“Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has therapeutic effects in different paradigms of brain injury, acting as a neuroprotectant.

As oxidative stress is a primary risk factor for brain damage after neonatal hypoxia, we tested the effect of CBD on oxidative status and non-protein-bound iron accumulation in the immature brain after hypoxia. Moreover, we tested whether cannabidiol affects the accumulation of hypoxia-inducible factor-1 alpha (HIF-1α) which plays a key role in the regulation of cellular adaptation to hypoxia and oxidative stress. We used 7-day-old mice randomly assigned to hypoxic or control groups. Immediately after hypoxia or control exposure, pups were randomly assigned to a vehicle or CBD treatment. 24 h later, they were decapitated and the brains were immediately removed and stored for further biochemical analyses.

We found that CBD reduced lipid peroxidation and prevented antioxidant depletion. For the first time, we also demonstrated that CBD upregulated HIF-1α protein level. This study indicates that CBD may effective agent in attenuating the detrimental consequences of perinatal asphyxia.”

https://pubmed.ncbi.nlm.nih.gov/38987284/

“Our results show that CBD applied in a short time after hypoxia attenuates hypoxia-induced oxidative stress, likely due to its antioxidant activity. To the best of our knowledge, this is also the first report showing that the post-hypoxia treatment with CBD increases the concentration of HIF-1α, which is directly involved in the maintenance of oxygen and iron homeostasis. This indicates that CBD is promising agent for new therapies developed for the treatment of hypoxic injury “

https://www.nature.com/articles/s41598-024-66599-5

“Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment.

This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats.

CBD prevented the long-lasting motor and cognitive consequences of IVH, reduced brain damage in the short- and long-term, protected oligodendroglial cells preserving adequate myelination and maintained BBB integrity.

The protective effects of CBD were associated with the modulation of inflammation, excitotoxicity and oxidative stress.

In conclusion, in immature rats, CBD reduced IVH-induced brain damage and its short- and long-term consequences, showing robust and pleiotropic neuroprotective effects.

CBD is a potential candidate to ameliorate IVH-induced immature brain damage.”

https://pubmed.ncbi.nlm.nih.gov/38301326/

“Cannabidiol (CBD), the main non-euphoric component of Cannabis sativa, has demonstrated neuroprotective effects in different models of acute diffuse or mild to moderate focal hypoxic-ischemic brain damage in newborn animals with a brain developmental stage similar to that of term human newborns.”

https://www.sciencedirect.com/science/article/pii/S1878747924000126?via%3Dihub

“The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.”

https://pubmed.ncbi.nlm.nih.gov/36635488/

https://link.springer.com/article/10.1007/s11095-023-03469-1

“Background: Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB₂ and serotonin 5HT_1A receptors included. These two receptors may interact to form heteromers (CB₂-5HT_1A-Hets) that are also a target of CBD. 

Aims: We aimed to assess whether the expression and function of CB₂-5HT_1A-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen-deprived neurons. 

Methods: We developed a quantitation of signal transduction events in a heterologous system and in glucose/oxygen-deprived neurons. The expression of receptors was assessed by immuno-cyto and -histochemistry and, also, by using the only existing technique to visualize CB₂-5HT_1A-Hets fixed cultured cells and tissue sections (in situ proximity ligation PLA assay). 

Results: CBD and cannabigerol, which were used for comparative purposes, affected the structure of the heteromer, but in a qualitatively different way; CBD but not CBG increased the affinity of the CB₂ and 5HT_1A receptor-receptor interaction. Both cannabinoids regulated the effects of CB₂ and 5HT_1A receptor agonists. CBD was able to revert the upregulation of heteromers occurring when neurons were deprived of oxygen and glucose. CBD significantly reduced the increased expression of the CB₂-5HT_1A-Het in glucose/oxygen-deprived neurons. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of CB₂-5HT_1A-Hets. 

Conclusions: Benefits of CBD in the hypoxia of the neonate are mediated by acting on CB₂-5HT_1A-Hets and by reducing the aberrant expression of the receptor-receptor complex in hypoxic-ischemic conditions. These results reinforce the potential of CBD for the therapy of the hypoxia of the neonate.”

https://pubmed.ncbi.nlm.nih.gov/36077095/

https://www.mdpi.com/1422-0067/23/17/9695/htm