Format

Send to

Choose Destination
Neonatology. 2017;112(2):143-149. doi: 10.1159/000471786. Epub 2017 Jun 1.

High-Dose Cannabidiol Induced Hypotension after Global Hypoxia-Ischemia in Piglets.

Author information

1
Division of Pediatric and Adolescent Medicine, Department of Pediatric Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Abstract

BACKGROUND:

Cannabidiol (CBD) is considered a promising neuroprotectant after perinatal hypoxia-ischemia (HI). We have previously studied the effects of CBD 1 mg/kg in the early phase after global HI in piglets. In contrast to prior studies, we found no evidence of neuroprotection and hypothesized that higher doses might be required to demonstrate efficacy in this animal model.

OBJECTIVE:

To assess the safety and potential neuroprotective effects of high-dose CBD.

METHODS:

Anesthetized newborn piglets underwent global HI by ventilation with 8% O2 until the point of severe metabolic acidosis (base excess -20 mmol/L) and/or hypotension (mean arterial blood pressure ≤20 mm Hg). Piglets were randomized to intravenous treatment with vehicle (n = 9) or CBD (n = 13). The starting dose, CBD 50 mg/kg, was reduced if adverse effects occurred. The piglets were euthanized 9.5 h after HI and tissue was collected for analysis.

RESULTS:

CBD 50 mg/kg (n = 4) induced significant hypotension in 2 out of 4 piglets, and 1 out of 4 piglets suffered a fatal cardiac arrest. CBD 25 mg/kg (n = 4) induced significant hypotension in 1 out of 4 piglets, while 10 mg/kg (n = 5) was well tolerated. A significant negative correlation between the plasma concentration of CBD and hypotension during drug infusion was observed (p < 0.005). Neuroprotective effects were evaluated in piglets that did not display significant hypotension (n = 9) and CBD did not alter the degree of neuronal damage as measured by a neuropathology score, levels of the astrocytic marker S100B in CSF, magnetic resonance spectroscopy markers (Lac/NAA and Glu/NAA ratios), or plasma troponin T.

CONCLUSIONS:

High-dose CBD can induce severe hypotension and did not offer neuroprotection in the early phase after global HI in piglets.

KEYWORDS:

Cannabidiol; Hypotension; Hypoxic-ischemic brain injury; Neonatal hemodynamics; Neonatal hypoxia-ischemia; Neuroprotection; Newborn piglet; Side effects

PMID:
28564654
DOI:
10.1159/000471786
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland
Loading ...
Support Center