by Sylent Jay on 24/08/2016 | Medicinal

Endocannabinoids and development: embryos, newborns, breastfeeding and more

Endocannabinoids The human body benefits from its own network of cannabinoids, called the endocannabinoid system. Especially considering the insanely serious taboo around the cannabis plant and its consumption, the general topic of cannabinoids naturally produced by the human body has been delved into manifold.


The topic of endocannabinoids and development has been well-fed as well, despite it being largely kept on the down-low. And perhaps with “reason”; what would legislators have to say about cannabinoids being in large part responsible for some of the very first attempts at survival of human embryos?

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Endocannabinoids: quick rundown of the basics

Cannabinoid receptors (CB) are present in numerous places throughout the human body. On one hand, CB1 receptors are located in many neural and non-neural tissues, notably in the brain, nervous system, digestive system, reproductive system, connective tissues, and glands. CB2 receptors, on the other hand, can be found in non-neural tissue, for instance in the immune system. Benefits brought by these receptors and their allocated cannabinoids are varied, but focused on a single goal: homeostasis, i.e. the capability of an organism to regulate its internal environment to adapt to external parameters.

For instance …
CB1 receptors are known to be the target of the famed cannabinoid THC, but other cannabinoids and endocannabinoids collaborate with CB1 receptors as well, such as anandamide.
CBD, another very popular cannabinoid famed for its multiple therapeutic properties, interacts with both CB1 and CB2 receptors.

Endocannabinoids and development: embryonal implantation

Endocannabinoids are detected in the human body extremely early, before said human body is fully formed in utero. In fact, both CB1 and CB2 receptors are present starting from the early stages of gestation, notably during the process of implantation of the embryo – that is, when the embryo successfully “attaches” itself to the mother/surrogate mother’s uterine wall.

Embryo implantation takes place 6 to 12 days after ovulation. It triggers the providing of oxygen and nutriments from the mother to the embryo in order to allow it to grow.
During that time, the uterus generally registers high levels of anandamide, and requires a very specific and very localized reduction in anandamide levels for the implantation process to succeed, that is, exclusively in the location where the embryo will make the adhesion. [1]

Due to their relation with anandamide, CB1 receptors are at the centre of this process. In case the implantation process is deficient, meaning that the endocannabinoid system is not fulfilling its role, the embryo would fail to survive, making the endocannabinoid anandamide not only important for growth in early stages of gestation, but also capital for the ultimate survival of the embryo.

What does it mean?
The process of embryo implantation is understood in a very limited manner. In particular, the numerous reasons why embryo implantation can fail are not always explainable.
A more in-depth study of anandamide and its effects when provided to the human body from external sources could be of use on the general topic of infertility.
Besides, a more democratic use of this knowledge could also improve odds regarding in vitro fertilization; one major obstacle of such procedures is the failure of the egg to implant itself in the mother’s uterus.

Embryo-in-utero

Endocannabinoids and development: the early post-natal neuronal link

Neural development

Further studies on functionalities managed by CB1 receptors in the brain have shown that these receptors are present in areas that are deserted once the body is at an adult stage.
Indeed, CB1 receptors are not only found in the cerebral cortex and the hippocampus, which are areas in which these receptors are known to be active in adult humans, but in the case of developing brains, also in white matter, notably in the capsula interna and pyramidal tract, as well as in the subventricular zone.
In other words, it is thought that CB1 receptors play a more than crucial role in the early development of the human brain. The receptors are later dismissed by the adult human body once this specific part of the neural development process is completed.
In an attempt to detect the very same process on other species, animal studies conducted on developing brains have also shown the presence of CB1 receptors up until postnatal day 5 in white matter regions such as the corpus callosum, and in the anterior commissure, which both link the two hemispheres of the brain together. [2] [3]

Both sets of results show a transitory presence of cannabinoid receptors in several regions of the developing brain, consistent with the theory that endocannabinoids play a role in brain development.

What does it mean?
Unfortunately, studies conducted on the topic of endocannabinoids and development, especially directly related to the human brain, are far too centred on the basics of this discovery to trigger any sort of concrete application. One could theorize that perhaps one day, certain nervous system-related congenital diseases (such as Cerebral Palsy) could be detected, and possibly treated before their onset.

Neuroprotective properties

Endocannabinoids also seem to have an impact on trauma-induced neuronal loss during a short amount of time after birth.
Experiments conducted postnatally on animals have shown that trauma of external origins responsible for provoking neuronal loss, could be impacted by the protective actions of a synthetic compound emulating THC. In these cases, the THC intake prevented both immediate and delayed neurotoxicity resulting from trauma.
More in depth studying of this process has shown that depending on the exact age of the subject, results could vary; it would appear that the neuroprotective properties provided by CB1 receptors are active only during a short, critical period after birth. [2] [4]

Observations based on this experiment and similar ones have shown a major increase of endocannabinoid anandamide levels following a head trauma. The hypothesis is that anandamide, which interacts with CB1 receptors, could be acting as an endogenous neuroprotectant.

What does it mean?
Evidently, the mammal body already has a way of fending off certain hazards that can occur after birth. Without any trigger other than trauma itself, anandamide protects the very young brain from neuronal loss. However, the THC component, administrated externally, could prove to be an important key element to treating early trauma in newborns. Most of these sources of early trauma are a result of complications in the birthing process, for instance asphyxia or cardiac arrest. However, due to the psychoactive nature of THC, it is likely certain adjustments would be needed. Say, a CBD-THC concoction?

human-brain

Endocannabinoids and development: Suckling response and breastfeeding

Suckling response and failure to thrive

The suckling response in a newborn, i.e. “the [instinctive suckling] of anything that touches the roof of [the] mouth, and simulates the way a child naturally eats”, is a crucial milestone in the human lifecycle. In cases when the newborn survives the absence of feeding response, it can condition future physical developments that can go as far as the adult age, such as growth, general relationship with the feeding process, and their respective by-products (weight gain in relation to age, gastrointestinal difficulties, etc.) It can also have an impact on the mother/caregiver-child relationship, or come from it.

Studies have been trying to prove CB1 receptors are a major parameter in the initiation of the suckling response in newborns. For instance, tests involving the injection of a CB1 receptor antagonist resulted in a failure in milk ingestion, with eventual deaths of the tested subjects a few days later. Such results could only be observed when the antagonist was administrated in the 24 hours following birth, later administration resulting in a smaller to non-existing percentage of consequential deaths. The CB1 receptor antagonist also triggered hypothermia and a lack of motor capabilities to feed. Again, it seems that the endocannabinoid system puts in place temporary coping mechanisms, only to deactivate them when the body does not require them anymore. [2]

What does it mean?
NOFTT, which is a failure to thrive without a known organic source, could be linked to a deficient endocannabinoid system. Despite studies linked having been conducted more than a decade ago, the hypothesis still has not been further studied.

Breastfeeding

The role of certain endocannabinoids in the feeding process of infants was recognized more than two decades ago by various studies. Both anandamide and fellow endocannabinoid 2-arachidonoylglycerol (2-AG) are found in human as well as bovine milk, with a level of 2-AG ten times higher than of anandamide.

Test results suggest that the purpose of 2-AG in the brain is to stimulate the suckling response, and that the resulting milk intake increases its levels, creating over a period of 2 days a pattern of milk suckling behaviour. In cases where an antagonist is administrated, the lack of milk-derived 2-AG results in a failure to develop this pattern, jeopardizing the survival of the breastfeeding subject. [2]

On the other hand, anandamide has been proven to increase food intake. According to scientists, “the underlying circuitry responsible for the therapeutic efficacy of cannabinoids in stimulating appetite is not yet known, although it is probably related to the fact that the CB1 receptor, anandamide, and 2-AG are present in the hypothalamus, which is known to be associated with feeding.” [5]

What does it mean?
Have you ever consumed cannabis recreationally, or medicinally? Have you ever found yourself in the middle of a fit of what is commonly called “the munchies”? If so, you have experienced first-hand the very mechanism that stimulates suckling and appetite, and generally promotes growth and development throughout the human lifecycle.
For reasons ranging from ethics to the current war on drugs, the very sensitive topic of endocannabinoids and development has not yet reached a peak in terms of proliferation of studies, not to mention clinical trials.
Hopefully, recent changes in legislation will result in more consequent funding of cannabinoid research.

Have you stumbled upon a new study on the topic? Would you like to share your personal experience with us?
Tell us about endocannabinoids and development, in the comment section below.

 

 

 

[1] Dysregulated cannabinoid signalling disrupts uterine receptivity for embryo implantation, 2001, USA, Germany

[2] The endocannabinoid-CB receptor system: Importance for development and in paediatric disease, 2004, Israel

[3] The endogenous cannabinoid system and brain development, 2000, Spain

[4] Cannabinoids: Well-suited candidates for the treatment of perinatal brain Injury, 2013, Spain

[5] Cannabis and endocannabinoid modulators: Therapeutic promises and challenges, 2008, USA

 

Comment Section

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Leanna

I think it's fantastic that this research is being conducted. My best friend wanted to do her neuro - psych thesis on this but couldn't get it past the ethics board at the University. I also have another friend who was having trouble conceiving with her (anti marijuana )ex, but found herself unexpectedly pregnant with her current (pro marijuana)bf. After reading this article, we think maybe it helped with implantation. Very interesting stuff that could have a major impact on infertility treatments!

26/08/2016

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