PT-141 (bremelanotide)
To my knowledge, PT-141 is the only substance that has shown any promise in increasing libido, and that's only in the case of women with depressed sexual response.
I think this is only partially correct. One question is how to you would go about operationalising libido in males? For example, one could argue that an intervention that gives a male an erection in the absence of any visual sexual stimuli is for all intents and purposes, an aphrodisiac.
PT-141 (bremelanotide) does seem to have these properties:
Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra®
PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following subcutaneous administration to healthy male subjects and to patients with erectile dysfunction (ED) who report an inadequate response to Viagra®. An inadequate response was defined for this study by patient report indicating that achievement of an erection suitable for vaginal penetration occurred ≤50% of the time while taking 100 mg Viagra®. Erectile responses were assessed by RigiScan™ in healthy subjects in the absence of visual sexual stimulation (VSS) and in ED patients in the presence of VSS. Doses ranging from 0.3 to 10 mg were administered to healthy male subjects, resulting in a statistically significant erectile response at doses greater than 1.0 mg. ED patients were treated with placebo, 4 or 6 mg PT-141 in a crossover design in the presence of VSS. The erectile response induced by PT-141 was statistically significant at both doses. PT-141 was safe and well tolerated in both studies. The erectogenic potential of PT-141, its tolerability profile and its ability to cause significant erections in patients who do not have an adequate response to a PDE5 inhibitor suggest that PT-141 may provide an alternative treatment for ED with a potentially broad patient base.
If some pheromone were effective in increasing libido in men then I would've expected to see a huge market for it and perhaps big pharma creating products that combine PDE5 inhibitors like "Viagra" with pheromones.
You're correct here. In fact, perhaps the closest currently available to this is concomitant administration of PT-141 with PDE-5 inhibitors:
Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response
Objectives To evaluate the safety and pharmacodynamic effect of co-administration of subtherapeutic doses of PT-141, a cyclic heptapeptide melanocortin analogue, and sildenafil to patients with erectile dysfunction.
Methods Nineteen patients with erectile dysfunction who were responders to either Viagra or Levitra by self-report were given 25 mg sildenafil and 7.5 mg intranasal PT-141, 25 mg sildenafil and an intranasal placebo spray, and a placebo tablet and an intranasal placebo spray in a randomized cross-over design. Erectile activity in response to two 30-minute episodes of visual sexual stimulation was assessed by RigiScan during a 6-hour postdose period.
Results The erectile response induced by co-administration of PT-141 and sildenafil was significantly greater than the response elicited by administration of sildenafil alone. Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy.
Conclusions Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated.
EDIT:
As correctly pointed out to me, in the above, I have mischaracterised the presence of an erection with male libido. One should not confuse raging passions for getting a raging clue. This is not a trivial point:
The Subjective Sexual Arousal Scale for Men (SSASM): Preliminary Development and Psychometric Validation of a Multidimensional Measure of Subjective Male Sexual Arousal
Male sexual arousal has been historically
described as a central physiological state, with
penile erection in a sexual context as its most valid
objective measure [21]. Bancroft defines sexual
arousal as a state that is motivated toward experi-
encing sexual pleasure and possibly orgasm, which
involves the processing of relevant stimuli, general
arousal, incentive motivation, and genital response
[22]. A multifaceted process of male sexual arousal
is supported by functional magnetic resonance
imaging data indicating different patterns of brain
stimulation during sexual arousal, penile tumes-
cence, and penile erection in healthy male volun-
teers [23]. Furthermore, studies in men without
sexual dysfunction have demonstrated that penile
erection is not always highly associated with sub-
jective mental aspects of sexual arousal [24,25].
Based on these findings, a lack of subjective sexual
arousal may explain why some men with ED fail to
respond to treatment with PDE5 inhibitors
despite having the physiological ability to achieve
and maintain an erection.
However, my reference to the role of exogenous testosterone may more accurately reflect what is meant by "libido" or sexual desire.
Exogenous testosterone
Alternatively, you might have some measure of sexual interest in males, in which case administration of exogenous testosterone displays efficacy in this regard:
The effects of exogenous testosterone on sexuality and mood of normal men
The effects of supraphysiological levels of testosterone, used for male contraception, on sexual behavior and mood were studied in a single-blind, placebo-controlled manner in a group of 31 normal men. After 4 weeks of baseline observations, the men were randomized into two groups: one group received 200 mg testosterone enanthate (TE) weekly by im injection for 8 weeks (Testosterone Only group), the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks (Placebo/Testosterone group). The testosterone administration increased trough plasma testosterone levels by 80%, compatible with peak testosterone levels 400-500% above baseline. Various aspects of sexuality were assessed using sexuality experience scales (SES) questionnaires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales. In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES (i.e. SES 2) following testosterone administration, but not with placebo. There were no changes in SES 3, which measures aspects of sexual interaction with the partner. In both groups there were no changes in frequency of sexual intercourse, masturbation, or penile erection on waking nor in any of the moods reported. The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo. The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone. However, these changes are not reflected in modifications of overt sexual behavior, which in eugonadal men may be more determined by sexual relationship factors. This contrasts with hypogonadal men, in whom testosterone replacement clearly stimulates sexual behavior. There was no evidence to suggest an alteration in any of the mood states studied, in particular those associated with increased aggression. We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships. Raising testosterone does not increase self-reported ratings of aggressive feelings.
If we consider both testosterone and PT-141 in tandem, sexual awareness and sexual arousal can be dissociated from one another.
Dopaminergic stimulants e.g. meth/amphetamine
There is some evidence from animal studies to suggest that amphetamine increases libido, as operationalised by frequency of sex. Again, I could suffer from the same folly as above where I confuse libido for some other construct, but this is also supported by subjective reports among meth users who like to have sex with other dudes. However, I will need to dig up some references.
Former Nobel laureates and other researchers at Harvard awarded the 2007 Ig Nobel Peace Prize to the creators of the "gay bomb" -- a non-lethal military weapon under development intended to induce demoralizing homosexual behavior with aphrodisiacs.
If the above regarding amphetamines is correct, it would be hilarious to see what effect acute administration of methamphetamine among a male prison population would be.
Marketability of aphrodisiacs in general
One problem is that the current milieu within which drugs are evaluated by the FDA is that a drug will only be approved for sale if it can treat a disease. Any use of the term "aphrodisiac" is effectively a no-no. What I imagine would happen is that eventually the diagnostic criteria for erectile dysfunction would be relaxed considerably, or some equivalent of sexual arousal disorder for males would enter into the vernacular.
I'm a little surprised that recreational use of some combination of testosterone/methamphetamine/PT-141/PDE-5 inhibitors as some sort of sex aid isn't "a thing". Well, I'm sure it is somewhere in the world.
