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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.

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