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Neuroprotection, Strokes & Traumatic Brain Injuries

Best reviews

2023: A review on using cannabinoids against neuroinflammation

2023: A review of targeting the endocannabinoid system for strokes & other diseases where blood flow to the brain stops
The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic–Ischemic Brain Injury

2023: A review of using CBD against fragile X syndrome (a genetic developmental disorder that causes intellectual disability)
Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment

2023: For HIV neurocognitive disorder, a review of targeting the endocannabinoid system for the related neuroinflammation & hormonal imbalance
The Endocannabinoid System as a Potential Therapeutic Target for HIV-1-Associated Neurocognitive Disorder

2022: A review of using CBD for strokes via aneurysm
Cannabidiol's Multifactorial Mechanisms Has Therapeutic Potential for Aneurysmal Subarachnoid Hemorrhage: a Review

2022: A review of PEA for neurodegenerative disorders
Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

2022: This review of 25 clinical studies of cannabinoids for neurodegenerative disorders finds that CBD helps with the motor symptoms of Parkinson’s & Huntington’s disease & that synthetic cannabinoids like dronabinol helped with the dementia of Alzheimer’s, Parkinson’s & Huntington’s
Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review

2022: A review of the neuroprotective effects of CBD against neurological disorders & neuroinflammation regulated by the microglia (the guardian immune cells of the brain)
Neuroprotection of Cannabidiol, Its Synthetic Derivatives and Combination Preparations against Microglia-Mediated Neuroinflammation in Neurological Disorders

2022: This review looks at the ability of PEA to help with neuromuscular diseases, especially those involving acetylcholine

Classical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function

2022: In a review of 33 studies on PEA for cognitive decline, it found that PEA improved neurobehavioral functions like memory & learning, reduced oxidative stress & inflammation, rebalanced glutamate (the brains most excitatory neurotransmitter), increased neuron survival & promoted neurogenesis (the creation of new brain cells) + so much more
Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence

2022: The usefulness of cannabinoids for neuroinflammation, neurodegeneration & pain
Editorial: Cannabinoids in neuroinflammation, neurodegeneration and pain: Focus on non-neuronal cells

2022: Strong review of all the mechanisms the cannabinoids use to help with neurodegeneration
Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

2022: A review on what does PEA does at our synapses for neurodegeneration & neuroinflammation
Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders

2022: A review of how the endocannabinoids work with the brain’s astrocytes (the most numerous cells in the CNS, these support cells help to guide the formation of axons, protect the synapses, modulate neuroinflammation & control the blood brain barrier as well as the release of neurotransmitters)
Astroglial cannabinoid signaling and behavior

2022: This review of stroke looks at the ability of the cannabinoids to protect the brain via the glial cells (support cells that maintain homeostasis)
Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection

2022: A review of how the brain’s oligodendrocytes (which synthesize the myelin sheaths around the axons) use the full range of endocannabinoid machinery & may be a target to promote remyelination for diseases like MS, ALS or Parkinson’s
Endocannabinoid signaling in oligodendroglia

2022: A chapter suggesting the use of cannabinoids for treating Huntington’s disease
Endocannabinoid System as a New Therapeutic Avenue for the Treatment of Huntington’s Disease

2022: A more general review of the mechanisms of the ECS underlying its ability to help with neurodegenerative disorders
Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty

2022: A review looking at targeting the CB2 receptor for neurodegenerative diseases

New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders

2022: In neuroinflammation, a review of the importance of the ECS & the microglia (often called the guardian cells of the brain)

The Dynamic Role of Microglia and the Endocannabinoid System in Neuroinflammation

2022: On the role of cannabis in neurology

Neurology - to be or not to be of the cannabis-based medicine?

2022: A review about treating central nervous system diseases by inhibiting the breakdown of endocannabinoids (nice chart)

Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition

2021: A review of the cannabinoids as anticancer drugs & neuroprotective agents

Cannabinoids as anticancer and neuroprotective drugs: Structural insights and pharmacological interactions—A review

2021: This review looks at how the endocannabinoid system helps to lower oxidative stress & how it works with our nitric oxide signaling system

Intertwined associations between oxidative and nitrosative stress and endocannabinoid system pathways: Relevance for neuropsychiatric disorders

2021: This review looks at CBD as a new fixture in pediatric neurology

Cannabidiol - A new fixture in childhood neurology

2021: A review of how the cannabinoids lower inflammation in the brain

Cannabinoid control of neurogenic inflammation

2021: A review of cannabis for traumatic brain injuries
The changing landscape of the use of medical marijuana after traumatic brain injury: a narrative review

2021: A review of the CB2 receptors & the microglia (immune cells of the brain)

CB2 Receptor in Microglia: The Guardian of Self-Control

2020: A review of the neuroprotective effects of the molecules found in cannabis

Cannabis Phytochemicals: A Review of Phytocannabinoid Chemistry and Bioactivity as Neuroprotective Agents

2020: A review of the minor cannabinoids & neuroprotection

A Systematic Review of Minor Phytocannabinoids with Promising Neuroprotective Potential

2020: The endocannabinoids & the microglia

Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology

2020: This review looks at how cannabinoids lower inflammation in the brain

Cannabinoid Control of Neurogenic Inflammation

2018: The ECS & the oligodendrocytes (large immune cells of the brain)

The Endocannabinoid System and Oligodendrocytes in Health and Disease

2017: CBD & the astrocytes

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

2016: A review of CBD’s brain protection properties

Cannabidiol, neuroprotection and neuropsychiatric disorders

2016: great charts on how the microglial work with the cannabinoids

Microglia activation states and cannabinoid system: Therapeutic implications

2016: A fascinating chart on the ECS & the glial cells

Endocannabinoids and Heterogeneity of Glial Cells in Brain Function

2015: Maccarrone on the cannabinoids & neuroinflammation

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses

2008: A review of CB2 receptors in neuroinflammation

Cannabinoid CB2 receptors in human brain inflammation

2008:The mechanisms of the ECS for protecting neurons

Mechanisms of control of neuron survival by the endocannabinoid system

2002: Mechoulam on ECS neuroprotection

Discovery of endocannabinoids and some random thoughts on their possible roles in neuroprotection and aggression

Chart Gallery

Timeline of Research

2023: In astrocytes (key brain support cells), CBD lowered damage in a model of neurodegeneration via several pathways
Effect of Cannabidiol in LPS-induced toxicity in astrocytes: Possible role for cannabinoid type-1 receptors

2023: In a songbird model of developmental delays via brain trauma, CBD improved their singing ability & reduced inflammation & oxidative stress in the brain
Cannabidiol Inhibits Neuroinflammatory Responses and Circuit-Associated Synaptic Loss Following Damage to a Songbird Vocal Pre-motor Cortical-Like Region

2023: In a mouse model of cognitive decline & Alzheimer’s disease, PEA protected memory & lessened shrinking of the hippocampus (memory center of the brain)
Chronic administration of palmitoylethanolamide counteracts cognitive decline in Tg2576 Mice

2023: In a mouse model of nerve injury, a cannabis extract sped up muscle function recovery
Comparative evaluation of ethyl acetate and n-Hexane extracts of Cannabis sativa L. leaves for muscle function restoration after peripheral nerve lesion

2023: In a mouse model of toxic brain damage from HIV antiretrovirals, activating the CB2 receptor protects the brain, causes painkilling effects & reverses morphine tolerance
Peripheral sensory neuron CB2 cannabinoid receptors are necessary for both CB2-mediated antinociceptive efficacy and sparing of morphine tolerance in a mouse model of anti-retroviral toxic neuropathy

2022: In obese mice, PEA lessened neuroinflammation as well as anxious behavior

Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice

2022: In rats with a traumatic spinal cord injury, CBD lowered their oxidative stress, reduced their hypersensitivity & lessened pain levels
Cannabidiol attenuates hypersensitivity and oxidative stress after traumatic spinal cord injury in rats

2022: In songbirds with brain damage, we already knew that CBD helped them to recovery their singing ability & then this research demonstrates that a low dose of THC helps the CBD to work better
Δ9-Tetrahydrocannabinol Differentially Alters Cannabidiol Efficacy in Recovery of Phonology and Syntax Following Damage to a Songbird Cortical-Like Brain Region

2022: In humans who had a stroke, nabiximols (a 1:1 CBD:THC mixture) did not alter blood pressure, heart rate or cardiovascular complications
Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled studyv

2022: In rats with loss of blood flow to their brains, CBD lowered cell death & protected against dysfunction of the mitochondria (powerhouse of the cell)
Mitofusin-2 mediates cannabidiol-induced neuroprotection against cerebral ischemia in rats

2022: In a rat model of methamphetamine abuse, CBD protected from the neurotoxicity via dopamine receptors
Cannabidiol prevents methamphetamine-induced neurotoxicity by modulating dopamine receptor D1-mediated calcium-dependent phosphorylation of methyl-CpG-binding protein 2

2022: In certain brain regions of rats, CBD increases BDNF (a brain growth factor)
Single and Repeated Exposure to Cannabidiol Differently Modulate BDNF Expression and Signaling in the Cortico-Striatal Brain Network

2022: In a model of neuroinflammation, a CBD & terpene enriched cannabis extract lowered pro-inflammatory cytokines via several pathways
Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling

2022: In a rat model of neuropathic pain, CBD & THCV worked together to reduce pain & protect the neurons via the CB1 receptor & a serotonin receptor
Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents

2022: In human sodium channels (which help control electrical signals in epilepsy), CBD-rich hemp extracts inhibited the channel at much lower doses than isolated CBD
A nutraceutical product, extracted from Cannabis sativa, modulates voltage-gated sodium channel function

2022: In a mouse model of epilepsy, giving CBD extracts before inducing seizures caused the microglial cells (immune system guardians of the brain) to not move as much & not over accumulate in the hippocampus (memory center) causing a decrease in inflammation
Prophylactic Administration of Cannabidiol Reduces Microglial Inflammatory Response to Kainate-Induced Seizures and Neurogenesis

2022: In a rat model of sciatic nerve damage, PEA decreased the intensity & duration of the pain, stabilized the microglia & astroglia (brain immune cells) & lowered neuroinflammation by several mechanisms
Analgesic Activity of Palmitoylethanolamide on Neuropathic Pain in Rats

2022: A look at how CBD promotes new brain cell growth via the Akt & Erk pathways & the CB1 receptor
Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling

2022: In a neuronal model of blood loss to the brain, CBD caused its benefits via lowering the amount of CB2/serotonin heteromer complexes (two receptors joined together)
Regulation of Expression of Cannabinoid CB2 and Serotonin 5HT1A Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons

2022: In a mouse model of stroke, CBD prevented neurological impairment, reduced neural deficits & protected against neurodegeneration
Cannabidiol Exerts a Neuroprotective and Glia-Balancing Effect in the Subacute Phase of Stroke

2022: In certain brain regions of rats, CBD increases BDNF (a brain growth factor)
Single and Repeated Exposure to Cannabidiol Differently Modulate BDNF Expression and Signaling in the Cortico-Striatal Brain Network

2022: In microglial cells (guardian immune cells of the brain), treatment with CBD increased levels of the mitochondrial fusion protein Mitofusin 2 that deals with inflammation – and in mice, CBD lessened the anxiety response & cognitive deficits from an inflammatory challenge as well as helping in a mouse model of multiple sclerosis
Mitofusin 2 confers the suppression of microglial activation by cannabidiol: Insights from in vitro and in vivo models

2022: In mice being fed a high-fat diet, CBD & omega-3 fatty acids caused them to live longer & protected from brain damage
Omega 3 Fatty Acid and Cannabidiol Prolong Lifespan and Ameliorates Brain Ischaemia in Mice Fed Chronic High Fat Diet

2022: In teens rats withdrawing from an alcohol binge, CBD increased their social exploration, reduced stress hormone levels, restored dopamine transmission & helped to strengthen & remodel their brain connections
Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats

2022: In brain cells, the toxicity of the chemo treatment paclitaxel is lessened by PEA
Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons

2022: In a rat model of stroke, β-caryophyllene (a predominant terpene of cannabis) caused significant neuroprotection via regulation of ferroptosis (a type of cell death, only recently discovered, caused by the accumulation of iron)
β-Caryophyllene Suppresses Ferroptosis Induced by Cerebral Ischemia Reperfusion via Activation of the NRF2/HO-1 Signaling Pathway in MCAO/R rats

2022: In a rat model of stroke, giving them beta-caryophyllene (a main terpene of cannabis) before the neural insult lowered neuroinflammation
Anti-Inflammatory Effect of Beta-Caryophyllene Mediated by the Involvement of TRPV1, BDNF and trkB in the Rat Cerebral Cortex after Hypoperfusion/Reperfusion

2022: A tissue test of the antioxidative & neuroprotective properties of two cannabis extracts
Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents

2022: In a mouse model of the loss of myelin (the sheaths around nerves that facilitate electrical signalling), activating their TRPV1 (a function of anandamide) increasing the functioning of the microglia (immune guardian cells of the brain)
Activation of TRPV1 receptor facilitates myelin repair following demyelination via the regulation of microglial function

2022: In a rat model of a heart attack causing blood loss to the brain, inhibiting the MGL enzyme (which breaks down 2-AG) was as effective as therapeutic hypothermia for fixing cerebral microcirculation, smaller brain swellings & protecting the blood brain barrier
The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest

2022: In a mouse model of spinal cord injury, activating the CB2 receptor lowered inflammation, reduced loss of the myelin sheaths, increased autophagy (recycling of damaged cellular components), caused less neuronal apoptosis (cellular suicide) & improved functionality of the hind legs
Cannabinoid receptor-2 attenuates neuroinflammation by promoting autophagy-mediated degradation of the NLRP3 inflammasome post spinal cord injury

2022: In a cellular model of excitotoxicity (neuronal damage due to too much stimulation), a cannabis extract protected the brain cells via several mechanisms including brain-derived neurotrophic factor levels, ERK modulation & a rescue of CB1 levels
Investigation on the neuroprotective effect of a cannabidiol-enriched non-psychotropic Cannabis sativa L. extract in an in vitro model of excitotoxicity

2022: In a mouse model of the poor muscle control (ataxia) caused by damage to cerebellum, activating the CB1 receptor improved their locomotor activity & almost completely protected their cerebellum neurons from degradation
The cannabinoid antagonist, AM251 attenuates ataxia related deficiencies in a cerebellar ataxic model

2022: In a patient with a genetic variant that causes epilepsy & neurodevelopmental problems, CBD helped to alter the voltage problems across their neurons
Cannabidiol counters the effects of a dominant-negative pathogenic Kv7.2 variant

2022: A study in former professional football players found that hemp extracts may help with cognitive performance & emotional processing
Automated Detection of Cognitive Performance and Resilience Changes in Former Professional American Football Players Following the Administration of a Hemp Extract

2022: In a computer simulation, the main cannabinoids seem to help with neurodegeneration via the alleviation of stress on the endoplasmic reticulum (the site of protein & lipid synthesis)
Promising Action of Cannabinoids on ER Stress-Mediated Neurodegeneration: An In Silico Investigation

2022: In oligodendrocytes (creators of the myelin sheaths around the axons of neurons), the cannabinoids cause a range of actions including cell proliferation, migration, regulation of carbohydrate & lipid metabolism, control of mitochondrial function & differentiation of oligodendrocyte progenitor cells
Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes

2022: This computer simulation study looked at the ability of THC, CBD, AEA & 2-AG to bind to the endoplasmic reticulum (final processing center for proteins) & how this helps to increase the breakdown of misfolded proteins
Promising action of cannabinoids on ER stress mediated neurodegeneration: An In Silico Investigation,forthcoming,40055.html

2022: In a model of brain damage from sepsis, activating the CB2 receptor prevented overactivation by the microglial cells (immune cells of the brain) & lowered neuronal pyroptosis (cell death from extreme inflammation)
Protective Effects of Cannabinoid Type 2 Receptor Against Microglia Overactivation and Neuronal Pyroptosis in Sepsis-Associated Encephalopathy

2022: In a mouse model of traumatic brain injury, the alterations to the endocannabinoid system exacerbates problems at the blood brain barrier & causes more neural deficits, suggesting cannabinoids as a treatment
Altered endocannabinoid metabolism compromises the brain-CSF barrier and exacerbates chronic deficits after traumatic brain injury in mice

2022: In traumatic brain injury, endocannabinoids help to control neuroinflammation via the MGL enzymes (that break down 2-AG) in the astrocytes (brain support cells)
Endocannabinoid control of neuroinflammation in traumatic brain injury by monoacylglycerol lipase in astrocytes

2022: In a model of traumatic brain injury, enhancing the endocannabinoid signaling of 2-AG promotes recovery of the astrocytes (important support cells of the neurons), greater resilience to injury, lessened neuropathology & protected from cognitive declines
Enhancing endocannabinoid signalling in astrocytes promotes recovery from traumatic brain injury

2022: In patients with traumatic brain injury, the use of THC before their injury led to no negative changes in outcome & was correlated to a decreased rate of hemorrhagic stroke
Thromboembolic Outcomes in Tetrahydrocannabinol-Positive Trauma Patients With Traumatic Brain Injury

2022: In a review of public health data on acute strokes, cannabis users had a lower overall mortality risk than non-users
Acute Ischemic Stroke Among Cannabis Users in the United States and Possible Risk Factors for Mortality

2022: In a model of intracerebral hemorrhage (bleeding in the brain – the second most common cause of stroke), PEA lowered neuroinflammation & improved motor function via the PPAR-α receptors (nuclear receptors that control genetic transcription) in microglial cells (the immune cells of the brain)

Palmitoylethanolamide ameliorates neuroinflammation via modulating PPAR-α to promote the functional outcome after intracerebral hemorrhage

2022: In humans using medical cannabis, six months of use increased the coherence of their white matter while CBD reduced their mean diffusivity (higher water content in their brain, neuroprotective against demyelination diseases like Parkinson’s)
Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment

2022: In rats with spinal nerve injuries, activating the CB1 receptor reduced pain as well as altering the plasticity of the relevant neurons
Endogenous Cannabinoid Receptors Modulate Plasticity at Immature Synapses

2022: In rats with spinal cord injuries, the increased expression of CB2 receptors helped to reduce neuropathic pain by lowering the transmission of pain signals into the spinal cord
Cannabinoid CB2 receptors are upregulated via bivalent histone modifications and control primary afferent input to the spinal cord in neuropathic pain

2022: In a mouse model of Huntington’s disease, as the disease progressed, the levels of CB1 decreased in their hippocampus (a memory center of the brain) & activating the CB1 receptor helped to prevent & rescue memory deficits
Cannabinoid receptor in hippocampal hippocampus as a potential therapeutic treatment for the cognitive deficits in Huntington diseases

2022: For Huntington’s disease, a look at why the disease’s disruption of the endocannabinoid system causes more disease progression
Cannabinoid signaling and risk in Huntington's disease

2022: An array of techniques determines when the body breaks down CBG, the resulting metabolites are also active in our system & when applied to brain immune cells, they reduce inflammation
Metabolites of Cannabigerol (CBG) Generated by Human Cytochrome P450s are Bioactive

2022: On treating neuroinflammation via targeting of the CB2 receptor

CB2 receptor activation inhibits the phagocytic function of microglia through activating ERK/AKT-Nurr1 signal pathways

2022: This look at the CB2 receptors of parrots finds that they help with neuroinflammation (as well as intriguing backstory on the evolution)

Revealing genomic changes responsible for cannabinoid receptor loss in parrots: mechanism and functional effects

2022: In a mouse model of traumatic brain injury, increasing the endocannabinoid signaling caused greater resilience to injury, lessened neuropathology & protected from cognitive declines

Enhancing endocannabinoid signalling in astrocytes promotes recovery from traumatic brain injury

2022: In a survey of military veterans with persistent symptoms after a mild traumatic brain injuries, the self-reported reasons for cannabis use include “neuropsychiatric symptoms, sleep disturbances, and pain for which standard treatments (both pharmacologic and nonpharmacologic) provided insufficient relief”

Cannabis Use in a Cohort of Healthcare-Seeking United States Military Veterans With Persisting Symptoms After Mild Traumatic Brain Injury: Preliminary Observations

2021: In a tissue sample of spinal discs, activating the CB2 receptor relieved oxidative stress & the inflammatory response

CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro

2021: In a rat model of traumatic brain injury, direct injection of CBD into the brain restored several measures of motor & cognitive function

Cannabidiol reduces lesion volume and restores vestibulomotor and cognitive function following moderately severe traumatic brain injury

2021: In a rat model of traumatic brain injury, direct injection of CBD into the brain restored several measures of motor & cognitive function

Cannabidiol reduces lesion volume and restores vestibulomotor and cognitive function following moderately severe traumatic brain injury

2021: A drug combining CBD with a derivative of a malaria drug helped to reduce neuroinflammation & protect the microglia (guardian immune cells of the brain)
Cannabidiol-dihydroartemisinin conjugates for ameliorating neuroinflammation with reduced cytotoxicity

2021: In a tissue sample of spinal discs, activating the CB2 receptor relieved oxidative stress & the inflammatory response

CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro

2021: The CB2 receptor is a key pathway to control homeostasis of our brain’s microglia (immune cells that respond to potential threats)

Cannabinoid receptor 2 is necessary to induce toll-like receptor-mediated microglial activation

2021: In rat neurons insulted by kainic acid (a toxin), 2-AG caused neuroprotection via modulation of the sodium channels

Modulatory effect of 2-arachidonoylglycerol on voltage-gated sodium currents in rat caudate nucleus neurons with kainic acid-induced injury

2021: In a rat model of a traumatic brain injury, CBD improved the integrity of the blood-brain barrier & reduced edema (brain swelling from excess fluids)

Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats

2021: In mice with no DAGL-β enzyme (which creates 2-AG), they had less neuroinflammation during traumatic brain injury & displayed gender differences

Diacylglycerol Lipase-β Knockout Mice Display a Sex-Dependent Attenuation of Traumatic Brain Injury-Induced Mortality with No Impact on Memory or Other Functional Consequences

2021: In baby rats with crushed spinal cords, CBD protected the neurons in the spine & reduced the reaction of the glial cells, probably via the CB1 receptor

Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy

2021: In rats with spinal cord injuries, activating the CB2 receptor helped mitigate their osteoporosis

Delayed Systemic Treatment with Cannabinoid Receptor 2 Agonist Mitigates Spinal Cord Injury-Induced Osteoporosis More Than Acute Treatment Directly after Injury

2021: In a patient with severe pain after a stroke, a 1:1 ratio of THC & CBD gave relief after 3 years of other therapies did not

Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?

2021: In an animal model of stroke, they already knew that PEA protects the blood-brain barrier & the brain itself. This study found that the effects weren’t only mediated by changes in genetic transcription (the PPARα receptor) but also by the regulation of the cell’s microfilaments

PEA prevented early BBB disruption after cerebral ischaemic/reperfusion (I/R) injury through regulation of ROCK/MLC signaling

2021: In mouse brain cells, CBD helps protects them via the process of autophagy

Cannabidiol induces autophagy via ERK1/2 activation in neural cells


2021: In neurons of the hippocampus, CBD provided neuroprotection against oxidative stress

Neuroprotective Effect of Cannabidiol Against Hydrogen Peroxide in Hippocampal Neuron Culture

2021: In mice, the researchers looked at the pathways that CBD used to protect the brain & found that it involved CB1, CB2, a serotonin receptor & the nuclear receptor PPAR-γ

Differential contribution of CB1, CB2, 5-HT1A, and PPAR-γ receptors to cannabidiol effects on ischemia-induced emotional and cognitive impairments

2021: In mice exposed to chemical warfare nerve agents that induce seizures, CBD increased their survival rate & attenuated seizure severity

Cannabidiol reduces soman-induced lethality and seizure severity in female plasma carboxylesterase knockout mice treated with midazolam

2021: In rats, the terpene β-caryophyllene protects against dementia caused by neuroinflammation

Beta-caryophyllene, a CB2R selective agonist, protects against cognitive impairment caused by neuro-inflammation and not in dementia due to ageing induced by mitochondrial dysfunction

2021: In the brains of mice, having no CB1 receptors leads to the brain aging faster

Lack of Cannabinoid Receptor Type-1 Leads to Enhanced Age-Related Neuronal Loss in the Locus Coeruleus

2021: In the immune cells of a mouse's brain, the neurodegeneration caused by HIV was lessened by inhibition of the FAAH enzyme via GPR18

GPR18 drives FAAH inhibition-induced neuroprotection against HIV-1 Tat-induced neurodegeneration

2021: In neural stem cells, they express the machinery of the endocannabinoid system & adding cannabinoids like 2-AG increased their proliferation

Cannabinoid Receptor Modulation of Neurogenesis: ST14A Striatal Neural Progenitor Cells as a Simplified In Vitro Model

2021: In mice with a central nervous system injury, early treatment with a CB2 agonist protected the brain & improved the immune response

Effect of Cannabinoid 2 Receptor Modulation on the Peripheral Immune Response in Central Nervous System Injury-Induced Immunodeficiency Syndrome

2021: In five cases of fetal alcohol spectrum disorder, cannabis helped with disruptive behavior & the authors note that CBD shows a "marked and statistically significant improvement"

Use of Cannabis in Fetal Alcohol Spectrum Disorder

2021: In a rat model of Fragile X Syndrome, the CB2 receptor is necessary for protection against neuropathic pain

Role of the endocannabinoid system in a mouse model of Fragile X undergoing neuropathic pain

2021: In microglial cells (the immune cells of the brain), the cannabinoid receptors help to regulate inflammation via genetic transcription

Cannabinoid receptors modulate LPS-induced increase of class-II transactivator expression levels in a microglial cell line

2021: In rats, nanoformulations of anandamide were administered & seemed to protect both the brain & the heart

Central nervous system, peripheral and hemodynamic effects of nanoformulated anandamide in hypertension

2021: In neurons of the hippocampus, an inhibitor of MGL protects them from injury during ischemia via the Nrf2/ARE signaling pathway

JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2/ARE signaling pathway

2021: In astrocytes (a type of immune cell in the brain), a synthetic cannabinoid inhibited inflammation

The Cannabinoid Receptor Agonist, WIN, Suppresses the Activation of Proinflammatory Genes Induced by Interleukin 1 Beta in Human Astrocytes

2021: In a neuronal model of neurodegeneration, three cannabinoids isolated from seized cannabis in Thailand were found to be neuroprotective

Neuroprotective activities of three cannabinoids separated from confiscated cannabis in Thailand

2020: In rats, CBD helps to protect the brain during injury by increasing apoptosis (programmed cellular suicide) via the PI3K/AKT pathway

Cannabidiol alleviates hemorrhagic shock-induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway

2020: In microglial cells, CBD potently inhibited proinflammatory cytokines (TNF-α and IL-1β) and that of glutamate, a noncytokine mediator of inflammation via NADPH oxidase-mediated ROS production and NF-κB-dependent signaling events – also found that the ability of CBD to prevent glucose uptake also contributes to the anti-inflammatory effect

Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS/NF-κB-dependent signaling and glucose consumption

2020: In a cell culture of hippocampus neurons, CBD protected against the insult of hydrogen peroxide

Neuroprotective Effect of Cannabidiol Against Hydrogen Peroxide in Hippocampal Neuron Culture

2020: In neuron tissue, CBD protects the cells against stress via the heme oxygenase (HO) system (the enzyme that catalyzes the degradation of heme in your blood)

Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin

2020: In mice, activating their CB receptors protected both their retinas & their brains

Effect of acute and subchronic administration of (R)-WIN55,212-2 induced neuroprotection and anti inflammatory actions in rat retina: CB1 and CB2 receptor involvement

2020: In diabetic rats, activating the CB2 receptor protected the brain via increased blood flow

A cannabinoid type 2 (CB2) receptor agonist augments NOS-dependent responses of cerebral arterioles during type 1 diabetes

2020: In mouse brain cells, this study examined how CBD, CBG & their acid forms protected the neurons

A Comparative In Vitro Study of the Neuroprotective Effect Induced by Cannabidiol, Cannabigerol, and Their Respective Acid Forms: Relevance of the 5-HT 1A Receptors

2020: In mice, their astroglia (immune cells in the brain) have their energy levels regulated by CB1 receptors on their mitochondria

Glucose metabolism links astroglial mitochondria to cannabinoid effects

2020: In mouse neurons, the protective molecule orexin-A seems to prevent cell death via 2-AG & the CB1 receptor

Role of 2-Arachidonoyl-Glycerol and CB1 Receptors in Orexin-A-Mediated Prevention of Oxygen-Glucose Deprivation-Induced Neuronal Injury

2020: In brain cells of rats experiencing neurotoxicity, both CBD & CBG rescued serotonin levels & acted as antioxidants – but only CBD helped to repair the release of neurotransmitters

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

2020: In neuronal tissue, the Tat protein of HIV is thought to be a major cause of the disease's neurocognitive disorders & the Tat protein cause CB1 receptors to not work as well on the presynaptic junctions where they usually cause neuroprotection

HIV Tat Protein Selectively Impairs CB 1 Receptor-Mediated Presynaptic Inhibition at Excitatory but Not Inhibitory Synapses

2020: In mice, a new mechanism found for how the CB2 receptor calms the brain's Purkinje cells via the inhibition of GABA-A

Cannabinoid type 2 receptors inhibit GABAA receptor-mediated currents in cerebellar Purkinje cells of juvenile mice

2020: In mice, CB1 agonist helps to repair myelin after a brain insult

Dose-dependent effect of cannabinoid WIN-55,212-2 on myelin repair following a demyelinating insult

2020: In rat brains, CBD & CBG protected and modulated the neurons

Neuroprotective and Neuromodulatory Effects Induced by Cannabidiol and Cannabigerol in Rat Hypo-E22 cells and Isolated Hypothalamus

2020: In mice, activating the CB2 receptor helped with pain via the microglia (the brain's immune cells)

Low-dose cannabinoid receptor 2 agonist induces microglial activation in a cancer pain-morphine tolerance rat model

2020: In humans, the difference between how sensitive we are to the psychoactive effects of THC is linked to how it affects our cortisol levels & the function of our glial cells (brain's immune cells) (16 participants)

Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol

2020: In cells, micronized PEA (FM-LipoMatrix®) combined with lipoic acid & vitamin D3 caused better absorption & reduced neuroinflammation

A New Palmitoylethanolamide Form Combined with Antioxidant Molecules to Improve Its Effectivess on Neuronal Aging

2019: In dopamine neurons, CBD protects against cadmium poisoning

Cannabidiol Protects Dopaminergic Neuronal Cells from Cadmium

2019: In diabetic rats, CBD protects from neurodegeneration & improved many metabolic measures

Cannabidiol improves metabolic dysfunction in middle-aged diabetic rats submitted to a chronic cerebral hypoperfusion

2019: In middle-aged diabetic rats, CBD treatment protected the brain from the declines of diabetes & reduced several inflammation markers in the hippocampus

Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats

2019: In people living with HIV, marijuana users tend to have lower cognitive impairment - perhaps because of anti-inflammatory effects

Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV

2019: In neuronal cells, CBD + CBG lowered inflammation & increased survival via PPARγ

Could the Combination of Two Non-Psychotropic Cannabinoids Counteract Neuroinflammation? Effectiveness of Cannabidiol Associated with Cannabigerol

2019: In cell cultures, CBD blocks inflammation of the brain's immune cells

Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS/NF-κB-dependent signaling and glucose consumption

2019: In human brain cells, THC lowered neuroinflammation by slowing monocyte activation

Δ 9-Tetrahydrocannabinol Suppresses Monocyte-Mediated Astrocyte Production of Monocyte Chemoattractant Protein 1 and Interleukin-6 in a Toll-Like Receptor 7-Stimulated Human Coculture

2019: In microglial cells, CBD had a greater effect than THC on changing levels of miRNAs controlling immune response, cell cycle regulation & cellular stress

miRNA expression profiles and molecular networks in resting and LPS-activated BV-2 microglia-Effect of cannabinoids

2019: In mice, PET study finds CB2 upregulated in neuroinflammation

Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study

2019: In humans, cannabis use in adolescence may impair the function of glial cells in the brain

Adolescent-onset heavy cannabis use associated with significantly reduced glial but not neuronal markers and glutamate levels in the hippocampus

2019: In mice, an antagonist at the adenosine A2A receptor may enhance neuroprotective effects of endocannabinoids

Potentiation of cannabinoid signaling in microglia by adenosine A2A receptor antagonists

2019: In a tissue culture, Cannflavin A shows neuroprotective effects against neurotoxicity

Novel cannabis flavonoid, cannflavin A displays both a hormetic and neuroprotective profile against amyloid β-mediated neurotoxicity in PC12 cells: comparison with geranylated flavonoids, mimulone and diplacone

2018: In rats overexposed to iron, CBD protected the brain from apoptosis & negative effects

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

2018: In neurons, CBD protected against neuroinflammation & oxidative stress

In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid

2017: CBD as a tool to improve stem cells taken from the mouth into neuronal stem cells

Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells

2017: In neuronal cells, THCA as a PPARγ agonist that protects the brain

Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity

2016: In microglial cells & T cells, a CBD derivative shows similar anti-inflammatory properties

Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells

2015: In microglial cells, activation can be lowered via the CB2 receptor

Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling

2015: In microglial cells, the endocannabinoids seem to be critical for their regulation & activation

Endocannabinoids drive the acquisition of an alternative phenotype in microglia

2015: In microglial cells, CBD’s reduction of glial activity could help explain antipsychotic properties

Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

2015: In neurons, CBD did not protect against neurotoxins & seemed to sensitize immature cells to them

Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins

2014: In rats overexposed to iron, CBD helped normalize levels & mitochondrial function

Cannabidiol normalizes caspase 3, synaptophysin, and mitochondrial fission protein DNM1L expression levels in rats with brain iron overload: implications for neuroprotection

2014: In stressed mice, the importance of neurogenesis & autophagy via CB1 receptor activation for neuroprotection

Behavioural effects of cannabidiol in chronically stressed mice is mediated by neurogenesis and autophagy through CB1 receptor activation


2014: In a cellular model of Alzheimer’s disease, CBD increased neuronal survival by reducing apoptosis & decreasing amyloid precursor protein levels via PPARγ receptor

Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement

2014: In microglia, CBD enhances phagocytosis (bacteria ingestion) via TRPV1

Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation

2012: In microglial cells, CBD upregulates many more genes (1298) than THC (58) related to oxidative stress and inflammation

Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells

2012: In microglial cells, CBD affects the genes involved with zinc homeostasis & might exert some of its antioxidant & anti-inflammatory effects via this pathway

Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells

2012: In microglial cells, CBD induces apoptosis via lipid rafts

Cannabidiol-induced apoptosis in murine microglial cells through lipid raft

2012: The mechanisms of how CBD protects the oligodendrocyte progenitor cells (OPCs) which can differentiate into myelinating cells to reduce cell death & free radical production

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

2012: In mice, altering the DAGL enzymes helped to regulate proinflammatory responses in macrophages

DAGLβ inhibition perturbs a lipid network involved in macrophage inflammatory responses

2012: In a rat model of meningitis, CBD treatment lessens damage by reducing TNF-α levels in frontal cortex

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis

2011: In a mouse model of sepsis-related encephalitis (brain swelling), CBD works by raising BDNF levels, lowering type-1 TNFα receptor levels & preserving the blood-brain barrier

Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: An intravital microscopy study

2011: In amphetamine-induced oxidative stress (mania) model in rats, CBD increased BDNF levels & protected against oxidative damage

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania

2011: In a rat model of Alzheimer’s disease, CBD’s ability to reduce damage from reactive oxygen species may be mediated by the PPARγ nuclear receptor

Cannabidiol reduces Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement

2011: In microglial cells, CBD affects the metabolism of cholesterol & lipid-gene expression

The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells

2010: In insulted microglial cells, both CBD & THC reduced production & release of proinflammatory cytokines, including interleukin-1beta, interleukin-6 & interferon (IFN)beta

Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells

2010: In a cell culture, a look at the mechanisms of how THC & CBD reduce inflammation in brain cells

Cannabinoids Δ-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-κB and Interferon-β/STAT Proinflammatory Pathways in BV-2 Microglial Cells

2009: In microglial cells, the neuroprotection mechanisms of 2AG

2-Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells

2009: In brain cells, CB2 activation protects via the PI3K/Akt pathway

Selective CB2 receptor agonism protects central neurons from remote axotomy-induced apoptosis through the PI3K/Akt pathway

2007: In a rat model of Huntington’s disease, CBD reduced brain atrophy & increased superoxide dismutase (antioxidant) machinery

Cannabidiol reduced the striatal atrophy caused 3-nitropropionic acid in vivo by mechanisms independent of the activation of cannabinoid, vanilloid TRPV1 and adenosine A2A receptors

2007: In a model of Parkinson’s disease, a test of an array of cannabinoids found their help was independent of CB1 & CB2 receptors – but CB2 activation may also be helpful – upregulated the Cu,Zn-superoxide dismutase antioxidant machinery

Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties

2006: In neurons, CBD prevented beta-amyloid induced neuronal death via its ability to scavenge reactive oxygen species & a reduction of the neurotoxic effects of an uncontrolled immune response

Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement

2006: In a rat model of diabetes, CBD reduced the levels of tyrosine nitration & malondialdehyde (MDA - a measure of lipid peroxidation) as well as decreased neural cell death

Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes

2006: In human spinal cords, the glial cells activated in MS & ALS show more COX2, P2X7 & CB2 receptors

COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord

2006: In glioma cancer cells, CBD induced ER stress and the production of free radicals to cause the cells to divide less

The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells

2005: In a mouse model of multiple sclerosis, the CB2 receptors are upregulated as the microglia are activated

Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli

2005: In brain cell cultures, cannabinoids protect by blocking microglial activation in senile plaques

Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation

2004: In a cellular model of Alzheimer’s disease, pretreatment with CBD reduced reactive oxygen species (free radicals) & other protective effects

Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells

2004: In rats, the neurotoxic aspect of AEA is mediated by TRPV1

The "dark side" of endocannabinoids: a neurotoxic role for anandamide

2003: In retinal cells, CBD & THC caused less tyrosine nitration (an indirect measure of free radical formation) & protected them via attenuation of peroxynitrite formation

Neuroprotective effect of (-)Delta9-tetrahydrocannabinol and cannabidiol in N-methyl-D-aspartate-induced retinal neurotoxicity: involvement of peroxynitrite

2003: In mice, PEA potentiates the ability of AEA to induce microglia migration – not mediated by CB1 or CB2

Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility

2003: In microglial cells, cannabinoid receptors regulate their movement during neuroinflammation

Nonpsychotropic cannabinoid receptors regulate microglial cell migration’

2002: in brain immune stem cells, cannabinoids help promote survival

Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling

2002: In cells, CB1 seems to not be involved with the antioxidative effects of cannabinoids

Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1

1998: early work on antioxidant properties of the cannabinoids – CBD found more effective than ascorbate or alpha-tocopherol

Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants

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