Have you ever heard that women get cranky and crave chocolate during a specific time of the month? Most people know that the menstrual cycle triggers certain behavior, but until recently science has failed to acknowledge that varying levels of hormones in females altered mood, behavior, and cognitive function (ie. memory, concentration, etc.). Because diseases such as Alzheimer’s, anxiety, depression, and arthritis occur more frequently in females, understanding female specific factors in therapeutics remains important.

Estrogen is abundant in the brain and plays an important role in how the brain communicates. Though both men and women have estrogen, its levels only vary in pre-menopausal women as a function of the menstrual cycle (see graph below). Females might not be surprised to hear that they may crave chocolate during certain points in their menstrual cycle, but may not think something like cannabis potency could vary as a result of hormonal fluctuation. However, studies show that the potency of THC on pain relief in female rats increases during times of high estrogen levels. Estrogen appears to play a two-fold effect in cannabis messaging within the brain. First, it increases the conversion of THC to active THC. This means that after THC consumption, more active THC will be produced when estrogen levels are high such as during the pre-ovulatory peak; thus less cannabis may be needed to produce the same effects. Secondly, it changes the availability and excitability of receptors. Since the therapeutic effects of cannabis occur through activation of receptors, the variability in receptors alters the ability of active THC to produce effects such as pain relief, sedation and euphoria. In modern medicine proper dosage is central to the effectiveness of the treatment. So is the case with medical marijuana. This makes understanding the variability in cannabis potency across the menstrual cycle important. This means women may need to experiment with their dosage at different menstrual cycle time points. Estrogen Levels This graph shows the change in estrogen levels across the normal menstrual cycle in pre-menopausal women not using hormonal birth control. Hormonal birth control, pregnancy, breast-feeding, menopause, and menstrual irregularities caused by medication or other reasons will all change variability in estrogen levels. The red line is the average estrogen level for women and the area between the blue and green line represents the range of estrogen levels. Estrogen levels peak right before ovulation, with a smaller rise post ovulation. The extent of change in estrogen levels varies between women and between cycles. This means that some women experience large fluctuations in estrogen and potentially cannabis potency, while others do not.

 

 

For review of other behavioral sex differences see (Craft, 2005) For review on sex differences in pharmacokinetics see (Rubino and Parolaro, 2011) Craft RM (2005) Sex differences in behavioral effects of cannabinoids. Life Sci 77:2471-2478. Rodriguez de Fonseca F, Cebeira M, Ramos JA, Martin M, Fernandez-Ruiz JJ (1994) Cannabinoid receptors in rat brain areas: sexual differences, fluctuations during estrous cycle and changes after gonadectomy and sex steroid replacement. Life Sci 54:159-170. Rubino T, Parolaro D (2011) Sexually dimorphic effects of cannabinoid compounds on emotion and cognition. Front Behav Neurosci 5:64. Tseng AH, Craft RM (2001) Sex differences in antinociceptive and motoric effects of cannabinoids. Eur J Pharmacol 430:41-47. Wakley AA, Craft RM (2011) Antinociception and sedation following intracerebroventricular administration of Delta-tetrahydrocannabinol in female vs. male rats. Behav Brain Res 216:200-206.