Elsevier

Archives of Medical Research

Volume 32, Issue 3, May–June 2001, Pages 221-226
Archives of Medical Research

Original article
Naltrexone-Induced Augmentation of Sexual Response in Men

https://doi.org/10.1016/S0188-4409(01)00279-XGet rights and content

Abstract

Background

To ascertain the role of endogenous opioids in sexual response, naltrexone, an opiate receptor antagonist, was administered to men, and its effect on selected self-report measures of sexual response to masturbation was recorded.

Methods

The data are based on results from 20 healthy, sexually active (alone or with a partner) men, aged 20–29 years, who ingested naltrexone (25 mg/day × 3) or placebo in a randomized, double-blind crossover design. There was at least a 14-day interval between drug and placebo treatment. Between 18 and 22 h after the most recent dose of drug or placebo, subjects viewed sexually explicit videos in privacy for 2 h. They were instructed to masturbate and have as many orgasms as desired. The following three different self-report measures of their responses were recorded: number of orgasms; intensity of sexual arousal, and orgasmic intensity.

Results

Under the naltrexone condition, the volunteers experienced a significantly greater mean number of orgasms (3.4 ± 0.2 SEM) than under the placebo condition (2.6 ± 0.3). The total number of orgasms was 67 under the naltrexone condition and 51 under the placebo condition. At the first orgasm, the measure of intensity of arousal was significantly greater in the naltrexone (3.9 ± 0.2) than placebo (3.4 ± 0.2) condition, and the measure of orgasmic intensity was significantly greater in the naltrexone (3.7 ± 0.2) than in the placebo (3.0 ± 0.3) condition.

Conclusions

The present study provides evidence that endogenous opioids modulate orgasmic response and the perceived intensity of sexual arousal and orgasm in men. The findings suggest that naltrexone could be clinically useful in cases of inhibited sexual desire and erectile dysfunction.

Introduction

Sexual arousal in men peaks prior to orgasm and usually declines rapidly immediately after orgasm, at which time there is a loss of desire during which the majority of the physiologic changes observed during orgasm revert to the pre-stimulation state 1, 2, 3. The pleasure and tension reduction associated with orgasm are evident reinforcers of sexual behavior. Which substances mediate these psychophysiologic phenomena?

Intravenous acute bolus administration of opiates, heroin, or morphine produces an orgasm-like subjective effect. With a higher dose, a pharmacogenic orgasm has been described (4). By contrast, chronic opiate usage produces erectile dysfunction, delayed or absent ejaculation, and/or a marked decrease in sexual desire 4, 5. Some addicts attempt to utilize the sexual inhibitory effect of opiates by titrating heroin administration. Some men with premature ejaculation utilize low doses of opiates to delay their ejaculation, although they experience loss of erection at higher doses (5).

Erectile dysfunction and decreases in both ejaculation and libido are reported in users of heroin, morphine, and methadone 6, 7, 8, 9. By contrast, in a single-blind placebo-controlled study, the opiate receptor antagonist naltrexone (50 mg/day) was reported to significantly increase the frequency of morning erections and spontaneous full penile erections in patients with idiopathic erectile dysfunction. Naltrexone treatment has also significantly increased the number of occurrences of coitus compared to placebo (10). When seven middle-aged men were given naltrexone (25–50 mg) for idiopathic erectile dysfunction, six reported return of erectile function as well as nocturnal penile tumescence. One man reported an increased frequency of ejaculation that was grossly deficient earlier (11). The observation that naltrexone facilitates the ejaculatory response suggests that endogenous opioids normally exert an inhibitory effect on ejaculation (12).

Administration of synthetic β-endorphin can induce profound analgesia, sedation, and euphoria in patients with intractable pain 13, 14. Genital (vaginal) stimulation also produces potent analgesia in laboratory animals (15) and in women (16). Women who reported experiencing an orgasm with vaginal self-stimulation had markedly increased pain tolerance thresholds and pain detection thresholds. By contrast, in women who reported that vaginal self-stimulation was neither pleasurable nor uncomfortable these thresholds showed only a slight increase (17). When animals are injected with large doses of opiate narcotics, enkephalin, or β-endorphin, either systemically or intracisternally in brain, a state of immobilization and generalized muscular rigidity is produced, accompanied by seizure discharges in the limbic system: effects that are reversible with naloxone (18). During orgasm, spasm of the various muscle groups is maximal and muscle tension declines rapidly once orgasm has passed. Not only the extent, but also the intensity, of these spasms, which have both tonic and clonic phases, vary considerably and in their most extreme forms resemble generalized convulsions, leading Kinsey and colleagues to compare such an orgasm with an epileptic seizure (3).

These findings led to an hypothesis that in humans there could be a paucity of endogenous opioids during sexual arousal followed by a sudden release of endogenous opioids, which could account for the euphoria of orgasm, post-orgasmic analgesia, and the subsequent transient loss of sexual desire, i.e., the refractory period (19). These events resemble the effects of the exogenous opiates heroin and morphine, suggesting that endogenous opioids modulate human sexual arousal, orgasm, and the refractory period. The present study was designed to test this hypothesis by ascertaining the effect of naltrexone, an opiate receptor antagonist, on sexual arousal, intensity of orgasm, and duration of the refractory period in men.

Section snippets

Methods

The research protocol was approved by the Maritosexual and Reproductive Research Institute (MARRI) Ethics Committee for Human Subjects (July 20, 1997). Participants were selected from among subjects who visited MARRI in Pune, India. Only heterosexual men between the ages of 18 and 30 years who came to the Institute for pre- or postmarital contraceptive advice or for information on sexually transmitted diseases were considered eligible for the study. Informed consent was obtained from all

Number of orgasms

As shown in Figure 1, the group mean (±SEM) number of orgasms was significantly greater during naltrexone treatment (3.4 ± 0.2) than during placebo treatment (2.6 ± 0.3) (p <0.0001, correlated t test) (25). The total number of orgasms for the 20 participants was 67 under the naltrexone condition and 51 under the placebo condition.

Arousal intensity

As shown in Figure 2, there was a significant overall effect of orgasm number declining over time (two-way ANOVA for repeated measures: F = 48.6, df = 4, 39 p <0.0001)

Discussion

The present findings, i.e., that the number of orgasms and the intensity of sexual arousal and orgasm were greater under the naltrexone condition than the placebo condition, imply that endogenous opioids may normally inhibit sexual arousal and sexual activity and prolong the post-orgasmic period. These findings are consistent with reports that in men, opiate usage depresses, whereas opiate withdrawal increases, libido 5, 26, 27, and that in three of six men, the opiate receptor antagonist

Acknowledgements

We are indebted to Drs. Pralhad Patki, Arvind Phadke (B.J. Medical College, Pune), Shivdeo Bapat (MMF Joshi Hospital), and Bhooshan Patwardhan (University of Pune) for their valuable help in conducting the research. Special thanks to Dr. Beverly Whipple (Rutgers–The State University of New Jersey) for her guidance in preparing the manuscript.

References (36)

  • J. Bancroft

    Human sexuality and its problems

    (1989)
  • B. Zilbergeld

    The new male sexuality

    (1992)
  • T. Crenshaw

    Sexual pharmacologydrugs that affect sexual functioning

    (1996)
  • P.J. Cushman

    Sexual behavior in heroin addiction and methadone maintenance. Correlation with plasma luteinizing hormone

    N Y State J Med

    (1972)
  • J. Mintz et al.

    Sexual problems of heroin addicts

    Arch Gen Psychiatry

    (1974)
  • D. Paar

    Sexual aspects of drug abuse in narcotic addicts

    Br J Addiction

    (1976)
  • J.A. Goldstein

    Erectile function and naltrexone

    Ann Intern Med

    (1986)
  • J. Hetta

    Effects of morphine and naltrexone on sexual behavior of male rat

    Acta Pharmacol Toxicol Suppl

    (1977)
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