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) and are then degraded by enzymes (FAAH, MAGL) or reuptaken by the cell. More information on the workings of the encocannabinoid system can be found here.
Sexual behaviour
The role of endocannabinoids in the sexual behaviour of males was seen as recent studies done on rats have shown that anandamide (AEA) injections 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 but are dose dependant, meaning that different doses can have opposite effects (3).
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 (Leydig cells). These effects are mediated trough 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 as cells and tissues of female reproductive organs are endowed with a fully functional ECS (7).
Both anadamide 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 cannabinoids (AEA and 2-AG) at crucial times in embryo development and implantation (5). The role of these enzymes is crucial as research has shown, that 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 an important role in the formation of the foetuses 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).
Postnatal suckling and appetite stimulation
Even after we leave the comfort of our mothers 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 breast feeding 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. The researchers also experimented with the co-administration of delta-9-THC which almost fully reversed the effects of the antagonist (9).
Cannabis use in pregnancy
All this research show 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 decremental effect. So the question arises: is cannabis consumption safe during pregnancy?
Women use cannabis during pregnancy for various reasons raging from health (nausea, vomiting, appetite, other 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 is who this effects the baby that the mother is caring.
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 neurobehavioral 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 but we defiantly need more studies to reach a definite conclusion. It seems to contradict the concept of that any disturbances to the ECS during pregnancy can have important consequences. Scientists theorize that maternal marijuana consumption, has significant, yet subtle effects on the offspring due to the framework of the intricate timing requirements and frequently biphasic effects of the (endo)cannabinoids (5).
In the end its 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.
In summary endocannabinoids have a crucial role in all the stages of reproduction and while they are a fine tuned machine, phytocannabinoids don’t seem to have a negative impact on this process.
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