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Neuroprotective effects of CBD in hypoxic—ischemic brain damage also involve adenosine A2 receptors. Specifically, CBD diminishes inflammation in acute models of injury and in a viral model of MS through adenosine A2 receptors. OPCs are highly vulnerable to inflammation and oxidative stress. Inflammation contributes to demyelinating diseases such as MS. Synthetic cannabinoids studies have shown they can protect OPCs possibly by controlling endoplasmic reticulum ER stress response that modulates the response to inflammatory stimuli.
It is an oral-mucosal spray containing a 1: The ability to modify pain may be attributed to a CB receptor-mediated regulation of supraspinal GABAergic and glutamatergic neurons.
The results of these studies were cited in the AAN review. A meta-analysis in reported that CB receptor-based medications were superior to placebo in the treatment of MS-related neuropathic pain. Overall, the analgesic response to cannabinoids was generally retained over time, at least for the 6—10 weeks follow-up period. CBD is recognized as a nonpsychoactive phytocannabinoid. Both human observational and animal studies, however, have demonstrated a broad range of therapeutic effects for several neuropsychiatric disorders.
CBD has positive effects on attenuating psychotic, anxiety, and depressive-like behaviors. The mechanisms appear to be related to the CBD's benefit to provide enhanced neuroprotection and inhibition of excessive neuroinflammatory responses in neurodegenerative diseases and conditions. Common features involving neuroprotective mechanisms influenced by CBD—oxidative stress, immune mediators, and neurotrophic factors—are also important in conditions such as posttraumatic stress disorder PTSD , postconcussion syndrome, depression, and anxiety.
Many studies confirm that the function of the ECS is markedly increased in response to pathogenic events like trauma. This fact, as well as numerous studies on experimental models of brain trauma, supports the role of cannabinoids and their interactions with CB1 and CB2 as part of the brain's compensatory and repair mechanisms following injury.
Animal studies indicate that posthead injury administration of exogenous CBD reduces short-term brain damage by improving brain metabolic activity, reducing cerebral hemodynamic impairment, and decreasing brain edema and seizures. These benefits are believed to be due to CBD's ability to increase anandamide.
Treatment with CBD may also decrease the intensity and impact of symptoms commonly associated with PTSD, including chronic anxiety in stressful environments.
In human studies, subjects introduced to fearful contexts exhibited decreased posttest anxiety when treated with CBD. In rodent models, CBD effectively blocked the formation of fearful memories. Rat trials also show CBD's potential in fear memory extinction, demonstrated through a significant decrease in freezing time when re-exposed to an anxiety-inducing situation.
Antidepressants, used for the treatment of depression and some anxiety disorders, also possess numerous neuroprotective properties, such as preventing the formation of amyloid plaques, elevation of BDNF levels, reduction of microglia activation, and decreased levels of proinflammatory mediators.
In rat models of neurobehavioral disorders, CBD demonstrated attenuation of acute autonomic responses evoked by stress, inducing anxiolytic and antidepressive effects by activating 5HT1A receptors in a similar manner as the pharmaceutical buspirone that is approved for relieving anxiety and depression in humans.
A double-blind, randomized clinical trial with CBD reported a significant clinical improvement similar to the antipsychotic amisulpride, but with less side effects. Human imaging studies have demonstrated CBD affects brain areas involved in the neurobiology of psychiatric disorders.
A study has showed that a single dose of CBD, administered orally in healthy volunteers, alters the resting activity in limbic and paralimbic brain areas while decreasing subjective anxiety associated with the scanning procedure. In healthy volunteers treated with CBD and submitted to a presentation of fearful faces, there was a decrease of the amygdala and anterior and posterior cingulate cortex activities and a disruption in the amygdala—anterior cingulated cortex connectivity.
Interestingly, THC, administered prior to a traumatic insult in human case studies and animal models has had measurable neuroprotective effects. In general, conditions associated with chronic stress appear to be positively responsive to phytocannabinoids. Studies in rat models reported that cannabinoids prevented the effects of acute stress on learning and memory and improved neuroplasticity, behavioral, and neuroendocrine measures of anxiety and depression.
Cancer is a disease characterized by uncontrolled division of cells and their ability to spread. Novel anticancer agents are often tested for their ability to induce apoptosis and maintain steady-state cell population. In the early s, phytocannabinoids were shown to inhibit tumor growth and prolong the life of mice with lung adenocarcinoma. Later studies have demonstrated cannabinoids inhibited tumor cell growth and induced apoptosis by modulating different cell signaling pathways in gliomas, lymphoma, prostate, breast, skin, and pancreatic cancer cells as well.
Glioblastoma multiforme GBM is the most frequent class of malignant primary brain tumors. CBD has also been shown to reduce the growth of different types of tumor xenografts including gliomas.
The mechanism of action of CBD is thought to be increased production of ROS in glioma cells, thereby inducing cytotoxicity or apoptosis and autophagy. CBD also reduces angiogenesis through actions on both tumor and endothelial cells. Median survival was greater than days compared with days in the placebo group.
Reports of cannabis use in the treatment of epilepsy appear as far back as BC. Scientific reports appear in from neurologists using Indian hemp to treat epilepsy with dramatic success. CBD, however, produces antiepileptiform and anticonvulsant effects in both in vitro and in vivo models.
More recently in , Cunha et al. Each patient received — mg daily of CBD or placebo along with antiepileptic drugs for up to 4 months. In the placebo group 1 of 8 responded with fewer seizures. These all suggest that CBD, the nonpsychoactive compound of cannabis, potentially can be helpful for controlling medication refractory seizures.
As with most cannabinoid research to date, conducting studies can be difficult due to limited legal access to medical grade marijuana and phytocannabinoid extracts. Hemp-derived CBD, however, has recently experienced less regulation and as a result research using CBD for refractory epilepsy has experienced a resurgence. CBD's overall effect appears to result in reduction of neuronal hyperactivity in epilepsy. Anandamide affects excitability in neuronal networks by activating the transient receptor potential TRP cation channel.
Endogenous cannabinoids appear to affect the initiation, propagation, and spread of seizures. Studies have identified defects in the ECS in some patients with refractory seizure disorders, specifically having low levels of anandamide and reduced numbers of CB1 receptors in CSF and tissue biopsy.
Although this study exclusively looked for effects on seizure incidence, no evidence suggests that the antiseizure effects of CBD are limited to the treatment of this condition. Development of synthetic forms of CBD is also in progress to treat seizure and other disorders responsive to the phytocannabinoid CBD. A comprehensive safety and side effect review of CBD in on both animal and human studies described an excellent safety profile of CBD in humans at a wide variety of doses.
CBD does have interactions with common hepatic drug -metabolizing enzymes, belonging to the cytochrome P family. Therefore, interactions with drug transporters and interactions with drugs must be considered. In contrast to THC, CBD does not alter heart rate, blood pressure, or body temperature, does not induce catalepsy, nor alter psychomotor or psychological functions.
The AAN review of 34 articles on MS using cannabinoids of various forms noted several adverse effects. Reported symptoms included nausea, increased weakness, behavioral or mood changes or both , suicidal ideation or hallucinations, dizziness or vasovagal symptoms or both , fatigue, and feelings of intoxication.
Psychosis, dysphoria, and anxiety were associated with higher concentrations of THC. However, no direct fatalities or overdoses have been attributed to marijuana, even in recreational users of increasingly potent marijuana possibly due to lack of endocannabinoid receptors in the brainstem. Like other cannabinoids, CBD produces bell-shaped dose—response curves and can act by different mechanisms according to its concentration or the simultaneous presence of other cannabinoid-ligands.
Ultimately, prescribing medical marijuana either as a primary treatment or adjunctive therapy will require extreme care and knowledge about the patient's goals and expectations for treatment. States that have allowed medical marijuana have generally required competency trainings and certification prior to prescribing. There are general screening questions that should be considered before recommending marijuana to a patient.
At minimum, these questions should include the following: Although these medications are often cited in human clinical research, their general use is limited based both on side effects and indication constraints.
Although federal and state laws are inconsistent about the legality of cannabis production, its increasingly documented health benefits make it once again relevant in medicine. Current research indicates the phytocannabinoids have a powerful therapeutic potential in a variety of ailments primarily through their interaction with the ECS.
CBD is of particular interest due to its wide-ranging capabilities and lack of side effects in a variety of neurological conditions and diseases. Because of the rapid legalization of medical marijuana by the majority of state legislatures in the U. Because of federal restrictions on human research in the U. This review of the neurological benefits of phytocannabinoids has demonstrated significant benefits for neuroprotection and disease reductions in a wide variety of neurological diseases and conditions in humans.
The Authors report the following conflicts: National Center for Biotechnology Information , U. Journal List Surg Neurol Int v. Published online Apr Author information Article notes Copyright and License information Disclaimer. Received Feb 5; Accepted Feb This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.
This article has been cited by other articles in PMC. Cannabidiol, deltatetrahydrocannabinol, endocannabinoid system, neurological disease, phytocannabinoids. Open in a separate window. Cannabinoid receptors Phytocannabinoid compounds and extracts can come from both hemp and marijuana subspecies, including CBD. Activation of neuronal CB1 receptors Activation of neuronal CB1 receptors results in inhibition of adenylyl cyclase and decreased neurotransmitter release through blockade of voltage-operated calcium channels.
Cultured microglial dells A study of cultured microglial cells showed c-interferon and granulocyte macrophage-colony stimulating factor GM-CSF , known as inflammatory response activators of microglial cell, were accompanied by significant CB2 receptor upregulation.
Research on the endocannabinoid system Research on the ECS is fervently ongoing with wide-ranging discoveries. Neuroprotective benefits of phytocannabinoids CBD research in animal models and humans has shown numerous therapeutic properties for brain function and protection, both by its effect on the ECS directly and by influencing endogenous cannabinoids.
Neurodegenerative diseases Overview Neurodegenerative diseases include a large group of conditions associated with progressive neuronal loss leading to a variety of clinical manifestations. Neuroprotection for AD AD is characterized by enhanced beta-amyloid peptide deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabidiol CBD is effective in an experimental model of Parkinsonism 6-hydroxydopamine-lesioned rats by acting through antioxidant mechanisms independently of cannabinoid receptors.
Multiple sclerosis CBD and deltaTHC MS is an autoimmune disease that promotes demyelination of neurons and subsequent aberrant neuronal firing that contributes to spasticity and neuropathic pain. Use of cannabis-based medicine for neurodegenerative conditions The use of cannabis-based medicine for the treatment of MS has a long history and its interaction with the ECS shares many of the same pathways of other neurodegenerative conditions.
American Academy of Neurology statement on medical marijuana In , the American Academy of Neurology AAN published a review article of 34 studies investigating the use of medical marijuana as extracts, whole plants and synthetic phytocannabinoids for possible neurological clinical benefits. MS animal models utilizing deltaTHC MS animal models using autoimmune encephalomyelitis EAE have been used that demonstrate demyelination, neuroinflammation, and neurological dysfunction associated with infiltration of immune cells into the CNS consistent with the human disease.
Neuropsychiatric and brain trauma Cannabidiol CBD is recognized as a nonpsychoactive phytocannabinoid. Antidepressant and neuroprotective properties Antidepressants, used for the treatment of depression and some anxiety disorders, also possess numerous neuroprotective properties, such as preventing the formation of amyloid plaques, elevation of BDNF levels, reduction of microglia activation, and decreased levels of proinflammatory mediators.
Rat models; efficacy of CBD in neurobehavioral disorders In rat models of neurobehavioral disorders, CBD demonstrated attenuation of acute autonomic responses evoked by stress, inducing anxiolytic and antidepressive effects by activating 5HT1A receptors in a similar manner as the pharmaceutical buspirone that is approved for relieving anxiety and depression in humans.
Human imaging studies correlated with CBD Human imaging studies have demonstrated CBD affects brain areas involved in the neurobiology of psychiatric disorders. Tetrahydrocannabinol Interestingly, THC, administered prior to a traumatic insult in human case studies and animal models has had measurable neuroprotective effects.
Utility for glioblastoma multiforme Glioblastoma multiforme GBM is the most frequent class of malignant primary brain tumors. CBD reduces growth different tumor xenografts CBD has also been shown to reduce the growth of different types of tumor xenografts including gliomas.
Intractable epilepsy Cannabidiol Reports of cannabis use in the treatment of epilepsy appear as far back as BC. CBDs reduce neuronal hyperactivity in epilepsy CBD's overall effect appears to result in reduction of neuronal hyperactivity in epilepsy.
Endogenous cannabinoids Endogenous cannabinoids appear to affect the initiation, propagation, and spread of seizures. Safety A comprehensive safety and side effect review of CBD in on both animal and human studies described an excellent safety profile of CBD in humans at a wide variety of doses. CBD — better safety profile vs. Adverse effects The AAN review of 34 articles on MS using cannabinoids of various forms noted several adverse effects.
Prescribing medical marijuana Ultimately, prescribing medical marijuana either as a primary treatment or adjunctive therapy will require extreme care and knowledge about the patient's goals and expectations for treatment.
Have you counseled the patient documented by the patient's signed informed consent regarding the medical risks of the use of marijuana—medical, psychological, and social such as impairment of driving or work skills and habituation?
Does your patient have a history of misused marijuana or other psychoactive, addictive prescription and illegal drugs? Will you know the standardization and potency content of the medical marijuana to be used and whether it is free of contaminants?
Legalization of marijuana in many states: Need for education Because of the rapid legalization of medical marijuana by the majority of state legislatures in the U.
Financial support and sponsorship Nil. Conflicts of interest The Authors report the following conflicts: Abush H, Akirav I. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Safety and side effects of cannabidiol: A Cannabis sativa constituent.
Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Molecular targets of cannabidiol in neurological disorders. The bad side of adenosine. Translating depression biomarkers for improved targeted therapies. Plastic and neuroprotective mechanisms involved in the therapeutic effects of cannabidiol in psychiatric disorders. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.
Cannabidiol, neuroprotection and neuropsychiatric disorders. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. The stress-regulated protein p8 mediates cannabinoid-induced ptosis of tumor cells. Cassan C, Liblau RS. Immune tolerance and control of CNS autoimmunity: From animal models to MS patients. The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic—ischemic brain damage in mice is mediated by CB2 and adenosine receptors.
Neuronal network plasticity and recovery from depression. The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. Controlled clinical trial of cannabidiol in Huntington's disease. The perceived effects of smoked cannabis on patients with multiple sclerosis. Open label evaluation of cannabidiol in dystonic movement disorders. Effects of cannabidiol CBD on regional cerebral blood flow.
Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: Pro-apoptotic effects and underlying mechanisms. Endocannabinoids block status epilepticus in cultured hippocampal neurons. Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome.
N Engl J Med. CB1 receptor selective activation inhibits beta-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons. Cannabidiol reduces ab-induced neuroinflammation and promotes hippocampal neurogenesis through PPARc involvement. Prospects for cannabinoid therapies in basal ganglia disorders. The effect of cannabis on urge incontinence in patients with multiple sclerosis: Role of endogenous cannabinoids in synaptic signaling.
Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. Gaoni Y, Mechoulam R. Isolation structure and partial synthesis of an active constituent of hashish. J Am Chem Soc. Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: Importance of antioxidant and cannabinoid receptor-independent properties.
Cannabinoid receptors in the human brain: Gloss D, Vickrey B. Cochrane Database Syst Rev. The multiplicity of action of cannabinoids: Implications for treating neurodegeneration. Grinspoon L, Bakalar JB. The use of cannabis as a mood stabilizer in bipolar disorder: Anecdotal evidence and the need for clinical research. Ended up spending a half an hour longer at the gym than I usually do.
Felt very energetic, it was a good day! This is the early morning strain I was looking for. For me, Cascade worked wonders as an early morning strain with the energy and pain-numbing effects.
In order to submit a comment to this post, please write this code along with your comment: Ganja Dutch Natural Healing. Nate Allen - Nov 09 , 0 Comment. This is Nate with the Dr. Ganja team, reviewing one of our new CBD flower strains, Cascade! Testing In my order I received the safety and potency test results of the CBD flower was about to sample, this batch of Cascade came in at Taste If you want to taste the Cascade hemp flower to its fullest, definitely use a vaporizer.
Effects I heard that Cascade had a nice sativa-esque, uplifting effect so I smoked some before heading to the gym. While it may be difficult to definitively say, oh such and such year was the biggest year for CBD, I personally feel that this My name is Nate with Dr. Here I am giving my review of a new strain of CBD flower that just came
Cascade Bred by Industrial Seed Innovations, and grown by Tweedle Farms! As always, this flower was grown without any kind of pesticides, sprays, Cascade is the result of an open-pollination between some of the world's most well-loved high-CBD strains: Ringo's Gift, Harle Tsu, Based on 13 reviews Write a review. 22 November This week we're counting down the 10 most affordable CBD Whole Flower products in Canada, sorted by price per gram. CBD Skunk Haze; Aphria Treasure Island; Canna Farms CBD Kush; Tantalus Cascade Newer Post Strain Review – Napali CBD by Solace Health Older Post Price Watch. The #1 Business-Focused Cannabis Podcast and Trusted reviews of CBD Oil, Hemp, and Cannabis, Marijuana Accessories.