The effects of cannabidiol on male reproductive system: A literature review

Abstract

Cannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plant Cannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of vertebrates and invertebrates. Thirty‐two citations (in vivo and in vitro) were identified. Among the vertebrates, the studies were carried out with men, monkeys, rats and mice. Studies with invertebrates are centered exclusively on the sea urchin. The CBD treatment periods include mostly acute and subacute evaluations. Exposure to CBD is associated with a reduction in mammalian testis size, the number of germ and Sertoli cells in spermatogenesis, fertilization rates, and plasma concentrations of hypothalamic, pituitary and gonadal hormones. Moreover, chronic doses of CBD have impaired sexual behavior in mice. From the studies identified in this review, it is possible to conclude that CBD has negative effects on the reproductive system of males. However, knowledge is still limited, and additional research is required to elucidate fully the mechanisms of action, as well as the reversibility of CBD effects on the reproductive system.

Statement on safety of cannabidiol as a novel food: data gaps and uncertainties

“…Alterations of testosterone production were substantiated by in vitro data on rat testicular microsomes, which demonstrate inhibition of the steroidogenic enzyme progesterone 17-a hydroxylase. Similar studies in rat liver microsomes suggested that CBD exposure could also alter hepatic metabolism of sex steroids (as reviewed in Carvalho et al, 2020).…”

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges

“…Pre-clinical studies, carried out on animal models, reported acute and chronic adverse effects of CBD on different organs and systems ( Table A2 ) [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ]. There are several highly recommended comprehensive reviews, which critically analyzed the CBD safety and toxicity experiments carried out in animal pre-clinical and human clinical trials [ 53 , 123 , 124 , 125 , 126 , 127 ]. The following important observations should be mentioned: (1) regarding the administration route, in most human trials, CBD was administrated orally or by inhalation, whereas predominantly intraperitoneal (i.p.)…”

“…caused acute CNS toxicity (tremor, sedation, and prostration) within 30 min of injection, whereas prolonged treatment for 9 days elicited bradycardia, hypopnea, cardiac failure, liver weight increase, and inhibition of spermatogenesis [ 113 , 125 ]. For the same model (rhesus monkeys), chronic oral CBD application (30–300 mg/kg/day, 90 days) caused systemic negative effects on the liver, heart, kidneys, and thyroids, and inhibited spermatogenesis [ 113 , 124 , 125 ]. Negative effects of chronic CBD on embryonic development were reported in rats when relatively high doses (75–250 mg/kg/day) were administrated orally during pregnancy, which included developmental toxicity, decreased fetal body weight, increased fetal structural variations, and embryofetal mortality [ 125 ].…”

“…Since CBD is suggested to be included in combined anticancer chemotherapy protocols, CBD’s hepatotoxicity, which can cause changes in drug metabolism, is an issue of special importance. A hepatotoxic effect was documented in pre-clinical and clinical studies when relatively high CBD doses were administrated for a prolonged time [ 53 , 123 , 124 , 125 , 126 , 127 ]. As was revealed by a randomized, double-blind trial that included 171 patients, hepatocellular injury represents the most frequent adverse effect, so it was recommended to test serum transaminases and total bilirubin levels in all patients prior to starting the treatment with Epidiolex ® , which is CBD in an oral solution [ 132 , 133 ].…”

Vapor cannabis exposure generationally affects male reproductive functions in mice

“…or oral gavage (p.o.) to assess the physiological and/or toxicological effects of cannabis (Carvalho et al, 2020). Approximately 120 unique phytocannabinoids are present in Cannabis sativa (Cather and Cather, 2020) and can vary depending on the cannabis chemovars.…”