Lion's Mane (Hericium erinaceus)

What is Lion's Mane?

Lion's mane is a medicinal wood-rotting fungus with a characteristic growth pattern that resembles the shaggy mane of a lion.

The fungus prefers temperate forests in North America, Europe, and Asia where it thrives on living oak, beech, or conifer trees.

The medicinal benefit of lions mane primarily involve the nervous system. Modern applications use the mushroom for general cognitive health and as a natural nootropic substance.

This mushroom is also eaten as a delicacy — with a flavor similar to lobster when cooked with butter.

In recent years lion's mane has caught the eye of the nootropic community for its ability to up-regulate nerve growth factor.

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How Is Lion's Mane Used?

Lion's mane is mainly used for neurodegenerative disorders like dementia and multiple sclerosis. It's also popular as a nootropic agent for supporting optimal cognitive function long term.

Most of the people using this fungus take it in the form of a powdered capsule or tincture on a daily basis. Like most medicinal mushrooms, the biggest benefit comes from using the herb on a regular basis over long periods of time — rather than short bursts for quick impact of effects.

Traditional Use of Lion’s Mane

Lion’s mane mushrooms have a long history of use in Eastern Asia — including China, Korea, and Japan. Each of these regions used the mushroom for treating neurological disorders, including neurasthenia, and age-related cognitive decline, as well as for general health.

Herb Details: Lion's Mane

Herbal Actions:

• Antibacterial
• Anticancer
• Antidiabetic
• Antioxidant
• Cardioprotective
• Hepatoprotective
• Nervine
• Immunomodulator

Weekly Dose

• (1:2 Liquid Extract)
  20-60 mL
• View Dosage Chart

Part Used

• Fruiting Body

Family Name

• Hericiaceae

Distribution

• North America, Europe, Russia, Mountainous regions of Asia

Constituents of Interest

• Hericnones
• Erinacines
• Lactones
• Polysaccharides

Common Names

• Lion's Mane
• Monkey's Head
• Hedgehog Fungus
• Pom Pom
• Houtou (China)
• Shishigashira (China)
• Yamabushitake (Japan)

Pregnancy

• Safe during pregnancy.

Duration of Use

• Long term use acceptable and recommended.

Mycological Information

The Hericiaceae family of fungi are saprophytic (consumes dead wood), yet can be found growing on living trees as well. Many experts believe the mushroom has a mutualistic relationship with the tree for some time — helping it resist disease and infection, but will eventually consume the tree after it dies.

Hericium mushrooms normally grow in cooler, mountainous regions across the globe. It contains a number of species used medicinally and nutritionally.

Hericium spp. has characteristic "tooth" structures on its fruiting body, giving it a hair-like appearance.

Pharmacology & Medical Research

+ Neuroprotective

Lion’s mane offers several different mechanisms to produce its overall neuroprotective benefits:

1. Antioxidant and free-radical scavenging activity [6]
2. Anti-inflammatory activity
3. Nerve-growth factor stimulation (hericium and erinacenes)
4. Reduction of endoplasmic reticulum stress-dependant cell death (dilinoleolyl-phosphatidylethanolamine (DLPE) [7]
5. Attenuation of beta-amyloid-related cognitive decline in animals (dementia model) [8]
6. Enhance mylenation of neurons [9, 10, 11]

In animal studies, lion’s mane has been shown to reduce the severity of damage after a stroke — effectively protecting the sensitive neurons from ischemic damage [6].

Clinical Trials:

Study: Mori et al., 2009 — Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double‐blind placebo‐controlled clinical trial. [5]

This randomized, double-blind, placebo-controlled clinical trial involving 30 Japanese men and women with mil cognitive impairment found that after 16 weeks, the lion’s mane group had significantly increased cognitive scores. These improvements were noted as early as the 8 week checkup, and continued to improve compared to placebo over the rest of the 16-week trial.

The dose of lion’s mane used in this study was 1 gram of dried lion’s mane taken three times per day.

Unfortunately, 4 weeks after the trial concluded, the scores had significantly decreased — indicating that these effects are not permanent and the mushroom needs to be continued to remain effective.

+ Nootropic

A nootropic is a substance that improves cognition without causing harm. There are a lot of nootropic substances that range from herbs like lion’s mane or rhodiola, to synthetic or prescription drugs like Modafinil or Noopept.

Lion’s mane is thought to be a nootropic through its ability to promote nerve-growth factor (NGF) in the brain. NGF is the most potent growth factor for the cholinergic neurons. it influences everything from the proliferation, differentiation, and survival of neuronal cells in the brain [8, 12].

Reductions in NGF has been considered a major implication in conditions such as depression, substance abuse, Alzheimer’s disease, and Huntington’s disease [12].

There have been a lot of studies looking at the role of lion’s mane and nerve growth factor — most of which have concluded that lion’s mane applications directly lead to an increase in NGF. This research has been done both in vivo and in vitro [13, 14, 15, 16].

This effect is very important. We can give peptides like NGF to people to treat these neurodegeneration, but these peptides rarely cross the blood brain barrier [9]. Therefore, finding alternative ways to boost NGF or other peptides in the brain are of the utmost importance in the treatment, prevention, and management of neurodegenerative disorders.

+ Immunomodulation

Like many other medicinal mushrooms, lion’s mane contains a high concentration of polysaccharides with immunomodulatory effects.

A lot of this study has been done in vitro with dendritic immune cells. These cells serve as the antigen-presenting cells that act as central mediators for the immune response as a whole. They’re responsible for a lot of the tolerance formed by the immune system to help maintain homeostasis.

Studies involving lions mane extracts have shown the fungus can stimulate the maturation of dendritic cells, induce dendritic cell activation, and modulate key T-helper (Th1) immune responses [17].

+ Anti-Inflammatory

Lion’s mane has been shown to influence a variety of inflammatory mediators, including:

Induces IL-1β expression through Nf-kB, NF-IL6, and activator protein 1 (AP-1) [18]

Induces iNOS gene expression to increase nitric oxide (NO) production in macrophages

Inhibits toll-like receptor 4 (TLR4)-JNK signalling on macrophages [19]

Phytochemistry of Lion’s Mane Mushrooms

Lion’s mane fruiting body and myclelia contain an exceptionally diverse range of unique bioactive substances — including polysaccharides, meroterpenoids (hericinones), cyathane diterpenoids (erinacines), steroids, alkaloids, and lactones.

The most significant constituents in terms of the mushrooms medicinal action are the hericenones and erinacines. Both of these substances have been shown to stimulate nerve growth factor in the central nervous system. This is thought to be the primary mechanism for which the fungus an improve the health and function of the nervous system.

Clinical Applications Of Lion's Mane:

Lion's mane has many uses, but the most well-known is as a neuroprotective, and nootropic benefits. It's useful for neurodegenerative disorders including multipple sclerosis, Alzheimer's disease, and Parkinson's disease.

Other uses include depression and anxiety, cancer, diabetes, gastrointestinal infection, and fatigue.

Cautions & Safety

Lion’s mane is a culinary mushroom that’s been used for both food and medicine by countless individuals over several hundreds of years. There are no expected short-term or long-term side effects from using the fungus.

Throughout the clinical research there have been no reports of serious side effects from using the fungus — including very high-potency extracts and long-term durations of use.

Caution advised with any blood clotting conditions or medications due to possible agonistic interactions — including haemophilia or other bleeding disorder, thrombocytopenia, or post-surgery. Lion’s mane may interact with blood thinners or anti-platelet medications.

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated April 2020)

Recent Blog Posts:

References

[1] — Friedman, M. (2015). Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (lion’s mane) mushroom fruiting bodies and mycelia and their bioactive compounds. Journal of agricultural and food chemistry, 63(32), 7108-7123.

[2] — Liu, J., Du, C., Wang, Y., & Yu, Z. (2015). Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus. Experimental and therapeutic medicine, 9(2), 483-487.

[3] — Thongbai, B., Rapior, S., Hyde, K. D., Wittstein, K., & Stadler, M. (2015). Hericium erinaceus, an amazing medicinal mushroom. Mycological progress, 14(10), 91.

[4] — Wong, K. H., Naidu, M., David, R. P., Bakar, R., & Sabaratnam, V. (2012). Neuroregenerative potential of lion's mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers.(higher Basidiomycetes), in the treatment of peripheral nerve injury. International journal of medicinal mushrooms, 14(5).

[5] — Mori, K., Inatomi, S., Ouchi, K., Azumi, Y., & Tuchida, T. (2009). Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double‐blind placebo‐controlled clinical trial. Phytotherapy Research, 23(3), 367-372.

[6] — Lee, K. F., Chen, J. H., Teng, C. C., Shen, C. H., Hsieh, M. C., Lu, C. C., ... & Huang, W. S. (2014). Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. International journal of molecular sciences, 15(9), 15073-15089.

[7] — Nagai, K., Chiba, A., Nishino, T., Kubota, T., & Kawagishi, H. (2006). Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuro2a cell death via protein kinase C pathway. The Journal of nutritional biochemistry, 17(8), 525-530.

[8] — Mori, K., Obara, Y., Moriya, T., Inatomi, S., & Nakahata, N. (2011). Effects of Hericium erinaceus on amyloid β (25-35) peptide-induced learning and memory deficits in mice. Biomedical Research, 32(1), 67-72.

[9] — Phan, C. W., David, P., Naidu, M., Wong, K. H., & Sabaratnam, V. (2015). Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Critical Reviews in Biotechnology, 35(3), 355-368.

[10] — Kolotushkina, E. V., Moldavan, M. G., Voronin, K. Y., & Skibo, G. G. (2003). The influence of Hericium erinaceus extract on myelination process in vitro. Fiziol Zh, 49(1), 38-45.

[11] — Moldavan, M., Grygansky, A. P., Kolotushkina, O. V., Kirchhoff, B., Skibo, G. G., & Pedarzani, P. (2007). Neurotropic and trophic action of lion's mane mushroom Hericium erinaceus (Bull.: Fr.) Pers.(Aphyllophoromycetideae) extracts on nerve cells in vitro. International Journal of Medicinal Mushrooms, 9(1).

[12] — Chao, M. V., Rajagopal, R., & Lee, F. S. (2006). Neurotrophin signalling in health and disease. Clinical science, 110(2), 167-173.

[13] — Zhang, C. C., Yin, X., Cao, C. Y., Wei, J., Zhang, Q., & Gao, J. M. (2015). Chemical constituents from Hericium erinaceus and their ability to stimulate NGF-mediated neurite outgrowth on PC12 cells. Bioorganic & medicinal chemistry letters, 25(22), 5078-5082.

[14] — Samberkar, S., Gandhi, S., Naidu, M., Wong, K. H., Raman, J., & Sabaratnam, V. (2015). Lion's Mane, Hericium erinaceus and Tiger Milk, Lignosus rhinocerotis (Higher Basidiomycetes) medicinal mushrooms stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina: an in vitro study. International journal of medicinal mushrooms, 17(11).

[15] — Lai, P. L., Naidu, M., Sabaratnam, V., Wong, K. H., David, R. P., Kuppusamy, U. R., ... & Malek, S. N. A. (2013). Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. International Journal of Medicinal Mushrooms, 15(6).

[16] — Mori, K., Obara, Y., Hirota, M., Azumi, Y., Kinugasa, S., Inatomi, S., & Nakahata, N. (2008). Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biological and Pharmaceutical Bulletin, 31(9), 1727-1732.

[17] — Sheu, S. C., Lyu, Y., Lee, M. S., & Cheng, J. H. (2013). Immunomodulatory effects of polysaccharides isolated from Hericium erinaceus on dendritic cells. Process biochemistry, 48(9), 1402-1408.

[18] — Son, C. G., Shin, J. W., Cho, J. H., Cho, C. K., Yun, C. H., & Han, S. (2006). Induction of murine interleukin‐1 beta expression by water‐soluble components from Hericium erinaceum 1. Acta Pharmacologica Sinica, 27(8), 1058-1064.

[19] — Mori, K., Ouchi, K., & Hirasawa, N. (2015). The anti-inflammatory effects of lion's mane culinary-medicinal mushroom, hericium erinaceus (higher basidiomycetes) in a coculture system of 3t3-L1 adipocytes and raw264 macrophages. International journal of medicinal mushrooms, 17(7).

Rhodiola (Rhodiola rosea)

Rhodiola Summary

Rhodiola was made famous by some earlier research done by Russian scientists in the 1960's. Although a lot of this research still hasn't been released to the public, there has been a lot of new studies put forward to make up for this loss.

Rhodiola is well revered as an adaptogen for treating fatigue, cognitive decline, depression, and for athletic enhancement. It's considered to be a mild stimulant, though it doesn't produce the "wired" feeling many other stimulants produce. It increases energy levels and makes us more tolerant of stressful situations.

Although there is still a lot of research lacking, we know that Rhodiola can reduce cortisol levels in the body after exposure to stress, however, the details on how this interaction exists is still not well understood. There is also a great deal of confusion around which chemicals are active in the herb, some studies showing the rosavins, others tyrosol and the rhodiolasides.

As a result, each manufacturer tends to have a preference for one chemical group over the other in their products.

What is Rhodiola Used For?

*Rhodiola rosea* is mainly used for its adaptogenic qualities, especially those specific to lowering cortisol levels. It's reliable for improving fatigue in debilitated or chronically fatigued people, as well as those experiencing generalized adaptive disorder, depression, or acute periods of extreme stress.

Rhodiola is a popular nootropic additive for increasing focus and mental endurance and is popular among athletes for increasing physical endurance as well.

Herb Details: Rhodiola

Weekly Dose

• (1:2 Liquid Extract)
  20–40 mL
• View Dosage Chart

Part Used

• Root/Rhizome

Family Name

• Crassulaceae

Distribution

• Northern climates of North America, Asia, and Europe

Herbal Actions:

• Adaptogen
• CNS Stimulant (mild)
• Antidepressant
• Cardioprotective
• Nootropic

Constituents of Interest

• Rosavin
• Tyrosol
• Salidroside
• Rhodiolaside

Common Names

• Rhodiola
• Rose Root
• Arctic Root
• Golden Root
• King's Crown

CYP450

Unknown

Duration of Use

• Long-term use of rhodiola is acceptable.

Botanical Information

Although Rhodiola rosea is the preferred species used, there are many species used in various indigenous medical systems such as Rhodiola alterna, Rhodiola brevipetiolata, Rhodiola crenulata, Rhodiola kirilowii, Rhodiola quadrifida, Rhodiola sachalinensis, and Rhodiola sacra.

The Crassulaceae family contains 34 genera and 1400 species. Most of the plants in this family can be found in colder climates.

Another medicinal species in this family is Kalanchoe.

Habitat Ecology, & Distribution:

Rhodiola grows at high altitude, mountainous regions of Europe, Asia, the Arctic, and North America.

Pharmacology & Medical Research

+ Altitude Sickness

Salidroside and Tyrosol from Rhodiola cerrulea extracts have been shown to regulate AMPK [11], which plays a major role in energy homeostasis [10]. It was also shown to maintain sodium channel transport by preserving NA+, K+, ATPase activity. The authors concluded that this mechanism may be responsible for Rhodiolas ability to reduce the symptoms of altitude sickness, particularly HAPE [11].

+ CNS Stimulant

Numerous clinical trials have demonstrated the CNS stimulating activity of Rhodiola rosea [8] based on various cognitive and fatigue scores.

Other studies have found the use of rhodiola at varying doses inconclusive as a stimulant [7].

+ Memory & Cognitive Performance

Rhodiola extracts have been shown in animal models to improve learning capacity and short/long-term memory in animals trained to perform certain tasks [2].

Rhodiola has been shown to inhibit monoamine oxidase (both MAO-A and MAO-B) in animal studies [4].

+ Depression

MAO-A inhibitors are effective in the treatment of depression [20]. Rhodiola has been shown to inhibit MAO-A & B in animal studies [4]. Other animal studies investigating the use of rhodiola on depression has shown a non-dose dependent improvement on depression scores in mice, which is due to the tyrosin and rhodiolaside content specifically [16, 18, 19].

A randomized double-blind clinical trial using a standardized Rhodiola rosea extract showed a significant antidepressant activity in the treatment group compared to placebo. This was based on various depressive symptoms including insomnia, emotional instability, and somatization. [17].

+ Stress And Fatigue (Adaptogenic)

A group of 56 healthy physicians in a double-blind randomized clinical trial were either given Rhodiola rosea extracts or placebo control for 2 weeks. Physicians were chosen based on criteria that investigated the likelihood that these physicians would experience mental exhaustion during a normal shift. A series of tasks were then given after each night shift to investigate any changes on mental fatigue as measured by a set of complex tasks. All of the physicians treated with Rhodiola rosea were noted to show improved test scores compared to those not treated with the herb. These effects were observed to be most active after two weeks of use, and not a single adverse reaction was reported during the study. [3].

Another study investigating the mental and physical effects of a long term, low dose (SHR-5 50 mg) on students during examination periods found significant improvements on test scores among the treatment group [9]. They were looking for the presence of mental and physical fatigue indications. The only test that showed no improvement in this study was the tapping test (muscular activation).

A study investigating the effects of Rhodiola rosea on free cortisol levels in chronically fatigues patients noted a reduction in cortisol levels after just a single treatment, and significantly after a 28-day course of treatment [21]. Rhodiola was also shown to reduce serum blood levels of cortisol after a stressful event in rabbits [22].

Animal research has shown that Rhodiola rosea extracts can reduce the expression of c-Fos in the hypothalamus of rats [23]. The expression of this gene is considered to be a valuable marker for identifying the activation of cells in the central nervous system associated with the stress response [24]. This suggests the mechanism of action for Rhodiola rosea on reducing cortisol levels is the result of HPA modulation in the hypothalamus, such as increasing feedback sensitivity and therefore reducing overall CRH release rather than acting directly on the adrenal glands.

+ Withdrawal

A Rhodiola rosea extract was shown to improve withdrawal symptoms in mice, with a noted increase in 5HT activity in treated animals. [1].

Clinical Applications Of Rhodiola:

Rhodiola serves as a reliable adaptogen with little to no side effects noted in any of the studies listed. It's useful for those suffering from high-stress conditions, chronically fatigued, or depressed.

This herb is also useful for increasing athletic performance in athletes and reducing the chances of being affected by altitude sickness when traveling above 2500 meters.

Cautions:

Caution when using Rhodiola with mania as the mental stimulation may produce negative side effects.

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated May 2019)

Recent Blog Posts:

References

1. Mannucci, C., Navarra, M., Calzavara, E., Caputi, A. P., & Calapai, G. (2012). Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. Phytomedicine, 19(12), 1117-1124. [animal studies]

2. Petkov, V. D., Yonkov, D., Mosharoff, A., Kambourova, T., Alova, L., Petkov, V. V., & Todorov, I. (1986). Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory. Acta physiologica et pharmacologica Bulgarica, 12(1), 3-16. [animal studies]

3. Darbinyan, V., Kteyan, A., Panossian, A., Gabrielian, E., Wikman, G., & Wagner, H. (2000). Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine, 7(5), 365-371. [RCT]

4. Van Diermen, D., Marston, A., Bravo, J., Reist, M., Carrupt, P. A., & Hostettmann, K. (2009). Monoamine oxidase inhibition by Rhodiola rosea L. roots. Journal of ethnopharmacology, 122(2), 397-401. [animal studies]

5. Ganzera, M., Yayla, Y., & Khan, I. A. (2001). Analysis of the marker compounds of Rhodiola rosea L.(golden root) by reversed phase high performance liquid chromatography. Chemical and pharmaceutical bulletin, 49(4), 465-467. [chemical analysis]

6. Panossian, A., Wikman, G., & Sarris, J. (2010). Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 17(7), 481-493. [review article]

7. Shevtsov, V. A., Zholus, B. I., Shervarly, V. I., Vol'skij, V. B., Korovin, Y. P., Khristich, M. P., ... & Wikman, G. (2003). A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine, 10(2), 95-105. [RCT]

8. Panossian, A., & Wagner, H. (2005). Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytotherapy Research, 19(10), 819-838. [Review]

9. Spasov, A. A., Wikman, G. K., Mandrikov, V. B., Mironova, I. A., & Neumoin, V. V. (2000). A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine, 7(2), 85-89. [RCT].

10. Lee, S. Y., Shi, L. S., Chu, H., Li, M. H., Ho, C. W., Lai, F. Y., ... & Chang, T. C. (2013). Rhodiola crenulata and its bioactive components, salidroside and tyrosol, reverse the hypoxia-induced reduction of plasma-membrane-associated Na, K-ATPase expression via inhibition of ROS-AMPK-PKCξ pathway. Evidence-Based Complementary and Alternative Medicine, 2013. [in vitro].

11. Reznick, R. M., & Shulman, G. I. (2006). The role of AMP‐activated protein kinase in mitochondrial biogenesis. The Journal of physiology, 574(1), 33-39.

12. Kerharo, J., & Adam, J. G. (1974). La pharmacopée sénégalaise traditionnelle: plantes médicinales et toxiques. (Pharmacopoeia).

13. Steinegger, E., & Hansel, R. (1992). Pharmakognosie 5 Aufl. Kap 6.2. 1. Freie Phenolcarbonsauren Springer Verlag Berlin. (Pharmacopoeia).

14. Hjaltalin, O. J. (1830). Islenzk grasafrædi. Koben havn.

15. insert

16. Kurkin, V. A., Dubishchev, A. V., Ezhkov, V. N., Titova, I. N., & Avdeeva, E. V. (2006). Antidepressant activity of some phytopharmaceuticals and phenylpropanoids. Pharmaceutical Chemistry Journal, 40(11), 614-619.

17. Darbinyan, V., Aslanyan, G., Amroyan, E., Gabrielyan, E., Malmström, C., & Panossian, A. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nordic journal of psychiatry, 61(5), 343-348.

18. Perfumi, M., & Mattioli, L. (2007). Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytotherapy Research, 21(1), 37-43.

19. Panossian, A., Nikoyan, N., Ohanyan, N., Hovhannisyan, A., Abrahamyan, H., Gabrielyan, E., & Wikman, G. (2008). Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine, 15(1-2), 84-91.

20. Priest, R. G., Gimbrett, R., Roberts, M., & Steinert, J. (1995). Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders. Acta Psychiatrica Scandinavica, 91(s386), 40-43.

21. Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta medica, 75(02), 105-112.

22. Panossian, A., Hambardzumyan, M., Hovhanissyan, A., & Wikman, G. (2007). The adaptogens Rhodiola and Schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug target insights, 2, 117739280700200011.

23. Xia, N., Li, J., Wang, H., Wang, J., & Wang, Y. (2016). Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress. Experimental and therapeutic medicine, 11(1), 353-359.

24. Luckman, S. M., Dyball, R. E., & Leng, G. (1994). Induction of c-fos expression in hypothalamic magnocellular neurons requires synaptic activation and not simply increased spike activity. Journal of Neuroscience, 14(8), 4825-4830.

Reishi (Ganoderma lucidum)

What is Reishi?

Reishi is a medicinal forest-grown fungus. It's revered in traditional medical systems across Asia for its powerful immune-enhancing and longevity-promoting benefits.

Medicinal mushrooms are notorious for their complex effects on the immune system — often working in both directions (stimulation and inhibition), depending on what’s needed.

Reishi is no different — it's one of the most important medicinal herbs for longevity and immune health in the world.

This saprophytic (tree-eating) fungus is often used for the prevention and treatment of immune-related illness — including cancer, autoimmunity, infection, inflammation, and allergic reaction.

Reishi is also used for anxiety, depression, insomnia, and as a general adaptogen for overall health and wellbeing.

What is Reishi Used For?

Reishi has the unique ability to act bidirectionally on the immune system — which means it can increase immune activity, and decrease immune activity. It appears it will push the immune system in whatever direction it needs to go. In patients with low immunity or cancer, reishi up-regulates the immune response.

however, in patients with hyperactive immune activity — such as autoimmune disease or allergic reaction — reishi has an opposite effect, toning down the immune response.

This is an effect not well understood to this day, but gives the mushroom an incredibly versatile set of benefits.

Traditionally, reishi is considered a shen tonic — which is used to calm the nerves, ease anxiety, and promote healthy sleep (without being directly sedative).

Most people use reishi as a general health and immune tonic. It’s used by people with known immune-related illness — such as frequent infection, autoimmunity, chronic inflammation, cancer, and more.

Others use the herb as a prophylactic against common infections like colds and flus, or to keep chronic viral infection at bay (such as herpes or shingles).

Traditional Uses of Reishi

+ Traditional Chinese Medicine

In Traditional Chinese Medicine this fungus has been used for (altitude sickness and is often combined with chrysanthemum, rhodiola, and safflower seed.

Taste:

Sweet [5]

Energy:

Neutral [5]

Channels:

Heart, liver, lung [5]

Actions:

Tonifies, the heart, calms and anchors the Shen, stops cough, stops wheezing, dislodges phlegm, tonifies the spleen, tonifies the Qi, tonifies blood [5]

Indications:

Suitable during pregnancy [5].

Dose:

3-15g decocted20 mins [5]

Considered to be warming, astringent, nourishing, detoxifying, and tonifying. Protects qi of the heart, used to repair a knotted, tight chest. Traditionally in this system, it was recommended to take this herb over long periods to reap the benefits of longevity.

The spores are suggested to contain high amounts of jing and considered an elixir of life [1].

Other uses include Hashimoto's disease, in foot baths for gout, altitude sickness prevention, and immune regulation. [1].

+ Ayurveda

A related species — Ganoderma applanatum — has been used extensively in Ayurvedic systems in the pine region of India. Its uses include stopping excessive salivation in the mouth, as a styptic.

+ Other Historical Uses

Reishi has been used medicinally in Asian countries for at least 4000 years and is the most widely depicted mushroom in Japan, Korea, and China, which can be found on temples, tapestries, statues, and paintings.

Reishis rarity and subsequent value made it most accessible to the privileged like emperors and royalty. It has long been associated with longevity and was included in many ancient medical texts for this purpose.

Used to treat liver ailments, lung conditions, kidney disease, nerve pain, hypertension, gastric ulcers, and insomnia. The antler growth pattern is considered very rare and is the most desired for promoting sexual function in both men and women.

Other uses include its use as a means to ward off evil by hanging dried specimens over the door. Similarly, it has been placed on the graves of shamans to protect from evil souls or spirits.

Reishi has been used in nearly every format imaginable including tinctures, teas/decoctions, powdered preparations, brewed into beers and wines, and eaten raw.

Herb Details: Reishi

Herbal Actions:

• Adaptogen
• Immunomodulator
• Analgesic
• Muscle relaxant
• Nervine Relaxant
• Hepatoprotective
• Pulmonary trophorestorative
• Cardiotonic
• Chemoprotective
• Anti-Cancer
• Antiviral
• Antibacterial

Weekly Dose

• (1:2 Liquid Extract)
  30-60 mL
• View Dosage Chart

Part Used

• Fruiting body, Spores, Mycelium

Family Name

• Ganodermataceae

Distribution

• Asia, Europe, and North America

Constituents of Interest

• Beta-glucans
• Ergosterol
• Triterpenoids
• Polysaccharides

Common Names

• Reishi
• Ling Zhi
• Saiwai-Take
• Kishiban

CYP450

• Unknown

Quality

• Neutral

Pregnancy

• No adverse reactions expected.

Taste

• Bitter

Duration of Use

• Suitable for long term use.

Mycological Information

There are about 80 different species of Ganoderma, many of which are used as medicine. The Ganodermataceae contains 8 genera and roughly 300 different species.

Reishi is a saprophyte, meaning it only eats dying or decaying organic matter such as wood. It's mainly found growing on dying trees, stumps, and fallen logs.

Ganoderma spp. is long-lived — releasing approximately 30 billion spores everyday for up to 6 months or a year [1].

Habitat Ecology, & Distribution:

Wild Ganoderma lucidum is rare but is indigenous to forested regions of Asia including Japan, China, and Russia. Other species are found in North America and Europe.

It grows on Elm (Ulmus spp.), alder (Alnus spp.), oak (Quercus spp.), maple (Acer spp.) and some strains on conifers. Other species of Ganoderma such as G. tsugae or G. oregonense grow better and almost exclusively on conifers. G. lucidum, however, prefers hardwoods.

G. lucidum can be found very rarely in the Pacific Northwest, and a similar species (G. curtisii), is seen more commonly in eastern Canada around the great lakes region [1]. This species is actually a yellow form of the red G. lucidum.

Most reishi products on the market are cultivated in a sterile environment on logs or sawdust in large laboratories.

Harvesting Collection, & Preparation:

Both the mycelium, fruiting body, and spores are used medicinally. The red and purple varieties are considered the most valuable. These phenotypes are also thought to be the most potent in their effects [1].

The spores can be either taken raw or can be cracked. This basically involves the germination, then drying of the spores and is suggested to provide stronger medicinal effects after this germination process has taken place.

Another, much more expensive way of ingesting the spores it to run it through a supercritical CO2 extractor. This method creates a product that is roughly equivalent to 20-40 of the raw spore capsules [1].

A mushroom oil can also be extracted from the fruiting body waxes, can be used as is topically, or added to lotions, and salves.

Cosmetically it is useful as a sunscreen due to its radio-protective effects, as well as in anti-aging creams, and to remove warts [1].

As with most hard, polypores, chop the fungus into strips (better when wet or a saw may have to be used), and crumble into small pieces.

Decoct in water, then strain and freeze the leftover mush, doing this will cause the cell walls to burst and allow more constituents to be extracted during the next process. Next, after it has been frozen for 24 hours or so, de-thaw, and mix with 95% alcohol for at least 2 weeks.

In the end, strain, and combine with the decoction made earlier to a standardized amount.

Pharmacology & Medical Research

+ Antibacterial

Ganoderma applanatum is an effective inhibitor of:

• Bacillus cereus
• Cornybacterium diphtheria
• Escherichia coli
• Pseudomonas aeruginosa
• Staphylococcus aureus
• Streptococcus pyogenes

Gram-positive bacteria were more affected than gram-negative [1].

It has been suggested that the polysaccharides in Ganoderma spp. are more antibacterial — while the triterpenoids are more antiviral.

More research is needed to elucidate on this further.

+ Anti-diabetic

Ganoderma has been reported to produce potent lens aldose reductase inhibition, and significant inhibition of serum glucose and sorbitol accumulation in the lens of the eye, red blood cells, and sciatic nerves in diabetic rats (based on earlier studies) [1]. This shows potential as a treatment for diabetic induced retinopathy and other diabetes-related damage in the body.

Has been shown to lower blood sugar levels in hyperglycemic models (fruiting body), and involved the ganoderan B and C [1].

In a study on type 2 diabetics not on insulin, were given reishi extracts, and compared to the placebo control group, were found to have significantly decreased glycosylated hemoglobin (8.4%-7.6%), in as little as 12 weeks. Fasting insulin levels, 2-hour -post-prandial insulin, fasting C-peptide, and post-prandial C-peptide all showed significant improvement in the reishi group [1].

Spores have also shown evidence for anti-diabetic effects [1].

+ Antioxidant

Methanol extracts of G. tsugae were found to be more potent in antioxidant effects that alpha-tocopherol, and exhibited significant inhibition of lipid peroxidation as such.

The antioxidant effects are not considered as reliable as G. lucidum but are very close. It is the phenol content that has been deemed responsible for these effects. [1].

G. tsugae fruiting body extract was shown to increase intracellular glutathione levels, which in turn protect against oxidative damage [1].

+ Antiulcer effects:

Polysaccharides from Ganoderma spp. protects the gastric mucosa by improving PGE2. This backs up some of its uses in the form of tea for treating ulcers.

+ Antiviral

G. lucidum fruiting body extracts have been shown to inhibit HIV, and HPV [1].

Rogers, (2011) reports that Ganaderiol-F, ganodermadiol, ganoderic acid beta, and lucidumol have all been identified as antiviral agents.

G. resinaceum (and most likely G. tsugae, and G. lucidum as well), have been shown to inhibit punta toro, pichinde, and H1N1 [1].

+ Blood Tonic

Reishi been shown to enhance the production of interleukin-1 in vitro, and increase white blood cell and haemoglobin levels in mice [1].

+ Cardiotonic

Reishi has been shown to improve symptoms of coronary heart disease [1].

G. lucidum has been shown to provide anti-cholesterol, anti-diabetic, reduced platelet aggregation, anti atherosclerotic, and antihypotensive effects, which all play a role in the development of cardiovascular disease.

Suggested to produce angiotensin-converting enzyme inhibition through its ganoderic acid B, C2, D, and F [1].

+ Chemoprotective

Has been shown to increase natural killer cell activity of splenocytes by up to 52% [1]

+ Hepatoprotective

The triterpenoids contained in the mycelium of G. tsugae have shown hepatoprotective activity [1].

Ganodereic acid B has shown hepatoprotective effects [1].

+ Immunomodulatory

The polysaccharides from the mycelium were found to be both anti-inflammatories, and immune-stimulating, Rogers, (2011), suggests contradiction from these two effects suggest bi-directional (immunomodulatory) effects on immune response, rather than just stimulating. This appears to be dose-dependent and may be through modulation of cytokine production.

Reishi has been shown to both reduce inflammation and increase immune response — which is contradictory in that an increased immune response should correlate with inflammation. It's has been suggested that G. lucidum produces this apparent modulatory effect through the enteric mucosal pathway. Its effects on the immune system do not appear to be through IgE antibody synthesis, rather through a modulating effect on immunoglobulin levels [1].

+ Sedative

The spores are suggested to produce sedative and hypnotic effects in mice [1].

+ Other

There's some evidence to support the effects of reishi towards bronchitis and other lung disorders . The chemicals suggested to be responsible for these effects are gonoderic acids A, B, C1, and C2 [1].

Phytochemistry

+ Compounds by Anatomy

Fruiting Body

Carbohydrates, amino acids (including adenosine), steroids (ergosterols), protease, lysosomes, lipids, triterpenes, alkaloids, vitamins B2 and C, minerals (zinc, manganese, iron, copper, germanium), beta-glucans (up to 40.6%), [1].

Mycelium

Sterols, alkaloids, lactones, erogone, polysaccharides, triterpinoids,

Spores

choline, triterpenes, betaine, palmitic acid, stearic acid, ergosta7,22-dien-3b-ol, tetracosanoic acid, behenic acid, nonadecanoic acid, ergosterol, beta sitosterol, pyrophosphatidic acid, hentriacontane, tetracosane, ganodermasides (A and B) [1].

+ Species Specific Breakdown

Ganoderma tsugae

3 α-acetoxy-5α-lanosta-8,24-dien-21-oic acid, 2β,3α,9α-trihydroxy-5α-ergosta-7,22-dien, 3alpha-acetoxy-16alpha-tsugarioside B and C, ganoderic acid C2, ganoderic acid B, lucidone A, and glycans (various) [1].

Ganoderma applanatum

Ergosterol (and its peroxide), ergosta-7,22-dien-3b-ol, ergasta-7,22-dien-3-one, β-D-glucan, fungisterol, alnusenone, friedelin, triterpenoids (including ganoderenic, furanoganoderic, ganoderic acids), applanoxidic acids (A, B, C, and D), lanostandoid triterpenes E-H, lucidone A, ganoderma aldehyde, 3 linoleic acid steryl esters. To compare with G. lucidum, ganoderenic acid, and ganoderic acid is found in both [1].

Ganoderma lucidum

Still compiling research.

Clinical Applications Of Reishi:

Reishi is used as a supportive agent for cancer, autoimmune conditions, cardiovascular dysfunctions, respiratory dysfunctions, viral and bacterial infection, and hypertension. It's rarely used on its own, but makes for a great addition to herbal formulations.

Cautions:

Caution advised in combination with ACE inhibitor medications due to potential drug interactions.

Synergy

For altitude sickness: Combines well with rhodiola for this purpose.

It has been suggested that vitamin C helps absorb this mushroom, however, more research is needed to confirm this. Pineapple and ginger may also increase the absorption of reishi constituents.

Author:

Justin Cooke

The Sunlight Experiment

(Updated May 2019)

Recent Blog Posts:

References:

1. Rogers, R. D. (2011). The fungal pharmacy: The complete guide to medicinal mushrooms and lichens of North America [Adobe Digital Editions version].

2. Berovic, M., J. Habijanic, I. Zore, B. Wraber, D. Hodzar, B. Boh and F. Pohleven. Submerged cultivation of Ganoderma lucidum biomass and immunostimulatory effects of fungal polysaccharides. J. Biotechnol. 103: 77–86, 2003

3. Jiang, Y., H. Wang, L. Lu and G.Y. Tian. Chemistry of polysaccharide Lzps-1 from Ganoderma lucidum spore and anti-tumor activity of its total polysaccharides. Yao. Xue. Xue. Bao. 40: 347–350, 2005.

4. Cheng, K.C., H.C. Huang, J.H. Chen, J.W. Hsu, H.C. Cheng, C.H. Ou, W.B. Yang, S.T. Chen, C.H. Wong and H.F. Juan. Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction. BMC Genomics 8: 411, 2007.

5. Hempen, C. H., & Fischer, T. (2009). A Materia Medica for Chinese Medicine: Plants, Minerals, and Animal Products. (Pg. 436-437).

6. Thyagarajan, A., J. Jiang, A. Hopf, J. Adamec and D. Sliva. Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through the suppression of interleukin-8 secretion. Int. J. Mol. Med. 18: 657–664, 2006.

7. Xie, J.T., C.Z. Wang, S. Wicks, J.J. Yin, J. Kong, J. Li, Y. C. Li and C.S. Yuan. Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells. Exp. Oncol. 28: 25–29, 2006.

8. Paterson, R.R. Ganoderma — a therapeutic fungal biofactory. Phytochemistry. 67: 1985–2001, 2006.

9. Lin, Y.L., Y.C. Liang, S.S. Lee and B.L. Chiang. (2005). Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NFkappaB and p38 mitogen-activated protein kinase pathways. J. Leukoc. Biol. 78: 533–543.

Cannabis (Cannabis sativa/indica)

Cannabis Overview

Cannabis is well known for its psychoactive effects, causing temporary changes in visual and auditory perception.

The cannabis plant is also a rich source of medicinal compounds. Cannabinoids related to THC exert medicinal action through the endocannabinoid system — a critical component of homeostasis.

Many of these cannabinoids aren't psychoactive, and wont produce the 'high' associated with the plant in their isolated forms.

Compounds like CBD, have become especially popular as a supplement recently for its broad medicinal benefits.

There are plenty of uses for cannabis — however, product selection, strain choice, and cannabinoid profiles make a big difference in the effects produced by the plant. It's important to use the right type of cannabis for the job.

Jump to Section

What is Cannabis Used For?
Technical Details
Botanical Information
Phytochemistry
— CBC
— CBD
— CBG
— THC
— THCV
— Other Cannabinoids
— Terpenes
Clinical Applications of Cannabis
Cautions
References

Buy CBD Oil

What is Cannabis Used For?

Using cannabis as medicine poses challenges due to the large variety of effects each cannabinoid possesses. Different cannabinoid and terpene ratios can produce different effect profiles.

The plant has many claimed benefits, and though a lot of them can be validated, it's not a miracle plant.

Cannabis is especially reliable for a few key symptoms:

• Lowering various forms of inflammation
• Improving microbiome diversity (through CB2 receptor activity)
• Reducing nervous excitability
• Reducing convulsions
• Improving sleep onset and maintenance
• Lowering pain

Using cannabis as medicine should be attempted with caution due to the degree of variability the plant produces in terms of effect profile. What this means is that some cannabis extracts will make symptoms like anxiety worse, while others can dramatically improve it.

Choosing the right strain or extract is of the utmost importance when using cannabis as medicine.

The effects of cannabis can be contradictory:

• It's both a stimulant and a sedative
• It increases appetite, and suppresses it
• It increases immune activity, and suppresses inflamamtion

These effects all contradict themselves in most cases. The reason this happens is because the cannabinoids work through a regulatory pathway (endocannabinoid system) rather than on a particular organ function.

It's similar to how adaptogens like ginseng, ashwagandha, or reishi produce often contradictory or bidirectional results.

+ Indications

• Anorexia
• Cancer
• Crohn's disease
• Dystonia
• Epilepsy
• General anxiety disorder
• Glaucoma
• Gout
• Insomnia
• Menstrual cramping
• Multiple Sclerosis
• Neuropathic pain
• Osteoarthritis
• Rheumatoid Arthritis
• Schizophrenia (Caution)
• Social anxiety disorder
• Substance abuse/addiction
• Ulcerative colitis
  

+ Contraindications

• Only use cannabis medicinally following the direction of a qualified medical practitioner.
• Caution with anxious or depression.
• May worsen symptoms of psychosis
• Avoid use alongside medications unless first discussing with your doctor.
  

+ Potential Side-Effects

• Apathy (long-term use)
• Bronchitis (smoking)
• Cough (smoking)
• Depression
• Dizziness
• Dry eyes
• Dry mouth
• Eye reddening
• Fatigue
• Hallucinations
• Headache
• Heart palpitations
• Hypertension/Hypotension
• Increased appetite
• Lightheadedness
• Menstrual changes
• Nausea/vomiting
• Numbness
• Paranoia
• Tachycardia

Herb Details: Cannabis

Weekly Dose

• (CBD content in mg)
  70–700 mg
• View Dosage Chart

Part Used

• Leaves, flowers, seeds

Family Name

• Cannabacea

Distribution

• Worldwide

Herbal Actions:

• Sedative/Stimulant
• Anti-emetic
• Anti-spasmodic
• Anti-convulsant
• Analgesic
• Antinflammatory
• Appetite Suppressant/Stimulant
• Adaptogen
• Anti-cancer
• Antioxidant

Common Names

• Cannabis
• Marijuana
• Hemp
• Mary Jane
• Herb

Pregnancy

• Avoid use while pregnant and nursing.

Duration of Use

• Long-term use acceptable. Recommended to take breaks periodically.

CYP450

• CYP2C9
• CYP3A4

Botanical Information

Cannabis plants are members of the Cannabacea family. This small family comprises only 11 different genuses, and about 170 species.

Some common members of the family are hops (Humulus spp.) and celtis (Celtis spp.). The celtis genus contains the largest collection of species by far, with over 100 different species. Cannabis and Humulus are the closest related genus' in the group by far.

There are three species of cannabis:

1. Cannabis sativa

Cannabis sativa is a tall, fibrous plant. It's high in cannabinoids, terpenes, and other phytochemicals — giving it many uses medicinally.

Cannabis sativa is the most commonly cultivated species. There are hundreds, if not thousands of different phenotypes of this species — the most important being hemp — which is a non-psychoactive, high fiber plant valued as both a health supplement and textile. It's also used for food (seeds), and to make biodeisel.

There are also Cannabis sativa strains high in the psychoactive component — THC — which make it popular as both medicine and recreational intoxicant.

2. Cannabis indica

Cannabis indica grows as s shorter, bushier plant. It's hgiher in THC, and there are few low-THC phenotypes available for this plant.

This species of cannabis is most often used recreationally.

3. Cannabis ruderalis

Cannabis ruderalis is a small, herbaceus plant more closely related to Cannabis sativa than Cannabis indica. It's low in cannabinoids, and terpenes, as well as fiber — limiting its value to humans.

This species has the unique ability to initiate flower production irrelevant to day length. Plant breeders have started mixing the plant with other species to gain these benefits. This makes cultivation easier in areas where day length is too short or too long for optimal cannabis cultivation.

Phytochemistry

There are 421 compounds in the cannabis plant [1], at least 66 of these are cannabinoids — some sources report as many as 112.

The top 6 cannabinoids in the plant (CBD, CBG, CNN, THC, THCV, and CBC), account for the vast majority of the cannabinoid profile.

The phenotype of the cannabis used is the primary determining factor for the cannabinoid profile of each plant.

Hemp plants for example, contain much higher levels of CBD, and lower levels of THC. Marijuana strains are the opposite, contianing high THC, and lower CBD.

Depending on the strain, this can vary dramatically — and you can find almost any combination of cannabinoid possible.

The Cannabinoids:

Cannabinoids are a class of phytochemical compounds resembling the structure of our naturally occurring ecosanoid endocannabinoids; anandamide, and 2-AG. There are roughly 66 of these compounds in the cannabis plant, and a few found in other species of plants as well — such as helichrysum and echinacea.

Although the cannabinoids are very similar, their binding activity varies a lot [14]. Some bind to CB1 receptors (located primarily in the central nervous system), others bind to CB2 receptors (found primarily in immune tissue). Some cannabinoids will even bind to both, or work by increasing the concentrations of naturally occurring endocannabinoids instead.

Due to the wide range of variability between each cannabinoid, it’s useful to go over them in greater detail individually.

1. CBC

Cannabichromene

CBC is the third most abundant cannabinoid in the cannabis plant.

It’s non-psychoactive.

CBC is far less studied than the two preceding cannabinoids CBD, and THC, though early research is starting to suggest it’s even better for treating conditions like anxiety than the famed CBD.

CBC content can be increased in the cannabis plant by inducing light-stress on the plant [5].

CBC Medicinal Actions

• Antidepressant

• Mild sedative

Receptors Affected

• Vanilloid receptor agonist (TRPV3 and TRPV4) [4]

2. CBD

Cannabidiol

In many cases, CBD is the most abundant cannabinoid. Only selectively bred cannabis strains will have higher THC concentrations than CBD.

CBD is famed for many reasons. It offers a wide range of medicinal benefits, and has been well-studied and validated over the past two decades.

CBD oils, e-liquids, and edibles have become highly popular in recent years as more of this research is being released and translated for the general public.

CBD Medicinal Actions

• Antinflammatory

• Mild appetite suppressant

• Lowers stress

• Adaptogenic

• Mild sedative

• Anti-emetic

Receptors Affected

• Adenosine (A2a) reuptake inhibitor [6]

• Vanilloid pain receptors (TRPV1, TRPV2, TRPV3) [7]

• 5HT1A receptor agonist (serotonin receptor) [6]

• FAAH (–) [6, 7]

• PPARγ nuclear receptor (+) [48]

• Mg2+‐ATPase (−) [11]

• Arylalkylamine N‐acetyltransferase (−) [44]

• Indoleamine‐2,3‐dioxygenase (−) [45]

• 15‐lipoxygenase (−) [46]

• Phospholipase A2 (+) [11]

• Glutathione peroxidase (+) [47]

• Glutathione reductase (+) [47]

• 5‐lipoxygenase (−) [46]

Metabolism

• CYP1A1 (−) [40]

• CYP1A2 & CYP1B1 (−) [40]

• CYP2B6 (−) [41]

• CYP2D6 (−) [42]

• CYP3A5 (−) [43]

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3. CBG

Cannabigerol

CBG is an early precursor for many of the other cannabinoids including THC.

Plants harvested early will be high in this compound.

Many users report that strains high in CBG are less likely to cause anxiety, and are good for people experiencing acute stress.

This is likely due to its role in blocking the serotonergic effects of THC through the 5-HT1A serotonin receptors [9].

CBG Medicinal Actions

• Anti-anxiety

• Adaptogenic

• Mild sedative

Receptors Affected

• A2-adrenoceptor antagonist [9]

• CB1 and CB2 receptors agonist [9]

• 5-HT1A receptors antagonist (serotonin receptor) [9]

• Vanilloid receptor agonist (TRPA1) [8]

• TRPM8 receptor antagonist [8]

4. CBN

Cannabinol

CBN is made from THC. As THC content breaks down with time, or heat, CBN levels increase overall.

Older harvested plants that have gone past their window of ripeness will be much higher in CBN.

It’s mostly non-psychoactive but may have some mild psychoactivity in some people.

Products or strains high in CBN will produce more of a heavy feeling and are best used for treating conditions like insomnia or anxiety.

This cannabinoid is potentially the most sedative of the group.

CBN Medicinal Actions

• Sedative

• Anti-anxiety

• Appetite stimulant

Receptors Affected

• CB1 receptor agonist [10].

Metabolism

• CYP2C9

5. THC

Tetrahydrocannabinol

THC is the main psychoactive compound in the cannabis plant.

There are two main types:

• Delta-8-THC — contained in very small amounts

• Delta-9-THC — the most abundant form of THC in the cannabis plant

THC activates both CB1 and CB2 endocannabinoid receptors, causing changes in neurotransmitters like dopamine, norepinephrine, and most importantly, serotonin. It’s this change in neurotransmitter levels that produce the bulk of the high experienced by this compound.

Aside from its psychoactive effects, THC has medicinal benefits of its own.

It’s mentally stimulating and has some potent antidepressant effects through its euphoric effects.

THC Medicinal Actions

• Appetite stimulant

• Sedative (low doses)

• Stimulant (high doses)

Receptors Affected

• CB1 and CB2 agonist [11]

• PPAR gamma receptor agonist [11, 15].

Metabolism

• CYP2C9

6. THCV

Tetrahydrocannabivarin

THCV is the fraternal twin of THC.

It’s virtually identical except for one slight chemical difference — THCV is missing two carbon atoms.

This makes the effects of THCV very similar to THC — but is much weaker in its effects.

One study reported THCV as being 20-25% as strong as THC in its psychoactive effects [12].

There are others affected by this, including CBCV, and CBDV, though they are in far less concentrations.

THCV Medicinal Actions

• Appetite suppressant

• Euphoric

• Antispasmodic

• Paranoic

Receptors Affected

• Vanilloid receptor agonist (TRPV3 and TRPV4) [13].

7. Other Cannabinoids

There are also a lot of cannabinoids that can be found in much lower concentrations.

These make up the bottom 5% of the cannabinoid profile.

Few of these cannabinoids have many studies on them aside from chemical mapping to identify their structure.

We may see more research on these cannabinoids in the near future.

Some Novel Cannabinoids Include:

• CBCV (cannabichromevarin)

• CBDV (cannabidivarin)

• CBE (cannabielsoin)

• CBGM (cannabigerol monomethyl ether)

• CBGV (cannabigerovarin)

• CBL (cannabicyclol)

• CBT (cannabicitran)

• CBV (cannabivarin)

A Note On Synthetic Cannabinoids

There are also synthetic cannabinoids. These are compounds that are similar in shape and function to cannabinoids produced in our bodies, or in the cannabis plant.

It’s recommended that you stay far away from the synthetic cannabinoids — not only do they lack many of the medicinal actions of cannabis, they have the potential to cause serious harm.

The street drug known as “spice” is a combination of various synthetic cannabinoids. They were designed as an attempt to circumvent the legal hurdles preventing the sale of cannabis products for recreational use — and have since become a major cause of addiction and abuse.

+ Side-Effects of Synthetic Cannabinoid Use

• Agitation and anxiety
• Blurred vision
• Chest pain
• Death
• Hallucinations
• Heart attack
• High blood pressure
• Kidney failure
• Nausea and vomiting
• Paranoia
• Psychosis
• Racing heart
• Seizures
• Shortness of breath

+ List of Synthetic Cannabinoids

• JWH-018
• JWH-073
• JWH-200
• AM-2201
• UR-144
• XLR-11
• AKB4
• Cannabicyclohexanol
• AB-CHMINACA
• AB-PINACA
• AB-FUBINACA

Cannabis Terpenes

Terpenes are a class of compounds characterized by their volatile nature, and hydrocarbon-based structure. These are contained in high amounts in the essential oil of plants.

Terpenes have a very low molecular weight, and will evaporate under low temperatures. This, combined with their characteristic aromas is what gives many plants their scent. Conifer trees, fruits, and many flowers (including cannabis) all owe their aroma to their terpene profile.

Each plant can contains hundreds of different terpenes — many of which will even overlap into unrelated plant species. Cannabis shares terpenes with pine trees, many different flowers, citrus fruits, and nutmeg, among others.

Terpenes add flavor as well as additional medicinal benefits. Terpenes often have antibacterial, antiviral, antinflammatory, and anxiolytic effects.

+ List of Cannabis Terpenes

• A-humulene
• a-Terpenine
• Alpha Bisabolol
• alpha-Terpineol
• Alpha/Beta Pinene
• Beta-Caryophyllene
• Bisabolol
• Borneol
• Camphene
• Caryophyllene oxide
• D-Linalool
• Eucalyptol (1, 8 cineole)
• Geraniol
• Guaiol
• Isopulegol
• Limonene
• Myrecene
• Nerolidol
• p-Cymene
• Phytol
• Pulegone
• Terpineol-4-ol
• Terpinolene
• Trans Ocimene
• Valencene
• ∆-3-carene

Pharmacokinetics/Pharmacodynamics

Cannabinoids work by mimicking the endocannabinoids anandamide and 2-AG.

Learn more about cannabinoid metabolism.

Clinical Applications of Cannabis

As an herb, cannabis is very useful. It works through a set of receptors most other plants don’t interact with — the endocannabinoid system.

The endocannabinoid system plays a major role in maintaining homeostasis. This gives cannabis an effect profile similar to adaptogens — but through different mechanisms.

Cannabis is similar to adaptogens in that it offers a bidirectional effect profile — which means it can both increase, and decrease tissue function according to its homeostatic baseline.

But cannabis isn’t quite an adaptogen because it can’t increase the bodies resistance to stress, and doesn’t appear to exert any action on the hypothalamus or adrenal glands directly.

Although cannabis has broad actions and therefore can provide benefit to a wide range of body systems — choosing the right product, strain, and phenotype for the job is critical.

An experienced herbalist or naturopath using cannabis will take into account the cannabinoid profile, terpene content, and anecdotal effects of each strain or CBD product being used.

Unlike other herbs, you have to be very particular about the type of cannabis being used for each condition.

What Constitutes “Medicinal” Cannabis?

There’s a big difference between using cannabis because “it’s healthy”, and using it as a therapeutic agent aimed at treating a specific disease process.

Although it can be used as both, daily supplementing cannabis or extracts like CBD don’t constitute medical cannabis.

However, you can use cannabis to address the symptoms, or underlying causes for some conditions.

Cautions:

Caution advised whenever using cannabis due to the potential for intoxicating side-effects. Without careful consideration of cannabinoid profile, some strains, or cannabis products may make symptoms for certain conditions worse — especially anxiety, psychosis, bipolar disorder, and insomnia.

Author

Justin Cooke, BHSc

The Sunlight Experiment

(Updated Jan 2019)

Recent Blog Posts:

References:

1. Sharma P, Murthy P, Bharath M.M.S. (2012). Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications. Iran J Psychiatry 2012; 7:4: 149-156

2. Aizpurua-Olaizola, O., Soydaner, U., Öztürk, E., Schibano, D., Simsir, Y., Navarro, P., ... & Usobiaga, A. (2016). Evolution of the cannabinoid and terpene content during the growth of Cannabis sativa plants from different chemotypes. Journal of natural products, 79(2), 324-331.

3. Shevyrin, V. A., & Morzherin, Y. Y. (2015). Cannabinoids: structures, effects, and classification. Russian Chemical Bulletin, 64(6), 1249-1266.

4. De Petrocellis, L., Orlando, P., Moriello, A. S., Aviello, G., Stott, C., Izzo, A. A., & Di Marzo, V. (2012). Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta physiologica, 204(2), 255-266.

5. De Meijer, E. P. M., Hammond, K. M., & Micheler, M. (2009). The inheritance of chemical phenotype in Cannabis sativa L.(III): variation in cannabichromene proportion. Euphytica, 165(2), 293-311.

6. Nelson, K., Walsh, D., Deeter, P., & Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. Journal of palliative care.

7. Bisogno, T., Hanuš, L., De Petrocellis, L., Tchilibon, S., Ponde, D. E., Brandi, I., ... & Di Marzo, V. (2001). Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. British journal of pharmacology, 134(4), 845-852.

8. De Petrocellis, L., Vellani, V., Schiano-Moriello, A., Marini, P., Magherini, P. C., Orlando, P., & Di Marzo, V. (2008). Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. Journal of Pharmacology and Experimental Therapeutics, 325(3), 1007-1015.

9. Cascio, M. G., Gauson, L. A., Stevenson, L. A., Ross, R. A., & Pertwee, R. G. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent α2‐adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. British journal of pharmacology, 159(1), 129-141.

10. Farrimond, J. A., Whalley, B. J., & Williams, C. M. (2012). Cannabinol and cannabidiol exert opposing effects on rat feeding patterns. Psychopharmacology, 223(1), 117-129.

11. Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin. British journal of pharmacology, 153(2), 199-215.

12. Hollister, L. E. (1974). Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of Δ9-tetrahydrocannabinol. Pharmacology, 11(1), 3-11.

13. Pertwee, R. G. (2006). The pharmacology of cannabinoid receptors and their ligands: an overview. International journal of obesity, 30(S1), S13.

14. Compton, D. R., Rice, K. C., De Costa, B. R., Razdan, R. K., Melvin, L. S., Johnson, M. R., & Martin, B. R. (1993). Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. Journal of Pharmacology and Experimental Therapeutics, 265(1), 218-226.

15. Burstein, S. (2005). PPAR-γ: a nuclear receptor with affinity for cannabinoids. Life sciences, 77(14), 1674-1684.García-Arencibia, M., González, S., de Lago, E., Ramos, J. A., Mechoulam, R., & Fernández-Ruiz, J. (2007). Evaluation of the neuroprotective effect of cannabinoids in a rat model of Parkinson's disease: importance of antioxidant and cannabinoid receptor-independent properties. Brain research, 1134, 162-170.

16. Martín-Moreno, A. M., Reigada, D., Ramírez, B. G., Mechoulam, R., Innamorato, N., Cuadrado, A., & de Ceballos, M. L. (2011). Cannabidiol and other cannabinoids reduce microglial activation in vitro and in vivo: relevance to Alzheimers′ disease. Molecular pharmacology, mol-111.

17. Dirikoc, S., Priola, S. A., Marella, M., Zsürger, N., & Chabry, J. (2007). Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. Journal of Neuroscience, 27(36), 9537-9544.

18. Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences, 97(17), 9561-9566.

19. Specter, S., Lancz, G., & Hazelden, J. (1990). Marijuana and immunity: tetrahydrocannabinol mediated inhibition of lymphocyte blastogenesis. International journal of immunopharmacology, 12(3), 261-267.

20. Klein, T. W., Kawakami, Y., Newton, C., & Friedman, H. (1991). Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. Journal of Toxicology and Environmental Health, Part A Current Issues, 32(4), 465-477.

21. McCoy, K. L., Gainey, D., & Cabral, G. A. (1995). delta 9-Tetrahydrocannabinol modulates antigen processing by macrophages. Journal of Pharmacology and Experimental Therapeutics, 273(3), 1216-1223.

22. Coffey, R. G., Yamamoto, Y., Snella, E., & Pross, S. (1996). Tetrahydrocannabinol inhibition of macrophage nitric oxide production. Biochemical pharmacology, 52(5), 743-751.

23. Formukong, E. A., Evans, A. T., & Evans, F. J. (1988). Analgesic and antiinflammatory activity of constituents ofCannabis sativa L. Inflammation, 12(4), 361-371.

24. Watzl, B., Scuderi, P., & Watson, R. R. (1991). Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon-gamma and suppress interleukin-1 alpha in vitro. International journal of immunopharmacology, 13(8), 1091-1097.

25. Srivastava, M. D., Srivastava, B. I. S., & Brouhard, B. (1998). Δ9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology, 40(3), 179-185.

26. Pan, H., Mukhopadhyay, P., Rajesh, M., Patel, V., Mukhopadhyay, B., Gao, B., ... & Pacher, P. (2009). Cannabidiol attenuates cisplatin-induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation, and cell death. Journal of Pharmacology and Experimental Therapeutics, 328(3), 708-714.

27. Mecha, M., Feliú, A., Iñigo, P. M., Mestre, L., Carrillo-Salinas, F. J., & Guaza, C. (2013). Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiology of disease, 59, 141-150.

28. Notcutt, W., Langford, R., Davies, P., Ratcliffe, S., & Potts, R. (2012). A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex®(nabiximols). Multiple Sclerosis Journal, 18(2), 219-228.

29. Woerly, S., Marchand, R., & Lavallée, G. (1991). Interactions of copolymeric poly (glyceryl methacrylate)-collagen hydrogels with neural tissue: effects of structure and polar groups. Biomaterials, 12(2), 197-203.

30. Wade, D. T., Collin, C., Stott, C., & Duncombe, P. (2010). Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Multiple Sclerosis Journal, 16(6), 707-714.

31. Brady, C. M., DasGupta, R., Dalton, C., Wiseman, O. J., Berkley, K. J., & Fowler, C. J. (2004). An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Multiple Sclerosis Journal, 10(4), 425-433.

32. Barnes, M. P. (2006). Sativex®: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert opinion on pharmacotherapy, 7(5), 607-615.

33. Leung, L. (2011). Cannabis and its derivatives: review of medical use. The Journal of the American Board of Family Medicine, 24(4), 452-462.

34. Grotenhermen, F., & Müller-Vahl, K. (2012). The therapeutic potential of cannabis and cannabinoids. Deutsches Ärzteblatt International, 109(29-30), 495.

35. Kwiatkoski, M., Guimaraes, F. S., & Del-Bel, E. (2012). Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury. Neurotoxicity research, 21(3), 271-280.

36. Chagas, M. H. N., Zuardi, A. W., Tumas, V., Pena-Pereira, M. A., Sobreira, E. T., Bergamaschi, M. M., ... & Crippa, J. A. S. (2014). Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. Journal of Psychopharmacology, 28(11), 1088-1098.

37. Iuvone, T., Esposito, G., De Filippis, D., Scuderi, C., & Steardo, L. (2009). Cannabidiol: a promising drug for neurodegenerative disorders?. CNS neuroscience & therapeutics, 15(1), 65-75.

38. Fernández‐Ruiz, J., Sagredo, O., Pazos, M. R., García, C., Pertwee, R., Mechoulam, R., & Martínez‐Orgado, J. (2013). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?. British journal of clinical pharmacology, 75(2), 323-333.

39. Yamaori, S., Kushihara, M., Yamamoto, I., & Watanabe, K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochemical pharmacology, 79(11), 1691-1698.

40. Yamaori, S., Maeda, C., Yamamoto, I., & Watanabe, K. (2011). Differential inhibition of human cytochrome P450 2A6 and 2B6 by major phytocannabinoids. Forensic Toxicology, 29(2), 117-124.

41. Yamaori, S., Okamoto, Y., Yamamoto, I., & Watanabe, K. (2011). Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for cytochrome P450 2D6. Drug Metabolism and Disposition, dmd-111.

42. Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., & Watanabe, K. (2011). Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life sciences, 88(15-16), 730-736.

43. Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., & Watanabe, K. (2011). Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life sciences, 88(15-16), 730-736.

44. Koch, M., Dehghani, F., Habazettl, I., Schomerus, C., & Korf, H. W. (2006). Cannabinoids attenuate norepinephrine‐induced melatonin biosynthesis in the rat pineal gland by reducing arylalkylamine N‐acetyltransferase activity without involvement of cannabinoid receptors. Journal of neurochemistry, 98(1), 267-278.

45. Jenny, M., Santer, E., Pirich, E., Schennach, H., & Fuchs, D. (2009). Δ9-Tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro. Journal of neuroimmunology, 207(1-2), 75-82.

46. Takeda, S., Usami, N., Yamamoto, I., & Watanabe, K. (2009). Cannabidiol-2', 6'-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metabolism and Disposition.

47. Usami, N., Yamamoto, I., & Watanabe, K. (2008). Generation of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone. Life sciences, 83(21-22), 717-724.

48. Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. H., Di Marzo, V., Elphick, M. R., ... & Mechoulam, R. (2010). International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacological reviews, 62(4), 588-631.

Graviola (Annona muricata)

What is Graviola?

Graviola is a large tropical tree with a rich history of traditional use for conditions like cancer, parasitic infection, insomnia, and dysentery. Modern use remains very similar, mainly focusing on tension headaches and muscle aches, insomnia, diabetes, cancer, hypertension, and parasitic infection.

Although the entire plant has been used as medicine by various traditional medical systems, the most common form the plant is available in today is as a leaf extract, and raw leaves intended for tea.

Graviola is gaining in popularity outside worldwide as a general health supplement, blood sugar regulator, and anticancer agent. As a result, it's getting easier to find the herb as time goes on. It is likely this tea will become a staple in Western herbal medicine in the coming years.

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How Is Graviola Used?

Graviola is mainly used as an adjunctive treatment for cancer, especially leukemia and other haematological cancers, as well as prostate, colon, and breast cancers.

Graviola is also popular as an anti-diabetic herb, and can be used to reduce hypertension, especially in combination with diabetes or metabolic syndrome.

Graviola is a potent anti-parasitic, useful for a wide range of different parasitic species, including worms, protozoa, and bacterial parasites.

Traditional Uses of Graviola

+ South America

Graviola originated from South America and/or the Carribean. All parts of the plant were used as medicine for a wide range of conditions.

The most common use of the plant appears to involve cancer treatment and parasitic infection.

The darkest leaves on the plants were used primarily as a sedative or antispasmodic. They were used to treat insomnia, arthritic pains, colic, dysentery, muscle aches, headaches, and diabetes. The leaves were often placed inside a pillow or bedsheets to improve sleep.

In Brazil, the leaves were made into a tea for treating various liver conditions. The oil of the leaves and unripe fruits were used topically for treating neuralgia, and arthritis.

In Peru, the leaves were used to treat excess catarrh, and the bark and root were used for treating diabetes, insomnia, and muscle aches.

In Guyana, the leaves were used as a heart tonic.

+ Southeast Asia

In Southeast Asia, graviola was an important treatment for malaria. It was made into candies, ice cream, and syrups for treating malaria and other parasites.

Herb Details: Graviola

Herbal Actions:

• Anticancer
• Antinflammatory
• Antioxidant
• Antispasmodic
• Anticonvulsant
• Antidepressant
• Antidiabetic
• Antibacterial
• Antiarthritic
• Antilithic
• Antimalarial
• Bradycardic
• Digestive stimulant
• Febrifuge
• Hepatoprotective
• Hypotensive
• Sedative
• Vasodilator

Weekly Dose

• (1:2 Liquid Extract)
  40-80 mL
• View Dosage Chart

Part Used

• Leaves

Family Name

• Annonaceae

Distribution

• North & South America, The Caribbean, Indonesia, Western Africa, Pacific Islands

Constituents of Interest

• Acetogenins
• Alkaloids (reticulin, coreximine, coclarine and anomurine)
• Essential oils (β-caryophyllene, δ-cadinene, epi-α-cadinol and α-cadinol)
• Quercetin

Common Names

• Graviola
• Custard Apple Tree
• Soursop
• Annona
• Guanabana (South America)

Quality

• Cool*

Pregnancy

• Unknown

Taste

• Sour

Duration of Use

• Avoid long term use.

Botanical Information

Graviola is a large tree, growing to a height of 10m. It requires high humidity, warm weather, and high annual rainfall in order to thrive. It produces large, edible fruits with an acidic taste (hence the common name soursop).

There are over 130 different genera in the Annonaceae family, and around 2300 different species. The Annona genus itself has about 70 different species. Annona muricata is the most commonly grown worldwide.

Phytochemistry

There are over 100 annonaceous acetogenins in the plant, which are considered to be the primary active constituents of the plant. Structurally these chemicals are derivatives of long chain (C35 or C37) fatty acids. These compounds are cytotoxic against tumour cell lines, and molluscicidal.

Graviola is also rich in alkaloids, saponins, terpenoids, flavonoids, coumarins, lactones, anthraquinones, tannins, cardiac glycosides, phenols, and phytosterols.

+ Complete Phytochemical Makeup

Annonaceous Acetogenins

The leaves contain annomuricins A and B, gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, goniothalamicin, muricatocins A and B, annonacin A, (2,4-trans)-isoannonacin, (2,4-cis)-isoannonacin, annomuricin C, muricatocin C, gigantetronenin, annomutacin, (2,4-trans)-10R-annonacin-A-one, (2,4-cis)-10R-annonacin-A-one, annopentocins A, B and C, cis- and trans-annomuricinD-ones, annomuricine, muricapentocin, muricoreacin and murihexocin C and annocatacin A and B.

Alkaloids

Graviola contains reticulin, coreximine, coclarine and anomurine.

Essential Oils

Graviola contains β-caryophyllene, δ-cadinene, epi-α-cadinol and α-cadinol.

Clinical Applications Of Graviola:

Graviola is useful for parasitic infection, including protozoan, and helminth parasites. It's used as a mild sedative and antispasmodic, and can be very useful for gastrointestinal inflammation and dysbiotic conditions.

Graviola is also a popular treatment for diabetes by slowing lipid per-oxidation, and restoring islet beta-cells in the pancreas.

It's commonly used as an adjunctive treatment of cancer, especially haematological cancers and colon cancer.

Cautions:

Graviola has been reported to increase symptoms of Parkinson's Disease.

Caution advised in combination with other hypoglycaemic drugs due to potential additive effect.

+ Contraindications

• May exacerbate Parkinson's Disease symptoms (Acetogenin content)
• Caution advised in combination with other hypoglycemic drugs due to potential additive effect.
  

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated November 2018)

Recent Blog Posts:

References:

1. Moghadamtousi, S. Z., Fadaeinasab, M., Nikzad, S., Mohan, G., Ali, H. M., & Kadir, H. A. (2015). Annona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities. International journal of molecular sciences, 16(7), 15625-15658.

2. De Sousa, O. V., Vieira, G. D. V., De Pinho, J. D. J. R., Yamamoto, C. H., & Alves, M. S. (2010). Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. International journal of molecular sciences, 11(5), 2067-2078.

3. Torres, M. P., Rachagani, S., Purohit, V., Pandey, P., Joshi, S., Moore, E. D., ... & Batra, S. K. (2012). Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer letters, 323(1), 29-40.

4. Coria-Tellez, A. V., Montalvo-Gónzalez, E., Yahia, E. M., & Obledo-Vázquez, E. N. (2016). Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arabian Journal of Chemistry.

5. Gavamukulya, Y., Abou-Elella, F., Wamunyokoli, F., & AEl-Shemy, H. (2014). Phytochemical screening, anti-oxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola). Asian Pacific journal of tropical medicine, 7, S355-S363.

6. Arroyo, J., Martínez, J., Ronceros, G., Palomino, R., Villarreal, A., Bonilla, P., ... & Quino, M. (2009, September). Efecto hipoglicemiante coadyuvante del extracto etanólico de hojas de Annona muricata L (guanábana), en pacientes con diabetes tipo 2 bajo tratamiento de glibenclamida. In Anales de la Facultad de Medicina (Vol. 70, No. 3, pp. 163-167). UNMSM. Facultad de Medicina.

7. Adewole, S., & Ojewole, J. (2009). Protective effects of Annona muricata Linn.(Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats. African journal of traditional, complementary and alternative medicines, 6(1).

8. Adeyemi, D. O., Komolafe, O. A., Adewole, O. S., Obuotor, E. M., Abiodun, A. A., & Adenowo, T. K. (2010). Histomorphological and morphometric studies of the pancreatic islet cells of diabetic rats treated with extracts of Annona muricata. Folia morphologica, 69(2), 92-100.

9. Adewole, S. O., & Caxton-Martins, E. A. (2006). Morphological changes and hypoglycemic effects of Annona muricata linn.(annonaceae) leaf aqueous extract on pancreatic β-cells of streptozotocin-treated diabetic rats. African Journal of Biomedical Research, 9(3).