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Copyright © 2021 Batalla, Bos, Postma and Bossong.

Keywords: Cannabis (marijuana); cannabidiol; delta9-tetrahydrocannabinol; functional MRI; neuroimaging.

Background: Accumulating evidence suggests that the non-intoxicating cannabinoid compound cannabidiol (CBD) may have antipsychotic and anxiolytic properties, and thus may be a promising new agent in the treatment of psychotic and anxiety disorders. However, the neurobiological substrates underlying the potential therapeutic effects of CBD are still unclear. The aim of this systematic review is to provide a detailed and up-to-date systematic literature overview of neuroimaging studies that investigated the acute impact of CBD on human brain function. Methods: Papers published until May 2020 were included from PubMed following a comprehensive search strategy and pre-determined set of criteria for article selection. We included studies that examined the effects of CBD on brain function of healthy volunteers and individuals diagnosed with a psychiatric disorder, comprising both the effects of CBD alone as well as in direct comparison to those induced by ∆9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis. Results: One-ninety four studies were identified, of which 17 met inclusion criteria. All studies investigated the acute effects of CBD on brain function during resting state or in the context of cognitive tasks. In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC. Furthermore, CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms, such as emotional processing (fronto-temporal), verbal memory (fronto-striatal), response inhibition (fronto-limbic-striatal), and auditory/visual processing (temporo-occipital). In individuals at clinical high risk for psychosis and patients with established psychosis, acute CBD showed intermediate brain activity compared to placebo and healthy controls during cognitive task performance. CBD modulated resting limbic activity in subjects with anxiety and metabolite levels in patients with autism spectrum disorders. Conclusion: Neuroimaging studies have shown that acute CBD induces significant alterations in brain activity and connectivity patterns during resting state and performance of cognitive tasks in both healthy volunteers and patients with a psychiatric disorder. This included modulation of functional networks relevant for psychiatric disorders, possibly reflecting CBD’s therapeutic effects. Future studies should consider replication of findings and enlarge the inclusion of psychiatric patients, combining longer-term CBD treatment with neuroimaging assessments.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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CBD may offer an option for treating different types of chronic pain. A study from the European Journal of Pain showed, using an animal model, CBD applied on the skin could help lower pain and inflammation due to arthritis. Another study demonstrated the mechanism by which CBD inhibits inflammatory and neuropathic pain, two of the most difficult types of chronic pain to treat. More study in humans is needed in this area to substantiate the claims of CBD proponents about pain control.

Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not. We need more research but CBD may be prove to be an option for managing anxiety, insomnia, and chronic pain. Without sufficient high-quality evidence in human studies we can’t pinpoint effective doses, and because CBD is currently is mostly available as an unregulated supplement, it’s difficult to know exactly what you are getting. If you decide to try CBD, talk with your doctor — if for no other reason than to make sure it won’t affect other medications you are taking.

The bottom line on cannabidiol

CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.

CBD stands for cannabidiol. It is the second most prevalent of the active ingredients of cannabis (marijuana). While CBD is an essential component of medical marijuana, it is derived directly from the hemp plant, which is a cousin of the marijuana plant. While CBD is a component of marijuana (one of hundreds), by itself it does not cause a "high." According to a report from the World Health Organization, "In humans, CBD exhibits no effects indicative of any abuse or dependence potential…. To date, there is no evidence of public health related problems associated with the use of pure CBD."

Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level in your blood of the blood thinner coumadin, and it can raise levels of certain other medications in your blood by the exact same mechanism that grapefruit juice does. A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication. Currently, the FDA does not regulate the safety and purity of dietary supplements. So, you cannot know for sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other (unknown) elements. We also don’t know the most effective therapeutic dose of CBD for any particular medical condition.

CBD is readily obtainable in most parts of the United States, though its exact legal status is in flux. All 50 states have laws legalizing CBD with varying degrees of restriction, and while the federal government still considers CBD in the same class as marijuana, it doesn’t habitually enforce against it. In December 2015, the FDA eased the regulatory requirements to allow researchers to conduct CBD trials. Currently, many people obtain CBD online without a medical cannabis license. The government’s position on CBD is confusing, and depends in part on whether the CBD comes from hemp or marijuana. The legality of CBD is expected to change, as there is currently bipartisan consensus in Congress to make the hemp crop legal which would, for all intents and purposes, make CBD difficult to prohibit.

Relatively few people have heard about the process of excitotoxicity in the brain, yet it plays a huge role in neurodegenerative diseases. It is a term used to describe the damage caused when the brain cells become excessively active due to too much stimulation. Excitotoxicity can happen after a stroke, traumatic brain injury, or even hearing loss.

CBD is one of over 110 cannabinoids produced by cannabis. It is also abundant in the hemp plant. THC is famed for its ability to cause an intoxicating high. In contrast, CBD is non-intoxicating. Nonetheless, there is evidence that both compounds have possible therapeutic effects. This is part of the reason why CBD for sale is now an exciting proposition.

Unfortunately, an excessive level of free radicals could result in the loss of DNA particles. This is especially the case if the body doesn’t create enough antioxidants. This process is linked to medical conditions such as Parkinson’s and Alzheimer’s.

How Do CBD Products Affect the Brain?

THC’s effects are akin to those caused by anandamide, nicknamed the ‘bliss’ molecule. It binds to our CB1 receptors, which are responsible for many of the cannabinoid’s intoxicating effects. In fact, THC binds more closely to anandamide’s CB1 receptors than the molecule itself! Anandamide prevents the release of other neurotransmitters, which is part of the reason why we feel a euphoric high after using marijuana.

The possible benefits attributed to both are down to their respective effects on the body’s endocannabinoid system (ECS). The ECS contains endocannabinoids, naturally produced cannabinoids, that bind to receptors located throughout the body. The ECS helps regulate various things such as appetite, pain, and memory.

CBD’s impact on CB2 receptors may help reduce oxidative stress. Cannabidiol also appears to have antioxidant properties. According to a study published in the Journal of Alzheimer’s Disease in 2014, CBD products’ long-term usage led to antioxidative and anti-inflammatory effects.

In contrast, CBD has a significantly less potent effect on the ECS’s receptors. It only binds loosely to CB1 receptors. This action actually blocks the receptors, thus reducing the effects of THC.