Adaptive Value

Adaptive Value - degree to which a characteristic benefits an organism by increasing its reproductive success

Reproductive hormones

Marijuana smoking is associated with the suppression of luetnizing hormone (LH)* secretion and shortened luteal phase in women (Mendelson et al., 1986).  Marijuana smoking also causes reductions of LH and testosterone plasma levels, leading to impotence and reduced sperm count in men (Kolodny et al., 1974).  Female and male genital tract fluids contain significant concentrations of endocannabinoids (Schuel et al., 2002a).  Smoking marijuana thus suppresses the mechanisms for regulating the hypothalamic- pituitary- gonad axis.  The presence of endocannabinoids and cannabinoid receptors suggest an important role for endocannabinoids in regulating the reproductive tract.  CB1 receptors are present in Leydig cells and  involvemed in testosterone secretion (Wenger et al., 2001).
*  Luteinizing Hormone (LH) is synthesized and secreted by gonadotropes in the anterior lobe of the pituitary gland. It is necessary for proper reproductive function. In females, an acute rise of LH levels triggers ovulation. In the male, it stimulates leydig cell production of testosterone

Endocannabinoids and Embryo Development/Implantation/Initiation of the Suckling Response

Endocannabinoid signalling via CB1 regulates cleavage of mouse eggs, oviductal transport of preimplantation embryos, blastocyst hatching from the zona pellucida, and implantation of blastocysts into the uterine mucosa (Schuel, 2006).  The expression of anandamide in the oviduct and uterus interacts with the developing embryo to ensure maternal preparation is coordinated with preimplantation embryo development and embryo implantation (Paria, 2002).  Failure of proper endocannabinoid signalling to occur results in ectopic pregnancy, where the embryo remains in the fallopian tube (Wang, 2004).  The anandamide gradient is controlled by FAAH (fatty-acid acyl hydrogenase), which is responsible for breaking down the endocannabinoid anandamide is formed from NAPE through a cleavage by the enzyme phospholipase-D (PLD).  The anandamide precursor with enzyme processor PLD is termed NAPE-PLD.  The image below demonstrates the gradient of FAAH to NAPE-PLD necessary for the embryo to survive.  Interestingly, Low FAAH in circulating maternal lymphocytes has been shown to be an early (<8 weeks of gestation) predictor of spontaneous abortion in humans (Maccarrone and Finazzi-Agrò, 2004)

The endocannabinoid system is essential for the initiation of the suckling response in mice, as demonstrated by receptor blockades.  If by day two the suckling response is not formed, the mouse will never developl the suckling response.  This finding compliments both what we know of endocannabinoid's initiation of feeding and  a baby-disease NOFTT, called Non-Organic Failure-to -Thrive, for up to now no reason for this disease had been found.

diagram of spermatozoon

Diagram of a Spermatozoa From:

Sperm and How they are like Neurons

Sperm, like neurons, have functional cannabinoid receptors. Human sperm express CB1 (but not CB2) in the head and middle section of the sperm. The activation of this receptor by anandamide reduces sperm motility and inhibits capacitation-induced acrosome reaction* (AR) (Rosato et al, 2005).  Cannabinoids and endocannabinoids negatively influence sperm functions.  Cannabinoids inhibit fertilization in the sea urchin by reducing the fertilizing ability of sperm (Schuel et al., 2002b). It is well known that marijuana smokers show an alteration in fertility potential. This could be due at least in part to a negative influence on the mechanisms regulating the hypothalamic-pituitary-testicular axis, but also to a direct inhibitory effect of cannabinoids on human sperm.  

Sertoli cells (the cells that nurture sperm maturation in the testes) in mice have been shown to express a complete endocannabinoid system (Macarrone, et al., 2004).  In mammals, ejaculated sperm is not automatically prepared to fertilize an egg.  Once the sperm are in the female reproductive tract, they become ‘capactiated' by undergoing a series of maturational changes including changes on the head enabling it to bind to the zona pellucida** and changes in the tail of the sperm, giving them motility (Yanagimachi, 1994).  

The presence of AEA, its precurors, and its processing enzymes in boar sperm has been demonstrated (Macarrone et al., 2005).    The authors present convincing evidence that the AEA present in both seminal plasma and uterine fluids functions to prevent premature capacitation in freshly ejaculated sperm through a mechanism regulated by the CB1 receptor.  Sperm are exposed to progressively reduced concentrations of AEA in the proximal female genital tract (Schuel etl al., 2002b).  By the time the sperm reach the oviduct, the sperm would be under capacitating conditions, with lowered AEA concentrations to allow for increased motility, metabolism, and the ability to fertilize the egg.   Endocannabinoids have been shown to reduce sperm motility by reducing the mitochondrial energetic output in sperm (Rosatto et al., 2005).  Furthermore, available data suggest that communication between eggs and sperm via AEA helps prevent polyspermy in animals ranging from sea urchins to humans by inhibiting sperm acrosomal release.  Cannabinoids modulate acrosomal release in sperm through a mechanism seemingly identical to that by which they inhibit neurotransmitter release from neurons.  For more information on how sperm are like neurons see the minireview a tale of two cells: Endocannabinoid-signaling regulates functions of Neurons andSperm (Schuel and Berckman, 2005).  In summary, a conserved physiological role for the endocannabinoid inhibition of sperm motility appears well-supported (Cobellis et al., 2006). 

*  The acrosome reaction (AR) occurrs when the sperm fuses with the zona pellucida, releasing digestive enzymes to allow the genetic contents of the sperm to enter the egg's cyptoplasm.

**  The Zona Pellucida is a glycoprotein membrane surrounding the plasma membrane of an oocyte.  This structure binds spermatozoa (sperm) and is required to initiate the acrosome reaction.

The Authors' Behavioral Conjectures

While a role for the endocannabinoid system in successful reproduction, one cannot help but postulate based on what we know.  If sex resulted in an increased concentration of endocannabinoids, it would facilitate a (possibly addictive) dopamine-reward response to sex similar to that involved in food, alcohol, and opiate reward (all of which are modulated by the endocannabinoid system).  Also, it would have an anxiolytic effect that would keep a femal reclining and inactive while the sperm would make their way toward an egg and away from the crucial area where they might spill out of the female stands up.  An increase in endocannabinoids would facilitate a decrease in peripheral metabolism and a reduction in motility.