Cannabidiol’s Multifactorial Mechanisms Has Therapeutic Potential for Aneurysmal Subarachnoid Hemorrhage: a Review

Abstract

Subarachnoid hemorrhage (SAH) is a major health burden that accounts for approximately 5% of all strokes. The most common cause of a non-traumatic SAH is the rupture of a cerebral aneurysm. The most common symptom associated with SAH is a headache, often described as “the worst headache of my life.” Delayed cerebral ischemia (DCI) is a major factor associated with patient mortality following SAH and is often associated with SAH-induced cerebral vasospasm (CV). Cannabidiol (CBD) is emerging as a potential drug for many therapeutic purposes, including epilepsy, anxiety, and pain relief. We aim to review the potential use of CBD as a treatment option for post-SAH critically ill patients. Through a literature review, we evaluated the known pharmacology and physiological effects of CBD and correlated those with the pathophysiological outcomes associated with cerebral vasospasm following subarachnoid hemorrhage. Although overlap exists, data were formatted into three major categories: anti-inflammatory, vascular, and neuroprotective effects. Based on the amount of information known about the actions of CBD, we hypothesize the anti-inflammatory effects are likely to be the most promising therapeutic mechanism. However, its cardiovascular effects through calcium regulation and its neuroprotective effects against cell death, excitotoxicity, and oxidative stress are all plausible mechanisms by which post-SAH critically ill patients may benefit from both early and late intervention with CBD. More research is needed to better understand if and how CBD might affect neurological and vascular functions in the brain following injury such as subarachnoid hemorrhage.

Anti-oxidant effects of cannabidiol relevant to intracerebral hemorrhage

“…In addition to the anti-oxidant effects covered in the current review, Henry and others, in their review, suggest that CBD may also have exciting anti-inflammatory, vascular effects, and neuroprotective function in subarachnoid hemorrhage ( Henry et al, 2023 ). We believe that these may also be potential protective mechanisms for ICH.…”

Neurological Complications of Cannabinoids

“…There is potential interest in the neuroprotective effects of cannabinoids in aneurysmal SAH also. Studies suggest a potential therapeutic role for cannabidiol in critically ill aneurysmal SAH patients, largely supported by evidence of anti-inflammatory effects of cannabinoids through their action on CB2 receptors 83 ; however, existing quality of data does not support use in current clinical practice.…”

Secondary headaches - red and green flags and their significance for diagnostics

“…More than one-third of patients with SAH have persistent headaches, hence the need to explore long-term analgesic options [ 44 ]. Some of the alternatives explored to reduce the need for opioid include magnesium and gabapentin as well as pterygopalatine blocks and cannabidiol [ [45] , [46] , [47] , [48] ].…”