water drop

I was asked a few months back by one of my awesome readers to provide more information on this powerful yet vaguely known oil. I put it off for a few weeks because I was in the midst of tapering down my novelettes on November 2014 Top Holistic Health Reads and my 14 page “summary” on A Look At Essential Oils Safety & Children Dosages.

I thought it would take some time to compile information on this hard to pronounce oil. (By the way, it’s pronounced koh-pey-buh, -pahy-buh) I mean this wasn’t a well-researched oil like frankincense (Boswellia serrata), right?! So, today I found some time while waiting for my car to pass inspection. (New brakes are needed! Oh no!! Cedarwood to the rescue!)

I thought I’d start to trudge up some information on this South American oil and I was prepared for some serious digging.

Diving into the studies, I found more than I expected on the mechanisms of this oil. The safety studies were also pretty encouraging. Below is the summary of what I found.

(Due to the FDA regulations, full abstracts are included in italics along with my summaries.)

 

6 Powerful Actions of Copaiba

 Playing a tough basketball game.

 

 

 

 

 

 

1. An In Vitro Study Demonstrated How Various Species of Copaiba Modulate Pathways Related to Inflammation and Oxidative Stress

This study investigated various species of Copaiba (Copifera L. genus) and noted that the main compound in most was the sesquiterpene, beta-carophyllene. (I love sequiterpenes!) Another important constituent was diterpenes. The study demonstrated that copaiba oil inhibited the inflammatory and free radical response of nitric oxide produced by protein-carbohydrate complex, zymosan.

Copaiba oil is an oleoresin obtained from the Copaifera L. genus (Leguminoseae) commonly featured in anti-inflammatory recipe prescribed by Amazonian traditional medical practitioners and featured in Europe and North America pharmacopeias of the past. Chemical and anti-inflammatory activity investigations from the copaiba oils obtained from Copaifera multijuga Hayne, Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke species have proved that, although similar, these oleoresins possess varied composition and anti-inflammatory activity. Chromatographic studies showed that the main compound among sesquiterpenes was beta-caryophyllene (57.5, 19.7 and 40.9%, respectively), followed by alpha-humulene, alpha-copaene, alpha-bergamotene, delta-cadinene, with different amounts in each oleoresin. Among the diterpenes, copalic acid was the main component from Copaifera multijuga Hayne (6.2%) and was found in all the oleoresins studied. In Copaifera cearensis Huber ex Ducke, clorechinic (11.3%) and hardwickiic acids (6.2%) were the major diterpenes while kaurenoic (3.9%) and kolavenic acids (3.4%) predominated in Copaifera reticulata Ducke. The pharmacologic effects of the three oleoresins were evaluated in vitro by measuring the NO production by murine macrophages and in vivo using the zymosan induced pleurisy model in mice. The Copaiba Oil from Copaifera multijuga Hayne (100 mg/kg) was the most potent, inhibiting both NO production and the pleurisy induced by zymosan. The oleoresins from Copaifera cearensis Huber ex Ducke and Copaifera reticulata Ducke were also able to inhibit NO production and the pleurisy but with less intensity.

Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne–a comparative study. J Ethnopharmacol. 2007 Jun 13;112(2):248-54. Epub 2007 Mar 7.

 

2. The “Killer” Diterpenes

When I went for training on the GI Module, a lot of the docs were discussing how hard it is to get rid of parasites. This article abstract discusses the in vitro action of copaiba in human red blood cells against a nasty tropical parasite. I also included the part about the diterpenes found in the species of copaiba that I use with my clients.

Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs.

Excerpt:

All of the diterpene acids from copaiba oil that were screened in this study had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate exhibited the most activity against promastigotes. However, pinifolic acid and kaurenoic acid exhibited the most activity against axenic amastigotes. The isolated compounds agathic acid, kaurenoic acid and pinifolic acid yielded significant increases in plasma membrane permeability and mitochondrial membrane depolarisation. In conclusion, copaiba oil and its diterpene acids should be further explored for the development of new antileishmanial drugs.

Dos Santos AO, Izumi E, Ueda-Nakamura T, Dias-Filho BP, da Veiga-Júnior VF, Nakamura CV. Antileishmanial activity of diterpene acids in copaiba oil. Memórias do Instituto Oswaldo Cruz 2013;108(1):59-64. doi:10.1590/S0074-02762013000100010.

Bugs 

An In Vitro Study on Copaiba Against Tropical Viruses

Another study that extracted different diterpenes from the same species of copaiba reported positive effects of several of them against mosquito-born illnesses:

The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-b-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-b-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95% confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited.

Diterpenos de Copaifera reticulata Ducke com atividade larvicida contra Aedes aegypti (L.) (Diptera, Culicidae). Revista do Instituto de Medicina Tropical de São Paulo. 2008. 50(1), 26-28. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0036-46652008000100006&lng=en&tlng=en. 10.1590/S0036-46652008000100006.

 

3. In Vivo Evidence of Brain Protection from Trauma

A rodent study was done to test if copaiba would protect and preserve damage in their little brains from an induced neurotoxin. Guess what happened? The copaiba yielded good results that suggested neuroprotection:

The oil-resin of Copaifera reticulata Ducke is used in the Brazilian folk medicine as an anti-inflammatory and healing agent. However, there are no investigations on the possible anti-inflammatory and neuroprotective roles of copaiba oil-resin (COR) after neural disorders. We have investigated the anti-inflammatory and neuroprotective effects of COR following an acute damage to the motor cortex of adult rats. Animals were injected with the neurotoxin N-Methyl-D-Aspartate (NMDA) (n = 10) and treated with a single dose of COR (400mg/kg, i.p.) soon after surgery (Group 1) or with two daily doses (200mg/kg, i.p.) during 3 days (Group 2) alter injury. Control animals were treated with vehicle only. COR treatment induced tissue preservation and decreased the recruitment of neutrophils and microglial activation in the injury site compared to vehicle animals. The results suggest that COR treatment induces neuroprotection by modulating inflammatory response following an acute damage to the central nervous system.

I think you’ll find this excerpt interesting on the constituents likely responsible for this effect. I did:

In this study, we provide the first experimental evidence that COR is an anti-inflammatory and neuroprotective agent following an acute damage to the CNS. COR sesquiterpenes, including ?-caryophyllene, are likely responsible for the anti-inflammatory and neuroprotective effects here described. This hypothesis should be investigated in further studies using molecular biology techniques in different in vitro and in vivo experimental models of CNS disorders. Considering that ?-caryophyllene is already an FDA-approved food additive, these natural sesquiterpenes have an enormous potential to decrease the burden of inflammation-induced damage following neural and nonneural diseases. (COR is copaiba resin)

(If you really want to geek-out, read the whole study for the mechanisms involved and how they compared copaiba’s efficacy to a certain antibiotic.).

Guimarães-Santos A, Santos DS, Santos IR, et al. Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury. Evidence-based Complementary and Alternative Medicine?: eCAM 2012;2012:918174. doi:10.1155/2012/918174.

 

4. A Mechanism Reported For Modulating Pain Pathways

This in vitro study demonstrated that copaiba has peripheral and central effects on pain pathways.

Copaiba oil resins are extensively commercialized in Brazil as capsules or crude oil and used as anti-inflammatory and anti-septic. Comparative pharmacological studies between different species of Copaiba oils are scarce. In the present work we compared the antinociceptive activity of two Amazonian Copaiba oils (Copaifera multijuga Hayne and Copaifera reticulata Ducke, Fabaceae) administered by oral route using peripheral (acetic acid-induced abdominal writhing and formalin), spinal (tail flick) and supra-spinal (hot plate) models. Results demonstrated that the Copaiba oils did not develop toxic effects. Doses ranging from 30 to 150 mg/kg were enough to significantly develop peripheral antinociceptive effect. All Copaiba oils demonstrate central activity but with less effect on supra-spinal regions of the brain. Administration of the opioid receptor antagonist, naloxone completely inhibited the antinociceptive effect induced by both Copaiba oils. Our results indicate that Copaiba oils demonstrate peripheral and central antinociceptive effect. This new comprobate effect may be useful in the treatment of algesic disorders.

Antinociceptive activity of Amazonian Copaiba oils (abstract). Journal of Ethnopharmacology. 2007. 109 (3): 486-492. doi: 10.1016/j.jep.2006.08.018

 

5. Copaiba’s Protective Effect When Used with Chemotherapy Agent in Pregnant Mice

This study reported on the protective effect against malformations induced with a chemotherapy agent in mice:

Cyclophosphamide is an anti-neoplastic chemotherapy drug which, when administered to animals during the gestational period, provokes visceral, skeletal and external malformations. Copaiba oil obtained from Copaifera L. genus is traditionally used in popular medicine for its anti-inflamma- tory and antimicrobial activities. However, the effect of copaiba oil onteratogenesis remains unknown. This study aimed to investigate the possible protector effects of copaiba oil on the model of teratogenesis induced by cyclophosphamide in mice. Pregnant female Swiss mice were divided into 8 groups (n = 15). Three groups received copaiba oil, via gavage, in the following doses: 0.3 mL?Kg?1, 0.6 mL?Kg?1 and 0.9 mL?Kg?1 (b.w.), associated to phosphate-buffered saline (PBS), intraperitoneal (i.p.). The negative control group received medium chain triglyceride (MCT) and PBS. The positive control group received cyclophosphamide (30 mg?Kg?1 (b.w.)) and MCT. The three treatment groups called associated groups (A) received one of the doses of copaiba oil, via gavage and an associated dose of cyclophosphamide intraperitoneally. Copaiba oil presented a protective effect against teratogenesis induced by cyclophosphamide in the following skeletal structures: metacarpals, forepaws proximal phalanges, and tail vertebras. It also reduced the hydrocephalus frequency. These data suggest that copaiba oil could be a potential candidate for an anti-teratogenic agent.

Effects of Copaiba Oil on Cyclophosphamide-Induced Teratogenesis in Mice American Journal of Plant Sciences. 2014. 5:23. DOI:10.4236/ajps.2014.523362

stress or relax

 

 

 

 

 

 

 

 

 

6. In Vivo Evidence of Its Calming Effect

A mice study reported on copaiba’s ability to calm mice while not negatively impacting activity level.

OBJECTIVES-Copaiba oil oleoresin exuded from Copaifera reticulata Ducke (CRD) is commonly used in anti-inflammatory, healing and anti-tumoral folk medicines. The purpose of this study was to investigate the putative anxiolytic effect of acute administration of CRD.
METHODS-CRD was administered (100, 400 and 800 mg/kg, p.o.) to male Wistar rats submitted to the elevated plus-maze model of anxiety using an ethopharmacological analysis.
KEY FINDINGS -In comparison with control rats, CRD increased the percentage of entries in the open arms over the entire dose range tested (vehicle, 33.6 +/- 4.5; CRD 100 mg/kg, 44.67 +/- 3.68; CRD 400 mg/kg, 47.2 +/- 2.3; CRD 800 mg/kg, 50.7 +/- 2.2) and the percentage of time spent in the open arms of the elevated plus-maze at the highest dose (800 mg/kg) (vehicle, 26.4 +/- 5.7; CRD 800 mg/kg, 52.0 +/- 2.7). A standard anxiolytic, diazepam (3 mg/kg, p.o.), was used as a positive control. In a similar way, diazepam increased the percentage of entries and time spent in the open arms when compared with vehicle (% open entries: vehicle, 45.4 +/- 1.3; diazepam, 50.7 +/- 1.9; % time spent in open arms: vehicle, 28.2 +/- 0.9; diazepam, 38.9 +/- 1.2). Regarding ethological measures, CRD at the highest dose (800 mg/kg) reduced peeping out (anxiety-related behaviour) (vehicle, 3.1 +/- 0.6; CRD, 0.9 +/- 0.2) and increased end-arm activity (vehicle, 0.2 +/- 0.2; CRD, 2.0 +/- 0.4), indicating an enhanced tendency of the rats to explore actively the potentially dangerous areas of the maze. Diazepam decreased peeping out (vehicle, 3.3 +/- 0.3; diazepam, 1.0 +/- 0.2) and flat-back approach (vehicle, 0.8 +/- 0.2; diazepam, 0.2 +/- 0.1) and increased end-arm activity (vehicle, 0.3 +/- 0.1; diazepam, 2.5 +/- 0.3) and head-dipping (vehicle, 8.2 +/- 0.4; diazepam, 12.0 +/- 0.5).
CONCLUSIONS -These data showed, for the first time, that acute treatment with CRD copaiba oil produced a dose-dependent anxiolytic-like effect over the dose range tested, on conventional and ethological parameters, without adversely affecting general activity levels.

Acute effect of Copaifera reticulata Ducke copaiba oil in rats tested in the elevated plus-maze: an ethological analysis. J Pharm Pharmacol 2009 Aug; 61(8) :1105-10.

 

I didn’t want to stop there!

Girl on phone

Here’s More Interesting Studies on Various Species and Chemotypes of Copabia

  • Promising Study for Tissue Repair in Rodents: Effects of the topical administration of copaiba oil ointment (Copaifera langsdorffii) in skin flaps viability of rats. Acta Cirurgica Brasileira, 2013. 28(12), 863-869. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502013001200009&lng=en&tlng=en. 10.1590/S0102-86502013001200009.

 

  • In Vivo Study Assessing for Treating Pneumothorax or Malignant Pleural Effusion: Westphal FL, Canzian M, Pieri FA, et al. Pleurodesis Induction in Rats by Copaiba (Copaifera multijuga Hayne) Oil. BioMed Research International 2014;2014:939738. doi:10.1155/2014/939738. Read full study here.

I found it interesting how this study with copabia showed that it promoted healing by inducing inflammation. Inflammation is initially a process of acute healing which turns on the immune response. Most of the studies I’ve listed demonstrate the opposite effect. What I infer from this contrast is that copaiba may have the power to modulate the immune system towards what direction towards it needs at time.

 

  • In Vitro and Rodent Studies for a Healthy Smile:
    • Bacteriostatic effect of copaiba oil (Copaifera officinalis) against Streptococcus mutans. Braz. Dent. J. 2012. 23( 1 ): 36-38. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-64402012000100006&lng=en. http://dx.doi.org/10.1590/S0103-64402012000100006.
    • Dias-da-Silva MA, Pereira AC, Marin MC, Salgado MA. The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats. Journal of Clinical and Experimental Dentistry 2013;5(4):e169-e173. doi:10.4317/jced.51104.

 

  • A Human Double-Blind Clinical Trial with Acne: Application of the essential oil from copaiba (Copaifera langsdori Desf.) for acne vulgaris: a double-blind, placebo-controlled clinical trial. Altern Med Rev. 2012 Mar;17(1):69-75. http://www.altmedrev.com/publications/17/1/69.pdf

 

  • Study in Rats with Endometriosis: Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii). Acta Cirurgica Brasileira. 2011. 26(Suppl. 2), 20-24. Retrieved December 07, 2014, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502011000800005&lng=en&tlng=en. 10.1590/S0102-86502011000800005.

 

  • Protective Effect on Liver Toxicity in Rats Dosed to Acetaminophen Toxicity: Effect of copaiba oil in hepatic damage induced by acetaminophen in rats. Acta Cirurgica Brasileira, 2014. 28(7), 526-530 http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502013000700008&lng=en&tlng=en. 10.1590/S0102-86502013000700008.
  • (Note: in this in vivo trial, there was some evidence of elevated bilirubin; however, toxicity of the liver wasn’t reported.)

 

What About Safety?

In an experiment with mice, doses of up to 2,000mg/kg were administered, and there was no evidence of DNA damage or alteration in red blood cells.

Copaiba oil-resin, extracted from the trunk of Copaifera, and traditionally used in folk medicine in the treatment of various disorders, has been shown to be an effective antiinflamatory, antitumor, antitetanus, antiseptic and anti-blenorrhagea agent. As, there are few studies evaluating its genotoxicity, this aspect of the commercial oil-resin, and its volatile and resinous fractions, were evaluated in mice by comet assay and micronucleus (MN) test. A single dose of oil resin, volatile or resin fractions (500; 1,000 or 2,000 mg/kg b.w.) was administered by gavage. The chemical compositions of Copaiba oil resin and its fractions was analyzed by gas chromatography. According to comet assaying, treatment with either one did not increase DNA damage, and as to MN testing, there was no alteration in the incidence of micronucleated polychromatic erythrocytes. Chromatographic analysis of the oil-resin itself revealed sesquiterpenes, diterpenic carboxylic acid methyl esters and high levels of ?-caryophyllene. Thus, it can be assumed that the oil resin and volatile and resinous fractions from the commercial product are not genotoxic or mutagenic.

Almeida MR, Darin JDC, Hernandes LC, de Souza Ramos MF, Antunes LMG, de Freitas O. Genotoxicity assessment of Copaiba oil and its fractions in Swiss mice. Genetics and Molecular Biology 2012;35(3):664-672. doi:10.1590/S1415-47572012005000052.

 

Rat Pregnancy Safety Study

Up to 15 drops a day was noted as safe in this study. There were some reports of lowered food intake, weight gain, decreased fetal body weight, and skeletal variations at higher doses, but no incidences of deaths or fetal malformations at any level.

The oleoresin of the copaiba tree (Copaifera sp., Fabaceae) is traditionally used in Brazilian herbal medicine to treat a variety of illnesses and symptoms. This study, conducted according to the OECD Guideline 414, provides data on the developmental toxicity of oleoresin from C. reticulata (COPA-R) in rats. Pregnant Wistar rats (25 per dose group) were treated by gavage with COPA-R (0, 500, 1000 and 1250 mg/kg bw/day) on gestation days (GD) 6-19 and Caesarean sections performed on GD20. Implantations, living and dead fetuses and resorptions were recorded. Half of the fetuses from each litter were examined for visceral abnormalities and the remaining were cleared and stained for skeleton evaluation. COPA-R was maternally toxic (reduced food intake and weight gain) and embryotoxic (lower fetal body weight and increased occurrence of fetal skeleton variations) at the two highest doses, but did not cause embryo deaths or fetal malformations at any dose level. The study derived an oral no-observed-adverse-effect-level (NOAEL) for maternal and developmental toxicity induced by COPA-R of 500 mg/kg bw/day. The results suggest that copaiba oleoresin does not pose a health risk to pregnant women when used according to the recommended doses (up to five drops, three times a day).

Developmental toxicity of copaiba tree (Copaifera reticulata Ducke, Fabaceae) oleoresin in rat. Food Chem Toxicol. 2011 May;49(5):1080-5. doi: 10.1016/j.fct.2011.01.015.

So, copaiba has some pretty interesting science behind it with variety of mechanisms.
I’ve used it successfully by applying 1-2 drops on location for minor aches and pains and for calming with good success.

I’m interested in hearing your experiences. I’ll keep you updated on my Facebook page as more studies are released, I’ll be specifically looking for more human clinical trials as this oil becomes more popular!

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Disclaimer: This information is applicable ONLY for therapeutic, Grade A essential oils. This information DOES NOT apply to essential oils that have not been AFNOR and ISO standardized. There is no quality control in the United States and oils labeled as “100% pure” need only contain 5% of the actual oil. The rest of the bottle can be filled with fillers and sometimes toxic ingredients that can irritate the skin. This information is for information purposes only and is not intended to diagnose, treat, or prescribe for any illness.

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