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Study The 2014): vs Brain (November Cancer Cannabis Latest



  • Study The 2014): vs Brain (November Cancer Cannabis Latest
  • Cannabis Therapeutics and the Future of Neurology
  • Cannabinoids Can be Used in Palliative Care for a Wide Range of Symptoms
  • Date: November 14, ; Source: University of St George's London; Summary: Experts have shown The new research by specialists at St George's, University of London, studied the treatment of brain cancer tumours in the laboratory and. Keywords: cannabis, pain, brain tumor, epilepsy, Alzheimer disease, et al., ), additionally supported by the National Academies of Science, . More recent studies have bolstered evidence for safety and efficacy of the As a result , it received US Food and Drug Administration approval in June Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. . Recent studies additionally showed that THC altered the balance between ceramides effects of cannabinoids in glioma/GBM treatment regimens (Scott et al., ). .. Jul; 16(7)

    Study The 2014): vs Brain (November Cancer Cannabis Latest

    Marijuana is used as a psychoactive i. Many states in the US have now legalized marijuana for medical or recreational use. However, according to federal law, the possession of marijuana cannabis is still illegal in the US, except within approved research settings. The main active chemical in marijuana is THC deltatetrahydrocannabinol , the psychoactive ingredient. The highest concentrations of THC are found in the dried flowers, or buds.

    When marijuana smoke is inhaled, THC rapidly passes from the lungs into the bloodstream and is carried to the brain and other organs throughout the body. THC from the marijuana acts on specific receptors in the brain, called cannabinoid receptors, starting off a chain of cellular reactions that finally lead to the euphoria, or "high" that users experience. Feeling of a relaxed state, euphoria, and an enhanced sensory perception may occur. With higher THC levels in those who are not used to the effects, some people may feel anxious, paranoid, or have a panic attack.

    Certain areas in the brain, such as the hippocampus, the cerebellum, the basal ganglia and the cerebral cortex, have a higher concentration of cannabinoid receptors. These areas influence memory, concentration, pleasure, coordination, sensory and time perception.

    Marijuana's strength is correlated to the amount of THC it contains and the effects on the user depend on the strength or potency of the THC. Different strains will contain different levels of THC. There are many other chemicals found in marijuana, many of which may adversely affect health. Marijuana may be smoked as a cigarette called a joint or a nail or in a pipe or bong.

    It may be smoked in "blunts", which are cigars that have been emptied of tobacco and refilled with marijuana, often in combination with another drug, such as crack. Some users also mix marijuana into food or use it to brew tea.

    In states that have now legalized sale of marijuana for recreational use, the marketing of edible products, such as cookies, brownies, and chocolates, are popular for those who prefer not to smoke the product. Vaporizers are also popular for those who prefer not to inhale smoke. The devices concentrate the THC from the marijuana into a storage unit and the person then inhales the vapor, not the smoke.

    Some vaporizers use a liquid marijuana extract that can be extremely high in THC content, and can be dangerous to novice users , resulting in emergency room admissions. In the United States, the Controlled Substances Act CSA of classifies marijuana as a Schedule I substance, which states it has no approved medical use and a high potential for abuse.

    This Federal definition is highly controversial, and can limit marijuana's availability for clinical research studies. Prescription medicines containing synthetic cannabinoids THC are also available. Dronabinol, a pharmaceutical form of THC, and nabilone, a synthetic cannabinoid, are approved by the FDA to treat certain conditions. Syndros is a liquid form of dronabinol. Both dronabinol and nabilone are approved to treat patients receiving anti-cancer medicine chemotherapy who have nausea and vomiting, particularly patients who do not respond to other treatments.

    Sativex, an oral sublingual spray, is approved for use in multiple sclerosis MS spasticity. In Israel, Sativex is approved for the indications of MS spasticity and for chronic cancer pain. Sativex is composed of standardized extracts of THC and cannabidiol and is available as an oral mucosal spray formulation.

    GW Pharmaceuticals and Otsuka Pharmaceuticals announced results of three US Phase 3 trials in for the use of Sativex for the treatment of pain in patients with advanced cancer who experience inadequate analgesia during optimized chronic opioid therapy. According to the study results, Sativex did not meet the primary endpoint of demonstrating a statistically significant difference from placebo for pain control. Epidiolex comes as an oral solution. These forms of epilepsy -- Lennox-Gastaut syndrome and Dravet syndrome -- are severe, rare, and begin in childhood.

    Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana -- CBD -- and the first treatment for Dravet syndrome. In pivotal Phase III studies with patients with either seizure type, Epidiolex, as an adjunct with other seizure drugs, was shown to be effective in reducing the frequency of seizures when compared with placebo.

    Common side effects with Epidiolex included sleepiness, diarrhea, sedation and lethargy, signs of possible liver damage, and decreased appetite, among others. Medications listed in Schedule V have a proven medical use but a low potential for abuse. In the past survey year , In the same survey, past year marijuana use among adolescents aged 12 to 16 years dropped from Side effects of marijuana use will be variable from person to person, depending upon strength and amount of marijuana used and if the user is occasionally or chronically exposed to THC.

    Side effects can be magnified in older people. Reaction time may be impaired while driving. NIDA research shows that drivers have slower reaction times, impaired judgment, and problems responding to signals and sounds if driving while under the influence of THC. Panic attacks, paranoia and psychosis may occur acutely and be more common in psychiatric patients, a reported by Heller.

    For chronic users, the impact on memory and learning can last for days or weeks after its acute effects wear off, as noted by the NIDA. Marijuana, if purchased on the street, may be cut or substituted with substances that can lead to unknown, dangerous side effects. THC in marijuana is strongly absorbed by fatty tissues in various organs. Generally, traces of THC can be detected by standard urine testing methods several days or more after a smoking session.

    In heavy chronic users, traces can sometimes be detected for weeks after they have stopped using marijuana. Long-term abuse of marijuana may lead to dependence in some people. McKenna, et al have reported on the addicting potential of marijuana, noting that "it is an erroneous belief widely held by the general public, and among many physicians, that marijuana is not addicting. Withdrawal symptoms can occur upon abrupt cessation of the drug, including:.

    Marijuana also may affect mental health. Also, rates of marijuana use are often higher in people with symptoms of depression or anxiety, as reported by the NIDA. There have been no reports of THC overdose leading to death. Shortly after smoking marijuana the heart rate increases drastically and may remain elevated for up to 3 hours. This effect may be enhanced if other drugs are taken with marijuana.

    One study from Mittleman, et al has suggested that the risk of heart attack may increase by up to 4. The effect may be due to the increased heart rate, as well as altered heart rhythms. The risk of heart attack may be greater in those with specific risk factors such as patients with high blood pressure, heart arrhythmia, or other cardiac disease.

    Harvard Health also reports that the risk of a heart attack is several times higher in the hour after smoking marijuana than it would be normally, and this should be a red flag for anyone with a history of heart disease. The risk of stroke may be increased, as well.

    After smoking marijuana, the bronchial passage relaxes and becomes enlarged. Marijuana smoke contains many of the same cancer-causing chemicals found in cigarette smoke, often in greater quantities, as reported by Mehmedic and colleagues.

    Both types of smoke contain cancer-causing nitrosamines, polycyclic aromatic hydrocarbons, vinyl chlorides, and phenol per research reported by Martinasek. Studies have shown that marijuana smoke contains 50 to 70 percent more carcinogenic hydrocarbons than tobacco smoke, and is an irritant to the lungs. Marijuana users tend to inhale more deeply and hold their breath longer than tobacco smokers do, which further increases lung exposure to carcinogenic smoke. People who smoke marijuana often have the same respiratory problems as cigarette smokers.

    These individuals may have daily cough and phlegm, symptoms of chronic bronchitis, shortness of breath, chest tightness, wheezing and more frequent chest colds. A systematic review of the respiratory effects of inhalational marijuana from Martinasek, et al indicates that there is a risk of lung cancer from inhalational marijuana as well as an association between inhalational marijuana and spontaneous pneumothorax, emphysema, or COPD.

    In the review, eight of the 12 studies indicated an increased risk of lung cancer from cannabis use or cases indicating lung cancer occurrence. These numbers could rise as more states continue to legalize marijuana for medicinal or recreational purposes. Due to possible adverse effects of marijuana on the fetus, ACOG recommends that marijuana should be avoided during pregnancy.

    Any drug of abuse can affect a mother's health. THC appears to cross the placenta, according to Davies et al. Human fetuses exhibit the cannabinoid receptor type 1 in the nervous system as early as 14 weeks of gestation, and animal studies suggest cannabinoid exposure may lead to abnormal brain development.

    As reported by de Moraes Barro and colleagues, babies born to adolescents who used marijuana during pregnancy have shown adverse neurological behavior effects of the newborns in the first 24 to 78 hours after delivery.

    Most reports do not show an association between marijuana use and preterm birth. However, as noted by ACOG, studies have suggested the use of marijuana with tobacco may increase the risk for preterm delivery. In addition, research demonstrates that babies born to mothers who used marijuana during pregnancy at least once per week or more were smaller than those born to mothers who used the drug less frequently.

    Studies on school performance have shown differing results: THC is excreted in breast milk, according to Davies, et al. ACOG recommends that marijuana use be discontinued during breastfeeding.

    The scientific data are not strong enough to determine the risk to the nursing infant. A drug is addicting if it causes compulsive, uncontrollable drug craving, seeking, and use, even in the face of negative health and social consequences. Research suggests that roughly 9 percent of users become addicted to marijuana, with higher rates if the user starts at a young age 17 percent and in those who use marijuana daily percent.

    While not everyone who uses marijuana becomes addicted, when a user begins to seek out and take the drug compulsively, that person is said to be dependent or addicted to the drug. Some heavy users develop a tolerance to marijuana; meaning that the user needs larger amounts to get the same desired results that he or she used to get from smaller amounts, as noted by the NIDA.

    Long-term users who try to quit could experience withdrawal symptoms such as sleeplessness, irritability, anxiety, decreased appetite and drug craving. Withdrawal symptoms usually begin about a day after the person stops using marijuana, peaks in 2 to 3 days and may take about 1 to 2 weeks to subside. McKenna reports that marijuana addiction is difficult to treat in the clinic. Patients can have a lengthy withdrawal and symptoms that can continue for months after stopping marijuana use.

    Marijuana has been used as a therapeutic and medicinal agent for centuries, dating back to the 27th century BC. Today, it is still used for medicinal purposes, although restrictive laws surrounding its use now exist. Medical marijuana is available in many different forms from dispensaries: Rules surrounding the use of medical marijuana vary by state. The first state in the union to legalize the medical use of marijuana was California in with Proposition States that allow medical marijuana include: It is important to recognize that these state medical and recreational marijuana laws do not change the fact that using marijuana continues to be an offense under Federal law.

    Medical marijuana in the US is controlled at the state level. Per federal law, cannabis, a schedule I drug, is illegal as noted in the Controlled Substances Act, but the federal government, under the previous Obama administration, had stated they would not actively prosecute patients and caregivers complying with state medical marijuana laws.

    However, use of medical marijuana outside of the state laws for illegal use or trafficking would not be tolerated by state or federal government. These rules may be changing under Attorney General Jeff Sessions. Political leaders, US government officials, health care providers and medical organizations take differing views of the benefits and risks of medical marijuana.

    Proponents state that marijuana has valid medical uses and further research should be pursued, while opponents list concerns about health risks, and the "gateway" effect of marijuana that can lead to more dangerous drug abuse, among other issues. Nonetheless, legalization of medical marijuana continues to be pursued at the state level, with California being the most recent state to legalize recreation use in January Three of the patients received 75 mg of CBD per day and 1 received mg per day.

    All 4 patients experienced a significant reduction in symptoms following treatment. Probably the most exciting property of cannabis, scientific evidence for anticancer effects, goes back to at the Medical College of Virginia at the behest of the US government, about 2 decades before the endocannabinoid system and mechanism of its actions had been detected.

    Funded by the National Institutes of Health to find evidence that marijuana damages the immune system, the study found instead that THC slowed the growth of 3 kinds of cancer in mice—lung and breast cancer, and a virus-induced leukemia.

    Astrocytomas and in particular glioblastomas are the most frequent brain tumors among approximately different types. Malignant glioma remains one of the most aggressive forms of brain cancer, with a median survival after resection, radiotherapy and chemotherapy of 12 to 15 months.

    In children, brain tumors constitute the second-most-common malignancy. When cells become malignant, they develop more cannabinoid receptors and become more susceptible to endocannabinoids, thus enabling an efficient intervention. In most brain tumors the endocannabinoid system is upregulated and seems to be under epigenetic control.

    Interestingly, some benign pediatric astrocytic tumors, such as subependymal giant cell astrocytoma, which may only occasionally cause mortality owing to progressive growth, also display high CB2 immunoreactivity. Cannabinoids decrease tumor progression by at least 2 mechanisms: Initial studies showed that THC and other cannabinoids induce the apoptotic death of glioma cells by CB1- and CB2-dependent stimulation of the de novo synthesis of the proapoptotic sphingolipid ceramide.

    Therefore, additional, nonreceptor mechanisms such as induction of reactive oxygen species seem to be plausible. The first and only published clinical study aimed at assessing antitumoral action of THC in humans was a pilot phase 1 trial in 9 patients with recurrent glioblastoma multiforme. All of them had previously failed standard therapy surgery and radiotherapy and had clear evidence of tumor progression at the time they received THC.

    The median duration of an administration cycle was 10 days; 5 patients received more than 1 cycle. In 3 of these 5 patients, a temporary reduction of tumor proliferation was observed. THC administration was safe without overt psychoactive effects. In 2 patients who received THC for 30 and 26 days, respectively, and in whom CB receptor expression had been determined after THC treatment, a slight decrease in CB1 receptor expression but no change in CB2 receptor expression was observed, which might reflect a predominant binding of THC to the former protein or its higher susceptibility to desensitization.

    Maximal doses of THC and CBD in these 2 trials are about 5- to times lower than doses that were effective in animal studies see below. In contrast to THC, CBD does not interact directly with CB1 and CB2 receptors but produces nonetheless a remarkable antitumor effect in glioma as well in a number of other animal models of cancer, including reduction of invasiveness and metastasis.

    The mechanisms by which CBD kills glioma cells, independently of cannabinoid receptor stimulation, both in vivo and in vitro, has not as yet been completely clarified. It seems to rely—at least in part—on its ability to inhibit the transcription of tumor-related genes eg, midkine, MDK and enhance the production of reactive oxygen species in cancer cells.

    CBD also decreases the activity and content of 5-lipoxygenase. It is therefore of particular interest that CBD significantly downregulates Id-1 gene expression and associated glioma-cell invasiveness and self-renewal at concentrations that can be achieved in vivo.

    A number of reports on treatment of various brain tumors with cannabis exist in the internet but are unfortunately restricted to inconclusive or poorly documented anecdotal testimonials on various cannabis extracts eg, hemp oil used by patients or their relatives 63 ; this includes also a report on spontaneous regression of pilocytic astrocytoma after incomplete resection in 2 children.

    A recent review article emphasized that all 16 in vivo studies that evaluated cannabinoid action on glioma so far showed statistically significant reductions of tumor volumes when comparing to controls.

    Duration of treatment was between 7 and 28 days. Results are summarized in Table 3 and also include publications since the data lock date of AM review, December Combinations with temozolomide, X-rays, or cannabinoids enhanced the activity further.

    One study demonstrated that higher doses of THC were more effective, thus confirming a dose-dependency observed already in vitro; differences in sensitivity of glioma cells to cannabinoids exist. In short, a number of experiments, in vitro and in vivo, have demonstrated that cannabinoids act synergistically, which is of great importance for the development of future anticancer therapies.

    The treatment of glioblastoma cells with both compounds, THC and CBD, led to significant modulations of the cell cycle and induction of reactive oxygen species and apoptosis as well as specific modulations of extracellular signal-regulated kinase and caspase activities. These specific changes were not observed with either compound individually, indicating that the signal transduction pathways affected by the combination treatment were unique.

    A steadily increasing number of publications demonstrate the high potential of cannabinoids in palliative care. They can be combined with other therapies and seem to be devoid of any significant toxicity. Effects differ, however, between cannabinoids and change also with increasing doses whereby many aspects remain unsolved.

    However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects.

    Generally, higher doses are needed to achieve analgesic and antiemetic effects. Such high doses preclude an oral use of THC as single substance in humans due to side effects. Many questions are also unsolved when it comes to chronic treatment with cannabinoids, a particularly important point in palliative care.

    Full recovery of CB1 receptors after stopping THC for example may take up to several weeks, with regional differences. Is a daily treatment, as commonly practiced, necessary or is a pulse-dosing concept with intermittent dosages given as short cycles a better alternative? How long last effects? CBD and possibly other non-psychotropic cannabinoids, may be a promising alternative for many indications, likely to include nausea, vomiting and improvement of sleep, although more studies in humans are necessary.

    Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations.

    However, for many pharmacological effects except against tumors roughly times higher daily doses are needed for CBD compared to THC. This leaves some doubts as to whether a 1: A further, unsolved question is whether the common intervention strategy of 1 to 3 applications of cannabinoids per day can be optimized.

    More recent findings demonstrate that the activity of the ECS is profoundly modulated by circadian rhythmicity. As an example, CB1 receptor protein is at its highest concentration when AEA levels are lowest and vice versa, whereas the expression of CB2 did not show striking diurnal differences, at least in the rat cerebral cortex. In contrast, levels of 2-AG, a full agonist to CB1 receptors and about times more abundant in brain than AEA, follow an opposite course. Concentrations are lowest around In rats, an AEA injection before experimentally induced traumatic brain injury significantly increased survival when traumatic brain injury was induced at This suggests that the time of administration of cannabinoids could also modulate effects.

    Last but not least, nutrition also plays an important role in palliative care. Some pathways of their degradation produce, among others, proinflammatory compounds.

    A recent study found that 2-AG plasma levels were significantly reduced by a diet high in omega-3 and low in omega-6 fatty acids H3-L6 intervention , which in turn significantly decreased severity of headaches. In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.

    Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account.

    Close mobile search navigation Article navigation. Cannabinoids Reduce Nausea and Vomiting. Cannabinoids Improve Other Cancer-related Symptoms.

    Anticancer Effects of Cannabinoids may be able to Prolong Life. The use of cannabis in supportive care and treatment of brain tumor Rudolf Likar. Abstract Cannabinoids are multitarget substances. Pharmacological and therapeutic secrets of plant and brain endo cannabinoids. Cannabinoids for control of chemotherapy induced nausea and vomiting: Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting.

    A prospective evaluation of deltatetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy.

    A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus house musk shrew. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT 1A somatodendritic autoreceptors in the dorsal raphe nucleus. Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus house musk shrew.

    Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A phase II study of deltatetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.

    Deltatetrahydrocannabinol as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. Comparison of orally administered cannabis extract and deltatetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: Dronabinol zur supportiven therapie metastasierter maligner Melanome mit Lebermetastasen.

    The efficacy and tolerability of long-term use of dronabinol in cancer-related anorexia: The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Cannabidiol decreases body weight gain in rats: Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT 1A receptors without diminishing nervous system function or chemotherapy efficacy.

    Initial experiences with medicinal extracts of cannabis for chronic pain: Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain. Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies. Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core. Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice.

    Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis.

    Antidepressant-like and anxiolytic-like effects of cannabidiol: The medical necessity for medicinal cannabis: The effects of cannabinoid administration on sleep: Effect of Deltatetrahydrocannabinol and cannabidiol on nocturnal sleep and early-morning behavior in young adults.

    The nonpsychoactive Cannabis constituent cannabidiol is a wake-inducing agent. Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers. Epigenetic silencing of miRc by DNA methylation in glioblastoma cell lines. Inhibition of glioma growth in vivo by selective activation of the CB 2 cannabinoid receptor.

    Cannabis Therapeutics and the Future of Neurology

    CBD is an investigational new drug (IND) in the United States, and a number of clinical Cancer Network, published in ,6 cautiously mention cannabinoids as a In Table 1, results of studies with THC in cancer patients are summarized. .. of pain only with THC + CBD (Numerical Pain Rating Scale): placebo THC. treatment for cancer over last 20 years. • Non-legal use in Smith LA et al Cochrane Review (): Cannabis- based medicine for Early studies using smoked marijuana or oral THC chronic pain. Systematic review: Whiting et al JAMA June patients with glioblastoma multiforme (GBM). • THC. PNAS November 25, (47) ; published ahead of print November 10, yaniq.xyz . For example, in a recent study by Battistella et al. (18) .. Hum Brain Mapp 35(5)– .. Several large or long-lived animals seem strangely resistant to developing cancer.

    Cannabinoids Can be Used in Palliative Care for a Wide Range of Symptoms



    CBD is an investigational new drug (IND) in the United States, and a number of clinical Cancer Network, published in ,6 cautiously mention cannabinoids as a In Table 1, results of studies with THC in cancer patients are summarized. .. of pain only with THC + CBD (Numerical Pain Rating Scale): placebo THC.


    treatment for cancer over last 20 years. • Non-legal use in Smith LA et al Cochrane Review (): Cannabis- based medicine for Early studies using smoked marijuana or oral THC chronic pain. Systematic review: Whiting et al JAMA June patients with glioblastoma multiforme (GBM). • THC.

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