGEREF _Toc516665640 h 30Non-linear predicting techniques PAGEREF _Toc516665641 h 30Human trials PAGEREF _Toc516665642 h 30Cannabinoid impacts on epileptic seizure by children PAGEREF _Toc516665643 h 31Treatment of epileptic seizure and Alzheimer’s disease PAGEREF _Toc516665644 h 34Epileptic seizure and hyperactive children PAGEREF _Toc516665645 h 35Cancer patients with epileptic seizure PAGEREF _Toc516665646 h 36Epileptic seizure treatment and depression PAGEREF _Toc516665647 h 37CHAPTER 3: METHODOLOGY PAGEREF _Toc516665648 h 39Data collection methods PAGEREF _Toc516665649 h 39Sources PAGEREF _Toc516665650 h 39Case study PAGEREF _Toc516665651 h 40Reports and survey PAGEREF _Toc516665652 h 41Clinical Trials PAGEREF _Toc516665653 h 42Treatment of Data PAGEREF _Toc516665654 h 43Research Limitations PAGEREF _Toc516665655 h 43CHAPTER FOUR: RESULTS PAGEREF _Toc516665656 h 45Positive effects PAGEREF _Toc516665657 h 45Anti-epileptic impacts of CBD PAGEREF _Toc516665658 h 47Anticonvulsant effects of CBDV PAGEREF _Toc516665659 h 48Anticonvulsant effects of CBN PAGEREF _Toc516665660 h 49Anti-seizure effects of delta-9-THCV PAGEREF _Toc516665661 h 49Antiseizure effects of CBG PAGEREF _Toc516665662 h 50Cannabidiol formulation and pharmacodynamics PAGEREF _Toc516665663 h 50Placebo Effect PAGEREF _Toc516665664 h 51Legal Concerns of Cannabis PAGEREF _Toc516665665 h 52CHAPTER FIVE: DISCUSSION PAGEREF _Toc516665666 h 54CHAPTER SIX: CONCLUSION AND RECOMMENDATION PAGEREF _Toc516665667 h 58Conclusion PAGEREF _Toc516665668 h 58Recommendations PAGEREF _Toc516665669 h 58
Influence of Cannaboidson Epilepsy in Adults and Other Neurological Problems
CHAPTER ONE: INTRODUCTION Epilepsy refers to the enduring of the predisposition of the brain to cause epileptic seizures while seizures are the clinical reflection of massive and synchronous electric activity within the mind (Fisher et al. 477). Also, Epileptogenesis is the process the brain neuron network change with time fostering the development of seizures. In 2004, The International League against Epilepsy (ILAE) added a complex definition is giving the following as the as the criteria of being an epilepsy patient; one has to have experienced one unprovoked, and there are high chances of recurrence.Cannabis in Epilepsy Cannabis has applied for medicinal purposes over an extended period. Around 2800BCE, the Chinese Emperor exemplified marijuana to be consisting of consecrated yin and yang characteristics, meaning they might re-establish homeostasis to an imbalanced body. Also, ancient medical doctors of Rome, Arabia, and Egypt used cannabis for medicinal purposes such as malaria, constipation, and beriberi. In the recent documents, marijuana has been used for seizures in the Arabian and Sumerian text. Early 1855, USA medical faculty used cannabis to treat tetanus, cholera, depression, insomnia, and insanity. Analgesic, anti-inflammatory and anti-biotic are the most valued properties of marijuana.
In 1906 the US “Pure Food and Drugs Act” regulated utilization of cannabis for the first time in history. Later this product was conflicted by the American Medical Association, who argued that many people abused this drug. Also, they insisted that cannabis didn’t meet the criteria of being a Schedule 1 drug. However, regulation on the application is initiated in council to shift marijuana into a Schedule II drugs. For the past 59 years, major substance components of marijuana have been extracted and manufactured. The extraction began with delta9-THC which was isolated in 1965 and processed in 1969. Then utilization of Cannabinoid was secluded in 1942 then produced in1964. After, the cannabinoid category 1(CB1R) and group 2(CB2R) receptors, that were attached to delta9TCH have duplicated in the 1990s subsidiary an endogenous structure intended for the significant cannabinoid pharmacological motion. These medicines and their effects described in table 1.1. (Santos, et al. 136).
Medication Possible common drug effect
PhenobarbitoneMarginal neuropathy, behavior alteration, cognitive impacts and dupytren’s contractures
Carbamazepine Patients gaining more weight, drug epidemic, leukopeania, and hyponatremiaSodium valproate Gaining weight, losing hair, tremor, endocrine transformations, hepatotoxicity, thrombocytopenia and hyper rammonemia.
Phenytoin The cosmetic transformation which includes overgrowing of the gum, coarsening in patient’s facies and hirsutism. Other effects include hypersensitivity responses and peripheral neuropathy
Table 1. Anti-seizure drugs types and their effect
Thesis Statement Given the improved increase of available data on the use of cannabis as a medical solution to epilepsy, most people and physicians have approved the use of the marijuana. Emphasis has thus moved to the possible impacts that marijuana have on their consumers. Mostly physicians are evaluating the cannabinoid as the suitable drug with less effect on human consumption.
Background of the Problem Since epilepsy mainly involves the destruction of the Central Nervous System (CNS) and the brain, it is therefore important to understand the neurobiology behind the CNS. Moreover, it will aid in determining the most effective drug that will have a minimal alteration of the CNS functioning. Below are the essential overview of the features and mechanisms.
The central nervous system has two main divisions; the spinal cord and the mind. The brain encased within the cranial cavity, known as a skull where the spinal cord finds its attachment as it extends as a spinal canal.
Histology Historically, CNS is made up of billion cells with neuron and neuroglial cells aligned to specific functions significant to the neuron system. Neurons are responsible for information transmission while neuroglial cells form a support system. In CNS, neuroglial cells are found in large numbers as they serve storage purpose. These cells insulate nerves to facilitate electrical transmissions, inactivate neurotransmitters, metabolize and repairs of damaged immune receptors. Also, they maintain a balanced environment for the delicate CNS. Lastly, neurons possess a cell body, which is responsible for the production of proteins and metabolic activities to take place. From the body cell are projection elongating termed to as neuritis? These neuritides play the role of communicating with other neurons and can further be termed as dendrites. Dendrites receive process and send information, and every nerve possesses these dendrites which help in transmission of information onwards.
Electrophysiology Potential actions facilitate the release of neurotransmitters which are responsible for transmitting information from the axon. While at rest the cell membrane acts as a barrier between the cell’s components` and the outside. Also, they generate negatively charged potential at rest which is known as resting membrane potential. In response, a chemical component is allowed to enter into the cell producing positively charged ions and thus decreasing the resting membrane potential. Once the reduced charge exceeds the set limit, immediate information is sent to the neurons to help counteract farther release of positively charged ions. This process ensures that a second action after the threshold does not follow automatically.
The Neuron Synapse and Neurotransmitters
The action potential reaches the axon, terminal, and neurotransmitters produced in the synaptic cleft where thus activating ligand, which are the channels for receiving neuron. Neurotransmitters classified as either inhibitory or excitatory depending on whether they decrease the potential action. An example of excitatory neurotransmitters is glutamate, which is responsible for increasing the chances of the occurrence of a potential occur. On the other hand gamma-amino-butyric acid (GABA), which perform on GABA receptors producing negatively charged ions which move away from threshold potential. Thus, they decrease the likelihood of starting another potential action.
Excitability of Neurons and Epileptogenesis The prospect of a potential occurring referred to as excitability. Metabolic, structural and genetic changes in CNS can modify excitability. Thus, they are said to be a foundation of the uncontainable synchronous electric action during seizures occurs in the brain. This process is called epileptogenesis.
Structural Changes Local neurons communicate with each other via interneurons, to ensure that only the desired neurons are active. Neurons inhibited with the firing neuron through a process called feed-forward inhibition. Likewise, the interneurons can respond to the firing neuron through the process of feedback inhibition. Combined,s they enable definite and complex signaling within the CNS. However, reorganization of these neuron connections results in seizures generation. Generation occurs through self- reign forcing stimulatory circuits or degeneration of the existing neurons.it is said that most common cause damage to the CNS includes; infection and illness. Generally, structural change based on synaptic, which undergoes a process known as synaptic plasticity. Synaptic plasticity alters the capability of receiving neurons. These alterations are as a result of different mechanisms including, shortening and widening as well as a change in the number of receptors receiving a neuron.
The distribution and type of the ion impact the excitation level. However, the behavior of the atoms altered by non-transmitters messenger systems such as endocannabinoid or other genetic modifications. Similarly, neurotransmitters produced at the axon terminals are transported by the neuroglial cells or firing neurons in the surrounding. Any reduction uptake of the neurotransmitters caused by genetic mutation will increase the number of nuerostrammiters in the synapse thus increasing the level of excitability of the target neurons.
The fluid surrounding neurons are called extracellular fluid, and the body controls the number of ions within this concentration. In case of changes, exchange of materials between the atoms and the extracellular fluid changes resulting in changing in excitability level. An illustration of this is dehydration. When thirsty the level of fluids reduces occurring to increase in ions concentration. Actually, after an action fires, neurons repolarize by moving potassium ions into out of the sell to the extracellular fluid. However, in case of dehydration, the neurons are opposed leading to failure of repolarization which results to neuron excitability. Similar factors include alcohol, fever, and infections which lead to increased excitability too.
Classification of Seizures As mentioned above, seizures are a real reflection of free synandrous electric activities of the brain. The action may begin at a small area of the brain or widely distributed neuron networks, with high firing levels location. Physical signs are used to distinguish the various seizure pathologies as it is hard to separate them in any other means. In case electrical activities originate from a localized region, they refer to as partial seizures. The signs of partial seizures differ relying on their location. Examples entail; perception of odd tastes, vocalization of sounds and complex voluntary activities. When a patient has partial seizures, they remain conscious while in case they lose conscientiousness it forms to as “complicated” limited seizure.
Moreover, partial seizures may reach out to the two hemispheres to develop into generalized, or on the other hand, it may begin as pervasive and caused by some unknown mechanisms. Widespread start and quickly engages widely spread to the bi- hemisphere, streaming through convulsive and non-convulsive seizures. The commonly known types of generalized seizures are absence seizure common in children. This condition identified through a few minutes of inactivity.
Epilepsy Syndrome Diagnosis is essential in identifying the actual epilepsy pathogen and is also necessary to dwell on the likely cause of the condition. Usually characterized by the type of the seizure, the age of the onset and associated EEG symptoms. These syndromes also provide directions on issuing drugs, and some syndromes have to be noticed positively or negatively to the anti-epileptic available medicines.
Lennox-Gastaut Syndrome Lennox- Gastaut syndrome is generally present in children at the age of 4-5 years old. However, the cause is still unknown, and thus it is deemed to be acquired or genetic. The affected children might have had an average birth history. However brain abnormalities, and as a result of infections, malfunctions and tumor are common. These types of syndrome vary and respond very poorly to drugs. A while after the beginning of this syndrome, cognitive development commence reduced and relapse accompanied with severe behavioral issues with autistic features. Seizures cannot be controlled thus once infected they run through a lifetime.
Dravet Syndrome This syndrome typically attacks children at the age of one and is highly associated with genetic mutations in the SCN1A gene. Usually, the infected children have a healthy childhood until their first encounter with seizure which comes accompanied with fever and infections. The symptoms of this syndrome differ, and they are intractable while they respond poorly to drugs. Within a year the physical and behavioral characteristics begin to cease and regress. At the age of four, the child reaches a steady state of repeated seizures and behavioral disorders.
Epileptic Encephalopathy This epilepsy is classified to form a group known as `epileptic encephalopathies. There is much emphasis on a concerning seizure themselves other than their causes. They lead to a continuous change in the CNS thus threatening the health results of an infected person. The invention is a medication that would reduce or stop this syndrome is the hope of the individuals and their families. In future, drugs, drugs, automatically improve the condition while reducing the health cost burden.
Drug-Resistant Epilepsies Drug-resistant epilepsy is yet another disease classification of patients whose condition cannot be controlled by the available anti-epileptic medication. This group involves patients suffering from different syndromes, but some diseases are more liable to drug resistance than others. Recently drug resistance classification is for those patients for which at least two consecutive treatment by the chosen AEDs have failed to do away with the seizures (Devinsky et al. 275). Further, the patients` accessed for their suitability for epilepsy surgery. In this case, accepting that the medications are unimportant is essential and thus focus should be directed on maximizing QOL health outcomes of the patient. Consequently, intense research on drug resistance mechanism and see how it could retreat is an important strategy.
Justification of the Problem There are many beliefs about the effects of Cannabinoids in epilepsy. These myths include; the idea that epilepsy is contagious, however, this fact is not true. The notion that one is born with is also a myth that is untrue since as proved medically it is a health disorder that involves the brain. Even the belief that epilepsy affects a person`s intelligence. Fourthly, there is a belief that people with epilepsy cannot have children or excel in school. This notion is untrue since there are people with epilepsy, yet achieved high grades at school while others bore children, like everyone else. Another myth is the belief that one can swallow their tongue during a seizure, it is not correct as it is impossible for a person to eat their language. Finally is the belief that epilepsy has always been an emergency, this belief is inaccurate because seizures are most often not a medical emergency. Thus, calls for a strategy to ensure that adequate information on epilepsy delivered to the public.
Deficiency in the Evidence Although many studies have been carried out to show anticonvulsants, more research needs to carry out for clarity. So far CBDV and CBD are ranked high towards treating epilepsy since they have a non-convulsant nature. Also, they have identified with their multi-pharmacological profile which likely contributes to their anticonvulsant aspects. Moreover, these compounds inhibit uptake of anandamide and enzymatic hydrolysis and have few side effects compared to other d
Mostly it is important to investigate the drugs to come up with improved medicines that are safe for use and with fewer side effects. Although these reports are encouraging further studies should be carried out to clarify the actual results and safety using CBD. This information is even more relevant since some patient experience severe effects such as elevation of the liver. Though this condition is reversible, it is safe to curb such influence to prevent such severe results in the future.
Definition of TermsEpilepsy: refers to a neurological disorder in which a person experiences frequent seizures. Seizures: refers to an abnormal disorder which affects the brain nerve cells and results from temporary disturbance of sensory, motor or mental functions.
Cannabinoids: refers to compounds and active constituents extracted from cannabis.
Anticonvulsant: refers to medications used to prevent and reduce the severity of the epileptic seizure.
The Rationale of the StudyThe main goal of research effect of cannabis on epilepsy is to:
1. Make sure that patients are given sufficient details concerning different cannabinoids to permit them to make knowledgeable decisions
2. Make sure that folklore rotating usefulness and side effects of cannabinoids are eradicated and replaced with life information.
3. Ensures that therapeutic organizations can regulate their intermediate in a method which will reach their object clients most efficiently.
4. Ensure that recommendations on research are made to help patients choose the most effective cannabinoids.
The research is important as it may facilitate in making certain that useful details are accessible to patients through their medical preferences. It will also ensure that advisements in research are embraced to meet the challenges of the future regarding epilepsy.
HypothesisThe following hypothesis tested in this study
1HO1 Cannabis reduces the epilepsy seizure
1HA1. Cannabis does not reduce the epilepsy seizure
2HO2 Cannabis is useful and safe on consumption
2HA2: Cannabis has side effects on human consumption
3HO3: Cannabis approved by the medics for reducing seizure.
3HA3: Cannabis not approved by the medics for reducing seizures.
SummaryThe change in the center by the patients and physicians put extra consideration on the use of cannabinoids. Moreover, of the use of cannabis is the primary step towards the advancement of new medical techniques. This will thus go a long way in introducing new medication that will curb other seizure. In essence, would reduce the frequency of seizure
CHAPTER 2: LITERATURE REVIEW This chapter consists of theoretical framework used to support this study and various studies, on the impacts of cannabis and epileptic seizures. Animal models have been developed to identify the potential beneficial influence of cannabidiol (CBD) to humans. In medical research, animals are used to test the effectiveness of medicine before using them on human beings. They provide reliable information on how the drug affects the body. Other animals such as individual dogs have been used to predict epileptic syndromes in patients before the manifestation of the disorder condition.
According to (Russo et al. 393), an animal model developed examined the administration of CBD to rats before inducing temporal lobe and partial seizures. The results showed that rats that received CBD experienced less seizure compared to those that did not. Administration of about 10mg of CBD reduced deaths in rats. Doses up to 200mg/kg of CBD were induced in rodents to test for primary mortal function. In contrast, to decrease in motor function caused by external defibrillators (AEDs), animals accurately completed all tests at the same time as controls.
In a similar study, the anticonvulsant effect of CBD was application involves comparison of CBD to ethosuximide and phenytoin. According to (Santos et al. 140), there was no unwanted motor impairment after the establishment of CBD does. Licensed automated Seizures were artificially generated using electric currents, in which the amount of present required to produce a seizure, record. An observation that those exposed to CBD and phenytoin needed the highest amount of present. Besides, seizure activity in CBD group was shorter and weak. Thus CBD was found to be lacking undesired excitatory compared to current AEDs.
Other studies show that some animals which satisfy specific criteria can illustrate intervention for treatment of epileptic seizures. Animal-assisted therapy involves four theories, mainly the learning theory, attachment theory, cognitive theory, and biophilia hypothesis. The attachment theory focuses on the social bond between people and animals. Pets develop an attachment to the caregiver. The social relationship takes time to develop. It lies in the notion that early childhood forms a base mark for personality development. The attachment system is most applicable where the person is ill, frightened or threatened and the animal, specifically the seizure dog, provides the needed comfort.
The cognitive theory focuses more on self-efficacy that results in the expected behavior of a person. One of the most effective methods of achieving self-efficacy is through accomplishing performance, a practice that was once feared. It elaborates why the mind is a main inconceivable system of information processing and how a person interprets things. Learning theory is used to describe a decrease in anxiety and arousal in animals during the animal-assisted therapy. Learning assumes concentration on pain results in the sense of control. Biophilia hypothesis applies to the genetic ability of humans to attend to and feel attracted to animals. Human responses to animals depend on the cultures and individual experience (Schoenberg, at.el. 20).
Historically, dogs are susceptible to observing human non- verbal communication. It speculated that dogs identify unremarkable changes in personal human smell before the seizure. Seizures are the common characteristic of a neurological condition caused by brain trauma. They cause pain to the patient, in which one can have arm jerk or stiffened muscles that make someone to fall and get hurt. Seizures, restriction by use of vagus nerve stimulator on the chest of the patient. The device produces electric pulses that help to block the seizures. Other patients alternatively undergo surgery to treat seizures. However, these techniques are only used to treat partial seizures. Some generalized seizures cannot be controlled using this machine. Thus, in such cases, seizures control dogs are used through animal-assisted therapy (AAT).
The biological effects of cannabinoids on seizure threshold are complex. These are chemical compounds and molecules from cannabis sativa plant, particularly the marijuana that is believed to treat epilepsy. Tetrahydrocannabinol (THC) is also molecule compounds in the marijuana plant used for epileptic seizure therapy. Animal studies have shown that anticonvulsant and ant-kindling properties for THC and more consistently for CBD. The results vary from one research to another efficacy of 9 -THC and 8 -THC found in many animals.
In preclinical studies, the CBD has been found to be active in rats and mice seizure models. In a study where 400mg of CBD oral dose administered, CBD was reported t rapidly absorbed within a period of 1.5 to 3 hours with a mean peak plasma concentrations of 110 to 120ng/ml. The use of cannabis sativa in the treatment of seizures disorders dates back in thousand years. Neurologists used cannabis preparations in the treatment of epilepsy in the late nineteenth century. With the gradual introduction of the automated external defibrillators (AEDs), the use of cannabis in epilepsy treatment has declined in the twentieth century.
A lot of research and case reports have been done to show the safety and efficacy of oral cannabis preparations. It was nothing that a little girl, Charlotte who had a confirmed draft syndrome experienced a remarkable improvement in her seizures after the administration of CBD. In a survey targeting a group of parents in the USA with approximately 200 participants, only about 12% responded with a negative response towards the efficacy and safety of the cannabis to their children. Over 80% responded that their children had fewer seizures while on 25mg/kg of CBD enriched cannabis each day. Compared to THC, CBD showed more positive outcomes in animal models. This compound is because the moderate to high THC associated with many undesirable effects such as addiction, cognitive and psychiatric discords and motor impairment.
Other animal studies continue to emerge. Scientists describe the anti-seizure drug effects of cannabidivarin (CBDV). Further CBD and CBDV do not act on CB1 receptors but rather on TRPM8 through antagonistic action and on TRPV1-4 and TRVA1 channels through agonistic. On the other hand, delta 9-THCV has anticonvulsant properties that showed hostile action on CB1. Thus many cannabinoids have sufficient and robust anticonvulsive impact than one cannabinoid. A study showed that sixty out of eighty children reported seizure frequency decrease. The results are more critical than those observed with pure cannabis.
The cannabis plant consists of many chemical compounds which include Delta 9- Tetrahydrocannabinol, cannabinol, Cannabidiol, cannabigerol, and olivetol. Scientists and medical practitioners have accepted all these chemicals. However, an indication that smoked cannabis has a distinction of effective dose. These variations are due to personality variation in liver metabolism and absorption, breath occurrence, inhalation depth and retention of inhaled smoke. Methods of identifying epileptic seizures in adults
There are varies of technological means used in detection and prediction of seizures. Some include the electroencephalography (EEG), ECG, accelerometers, and use of electro-dermal systems. Some animals such as individual dogs are used to detect seizures in human beings. Closed loop systems are used to prevent and in the treatment of the seizure conditions. Early methods of detecting seizures are accompanied by several challenges. Intracranial conductors help in detecting the seizure condition at the early stage for most epileptic patients. However, use of scalp recordings does not provide reliable information for early seizure detection. If the whole seizure would be employed, together with intracranial recordings in particular fields. Thus, is possible to relatively detect seizures using equal sensible and specific measures as treating these events last for more than one minute. Much greater problems are experienced when one wants to detect the seizure within seconds of its beginning. EEG dimensions from patients with epilepsy can be used to detect seizure.sElectroencephalography (EEG) It is not always easy to detect seizures in adults. Clinical experts, however, use a unique technique in identifying epileptic seizures in human beings. The implementation of visual observation of electroencephalography (EEG) signals helps the expert technicians in the detection of the epileptic seizure condition. This technique, however, is susceptible to prejudice and also time overwhelming. Hence, epileptic recognition is affected by low power and lack of large processing datasets.
The EEG signals have the weak and short amplitude that results in low occurrence noise such as system obstruction. The pre-processing of the signal which involves noise elimination regarded as an essential step for the epileptic seizure examination and exposure. Wavelength threshold method is used to remove the noise. It has a higher performance compared to the Fourier transform method of noise removal. Noise removal is an essential phase in medical signal processing and analysis. Higher signals are formed in the study of time-frequency sphere as they contain both time and frequency gears.
ECG Epileptic seizures could lead to immediate and prolonged heart rate disturbances as well as SUDEP path physiology. Changes in heart rate are relevant to autonomic biomarkers in epilepsy. An estimate of ECG changes in fifty-eight patients. Having noted that tachycardia occurred throughout the seizures in further than 90% of the patients. Employment of the tachycardia in seizure is mostly applicable to newborns whose seizure signs are slight.
The method is usually tricky in use of EED and requires adjunct systems and specialists by heart rate. The application of tachycardia seizures caution systems in adult’s complication is due to complex changes in the ECG. Difficulties arise in physical, logical and pathological conditions which include emotional states, disease, and exercise among others.
In a simple study, six patients who had epilepsy in a chronological section were monitored using power spectral analysis. Their heart speed indicated the capability of these systems to predict warnings. Use of algorithms before seizure occurrence showed that the technique could be of use in seizure detecting. Use of VNS has evaluated other ECG methods such as closed-loop systems. The research is ongoing to provide better techniques for predicting seizure in patients diagnosed with epilepsy.
Accelerometers An accelerometer is a device that detects changes in speed and direction. Three dimension 3-D accelerometers can detect differences in length, width and height planes. Use of such devices in identifying seizures which are motion sensors is a new technology that clinicians are using to detect seizures in epileptic patients. These systems help in identification of tonic-clonic and cyclonic seizures. Accelerometers detect ongoing seizure in which sudden motions indicate seizure movement. They are also applicable for detection of additional types of motor seizures. These devices use timescale, linear threshold, and frequency functions in the identification of nocturnal hyper motor seizures.
Video Detection Systems Video systems are used to analyze a range of essentials to detect seizures. Many models have been introduced recently to identify seizure by use of video monitoring. Video detection systems use moving substance through space over time. Velocity, area, duration and angular speed are among the elements used in this analysis. Some video analysis depends on the application with markers, put in the patient’s joints. Present video systems, restriction sheltered by the film camera and detectors incapability such as to record events that happen with patient observation view. An example of such inabilities is undercover.
Mattress Antenna Mattress monitor is intended to identify seizures that occur when the patient is asleep. The sensor is positioned linking the mattress and box leap. The microphone in the sensor identifies beating along with bounces noise that has a modifiable feeling. In research with eight tonic-clonic seizures, is capable of detecting five events in which the device has poor predictive values. Detection might give the epileptic patients a strong astuteness of defense.
Audio Baby Alarm Baby sensors use a passive vision camera that can work at night. It uses wireless network (WIFI) connection to pay attention to the sound made by epileptic children remotely. It is usually put near to the child. Radio waves are used to transmit the sounds to the receiver unit which is generally close to the child caregiver or parent. The group enables the caregiver to do other duties or sleep in a separate room with the child. The sounds received alert them to check on the child. This method is useful as it protects epileptic children from dying or gets injured when they have seizures.
Detection of a Seizure Using Seizure Helps Dogs Particular types of dogs have been trained to offer services to people with the epileptic condition. They are mainly two types; seizure alert dog (SAD) and seizer response dog (SRD). The two dogs have skills to detect seizures occurrences by a human. Generally, dogs can communicate and observe human behavior through nonverbal communication.
Seizure Alert Dogs Seizure alert dogs usually warn a person with epileptic seizures minutes or hours before the medical indication of seizure. These dogs are more helpful to people with incapacities. They typically predict that seizure will occur. At this position, canine physically reacts to that detection. Few conducted theories indicate that the canine can observe little changes in a human being’s nonverbal communication before the occurrence of a seizure.
It speculated that dog sees a minor difference in human stench before a seizure. Studies show that the seizure alert dog becomes a friend to their masters and can warn them on any unusual thing fifteen to forty minutes before it happens. Dogs trigger the person to be aware and take precautions. Seizure alert dogs provide warning information in different ways. For example, they may lie next to the individual who is almost having a seizure. It might also rest on top of them to relieve and avoid accidental injuries. Some dogs are trained to lick and bark at their masters to caution them of any risky activities such as careless driving and rock climbing. The forewarning symbols help stave off a seizure meant for patients with vagal nerve stimulator by administering a little lure above it.
Animals, unlike human beings, are unique as they are receptive to little physical and biological changes in human beings. They are super sensitive to smell and movement of their masters’ body. The seizure alert dog is trained in basic respect and advanced skills to protect the patient. Canine partners for life (CPL) are training organizations that evaluate every dog’s capability in alerting patients on the prior seizure. Positive reinforcement’s methods such as treat and click training techniques are encouraged to the capable dogs. After knowing that a dog can warn the person, they attend team training which may last from three weeks to two months depending on the dog capacity to alert.
About 70 million people around the globe experiences epileptic conditions. The experiment was less productive as they may have to avoid specific daily actions in the panic of having a seizure. The United States alone contributes the most significant number of patients with epilepsy. Epilepsy patients estimated that each year around one fifty people including adults and children have diagnosed with neurological conditions specifically epilepsy. Most patients do not understand the origin of the disease. The high number of patients reported per annum has increased the demand for seizure alert dogs.
Seizure Response Dog The other category of dog referred to as seizure response dog. They are trained to provide services to the person throughout the occurrence of the seizure. They help by finding someone to help the patient, uses its body power to put the patient in satisfied enviable condition or trigger the emergency reply system. They can also rescue a phone or patient’s medicine, encourage the person to enable them to wake up after seizure and remove the patient from the unsafe situation for example in fire or water.
Seizure response dogs are not trained to predict the seizure occurrence. However, they may develop the knowledge of alerting their masters on seizure occurrence after some years of experience. The experience of informing the patent, in this case, is not guaranteed. The seizure dogs are found to offer services to patients with disabilities. For example, Spencer is a young boy who has a seizure dog called Lucia. In many cases, epileptic patients are not able to live healthy lives because of the occurrences of seizure which other people may not understand. Thus, seizure response dogs offer absolute love, support, and friendship to the patients through their companionship. Many people such as Travis confess how these particular dogs have been of help when they experience a seizure.
The particular type of dog is calm and gentle and excellent skilled in basic obedience and respect. Dogs are usually neutral to their environment. They are, by no means timid or violent as many people who have epileptic depend on the service they provide to them during a seizure. A conveniently sized dog is preferred. Many organizations have been established to train these dogs donated to the people in need. Some people who have seizure may coach their dogs to carry out simple responsibilities themselves without the help of a specialized instructor.
Anecdotal evidence is used to support the evidence that individual seizure alert dogs can detect seizures in human beings. However, these dogs are only able to identify and provide assistance when seizure happen but are not reliable in the prediction of seizure. On the other hand, the available evidence is conflicting thus need for more research to understand how these dogs can detect oncoming seizures.
Visual consistency tomography used in vivo test in rats. The results indicated that NIR (near infrared) light could record the progress of seizures. High-resolution intensity determined cross-sectional imagery can be generated using this method. The images help in detecting changes in cortical tissue before and after a seizure. Near-infrared spectroscopy is another device used in focus on identification of epileptic genes. Gene is a non-invasive technique that it has been proved to be better than SPECT. Seizures detected by measuring the hormonal intensity. In this experiments, all the rats recorded according to the ARRIVE guidelines for pharmacology journal of the British. Other devices have been invented to help detect and control seizures. A smart watch is a signal sensing device; that monitors the patient’s movement and alerts the caregiver through text or phone call alerts.
Methods for Seizure Prediction Early prediction of seizures helps to reduce the burden of the illness. Many researchers and medical practitioners have developed an interest in the study of early forecasting of seizures. Quantitative research that seizure occurs minutes to hours earlier to medical commencement. The following methods have been designed to help in the efficient prediction of seizure. Frequency designated methods, statistical analysis of EEG signals, fine specialist structure and nonlinear dynamics.
Frequency and statistical analysis based techniques do well for univariate quantify while nonlinear dynamics and sharp, expert schemes show potential in models for seizure prediction. Present researches have introduced more advanced seizure prediction minutes or hours before the seizures. It is believed that the method will be able to predict seizures in a tie and avert before its physical and medical indication. Seizure prediction methods have been in use since the 1970s and 80s mainly based on pattern detection and spectral examination. Time chain methods have also emerged to help predict seizure.
Phase Synchronization This phase is one of the most significant techniques for predicting seizure. This method involves more than one recurrent signal which seems to oscillate with a recurring series of corresponding phase angles above successive cycles. The number associations are known as Arnold tongues that monitor from the subdivision of the map cycle. Researchers have attracted in the study of this method which the nonlinear changes have established in other applications such as laser dynamics. A particular type of synchronization invented initially for multiple chaotic examinations. In present times, the concept has been of help when applied to the natural biological period such as respiratory rating in human beings and use of magnetic encephalogram for epileptic patients.
In research work done on the phase synchronization on the middle state of patients with epileptic conditions indicated that about 70 % of seizures were in a precise state of the mind synchronization which could be seen few hours before the happening of seizure. Increase and decrease in sync was detected within 5- 20 Hz regularity band. The researchers concluded that the analysis could not genuinely predict seizure. However, it might provide more data used as warning signs of a seizure.
Entropy Generally, this is a nonlinear method that is used to predict seizures. Four entropy components removed from EEG recordings. They include phase S1, sample, approximate and phase S2 entropy. The four are then nourished to recognize patterns and classify ideas in the production of associated measures with ictal periods. Some researchers have used entropy in the prediction of seizures in pediatric patients.
Intelligent Expert Schemes Intelligent expert systems are an artificial network like show potential in recognizing of EEG pattern as well as classify measures that can be used to predict seizure. Different people have used adaptive neural fuzzy assumption structure to predict seizures. Various artificial neural networks used in seizure forecast models. For example, the neural mass model was used by Arabia to arouse the overall vibrant of intracranial EEG information to predict seizure.
Non-linear Predicting Techniques The human brain has irregular behavior which changes with physically dominant nonlinear characteristics. Decisive chaos provides essential clarifications for possible unusual conduct. The new concepts developed by the nonlinear theory helps in time sequence analysis through powerful algorithms. Specific factors, however, limit the application of nonlinear techniques in seizure prediction. Problems such as noise and moving data may eliminate the use of these techniques to describe the changes in EEG signals. This type of difficulty can be resolved by applying differential methods. Lyapunov exponents are one of the means for predicting seizure. L is a measure of capacity level in which studies have indicated an abrupt reduction in L when a seizure occurs.
Human Trials Recently, controlled human trials in the examination of the anticonvulsant impacts of CBD are missing. In 1980, Cunha administered about 400mg of CBA to eight patients who had secondarily generalized seizures. The analysis done for 18 days showed clarity. Data observed that all the patients were resistant to AEDs available. Four of the eight patients showered strong reduction in seizure activity. Blood tests and neurological examinations revealed that there were no side effects or toxicity apart from mild sedation. The similar results observed after administering nine patients to 200mg of CBD or a placebo each day for three months.
GW Pharmaceuticals and clinics have started scientific researchers in the clinical trials with Epidiolex. The liquid formulation derived from pure plant Of CBD. Epidiolex has been used recently in the US on the cure of draft and Lennox-gastaut syndrome. It has received a stray drug designation by the US food and drug administration. Preliminary results for stage three trials have indicated a reduction of 36% in motor seizures in every month.
Lack of positive benefit from the medications available has lead parents of those children with severe resistant seizures to take action. They have gained access to CBD which they administer to their children. CBD has been proofed to be highly promising and efficient in children with drug-resistant epilepsies.
Cannabinoid Impacts on Epileptic Seizure by Children Children between the age of three and thirteen years who suffer from rolandic epilepsy may have seizure experiences while sleeping. This kind of disorder is usually genetically inherited. The first stage of seizure involves vocalization, clonic action on the child’s face and frowning. These occurrences affect the child by waking him or her from sleep. Children with west’s symptoms are seen within four to eighteen months of age. The boy child is more distressed than the female child. Incidents of jerks usually occur abruptly leading to contraction of head and chest. These incidences hardly happen while the patient is asleep. Seizures in children may result from birth injuries, meningitis infections, encephalitis, and congenital anomalies among others.
It is usually difficult to distinguish between a seizure and other neurological conditions that are non-epileptic. Every parent thus needs to carefully understand the causes of such abnormal conditions in the child to accurately and efficiently determine the accurate diagnosis measures. The assessment is because non-epileptic conditions are standard in children and can easily be mistaken for epilepsy. An approximate of 7 % of children of ages six months to five years experience breathing difficulties, stiffness, walk lamely and cry often. The exercises follow stiff pain and unconsciousness which results in a headache. After recovery, the child appears to be pale and diaphoretic though response positively.
Some non-epileptic conditions related to sleep. They can be easily distinguished from seizures by the attributes they portray. Sudden awakening followed by cry and screaming does not indicate that a child is having seizures; these are night panics and terrors that occur in little children preferably preschool-aged children. Other conditions include sleepwalking and sleep talking. These anomalies only last for few seconds, and later the child falls asleep
Children who have seizure conditions can use Cannabinoid in the treatment of an epileptic seizure. In present days, the food and drug administration (FDA) has approved two synthesized cannabinoids as medications in the United States. Nabilone and Dronabinol are constituents of Cannabinoid which imitate the THC. The two medicines are the only prescribed medications by clinicians and medical physicians. Dronabinol dosage is used for chemotherapy. It may lead to nausea and vomiting which is chemotherapy-induced (CINV) to both children and adults. However, this medication, not recommended to children with AIDs related anorexia. Lack of pediatric studies discourages the use of such medicines to children due to psychoactive effects. Use of nabilone in children has also been cautioned in patients with pediatric seizures as they have psychoactive impacts while being short of existing usefulness and safety. On the other hand, ordinals extraction of cannabis products includes marijuana and oral Cannabinoid. Marijuana consists of dried leaves and flowers which are smoked. Both constituents have different concentrations of cannabinoids depending on the damage of the plant.
There are two more medications obtained from cannabinoid with standardized THC and CBD components that are currently undergoing food and drug administration (FDA) regulations of clinical experiments. Medical marijuana has legalized in most parts of the United States through medical doctor’s certification. All nations with the accreditation of use of such products allow use by children although it requires one to have legal guidance by the doctor. Some states entail the approving physician to be in charge of dosage and frequency of use. Besides, other countries call for a second doctor or clinician for the qualifications of a child’s use.
Six studies of Cannabinoid have conducted for the healing of chemotherapy-induced nausea and vomiting (CINV) in minors and adolescents. Results indicated a decrease in nausea sternness and numerous vomiting when using nabilone medication as compared with domperidone dose in a double-blind crossover RCT of twenty-three minors. Having observed that in a cycle of five days chemotherapy patients are diagnosed with nabilone had an average of six series of emesis as compared to patients treated with Domperidone who showed about seventeen sequences of emesis. Nausea severity rate was also found to have reduced 1.5 in nabilone while a two and a half severity rating observation in domperidone treatment group.
Scientific research in Cannabinoid for treatment of seizure in children has increased recently in which some researchers investigate it as a no epileptic condition while others study it as a pediatric condition. Many studies indicate that Cannabinoid has benefits for seizures which include treatment-refractory epilepsy. Febrile seizures happen mostly in healthy children who have no signs of any neurological disorders such as meningitis and encephalitis. In children of less than one year old, clinical symptoms of meningitis may not manifest. Anoxia and perinatal hypoxia are the leading causes of seizures in newborns. The approximated cases were about 50% to 70% of newborn seizures results from hypoxic-ischemic encephalopathy.
Treatment of Epileptic Seizure and Alzheimer’s Disease Alzheimer is a chronic neurodegenerative disease which starts at a lower rate without the patient notice and becomes worse over time. It accounts for over 60% of dementia cases. Loss of memory is the most common signs of this condition. Other symptoms that develop include mood swings, language problems, lack of self-care and unusual behaviors. Alzheimer disease (AD) is related to increased incidences of seizures. This condition rarely affects young, energetic individual but instead change the old people mainly over 65 years of age. Hypertension, head injuries, and depression can mostly cause Alzheimer disease.
The brain distinguished by several levels of complexity that ranges from molecules and personal synapses to connect the networks. The combination of the two conditions mainly occurs in old patients. A journal found that antiepileptic drugs used in seizure prevention can also be used to treat patients with seizure-like brain function in individuals with Alzheimer’s.
A study conducted to assess the impacts of the antiepileptic drugs on ten patients diagnosed with Alzheimer’s disease in its early stages. The entire patient injected with either high or low dose of LEV or placebo. They were administered with EEG to discover any unusual electrical functioning in the head (Kavalali & Ege 5). The ten participants were also with cognitive examinations to identify changes in language and memory function of the patients. The results indicated that those who had obtained a high dose of LEV showed a decrease in unusual activities of the brain. However, there was no advancement in cognitive test outcomes. It proved that there is the need for more research on the drug before broad use for patients with dementia. It is essential to evaluate how the medication would affect Alzheimer’s patients if utilized for a more extended period.
Epileptic Seizure and Hyperactive Children Hyperactive children who have epilepsy have an attention- deficit hyperactivity disorder (ADHD). The disease is a general neurodevelopment disorder that develops with epilepsy condition. Children with ADHD may increase chances of epilepsy. Epileptic children may also evident signs and symptoms of the ADHD. Children with epilepsy tend to have behavioral problems such as cognitive destruction. Frontal lobe seizures, complex partial seizures (CPS), rolandic and benign childhood epilepsies are said to be prone to ADHD and other behavioral predicaments (Brenda &Jacobson, 574)).
Very young children whose epileptic seizures are uncontrolled tend to experience worse cognitive performances. At this point, treating improves the behavior and attention. It involves the use of antiepileptic halts. The antiepileptic rarely has severe impacts on the cognitive growth of the minors. Certain antiepileptic, however, affects child’s performance and concentration although administered within their healing range. Example of such includes the topiramate, gabapentin and phenobarbitone medications. Sometimes it’s difficult to distinguish whether lack of performance is caused by a seizure or by the ADHD. To this, physicians perform neuropsychological tests as well as video electroencephalograph.
Non-epileptic young people who have ADHD have the higher rate of EEG abnormalities compared to those without such problems. According to some research works, methylphenidate and atomoxetine are safe to children who portray ADHD without any history of epileptic seizures. However, uncertainty remains in situations where these medications used in children with ADHD and epilepsy or those who have abnormal EEG with no historical records of epilepsy. In cases where both ADHD and epilepsy reported in a child, lamotrigine may be more helpful compared to another antiepileptic.
Cancer Patients with Epileptic Seizure Many causes are resulting in epileptic seizures in patients who have cancer. Seizures are the first noticeable signs of brain tumors. In most cases, they develop from metabolic difficulties or CNS infections. They may also arise from the side effects of chemotherapy drugs. Cancer patients with pre-diagnosed epilepsy have always encountered series of seizure. Presence of cancer in a patient with epilepsy and still having seizures complicates the use of drug therapy and treatment for both situations. Pathology, epidemiology and drug treatment of epileptic seizures in cancer diagnosed patients is usually complicated.
Various researchers indicate that seizures are more common in patients who have a small rating and deliberately developing brain tumors as compared to patients with highest rates of glioblastoma multiform. Mostly Dysembryoplasticneuroepithelial tumors result in one seizure. Meningiomas only cause seizure occurrence in rare cases.
Clinical physicians find complications when diagnosing patients with both cancer and epileptic seizure conditions. The interaction between the two chemotherapy medication and anti-epileptic drugs is complicated. Numerous anticonvulsant drugs used in the treatment of epilepsy have a little healing gap. The co-prescription of medicines which changes their pharmacokinetic has severe impacts on their functioning. Consequently, co-prescription of antiepileptic drugs might affect the pharmacokinetic and functioning outline those without cancer diseases. Many studies state anticonvulsant medicines that result in few problematic conditions in merging with chemotherapeutic medications.
Epileptic Seizure Treatment and Depression A study published in epilepsy and behavior indicated that depression is one of the general mental problems affecting individuals with epilepsy. Depression always has an unenthusiastic impact on one’s being and affiliations. It is therefore essential to seek treatment. Depression is mood disorders which make people feel down, angry, scared or anxious. When one is depressed, they lack concentration, sleep too much or have insomnia. One can lose curiosity in their daily activities, feel more or less hungry than usual or have an unusual headache and tenderness. Depression usually affects an individual’s work and personal relationship with other people. A person cannot have peace of mind when depressed.
People with epilepsy may experience depression as an aura which provides caution signal of an oncoming seizure. Depression can be long-term thus attaching the patient at any moment. In people with epileptic seizures experiences despair which may be the product of many factors. Some factors such as seizure type, side effects of drugs, hormones and psychological factors contribute to depression in patients who have seizures.
Studies suggest that sex hormones can affect an individual by increasing chances of both depression and epilepsy to develop. The hormones affect females more than males. Antiepileptic medication especially Barbiturates may affect the feelings thus increasing chances of a recession. Seizures also affect the patient’s mood leading to rare mood disorders. People with epileptic seizures are psychologically tortured thus feeling sad, unloved, and embarrassed by their condition. These emotions and feelings may contribute to depression and stress.
Treatment of both depression and epilepsy at the similar moment may be challenging. The patient’s symptoms may be affected when he or she uses antiepileptic drugs together with antidepressant medications. For example, it is advisable not to take Wellbutrin drug for depression when one diagnosed with epilepsy. The result is because the medicine raises the incidence of seizures. Doctors advise patients to use an effective dose that may differ from one patient to another. Sunlight helps to enhance moods. Patients are recommended to get enough sunlight which not only boosts their feelings but also provide many essential health benefits. When all antidepressant drugs fail to work, electroconvulsive therapies are the recommended option. Although there are no proofs of spreading depression, it’s likely for one to experience depression when one that has depression flu is close to you.
CHAPTER 3: METHODOLOGY In scientific research, the methodology is one of the critical areas to be included in thesis work. It acts as a basis for the results of the research findings. Improper methods of data collection may affect the purpose of the research since wrong conclusions recorded. Therefore, a researcher should have a good plan so as achieve the reliable results. Reliability of the results relies on its consistency even after when the study is repeatedly done by other researchers. The functional structure of the methodology helps in achieving reliable information.
Data Collection MethodsThe main reason for data collection was to fetch sufficient information was achieved. For this attained, the interviews were given in the actual time by the researcher. The responses received were then compiled and analyzed using the data codification techniques. The process accomplished by case study, surveys and review of a relevant literature review.
Sources This study gathered data from a wide range of available articles and journals about cannabis in epilepsy. Both academic and non-academic documents were resourcefully used to collect all the necessary information. First, memoirs about epilepsy utilized. Second, online search titled `cannabinoids in epilepsy` were searched, followed by `positive influences of cannabinoids on epilepsy in adults. ` Finally, the literature review carried much information on both conceptual and empirical works, with more than ten articles overviewed.
Case Study Case reports explain both anticonvulsant and proconvulsant of cannabis and how they diverse spectrum of reported responses. Within three weeks cannabis was used seven times and associated with repeatedly tonic-clonic- seizures. The patient was said to have been seizure free for six months. However, seizures were not occasionally correlated with quick intoxication or with withdraw. In a 29- year old man with a strong history and bipolar disorder, halting the use of cannabis resulted in increased seizure frequency.
In another part of-of the case study, a 43-year old Carbamazepine followed with 6-7 nights of-of one-minute violent seizures. But once they consumed 40mg C.sativa, his seizure declined while withdrawal doubled his previous seizure frequency. In the same study, a 60-year-old with a 39 years history of cannabis use in cigarette developed seizures condition after he stopped using the cannabis. The toxicity of these human-made agents may result from the properties of agonist in the Delta9-THC, compound.
Many of the studies showed an anticonvulsant effect of cannabis. In a trial conducted in 1949 showed that use of Delta-9THC lowered the seriousness of seizures. A patient using 3cigarretes a day was observed to have minimal intervals of seizure frequency. Parents with children suffering from seizures reported the case of more relaxation and alertness once they used the product. Also, an adult, 45 years old when used marijuana daily was seen to have a reduction of subsequent seizures. Recent cases support the report of reduced seizure accompanied by the increase in case of withdrawal. Below is a graph that was used in Europe to indicate the relationship between prevalence and age (Merrik et al., 700).
Fig1.1. A relationship between prevalence and age
Reports and SurveyThe recent reports analyzed research data, collected and enforced using Redcap electronic data capturing tools grounded at the Stanford Center for medical informatics. Redcap (Research Electronic Data Capture which is a safe web-based application planned to promote data capture for research studies. This review had twenty-four questions measuring clinical aspects, together with seizure types and diagnosis. Also reported effects of cannabidiol, frequency and side effects were some of the issues asked. A Facebook group was created to present the survey with 150 people in support of the use of cannabis as a means to develop seizure. Further, the study was sent for two weeks in the group and later reposted at the headline of the group. Out of twenty response, only one response was invalid since the diagnosis skipped. However, the nineteen responses included the use of cannabis and their determination (Press, Craig, Kelly, and Kevin 180).
Study outcomes had a huge number of people suffering from Dravet Syndrome and responded typically positive results for both seizure control and their negative impacts; the aim was to evaluate patients outcomes based on the similarity of their responses. Specializing on stiripentol, which proved to be well known to most parents would allow for efficient comparison between this response and the available clinical trials. Likewise, side effects from the two sources compared. To this point, the same survey posted to a different facebook group comprised of patients with Dravet syndrome consisting approximately 700 members. Similarly, this study was posted for ten days on the facebook page and later reposted for two weeks as the heading of the group`s platform for another two weeks. Twenty responses were received accompanied by their analysis. Then these surveys were carefully evaluated and analyzed.
Clinical Trials A recent review accessed five first clinical trials to evaluate the efficiency of marijuana on seizures. Two of these trials illustrated no effects while the three tests showed partial results. The fundamental goal of this study was to weigh the safety using cannabis, but seizure diaries obtained for convulsive progress. Also, the total possible signal was regarding efficiency. Some of the things noted were that most of the data received from the patients utilized efficiently. A median of atonics seizure reduced by 58% after using marijuana, 17% experienced diarrhea, and 4% discontinued the medication. The conclusion was that CBD was decreasing seizures frequency continuously.
Treatment of Data Data collected in the survey context are analyzed and presented in a way that it can easily be understood. The data from the survey was analyzed to obtain all the information in them. Then graphs were used to present the information derived from the clinical trials and investigations. Finally, data in the case study keenly overviewed and a comparison between the different sources.
Research Limitations The limitations of this study are the open-label, caused by single case reports that are compounded by variability in epilepsy syndrome. Also, variation in dosage composition, difference cannabis medication led to bias in the data presentation.
CHAPTER FOUR: RESULTSPositive Effects Reports concerning the anti-epileptic capability of cannabis have lasted since ancient times. Anecdotal reports indicate that sudden stoppage of cannabis treatment would lead to re-emergence of the condition in future. Continuous use of marijuana has proved to be the only path towards controlling epilepsy (Emilie et al. 189). Some anecdotal proof was promoting the anti-epileptic. Furthermore, marijuana is made up of extra components together with Phytocannabinoids and non-cannabinoid compounds.
Anecdotal evidence also shows that in some patients the use of cannabis may not affect the seizures or at times the condition is worsened. Even though there is no sufficient information, some states such as Canada and the United States have licensed the use of cannabis in epilepsy treatment. Some physicians have justified the use of marijuana for epilepsy syndrome treatment. Otherwise, quality information on safety and effects of their use should adequately give to the patient before use.
The focus on selectively reporting the issues surrounding cannabis effects and benefit was meant to reach as many people as possible. According to recent reports, this report moved many parents who had children suffering from epilepsy. As a result, many put their children under the cannabis treatment. A beneficial report is that seizures reduced by up to 50%, this was mostly with new residents compared to the ancient residents of the city of Colorado. There is no other method of treating epilepsy that would yield such results compared to cannabis products.
The graph below shows a comparison of a clinical trial for the Colorado residents (Glauser et al. 48).
Fig 2.1Clinical trials in Colorado
Anti-seizure drug effects of THC
THC usually identified as the central composite in cannabis. It acts as a fractional agonist at the cannabinoid CB1 receptors allocated in the CNS and CB2 receptors found in immune system cells. The anticonvulsant anciently investigated in the 1980s. The study yielded primary anticonvulsant effects though in some studies there were pro-convulsant effects, and in others, there were no effects. Although past reports showed anticonvulsant an impact of TCH, there was no indication of pro-convulsant effects, to achieve these conflicting results, it depends on the neurochemical action of the TCH on the CB1 receptors found in glutamatergic.
Proconvulsant achieves anticonvulsant effects by inhibiting glutamatergic excitatory diffusion and reducing the release of GABAergic neurons. According to these findings, the stimulation of CB1 receptors might be insufficient to produce therapeutic significance for patients diagnosed with epilepsy. Additionally, the advancement of acceptance plus the significant effects of THC restricted the examination of this complex in medical trials.
Anti-epileptic Impacts of CBD CBD is one of the major important Phytocannabinoids. This compound is complicated in understanding due to the numerous mechanisms it undergoes to produce several pharmacological effects. The functions of CBD are independent of the CB1/2 receptors since it contains a very low infinity of these receptors. But they antagonize the CB1/2 agonists at molar level; also they the compound inhibits anandamide at the micromolar range and inhibit enzymatic hydrolysis .further, at nanomolar concentration, it activities the function of the inhibitory glycine-receptor and antagonizes opioid receptors as well as adrenergic.
Furthermore, CBD lowers hydroperoxide- prompted impairment tissue activity and fabrication of nitric oxide (NO), and T- cells reaction. Their multi-pharmacological profile motivates the response of CBD to the vast therapeutic potentials. Nevertheless, the many effects produced at the micromolar level are of no significance to the impact of CBD. Although extra research needs to be carried out to identify rich information about CBD therapeutic effects than in the past this drug has been so much interest to many patients. Generally, this complex used as a mood stabilizer, anticancer, sedative and to on cannabis withdrawal syndrome to state a few. Currently, there are 20 medical trials on CBD management together with six evaluations on multiple series, two researchers on cancer pain and four studies on schizophrenia and bipolar mania. The table below shows the efficiency of antiepileptic medication established by American Herbal Pharmacopoeia ( Schönenberg 23).
Compound species Number of discrete models/design Dose (mg/kg) Anticonvulsant
(%) Proconvulsant(%) No effect (%)
CBD 3 25 1-500 85 20 0
THC 8 35 0.5-250 64 29 10
Other plant cannabinoids 4 8 Not applicable (N/A) 100 0 0
CB1 receptor agonists 3 60 Not applicable N/A 85 20 4and 10%mixed effect
Table 2.1. the efficiency of Cannaboids as Antiepileptic drug
Anticonvulsant Effects of CBDV CBDV is the possible version of CBD, extracted from cannabigerovarin which is an anti-epileptic agent. This compound is reported to be independent of the CB1 receptors as it contains very weak infinity of the receptor. Besides CBDV constrains endocannabinoid enzyme synthesis at the nanomolar range; also it acts through CB2 receptors. Unfortunately, the clinical significance of these special effects is at a halt sure. The CBD antiseizure side view was examined employing multi-electrode display soundtracks on a confined field.
Latest studies were carried out to access whether the epileptiform function of CBDV correlated to the simulation of transient receptor potential (TRP) channel. Tests carried out on the brain showed mg+ free solution using multi-electrode arrays. These slices are extracted from the hippocampal brain reducing both epileptic height and period. The fact that a discerning TRPV1 antagonist did not invert the effects caused by CBDV; TRPV does not exclusively intercede them. In conclusion, CBDV shows antiepileptic aspects for various premedical structures also released fewer speed effects. Therefore CBDV could be useful in many epileptic syndromes with less poisonous than further anti-epileptic medicines.
Anticonvulsant Effects of CBN A small number of studies explored the ant seizure aspects of CBN. Like CBD and CBDV, micromolar concentration hinders intake of anandamide. An illustration was carried out on rats and exposed to AS experiments and for CBN antiepileptic influence be counted. For this case of MES check, CBN released anti-epileptic results while when AS used, it showed just a negligible efficiency in the AS examination.
Antiepileptic effects of delta 8-TCH
Delta-8- TCH outcomes as of the isomerization of THC along with are characterized by uniform pharmacology, even though weaker than delta-9-TCH. A study was conducted using a rat said to be unceasingly epileptic by bilateral incorporation of cobalt hooked on fore cortices. The Delta-8-TCH abridged the occurrence of a seizure. After 25 minutes of introduction of delta-8-TCH, the active seizure activity completely ended. All the same, tolerance cropped up after six days in the chronic delta-8-THC medication.
Anti-seizure Effects of Delta-9-THCV As seen with CBG, delta-9-THCV product, extracted as of cannabigerovarin. Compiled articles stated a moderately high-infinity combination of delta-9-THCV with CB1 receptors. This reaction lacks agonist action resulting in being termed as a CB1 antagonist. An evaluation of the anticonvulsant potential of delta-9-THCV, in a mold of induction, was conducted using Ma+ free extracellular channel. When tested using PTZ test, a substantial drop burst multiple incidences in addition to the height and intervals of paroxysmal depolarization movement. Also, delta-9-THCV displays a significant reduction in the burst dressy occasion and PDS peak height. Demonstrably, CBG reduces seizure incidence in the PTZ assessment.
Antiseizure Effects of CBG CBG forms antecedent of CBD along with THC. CBG hinders uptake of anandamide in the micromolar concentration. Next, the phytocannabinoid activates TRPVI routes and becomes an agonist at adrenoceptors and antagonist receptors. The impacts of CBG on the canals were experimented using being neuroblastoma cells. Also the effect of CBG on PTZ- induced seizures when evaluated in rats. When tested in both cases there were no effects. In summary, it concluded that CBG does not correlate with anticonvulsant influence.
Cannabidiol Formulation and Pharmacodynamics Currently, there are three pharmaceutical products in trials or development. They include epidiolex, extracted from sativa plants. Synthetic CBD derived from Insys Therapeutics, and the last product is Transdermal CBD gel from Zynerba Pharmaceuticals. More CBD products are commercially available, and some obtained from the internet. However, the consistency and the quality regulations of these drugs are indefinite. Otherwise just 18 CBD products have been authorized by the US Food and Drug Administration.
The CBD cannabinoids are highly soluble in water, and traditionally this drug is delivered orally inform of an oil-based or as a sublingual spray. Being a soluble drug, it lowers variance in absorption. CBD is protein-bound in the blood and efficiency into the adipose cells and the brain. These drugs are essentiallymetabolized by the liver P-450 (CYP-450) enzymes. Similarly, Delta9-THC can inhibit the same enzymes activity as CBD. Generally, these two products are capable of inhibiting other different enzymes raising the metabolic level of clobazam, thus translates to be sedative and efficiency of CBD.
Placebo Effect Impact of placebo is dependent on the power of belief. An illustration of this communication is Charlotte’s Web. The drug is a specific extract of the cannabis plant, manufactured by the Stanley brothers of Colorado. The product had a high CBD level and low THC level. The name of the company originated from a patient who was reported to suffer from Dravet syndrome. The girl had a history of experiencing seizures 300 times a week. Fortunately, her parents identified someone who would supply cannabis extracts. The supplier convinced the parents that his product contained high levels of CBD. The parents were satisfied, and their daughter began the medication immediately. Following the dosage, her condition improved positively, to four seizures in a month. Her experience attracted attention globally and the media too concerning. After this scenario, the extract branded the name Charlotte`s web. The graph below shows a comparison of a clinical trial for the Colorado residents.
While reports are showing an increase in response of the adult patients, the target is unachieved yet. Placebo reports are generally high among children and adolescents with different disorders such as significant depressions and anxiety. Among patients with resistant towards epilepsies treatment, children’s number was higher than for adults. In predominately pediatric trials were lowered by a high percentage of drug-treated patients (Porter, Brenda & Catherine 575). In contrast, the extreme attention and rigid values in the competence of cannabis intended for epilepsy might increase placebo reactions making it harder to demonstrate an actual gain in RCTs.
Legal Concerns of Cannabis Cannabis and substances derivative from it are classified the same as Schedule I medication by the Drug Enforcement Agency (DEA). The Schedule I drugs are the highly abused drugs since they allow a lot of physical dependence. Additionally, they are currently not considered as medicines. It is ironical that drugs such as benzodiazepines and opiates are classified as Schedule II drugs in spite of their high dependence compared to cannabis. According to the drug regulatory, they argue that marijuana is unapproved yet for medicinal use. It is unjustified since some of these products remain authorized by the FDA.
Other substances are a permit by the regulatory organizations in 23 nations. The authorizations generally founded on RCTs generate effectiveness and favorable secured outline, including an abridged probable for misuse. The Schedule I classification formulates it to be hard for researchers to examine cannabis-derived cannabinoids in critical and medical science. There is usually a costly and lengthy procedure to obtain an extensive, lengthy and weight which may require clarity from expertise and security schemes. This clarity is about the room and building for storage.
Schedule I usually omit the residents and people living in developed towns from undertaking clinical trials. The purpose of primary and participation in studying cannabis is still on and vigorous as ever. While substance to give to children, is readily available to their parents at when required. This process has thus widened the gap between exposure and knowledge. Especially interest is shifted to the children since the requested data from them yet obtained.
Therefore both CBD and THC might potentially subsidize bidirectional drug-drug collaborations when used with additional medicines.
CHAPTER FIVE: DISCUSSION Information supporting proconvulsant and anticonvulsant effects of pre-clinical tests and smoked tobacco very contradicting. Contrast arise in the cannabinoid antagonists as some studies show anticonvulsant while others fail to provide such information. Others are reporting on reduction in seizure threshold while others talk of increased seizures as a result of CB1 receptors and depletion of genes.
Nevertheless, concerning the Phytocannabinoids precisely, the reviewed literature review indicates that CBD and CBDV are intoxicating antiseizure associated with few resultant effects. There is a need for explanation by different Phytocannabinoids for clarity about the contracting reports. Alternatively, the actions of THC on CB1 allocated in GABAergic could produce pro-convulsant effects. Analyzing TCH and synthetic cannabinoids, they were reported to activate CB1 for production of their anticonvulsant effects; in contrast, several clinical reports suggested that Delta-9-THC, CBD, CBN, and CBDV produced their anticonvulsant effect independent of the CB1.
Furthermore, the different outcomes could be partially reconciled using several mechanisms. Most of the methods used are animals’ models of seizures which could inconvenience the results. These inconveniences come up as a result of the differences in glutamatergic receptors, GABAergic, and availability of cannabinoid. Also, different rodents could produce both pharmacodynamics and pharmacokinetic interactions. As a result, there would be differences in mechanism of actions, methods of issuing and given doses. In this case, the likely effect of the drugs on the neurotransmitter system.
Clinical reports argue that a physiological role of endocannabinoid system in reducing seizures severity into consideration. Cannabinoid antagonist usually regulates the seriousness of seizures. Besides, the role of anandamide is protecting the hippocampal neuron against electric shock and excitability. More so, cannabinoids and 2-AG lowers the frequencies of excitability while anandamide inhibitors have anticonvulsant effects (Merrick 103). The rapid reduction, of CB1 results in severe seizures and animals CB1 in the dentate gyrus with temporal lobe epilepsy.
These results combined with the hypothesis that show that on-demand synthesized endocannabinoid strengthen fight against acute excitotoxicity .this process involves signaling the protective effects which might include opening path for K+ and reticence of Ca+ that is mediated by CB1 receptors. Often, the endocannabinoid systems produce neuroprotective stimulated impacts system. Such mechanism is independent of theCB1, during intake anandamide and enzymatic hydrolysis for inhibition.
Although many studies have been carried out to show anticonvulsants, more research needs to carry out for clarity. So far CBDV and CBD are ranked high towards treating epilepsy since they have a non-convulsant nature. Also, they have identified with their multi-pharmacological profile which likely contributes to their anticonvulsant aspects. Moreover, these compounds inhibit uptake of anandamide and enzymatic hydrolysis and have few side effects compared to other drugs. Mostly it is important to investigate the drugs to come up with improved medicines that are safe for use and with fewer side effects.
The main reason cannabis has become common among many people is that of its minimal side effects compared to other traditional remedies. Partially this is a myth that natural extracts are unexpected to be harmful. In a survey previously conduct affirmed that about 90% of the residents believe that there is inform information indicating cannabis safety for medicinal use. In fact, further randomized trials showed that previous treatment using CBD resulted in less severe effects among the patients interviewed. Although these reports are encouraging further studies should be carried out to clarify the actual results and safety using CBD. This information is even more relevant since some patient experience severe effects such as elevation of the liver. Though this condition is reversible, it is safe to curb such influence to prevent such severe results in the future.
CHAPTER SIX: CONCLUSION AND RECOMMENDATIONConclusion Over an extended period, clinical and preclinical studies have approved the use of CBD as the most reliable cannabinoids. Approval is so since they can reduce seizures efficiently especially with patients with resistant to anti-epileptic. However, there are numerous questions to be concerning cannabinoids. The questions revolve around methods, safety, and efficiency of cannabinoids in short-term and prolonged use. Further research covering cannabinoid functions and their side effects will be of much benefit.
Everyone needs to join together with the government, researchers and the entire community to establish a foundation which reliable research operation. Hence drug safety and their efficiency require a reassessing the basis for recent clinical trials and evidence. Therefore a formal set up will be evaluated whether it is quick enough. Conducting a follow-up on the patient suffering from the drug resistance epilepsy syndrome is important.
Recommendationsmedical practitioners and researchers should involve more research work on the treatment and effects of Cannabinoids on epileptic seizures
the government should provide enough financial support and resources in seizure studies
there is a need for public awareness of the medical uses of Cannabinoids
Patients should be monitored by the physicians not to misuse or use the medicine for the wrong purpose.
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