Cannabinoids co-creators of life: from conception to breastfeeding

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Endocannabinoids are lipid messenger molecules that play and important role in our daily lives regulating and maintaining homoeostasis in our bodies.

Their role is so crucial that they effect all the major stages of our lives from conception, embryo implantation, birth to the early days of our lives.

Endocannabinoids deliver their message by binding to cannabinoid receptors (CB1 and CB2). They are then degraded by enzymes (FAAH, MAGL) or reuptaken by the cell. More information on how the encocannabinoid system works can be found here: “Caution: Understanding the Endocannabinoid System might change your life”.

Sexual behaviour

The role of endocannabinoids in the sexual behaviour of males has been observed. Recent studies done on rats have shown that the endogenous cannabinoid Anandamide (AEA), when injected, initiated sexual behaviour in non-copulating males (1) and reduced ejaculatory thresholds for sexually sluggish males (2) .

These effects of Anandamide are mediated via CB1 receptor activation and are effective even in normal rats and are dose dependant, meaning that different doses can have opposite effects (3).

https://www.plannedparenthood.org

 

Male fertility

Both CB1 and CB2 receptors are found on sperm cells. The level of endocannabinoid AEA is crucial for control of the percentage of swimming and live sperm (viability and motility), the modulation of the energy expenditure and control of the number of testosterone producing cells (also known as Leydig cells).

These effects are mediated through the CB1 receptor. CB2 receptor activation is responsible for the start of the production of sperm and the regulation of its swimming speed (4).

Embryo implantation

Virtually all steps of female reproductive events are affected by one or more elements of the endocannabinoid system (ECS). In fact cells and tissues of female reproductive organs are endowed with a fully functional ECS (7).

Both Anandamide and 2-AG have been found in the uterus and the fine tuning of their levels are essential for successful embryonic passage through the oviduct and implantation into the uterus. This is done via enzymatic degradation, by the enzymes FAAH and MAGL, of the two endocannabinoids (AEA and 2-AG) at crucial times in embryo development and implantation (5).

The role of these enzymes is crucial. As research has shown, they could even provide a great diagnostic tool, as lower levels of FAAH enzymes were found in women who miscarried than those who gave birth (6).

Foetal development

The CB1 receptor has been found to play a pivotal role in the formation of the fetus’s brain. These receptors are responsible for the differentiation of neuronal progenitor cells into neurons or glia cells. They also act as tour guides for the connections between neuronal cells (axons) by showing them the right path to take and where to make connections to other cells (5).

Life is not possible devoid of cannabinoid receptors: depleting the gene encoding CB1 receptor sequence (in order to obtain a mice CB1 KO -/-), prevents embryo development and survival to birth.

 

breastfeeding http://www.cannabis.es/web/images/cannabis_hiperemesis.jpgCannabis use in pregnancy

Research shows the importance of the endocannabinoid system as a finely tuned machine regulating important aspects in each phase of the reproductive cycle. One would assume that any interference by outside ECS modulators, such as phytocannabinoids, could have a detrimental effect during pregnancy. So the question arises: is cannabis consumption safe during pregnancy?

Women use cannabis during pregnancy for various reasons raging from health (nausea, vomiting, increasing appetite, other chronic medical conditions), spiritual (Rastafarians) to recreational.

A majority of women experience nausea or/and vomiting during pregnancy and cannabis is often effectively used as a relief therapy. In a survey done in Canada, cannabis was rated as extremely effective or effective by 92% of the respondents who had used it as a therapy for nausea and vomiting (morning sickness) (10).

While it has certainly proven to have a beneficial effect on the mothers, the concern remains on whether this affects the baby that the mother is carrying.

The studies

The results of a well known study done in Jamaica by Dr. Dreher, compared mothers that used cannabis to mothers that did not use it during pregnancy and found that there were no positive or negative neuro-behavioral effects at 3 days of life, while there were significant differences between the exposed and non-exposed neonates at the end of the first month.

The exposed babies showed better physiological stability, required less examiner facilitation to reach an organized state and become available for social stimulation (11).

It should be noted that a lot of the cannabis using mothers, besides smoking, also used cannabis tea.

In a follow up study done on the same children at the age of 5 showed no significant differences in developmental testing outcomes between children of marijuana-using and non-using mothers (12).

A later study on infant mortality rate showed even more interesting results.

They examined 2,964 infants and divided them into categories of those who had no drugs in their organism and those who tested positive (cocaine, opiates, cannabinoids). Those who were drug-negative had an average mortality rate of 15,7 deaths per 1000 live births. Those who tested positive to cannabis and cocaine and/or opiates had a lower mortality rate of 8,9 deaths per 1000 live births. Of the infants who tested positive only to cannabinoids (157 babies) not a single one had died which meant a 0 mortality rate (13).

All these results shed a positive light on the use of cannabis during pregnancy. However, we definitely need more studies to reach a definite conclusion. Surely, cannabis consumption via smoking should better be avoided at all costs, as it clearly counteract the putative protective effects of cannabis itself.

Scientists theorize that maternal cannabis consumption, has significant, yet subtle effects on the offspring. This is due to the framework of the intricate timing requirements and frequently bi-phasic effects of the (endo)cannabinoids (5).

In the end it’s up to the mother to decide which is best for her baby. For “morning sickness” troubles mothers should first try acidic cannabinoids, especially CBD acid. CBD acid has been shown to be a strong inhibitor of nausea and vomiting (14,15) and it does not act on the cannabinoid receptors.

We recommend that if you intend to consume cannabinoids during pregnancy, visit our article on “Cannabis Juicing: the green elixir of life” .

 

Breastfeeding and appetite stimulation

Even after we leave the comfort of our mother’s womb, endocannabinoids are crucial for the survival of the newborn.

Endocannabinoids, oxylipins and other related compounds have been found in human milk (8). The endocannabinoid 2-AG (2-arachidonoylglycerol) has been found to be the most abundant and has an important role for the infants postnatal suckling behaviour and appetite stimulation.

Studies on mice have shown that 2-AG binding to CB1 receptors stimulate the initiation of milk suckling in mouse pups, stimulate appetite and might have a role in the correct innervation of the tongue muscles (5).

When researchers blocked the CB1 receptors, with a CB1 antagonist, the growth of the mouse pups stopped and caused death within one week. Scientists also experimented with the co-administration of delta-9-THC,  which almost fully reversed the effects of the antagonist (9).

In summary, endocannabinoids have a crucial role in all the stages of reproduction. While they are a fine tuned machine, phytocannabinoids don’t seem to have a negative impact on this process, and might even prove beneficial to conceiving parents.

 

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References:

1.  Anandamide transforms noncopulating rats into sexually active animals. Canseco-Alba et al.2013, The journal of sexual medicine

2. Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: possible relevance for human lifelong delayed ejaculation disorder. Rodríguez-Manzo G 2015, The journal of sexual medicine

3. Low anandamide doses facilitate male rat sexual behaviour through the activation of CB1 receptors. Canseco-Alba et al. 2014, Psychopharmacology

4. The role of endocannabinoids in gonadal function and fertility along the evolutionary axis Battista et al. 2012, Molecular and Cellular Endocrinology

5. Multiple Roles for the Endocannabinoid System During the Earliest Stages of Life: Pre- and Postnatal Development Fride et al. 2008, Journal of Neuroendocrinology 20 (Suppl. 1), 75–81

6. Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage Maccarone et al. 2000, Lancet (London, England)

7. Endocannabinoid signaling in female reproductive events: a potential therapeutic target? Maccarone et al. 2015, Expert Opinion on Therapeutic Targets, Volume 19, Issue 11, 2015

8. Oxylipins, endocannabinoids, and related compounds in human milk: Levels and effects of storage conditions. Wu et al. 2015, Prostaglandins and other lipid mediators

9. Endocannabinoids, feeding and suckling – from our perspective. Mechoulam et al. 2006, International Journal of Obesity

10. Survey of medicinal cannabis use among childbearing women. patterns of its use in pregnancy and retroactive self-assessment of its efficacy against ‘morning sickness’. Westfalla et al. 2006, Complementary therapies in clinical practice

11. Prenatal Marijuana Exposure and Neonatal Outcomes in Jamaica: An Ethnographic Study. Dreher et al. 1994, Pediatrics

12. Five-year follow-up of rural Jamaican children whose mothers used marijuana during pregnancy. Hayes et al. 1991, West Indian Medical Journal

13. Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Ostrea et al. 1997, Pediatrics

14. Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Bolognini et al. 2013, British Journal of pharmacology

15. A comparison of cannabidiolic acid with other treatments for anticipatory nausea using a rat model of contextually elicited conditioned gaping. Rock et al. 2014, Psychophramacology

 

Gregor Zorn

Viola Brugnatelli is a Neuroscientist specialised in Cannabinoid circuitry, GPCRs signalling, and neuropharmacology. Her academy and research training let her gain extensive experience on medical cannabis and phytoceuticals both from preclinical as well as clinical perspective. She works as a consultant and speaker at seminars, workshops & tutorials for MDs, Universities and individual patients. She has been raised by the concepts of equality, responsibility and love towards the environment, others and oneself. In her vision, collective human knowledge behold the power for overall improvement of life at all its forms, thus, it should be accessible and shareable. Viola is currently researching therapeutic potentials of terpenes at University College of Dublin, Ireland, and established since 2014 the Science Online Magazine Nature Going Smart.

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4 Responses

  1. Marie says:

    Thank you for using our image at the top of this article. Would you mind giving us photo credit and a link, please? The credit can be given to Whaxy and linked to https://www.whaxy.com/

    • Viola Brugnatelli says:

      We have, in our alt-test. But if there is a specific article that you would like us to link to, we are happy to do that! Keep up the great job! Thank you

  2. Mike L. Wallace Jr. says:

    Most illnesses either born with or developed over time are caused by cannabinoid deficiencies .

  3. BrotherDank says:

    Endocannabinoid Deficiencies result in mothers nursing and cooing their pups less. 🙁
    https://www.ncbi.nlm.nih.gov/pubmed/2389542“”Thus, it appears that the disruption of endocannabinoid signalling by CB1R deletion alters expression of the OXTR, apparently leading to deleterious effects upon maternal behaviour.”
    © 2013 British Society for Neuroendocrinology.

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