How Do Cannabinoids Kill Cancer? – Dennis Hill

I was recently inspired to write something I’ve been thinking about for a long time. I notice in the popular literature, and even in the research, we really don’t see how cannabis kills cancer. I wanted to be able to write a one page piece on How It Works that anyone could understand in order to have confidence with this process that has generated a wide range of opinions.
~Dennis

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How Do Cannabinoids Kill Cancer?

There is a plentiful supply of research articles and personal testaments that show the efficacy of cannabis effecting cancer remission. However, only a few point to the mechanism by which the cancer cells die. To understand this better we need to know what metabolic processes provide life to the cells.

There are two structures in most cells that sustain life; one is the mitochondria, and the other is the endoplasmic reticulum. The mitochondria primarily produces adenosine triphosphate (ATP) that provides the necessary energy. The endoplasmic reticulum (ER) is a loosely bound envelope around the cell nucleus that synthesizes metabolites and proteins directed by the nuclear DNA that nourish and sustain the cell.

Let us look first at tetrahydrocannabinol (THC) and observe that THC is a natural fit for the CB1 cannabinoid receptor on the cancer cell surface. When THC hits the receptor, the cell generates ceramide that disrupts the mitochondria, closing off energy for the cell.

Disruption of the mitochondria releases cytochrome c and reactive oxygen species into the cytosol, hastening cell death. It is notable that this process is specific to cancer cells. Healthy cells have no reaction to THC at the CB1 receptor. The increase in ceramide also disrupts calcium metabolism in the mitochondria, completing the demise to cell death.

The other cannabinoid we know is effective in killing cancer cells is cannabidiol (CBD). The primary job of CBD in the cancer cell is to disrupt the endoplasmic reticulum through wrecking of the calcium metabolism, pushing calcium into the cytosol. This always results in cell death. Another pathway for CBD to effect cancer cell death is the Caspase Cascade, which breaks down proteins and peptides in the cell. When this happens the cell cannot survive. Again, these processes are specific to cancer cells, no normal cells are affected.

Reference:

1. The Journal of Neuroscience, February 18, 2009 • 29(7):2053–2063 • 2053 

Cannabidiol Targets Mitochondria to Regulate Intracellular Calcium Levels.

 Duncan Ryan, Alison J. Drysdale, Carlos Lafourcade, Roger G. Pertwee, and Bettina Platt.

School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.

2. Mol Cancer Ther July 2011 10; 1161

Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy

Ashutosh Shrivastava, Paula M. Kuzontkoski, Jerome E. Groopman, and Anil Prasad.

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

See also:

4 thoughts on “How Do Cannabinoids Kill Cancer? – Dennis Hill

  1. Since many people take calcium supplements, would this have to stop if they are taking cannabis to cure cancer or is ensuring an adequate calcium intake beneficial? It’s good to know that the “breast cancer gene” is downregulated too🙂

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    • No need to change calcium or any other nutritional supplements. Cannabinoids work naturally to support the body and does not interfere with our essential chemistry. ~Dennis

      Liked by 1 person

  2. http://historynewsnetwork.org/article/157808
    The Secret History of Cannabis in Japan

    tags: Japan, Cannabis
    See original for 4 illustrations

    by Jon Mitchell
    Jon Mitchell is a Welsh journalist based in Japan and an Asia-Pacific Journal Contributing Editor. He writes about human rights issues – particularly on Okinawa – and more of his work can be found at http://www.jonmitchellinjapan.com. This article was first published on the website of the Asia-Pacific Journal.

    Today Japan has some of the strictest anti-cannabis laws in the world.

    Punishment for possession is a maximum 5 years behind bars and illicit growers face 7-year sentences. Annually around 2000 people fall foul of these laws – their names splashed on the nightly news and their careers ruined forever. The same prohibition that dishes out these punishments also bans research into medical marijuana, forcing Japanese scientists overseas to conduct their studies.

    For decades, these laws have stood unchallenged. But now increasing numbers of Japanese people are speaking out against prohibition – and at the heart of their campaign is an attempt to teach the public about Japan’s long-forgotten history of cannabis.1

    Visitors to a legal cannabis farm in Tochigi Prefecture learn more about the plant. Takayasu Junichi.

    “Most Japanese people see cannabis as a subculture of Japan but they’re wrong. For thousands of years cannabis has been at the very heart of Japanese culture,” explains Takayasu Junichi, one of the country’s leading experts.

    According to Takayasu, the earliest traces of cannabis in Japan are seeds and woven fibers discovered in the west of the country dating back to the Jomon Period (10,000 BC – 300 BC). Archaeologists suggest that cannabis fibers were used for clothes – as well as for bow strings and fishing lines. These plants were likely cannabis sativa – prized for its strong fibers – a thesis supported by a Japanese prehistoric cave painting which appears to show a tall spindly plant with cannabis’s tell-tale leaves.

    “Cannabis was the most important substance for prehistoric people in Japan. But today many Japanese people have a very negative image of the plant,” says Takayasu.

    In order to put Japanese people back in touch with their cannabis roots, in 2001 Takayasu founded Taima Hakubutsukan (The Cannabis Museum) – the only museum in Japan dedicated to the much-maligned weed.2

    The museum is located in a log cabin 100 miles from Tokyo in Tochigi Prefecture – an area long-associated with Japanese cannabis farming. The prefecture borders the Tohoku region which was devastated by the March 11, 2011 earthquake – but being inland from the tsunami and shielded by mountains from radioactive fall-out, it largely escaped the effects of the disaster

    Takayasu Junichi, curator of Taima Hakubutsukan, Japan’s only cannabis museum. Tanaka Hiroko.

    The museum is packed with testimony to Japan’s proud cannabis heritage. There are 17th century woodblock prints of women spinning fibers and photos of farmers cutting plants. In one corner sits a working loom where Takayasu demonstrates the art of weaving. He points to a bail of cannabis cloth – warm in winter, cool in summer, it’s perfectly suited to Japan’s extreme climate.

    “Until the middle of the twentieth century, Japanese cannabis farming used to be a year-round cycle,” explains Takayasu. “The seeds were planted in spring then harvested in the summer. Following this, the stalks were dried then soaked and turned into fiber. Throughout the winter, these were then woven into cloth and made into clothes ready to wear for the next planting season.”

    Playing such a key role in agriculture, cannabis often appeared in popular culture. It is mentioned in the 8th century Manyoshu – Japan’s oldest collection of poems and features in many haiku and tanka poems. Ninjas purportedly used cannabis in their training – leaping daily over the fast-growing plants to hone their acrobatic skills.

    According to Takayasu, cannabis was so renowned for growing tall and strong that there was a Japanese proverb related to positive peer pressure which stated that even gnarly weeds would straighten if grown among cannabis plants.

    In a similar way, school songs in cannabis-growing communities often exhorted pupils to grow as straight and tall as cannabis plants. Due to these perceived qualities, a fabric design called Asa-no-ha based upon interlocking cannabis leaves became popular in the 18th century. The design was a favorite choice for children’s clothes and also became fashionable among merchants hoping for a boom in their economic fortunes.

    Accompanying these material uses, cannabis also bore spiritual significance in Shintoism, Japan’s indigenous religion, which venerates natural harmony and notions of purity. Cannabis was revered for its cleansing abilities so Shinto priests used to wave bundles of leaves to exorcise evil spirits. Likewise, to signify their purity, brides wore veils made from cannabis on their wedding days. Today, the nation’s most sacred shrine – Ise Jingu in Mie Prefecture – continues to have five annual ceremonies called taima dedicated to the nation’s sun goddess. However many modern visitors fail to connect the names of these rituals with the drug so demonized by their politicians and police.3

    A woodblock print from the 17th century shows women preparing the fibers from cannabis plants. Tanaka Hiroko.

    Early 20th century American historian George Foot Moore also recorded how Japanese travelers used to present small offerings of cannabis leaves at roadside shrines to ensure safe journeys. Families, too, burned bunches of cannabis in their doorways to welcome back the spirits of the dead during the summer obon festival.

    Given this plethora of evidence that cannabis was essential in so many aspects of Japanese life, one question remains in doubt: Was it smoked?

    Takayasu isn’t sure – and nor are many other experts. Historical archives make no mention of cannabis smoking in Japan but these records tends to focus primarily on the lifestyles of the elite and ignore the habits of the majority of the population. For hundreds of years, Japanese society used to be stratified into a strict class system. Within this hierarchy, rice – and the sake wine brewed from it – was controlled by the rich, so cannabis may well have been the drug of choice for the masses.

    Equally as important as whether cannabis was smoked is the question of could it have been? The answer to that is a clear yes. According to a 1973 survey published by the United Nations Office on Drugs and Crime, THC levels of indigenous Japanese cannabis plants from Tochigi measured almost 4%. In comparison, one study conducted by the University of Mississippi’s Marijuana Potency Monitoring Project found average THC levels in marijuana seized by U.S. authorities in the 1970s at a much lower 1.5%.4

    Until the early 20th century, cannabis-based cures were available from Japanese drug stores. Long an ingredient in traditional Chinese medicine, they were taken to relieve muscle aches, pain and insomnia.

    Meanwhile the Tohoku region was renowned for wild wariai kinoko (laughing mushrooms). In a country in love with its fungi – think shiitake, maitake and thousand-dollar matsutake – the sale of a range of psychedelic mushrooms was legal until 2002 when they were prohibited to improve the country’s international image prior to the Japan-South Korea World Cup.5

    The prohibition against the Japanese cannabis industry also has a foreign origin.

    According to Takayasu, the 1940s started well for cannabis farmers as the nation’s military leaders – like those in the U.S. – urged farmers to plant cannabis to help win the Asia-Pacific War.

    “The Imperial navy needed it for ropes and the air force for parachute cords. The military categorized cannabis as a war material and they created patriotic war slogans about it. There was even a saying that without cannabis, the war couldn’t be waged,” says Takayasu.

    However after Japan’s surrender in 1945, U.S. authorities occupied the country and they introduced American attitudes towards cannabis. Having effectively prohibited its cultivation in the States in 1937, Washington now sought to ban it in Japan. With the nation still under U.S. control, it passed the 1948 Cannabis Control Act. The law criminalized possession and unlicensed cultivation – and more than 60 years later, it remains at the core of Japan’s current anti-cannabis policy.

    At the time, the U.S. authorities appear to have passed off the Act as an altruistic desire to protect Japanese people from the evils of drugs. But critics point out that occupation authorities allowed the sale of over-the-counter amphetamines to continue until 1951. Instead, several Japanese experts contend that the ban was instigated by U.S. petrochemical lobbyists who wanted to overturn the Japanese cannabis fiber industry and open the market to American-made artificial materials, including nylon.

    Workers harvest cannabis at a licensed farm in Tochigi Prefecture. Takayasu Junichi.

    Takayasu sees the ban in a different light, situating it within the wider context of U.S. attempts to reduce the power of Japanese militarists who had dragged Asia into war.

    “In the same way the U.S. authorities discouraged martial arts such as kendo and judo, the 1948 Cannabis Control Act was a way to undermine militarism in Japan. The wartime cannabis industry had been so dominated by the military that the new law was designed to strip away its power.”

    Regardless of the true reasons, the impact of the 1948 Cannabis Control Act was devastating. From a peak of more than 25,000 cannabis farms in 1948, the numbers quickly plummeted – forcing farmers out of business and driving the knowledge of cannabis cultivation to the brink of extinction. Today there are fewer than 60 licensed cannabis farms in Japan – all required to grow strains of cannabis containing minimal levels of THC – and only one survivor versed in the full cannabis cycle of seed-to-loom – an 84 year-old woman.

    Simultaneously, a sustained propaganda campaign has cleaved the Japanese public from their cannabis cultural roots – brainwashing them into perceiving marijuana as a poison on a par with heroin or crack cocaine.

    These campaigns might have stamped out all traces of Japan’s millennia-long history were it not for one factor – the resilience of the cannabis plants themselves. Every summer millions of these bushes – the feral offspring of cannabis legally cultivated before 1948 – pop up in the hills and plains of rural Japan. In 2006, 300 plants even sprouted in the grounds of Abashiri Prison in Hokkaido – much to the embarrassment of the powers-that-be.6

    Every year, the Japanese police wage well-publicized eradication campaigns against these plants. On average, they discover and destroy between one and two million of them. But like so many other aspects of the drug war, theirs is a losing battle and the next year, the plants grow back in larger numbers than ever.

    Due to the taboos surrounding discussions of cannabis, many people had been reluctant to condemn these police campaigns. But now critics are beginning to attack both the waste of public resources and the needless destruction of such versatile plants.

    Nagayoshi Hideo, author of the 2009 book, Taima Nyuumon – An Introduction to Cannabis – argues for the wild cannabis plants to be systematically harvested and put to use as medicines, biomass energy and in the construction industries.

    Funai Yukio – another advocate and author of Akuhou! Taima Torishimarihou no Shinjitsu – Bad Law! The Truth Behind the Cannabis Control Act (2012) – calls cannabis a golden egg for Japan. In a detailed breakdown of the potential economic benefits of legalization, he factors in savings from reduced policing and incarceration – concluding the country could reap as much as 300 billion dollars in the long term.

    In a nation facing unprecedented economic problems, and at a time when marijuana legalization is advancing in the United States and other countries, it appears these arguments are striking a chord. Recently Japan slipped behind China as the world’s third economic power and the country owes more than ten trillion dollars in debt – double its GDP. These problems contribute to the human toll of an estimated 6.5 million alcoholics and a suicide rate that hovers at around 30,000 a year.

    The legalization of cannabis could solve some of these problems. By luring young entrepreneurs back to the land, it could counter agricultural decline – particularly in post-earthquake Tohoku. It might improve the quality of care for thousands of cancer patients and halt the brain drain of scientists forced overseas to research medical cannabis. Legalization would also prevent the annual arrests of 2000 Japanese people – many in their 20s and 30s – whose lives are destroyed by their nation’s illogical and ahistorical laws.

    In years to come, Taima Hakubutsukan might be seen as a true beachhead in this struggle.

    “People need to learn the truth about the history of cannabis in Japan,” says Takayasu. “The more we learn about the past, the more hints we might be able to get about how to live better in the future. Cannabis can offer Japan a beacon of hope.”

    Cannabis: What’s in a name?

    Botanists usually divide the cannabis family into three broad categories – tall cannabis sativa, bushy cannabis indica and small cannabis ruderalis. However this simple taxonomy is often frustrated in practice by the interfertility of these three types, which allows them to be crossbred into limitless new varieties.

    The desired properties of these hybrids tend to determine the name by which they are commonly known.

    Marijuana, for example, usually refers to cannabis plants that are grown for ingestion for medical or recreational uses. Cannabis sativa is said to give users a feeling of energetic euphoria and can be prescribed for depression, whereas cannabis indica is apparently more sedating so can be used as a muscle relaxant or to treat chronic pain.

    Hemp, is the name often applied to tall plants from the cannabis sativa category which are primarily grown for their strong fibres – but may also contain significant levels of THC.

    Most recently, the term industrial hemp has been coined in the U.S. to refer to cannabis plants which have been specially-bred to contain very low levels of THC (less than 1%) in order to conform to current drug laws. Today, many of Japan’s licensed cannabis farms grow a low-THC strain called Tochigi shiro which was first developed in the post-War period.

    Jon Mitchell is a Welsh journalist based in Japan and an Asia-Pacific Journal Contributing Editor. He writes about human rights issues – particularly on Okinawa – and more of his work can be found at http://www.jonmitchellinjapan.com

    Recommended citation: Jon Mitchell, “The Secret History of Cannabis in Japan,” The Asia-Pacific Journal, Vol. 12, Issue 48, No. 1, December 8, 2014.

    Notes

    1 Two of the best Japanese texts on the nation’s cannabis history are Nagayoshi Hideo, Taima Nyuumon (An Introduction to Cannabis), Gentosha, 2009 and Funai Yukio, Akuhou! Taima Torishimarihou no Shinjitsu (Bad Law! The Truth Behind the Cannabis Control Act), Business Sha, 2012. Although not updated since 2010, the most detailed English website about cannabis in Japan is at taima.org accessible here.

    2 For more information on the museum, see here. For a Japanese interview with Takayasu about the origins of the museum, see here.

    3 For more details about the religious role of cannabis in Japan, see here.

    4 For the text of the UN report, see here; for the THC levels in the 1970s, see for example here.

    5 CBC News, “Japan stuffs magic mushroom loophole”, May 14 2002. Available here.

    6 Sydney Morning Herald, “Japanese jail bugged by marijuana plants”, August 29 2007. Available here.
    – See more at: http://historynewsnetwork.org/article/157808#sthash.rmnXOLl0.dpuf

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