Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice

Carvalho, Renata Karine de; Souza, Maingredy Rodrigues; Santos, Mateus Pereira dos; Guimarães, Francisco Silveira; Pobbe, Roger L.H.; Andersen, Mônica Levy; Mazaro-Costa, Renata

doi:10.1016/j.reprotox.2018.06.013

Cited by 42 publications

(17 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this context, a recent study showed that repeated cannabidiol administration during adolescence (0.5, 1, or 5 mg/kg from PND 30-60) did not alter body weight and did not promote motor or metabolic side effects in rodents (Peres et al 2018), in line with the present results, and suggesting cannabidiol, both acutely and/or repeatedly seems to be well tolerated during adolescence. Moreover, cannabidiol (15 and 30 mg/kg, oral administration during 34 days, PND 21-55) did not alter body weight in mice (Carvalho et al 2018). Interestingly, when revising the current literature exploring the effects of cannabidiol in adult rats, some prior studies suggested that while acute cannabidiol did not affect body weight (de Morais et al 2018), its repeated treatment decreased body weight in rodents (e.g., Ignatowska-Jankowska et al 2011;Santiago et al 2019), an effect that was prevented by a CB 2 receptor antagonist (Ignatowska-Jankowska et al 2011).…”

Section: Discussionmentioning

confidence: 90%

Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

2020

View full text Add to dashboard Cite

Rationale Cannabidiol is a non-psychoactive phytocannabinoid with great therapeutic potential in diverse psychiatric disorders; however, its antidepressant potential has been mainly ascertained in adult rats. Objectives To compare the antidepressant-like response induced by cannabidiol in adolescent and adult rats and the possible parallel modulation of hippocampal neurogenesis. Methods Male Sprague-Dawley rats were repeatedly treated with cannabidiol (3, 10, and 30 mg/kg) or vehicle (1 mL/kg) during adolescence (postnatal days, PND 27-33) or adulthood (PND 141-147) and exposed to 3 consecutive tests (forced swim, open field, two-bottle choice) that quantified behavioral despair, anxiety, and sucrose intake respectively. Results Cannabidiol induced differential effects depending on the age and dose administered, with a decreased sensitivity observed in adolescent rats: (1) cannabidiol (30 mg/kg) decreased body weight only in adult rats; (2) cannabidiol ameliorated behavioral despair in adolescent and adult rats, but with a different dose sensitivity (10 vs. 30 mg/kg), and with a different extent (2 vs. 21 days post-treatment); (3) cannabidiol did not modulate anxiety-like behavior at any dose tested in adolescent or adult rats; and (4) cannabidiol increased sucrose intake in adult rats. Conclusions Our findings support the notion that cannabidiol exerts antidepressant-and anorexigenic-like effects in adult rats and demonstrate a decreased potential when administered in adolescent rats. Moreover, since cannabidiol did not modulate hippocampal neurogenesis (cell proliferation and early neuronal survival) in adolescent or adult rats, the results revealed potential antidepressant-like effects induced by cannabidiol without the need of regulating hippocampal neurogenesis.

show abstract

Section: Discussionmentioning

confidence: 90%

Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

2020

View full text Add to dashboard Cite

show abstract

“…Apart from its purported salutary effects, accumulating evidence from pre-clinical in vivo studies and large-scale clinical trials, implies that CBD may elicit several potentially negative health outcomes. Specifically, numerous reports have demonstrated neurological, cardiovascular and reproductive toxicities subsequent to CBD use [6,7,8,9,10,11,12,13,14]. The authors of a large clinical trial that utilized CBD (dose regimen 2.5–30 mg/kg/day) to treat 278 patients with Dravet syndrome reported adverse events in 93% of subjects [15].…”

Section: Introductionmentioning

confidence: 99%

Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model

et al. 2019

View full text Add to dashboard Cite

The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg for 10 days (sub-acute toxicity). These doses were the allometrically scaled mouse equivalent doses (MED) of the maximum recommended human maintenance dose of CBD in EPIDIOLEX® (20 mg/kg). In the acute study, significant increases in liver-to-body weight (LBW) ratios, plasma ALT, AST, and total bilirubin were observed for the 2460 mg/kg dose. In the sub-acute study, 75% of mice gavaged with 615 mg/kg developed a moribund condition between days three and four. As in the acute phase, 615 mg/kg CBD increased LBW ratios, ALT, AST, and total bilirubin. Hepatotoxicity gene expression arrays revealed that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways and drug metabolizing enzymes. In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD.

show abstract

“…In one study of male mice, chronic CBD exposure resulted in a decreased sexual behavior, as demonstrated by a reduced number of mounts and ejaculations, whereas THC exposure has been linked to a heightened sexual behavior in female mice. 26 , 27 Ultimately, the effect of cannabis chemovar on sexuality is not well defined and should be further explored. Finally, cannabis use can induce an altered perception of time, potentially leading to artificially prolonged feelings of sexual pleasure and excitement.…”

Section: Discussionmentioning

confidence: 99%

A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men

Bhambhvani

Kasman

Wilson-King³

2020

Sexual Medicine

View full text Add to dashboard Cite

Introduction Cannabis is the most commonly used drug in the United States; however, the effects of cannabis use on male sexual function are poorly understood. Aim To characterize the contemporary landscape of cannabis use and to assess the associations between male sexual function and the frequency of use, the primary method of consumption, or cannabis chemovar (tetrahydrocannabinol or cannabidiol) among current users. Methods We surveyed adults who visited a single cannabis dispensary for baseline demographic information, medical history, cannabis use habits, and sexual function as assessed by the International Index of Erectile Function (IIEF). An IIEF-5 < 21 was considered erectile dysfunction. Main Outcome Measures The main outcome measure of the study was male sexual function via the IIEF domain scores. Results A total of 325 men completed the survey with a mean age of 46.7 years. 71.1% of the men were Caucasian and 52.6% were married. 13 men (4%) were never users; 29 men (8.9%) used 1–2 times/week; 51 men (15.7%) used 3–5 times/week, and 232 men (71.4%) used 6+ times/week. The average IIEF-5 score was 22.3 with 19.4% of the men having erectile dysfunction. In univariate analysis, men using cannabis more frequently had a higher overall IIEF (65.36 vs 60.52, P = .001), erectile domain (27.32 vs 25.74, P = .03), orgasm domain (9.08 vs 8.12, P < .001), intercourse satisfaction domain (12.42 vs 11.31, P = .006), and overall satisfaction domain (8.11 vs 7.05, P = .002). In multivariable analysis, compared to men who used cannabis 0 times/week, those who used 6 times/week had an increased overall IIEF (69.08 vs 64.64, P -value adjusted = 0.02), intercourse satisfaction domain ( P -value adjusted = 0.04), and overall satisfaction domain ( P -value adjusted = 0.02). The primary method of consumption (eg, smoking, edibles, etc.) and cannabinoid composition (eg, cannabidiol vs tetrahydrocannabinol dominant) were not associated with sexual function. Conclusion We report an association between the increased frequency of cannabis use and increased male sexual function. However, while the increased frequency of use was statistically significant with regard to the IIEF scores, the clinical significance of this is likely low, and selection bias may limit the generalizability of these findings. The method of consumption and cannabis chemovar were not associated with sexual function. Bhambhvani HP, Kasman AM, Wilson-King G, et al. A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. J Sex Med 2020;8:436–445.

show abstract

Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice

Cited by 42 publications

References 41 publications

Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model

A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men

Contact Info

Product

Resources

About