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Glaucoma

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Promising results hint that THC might one day treat glaucoma.

Glaucoma is an umbrella term for a group of diseases that damage the optic nerve—the signalling pathway bringing color and image information from the retina to the brain.1 Damaged nerve cells in the eye can narrow a person’s field of vision and even lead to complete blindness. According to the World Health Organization, about 4.5 million people are blind as a result of glaucoma in the world—that’s slightly more than 12 percent of all human blindness.2 About three million people who suffer from glaucoma are in the United States, according to the American Glaucoma Society.3 Unfortunately it’s a bit sneaky in that patients often only notice the decrease in their peripheral vision after a large swath of cells is already dead and the disease is in the advanced stages.3,4 Currently, there is no known cure, and patients typically manage the condition for the rest of their lives with medicine, surgery, or both. 

Although the exact ways in which the diseases work are poorly understood, two aspects are well known: damage to the cells of the optic nerve, and in most cases, there is an increase in pressure within the eye. The most effective medicines used to treat glaucoma aim to lower the pressure within the eye.1,5 Researchers published a study in 1971, in the prestigious “Journal of the American Medical Association” showing that smoking marijuana decreased intraocular pressure.7 We know today that THC is at least one of the components responsible for this effect. 

Keeping intraocular pressure low seems to work to hold off the worst glaucoma has to offer. Even so, for a minority of patients who are successfully keeping eye pressure low, the disease still progresses. That is why some researchers are looking beyond pressure-lowering medicines and taking a closer look into medications that can also protect the nerve cells from damage4—something THC has also been shown to do.5

THC seems like a good candidate to treat glaucoma because of the combination of its ability to protect neurons as well as lower intraocular pressure. THC affects change in the body by connecting to at least two cannabinoid receptors.7 One of these is the well-known cannabinoid CB1 receptors. They are found throughout the brain and eyes and can affect pain, mood, movement and memory.5,8,9 As it turns out, CBD is actually not well-suited to the job according to results we’ll get to below.

Smoking cannabis as a way to treat glaucoma has drawbacks. It lasts a short duration (three to four hours according to the American Glaucoma Society),10 has potentially undesirable psychoactive and other side-effects, as well as the possibility of building up resistance. The society issued a position statement in 2009 saying it does not recommend cannabis for glaucoma treatment. However, the statement hints that the position might change if more promising research becomes available.

In the 11 years since the statement came out, there have been more studies. Recent research in animal models highlights the possibility that some form of THC might one day be available to treat glaucoma.

Since smoking has its challenges, researchers have tried delivering THC and CBD under the tongue (THC lowered eye pressure for four hours and CBD had no effect or raised the pressure) and via eye drops.11 The eye drops failed at first, because the THC didn’t get very far into the eye, due to its love of lipids or lipophilic nature. A team of pharmaceutical researchers from the University of Mississippi has been tackling this problem. They published a study last year in the journal “Translational Vision Science and Technology” pointing to early success in developing a new eye drop.12,13 It allowed the THC to penetrate more deeply into rabbits’ eyes and decreased intraocular pressure for six hours. They were able to override THC’s hydrophobic nature by attaching it to molecules that made the whole nano-sized medicine able to sink all the way into the rabbit’s eye. In their paper, the researchers also point out that, if recent findings are correct, THC can protect the cells in the optic nerve from damage and deeper penetration may help increase this positive effect.

In a 2018 study published by the online journal “Investigative Ophthalmology & Visual Science,” Indiana University researchers investigated on which receptors THC and CBD were working in mice.7 They found the two compounds were working with different receptors. THC lowered eye pressure. CBD, though it may have neuroprotective effects, worked against THC and kept the pressure from decreasing and, in some cases, could even have the unwanted effect of increasing eye pressure. 

In one surprise result, they found a marked difference in how the cannabinoids affected male and female mice. Males had a much more pronounced decrease in eye pressure from THC. When they looked into this, they found the males had more of the relevant receptors.7

In short, before THC could be a good long-term solution to this life-long condition, there are some hurdles to overcome. In their position statement, the American Glaucoma society states: “Unless a well tolerated formulation of a marijuana-related compound with a much longer duration of action is shown in rigorous clinical testing to reduce damage to the optic nerve and preserve vision, there is no scientific basis for use of these agents in the treatment of glaucoma.”10 Rigorous clinical testing is the gold standard for choosing a safe and effective treatment. Such research will continue to be difficult to conduct as long as cannabis is still listed as “Schedule 1” under the Controlled Substances Act, meaning it is considered to be a substance with no medical use and a high potential for abuse. If Congress or the federal administration changes the classification, researchers will likely have more opportunities to conduct relevant research in humans.


References:

1.https://higherlogicdownload.s3.amazonaws.com/AMERICANGLAUCOMASOCIETY/4ca07187-fb0f-4dc3-a19c-33093862484d/UploadedImages/Documents/559_cyclophoto4_final.pdf

2. https://www.who.int/blindness/causes/priority/en/index6.html

3. https://www.americanglaucomasociety.net/patients/glaucoma-faqs

4. Bucolo, C., Plantania, C.B.M., Drago, F., Bonfiglio, V., Reibaldi, M., Avitabile, T., Uva, M. (2018). Novel Therapeutics in Glaucoma Management. doi: 10.2174/1570159X15666170915142727.

5. Rapinoa, C., Tortolania, D., Scipionib, L. & Maccarroneb, M. (2018). Neuroprotection by (Endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases. Current Neuropharmacology (16), 959-970.

6. Hepler R.S., Frank I.R. (1971) Marihuana smoking and intraocular pressure. JAMA (217),1392.

7. Miller S., Daily L., Leishman E., Bradshaw H., Straiker A. (2018). D9-tetrahydrocannabinoland cannabidiol differentially regulate intraocular pressure. Invest Ophthalmol Vis Sci (59), 5904–5911.

8. Piomelli D. (2003). The molecular logic of endocannabinoid signalling. Nat Rev Neurosci (4), 873–884.

9. Straiker, A.J., Maguire, G., Mackie, K., Lindsey, J. (1999). Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci. Sep (40:10), 2442-2448. 

10. https://www.americanglaucomasociety.net/about/statements

11.  Tomida, I., Azuara-Blanco, A., House, H., Flint, M., Pertwee, R.G., Robson, P.J. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. Journal of Glaucoma: Oct15(5), 349-53.

12. 2019: Taskar, P.S., Patil, A., Lakhani, P., Ashour, E., Gul, W., El Sohly, M.A., Murphy, B., Majumdar, S. (2019) D9-Tetrahydrocannabinol derivative-loaded nanoformulation lowers intraocular pressure in normotensive rabbits. Trans Vis Sci Tech: 8(5),15.https://doi.org/10.1167/tvst.8.5.15

13. Adelli, G.R., Bhagav, P., Taskar, P., et al. (2017). Development of a D9-tetrahydrocannabinol amino acid-dicarboxylate prodrug with improved ocular bioavailability. Invest Ophthalmol Vis Sci. (58), 2167–2179. doi: 10.1167/iovs.16-20757

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Turmeric

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Turmeric is a root vegetable commonly used as a spice in various Indian and other cultures’ dishes. Turmeric is in the zingiberaceae family, as is ginger. The turmeric plant is native to the southeastern region of Asia and commonly harvested in places like India, Sri Lanka, China, Indonesia, and Taiwan. It is responsible for curry’s signature orange color, and its vibrant pigment will give essentially any meal an orange hue. 

Turmeric contains a substance called curcumin, and curcumin has been shown through research to offer anti-inflammatory and other therapeutic benefits. The scientific name for the turmeric plant is Curcuma Longa, and likely where the name curcumin comes from. When people are talking about the health benefits of turmeric, they are referencing curcumin so you may hear the two names used interchangeably. Curcumin is part of a group called curcuminoids, with curcumin being the most active and the most beneficial for health. Flavonoids are another substance found in various plants and give these plants their color. Curcumin is a flavonoid and is responsible for providing that bright orange color to turmeric. In addition to providing aesthetic value, flavonoids are also strong antioxidants with anti-inflammatory and immune-boosting properties.

The Journal of Biological Chemistry published a study done by Sanjaya Singh and Bharat B. Aggarwal of the Cytokine Research Laboratory at the world-renowned cancer hospital, M.D. Anderson. The study found that curcumin suppressed NF-κB, a protein complex responsible for controlling inflammatory responses. In other words, turmeric shuts off the body’s inflammatory response. Anti-inflammatories can be beneficial for many different ailments, including chronic pain and digestive disorders. A lot of CBD companies even put curcumin in their products because of its benefits. It is believed to be a synergistic pair with complementary therapeutic properties. The thought is that the two plant medicines are powerful on their own; as a combination, they can deliver even more anti-inflammatory and medicinal benefits. 

Many people simply add turmeric to their dishes as a way to easily incorporate it into their daily routine. It is pretty mild in flavor and can be added to many dishes without changing the overall taste too drastically. Some say that turmeric isn’t strong enough on its own to receive the anti-inflammatory properties that curcumin provides, and therefore recommend a curcumin supplement. Research varies on that, so in the end it is just up to personal preference and your doctor’s approval. Curcumin supplements come most available in capsules. Pregnant women can safely use turmeric as an addition to their food, but should avoid taking high-dosage supplements. Those who are interested in supplementing with curcumin products should talk with their doctor first. 

M.D. Anderson Cancer Center did another study in 2007 exploring curcumin for cancer treatment. The study found that curcumin inhibits ovarian cancer growth and angiogenesis (the development of new blood vessels). It does this by targeting and manipulating the NF-κB pathway, the same protein complex responsible for controlling inflammatory response. According to a report published by the National Center for Biotechnology Information, “The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules.”  

The trend with curcumin seems to be it’s ability to control inflammatory responses in the body. It does this by multiple pathways, but a commonly researched one is the NF-κB protein complex. Because this pathway is able to be manipulated by curcumin to encourage anti-inflammatory expressions, its potential for successfully treating various ailments is there.

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Psilocybin + Magic Mushrooms

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When many think of plant medicine, specifically those plants with psychoactive effects, they think of “magic mushrooms,” or fungi containing psilocybin and psilocin that can cause hallucinations depending on the dosage consumed. In many states, there are active efforts to decriminalize these otherwise scheduled substances, lowering penalties for their use and possession. But what value do psilocybin-containing mushrooms offer? New research suggests a range of therapeutic and psychological value ranging from the treatment of substance abuse to anxiety and depression management.  

What are Magic Mushrooms?

Magic Mushroom use dates back to 10,000 BCE and references continue throughout the era. Their modern popularity began when the term “magic mushroom” was coined by two etnomycologists who learned of a Harvard study on local doctors in Mexico using these substances, noting the substance’s ability to affect the nervous system. These findings were eventually published in Life magazine in 1957, and the term became the universal reference for psychoactive fungi and truffles, specifically those containing high concentrations of psilocybin and psilocin.

Psilocybin & Psilocin: The “Magic” in Magic Mushrooms

Psilocybin and psilocin are part of a family of psychedelic compounds found in magic mushrooms. Psilocin is pharmacologically active, and psilocybin is converted into psilocin when consumed or activated. Similar in structure to serotonin, there are more than 50 species of mushrooms and a variety of truffles that produce both the precursor, psilocybin, and the psychoactive compound, psilocin. Unlike LSD, magic mushrooms do not affect dopamine receptors, solely targeting serotonin sites

How are Magic Mushrooms used?

Magic mushrooms are often used for recreational, therapeutic and medicinal reasons. “Effects range from mild feelings of relaxation, giddiness, euphoria, visual enhancement (seeing colors brighter), visual disturbances (moving surfaces, waves), to delusions, altered perception of real events, images and faces, or real hallucinations.” Recreationally, this is often known as “tripping.” As an alternative health option, these fungi are being used for anxiety, depression, PTSD, and trauma, as well as psychological disorders such as substance abuse disorders, and science is beginning to back the potential for these applications.

Research on Mushrooms

Evaluations of currently available scientific studies suggest a growing number of therapeutic benefits and treatment options. “In the past few years, a growing number of studies using human volunteers have begun to explore the possible therapeutic benefits of drugs such as psilocybin…looking at psilocybin and other hallucinogens to treat a number of otherwise intractable psychiatric disorders, including chronic depression, post-traumatic stress disorder, and drug or alcohol dependency.”

Magic mushrooms have been respected as a “safe & natural healing sacrament for millennia throughout Mexico, Central America and the world,” and are known to be beneficial for depression, recidivism (the tendency to repeat past transgressions), and encourages openness, creativity, as well as personal and spiritual growth. UCLA and NYC have done studies on the applications of magic mushrooms in the treatment of end-of-life anxiety and other studies have backed up the use of psilocybin and psilocin in the treatment of substance use disorders, depression (especially in cases of terminal conditions like cancer as well as treatment-resistant depression), and reducing depression and anxiety overall.

Best way for people to consume?

When it comes to the consumption of mushrooms, advice on dosage is about as specific as it was with cannabis under prohibition. Consumers must purchase on the black market and are subject to whatever may be available. 

“Recreational doses range from 1–5 grams of dry mushrooms depending on the species and individual strength of the specimens… After ingestion, the psilocybin is enzymatically converted to psilocin. Absorbed from the gastro-intestinal tract, hallucinogenic effects usually occur within 30 minutes of ingestion with a duration of effect of 4–6 hours.” 

My recommendation as someone who has used magic mushrooms both for recreational and therapeutic purposes, is to grind the mushrooms into a fine powder and either encapsulate them in small increments and/or combine with lemon juice. Capsules will allow you to titrate your dosage as needed with a recognizable increment, while lemon juice will expedite onset time.  

The Legality of Magic Mushrooms

In the United States, psilocybin is a Schedule I controlled substance, with no accepted medicinal value and a high potential for abuse. In contrast, the Drug Policy Alliance states that “Physically, psilocybin mushrooms are considered to be one of the least toxic drugs known.” With that being said, local efforts such as Decriminalize Nature – Oakland and Decriminalize Denver have pushed for and successfully passed initiatives and legislation to reduce penalties and make enforcement a low priority, as was done in the early days of cannabis activism. This has spurred multiple local and international efforts to “Decriminalize Nature,” efforts that we learn more about in this month’s feature.

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Ginkgo Biloba

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Ginkgo biloba is an ancient tree; its roots originate in China. The ginkgo biloba tree is also sometimes known as the maidenhair tree or the Japanese silver apricot, and it produces a foul-smelling fruit commonly harvested for its seeds known as “ginkgo nuts”. Ginkgo nuts are popularly used in Asian cuisine. 

The ginkgo biloba tree’s fan-shaped leaves are used to make ginkgo biloba extract, a supplement traditionally used in Chinese medicine, but has since garnered the attention of cultures worldwide. The supplement comes in liquid extracts, capsules, and tablets. The leaves can also be dried to make tea. The type of ginkgo biloba extract supplement someone takes is all a matter of personal preference, and depends on the user’s already existing regimen. If you do not already drink tea, a ginkgo biloba tea may not implement easily into your lifestyle, thus a greater chance for inconsistency or erratic results. But if you take vitamins or other supplements regularly, after a doctor’s approval you can easily incorporate an additional capsule or tablet into your daily routine. 

The 16th-century Compendium of Materia Medica or Ben Cao Gang Mu is revered as the most comprehensive text ever written in the history of traditional Chinese medicine. This text reveals that ginkgo biloba seeds were used as a topical extract for antimicrobial purposes on the skin. Traditional Chinese Medicine also uses the leaves for tea and attributes it to soothing coughs and activating blood circulation, as well as other benefits like respiratory and digestive ailments. 

A common use for ginkgo biloba is to preserve memory and prevent cognitive decline. Dr. Hiroko Dodge of Oregon State University at Corvallis and his research team followed 118 people for three years aged 85 years and older, in good health, and showing no signs of dementia or memory loss at the beginning of the study. Half took ginkgo biloba and half took a placebo over three years. The patients taking it regularly had a 70% lower risk of developing dementia. According to the study, the other variables included considered “basic demographic variables including age, sex, years of education, and living arrangement (living alone vs living with someone).” 

The National Center for Biotechnology and Information published a study exploring ginkgo as a potential remedy for anxiety and, “The authors reported a significant improvement in psychopathological symptoms. Response rates were 44% in the high-dose group, 31% in the low-dose group, and 22% with placebo. Additionally, the percentages of clinically significant responses were 81%, 67%, and 38% for the high-dose, the low-dose, and the placebo groups, respectively.”2

A 2008 study reinforced the idea behind Traditional Chinese Medicine that ginkgo biloba improves blood circulation. The study shows ginkgo biloba extract to improve coronary artery circulation in patients with coronary artery disease. The study notes, “GBE (ginkgo biloba extract) treatment demonstrated a significant improvement in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with controls.”3 In other words, ginkgo biloba extract is a great contender as a treatment to improve blood flow. 

Like cannabis and other medicinal plants, ginkgo has terpenes and flavonoids. Both of these compounds have therapeutic properties, and can provide anti-inflammatory benefits as well as being packed with antioxidants. Anti-inflammatory effects can serve many different ailments, especially relieving pain of various kinds. Antioxidants are thought to protect our bodies from free radicals, which are unstable molecules that can cause harm to the body. Terpenes are also responsible for giving plants their unique and flavorful smell. Flavonoids are the compounds that give plants their vibrant and diverse colors, and are the largest group of phytonutrients. There are approximately 6,00 different types of flavonoids. 

A few years back, the National Toxicology Program released a detailed report on ginkgo biloba extract. It dissects the toxicity and carcinogenic properties of ginkgo biloba using rodent test subjects. The report made its rounds as proof that ginkgo biloba causes cancer, because the rodents developed cancer at high-rates over two year periods. Per the American Botanical Council, “Adjusted for bodyweight, dosage levels given to the animals were up to 55 to 108 times higher than levels of ginkgo normally ingested by human beings taking ginkgo supplements.” Many people have been using this report to warn against the supplement, but Bill J. Gurley, Ph.D., a professor of pharmaceutical sciences at the University of Arkansas School for Medical Sciences, Little Rock said, “Almost anything will create cancer in rats and mice when it’s fed to them at high doses for two years.” The American Botanical Council also claims the ginkgo biloba extract used in the rodent experiment was of lesser quality, and not meeting European standards. 

Though this seemingly negative research on ginkgo can be explained, it is still important to discuss any kind of supplement addition with your doctor, especially if you are on other supplements or pharmaceutical prescriptions.

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