panaceachronicles

Pure, Natural Coca Leaf – A Healing Gift Of The Divine Plant

Tag Archives: Cannabis medicine


by Leave a comment

Holistic Terpenes & Healing Forests: The Science Behind The Entourage Effect

Sanrakuso at Kansho-in Temple

Are you as tired as I am of smug drug warriors who have all the research dollars locked up and then sneer that the Cannabis community can’t prove what we all know to be true because there isn’t any research? Well, now maybe there is – at least a little.

I’ll wait for others to voice their thoughts, but I’m thinking the research we’ll cover in this post means no more “You can’t prove it” bullshit about the Cannabis Entourage Effect from Pig Pharma & their federal shills.

The studies cited throughout this blog post reference terpenes and other phytochemicals found in the natural emissions and vapors of “Forest Bath” environments and prove their wide-ranging efficacy as inhaled and absorbed therapeutic & healing agents.

(Please see my previous post for a full discussion of “Forest Bathing” and Cannabis.)

The “Forest Bath” research also shows clearly that the healing potential of this class of phytochemicals is far from fully understood.

These same “Forest Bath” terpenes and other phytochemicals, exactly the same ones, are found in Cannabis emissions and vapors, in almost the same proportions, and they vary among Cannabis strains the same way that emissions from tree species vary among Healing Forests.

Hundreds of peer-reviewed scientific and medical research studies support the therapeutic validity of the ancient practice of Forest Bathing. Perhaps this same body of science, properly interpreted, would allow the Cannabis community to checkmate the anti-Cannabis propagandists and their scientific pretensions with some solid, relevant data. The planet is tight.

A Little Background

The totality of “Forest Bath” research provides precisely the range of scientific experimental evidence needed to validate ancient Cannabis wisdom and provide strong data-based support for the healing powers of the Cannabis “Entourage Effect”.

South Korean scientists and public health researchers have documented a wide range of positive health benefits from exposure to terpenes in the air of coniferous forests. They have established that variations among the emitted terpenes of different species of trees create highly diverse, differently beneficial micro-environments.

South Korean, Japanese & Taiwanese healing forests are all well mapped – this tall forested mountain valley for asthma; that craggy seaside forest for dermatitis. These healing forests have been well-known for hundreds of generations, and thousands of ancient shrines celebrate the spiritual qualities & health benefits of forested environments throughout Northeast Asia. Legends are filled with heroes suffering grievous battle wounds going alone into the forests and emerging weeks later miraculously healed.

Forest Bath research shows that the dominant terpenes in the air of the most highly-rated “healthy forests” are the same terpenes, primarily a-pinene, myrcene, linalool, and d-limonene, that dominate and differentiate the aromas, tastes and effects of various Cannabis strains.

Because inhaling both Forest terpenes and Cannabis terpenes involves inhaling virtually the same phytochemical mix, “Forest Bath” research pretty well refutes those smug anti-Cannabis arguments against the “Entourage Effect” that boil down to “You can’t prove it because there’s no research”.

Until now, we’ve been limited to a justifiably angry “Of course there isn’t any research you assholes – you’ll have anyone who tries to do the damn research arrested!” Which of course immediately provokes: “Well, that Cannabis certainly does make you people touchy,” followed by further self-satisfied smirks.  

Maybe Forest Bath research changes the balance of smirk-entitlement.

Forest Bath research provides a thoroughly validated database in support of the health benefits of inhaling the precise aerosolized natural terpenes involved in the Cannabis “Entourage Effect”, clearly establishing the link between inhaling a natural blend of specific aerosolized or vaporized terpenes and associated phytochemicals and obtaining cumulative, lasting, measurable health benefits..

Some of the research references that follow this introduction focus on studying the biological activity of a single terpene in a laboratory environment, such as a-pinene’s effect on cardiac cell inflammation in vitro, while others focus on measuring variables like blood pressure in people exposed to natural forest environments under experimental conditions. Taken as a whole they form a good platform for launching further Cannabis “Entourage Effect” research even in the presence of the Federal war on Citizens.

Note of caution in applying Forest Bath research to Cannabis:

When we’re looking at the science behind “Forest Bathing” to inform our understanding of inhaling/ingesting Cannabis terpenes, it’s important to differentiate between the terpene/phytochemical content of the smoke stream of combusted Cannabis and the terpene/phytochemical content of the vapors emitted under various conditions by the whole, non-combusted but “vaporized” Cannabis flower.

A combustion smoke stream contains both the byproducts of combustion itself, including particles of toxic soot, and vaporized organic compounds including THC and all the cannabinoids, terpenoids, flavonoids and other phytochemicals. These compounds are heated to the point of “boiling off” the plant materials ahead of advancing combustion, and those that are especially vulnerable to heat are partially degraded by that process.

On the other hand, dry distillation of Cannabis flowers, also called vaporizing, does not create combustion byproducts in the vapor stream – no toxic soot- because the heating process leading to the change of state from resin to vapor is non-destructive. Nothing burns. The terpene profile in a vapor stream is close to the natural profile of the terpenes in the whole flower before vaporizing occurs because even the most heat-sensitive Cannabis flower phytochemicals survive well-calibrated vaporizing, while far fewer survive even the gentlest combustion.

That difference may be medically significant. It seems likely that the “Forest Bath” science applies directly to an “Entourage Effect” from vaporized Cannabis flowers but somewhat less to combusted flowers.

In other words, inhaling Cannabis vapor is more like taking a pleasant walk through a forest, and inhaling Cannabis smoke is more like being in front of a nice campfire. Both excellent experiences; each very different.

So I’m suggesting that “Entourage Effect” discussions focus more on the health and sensual benefits of inhaling the natural emissions and vapors of Cannabis, as well as ingestion of the natural Cannabis flower by other means, and maybe focus a little less on inhaling Cannabis smoke which has the same toxic effects as inhaling any smoke regardless of benefits, and can’t be dismissed as a serious health hazard.

The following “Forest Bath” research literature citations, all from peer-reviewed scientific journals, are all curated in the US National Institutes of Health “PubMed” database. This provenance means that anti-Cannabis “scientists” cannot challenge the validity of the large body of “Forest Bath” research, nor its applicability to Cannabis and the “Entourage Effect”.

So, if you want to dig deeper into the science, here are the results of the “Forest Bathing” literature research brilliantly elucidated by the Korean Society of Toxicology team. I’ve added revised PubMed links to the original citations and edited a bit for clarity where I thought it was needed:

Therapeutic Potential Of Inhaled Conifer Forest Terpenes

Pinene

“ α-Pinene, found in oils of coniferous trees and rosemary, showed anti-inflammatory activity by decreasing the activity of mitogen-activated protein kinases (MAPKs), expression of nuclear factor kappa B (NF-κB), and production of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in lipopolysaccharide (LPS)-induced macrophages (link to original research).”

“In ovalbumin-sensitized mouse model of allergic rhinitis, pretreatment with α-pinene decreased clinical symptoms and levels of immunoglobulin E and IL-4 (link to original research).”

“In human chondrocytes, α-pinene inhibited IL-1β-induced inflammation pathway by suppressing NF-κB, c-Jun N-terminal kinase (JNK) activation, and expression of iNOS and matrix metalloproteinases (MMP)-1 and -13, suggesting its role as an anti-osteoarthritic agent (link to original research).”

“Strong anti-inflammatory activity was observed when α-pinene was used in combination with two active ingredients of frankincense, linalool and 1-octanol (link to original research).”

“The Anti-tumor effects of pinenes are well established on tumor lymphocytes as well as tumor cell lines (link to original research).”

“Matsuo et al. (link to original research) identified proapoptotic and anti-metastatic activities of α-pinene in a melanoma model.”

“Later, it was revealed in human hepatoma Bel-7402 cells that the proapoptotic effect of α-pinene is associated with induction of G2/M cell cycle arrest (link to original research).”

“In addition, α-pinene triggers oxidative stress signaling pathways in A549 and HepG2 cells (link to original research).”

“Kusuhara et al. (link to original research) reported that mice kept in a setting enriched with α-pinene showed reduction in melanoma sizes, while in vitro treatment of melanoma cells with α-pinene had no inhibitory effect on cell proliferation, suggesting that the in vivo result may not be due to a direct effect of α-pinene.”

“Investigation of β-pinene also revealed its cytotoxic activity against cancer and normal cell lines with a more pronounced effect on neoplastic cells in the majority of cases, showing acceptable chemotherapeutic potency (citation #1,citation #2).”

“α-pinene and 1, 8-cineole also exert neuroprotective effects by regulating gene expression. They protected PC12 cells against oxidative stress-induced apoptosis through ROS scavenging and induction of nuclear Nrf2 factor followed by enhanced expression of antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and HO-1 (link to original research).”

Myrcene

“Myrcene, the acyclic monoterpene, also exhibits significant antiproliferative and cytotoxic effects in various tumor cell lines such as MCF-7 (breast carcinoma), HeLa (human cervical carcinoma), A549 (human lung carcinoma), HT-29 (human colon adenocarcinoma), P388 (leukemia), and Vero (monkey kidney) as well as mouse macrophages (citation #1,citation #2).”

“Essential oil from Vepris macrophylla demonstrated a strong cytotoxic effect, suggesting that the effect may be attributed to the presence of specific components, among which is myrcene (link to original research).”

Linalool

“Treatment with linalool, a natural compound found in essential oils of aromatic plants, inhibited cigarette smoke-induced acute lung inflammation by inhibiting infiltration of inflammatory cells and production of TNF-α, IL-6, IL-1β, IL-8, and monocyte chemoattractant protein – 1 (MCP-1), as well as NF-κB activation (link to original research).”

“In another lung injury model, linalool attenuated lung histopathologic changes in LPS-induced mice. In in vitro experiments, linalool reduced production of TNF-α and IL-6 and blocked phosphorylation of IκBα protein, p38, and JNK in LPS-stimulated RAW 264.7 macrophages (link to original research).”

“Similarly, linalool inhibited production of TNF-α, IL-1β, NO, and PGE2 in LPS-stimulated microglia cells (link to original research).”

“Li et al. (link to original research) showed that the anti-inflammatory effect of linalool is involved in activation of Nrf2/heme oxygenase-1 (HO-1) signaling pathway.”

“Frankincense oil extract, which contains linalool, exhibited anti-inflammatory and analgesic effects in a xylene-induced ear edema model and a formalin-inflamed hind paw model by inhibiting COX-2 (link to original research).”

Limonene

“The anti-tumorigenic activity of d-limonene is well-established. Numerous studies have demonstrated the protective effects of d-limonene against chemical-induced tumors in various tissue types such as breast, intestine, pancreas, liver, and colon (citation #1–citation #2).”

 “Another naturally occurring monoterpene d-limonene was reported to reduce allergic lung inflammation in mice probably via its antioxidant properties (link to original research).”

“It also reduced carrageenan-induced inflammation by reducing cell migration, cytokine production, and protein extravasation (link to original research).”

“Similar to α-pinene, d-limonene exerted an anti-osteoarthritic effect by inhibiting IL-1β-induced NO production in human chondrocytes (link to original research).”

“d-Limonene treatment reduced doxorubicin-induced production of two proinflammatory cytokines, TNF-α and prostaglandin E-2 (PGE2) (link to original research).”

 “Lu et al. (link to original research) revealed that d-limonene could inhibit the proliferation of human gastric cancer cells by inducing apoptosis.”

“Later, it was demonstrated that apoptosis of tumor cells by d-limonene could be mediated by the mitochondrial death pathway via activated caspases and PARP cleavage as well as by the suppression of the PI3K/Akt pathway (citation #1,citation #2).”

Cymene

“Monoterpene p-cymene treatment reduced elastase-induced lung emphysema and inflammation in mice. It reduced the alveolar enlargement, number of macrophages, and levels of proinflammatory cytokines such as IL-1β, IL-6, IL-8, and IL-17 in bronchoalveolar lavage fluid (BALF) (link to original research).”

“Similarly, p-cymene showed a protective effect in a mouse model of LPS-induced acute lung injury by reducing the number of inflammatory cells in the BALF and expression of NF-κB in the lungs (link to original research) and by reducing production of proinflammatory cytokines and infiltration of inflammatory cells (link to original research).”

“Mechanistically, p-cymene blocks NF-κB and MAPK signaling pathways. It has been reported that p-cymene reduces production of TNF-α, IL-6, and IL-β in LPS-treated RAW 264.7 macrophages. In C57BL/6 mice, TNF-α and IL-1β were downregulated and IL-10 was upregulated by p-cymene treatment. It also inhibited LPS-induced activation of ERK 1/2, p38, JNK, and IκBα (citation #1,citation #2).”

“p-Cymene has been reported to have cytotoxic effects on tumor cell lines (link to original research).”

“Recently, Li et al. (link to original research) evaluated beneficial effects of p-cymene on in vitro TPA-augmented invasiveness of HT-1080 cells, and found that it inhibits MMP-9 expression, but enhances TIMP-1 production along with the suppression of ERK1/2 and p38 MAPK signal pathways in tumor cells, suggesting that p-cymene is an effective candidate for the prevention of tumor invasion and metastasis.”

Terpinene

“The monoterpene γ-terpinene, present in the essential oil of many plants including Eucalyptus, reduced the acute inflammatory response. It reduced carrageenan-induced paw edema, migration of neutrophil into lung tissue, and IL-1β and TNF-α production and inhibited fluid extravasation (link to original research).”

“Terpinene-containing essential oil from Liquidambar formosana leaves reduced inflammatory response in LPS-stimulated mouse macrophages by reducing reactive oxygen species (ROS), JNK, ERK, p38 MAP kinase, and NF-κB (link to original research).”

“Another terpinene-containing essential oil from Citrus unshiu flower or fingered citron (C. medica L. var. sarcodactylis) reduced LPS-stimulated PGE2 and NO production in RAW 264.7 cells. Furthermore, production of inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, was also reduced in macrophages (citation #1,citation #2).”

Boneol

“Borneol, a bicyclic monoterpene present in Artemisia, Blumea, and Kaempferia, has been used in traditional medicine. Borneol alleviated acute lung inflammation by reducing inflammatory infiltration, histopathological changes, and cytokine production in LPS-stimulated mice. It suppressed phosphorylation of NF-κB, IκBα, p38, JNK, and ERK (link to original research).”

“Oral administration and intrathecal injection of borneol showed antihyperalgesic effects on inflammatory pain in complete Freund’s adjuvant-induced hypersensitive animal models by enhancing GABAAR (Gamma-Aminobutyric Acid Type A Receptor)-mediated GABAergic transmission (link to original research).”

“Borneol inhibited migration of leukocytes into the peritoneal cavity in carrageenan-stimulated mice, suggesting its anti-inflammatory function (link to original research).”

“In addition, borneol inhibited TRPA1, a cation channel that is involved in inflammation and noxious-pain sensing, suggesting that its use as an anti-inflammatory agent for neuropathic-pain and trigeminal neuralgia (link to original research).”

“Previous studies showed that borneol has free radical scavenging activity (link to original research) and is a major component of essential oil of SuHeXiang Wan (link to original research) whose neuroprotective function has been reported in in vivo and in vitro models of Alzheimer’s disease (AD) (citation #1,citation #2).”

“Moreover, a recent study showed that borneol exerts a neuroprotective effect against β-amyloid (Aβ) cytotoxicity via upregulation of nuclear translocation of Nrf2 and expression of Bcl-2 (link to original research).”

“In addition, treatment with isoborneol, a monoterpenoid alcohol, significantly reduced 6-hydroxydopamine-induced ROS generation and cell death in human neuroblastoma SH-SY5Y cells, suggesting that isoborneol may be a potential therapeutic agent for treatment of neurodegenerative diseases associated with oxidative stress (link to original research).”

Caryophyllene

“α-Caryophyllene, known as humulene, is a naturally occurring monocyclic sesquiterpene. BCP, an isomer of α-caryophyllene, has been identified as an active component of an essential oil mixture that not only prevents solid tumor growth and proliferation of cancer cell lines but also inhibits lymph node metastasis of melanoma cells in high-fat diet-induced obese mice (citation #1,citation #2).”

“Sarvmeili et al. (link to original research) reported that Pinus eldarica essential oil, of which BCP was the major component, exerts cytotoxic effects on HeLa and MCF-7 cell lines.”

“β-caryophyllene (BCP) was reported to protect against neuroinflammation in a rat model of Parkinson’s disease (PD) by attenuating production of proinflammatory cytokines and inflammatory mediators such as COX-2 and iNOS (link to original research).”

“Chronic treatment with BCP attenuated alcohol-induced liver injury and inflammation by reducing the proinflammatory phenotypic switch of hepatic macrophages and neutrophil infiltration. The beneficial effects of BCP on liver injury are mediated by cannabinoid 2 (CB2) receptor activation (link to link to original research).”

“Prolonged administration of BCP reduced proinflammatory cytokines in pancreatic tissue of streptozotocin-induced diabetic rats (link to original research).”

“BCP reduced expression of Toll-like receptor 4 and macrophage inflammatory protein-2, and phosphorylation of ERK, p38, JNK, and NF-κB in D-galactosamine and LPS-induced liver injury mouse model (link to original research).”

“BCP has antioxidant effects (link to original research), and functions as a regulator of several neuronal receptors and shows various pharmacological activities including neuroprotection (link to original research).”

“Neuroprotective effects of BCP have been reported in both AD and PD animal models. Oral treatment with BCP prevented AD-like phenotype such as cognitive impairment and activation of inflammation through CB2 receptor activation and the PPARγ pathway (link to original research).”

RESEARCH BIBLIOGRAPHY: THE ROLE OF FOREST BATH TERPENES IN HUMAN HEALTH

No more “You can’t prove it” bullshit. The studies cited throughout this post reference terpenes and other phytochemicals found in natural emissions and vapors of “Forest Bath” environments. These same terpenes and other phytochemicals, exactly the same, are found in Cannabis emissions and vapors, in almost the same proportions, and vary between Cannabis strains the same way that emissions from tree species vary among Healing Forests. I hope that the connection between hundreds of peer-reviewed scientific and medical research studies that support the ancient practice of Forest Bathing and their direct applicability to the  Entourage Effect will allow the Cannabis community to finally checkmate the anti-Cannabis propagandists and their scientific pretensions.

REFERENCES: from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402865/

  1. Frumkin H. Beyond toxicity: human health and the natural environment. Am J Prev Med. 2001;20:234–240. doi: 10.1016/S0749-3797(00)00317-2. PubMed    

  2. Tsunetsugu Y, Park BJ, Miyazaki Y. Trends in research related to “Shinrin-yoku” (taking in the forest atmosphere or forest bathing) in Japan. Environ Health Prev Med. 2010;15:27–37. doi: 10.1007/s12199-009-0091-z. PMC free article  PubMed  

  3. Seo SC, Park SJ, Park CW, Yoon WS, Choung JT, Yoo Y. Clinical and immunological effects of a forest trip in children with asthma and atopic dermatitis. Iran J Allergy Asthma Immunol. 2015;14:28–36. PubMed

  4. Douglass RW. Forest recreation. 3rd edition. Pergamon Press; 1982.

  5. Spievogel I, Spalek K. Medicinal plants uesed in pediatric prophylactic method of Sebastian Kneipp. Nat J. 2012;45:9–18.

  6. Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B. Use of complementary and alternative medicine in Germany: a survey of patients with inflammatory bowel disease. BMC Complement Altern Med. 2006;6:19. doi: 10.1186/1472-6882-6-19. PMC free article  PubMed  

  7. Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y. The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan. Environ Health Prev Med. 2010;15:18–26. doi: 10.1007/s12199-009-0086-9. PMC free article  PubMed  

  8. Song C, Ikei H, Miyazaki Y. Physiological effects of nature therapy: A review of the research in Japan. Int J Environ Res Public Health. 2016;13:E781. doi: 10.3390/ijerph13080781. PMC free article  PubMed  

  9. Gershenzon J, Dudareva N. The function of terpene natural products in the natural world. Nat Chem Biol. 2007;3:408–414. doi: 10.1038/nchembio.2007.5. PubMed

  10. Chappell J. The genetics and molecular genetics of terpene and sterol origami. Curr Opin Plant Biol. 2002;5:151–157. doi: 10.1016/S1369-5266(02)00241-8. PubMed

  11. Mewalal R, Rai DK, Kainer D, Chen F, Külheim C, Peter GF, Tuskan GA. Plant-derived terpenes: A feedstock for specialty biofuels. Trends Biotechnol. 2016 S0167-7799(16)30128-7. PubMed

  12. Kirby J, Keasling JD. Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol. 2009;60:335–355. doi: 10.1146/annurev.arplant.043008.091955. PubMed

  13. Zulak KG, Bohlmann J. Terpenoid biosynthesis and specialized vascular cells of conifer defense. J Integr Plant Biol. 2010;52:86–97. doi: 10.1111/j.1744-7909.2010.00910.x. PubMed

  14. Lange BM, Ahkami A. Metabolic engineering of plant monoterpenes, sesquiterpenes and diterpenes: current status and future opportunities. Plant Biotechnol J. 2013;11:169–196. doi: 10.1111/pbi.12022. PubMed

  15. Dubey VS, Bhalla R, Luthra R. An overview of the non-mevalonate pathway for terpenoid biosynthesis in plants. J Biosci. 2003;28:637–646. doi: 10.1007/BF02703339. PubMed

  16. Matsuba Y, Nguyen TT, Wiegert K, Falara V, Gonzales-Vigil E, Leong B, Schäfer P, Kudrna D, Wing RA, Bolger AM, Usadel B, Tissier A, Fernie AR, Barry CS, Pichersky E. Evolution of a complex locus for terpene biosynthesis in solanum. Plant Cell. 2013;25:2022–2036. doi: 10.1105/tpc.113.111013. PMC free article  PubMed  

  17. Martin DM, Gershenzon J, Bohlmann J. Induction of volatile terpene biosynthesis and diurnal emission by methyl jasmonate in foliage of Norway spruce. Plant Physiol. 2003;132:1586–1599. doi: 10.1104/pp.103.021196. PMC free article  PubMed  

  18. Lee DH, Kim MH, Park OH, Park KS, An SS, Seo HJ, Jin SH, Jeong WS, Kang YJ, An KW, Kim ES. A study on the distribution characteristics of terpene at the main trails of Mt. Mudeung. J Environ Health Sci. 2013;39:211–222. doi: 10.1080/10934529.2012.717818.

  19. Rufino AT, Ribeiro M, Judas F, Salgueiro L, Lopes MC, Cavaleiro C, Mendes AF. Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity. J Nat Prod. 2014;77:264–269. doi: 10.1021/np400828x. PubMed

  20. Ma J, Xu H, Wu J, Qu C, Sun F, Xu S. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation. Int Immunopharmacol. 2015;29:708–713. doi: 10.1016/j.intimp.2015.09.005. PubMed

  21. Rodrigues KA, Amorim LV, Dias CN, Moraes DFC, Carneiro SM, Carvalho FA. Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro. J Ethnopharmacol. 2015;160:32–40. doi: 10.1016/j.jep.2014.11.024. PubMed

  22. Li XJ, Yang YJ, Li YS, Zhang WK, Tang HB. α-Pinene, linalool and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol. 2016;179:22–26. doi: 10.1016/j.jep.2015.12.039. PubMed

  23. Yu PJ, Wan LM, Wan SH, Chen WY, Xie H, Meng DM, Zhang JJ, Xiao XL. Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice. Pharm Biol. 2016;54:3211–3216. doi: 10.1080/13880209.2016.1216132. PubMed

  24. Kim DS, Lee HJ, Jeon YD, Han YH, Kee JY, Kim HJ, Shin HJ, Kang J, Lee BS, Kim SH, Kim SJ, Park SH, Choi BM, Park SJ, Um JY, Hong SH. Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and the NF-κB pathway in mouse peritoneal macrophages. Am J Chin Med. 2015;43:731–742. doi: 10.1142/S0192415X15500457. PubMed

  25. Nam SY, Chung Ck, Seo JH, Rah SY, Kim HM, Jeong HJ. The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis. Int Immunopharmacol. 2014;23:273–282. doi: 10.1016/j.intimp.2014.09.010. PubMed

  26. Hansen JS, Nørgaard AW, Koponen IK, Sørli JB, Paidi MD, Hansen SW, Clausen PA, Nielsen GD, Wolkoff P, Larsen ST. Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice. J Immunotoxicol. 2016;13:793–803. doi: 10.1080/1547691X.2016.1195462. PubMed

  27. Amorim JL, Simas DLR, Pinheiro MM, Moreno DS, Alviano CS, da Silva AJ, Fernandes PD. Antiinflammatory properties and chemical characterization of the essential oils of four citrus species. PLoS ONE. 2016;11:e0153643. doi: 10.1371/journal.pone.0153643. PMC free article  PubMed

  28. Rufino AT, Ribeiro M, Sousa C, Judas F, Salgueiro L, Cavaleiro C, Mendes AF. Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur J Pharmacol. 2015;750:141–150. doi: 10.1016/j.ejphar.2015.01.018. PubMed

  29. Rehman MU, Tahir M, Khan AQ, Khan R, Oday-O-Hamiza, Lateef A, Hassan SK, Rashid S, Ali N, Zeeshan M, Sultana S. D-limonene suppresses doxorubicin-induced oxidative stress and inflammation via repression of COX-2, iNOS and NFκB in kidneys of Wistar rats. Exp Biol Med (Maywood) 2014;239:465–476. doi: 10.1177/1535370213520112. PubMed

  30. Games E, Guerreiro M, Santana FR, Pinheiro NM, de Oliveira EA, Lopes FD, Olivo CR, Tibério IF, Martins MA, Lago JH, Prado CM. Structurally related monoterpenes p-Cymene, carvacrol and thymol isolated from essential oil from leaves of lippia sidoides cham. (Verbenaceae) protect mice against elastase-induced emphysema. Molecules. 2016;21:E1390. doi: 10.3390/molecules21101390. PubMed

  31. Chen L, Zhao L, Zhang C, Lan Z. Protective effect of p-cymene on lipopolysaccharide-induced acute lung injury in mice. Inflammation. 2014;37:358–364. doi: 10.1007/s10753-013-9747-3. PubMed

  32. Xie G, Chen N, Soromou LW, Liu F, Xiong Y, Wu Q, Li H, Feng H, Liu G. p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation. Molecules. 2012;17:8159–8173. doi: 10.3390/molecules17078159. PubMed    

  33. Zhong W, Chi G, Jiang L, Soromou LW, Chen N, Huo M, Guo W, Deng X, Feng H. p-Cymene modulates in vitro and in vivo cytokine production by inhibiting MAPK and NF-κB activation. Inflammation. 2013;36:529–537. doi: 10.1007/s10753-012-9574-y. PubMed    

  34. Huo M, Cui X, Xue J, Chi G, Gao R, Deng X, Guan S, Wei J, Soromou LW, Feng H, Wang D. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J Surg Res. 2013;180:e47–e54. doi: 10.1016/j.jss.2012.10.050. PubMed    

  35. Li Y, Lv O, Zhou F, Li Q, Wu Z, Zheng Y. Linalool inhibits LPS-induced inflammation in BV2 microglia cells by activating Nrf2. Neurochem Res. 2015;40:1520–1525. doi: 10.1007/s11064-015-1629-7. PubMed    

  36. de Oliveira Ramalho TR, de Oliveira MT, de Araujo Lima AL, Bezerra-Santos CR, Piuvezam MR. Gamma-terpinene modulates acute inflammatory response in mice. Planta Med. 2015;81:1248–1254. doi: 10.1055/s-0035-1546169. PubMed    

  37. Hua KF, Yang TJ, Chiu HW, Ho CL. Essential oil from leaves of Liquidambar formosana ameliorates inflammatory response in lipopolysaccharide-activated mouse macrophages. Nat Prod Commun. 2014;9:869–872. PubMed

  38. Kim KN, Ko YJ, Yang HM, Ham YM, Roh SW, Jeon YJ, Ahn G, Kang MC, Yoon WJ, Kim D, Oda T. Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. Food Chem Toxicol. 2013;57:126–131. doi: 10.1016/j.fct.2013.03.017. PubMed    

  39. Kim MJ, Yang KW, Kim SS, Park SM, Park KJ, Kim KS, Choi YH, Cho KK, Hyun CG. Chemical composition and anti-inflammation activity of essential oils from Citrus unshiu flower. Nat Prod Commun. 2014;9:727–730. PubMed

  40. Zhong W, Cui Y, Yu Q, Xie X, Liu Y, Wei M, Ci X, Peng L. Modulation of LPS-stimulated pulmonary inflammation by borneol in murine acute lung injury model. Inflammation. 2014;37:1148–1157. doi: 10.1007/s10753-014-9839-8. PubMed    

  41. Jiang J, Shen YY, Li J, Lin YH, Luo CX, Zhu DY. (+)-Borneol alleviates mechanical hyperalgesia in models of chronic inflammatory and neuropathic pain in mice. Eur J Pharmacol. 2015;757:53–58. doi: 10.1016/j.ejphar.2015.03.056. PubMed    

  42. Almeida JR, Souza GR, Silva JC, Saraiva SR, Júnior RG, Quintans Jde S, Barreto Rde S, Bonjardim LR, Cavalcanti SC, Quintans LJ., Jr Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. ScientificWorldJournal. 2013;2013:808460. doi: 10.1155/2013/808460. PMC free article  PubMed     

  43. Sherkheli MA, Schreiner B, Haq R, Werner M, Hatt H. Borneol inhibits TRPA1, a proinflammatory and noxious pain-sensing cation channel. Pak J Pharm Sci. 2015;28:1357–1363. PubMed

  44. Ojha S, Javed H, Azimullah S, Haque ME. β-Caryophyllene, a phytocannabinoid attenuates oxidative stress, neuroinflammation, glial activation and salvages dopaminergic neurons in a rat model of Parkinson disease. Mol Cell Biochem. 2016;418:59–70. doi: 10.1007/s11010-016-2733-y. PubMed    

  45. Varga ZV, Matyas C, Erdelyi K, Cinar R, Nieri D, Chicca A, Nemeth BT, Paloczi J, Lajtos T, Corey L, Hasko G, Gao B, Kunos G, Gertsch J, Pacher P. Beta-caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. Br J Pharmacol. 2017 doi: 10.1111/bph.13722. PubMed    

  46. Basha RH, Sankaranarayanan C. β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia mediated oxidative and inflammatory stress in experimental diabetic rats. Chem Biol Interact. 2016;245:50–58. doi: 10.1016/j.cbi.2015.12.019. PubMed    

  47. Cho HI, Hong JM, Choi JW, Choi HS, Kwak JH, Lee DU, Lee SK, Lee SM. β-Caryophyllene alleviates d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways. Eur J Pharmacol. 2015;764:613–621. doi: 10.1016/j.ejphar.2015.08.001. PubMed    

  48. Kim MJ, Yang KW, Kim SS, Park SM, Park KJ, Kim KS, Choi YH, Cho KK, Lee NH, Hyun CG. Chemical composition and anti-inflammatory effects of essential oil from Hallabong flower. EXCLI J. 2013;12:933–942. PMC free article  PubMed

  49. Chaiyana W, Anuchapreeda S, Leelapornpisid P, Phongpradist R, Viernstein H, Mueller M. Development of microemulsion delivery system of essential oil from Zingiber cassumunar Roxb. Rhizome for improvement of stability and anti-inflammatory activity. AAPS PharmSciTech. 2016:1–11. PubMed

  50. Yang H, Zhao R, Chen H, Jia P, Bao L, Tang H. Bornyl acetate has an anti-inflammatory effect in human chondrocytes via induction of IL-11. IUBMB Life. 2014;66:854–859. doi: 10.1002/iub.1338. PubMed    

  51. Sobral MV, Xavier AL, Lima TC, de Sousa DP. Antitumor activity of monoterpenes found in essential oils. Scientific World Journal. 2014;2014:953451. doi: 10.1155/2014/953451. PMC free article  PubMed     

  52. Broitman SA, Wilkinson J, 4th, Cerda S, Branch SK. Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic “Metastases” in vitro. Adv Exp Med Biol. 1996;401:111–130. doi: 10.1007/978-1-4613-0399-2_9. PubMed    

  53. Uedo N, Tatsuta M, Iishi H, Baba M, Sakai N, Yano H, Otani T. Inhibition by d-limonene of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Cancer Lett. 1999;137:131–136. doi: 10.1016/S0304-3835(98)00340-1. PubMed    

  54. Stratton S, Dorr R, Alberts D. The state-of-the-art in chemoprevention of skin cancer. Eur J Cancer. 2000;36:1292–1297. doi: 10.1016/S0959-8049(00)00108-8. PubMed    

  55. Kaji I, Tatsuta M, Iishi H, Baba M, Inoue A, Kasugai H. Inhibition by D-limonene of experimental hepatocarcinogenesis in Sprague-Dawley rats does not involve p21ras plasma membrane association. Int J Cancer. 2001;93:441–444. doi: 10.1002/ijc.1353. PubMed    

  56. Guyton KZ, Kensler TW. Prevention of liver cancer. Curr Oncol Rep. 2002;4:464–470. doi: 10.1007/s11912-002-0057-4. PubMed    

  57. Lu XG, Zhan LB, Feng BA, Qu MY, Yu LH, Xie JH. Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene. World J Gastroenterol. 2004;10:2140–2144. doi: 10.3748/wjg.v10.i14.2140. PMC free article  PubMed     

  58. Ji J, Zhang L, Wu YY, Zhu XY, Lv SQ, Sun XZ. Induction of apoptosis by d-limonene is mediated by a caspase-dependent mitochondrial death pathway in human leukemia cells. Leuk Lymphoma. 2006;47:2617–2624. doi: 10.1080/00268970600909205. PubMed    

  59. Jia SS, Xi GP, Zhang M, Chen YB, Lei B, Dong XS, Yang YM. Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells. Oncol Rep. 2013;29:349–354. PubMed

  60. Li Q. Effect of forest bathing trips on human immune function. Environ Health Prev Med. 2010;15:9–17. doi: 10.1007/s12199-008-0068-3. PMC free article  PubMed     

  61. Bansal A, Moriarity DM, Takaku S, Setzer WN. Chemical composition and cytotoxic activity of the leaf essential oil of Ocotea tonduzii from Monteverde, Costa Rica. Nat Prod Commun. 2007;2:781–784.

  62. Matsuo AL, Figueiredo CR, Arruda DC, Pereira FV, Scutti JA, Massaoka MH, Travassos LR, Sartorelli P, Lago JH. α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem Biophys Res Commun. 2011;411:449–454. doi: 10.1016/j.bbrc.2011.06.176. PubMed    

  63. Chen W, Liu Y, Li M, Mao J, Zhang L, Huang R, Jin X, Ye L. Anti-tumor effect of α-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest. J Pharmacol Sci. 2015;127:332–338. doi: 10.1016/j.jphs.2015.01.008. PubMed    

  64. Jin KS, Bak MJ, Jun M, Lim HJ, Jo WK, Jeong WS. α-Pinene triggers oxidative stress and related signaling pathways in A549 and HepG2 cells. Food Sci Biotechnol. 2010;19:1325–1332. doi: 10.1007/s10068-010-0189-5.  

  65. Kusuhara M, Urakami K, Masuda Y, Zangiacomi V, Ishii H, Tai S, Maruyama K, Yamaguchi K. Fragrant environment with α-pinene decreases tumor growth in mice. Biomed Res. 2012;33:57–61. doi: 10.2220/biomedres.33.57. PubMed    

  66. Bakarnga-Via I, Hzounda JB, Fokou PVT, Tchokouaha LRY, Gary-Bobo M, Gallud A, Garcia M, Walbadet L, Secka Y, Dongmo PMJ, Boyom FF, Menut C. Composition and cytotoxic activity of essential oils from Xylopia aethiopica (Dunal) A. Rich, Xylopia parviflora (A. Rich) Benth. and Monodora myristica (Gaertn) growing in chad and cameroon. BMC Complement Altern Med. 2014;14:125. doi: 10.1186/1472-6882-14-125. PMC free article  PubMed     

  67. Li YL, Yeung CM, Chiu L, Cen YZ, Ooi VE. Chemical composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Schefflera heptaphylla. Phytother Res. 2009;23:140–142. doi: 10.1002/ptr.2567. PubMed    

  68. Meadows SM, Mulkerin D, Berlin J, Bailey H, Kolesar J, Warren D, Thomas JP. Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer. Int J Gastrointest Cancer. 2002;32:125–128. doi: 10.1385/IJGC:32:2-3:125. PubMed    

  69. Chen TC, Cho HY, Wang W, Wetzel SJ, Singh A, Nguyen J, Hofman FM, Schönthal AH. Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. J Biomed Sci. 2015;22:71. doi: 10.1186/s12929-015-0175-6. PMC free article  PubMed     

  70. Bardon S, Foussard V, Fournel S, Loubat A. Monoterpenes inhibit proliferation of human colon cancer cells by modulating cell cycle-related protein expression. Cancer Lett. 2002;181:187–194. doi: 10.1016/S0304-3835(02)00047-2. PubMed    

  71. Yeruva L, Pierre KJ, Elegbede A, Wang RC, Carper SW. Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non small cell lung cancer cells. Cancer Lett. 2007;257:216–226. doi: 10.1016/j.canlet.2007.07.020. PubMed    

  72. Ferraz RP, Bomfim DS, Carvalho NC, Soares MB, da Silva TB, Machado WJ, Prata APN, Costa EV, Moraes VRS, Nogueira PCL, Bezerra DP. Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae) Phytomedicine. 2013;20:615–621. doi: 10.1016/j.phymed.2013.01.015. PubMed    

  73. Li J, Liu C, Sato T. Novel antitumor invasive actions of p-Cymene by decreasing MMP-9/TIMP-1 expression ratio in human fibrosarcoma HT-1080 cells. Biol Pharm Bull. 2016;39:1247–1253. doi: 10.1248/bpb.b15-00827. PubMed    

  74. Saleh M, Hashem F, Glombitza K. Cytotoxicity and in vitro effects on human cancer cell lines of volatiles of Apium graveolens var filicinum. Pharm Pharmacol Lett. 1998;8:97–99.

  75. Silva SLD, Figueiredo PM, Yano T. Cytotoxic evaluation of essential oil from Zanthoxylum rhoifolium Lam. leaves. Acta Amaz. 2007;37:281–286. doi: 10.1590/S0044-59672007000200015.  

  76. Maggi F, Fortuné Randriana R, Rasoanaivo P, Nicoletti M, Quassinti L, Bramucci M, Lupidi G, Petrelli D, Vitali LA, Papa F, Vittori S. Chemical composition and in vitro biological activities of the essential oil of Vepris macrophylla (Baker) I. Verd. endemic to Madagascar. Chem Biodivers. 2013;10:356–366. doi: 10.1002/cbdv.201200253. PubMed    

  77. Kuo YH, Kuo YJ, Yu AS, Wu MD, Ong CW, Kuo LMY, Huang JT, Chen CF, Li SY. Two novel sesquiterpene lactones, cytotoxic vernolide-A and-B, from Vernonia cinerea. Chem Pharm Bull. 2003;51:425–426. doi: 10.1248/cpb.51.425. PubMed    

  78. Dahham SS, Tabana YM, Iqbal MA, Ahamed MB, Ezzat MO, Majid AS, Majid AM. The anticancer, antioxidant and antimicrobial properties of the sesquiterpene β-caryophyllene from the essential oil of Aquilaria crassna. Molecules. 2015;20:11808–11829. doi: 10.3390/molecules200711808. PubMed    

  79. Jung JI, Kim EJ, Kwon GT, Jung YJ, Park T, Kim Y, Yu R, Choi MS, Chun HS, Kwon SH, Her S, Lee KW, Park JH. β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice. Carcinogenesis. 2015;36:1028–1039. doi: 10.1093/carcin/bgv076. PubMed    

  80. Sarvmeili N, Jafarian-Dehkordi A, Zolfaghari B. Cytotoxic effects of Pinus eldarica essential oil and extracts on HeLa and MCF-7 cell lines. Res Pharm Sci. 2016;11:476–483. doi: 10.4103/1735-5362.194887. PMC free article  PubMed     

  81. Legault J, Pichette A. Potentiating effect of β-caryophyllene on anticancer activity of α-humulene, isocaryophyllene and paclitaxel. J Pharm Pharmacol. 2007;59:1643–1647. doi: 10.1211/jpp.59.12.0005. PubMed    

  82. Lesgards JF, Baldovini N, Vidal N, Pietri S. Anticancer activities of essential oils constituents and synergy with conventional therapies: a review. Phytother Res. 2014;28:1423–1446. doi: 10.1002/ptr.5165. PubMed    

  83. Savelev SU, Okello EJ, Perry EK. Butyryl-and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res. 2004;18:315–324. doi: 10.1002/ptr.1451. PubMed    

  84. Liu ZB, Niu WM, Yang XH, Yuan W, Wang WG. Study on perfume stimulating olfaction with volatile oil of Acorus gramineus for treatment of the Alzheimer’s disease rat. J Tradit Chin Med. 2010;30:283–287. doi: 10.1016/S0254-6272(10)60057-X. PubMed    

  85. Majlessi N, Choopani S, Kamalinejad M, Azizi Z. Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer’s disease. CNS Neurosci Ther. 2012;18:295–301. doi: 10.1111/j.1755-5949.2011.00237.x. PubMed    

  86. Cioanca O, Hritcu L, Mihasan M, Trifan A, Hancianu M. Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1–42) rat model of Alzheimer’s disease. Physiol Behav. 2014;131:68–74. doi: 10.1016/j.physbeh.2014.04.021. PubMed    

  87. Oboh G, Olasehinde TA, Ademosun AO. Essential oil from lemon peels inhibit key enzymes linked to neurodegenerative conditions and pro-oxidant induced lipid peroxidation. J Oleo Sci. 2014;63:373–381. doi: 10.5650/jos.ess13166. PubMed    

  88. Abuhamdah S, Abuhamdah R, Howes MJ, Al-Olimat S, Ennaceur A, Chazot PL. Pharmacological and neuroprotective profile of an essential oil derived from leaves of Aloysia citrodora Palau. J Pharm Pharmacol. 2015;67:1306–1315. doi: 10.1111/jphp.12424. PubMed    

  89. Ayaz M, Junaid M, Ullah F, Sadiq A, Khan MA, Ahmad W, Shah MR, Imran M, Ahmad S. Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: A Preliminary anti-Alzheimer’s study. Lipids Health Dis. 2015;14:141. doi: 10.1186/s12944-015-0145-8. PMC free article  PubMed     

  90. Klein-Júnior LC, dos Santos Passos C, Tasso de Souza TJ, Gobbi de Bitencourt F, Salton J, de Loreto Bordignon SA, Henriques AT. The monoamine oxidase inhibitory activity of essential oils obtained from Eryngium species and their chemical composition. Pharm Biol. 2016;54:1071–1076. doi: 10.3109/13880209.2015.1102949. PubMed    

  91. Mühlbauer R, Lozano A, Palacio S, Reinli A, Felix R. Common herbs, essential oils and monoterpenes potently modulate bone metabolism. Bone. 2003;32:372–380. doi: 10.1016/S8756-3282(03)00027-9. PubMed    

  92. Koo BS, Lee SI, Ha JH, Lee DU. Inhibitory effects of the essential oil from SuHeXiang Wan on the central nervous system after inhalation. Biol Pharm Bull. 2004;27:515–519. doi: 10.1248/bpb.27.515. PubMed    

  93. Lima B, López S, Luna L, Agüero MB, Aragón L, Tapia A, Zacchino S, López ML, Zygadlo J, Feresin GE. Essential oils of medicinal plants from the central andes of Argentina: chemical composition, and antifungal, antibacterial, and insect-repellent activities. Chem Biodivers. 2011;8:924–936. doi: 10.1002/cbdv.201000230. PubMed    

  94. El-Seedi HR, Khalil NS, Azeem M, Taher EA, Göransson U, Pålsson K, Borg-Karlson AK. Chemical composition and repellency of essential oils from four medicinal plants against Ixodes ricinus nymphs (Acari: Ixodidae) J Med Entomol. 2012;49:1067–1075. doi: 10.1603/ME11250. PubMed    

  95. Mkaddem M, Bouajila J, Ennajar M, Lebrihi A, Mathieu F, Romdhane M. Chemical composition and antimicrobial and antioxidant activities of Mentha (longifolia L. and viridis) essential oils. J Food Sci. 2009;74:M358–M363. doi: 10.1111/j.1750-3841.2009.01272.x. PubMed    

  96. Hong YK, Park SH, Lee S, Hwang S, Lee MJ, Kim D, Lee JH, Han SY, Kim ST, Kim YK, Jeon S, Koo BS, Cho KS. Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer’s disease. J Ethnopharmacol. 2011;134:1028–1032. doi: 10.1016/j.jep.2011.02.012. PubMed    

  97. Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS. Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer’s disease. Biol Pharm Bull. 2013;36:390–398. doi: 10.1248/bpb.b12-00792. PubMed    

  98. Liu QF, Jeong H, Lee JH, Hong YK, Oh Y, Kim YM, Suh YS, Bang S, Yun HS, Lee K, Cho SM, Lee SB, Jeon S, Chin YW, Koo BS, Cho KS. Coriandrum sativum suppresses Aβ42-induced ROS increases, glial cell proliferation and ERK activation. Am J Chin Med. 2016;44:1325–1347. doi: 10.1142/S0192415X16500749. PubMed    

  99. Liu QF, Lee JH, Kim YM, Lee S, Hong YK, Hwang S, Oh Y, Lee K, Yun HS, Lee IS, Jeon S, Chin YW, Koo BS, Cho KS. In vivo screening of traditional medicinal plants for neuroprotective activity against Aβ42 cytotoxicity by using Drosophila models of Alzheimer’s disease. Biol Pharm Bull. 2015;38:1891–1901. doi: 10.1248/bpb.b15-00459. PubMed    

  100. Hur J, Pak SC, Koo BS, Jeon S. Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y cells. Pharm Biol. 2013;51:30–35. doi: 10.3109/13880209.2012.700718. PubMed    

  101. Tian LL, Zhou Z, Zhang Q, Sun YN, Li CR, Cheng C, Zhong ZY, Wang SQ. Protective effect of (±) isoborneol against 6-OHDA-induced apoptosis in SHSY5Y cells. Cell Physiol Biochem. 2007;20:1019–1032. doi: 10.1159/000110682. PubMed    

  102. Han M, Liu Y, Zhang B, Qiao J, Lu W, Zhu Y, Wang Y, Zhao C. Salvianic borneol ester reduces β-amyloid oligomers and prevents cytotoxicity. Pharm Biol. 2011;49:1008–1013. doi: 10.3109/13880209.2011.559585. PubMed    

  103. Calleja MA, Vieites JM, Montero-Meterdez T, Torres MI, Faus MJ, Gil A, Suárez A. The antioxidant effect of β-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br J Nutr. 2013;109:394–401. doi: 10.1017/S0007114512001298. PubMed    

  104. Sharma C, Al Kaabi JM, Nurulain SM, Goyal SN, Kamal MA, Ojha S. Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des. 2016;22:3237–3264. doi: 10.2174/1381612822666160311115226. PubMed    

  105. Cheng Y, Dong Z, Liu S. β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 mice through CB2 receptor activation and the PPARγ pathway. Pharmacology. 2014;94:1–12. doi: 10.1159/000362689. PubMed    

  106. Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z Naturforsch, C, J Biosci. 2016;71:191–199. PubMed

  107. Sammi SR, Trivedi S, Rath SK, Nagar A, Tandon S, Kalra A, Pandey R. 1-Methyl-4-propan-2-ylbenzene from Thymus vulgaris Attenuates Cholinergic Dysfunction. Mol Neurobiol. 2016 doi: 10.1007/s12035-016-0083-0. PubMed   

  108. Lee Y. Cytotoxicity evaluation of essential oil and its component from zingiber officinale roscoe. Toxicol Res. 2016;32:225–230. doi: 10.5487/TR.2016.32.3.225. PMC free article  PubMed     

  109. Bakkali F, Averbeck S, Averbeck D, Idaomar M. Biological effects of essential oils-a review. Food Chem Toxicol. 2008;46:446–475. doi: 10.1016/j.fct.2007.09.106. PubMed    


by Leave a comment

Forest Bathing Scientifically Validates The Cannabis Entourage Effect

Introduction

The extensively-studied phenomenon known as “Forest Bathing” in Japan and South Korea and as “Kneipp Therapy” in Germany involves exposure to high concentrations of naturally-occurring aerosolized phytochemicals in conifer & deciduous forests.

This natural treatment for conditions ranging from asthma to dermatitis has been documented and validated by a raft of high-quality medical and scientific research.

There is no question that “Forest Bathing” has therapeutic benefits. For example, positive effects on NK (Natural Killer) cell activity have been shown with in vitro treatment of tumor cell lines with monoterpenes released from trees (and of course present in Cannabis flowers) such as d-limonene and α-pinene, and also in forest bathing trips. The anti-tumor effects act by increasing intra-cellular levels of anti-tumor proteins such as perforin, granulysin, and granzymes A/B.

Haven’t heard of “Forest Bathing”? I hadn’t either until I ran across it during some intense research into naturally-occurring environmental Cannabis terpene aerosols. The ancient Japanese natural health practice called “Shinrin Yoku”, defined as “taking in the forest atmosphere” or “forest bathing”, has a wide range of rigorously tested and proven health benefits.

In 2005 the Japanese government introduced a nationwide “Therapeutic Effects of Forests Plan” that pays “Forest Bathing” health benefits. The government says that it pays for this therapy because of the proven reduction in other health care costs across the spectrum.

South Korean scientists and public health researchers have documented a wide range of positive health benefits from exposure to terpenes in the air of coniferous forests, with variations among the terpenes in different species of trees at different locations accounting for differences in the health benefits of inhalation of forest air.

They have divided the country into numerous micro-climes where particular combinations of coniferous tree species co-exist and perfume the air, each location offering a particular healing, stimulating mix of terpenes and other phytochemicals.

Interestingly, the dominant terpenes in the air of these forests are the same terpenes that characterize different Cannabis strains and the same kinds of variability in Cannabis strains similarly account for their differing health benefits.

There is also a natural medicinal therapy in Germany called “Kneipp Therapy”, that involves a series of exercise routines done in a terpene-rich forest environment. Kneipp Therapy has been studied using quality clinical research protocols and the exercises have been found to be significantly more beneficial when performed in a forest environment compared to other kinds of locations. 

So, it’s both very interesting and very significant for establishing the validity of the Cannabis “Entourage Effect” that the dominant terpene profiles of all of the therapeutic forests studied in the Japanese and Korean “Forest Bath” scientific literature (cited below) appear to be various combinations of myrcene, pinene, limonene, linelool, and a number of less-celebrated but still important Cannabis terpenes like cynene, terpinene and boneal. There are many other “minor” phytochemicals shared between the airborne perfumes of Cannabis flowers and therapeutic forests, and almost certainly many of these will ultimately be shown to play significant roles in both the Forest and the Cannabis “Entourage Effect”.

Bottom line – I believe that there is an inescapable argument in favor of the Cannabis “Entourage Effect” presented by the “Forest Entourage Effect”, which itself is definitively established in international, if not US, scientific and medical literature.

Discussion:

There has been extensive research in multiple advanced countries on the health benefits of exposure by inhalation and skin absorption to the airborne terpenes in forest environments – interestingly enough, these turn out to be the same terpenes that are inhaled in the vapors from Cannabis flowers.

“Forest Bathing” research establishes that inhaling a naturally-occurring mix of terpene emissions or vapors has far greater health benefits than exposure to or ingestion of any of the terpenes and other phytochemicals singularly, like in a pill or other oral or topical medication.

Cannabis visionaries have always known that the THC was only one element of the sensual pleasures and only one of the sources of health benefits from the sacred flower, just as wine lovers have always known that the alcohol is only a relatively small part of their total experience. Nobody drinks a bottle of Etude Pinot Noir or Chateau Pomerol Bordeaux for the alcohol, and nobody chooses which Cannabis flower to enjoy simply on the basis of THC content, although that approach seems to dominate much of today’s adolescent-style Cannabis marketing. Even the most dedicated couch-locked stoner knows very well that there is a world beyond THC and may spend a lot of time (if they’re not too ripped)  thinking about taste and aroma options when they’re choosing between Durban Poison and Granddaddy Purple.

However, the concept of a Cannabis “Entourage Effect” has been universally ridiculed by anti-Cannabis forces who say that the supposed variety of effects of different Cannabis strains is simply a kind of mass delusion.  They claim that there is no evidence that different phytochemical profiles of different Cannabis strains signal different health and well-being effects, and say that in their expert, informed scientific opinion such observations are imaginary. While their criticisms are couched in the careful, apparently rational language of science, and even rated a major article in Scientific American in 2017, all of the criticisms amount to a simple “It’s all in your head” dismissal.

In other words, the anti-Cannabis establishment says tough, there’s no scientific evidence to support your claim, and there’s not going to be any evidence either because we aren’t going to fund research.

Well, I’ve got some news for these die-hard prohibitionists.

OK, they have managed to impede research that could validate many of the medical benefits of the whole Cannabis Flower as opposed to plain old THC extract. With notable medical research exceptions, many of the health and sensual benefits ascribed to the Cannabis Flower are currently only validated by experience and consensus, both of which the scientists are fond of reminding us can be way off target. They point to the flat earth delusion, or to many other instances where “everybody knows” something that simply isn’t true, and smugly point out that nobody can prove all these marvelous things we’re saying about Cannabis.

It’s hard to find a reasonable explanation of why the Federal government has arrayed its dark-side powers against the Cannabis flower, but in this match between the Flower and the Power it’s beginning to look like the Power is going to lose this one because Forest Bathing research actually provides plenty of evidence . The research unequivocally supports the validity of the “Entourage Effect” by demonstrating that naturally-occurring environmental terpene and phytochemical aerosols do have measurable, verifiable positive impacts on overall health as well as on specific diseases and conditions, and do vary among forest tree species and environments in the same ways that Cannabis flowers vary among strains in response to environmental variables.

Forest Bathing research is directly applicable to validating the “Entourage Effect” of Cannabis terpenes and phytochemicals that are widely observed but, according to the Federal propagandists,  not “scientifically verified”. As an example, there is solid research that says that terpene emissions from plants are directly correlated with the concentration of terpenes in the plant. The higher the concentration of terpenes, the greater the emissions from the plant. “Forest Bathing” research naturally focuses on terpene emissions from coniferous and to a lesser degree deciduous trees, but the relationship between terpene concentrations and emission rates has been widely replicated in studies with agricultural crops and seems to apply to all plants.

The bottom line is that clinical literature as well as popular wisdom in several countries points to the health benefits of inhaling and “bathing in” an atmosphere rich in terpenes and other phytochemicals. While the health benefits of many of the individual components of this phyto-soup are only recently becoming well-known, the benefits of exposure to the entire environmental complex of a pine/conifer forest are familiar to anyone who has ever walked outdoors that first morning in a forest campground.

A recent study concluded: “Exposure to natural environment is beneficial to human health. Among environmental exposures, the effects of forest have been emphasized in many studies. Recently, it has been shown that a short trip to forest environments has therapeutic effects in children with asthma and atopic dermatitis. Based on these studies, healthcare programs to use forest have been developed in several countries. Forest bathing has beneficial effects on human health via showering of forest aerosols. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds.”

So, it’s clear that relaxing for a few hours in a forest environment filled with terpenes can be beneficial and even therapeutic for people with a wide range of diseases and conditions from dermatitis to cancer. Do a simple internet search for “forest bathing’ and you’ll find books, resorts, videos and even classes. But enter “cannabis bathing” into a search and you’ll get bath salts, bubble bath, and a lot of fruit-flavored massage and lubricating oils.

For the past year or so I have been exclusively using a vaporizer to enjoy Cannabis flowers and I can add my experiences to the observations of many others that whole flower Cannabis vapor is a marvelous clean, natural high which, now that I realize it, is almost exactly like stepping out of my tent high in the pine forests of the Oregon Cascades and inhaling that first breath of vibrant, aromatic, high-energy mountain air.

So in my opinion all this research on “Forest Bathing” makes the smug “You can’t prove it and we’re not going to let you” chant of the anti-Cannabis “scientists” pretty much irrelevant. Sooner or later there will actually be research on every aspect of inhaled and absorbed Cannabis terpenes and other phytochemicals but until then the parallel research on Forest Bathing should be more than adequate scientific evidence for any reasonable person of the validity of the Cannabis “Entourage Effect”.

Selected Bibliography

Frumkin H. Beyond toxicity: human health and the natural environment. Am J Prev Med. 2001;20:234–240. doi: 10.1016/S0749-3797(00)00317-2. [PubMed]

Tsunetsugu Y, Park BJ, Miyazaki Y. Trends in research related to “Shinrin-yoku” (taking in the forest atmosphere or forest bathing) in Japan. Environ Health Prev Med. 2010;15:27–37. doi: 10.1007/s12199-009-0091-z. [PMC free article] [PubMed]

Seo SC, Park SJ, Park CW, Yoon WS, Choung JT, Yoo Y. Clinical and immunological effects of a forest trip in children with asthma and atopic dermatitis. Iran J Allergy Asthma Immunol. 2015;14:28–36. [PubMed]

Spievogel I, Spalek K. Medicinal plants used in pediatric prophylactic method of Sebastian Kneipp. Nat J. 2012;45:9–18.

Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B. Use of complementary and alternative medicine in Germany: a survey of patients with inflammatory bowel disease. BMC Complement Altern Med. 2006;6:19. doi: 10.1186/1472-6882-6-19. [PMC free article] [PubMed]

Kawakami, K., Kawamoto, M., Nomura, M., Otani, H., Nabika, T., & Gonda, T. (2004). Effects of phytoncides on blood pressure under restraint stress in SHRSP. Clinical and Experimental Pharmacology and Physiology, 31, S27–S28.

Li, Q., Kobayashi, M., Wakayama, Y., Inagaki, H., Katsumata, M., Hirata, Y., Hirata, K., Shimizu, T., Kawada, T., & Park, B. (2009). Effect of phytoncide from trees on human natural killer cell function. International Journal of Immunopathology and Pharmacology, 22, 951–959.

Li, Q. (2010). Effect of forest bathing trips on human immune function. Environmental Health and Preventive Medicine, 15, 9–17.

Ormeño, E., Gentner, D. R., Fares, S., Karlik, J., Park, J. H., & Goldstein, A. H. (2010). Sesquiterpenoid emissions from agricultural crops: correlations to monoterpenoid emissions and leaf terpene content. Environmental Science & Technology, 44, 3758–3764.

Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y. The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan. Environ Health Prev Med. 2010;15:18–26. doi: 10.1007/s12199-009-0086-9. [PMC free article] [PubMed]

Song C, Ikei H, Miyazaki Y. Physiological effects of nature therapy: A review of the research in Japan. Int J Environ Res Public Health. 2016;13:E781. doi: 10.3390/ijerph13080781. [PMC free article] [PubMed]


by Leave a comment

Withholding The Cannabis Chorea Cure = Pig Pharma Profits

What if there was a natural medicine that could not only control Huntington’s Chorea, as well as chorea stemming from other non-genetic diseases and conditions, but quite possibly cure it?

What if instead of having to take a medicine that may force you to think about suicide, you could take the extract of a simple flower and re-discover how good life is without chorea?

What if the medical profession published numerous medical journal articles about this natural medicine 150 or so years ago, when it was a standard successful treatment for chorea?

And finally, what if for the last 80 years or so the combined power of the US government and Pig Pharma corporations had made possession of this natural medicine grounds for slamming you in prison for a long, long time? That would be – let’s see, what’s the opposite of “Awesome”?

Huntington’s disease is a neurodegenerative disease and most common inherited cause of chorea. Other non-inherited causes of chorea are show in the graphic above.

Chorea is characterized by brief, semi-directed, irregular movements that are not repetitive or rhythmic, but appear to flow from one muscle to the next. When chorea is serious, slight movements will become thrashing motions.

The characteristic movements of chorea often include twisting and writhing. Walking may become difficult because of uncontrollable body postures and leg movements.

Unlike ataxia, which affects the quality of voluntary movements, or Parkinsonism, which is a inhibition of voluntary movements, the movements of chorea occur involuntarily, without any conscious effort to move a limb, an extremity (hands or feet), the head or neck, or any other part of the body. Because all movements associated with chorea are involuntary, it is classified as a hyperkinetic movement disorder.

The only answers that Pig Pharma has for Chorea are treatments, not cures. One of the most commonly prescribed “medicines” is tetrabenazine. Among the risks associated with tetrabenazine’s use are: sedation, fatigue, insomnia, akathisia, anxiety and nausea. Oh, and also tetrabenazine increases the risk of depression and suicidal thoughts and behavior in people afflicted with Huntington’s disease. So it doesn’t cure you, but it may make you decide to kill yourself. Nice drug. All the other Pig Pharma answers to Huntington’s Disease pose similar risks and do not cure Chorea.

In fairness, it is important to point out that one of the following reported cases of someone with chorea who was healed by Cannabis, was a young girl who had suffered from a bout of rheumatic fever a month prior to the onset of Chorea. It is well-established (in 2018) that one type of Chorea, Sydenham’s chorea, occurs as a complication of streptococcal infection, and that twenty percent of children and adolescents with rheumatic fever who are left untreated with antibiotics develop Sydenham’s chorea as a complication. So it is possible, even likely, that what Dr. Douglas is describing is a strep infection leading to Chorea – in other words, a sub-set of Chorea. However, since Cannabis is not an antibiotic, it seems unlikely that in this case being described its beneficial use in the treatment of Chorea would be confined to this single sub-set of the disease. Plus the instance of this young girl is only one of many Cannabis chorea cures that are described in this medical journal article from 1869.

Fortunately for people suffering from Huntington’s today, in most places Cannabis is available for self-treatment, and in the more advanced states there are even physicians who have bothered to learn and build on what their colleagues discovered 150 years ago, ignoring the poisons being pushed by Pig Pharma.

Here is one example of what has been known and withheld from those who suffer for eight generations. The research isn’t perfect, and the doctor is very much trapped in many of the false assumptions of his day, but he is clear on one thing – Cannabis is a powerful natural medicine that is safe and effective for treating neurological diseases like Chorea.

FROM THE EDINBURGH MEDICAL JOURNAL FOR MARCH 1869.

By Dr. Douglas F.R.G.P.E.

Vice-President of the Medico-Chirurgical Society of Edinburgh

February 4th, 1869

THE USE OF INDIAN HEMP IN CHOREA

The value of Indian hemp as a therapeutic agent is well established, but a singular difficulty has been experienced in securing for it the confidence to which it is evidently entitled. Without attempting to explain or to excuse this difficulty, I propose to illustrate what appears to me one of its most useful applications.

The negative virtues of the drug are amongst its chief merits. Dr. Russell Reynolds, who writes one of the most recent, and one of the best expositions of the value of this remedy, tells us, as the result of a manifestly practical and thoughtful experience, that it is a soporific, anodyne and antispasmodic; and that it relieves pain and spasm: that it does not leave behind it headache nor vertigo; nor does it impair the appetite nor confine the bowels. These important virtues accord with anything I have seen of its action; nor have I met with any annoyance in practice from its peculiar action on the emotional or intellectual state of the sick. We are apt to be deterred from the use of a remedy by such pictures of its more peculiar actions, as are given of the abuse of the drug in countries where it is resorted to as a means of intoxication, and of its action in the cases of patients who under its use became tortured by ocular illusions and spectres of horrible form.

I do not doubt that such effects result from the use of the drug; but, in prescribing it, I have not met with them, and I am disposed to think that they are to be avoided even more certainly than we can guard against the unpleasant effects of opium.

As in the case of other useful drugs, the contradictory and extreme views of the efficacy and certainty of its therapeutic action, urged by writers of high authority, have retarded confidence in cannabis Indica; and indeed its applications to disease seem scarcely to have been investigated with the reliance which its demonstrated energy would justify. It is now many years since Dr. Dominic Corrigan published a series of cases which underwent cure in the course of four or five weeks, mainly by the use of the cannabis Indica, in doses of five minims of the tincture, increased to twenty-five: one of the cases, being of ten years standing, was cured in a month. (Archives of Medicine. Edited by Lionel S. Beale, M.B. Vol. ii. London Medical Times, 1845.)

One cannot resist the impression that other elements in the treatment, besides the administration of the cannabis, had need to be taken into account in the explanation of such cures; and moreover, before the actual value of the drug in such cases can be determined, a minute statement of the clinical and pathological relations of each case would be required i.e., how far the case might be one of chorea arising in connexion with rheumatism, struma, cerebral or spinal disease, or in connexion with some more temporary source of irritation in the system, as from derangement of the digestive or of the generative or other functions.

Again, we find Dr. Wilks of Guy’s Hospital arguing that, because fifty remedies have been found to cure such a disease as chorea, it may be safely left to itself. Accordingly, Dr. Wilks, admitting the usefulness of Dr. Hughes favourite and useful remedy, rhubarb steeped in port wine, prescribes to his patients the syrup of orange, that students may witness the spontaneous cure of the disease; and his patients, like Dr Corrigan’s, left the hospital cured in about a month.

Nevertheless, whatever preference we may have for a medicine expectant, that permits the sick to recover, over the heroic measures, whose advocates claim to have cured the patients who escape out of their hands, thoughtful practitioners will not be prevented from inquiring into the nature and the extent of special therapeutic actions by the scepticism of doubters nor by the rash generalizations of hasty observers.

Jane Williamson, aged 13, was admitted into the Chalmers Hospital under my care on the 15th of October last. She had the look of previously good health, and she was well nourished, but not robust. At the date of her admission, she presented the awkward gesture and the grimace of established chorea, though not severe in its degree. Temperature was natural; pulse 90, rather small; there was slight rheumatic pain of the knees and elbows, and an excited state of the heart’s action. The urine was loaded with lithates, it was normal in density, about 30 oz. in twenty-four hours. The bowels were easily regulated.

The treatment, in the first instance, consisted in the administration of a solution of the acetate of potash, with infusion of digitalis, and four minims of Fowler’s solution thrice a day.

The history of her previous illness given by herself and her friends was that, about a month previously, she was taken with a not intense attack of rheumatic fever. She suffered a good deal from the state of the larger joints; no symptom of cardiac inflammation appeared to have existed, but, for about a fortnight preceding her admission, she presented choreal action, gradually increasing indegree and affecting the extremities and face. . .

During the days immediately succeeding her admission, a rapid change occurred in the degree of the choreal movements, and in the state of the heart’s action. The latter became so disturbed, feeble, and excited, with feeble arterial pulse, as to cause serious anxiety for the safety of the patient, and at the same time the choreic agitation increased with such violent restlessness and 1 oiling in bed that excoriation occurred over the sacrum and both nates, while contortion of the features and tossing of the extremities, especially when their movement was attempted, continued excessive, the articular effects of rheumatism decreased, temperature became more natural, and urine healthy, but the bowels became torpid. The arsenic was persevered with, and a few 30-grain doses of bromide of potassium were given. Each dose was followed by a short period of quiescence, but, on the 20th, the excitement of the heart’s action became so alarming that 25-minim doses of tincture of Indian hemp were administered, followed by apparently marked, but only transient abatement of the spasmodic movement, which, as Dr. Hogg, the resident physician, reported, seemed to recur subsequently with increased and distressing severity.

On the following day, that is, the sixth of her residence in the Hospital, her condition seemed desperate, chiefly on account of the protracted and uncontrollable hurry of the heart’s action. She was ordered to have six minims of the tincture of cannabis every hour, the arsenic and other remedies being intermitted. The bowels were now well regulated, the excoriations of the back and nates had increased so as to form superficial sloughs of considerable extent, the pulse was small and so rapid as not to be counted, and the heart’s action was still feeble, rapid, and disturbed. She had four ounces of brandy per day. On the following day, having had twenty doses of the tincture, there was marked and increasing improvement. The violence of the tossing and rolling had diminished materially, though still it was necessary to have her secured in bed to prevent her falling or rolling over. From this time till the 15th day of her residence in the hospital, the tincture was administered from hour to hour, and she continued to make daily and progressive improvement. At that date (the 28th) she had been free of all the more violent spasmodic movements for two days and the heart’s action was quiet, pulse about 80, appetite good, bowels regular. She still presented a degree of the peculiar grimace, with awkwardness in protruding the tongue and in movement of the arms and hands. There was great mental lethargy, with languor and exhaustion, which made it impossible for her to be out of bed.

The tincture of hemp was now discontinued, and arsenical solution in four-minim doses resumed.

The subsequent progress of the case, though tedious, and so far disappointing, may be told in a few sentences. On the 1st of November, and on several occasions during the rest of that month, there occurred a renewal of the choreal state, which had not indeed absolutely disappeared, though it was often so trivial and even absent as to encourage the hope of an early recovery. Arsenic was perseveringly employed, with a carefully-regulated diet and general management, but on each occasion, of which three were noted, when an exacerbation of the choreic condition arose, a marked abatement of the muscular action resulted from the administration of small and hourly-repeated doses of tincture of hemp, relief sometimes arising so speedily as within six or eight hours. On one occasion the improvement was not decided for three or four days.

In the beginning of December, rheumatic symptoms recurred with slight febrile action and articular pains and renewal of choreic agitation. At the same time, marked excitement of the heart’s action was renewed, and now, for the first time, a faint soft diastolic murmur, indicative of aortic regurgitation, was with difficulty perceived. A weak solution of acetate and nitrate of potash was administered, and grain doses of opium four or five times in twenty-four hours. Pain arid fever abated, but not the spasmodic movement, and on the third day afterwards six-minim doses of tincture of hemp were given every two hours, followed by an immediate decrease of the chorea, which at once declined to its slightest degree in two or three days.

The patient now presented more marked indications of returning health. The state of mental lethargy into which she had early lapsed was now passing off; her appetite was revived, and on the 20th December she was able to be out of bed and to walk with assistance. Small doses of the iodide of potassium with the infusion of quassia were given, and improvement went on uninterruptedly; she did not, however, cast off the choreic jerk and awkwardness till the second week of January 1869. She has since had a very comfortable convalescence, but the diastolic murmur noted above continues strongly developed.

In the remarks I have to offer on this case, I confine myself to the points which illustrate the value and application of cannabis Indica in the treatment of choreal spasm. It is well said by Dr. Hughes, that each case of chorea, like each case of every other disease, should be separately studied; and though it may be regarded as one of a class, should still be viewed as a distinct individual of the class. In the case of my patient, the general characteristics of the attack point it out as an example of a large class of cases in which acute rheumatism constitutes the primary and originating source of chorea, while its special features simply declare the degree of chorea, with its repeated recurrences, and the unusual violence of agitation, to have been more than ordinarily severe, without any such personal or inherited constitutional peculiarity as exists in certain forms of this and of other nervous diseases.

Connected with the severity of the chorea, an inquiry of some difficulty arises out of the condition of the heart, particularly its disturbed action in the early stage, and the endocarditic lesion which occurred later, and which declared its presence only with the renewed rheumatic attack in the beginning of December. At the time of her admission and subsequently, notwithstanding the extra-ordinary hurry of the heart’s action, I persuaded myself that there was no organic nor inflammatory lesion, and I came to the conclusion that the severity of the choreic state had extended to the heart. The evidences of endocarditis subsequently developed cast doubt on my view of the previously choreic state of the heart; and there does not appear to be any means of solving the question beyond the opinion of those who saw the patient.

It certainly seems unlikely that endocarditis capable of causing such extreme disturbance of the heart’s action should have existed, unaccompanied from the outset by other indications of its presence.

This point possesses some interest in connexion with the view advanced by Dr. Russell Reynolds, that Indian hemp has been of no service in those affections of mind, sensation, or motility, which are simply functional in their character, or, at all events, have no established morbid anatomy. On the other hand, that it has afforded notable relief in cases where organic disease existed.

I do not agree with this view, but it would be beside my object to discuss it here. On the supposition, however, that the view is a sound one, it suggests that, in my patient, the organic lesion had originated in the heart at an early stage of the attack, and, consequently, the beneficial effects of the cannabis were so readily exerted. On the whole, the conclusion is a fair one, that endocarditis was present earlier than appeared; though still, I cling to the view that the disturbed action was, in the first instance, functional and choreic.

The practical interest of my case, however, consists in the illustration it affords of the special use and application of cannabis in the treatment of choreal spasm, and of the mode in which the remedy may be administered in many cases, if not in all. I have already remarked on the mistake, as it seems to me, of looking for general curative results in this or in any disease from the mere general application of special therapeutic observation or experience.

I think the cases and cures of chorea by tincture of hemp reported, to whlch I have referred, illustrate the fallacy of such reasonings; but, on the other hand, the case of my patient suggests that there is a special, and perhaps a frequently useful, application of the drug in such circumstances. The impression which the case leaves on my mind is, that cannabis has a peculiar value and power in controlling the irregular movements of chorea, which ever and again are terribly distressing, and possibly even dangerous, to the patient; and it would be of no small moment to determine the extent and limit of its influence, and to ascertain whether or not choreic action, even in slighter cases, might not be moderated by this remedy.

The result of repeated trial in my patient seems to show, on the one hand, that the violence of choreal action was speedily moderated; and the protracted duration of the case, on the other hand, makes it sufficiently evident that the virtue of the remedy did not reach farther in the direction of removal and radical cure of the disease. This points to an important question in the treatment of chorea, which has been mooted by many writers on the subject, viz., how far the chorea is to be dealt with as an independent condition, and how far its treatment and removal will be best achieved by the treatment of the diseased state out of which it has sprung?

I think that systematic writers and clinical lecturers have dealt with the subject of chorea too much as an independent disease, and that the late Dr. Babington, of London, in his justly-admired paper on chorea, indicated a sound and philosophic principle, when he advised that when the disease has arisen by metastasis of rheumatism, it should be treated in the same way as pericarditis is treated.

Recognising, then, the principle that our chief aim in the treatment is to combat the constitutional state, or the local disease in connexion with which the chorea has arisen, I conclude farther, from the case I have read, that an important aim must sometimes, if not at all times, be to allay the severity of the choreal state by the use of cannabis, or by other means. On this point, I cannot resist quoting from M. Trousseau his earnest utterances in the behalf of tartar emetic as a means of subduing the violence of choreal agitation: “Unfortunately,”says that learned physician, “there are cases in which the convulsive agitation is of such violence that all known means are without avail, and the physician too often sees poor young girls perish miserably, the skin rubbed and deeply ulcerated by incessant friction, that no appliance can obviate.

But surely, in such circumstances, cannabis Indica is a far more appropriate remedy than tartar emetic, affording, as M. Trousseau adds, “if  though only in exceptional cases, a chance of success where  we appeared impotent.”

The limit of the therapeutic action of cannabis Indica in these cases is incidentally indicated, with a thoroughly practical wisdom, by Dr Williams and by Dr Walshe. So long ago as in 1843, Dr Williams is reported to have said, in the course of a discussion, that he had found it “ relieves chorea during its exhibition, but without radical effect on the disease.”

In 1849, Dr Walshe, in a clinical lecture, says: “Not only was its sedative effect marked in degree, but it was almost immediate in point of time, leaving no doubt on my mind as to the reality of its influence.”

The recurrent attacks of chorea in the case of my patient afforded the means of direct illustration of the efficacy of the drug in subduing the choreal state. for repeatedly the same result was witnessed in the speedy and more or less complete subsidence of the agitation under the use of the remedy, and the decided effect produced on the heart’s action tends to confirm me in the impression that the disturbed state of that organ was largely choreal.

As to the mode of administering the remedy, small and frequent doses proved both safe and effective, and great advantage appeared to arise from increasing the frequency of the dose rather than its amount. Believing, as I do, that cannabis Indica is a remedial agent of value in many and various maladies, I am prepared to recommend this mode of seeking its effects by frequent rather than by larger doses at longer intervals. Such a mode of prescribing it has not been usual; but I find, quoted from an American source, the account of a case of hiccup treated in this way by eight-drop doses of a fluid extract, administered hour by hour, in which recovery from an attack that had defied treatment for five days took place in a few hours.

I have brought this case under the notice of the Medico-Chirurgical Society, not on account of any novelty in its history, nor on account of any conclusions it very positively points to, but simply to bring anew to the light of day an important therapeutic fact, which seemed like to be buried in the pages of undisturbed magazines, and which, probably, has an important application, not only to distressing and dangerous cases of chorea, but even to slight and ordinary cases, as well as to cases of other spasmodic diseases, such as hiccup, irritable heart, asthma, tetanus, and the like.

If you would like to have a copy of this 1869 article by Dr. Douglas as a PDF file please email me with your request.