Muira puama

The herbs Ptychopetalum olacoides or uncinatum are used for a medicince colloquiolly known as Muira Puama or Marapuama (commonly known as Potency Wood) which grows in regions surrounding Brazil and is said to enhance sexual function, especially in older men.^[1] It has usage as both a vitality and sexuality enhancer as well as a nerve tonic, treating chronic degenerative nervous ailments by the Amazonian people.^[2] There is some confusion as to whether 'nervous ailments' refers to the nerves themselves, or to something referred to by the locals as nervous weakness consisting of lassitude, a general lack of desire or motivation, tremors and sexual impotence.^[3][4]

The tree itself is medium-sized (4-5m) and both the roots and bark are sometimes used medicinally.

• Ptychonal and Ptychonal Hemiacetal (exist as mixture and interconvert) in the methanolic extract of bark,^[2] which may exist as a series of related structures with Ptychonal I-IV known and I-II existing as a mixture^[5]
• Kolavelool (and 7-oxo-kolavelool) and Kolavenol^[5]
• 7alpha-hydroxykolavelool and 6alpha-7alpha-hydroxykolavelool^[5]
• Hardwickiic acid and 12-oxo-hardwickiic acid^[5]
• Ptychonolide^[2] (methanolic extract of bark) and ptycho-6alpha,7alpha-diol^[6]
• 20-O-methylptychonal Acetal^[2] (methanolic extract of bark)
• 6alpha,7alpha-dihydroxyannonene and 7alpha,20-dihydroxyannonene^[6]
• 7alpha-hydroxysolidagolactone I^[6]

Ptychonal might be the most active terpenoid, and the terpenoids appear to be the active components at least; not much information on how the constituents relate to biological effects

There are some reports in the past regarding "Muyrapuamin" which state the presence of alkaloids which may be due to taxonomical misclassification; some studies do not note the presence of alkaloids, which do not include the aforementioned diterpenoid structures.^[7]

Some other flavonoids and methylxanthines have been reported.^[7]

One intervention conducted in 202 pre and postmenopausal women (although confounded with the inclusion of Ginkgo Biloba) using 175mg of a 4:1 Muira Puama extract and 16mg Ginkgo per tablet (and either 2 or 6 tablets daily) noted significantly improved scores on a self-assessment of sexuality in 65% of respondents, with 71% of respondents reporting improvement on at least one parameter.^[8] In these women, no significant difference was noted between low and high dose regimens.

The parameters of the survey that improved were frequency of sexual thoughts and fantasies as well as enticement of said fantadies; improvements in sexual frequency and satisfaction with sexual encounters were also significantly improved as were the ability to reach orgasm and the intensity thereof.^[8] Average improvements were 1-1.5 point improvements on a 9-point rating scale, and the average improvements in satisfaction with sex life, ability to reach orgasm, and intensity of orgasm were 27%, 43.5%, and 38% respectively.^[8]

An older study of 262 men (cannot be located online, mentioned in other sources)^[1][9][8] notes improvements in self-reported libido in 62% of men and improved erectile function in 51% of persons following ingestion of 1000-1500mg of a 4:1 concentrated extract of the herb after two weeks.

Two studies on Muira Puama and sexuality in humans noting improvements, although conclusions drawn from these two are limited due to the inclusion of Ginkgo Biloba and the other being unable to be found online; neither study appears to be blinded, but both are compared against baseline (important to note on the topic of aphrodisia)

Appears to be a small to moderate improvement in sexuality in both genders affecting approximately 2/3^rds of participants

Some diterpenoids appear to have NGF-promoting properties, and at 50mcg/mL can induce neurite outgrowth.^[2] Four diterpenoids were tested in PC12 cells and a mixture of ptychonal and ptychonal hemiacetal was able to augment the neurite outgrowth by 20mcg/mL NGF at 0.1, 1, and 10mcg/mL by 14%, 27%, and 40% respectively.^[2] A later study isolated related diterpenes 6alpha,7alpha-dihydroxyannonene and 7alpha,20-dihydroxyannonene and, under the same experimental conditions, found enhancement of neurite outgrowth in a concentration-dependent manner from 0.1uM to 30uM by 21.2-21.3% (1uM) and 135-200% (30uM) respectively; although the latter molecule (7alpha,20-dihydroxyannonene) experienced weak effects until 30uM when it spiked and the former was linearily concentration-depenent.^[6]

May potentiate Nerve-Growth Factor induced growth

A study measuring Brain-Derived Neurotrophic Growth Factor (BDNF) failed to find differences between groups in rats following 800mg/kg ethyl alcohol fraction, although a trend towards a decrease was seen.^[10]

May not influence BDNF

Muira Puama appears to have acetylcholinesterase inhibiting properties, one study using oral administration of Muira Puama (extraction undisclosed) at 300mg/kg or 800mg/kg noted only the latter dose was able to exert acetylcholinesterase effects in the hippocampus (33% in CA1, 22% in CA3) and striatum (17%), Galantamine at 5mg/kg was used as an active control and outperformed Muira Puama.^[11] These areas appeared to correlate with inhibition of the G4 isomer of the AChE enzyme, while inhibition was also noted with G1 in vitro,^[11] and have been noted with injections of 100mg/kg.^[12] These conclusions were later tested at an oral intake of 800mg/kg in mice appeared to prevent Beta-amyloid induced neurodegeneration in hippocampal CA1 neurons and GFAP expression in astrocytes were attenuated to about half (derived from graph) with Muira Puama.^[10]

These studies do not cite the extract due to patent issues (PI0307647-4, US61/297442), but this appears to be an ethyl alcohol:water extract varying between 50:50 and 95:5 characterized by the presence of a marker called Pov-2

Systemic injection of 100mg/kg Muira Puama to aged mice appears to acutely induce anti-oxidative effects in the brain of aging mice.^[13] Relative to saline injections (control), injections of Muira Puama reduced free radicals in the hypothalamus (16.3%) and reduced protein carbonyls in the cerebellum (43%) and striatum (51%); reductions in lipid peroxidation were seen in the frontal cortex, striatum, and hypothalamus assessed by TBARS.^[13] An increase in Glutathione Peroxidase was noted in the hippocampus only, while Catalase appeared to increase universally.^[13]

In response to toxins that induce amnesia, Muira Puama (100mg/kg injections; 800mg/kg oral ingestion) was able to attenuate the effects of MK-801 (NMDA-antagonist) on memory consolidation but failed to exert protective effects on aquisition; Muira Puama abolished the effects of scopolamine, an anti-cholinergic.^[14]

Mechanistically, the pro-learning effects of Muira Puama appear to be mediated via serotonin as Spipirone (5-HT_2A antagonist) appeared to increase the effects of Muira Puama, but not a 5HT_1A antagonist (pindolol).^[15]

Acetylcholine inhibition has been noted at oral doses of 800mg/kg, but not 300mg/kg.^[11]

Finally, one study has noted that Muira Puama was able to augment the toxic doses of yohimbine; a supplement mediated mostly by catecholamine release. This suggests involvement of catecholamines (dopamine and noradrenaline primarily) in the actions of Muira Puama.^[16]

May be mediated via serotonergic mechanisms

Single IP injections of 50-100mg/kg Muira Puama appear to enhance learning (step-down avoidance task) acutely when administrated prior to testing or after, indicating an improvement in short-term memory acquisition and consolidation respectively; these effects were mimicked in part with oral administration of 800mg/kg.^[17] These effects have been replicated over a long period of time with similar doses of 800-1000mg/kg bodyweight oral intake or 50-100mg/kg injections.^[18]

In aged rats, the memory consolidation was restored to the levels of adult control at 50-100mg/kg Muira Puama (800mg/kg oral intake) when measured a day after testing.^[17] This restoration of learning rate in adults appears to extend to the long term.^[18]

Appears to enhance short and long term memory acquisition and consolidation in rats; studies are preliminary

In a model of Unpredictable Chronic Mild Stress (chronic series of random mild stressors^[19]) oral intake of 100 or 300mg/kg (not 50mg/kg) outright prevented the increase in anxiety (outperforming 20mg/kg Imipramine) but did not exert an anxiolytic effect in mice not subject to stress (where Diazepam at 1mg/kg was very effective in doing so).^[7] Stress-induced changes in glycemia were also abolished by either 100mg/kg or 300mg/kg Muira Puama, outperforming 20mg/kg Imipramine.^[7] Resistance to hypoxia, an anti-stress test dependent on hyperventilation, was improved 38-59% at all three doses, with 50mg/kg underperforming 100 and 300mg/kg which were not significantly different (intravenous) or 800mg/kg oral intake.^[7] This study appears to be duplicated in Medline.^[20]

At least one study indicates remarkable adaptogenic effects in a Chronic Unpredictable stress test

One study noted injections of 30, 100, and 300mg/kg Muira Puama was able to (in a dose-dependent manner) induce anxiety-like symptoms in a hole-board test.^[21]

300mg/kg of oral Muira Puama, but not 100mg/kg, decreases immobility in a Forced Swim Test model in rats, although to a lesser degree than the active control of Imipramine at 15mg/kg.^[3] Due to interactions with other drugs tested, it was thought that these anti-depressive effects may be mediated by dopamine D₁ receptors of B-adrenergic receptors.^[3]

May have putative anti-depressive effects

One study conducted in men using 1000-1500mg of a 4:1 extract of Muira Puama noted that 51% of respondents reported an improvement in erectile function after 2 weeks of usage.^[9]

Catuama is a mixture of the herbs Guarana, Muira puama, Trichilia catigua, and ginger (their relative concentrations being 40.31%, 28.23%, 28.23%,, and 3.26% respectively).^[22] This herbal combination therapy has been noted to have vasorelaxing effects in isolated endothelium via nitric oxide^[23] (which has also been noted in the corpus cavernosum^[24]) and has been noted to fully revert ventricular fibrillation in isolated rabbit hearts at 200µg/mL and protected from induced arrhythmia.^[22] This study noted that ginger and guarana in isolation failed to have such effects on the myocardium, but muira puama showed some efficacy although Trichilia catigua at 25µg/mL showed similar potency to Catuama, which outperformed the reference drug of lidocaine at 3μg/mL.^[22]

Catuama has also been associated with anti-depressive effects in rodents associated with preventing monoamine (noradrenaline, dopamine, serotonin) reuptake.^[25]

Muira puama is one of four herbs in Catuama, and may play a role in exerting the anti-depressive effects. It may also contribute to cardioprotective effects, but appears to be less significant than Trichilia catigua. Currently, no synergism between active ingredients has been recorded