Addiction Treatment Blog

Effects of Drugs on Sex

Table of Contents

• Potency
• Orgasm
• Libido
• Aphrodisiacs
• Yohimbine
• Trazodone
• Nefazodone and Cyproheptadine
• Glyceril Trinitrate
• Transcutaneous Absorption
• Intracaversonal Injections
• Bethanecol
• Dyspareunia and Orgasm
• Libido
• Anaphrodisiacs
• Sex Addiction Treatment Clinic
• Do You Need Help?

Potency

The central factor that determines potency is blood supply to the relevant tissues. In general, blood supply increases during sexual activity, leading to tumescence. Anything that interferes with this will compromise performance. Anything that improves this will enhance performance (1,2). In theory, these increases could be brought about by stimulating or blocking a variety of receptors in the penis or vagina on which noradrenaline acts. In practice, drugs that enhance or impair potency appear to do so by acting centrally (in the brain) to increase or decrease noradrenaline release.

Noradrenergic inputs to sexual functioning are mediated through the sympathetic system. This system handles ‘psychogenic’ responses – lubrication or tumescence in response to sexual stimuli. There is also parasympathetic system input, mediated by acetylcholine, which handles the rhythmic inputs to sexuality – the rhythmic increase and decrease in tumescence that takes place, usually unobtrusively throughout the day and night, Either of these systems may be damaged independently.

Orgasm

While erectile responses depend critically on the action of noradrenaline on its receptors, the dopamine and 5-HT systems appear to affect the threshold for ejaculatory or orgasmic responses, so that while not actually responsible for erections, effects on these systems may make erectile and ejaculatory / orgasmic responses more or less likely.

The development of the SSRIs and growing awareness of the changes in sexual functioning associated with their use has triggered off renewed interest in this area, and increased understanding of the various mechanisms involved. In brief, 5-HT is inhibitory to orgasmic functioning, in practice, 5-HT-1 agonists such as buspirone, and 5-HT-2 antagonists, such as cyproheptadine or yohimbine will tend to bring orgasm forward, while 5-HT-1 antagonists, such as the SSRIs, and 5-HT-2 agonists, such as LSD, will delay it in nine out of ten subjects (see 5-HT Receptors and Drugs article). There is a profound interplay between the sexual hormones and 5-HT in this area, such that the sexual hormones mediate their effects by leading to increases or decreases in 5-HT synthesis while, in turn, 5-HT doesn’t act other than in the presence of a normal hormonal milieu (3).

Libido

It can be very difficult to tease apart libido, potency and orgasmic functioning. A change in one will tend to affect the others. But where 5-HT seems responsible for orgasm, and noradrenaline and acetylcholine to be responsible for potency, dopamine appears more responsible for libido.

Aphrodisiacs

For millennia there has been a search for agents which would reliably enhance sexual functioning (4). In general, this has tended to mean agents which increase male potency, although some agents such as cocaine may increase sexual interest quite separately from any effect on potency (see below). Among the agents, most consistently quoted as being aphrodisiac is ginseng, especially powdered ginseng root, which probably acts to increase noradrenaline release.

Another widely cited aphrodisiac is cantharides, also called Spanish fly, which is the dried and ground parts of the Lytta (Cantharis) vesicatoria beetle. This can be sprinkled on the penis and it leads to erections by virtue of being an irritant. It can also be taken orally and when excreted through the kidneys it leads to irritation of the genitourinary passages, which in turn makes erections more likely or prolonged. As it is a frank irritant, the effects are unpleasant.

A wide range of other herbs and vegetables have been cited as aphrodisiac, including garlic, leeks, khat (quat: Abyssinian tea), liquorice and sea-foods, especially oysters. In Japan, the puffer fish or fugu is used; shark fin is sought after elsewhere in the Orient while eels enjoyed the same reputation in the Occident. In the West Indies, the conch is the seafood most used as an aphrodisiac.

Yohimbine

While ginseng and cantharides are better known aphrodisiacs, the agent for which the best evidence was available, before the advent of the SSRIs, was yohimbine. This compound, which is derived from the bark of the yohimbine tree, has a long-standing reputation as an aphrodisiac. Its use, however, was discouraged somewhat in recent years owing to doubts about its efficacy and a concern about possible side effects. However, recent studies (5,6) appear to have laid these doubts and concerns to rest, showing that about two-thirds of men with erectile difficulties respond to it, without troublesome side effects. The theoretical side effects are an increase in blood pressure or in anxiety. These can happen but appear to be infrequent. The response seems better in cases where there appears to be psychogenic component to the problem but is not absent in straightforward cases of organic impairment.

In the case of yohimbine, it seems likely that benefits are brought about by a combination of actions on receptors for noradrenaline and 5-HT. It is both an alpha-2 adrenergic antagonist and a 5-HT-2 antagonist. Each of these systems appear to affect the threshold for erectile and ejaculatory responses, so that, while not actually responsible for erections, effects on these systems may make erectile responses more or less likely.

Trazodone

A compound with a very similar profile, which is more widely available at present, is trazodone. This has been in use in recent years as an antidepressant (see All You Need to Know of Antidepressants blog article). One of the notable side effects of its use as an antidepressant has been priapism (sustained erections). While this side effect has been widely publicised, what has been less touted is the fact that a great number of people, male and female, show an enhancement of sexual interest and potency while on it.

Priapism, which can be a complication of any of these treatments involves erections that fail to reduce over several hours. At present, it is considered that any erections lasting longer than 8 to 12 hours warrant medical attention. The problem is that if such erection are not reduced, there is a risk of damage to the penis owing to a compression of the blood supply to its component tissues, which can lead to cell death. The reduction of priapism involves aspirating blood from the penis by syringe, usually accompanied by the injection of drugs which lead to vasoconstriction (closing down) of the blood vessels in the area.

Nefazodone and Cyproheptadine

Nefazodone is a recently released antidepressant (Dutonin), which has potent 5-HT-2 blocking effects and such can be expected to facilitate orgasms and, perhaps as a consequence, increase libido. It is very similar in its profile of actions to trazodone and to cyproheptadine, which was first developed in the 1950s. This agent increased appetite and improved sleep but failed to find a niche after development, other than as a tonic. It would now seem that along with trazodone, yohimbine and nefazodone, it facilitates orgasm and enhances libido. Neither nefazodone or cyproheptadine, at present, are associated with the development of priapism, possibly owing to their more specific effects on the 5-HT system.

Glyceril Trinitrate

This compound has been used for years for the treatment of angina. Until recently, it was available as a pill, which was put beneath the tongue when chest pain started or was likely. It was quickly absorbed from there and eased pain by dilating the coronary arteries. However, once absorbed, it remains active for several hours and leads to the dilation of a range of arteries throughout the body. This action brings about its most troublesome side effect, headaches.

In an attempt to overcome this problem, a number of companies have produced GTN paste and GTN patches, which can be applied to the chest wall. The drug is absorbed through the skin and leads to a preferential dilation of the coronary arteries. Once the pain is gone, the patch can be peeled away and further absorption stopped. Application of such patches to the penis have been reported to bring about vigorous erections.

Transcutaneous Absorption

Perhaps related to the above are anectodes reported from a variety of places world-wide that the sprinkling of various compounds on the penis may lead to erectile responses. In this case, everything depends on the preparation of the compound. Capsules that can be opened up may be of use where tablets would not be. The antidepressants have been among the compounds used for this purpose. Dothiepin, in capsule form, appears useful. However, other compounds, even though in capsule form, appear relatively ineffective and indeed may cause side effects such as local irritation. At present it is not certain whether those drugs producing useful effects do so by virtue of an irritation they cause, or whether they are absorbed transcutaneously and act that way.

Intracaversonal Injections

One way to get over the problem of absorption through the skin of the penis is to inject compounds into the body of the penis, the corpora cavernosa (the cavernous bodies, one for each side). This is done by plunging a needle into the side of the penis about an inch back from the tip. Surprisingly, it is relatively painless. The method was first described in 1982.

The compound most often administered in this way was papaverine, which is a smooth muscle dilator. Doses range from 20 to 120 mg. Sometimes papaverine is coadministered with drugs, such as phentolamine, that act to increase noradrenaline release from sympathetic nerve endings. More recently, prostaglandin E1, found naturally in the sexual tissues and whose levels increase during sexual activity, has been used. This appears to lead to a lower incidence of priapism.

Apart from priapism, the side effects of intracavernosal injections include bruising, discomfort and more seriously the production of plaques or nodules. Essentially, these latter indicate a proliferation of scar tissue at the site of injection. The exuberant growth of scar tissue is something that can occur after any wound or bum. If it happens on the penis, it can lead to the distortions of its shape. This, however, seems a relatively rare occurrence (7).

The use of prostaglandins to stimulate erectile function in this manner raises the possibility that many analgesics, such as aspirin other drugs used to treat arthritic conditions, which act to inhibit prostaglandin synthesis, might in susceptible individuals lead to impairments of performance. Any screening of people with difficulties therefore should check for this possibility.

Bethanecol

The role of the cholinergic system in erectile and sexual functioning is less certain than the 5-HT and other systems. A series of cases have been reported, however, of sexual dysfunction precipitated by a range of different agents proving responsive to the addition of bethanecol (Myotonine). Bethanecol also appears to have a place in impotence or erectile failure stemming from back-injuries. This may have something to do with the fact that the parasympathetic nerves to the sexual areas travel in nerves from the sacral area of the spine.

Bethanecol has also been reported to reverse problems produced by antidepressants or neuroleptics. This raises the issue of what role the anticholinergic effects of these compounds may have in producing any of the observed problems. Whether the anticholinergic drugs widely used in clinical practice (see The Management of Side Effects blog article) may also produce sexual dysfunction more widely is at present uncertain. One effect that anticholinergic drugs are likely to have is a drying of secretory responses, such as the lubricant fluids produced by both men and women during arousal, which of course would make sexual interaction less comfortable.

Dyspareunia and Orgasm (1,8)

There is a complex functions involved in ejaculation and orgasm as described. While ejaculation itself is a peripheral act, it is linked intimately to a central event, orgasm, so that disruption of one set of functions tends to compromise the other. It is also difficult to disentangle this complex from general questions of libido, or sex drive. Drugs which reduce potency can be expected also to interfere with orgasm and ejaculatory responses. This ranges from agents with anticholinergic side effects causing dyspareunia, by drying up vaginal secretions, to inhibiting erectile or tumescent responses.

While there are areas of overlap, however, there are also clear differences between erectile and orgasmic functions, that have become more apparent with the widespread use of the SSRIs. The commonest effect of the SSRIs on sexual functioning in both women and men is a delay of orgasm. There are varying estimates of the frequency with which happens and the severity of any problem it may cause but the data sheets for the agents involved suggest that up to 80% of individuals taking an SSRI or clomipramine may experience changes in sexual functions. For men, this may be a benefit rather than a problem, as survey suggest up to one-third of men may have problems with premature ejaculation. Contrary to popular mythology, premature orgasm is something that may afflict women also, although the extent of the problem is unknown. Cases of premature ejaculation/orgasm may be treated with an SSRI, whether or not there is a concomitant depression. In this case, a small dose of an SSRI, such as paroxetine 20 mg or clomipramine 10 or 25 mg, taken an hour or two before intercourse, may make an appreciable difference to the length of time intercourse can be sustained before orgasm.

When used in antidepressant doses, the SSRIs and clomipramine may lead to unhelpfully retarded ejaculation in men or anorgasmia in women, in up to 80% of takers. For some men, there may be complete erectile failure. Discontinuing these drugs may also lead to problems with complaints of anorgasmia being replaced by problems with uncomfortable spontaneous orgasms.

Spontaneous orgasm also appears to be a side effect of SSRI in a small portion of takers. This seems to happen because we are all ‘wired up’ slightly differently. In the same way, a few people given a beta-blocker, which slows heart rate in over 90% of cases, will find an increase in their heart rate.

For spontaneous of drug-induced anorgasmia or retarded ejaculation, a number of 5-HT antagonists are currently being used. Of these the one used more frequently is cyproheptadine but, in theory, buspirone should also help, and buthanechol has been reported to be helpful. Whether buspirone or cyproheptadine taken in modest doses shortly before sexual activity will act as specifically as the SSRIs, or whether they have to be taken regularly is uncertain.

Libido

In terms of libido, the primary neurotransmitter appears to be dopamine although both 5-HT and noradrenaline appear to have some role. Thus cocaine, the psychostimulants generally (see The Use of Psychostimulants in Schizophrenia blog article), L-dopa, apomorphine, amantadine, pergolide and bromocriptine, all of which enhance dopaminergic functions, have been reported to bring about increases in libido.

Conversely drugs which reduce the effects of dopamine in the brain will tend to antagonise sexual functioning generally, as well as decrease libido. The most obvious such compounds are the neuroleptics (see The Neuroleptics and Side Effects of Neuroleptics blog articles). It has been estimated that up to 50% of individuals taking neuroleptics have impairments of sexual functioning of some sort. This appears to be dose related, so that the higher the dose of neuroleptics, the likelier the sexual problem. One of these agents, benperidol, has been marketed for the management of hypersexuality, although there is little evidence to suggest that it has anymore marked effects on libido and potency than any of the other neuroleptics.

Other drugs having effects on libido are the sex hormones, in particular testosterone. Surprisingly, testosterone may lead to increases in libido in both men and women – indeed, in women, the androgens (male sex hormones) appear to be primarily responsible for libido. This may be one reasons why a number of takers of contraceptive pills that are hormonally based report a decrease in libido – what is happening in these cases is presumably an alteration in the ratio of androgens to oestrogens, so that there are proportionally fewer androgens.

The ratio of androgens to oestrogens, in both men and women, is also what is likely to determine the incidence of side effects from hormonal preparations. These can include excessive sexual interest and drive ‘masculinization’ – increase in male secondary sexual characteristics, such as facial hair etc.

Broadly speaking the opiates, heroin, morphine, pethidine, etc., have been associated with a decrease in sexual libido. This is perhaps surprising in that papaverine is an opiate, and there are opiate receptors in the sexual tissues. The reduction in libido may be in part a consequence of long-term opiate use often leading to a more general impairment of health and nutritional status, etc. It may also, in part, be a secondary impairment of libido rather than a primary impairment, in that the consuming focus of appetitive interest has become the getting and taking of opiate drugs, and this displaces sexual libido from its usual place in the emotional economy.

Anaphrodisiacs

There are a great number of compounds used mainly for the control of blood pressure that may lead to a reduction in noradrenaline output, and hence to a reduced ability to dilate the sexual blood vessels. These include clonidine, guanethidine and alpha-methyldopa (Aldomet).

In many places, the actions of alpha sympathetic receptors are antagonised by those of beta sympathetic receptors. In this case, one might expect beta-blockers, such as propranolol, to interfere with sexual potency and there are some reports that this is the case, although it is unlikely to be a common effect, as there are far more alpha receptors in the sexual tissues rather than there are beta receptors.

There are also problems associated with some of the neuroleptics that appear to have nothing to do with their effects on libido or dopamine. Chief among these has been the ‘brewers droop’ associated with thioridazine. This appears because of an action on alpha-1 receptors, which reduces blood supply to the sexual vasculature. The incidence of this problem with other neuroleptic remains uncertain.

As mentioned above, the oestrogens antagonise the effects of androgens on libido. Accordingly they are sometimes given to suppress sexual libido. Ordinarily, this is only likely to happen if an individual’s sex drive is such that it has been getting them into trouble. Clinically, however, one occasionally meets individuals who in the past have been given oestrogens for nothing more than worries about masturbation, with shocking consequences such as a relatively permanent development of breast tissue.

The steroid hormones are closely related to the sex hormones – more closely to the oestrogens than to the androgens. A not infrequent side effect of closely to the oestrogens than to the androgens. A not infrequent side effect of steroid therapy, therefore, may be a loss of libido along with a development of female sexual characteristics, such as breast development or milk production.

A number of diuretic treatments (agents aimed at assisting the excretion of body fluid, which are often used in cardiac failure or hypertension) are also closely related to the steroid hormones. The best known of these are spironolactone and Aldactone, whose use may also lead to loss of libido. It would appear, however, that almost all diuretics may lead to sexual problems in about 5% of users. Given that other antihypertensive agents, such as propranolol, and centrally acting agents like clonidine or alpha-methyldopa may also cause sexual problems, it would seem that impairments of sexual functioning are a potential complication of any treatment for hypertension (although the effects of ACE inhibitors in this regard are at present unknown).

Two other agents sometimes given are cyproterone and medroxpyrogestorne. These are synthetic anti-androgens that block brain androgen receptors. They produce a decrease in libido, a reduction in sperm count, an impairment of erectile capacity and decreased ability to achieve orgasm without producing overt feminization. Their use is largely restricted to individuals convicted of sexual crimes.

Antihistamines have also been implicated as having an inhibitory effect on sexual functioning, although the locus of action is uncertain. They may in some cases reduce vaginal lubrication, cause increased breast size in both men and women, and reduce libido generally. Such effects may happen to some extent with the anti-ulcer treatments cimetidine (Tagamet) and ranitidine (Zantac).

References

1. Segraves RT: Effects of psychotropic drugs on human erection and ejaculation. Arch Gen Psychiatry 1989, 46:275-284.
2. Sullivan G, Lukoff D: Sexual side effects of antipsychotic medication: Evaluation and interventions: Hosp Community Psychiatry 1990, 41:1238-1241
3. Kafka MS: Sexual impulsivity. In Impulsiveness and aggression. Edited by Hollander D. Chichester: J Wiley and Sons; 1995.
4. Meyer C: Herbal aphrodisiacs from world sources. Glenwood, Illinois: Meyerbooks; 1986.
5. Riley AJ, Goodman RE, Kellett JM, Orr R: Double blind trial of Yohimbine hydrochloride in the treatment of erection inadequacy. Sexual Marital Ther 1989, 4:17-26.
6. Reid K, Surridge D, Morales A, Condra M, Harris C, Owen J, Fenemore J: Double-blind trial of yohimbine in treatment of psychogenic impotence. Lancet 1987, ii:421-422.
7. Kirby RS: Impotence: diagnosis and management of male erectile dysfunction. BMJ 1994, 308:957-961.
8. Sullivan G, Lukoff D: Sexual side-effects of antipsychotic medication: evaluation and interventions. Hosp Community Psychiatry 1990, 41:1238-1241.