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            <sup>9</sup>
            -Tetrahydrocannabinol Increase Plasma Testosterone Concentrations in Mice

Dalterio, S.; Bartke, Andrzej; Mayfield, D.

doi:10.1126/science.6264607

Cited by 33 publications

(11 citation statements)

References 22 publications

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“…Other investigators showed that AEA and THC produce similar biphasic responses on Ca 2þ channels in neurons, testosterone secretion in vivo and in vitro, phagocytosis in neutrophils, blastocyst implantation in vivo, trophoblast outgrowth in culture, and behavior of mice (Burstein et al, 1978;Dalterio et al, 1981Dalterio et al, , 1983Mackie et al, 1993;Wang et al, 1999; Munro et al (1993), f Bouaboula et al (1993). NR, not reported.…”

Section: Discussionmentioning

confidence: 99%

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Schuel

Burkman

Lippes

et al. 2002

Molecular Reproduction Devel

128

123

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Ejaculated mammalian sperm require several hours exposure to secretions in female reproductive tracts, or incubation in appropriate culture medium in vitro, before acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also known as anandamide, is a novel lipid-signal molecule that is an endogenous agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by high-performance liquid chromatography/mass spectrometry. Sperm are sequentially exposed to these reproductive fluids as they move from the vagina to the site of fertilization in the oviduct. Specific binding of the potent cannabinoid agonist [3 H]CP-55,940 to human sperm was saturable (K D 9.71 AE 1.04 nM), suggesting that they express cannabinoid receptors. R-methanandamide , a potent and metabolically stable AEA analog, and (À)D 9 tetrahydrocannabinol (THC), the major psychoactive constituent of Cannabis, modulated capacitation and fertilizing potential of human sperm in vitro. AM-356 elicited biphasic effects on the incidence of hyperactivated sperm motility (HA) between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM) it stimulated HA. Both AM-356 and THC inhibited morphological alterations over acrosomal caps between 2 and 6 hr (IC 50 5.9 AE 0.6 pM and 3.5 AE 1.5 nM, respectively). Sperm fertilizing capacity, measured in the Hemizona Assay, was reduced 50% by (1 nM) AM-356. These findings suggest that AEA-signaling may regulate sperm functions required for fertilization in human reproductive tracts, and imply that smoking of marijuana could impact these processes. This study has potential medical and public policy ramifications because of the incidence of marijuana abuse by adults in our society, previously documented reproductive effects of marijuana, and the ongoing debate about medicinal use of marijuana and cannabinoids.

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Section: Discussionmentioning

confidence: 99%

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Schuel

Burkman

Lippes

et al. 2002

Molecular Reproduction Devel

128

123

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“…In a survey of 60 men Halikas et al (1982) reported 68% felt marijuana improved the quality of their orgasm, 39% believed erection duration improved and 90% reported a global sexual improvement. The mechanism may be linked to elevated testosterone levels as shown by Dalterio's mouse model in which there was an acute rise in serum testosterone with THC (Dalterio et al 1981). …”

Section: Marijuanamentioning

confidence: 99%

Drug-Induced Male Sexual Dysfunction

Brock

Lue

1993

Drug Safety

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Impotence, defined as the consistent inability to maintain an erect penis of sufficient rigidity for sexual intercourse, has been estimated to affect 10 million American men. An age dependence has been shown to exist, with 25% of men over age 65 affected. A large body of clinical experience and published reports in the literature link many commonly prescribed drugs with sexual dysfunction. Drugs can affect sexual function at a variety of points such as inhibition of ejaculation or sedation/depression leading to reduced libido. Antihypertensive drugs have been most commonly associated with impotence. There have been reports of sexual dysfunction with almost all classes of antipsychotics, but little clinical investigation has been performed. Other drugs associated with sexual dysfunction include digoxin, clofibrate, cimetidine and various hormonal agents and antineoplastics. An important first step in approaching all impotent patients is the taking of a detailed medical, surgical, sexual and drug/substance abuse history. The least invasive form of therapy should be employed. Recent studies have shown intracavernous injections of alprostadil (prostaglandin E1) to be safe and effective for long term use. Vacuum constriction devices may also be of help. Better and more durable prostheses are now available should other treatment be unsuccessful.

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“…an immediate low ering following treatment with a subsequent marked recovery. In studies with male mice, Dalterio et al [23] have reported that acute oral administration of THC had a biphasic effect on plasma testosterone concentrations, causing rapid sustained increases at low doses (5 mg/kg) and subsequent decreases at high doses (50 mg/kg). This is consistent with our finding of increased testosterone levels at 5.0 mg/kg THC or 15 mg/kg CME, and sug gests that dose, time of administration of cannabinoid, as well as feeding pattern would all contribute to diurnal changes in circulat ing androgens.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cannabinoids on Function of Testis and Secondary Sex Organs in the Fischer Rat

Morrill¹,

Kostellow²,

Ziegler³

et al. 1983

Pharmacology

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Chronic oral treatment of young adult male Fischer rats with Δ⁹-tetrahydrocannabinol (THC), 1, 5 and 25 mg kg^–1 day^–1, or crude marihuana extract (CME), 3, 15 and 75 mg kg^–1 day^–1, reduced body weight gain by about 50–80% at the high CME or THC dose and was correlated with decreased food intake. When cannabinoid was administered early in the light cycle (9–11 a.m.), cauda epididymis sperm count and seminal vesicle fluid and fructose content were depressed to 50–65% at the high dosages but were not significantly different from those of pair-fed controls. Administration late in the light cycle (4–5 p.m.) depressed epididymal sperm count, seminal vesicle fluid content, and weight of testis, seminal vesicles and epididymis to 40–80% below that seen for pair-fed controls. 24 h after the last treatment, serum testosterone was unchanged in intubated control and low-dose treated rats, compared with untreated controls, but was elevated nearly twofold in medium-dose-treated rats (p < 0.05). The results indicate that time of cannabinoid administration as well as feeding pattern are critical in studies of the rat reproductive system.

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Δ ⁹ -Tetrahydrocannabinol Increase Plasma Testosterone Concentrations in Mice

Cited by 33 publications

References 22 publications

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Drug-Induced Male Sexual Dysfunction

Effects of Cannabinoids on Function of Testis and Secondary Sex Organs in the Fischer Rat

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Δ 9 -Tetrahydrocannabinol Increase Plasma Testosterone Concentrations in Mice

Cited by 33 publications

References 22 publications

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Evidence that anandamide‐signaling regulates human sperm functions required for fertilization

Drug-Induced Male Sexual Dysfunction

Effects of Cannabinoids on Function of Testis and Secondary Sex Organs in the Fischer Rat

Contact Info

Product

Resources

About

Δ ⁹ -Tetrahydrocannabinol Increase Plasma Testosterone Concentrations in Mice