CBD, or cannabidiol, has been the subject of acclaim over the last decade as knowledge of its extensive biological activity has become more common. Individuals with conditions from arthritis to Alzheimer’s disease have found supposed relief with the use of CBD oil or topicals for their condition. The growing demand for CBD from the general population has lead to much research into the mechanisms of how it, and other phytocannabinoids including THC, produce their various effects within the body.
Of all of the properties of CBD, its neuroprotective effects have been the subject of intensified research. Improvements in our understanding of the implication of the endocannabinoid system (ECS) in many neurodegenerative and neuropsychiatric diseases, from autism to Parkinson’s, has lead scientists to question whether or not modulation of the endocannabinoid system could be a therapeutic target for these types of disorders. This is a review of the various neuroprotective properties of CBD.
What is neuroprotection?
Neuroprotection refers to the relative preservation of the structure and function of neurons and brain tissue. Many diseases involve the breakdown of neurons in specific regions of the brain, or degradation of the chemicals these neurons use to signal one another. A diet rich in antioxidants is a common neuroprotective measure recommended by doctors, and several pharmaceutical drugs cause neuroprotective changes first, which subsequently alleviate the symptoms of the condition they’re intended to treat. CBD along with other phytocannabinoids (plant cannabinoids) like THC and CBG have many neuroprotective qualities.2 Moreover, many processes are neurodegenerative, so any compound that blocks the activity of one of those processes is considered to be neuroprotective.
Neuroprotective effects of CBD
Antioxidant effects of CBD
Oxidative stress is a scenario in which highly reactive oxygen molecules called reactive oxygen species (ROS), or free radicals, accumulate in a cell and start causing problems. Oxygen is completely necessary for life, but as molecules get built and broken down by our cells, waste products containing oxygen are produced that react with other important cellular structures, including DNA and cell membranes. When these ROS bind with a cellular component, they change its shape and chemical composition: they effectively make it no-longer be what it was before. By changing the structure and function of DNA or a cell membrane, ROS can cause cell-death in high enough quantities.1, 2
Antioxidants bind with free radicals before they can bind with some more important cellular structure. Vitamins C and E are well-known antioxidants, and CBD has been shown in various studies to actually have a much higher antioxidant ability than either of these vitamins.1, 4 The studies showed that CBD is more comparable to the activity of the much stronger synthetic antioxidant BHT, which is used as a food and drug preservative.
CBD’s effects on other antioxidants
In addition to acting as an antioxidant itself, CBD causes a noted increase in the presence of other antioxidants as well. Glutathione, one of the body’s strongest antioxidants, is upregulated by CBD. Glutathione and creatine work in tandem to control the concentration of water and electrolytes in the body, and CBD has shown several times the ability to regulate the proper ratio between these two compounds.1, 3
Superoxide dismutase (SoD) is an enzyme, and it’s the body’s strongest antioxidant. It’s present in every cell, and it’s responsible for around a third of the total antioxidation in our bodies. After administration of CBD, cells exhibit much higher amounts of SoD mRNA, which is the leftover DNA following protein synthesis: more mRNA = more of whatever the mRNA codes for; in this case, it means CBD increased the amount of SoD present in the cells.
By acting on PPAR-γ, a receptor system that controls the expression of genes, CBD consistently affects the transcription of genes that are involved in antioxidant synthesis like SoD and glutathione, ROS-productive activities, mitochondrial dysfunction, excitotoxicity, and most importantly inflammatory pathways.
Excitotoxicity refers to a condition in which too much excitatory brain activity is not balanced by an increase in inhibitory activity. This causes a rapid increase in the production of ROS, so antioxidants secondarily relieve the symptoms of excitotoxicity. However, CBD also has some unique properties that make it useful for preventing the original overstimulation.
Glutamate is the brain’s primary excitatory neurotransmitter, and when it’s levels are too high, excitotoxicity and oxidative stress both occur. CBD was shown to prevent this by agonizing serotonin 5-HT1a receptors, which have the opposite effect of glutamate receptors. It also binds directly to glutamate receptors, but as an antagonist, meaning it reduces their effects.2, 4
Many neurodegenerative diseases are characteristic of excitotoxicity, including Alzheimer’s, ALS, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. Depression, anxiety, schizophrenia, and even autism also have elements of excitotoxic cell death, so CBD’s action as a buffer against excitotoxicity could explain the success that many have found using CBD to add to their management of these conditions and many others. In fact, CBD’s effect on PD is attributed to its ability to reduce the concentration of ROS in the part of the brain that produces dopamine, an excitatory neurotransmitter; dopamine is key for movement, but in PD, the brain loses the ability to produce it, possibly due to the ROS that are produced as a byproduct of dopamine production.2
All in all, CBD is highly active in many different pathways that have a neuroprotective end result. CBD’s ability as an anti-inflammatory agent further augments the beneficial effects it can have on damaged or inoperant tissue, especially in the brain. More research into its ability to aid in these and many other ways will surely add to the consensus that CBD is a safe and effective remedy for many neurodegenerative conditions.
- Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (−)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(14):8268-8273.
- Borges RS, Batista J, Jr, Viana RB, Baetas AC, Orestes E, Andrade MA, Honório KM, da Silva ABF. Understanding the Molecular Aspects of Tetrahydrocannabinol and Cannabidiol as Antioxidants. Molecules. 2013; 18(10):12663-12674.
- Campos AC, Fogaça MV, Scarante FF, et al. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders. Frontiers in Pharmacology. 2017;8:269. doi:10.3389/fphar.2017.00269.
- Rajesh M, Mukhopadhyay P, Bátkai S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology. 2010;56(25):2115-2125. doi:10.1016/j.jacc.2010.07.033.