CBD for newborn babies

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Perinatal acute ischemic stroke

Acute arterial ischemic stroke affects 4 over 1000 live newborns and is the most frequent type of acquired neonatal brain injury;

The incidence is even higher in pre-term newborns, affecting approximately 60% of the babies, leading to long-lasting complications of the disease.

Around one third of the newborns affected by stroke develop unilateral cerebral palsy (which usually impairs use of one hand), and learning and cognitive deficits are also frequent. (1,2)

The manifestation of brain injury differs depending on the maturational status of the brain at the time of the insult. In pre-term babies white matter injury is predominant, being more vulnerable to glutamate toxicity and neuroinflammation as some brain cell populations are still developing.

In contrast, in term babies, in which the maturation of the white matter is more advanced, neuronal degeneration in grey matter structures is the most commonly observed manifestation of injury (3,4).

http://stroke.ahajournals.org/content/strokeaha/44/11/3265/F1.large.jpg

Cannabinoids to the rescue

So far, hypothermia (applied as head or whole-body cooling) is the only clinical intervention used in hypoxic-ischemic newborn babies. However, hypothermia does not prevent injury in all cases and, the treatment does not always lead to complete functional recovery (14).

Currently, no other treatment is available to patients.

Cannabinoids affect multiple endogenous processes involved in brain injury and recovery. Cannabinoids are also known to control the cell cycle and the proliferation, survival and differentiation of neural stem cells (fundamental for new births, as we have already described in a previous article titled “Endocannabinoids: co-creator of life? Their role from conception to breast-feeding”), capabilities that target them as interesting experimental drugs for the enhancement of endogenous brain repair responses to perinatal brain injury. (5,6)

Cannabinoids modulate neuronal excitability and counteract glutamate excitotoxicity, as we have explained further in a video on Cannabis for ALS.

Moreover, through the activation of CB2 receptors in immune cells cannabinoids can modulate the intensity and extension of neuroinflammatory responses to injury, which we have been extensively describing in: “Caution: understanding the Endocannabinoid System might change your life!

Finally, cannabinoids have been shown to decrease vascular reactivity (increased blood flow in response to ischemia), overall reducing the rolling and adhesion of circulating leukocytes and preventing their infiltration into the inflamed brain, which is key for a number of disorders, from ischemia to Multiple Sclerosis. (7)

To put these concepts onto test:

in-vitro experiments have been carried out with a synthetic cannabinoid (WIN-55) in an animal model of acute hypoxic-ischemic strokes.

Pre-incubation of the brain slices with WIN (50 mM) prevented glutamate release (neurotoxic), TNFα accumulation and iNOS induction (pro-inflammatory markers), resulting in a reduction of cell death. (8)

This has been further examined in in-vivo studies which administered WIN (1 mg/kg) immediately after hypoxia-ischemia event, resulting in reduced diffusion of injury around brain areas. (9)

CBD as a treatment

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It has been demonstrated that CBD has neuroprotective effects in models of acute hypoxic-ischemic brain damage in newborn animals as well as in adult rodent stroke models.
CBD (1 mg/kg) was shown to induce a sustained reduction in excitotoxic damage, oxidative stress and inflammation up to 7 days after injury, addressing the three major pathophysiological mechanisms involved in the generation of permanent brain damage after arterial ischemic strokes. (10)

In a more recent study, an animal model of severe stroke in newborn rats, CBD (5mg/kg) was administered post-insult, overall reducing peri-infarct brain-damage and restoring neurobehavioural function in the short and long term.

The volume of the infarct was not modified by CBD, but its beneficial effects were apparent already one week after the stroke, including prevention of long-lasting functional impairment, while no side effects of the drug were observed.

Following CBD administration, movement impairment was restored, it improved neurobehavioural functions controlling strength, coordination and sensorimotor performance , as well as other cognitive deficits, whilst further neuronal loss was prevented. (11)

Cannabidiol to newborns

http://media.web.britannica.com/eb-media/07/82607-004-7F32EAE4.jpgThe prospects of cannabidiol (CBD) becoming effective and safe therapeutic drug against neonatal hypoxia-ischemia increased considerably after several studies demonstrated the beneficial effects of CBD on multiple neurophysiological parameters commonly used for the bedside monitoring of asphyxiated newborns.

In one of those studies the intravenous administration of CBD (0.1 mg/kg) improved brain tissue oxygenation during the first 3 h after hypoxia-ischemia, and induced a partial recovery of EEG amplitude from 1 to 6 h in newborn piglets.

Similarly to the studies with rodents, it was also proved that CBD exert a long-lasting protection;

The neurobehavioral analysis showed that the animals that were treated with CBD had a faster and more significant functional recovery compared to animals that received vehicle. (12,13)

Altogether, these studies using both rodent and non-rodent animal models strongly suggest that CBD may be a safe and effective drug to be used during the acute and sub-acute phases after ischemic stroke, and is currently the best suited cannabinoid to be implemented for clinical use in babies affected by neonatal encephalopathy.

How to supplement

Although the best source of CBD derives from high-CBD cannabis strain, many CBD oil preparations are also extracted from hemp, for legal reasons.

Amongst the commercially available CBD oils, the mean average contents are a mere 0.173% THC while providing levels of CBD measuring at > 3%, which ensures safe consumption free of significant psychoactive effects.https://www.whaxy.com/wp-content/uploads/2015/10/will-cbd-oil-get-you-fired-1.jpg Strains are considered CBD-rich when the CBD content level 4% or above.

CBD for newborns is best administered as an oil or extract, or even as a suppository; however, if you choose the latter, we recommend checking out our latest article regarding absorption of suppositories.

Feel free to learn more about CBD in other articles!

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References:

1) Ferriero, D.M. Neonatal brain injury. N. Engl. J. Med. 2004, 351, 1985–1995.

2) Vannucci, R.C. Hypoxic-ischemic encephalopathy. Am. J. Perinatol. 2000, 17, 113–120.

3) Back, S.A.; Luo, N.L.; Borenstein, N.S.; Levine, J.M.; Volpe, J.J.; Kinney, H.C. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J. Neurosci. 2001, 21, 1302–1312.

4) Kirton, A.; Armstrong-Wells, J.; Chang, T.; Deveber, G.; Rivkin, M.J.; Hernandez, M.; Carpenter, J.; Yager, J.Y.; Lynch, J.K.; Ferriero, D.M. Symptomatic neonatal arterial ischemic stroke: The international pediatric stroke study. Pediatrics 2011, 128, e1402–e1410.

5) Alonso-Alconada, D.; Alvarez, A.; Hilario, E. Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury. Neurosci. Bull. 2011, 27, 275–285.

6) Galve-Roperh, I.; Aguado, T.; Palazuelos, J.; Guzman, M. The endocannabinoid system and neurogenesis in health and disease. Neuroscientist 2007, 13, 109–114.

7) Ramirez, S.H.; Hasko, J.; Skuba, A.; Fan, S.; Dykstra, H.; McCormick, R.; Reichenbach, N.;Krizbai, I.; Mahadevan, A.; Zhang, M.; et al. Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J. Neurosci. 2012, 32, 4004–4016.

8) Fernandez-Lopez, D.; Martinez-Orgado, J.; Nunez, E.; Romero, J.; Lorenzo, P.; Moro, M.A.;Lizasoain, I. Characterization of the neuroprotective effect of the cannabinoid agonist WIN-55212 in an in vitro model of hypoxic-ischemic brain damage in newborn rats. Pediatr. Res. 2006, 60, 169–173.

9) Fernandez-Lopez, D.; Pazos, M.R.; Tolon, R.M.; Moro, M.A.; Romero, J.; Lizasoain, I.; Martinez-Orgado, J. The cannabinoid agonist WIN55212 reduces brain damage in an in vivo model of hypoxic-ischemic encephalopathy in newborn rats. Pediatr. Res. 2007, 62, 255–260.

10) Castillo, A.; Tolon, M.R.; Fernandez-Ruiz, J.; Romero, J.; Martinez-Orgado, J. The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol. Dis. 2010, 37,434–440.

11) Ceprian, M Vargas, C Cora, A Barata, L et al.. (2016). Neuroprotective effect of cannabidiol in a newborn rat model of acute ischemic stroke.International Cannabinoid Research Society 26th annual symposium. 26 (1), 27.

12) Alvarez, F.J.; Lafuente, H.; Rey-Santano, M.C.; Mielgo, V.E.; Gastiasoro, E.; Rueda, M.;Pertwee, R.G.; Castillo, A.I.; Romero, J.; Martinez-Orgado, J. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets. Pediatr. Res. 2008, 64, 653–658.

13) Lafuente, H.; Alvarez, F.J.; Pazos, M.R.; Alvarez, A.; Rey-Santano, M.C.; Mielgo, V.; Murgia-Esteve, X.; Hilario, E.; Martinez-Orgado, J. Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs. Pediatr. Res. 2011, 70, 272–277.

14) Higgins, R.D.; Raju, T.; Edwards, A.D.; Azzopardi, D.V.; Bose, C.L.; Clark, R.H.; Ferriero, D.M.; Guillet, R.; Gunn, A.J.; Hagberg, H.; et al. Hypothermia and other treatment options for neonatal encephalopathy: An executive summary of the Eunice Kennedy Shriver NICHD workshop. J. Pediatr. 2011, 159, 851–858.e1.

Viola Brugnatelli

Viola Brugnatelli is a Neuroscientist specialised in Cannabinoid circuitry & GPCRs signalling. Her academy and research training let her gain extensive experience on medical cannabis and terpenes both from preclinical as well as clinical perspective. In her vision, collective human knowledge behold the power for overall improvement of life, thus, it should be accessible and shareable. Viola is Founder of the science online magazine Nature Going Smart, and works as a consultant for companies & individual patients, as a speaker at seminars and workshops and as a lecturer in a CME course on Medical Cannabis in Italy, at the University of Padua.

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