Prosexual Enhancement

The Search for Prosexual Substances, Aphrodisiacs,
Sexual Enhancing Herbs and More...

The search for prosexual substances, aphrodisiac herbs and other substances that enhance sexual desire, performance, and enjoyment is probably as old as the human race itself. Some really work; others are mere legend. Scientific studies conducted in recent years have gone a long way toward isolating the crucial physiologic factors involved in sexual arousal, thus helping narrow the search for these substances. Consider the exciting results of a clinical trial recently published by two urologists.

The 15 men in the study had several things in common. First, they were all relatively young - under 65 years of age - and in relatively good health. None of them had severe hypertension, nor were any of them taking medication for high blood pressure. They were not heavy smokers, and their vascular systems were in relatively good shape. The most important thing they had in common, and the reason they entered this study, was a long-standing inability to have erections.

Under the direction of two urologists, Adrian Zorgniotti, M.D., of the New York University School of Medicine, and Eli F. Lizza, M.D., of the University of Medicine and Dentistry of New Jersey, the men began a four-week long trial during which they were given 2.8 g of arginine/day or a placebo and kept a diary of how they felt, with special focus on their sexual behavior.

During the first two weeks of the study, none of the men reported anything out of the ordinary. During the second two weeks, though, something began to happen. By the end of the second two weeks, six of the men were reporting a marked improvement in their ability to perform sexually. Specifically, their erections were harder and longer-lasting than they had been before, and they were now able to achieve vaginal penetration, where this had been impossible before. Moreover, these men were able to sense that something was different when comparing the first and last two weeks of the study. None of the men reported any unpleasant side effects.¹ What was the difference between the first and second phases of this study? During the first two weeks, the capsules the men took contained cellulose, a placebo. During the second two weeks, unbeknownst to the men, the capsules each contained 1,400 mg of the amino acid L-arginine.

Molecule of the Year

The latest round of excitement about arginine has been triggered by strong indications from a wide variety of research studies that arginine is a key player in the physiology of sexual performance in both men and women. Arginine has been the focus of increasing interest since the early 1980s when its use was first popularized as a safe and effective way to increase the amount of growth hormone (GH) released from the pituitary gland. GH is now well-known to retard many aspects of aging by increasing lean muscle mass, decreasing fat storage, strengthening bones and bringing skin back to a youthful thickness and flexibility.² Later, scientists discovered that arginine could also enhance immune function and accelerate healing in people undergoing major surgery.^3,4

But arginine didn't really take off until the early 1990s. That's when scientists discovered that arginine was the primary supplier of nitrogen (N) atoms which the body uses to create molecules of a simple gas known as nitric oxide (NO). As NO research has exploded in recent years, it is now being widely acclaimed as one of the most important molecules in the body.

In 1992, Science magazine named NO as "Molecule of the Year." One researcher, in summarizing what is known about it observed in The Lancet, that "NO research is now riding on a crest of enthusiasm.... So far the basic research on NO has only just begun to make an impact on clinical medicine."⁵ Another called work on NO, "One of the hottest, most exciting things in neurobiology. Now a new kind of neurotransmitter turns out to be a gas. Good God!"⁶

What's all the excitement about?

Many people have heard about NO's dark side. Just a decade ago, NO was thought of only as a toxic by-product of automobile exhaust and other sources that contributed to serious air pollution, caused acid rain, and destroyed the ozone layer. Although NO is indeed dangerous in high concentrations (as are many otherwise safe and useful natural substances), in the human body, it exists only in tiny amounts and plays a vital role in many important bodily functions. Many recent studies have confirmed that NO:

• Is a major factor in the control of blood pressure
• Boosts immune function
• Kills cancer cells and microorganisms
• Helps control muscular activity, balance, and coordination

While these functions are all of crucial importance, what really grabbed the imagination of Zorgniotti, Lizza, and other researchers was a substantial body of evidence indicating that NO is the primary physiological mediator of penile erection.⁷ Putting all the pieces together, the picture looks like this:

• Dietary arginine is the primary source of nitrogen molecules for NO.
• Without arginine in the diet, there would be no NO.
• Without NO, there would be no erections.
• Arginine, via NO, may also play a significant role in sexual function for women.

Greater Staying Power and Intensity

While Zorgniotti & Lizza's small pilot study employed men with impotence probably due to cardiovascular disease, there is every reason to believe that arginine supplementation can also enhance the sexual performance of men and women with normal sexual performance.

According to numerous anecdotal reports from highly satisfied arginine users since the early 1980s, dietary L-arginine can give men erections that are bigger, harder, more frequent, and longer lasting. Some men also report that L-arginine gives them greater endurance. In women, L-arginine has been reported to increase the intensity of sensation during sex. One highly athletic 30-something woman tells about the time she told her doctor about her L-arginine use. "My doctor almost fell off his chair when I told him how many times a night I do it - six-times," she said. "He's definitely taking arginine now, too."

Enhanced Libido

Both men and women have remarked about the way L-arginine increases their libido, or desire for sex. Exclaimed one 21-year-old woman when asked about arginine, "My god, that stuff! I had to stop taking it. I was doing it with every guy that came along!" While her reaction may have been a bit extreme, some women have been reported to have given L-arginine to their husbands who had lost interest in sex and soon found they had a rearoused mate on their hands.

The Erection Builder

The prosexual effects of L-arginine are directly related to its ability to generate NO.⁸ NO molecules are produced on demand inside generator cells, such as the endothelial cells that line the inside of artery walls. An NO molecule is generated when an enzyme called NO synthase (NOS), which is abundant in these cells, strips away a nitrogen atom (N) from a passing L-arginine molecule and combines it with an oxygen atom (O).

Since NO molecules have a very brief life span (their half-life is measured in seconds), their site of activity has to be very close to home. NO formed in arterial endothelial cells passes directly and immediately to adjacent smooth muscle cells that surround the artery. This causes them to relax and leads to a reduction in blood pressure. A constant seepage of NO molecules is now identified as being crucial for controlling blood pressure.⁵ The more NO that is present, the lower the blood pressure. If NO levels drop, however, blood pressure will rise.

When people have hypertension (high blood pressure) because their arterial endothelial cells are damaged and cannot make NO (a common finding in cardiovascular disease), their blood pressure drops soon after they receive an intravenous infusion of L-arginine.⁹

Dr. Salvador Moncada, research director at Wellcome Research Laboratories, has pointed out that if you place a drop of NO on a sample of muscle tissue that encircles a blood vessel, the tissue instantly relaxes. Relaxation of the muscle cells surrounding an artery allows more blood to flow through.

Moncado calls NO a "universal transducer." This means it is a kind of universal biochemical interpreter that translates chemical /electrical messages from one form to another.¹⁰

Thanks apparently to its relaxing effect on smooth muscle cells, NO is now widely recognized as the major - if not the sole - neurochemical responsible for causing penile erections. Although acetylcholine (ACh) in the parasympathetic nerves that serve the penis has long been thought to be the major neurotransmitter (called cholinergic transmission) responsible for causing the penis to become erect, the most recent findings do not support this conclusion.

Cholinergic neurotransmission is certainly important for erections, but it is not the final step in the process. In laboratory experiments, blocking the activity of these cholinergic nerves does not necessarily affect the ability to have an erection. If you bypass the cholinergic switches, for example, you can still incite an erection in an experimental animal by electrically stimulating the appropriate nerves in the appropriate place, i.e., "downstream" from the cholinergic neurons.¹¹ Evidence suggests that when NO contacts a vascular muscle cell, it stimulates the formation of a potent secondary messenger molecule called cGMP.⁷ However, if you disrupt NO synthesis by applying chemicals that interfere with NOS activity, you can completely prevent erections by any means. NO synthesis can be restored after blocking NOS by supplying additional L-arginine.¹¹

Dr. Arthur Burnett, a urologist at The Johns Hopkins University Medical School and a leading NO researcher, calls NO an "unconventional form of signal transduction," but an "essential chemical trigger in producing erections." "It's like turning on a light switch," he says. Noting that all you need to light up a room are wires, lamps and light bulbs, he adds, "It is the switch that starts the process."¹² To light up your sexual life, it seems, you need to flick on your NO switch.

To really understand the value of NO in erections, it helps to understand how erections happen in the first place. Men get erections when sexual thoughts originating in the brain initiate a flow of nerve signals down the spinal cord to the arteries and smooth muscle in the penis. Upon receiving these signals, the arteries that supply the penis dilate and the muscles that control the two rods of sponge-like tissue filling the core of the penis - the corpora cavernosa and the corpus spongiosum - relax.

As the arterial muscles relax, they allow an increased flow of blood through the penile arteries, and this blood quickly fills the spongy space. The penis becomes and remains erect because the rapid inflow of blood raises the pressure in the penis and compresses the veins that normally drain the blood from the penis, preventing any significant outflow. The more blood that fills the penis, the larger and harder the erection will be because as long as blood is flowing in rapidly through the arteries, the outflow remains severely restricted. The penis returns to its flaccid state when the penile arteries constrict, relaxing pressure on the veins and allowing the blood to drain out.

All these activities are under the control of NO molecules. The nerves that serve the spongy tissue and the penile arteries are, not surprisingly, rich in NOS. Thus, when you become sexually aroused, the NOS-rich nerves leap into action, kicking the conversion of L-arginine to NO into overdrive. The relatively large amounts of NO produced quickly diffuse to nearby arteries and smooth muscle, causing them to dilate and relax. NOS can be activated by a number of common substances released from nerves. In fact, this is what ACh normally does.

The role of NO in penile erection has been studied in a variety of animal and in vitro (test tube) experiments. In one animal study, Dr. Wayne Hellstrom and colleagues at the Tulane University School of Medicine injected one of three drugs into the corporal cavernosal tissue of primates. Two of the drugs, s-nitrocysteine (NO-CYS) and sodium nitroprusside (SNP), are direct sources of NO molecules. The third, acetylcholine (ACh), stimulates NOS to produce NO. For all three drugs, as the dose increased, so did the length, duration and hardness of the erections.¹³ Doing the same thing to cats gives a similar result.¹⁴ "Nitric oxide donors show promise in the treatment of cardiovascular disease, hypertension and vascular impotence," Hellstrom et al concluded.¹³ Many people have experienced the prosexual effects of an NO-donating drug without even realizing it. That drug is amyl nitrate, which has been popular as a potent and short-acting vasodilator when inhaled. Many people inhale amyl nitrate just prior to sex. By rapidly lowering blood pressure, it can cause a momentary light headedness as well as a large and rapid influx of blood into genital tissues in both men and women. In so doing, it has been reported to significantly intensify the physiologic sensations.

How Does Arginine Work in Women?

While anecdotal reports indicate that L-arginine has potent prosexual effects in women as well as men, the actual mechanism of action in women has not been defined as clearly. In female rats, NO release initiates a chain of events that begins with the pulsatile release of luteinizing hormone-releasing hormone (LHRH), followed by the release of LH, which leads to ovulation and also to behaviors like lordosis, which attract the male and facilitate mounting. Giving rats a drug that inhibits the production of NO (by blocking NOS activity), breaks this chain of behavior.¹⁵ Another rat study showed that NO produced in the rat uterus keeps the uterine muscle from contracting during pregnancy, but not during delivery and that NO levels were controlled by the female hormone estrogen.¹⁶

Yohimbe: Legendary Sexual Enhancer

Corynanthe Yohimbe is the botanical name for a tree that grows in West Africa. For centuries - perhaps millennia - the folk medicine practiced by tribes in this region and the nearby West Indies has included a tea distilled from the inner bark of this tree. The brew is used to amplify male virility and sexual prowess. It is the traditional fuel for intense tribal sex ceremonies reported to last as long as half a month - rituals which might never have been possible but for the power of this concoction.¹⁷

Not Just for Impotence Anymore

Current scientific and medical literature offers a rather limited portrayal of yohimbine's sexual properties in human beings that focuses almost exclusively on the treatment of male impotence. These discussions leave untouched the broad range of intense prosexual effects widely reported by men who have no sexual dysfunction at all. An impressive body of anecdotal evidence surrounds the use of yohimbe and yohimbine (the active ingredient in yohimbe) for making good sex even better. The recent history of yohimbe and yohimbine has followed a contorted path marked by confusion and reversal. A prescription impotence pill called Afrodex containing small quantities of yohimbine and other compounds was withdrawn from the American market in 1973 due to controversy about efficacy and safety.¹⁹

In the '60s, '70s, and early '80s, the existing literature on yohimbine often acknowledged that it could facilitate erection but usually claimed that it had no impact on libido.¹⁹ These sources stated that yohimbine was therefore definitely not a real aphrodisiac. Such pronouncements persisted until a widely acclaimed animal study published in 1984 provided strong evidence that yohimbine stimulates libido (at least in male rats) and thereby qualifies as a true aphrodisiac.²⁰

The next few years saw the publication of a series of studies concerning yohimbine's efficacy in treating male impotence.^21-24 FDA approval for this indication soon followed, and, after a 20-year absence, yohimbine reappeared on the roster of drugs that could be dispensed legally by prescription.

Perhaps the most historically significant aspect of these events was the appearance in the Physicians' Desk Reference of the following words: "It may have activity as an aphrodisiac."²⁵ However tentatively phrased, this sentence is almost surely the first appearance of the term "aphrodisiac" in any edition of the PDR - which lists only those indications for a drug that have been sanctioned by the FDA - as well as its first use for decades in information released officially by a pharmaceutical firm. The second coming of prescription yohimbine became an opportunity for many physicians and medical authorities to warn the public against purchasing over-the-counter herbal yohimbe products (which had remained available during the decades of yohimbine's absence from approved medicine). These cautions were issued based on the questionable assertion that the herbal alternatives supposedly contained so little - if any - yohimbine hydrochloride as to offer no possibility of therapeutic benefit.

But when the technical director of the U.S. Food and Dairy Labs performed a chemical analysis of ten different mail-order brands of herbal yohimbe, expecting the results to prove this claim definitively, all of the samples turned out to contain significant quantities of yohimbine hydrochloride. In fact, most of these brands featured more yohimbine per capsule than the 5.4 mg contained in one prescription tablet. Better yet, in terms of cost per unit of yohimbine, many of the herbal extracts offered a better deal than the pharmaceutical products.

Now that both yohimbine and its herbal antecedents have emerged from this checkered history with their value firmly established, these chemical "comeback kids" are doubtless here to stay. And although herbal preparations containing this compound have a long history of traditional use in other cultures, yohimbine has so recently appeared in modern medical practice that, as far as contemporary Western society is concerned, it is considered a new prosexual drug.

How Does it Work?

Yohimbine's primary path of action duplicates a biochemical event believed to play a key role in producing male erection. Yohimbine acts upon a very specific network of nerve cells called the alpha-2 adrenergic system (a subsystem of the larger adrenergic system, so named because its functions are closely tied to the hormone adrenaline). Yohimbine effectively shuts down the alpha-2 adrenergic system by blocking receptor sites for the neurotransmitters that stimulate its activity. This blockade could be compared to placing tape over a light-switch to prevent the lights from being turned off.

Research has indicated that a natural alpha-2 adrenergic blockade performed by the body's own chemicals is part of the normal physiology of erection. According to theory, inhibition of the alpha-2 adrenergic system should increase the flow of blood through arteries into the penis, while at the same time decreasing the flow of blood out from the penis through veins. It may also result in higher levels of the neurotransmitter ACh, which as noted earlier, causes erections by stimulating the production of NO in the arteries that supply the penis.

In addition to promoting erection, yohimbine's blockade of alpha-2 adrenergic receptors is probably the central means by which this compound stimulates sex drive. Recent research has demonstrated that the adrenergic system affected by yohimbine is a critical factor in libido and sexual behavior.^20,26,27

Further explanation for yohimbine's prosexual properties comes from a recent study with humans showing that this compound increases blood levels of the neurotransmitter norepinephrine by 66%.²⁸ Norepinephrine stimulates the brain's sex center in the hypothalamus and is usually considered one of the body's natural prosexual chemicals. (Ironically, yohimbine was once believed to inhibit release of norepinephrine.)

Surprisingly, animal studies have demonstrated that the heightened sex drive induced by yohimbine does not involve an increase in testosterone levels.²⁹ Furthermore, this compound stimulates sexual activity in castrated male rats with negligible testosterone, as well as in female rats during the non-receptive stage of their sexual cycle (when testosterone levels are quite low).³⁰ Apparently, yohimbine's libido-enhancing power is quite independent of this hormone, which is commonly credited with a crucial role in sexual motivation.

Rats Revisited

In several experiments conducted by various researchers, yohimbine has consistently produced an impressive acceleration of sexual activity in male rats. Perhaps the most remarkable finding of these studies was the stimulation of mating behavior by yohimbine in rats that had previously displayed no sexual activity at all.²⁰ Yohimbine also increased the percentage of sexually inexperienced male rats able to achieve ejaculation in their first sexual encounter with a female - thereby meeting researchers' criteria for successful completion of the mating act.

As mentioned earlier, it was believed until fairly recently that yohimbine did not stimulate sex drive. Oddly enough, scientists maintained this conclusion even though yohimbine had already been shown to facilitate sexual behavior among animals. This effect, however, was attributed not to increased sex drive, but instead to one of two other factors. It was seen either as one manifestation of a generalized behavioral stimulation that was not specifically sexual in nature, or as a response to the penile erections induced by yohimbine.

For Whom Does it Work Best?

There have been some interesting results regarding yohimbine's varying success rates among the different groups of male patients with impotence. In one study, for instance, yohimbine demonstrated much greater efficacy for relatively mild, short-term problems with erection than for the longer-lasting, more severe cases.^18,21

A more surprising finding occurred when researchers then compared yohimbine's relative success in treating the two major diagnostic categories of impotence: psychogenic impotence, which results from psychological issues; and organic impotence, which can be traced to an underlying medical problem.

Treatment approaches for these two types are usually very different. Quite unexpectedly, yohimbine produced the same overall response rate in both categories. In fact, yohimbine's level of success for psychogenic impotence was roughly equal to that of sex therapy and marital counseling - two commonly recommended approaches to this type of problem.²⁴

Yohimbine & Age-Related Male Sexual Decline

One experiment was performed specifically to find out whether yohimbe could restore the flagging libidos of aging male rats. The researchers reported that yohimbine increased the rate of sexual activity in a group of such animals according to all of the criteria used for this type of measurement. In fact, the older rats reached a level of sexual vigor that was comparable to that observed in a group of much younger males. Neither of these groups, however, managed to match the pace of a third team benefiting from the combined advantages of both youth and yohimbine.³¹ Elderly men suffering from chronic problems with erection participated in a month-long controlled study using relatively high doses of yohimbine. Thirty-four percent of those given the yohimbine experienced improvement, as compared with only 5% of those given placebo. This response rate falls well within the guide lines and range reported by other impotence studies with yohimbine.

However, the patients in this trial were advanced in age and featured a particularly high incidence of medical conditions that can interfere with male potency. Given these factors, researchers found the response rate of 34% encouraging. Furthermore, although many medications cause a greater frequency of side effects among the aged, the fairly high doses of yohimbine used here produced "only a few and benign side effects" among the elderly men who participated.²¹

What About Women?

Although yohimbine is known primarily as a treatment for male impotence, we were nevertheless surprised that the literature researched for this article did not contain a single reference to yohimbine's effects in women. The only even remotely relevant statement was found in the PDR: "Generally, this drug is not proposed for use in females."²⁵

The very absence of data in this area leaves open the possibility that this substance may offer substantial prosexual benefits to women. (Most prosexual drugs, after all, appear to work for both sexes.) And the few isolated bits of evidence that we have managed to gather - from animal research and personal interviews - hint at exciting prospects.

A study published in 1985 reports that "yohimbine induced mounting in . . . nonreceptive female rats." In other words, this compound stimulated sexual activity in female rats during a stage of their sexual cycle normally characterized by the complete absence of such behavior - a noteworthy finding. In a study with female rats in heat, yohimbine was able to counteract the suppression of sexually receptive behavior induced by another compound.³²

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