**1. Introduction**

*Cannabis* which is a type of marijuana has been used by the people of Indian subcontinent from time unknown [1]. They not only use this herb as a part of holy practice but also use it for recreational purposes [2]. Irrespective of sex, this hallucinogenic agent is used by most part of the world particularly by the populations of South America, India, Bangladesh, and Pakistan from a long time ago [3]. Reports suggesting the roles of *Cannabis* causing systemic neuropathy [4], neuronal disability [5], impaired fetal development [6], and mal-functioning of male reproductive system [7–10] are documented. But no reports available are depicting the effects of marijuana in female reproductive system.

The main causative agent of marijuana/cannabinoids is the endocannabinoid. This is a neutral lipid and highly conserved molecule throughout evolutionary history [11]. They are having different derivatives like anandamide [12], 2-arachidonoylglycerol [13] and Δ<sup>9</sup> -tetrahydrocannabinol (THC) [14]. However, among all of the fatty acid derivatives of cannabinods or endocannabinoids (eCBs) the Δ<sup>9</sup> -tetrahydrocannabinol (THC) has now been established as the most

important hallucinogenic agent of this molecule [15]. There are literatures suggesting the role of this Δ<sup>9</sup> -tetrahydrocannabinol (THC) in regulation of functions of central nervous system and thus regulating the reproductive functions by affecting/ modulating hypothalamo-pituitary-gonadal axis (HPG-axis) [16] *via* its receptor CB1 and CB2 [17]. Now it has been reported that CB1 receptors are localized mostly in whole vertebrate central nervous system (CNS) and some peripheral tissues, whereas CB2 receptors are mostly expressed in peripheral tissues and immune cells, however, they have recently been found also in the CNS [18]. But, with all the advancement in psycho-neuro-endocrine research, till date it is a matter of debate how THC is going to regulate reproductive system at peripheral level. Some literatures suggest that, there is a general agreement on the inhibitory effect exerted by cannabinoids and eCBs on GnRH release [19] Thus, it is affecting the subsequent FSH and LH release in females and impairing female reproduction [20].

But, all the above mentioned reported phenomenon are occurring in the central nervous system and no definitive proof has been reported till date how the enocannabinoids are affecting peripheral reproductive performances in females (in terms of gonadal activity, steroidogenesis, receptor expressions, free radical generations). Thus, aim of the present study was to note the cannabinoid (particularly endocannabinoid) induced oxidative stress and reproductive impairments in female mice specifically taking peripheral reproductive organs (ovary) in consideration.
