4.Cannabis Renaissance

From ancient times cannabis for treatment was used exclusively as the plant or its parts. At present time the most studied compounds are cannabinoids. Is it enough to know concentrations of these compounds in a particular strain or are in a game also the other content compounds. This lecture tries to answer this question.

Lecture will discuss the barriers to Cannabis efficacy research and myriad ways US government has systematically impeded this work. We will use our recent battle to implement the veterans research as prime example of this research blockade trying to use medical marijuana to treat patients with treatment-resistant Post-Traumatic Stress Disorder (PTSD).

This FDA approved Phase 2 cannabis clinical trial is supported by a number of sources, including research in lab animals, fMRI imaging in humans, and anecdotal reports from countless health practitioners and patients.  Additionally, clinical research in Israel evaluating medical marijuana as treatment for PTSD has been promising.  MAPS' study will test four strains of smoked marijuana, each containing different concentrations of active cannabinoids, in two three-week stages, as a pharmacological agent to manage PTSD symptoms among 76 American war veterans.  This study is a collaboration between Dr. Sue Sisley, and researchers from Johns Hopkins University, University of Colorado, and University of Pennsylvania.  This will be the first randomized controlled crossover clinical trial in the United States testing the therapeutic potential of marijuana for PTSD.  The primary measured outcome will be the Clinician Administered PTSD Scale (CAPS-5), alongside extensive secondary outcomes including sleep patterns, depression, withdrawal symptoms, metabolic and inflammation panels, and self-reporting by the patients.

Four Learning objectives:

• Learn about existing/current state of both anecdotal & observation data.
  
• Learn about the design of the first ever triple blind randomized controlled trial evaluating use of Marijuana for military-related PTSD.
  
• Learn about regulatory obstacles to conducting this scientific study and developing medical marijuana into FDA approved medicine.
• Learn about hypothesized mechanisms of action for use of MMJ in treatment of military-related PTSD.

Seeds of the cannabis plant have been carried with humans for thousands of years, planted and cultivated in virtually every corner of the planet and utilized for its many qualities, by peoples everywhere. It is only in the past 100-odd years that cannabis has come under prohibition as a result of competition with various industrialists near the turn of the last century, (Nylon, Petroleum, Pulp and Paper, to name a few). But it’s hard to keep a good plant down…  

Even under prohibition a few committed researchers continued to investigate the properties and attributes of cannabis, that eventuallylead to a number of extremely important and groundbreaking discoveries. In the seminar we will discuss the discovery of THC, the finding of the receptor that is activated by THC, the elucidation of, what is now called the endocannabinoid system and the resultant innovation of “the entourage effect”, a concept that could potentially revolutionize modern medicine.

The pharmaceutical industry, that now controls most of the medicines we use and indeed have access to, has always had the mandate of synthesizing ‘single’ molecule medicine that it can patent and own (no one can patent and own a plant or natural compound). These synthetic medicines are well known to cause serious side effects, that are often fatal, killing more than 100,000 people per year in the United States, alone.This does not occur with natural, plant medicines.

There has never been a reported death due to cannabis, alone. In fact many consider the plant as an anti-toxin. Interestingly, new research is demonstrating, time and time again, that single active molecules from cannabis that are synthesized have a completely different effect than plant extracts, or the whole plant medicine. And this is where the revolution begins. The entourage effect (active plant molecules or compounds together in a natural mixture), make the safest and most efficacious cannabis medicine. This concept has the power to revolutionize modern medicine, as we know it.  

In the seminar we will discuss the efficacy of cannabis extracts compared to synthetic cannabinoids and drugs and, more importantly their safety. We will also review recent scientific literature demonstrating the difference in effectiveness of natural vs. synthetics and how the entourage effect has the potential to revolutionize modern medicine.

The power of the cannabis!

A. Paul Hornby Ph.D.

December 2016.

In all body systems, cannabinoids, including THC, function as anti-aging compounds through their ability to inhibit the negative consequences of excess free radical production. Cannabinoids, both from the plant (phytocannabinoids) as well as those we produce (endocannabinoids) should be viewed as the “oil” of life, as an essential nutrient, as a food. They help protect us from the “friction” of life created by the free radicals that are responsible for all age-related illnesses including cancers. Keep in mind that free radicals are also necessary for life because they provide feedback control for homeostasis of all biochemistry. Free radicals are both necessary and destructive. They must be appropriately controlled for optimal survival.

THC protects differentiated cells that are, for required efficiency, largely burning free radical producing carbohydrates as fuel. THC also helps protect cells when they are overworked and producing too many free radicals by turning on safe and efficient, cellular recycling  (autophagy) pathways. Autophagy occurs when cells are burning fat as their main energy source. As a consequence of cannabinoid’s ability to regulate cellular energy sources to optimize homeostasis, they have profound health benefits.  

Because of their global metabolic homeostatic capacity, cannabinoids function as adaptogens. Hence, they have profound healing properties.  The global cannabis awakening is driven by individuals who seethe improvement in human health that cannabis provides. All around the world, people have clearly demonstrated these benefits to themselves from direct personal experience.  Cannabis benefits most of man’s illnesses becauseour endocannabinoid system is a fundamental regulator of all aspects of human existence. The use of genetic engineering, to eliminate the CB1 receptor in a strain of mice,thereby creating a knockout mouse, has demonstrated the essential nature of CB1 activity. These mice die very prematurely, and are too afraid to move around the cage because they're so stressed without any CB1 simulation.

Today, the greatest global harm to humanity results from illnesses that characteristically produce excess free radicals. HIV, for example, has evolved in the highly differentiated immunological cells of primates and man. It requires the carbohydrate-based metabolic machinery that supported its evolution. When electron transport carbohydratecatabolism is reduced sufficiently, and replaced by safer fat burning, the viral infective process does not have the energy and resource support required for a successful infection.

The cannabis awakening is spreading around the world because of the beneficial experiences that people everywhere are having. People are demanding change. As governments protect the special interests that have helped support them, many people are choosing safer, cheaper more efficacious cannabis-based medicines and nutritional support. High THC, whole plant cannabis oil extracts can efficiently and effectively control both HIV and Kaposi sarcoma.  

HIV is the leading cause of death on the African continent. Most people infected with the virus go untreated. HIV can inexpensively and successfully be controlled with cannabis extracts in the absence of antiretroviral drugs. HIV-associated Kaposi's sarcoma is the number one cancer in Africa. There is no effective treatment for people suffering from Kaposi. They die painful horrible deaths. Cannabis extracts completely control this deadly virus-induced cancer.

The scientific perspective presented can be extended to metabolic syndrome and it's associated consequences, heart disease and diabetes. Additionally, The matrilineal inheritance of mitochondria is readily explainable. 

The medicinal, nutritional and industrial benefits documented herein only scratch the surface of the benefits that this plant can provide humanity now that the true value of the cannabis plant is becoming common knowledge. People resist change, but most will embrace it when it cures cancer and relieves pain and suffering. The synergy between the people's observations and modern science makes the continued expansion of cannabis use inevitable, unstoppable and irreversible.

Cannabinoids fine-tune a cell's energy production in order to protect it from excess free radical production. Consequently, cannabinoids have allowed for the evolution of the vertebrate brain, reaching its high point with humans. Evolution is the direct manifestation of the universal creative force. It selects for adaptability. The entire biosphere is one large unfolding chemical reaction. All life forms are simply quantized probes for adaptability. There is a constant back-and-forth between an organism adapting to his changing environment and changing its environment by doing so. 

Today the planet is undergoing a far from equilibrium phase change. The fluctuations of all the variables representing man’s interface with nature, and of nature itself, have become extreme. The decline of species, the variability of nature's chemicals interactions altered by man-made pollutants, the fluctuations of our financial establishments, of human migration, and of human behavior in general, are indicators of the gross rearrangement that has begun. It will result in either the collapse of societies or their rearrangement into a more cooperative, peaceful, and healthy world as cannabinoid content of human biochemistry globally increases as it always has.

A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer and specifically of gliomas. The mechanism of cannabinoid anticancer action relies, at least largely, on the ability of these agents to stimulate autophagy-mediated cancer cell death. Moreover,the combined administration of cannabinoids and temozolomide produces a strong anticancer effect, which correlates with an intense activation of the signalling route that triggers the activation of cytotoxic autophagy. Research conducted in our group has also led to the identification of mechanisms of resistance to cannabinoid anticancer action. For example, up-regulation of the growth factor Midlkine (MK) promotes resistance to cannabinoid anticancer action in gliomas via stimulation of the Anaplastic Lymphoma Kinase tyrosine kinase receptor (ALK); and could be a factor of bad prognosis in GBM patients. All these preclinical findings have facilitated the promotion of a clinical study to investigate the safety and efficacy of the combined administration of the cannabis-based medicine Sativex and temozolomide in recurrent GBM. In this presentation I will discuss these issues and also other possible future studies that may help to clarify whether cannabinoids may be useful as anticancer agents in patients with gliomas or other cancers.

Co-author: Khadija Benlhassan, PhD

A growing number of clinical studies indicate that cannabis or cannabinoids may have medicinal value for certain diseases and under certain conditions. In 2016 a review by Mikael A. KowaL et al., covered controlled clinical trials of the years 2010–2014 on cannabis-based medicines, which followed the reviews published by Hazekamp and Grotenhermen (2010) and by Ben Amar (2006). We have applied the same methodology as the threeprevious reviews to the period that followed – January 1, 2015 to December 31, 2016. A systematic search was performed in the scientific database of PubMed, which is hosted by the U.S. National Library of Medicine. This database contains about 20 million scientific publications from the field of life sciences and biomedical information. The search focused on clinical studies that were randomized, (double) blinded, and placebo-controlled. The key words used were: cannabis, marijuana, marihuana, hashish, cannabinoid(s), tetrahydrocannabinol, cannabidiol, THC, CBD, dronabinol, marinol, nabilone, nabiximols and Sativex. Forty-five controlled studies evaluating the therapeutic effects of cannabinoids were identified. For the final selection, only properly controlled clinical trials were retained.Pure THC and several analogs have shown significant therapeutic benefits in the relief of chronic neuropathic pain, nausea and vomiting, and stimulation of appetite in cancer and AIDS. CBD (cannabidiol) emerges as another valuable cannabinoid for therapeutic purposes besides THC.
Keywords: cannabinoids, cannabis, therapeutic potential, controlled clinical trial, efficacy, safety, cannabidiol.

At the present time the cultivars of hemp with a higher THC content are used for treatment in the humane medicine. However a high THC content in these breeds limits the number if patients under treatment due to its psychogonical effects. The breeds with a low THC content, i. e. up to 0.2%  THC in the dry matter are used for pharmaceutical industry for the production of CBD eventually CBG. The goal of the development was to find out the possibilities of the use of the breeds with a low THC content for the treatment of various illnesses. A completely new procedure to process the sown hemp for the curative purpose was developed in 2015. This way of treatment by hemp was applied at a vast pool of patients with various diagnoses. The results denote an extraordinary potential of the use of breeds of sown hemp with the low THC content in the humane medicine.

The beneficial medical properties of cannabis plant (Cannabis sativa L.) are widely recognized. Yet the plant is still listed in the most tightly restricted category reserved for illict  drugs that have "no currently accepted medical use". This status has prevented the medical use of cannabis and relevant research and triggered the debate between government officials on one side, and active members of civil society, patients and individual doctors  on the other side, whether to legalize the production, possession and use of the plant for medical purposes.

Public health is what we, as a society, do collectively to assure the conditions for people to be healthy, happy and feel-well. It refers to "the science and art of preventing disease, prolonging life and promoting human health through organized efforts and informed choices of society, organizations, public and private, communities and individuals." In many countries public health is already  providing leadership on matters critical to medical cannabis and  health and engaging in partnerships where joint action is needed. Also, it helps  shaping a  research agenda and stimulating the generation, translating  and dissemination of the  relevant knowledge and  articulating ethical and evidence-based medical cannabis policy options.  Human rights lens also inform the decision making processes and development of optimal medical cannabis policies. Human rights are often divided between those that protect individual, civil and political rights on the one hand,  and economic, social, and cultural rights on the other. Human rights perspective recognizes, among others,  the right of everyone to the highest attainable standard of physical and mental health and well being, including the right to treatment with medical cannabis and necessary  services.

However, in most countries, including Slovenia, medical cannabis policies are still the product of controversy and  remain surrounded by controversy as they are implemented.  Related ethical issues  pose many moral and social  dilemmas rather than  black and white moral questions.  The scientific considerations blend with political and ethical conflicts, questions of public and  individual rights are central and scientific evidence should become imperative to inform appropriate regulation and prescription of the plant.  Public health ethics requires careful balancing between individual interests in personal (e.g., autonomy, privacy, and liberty) and economic (e.g., contracts and property) freedoms on the one hand and collective interests in health safety and security on the other.   

Part of the public (society)  already recognizes that cannabis prohibition clearly causes more harm than good. Many individuals and groups began advocating for effective government regulation of cannabis. Until recently, many medical doctors have been reluctant to publicly voice their opposition to the prohibition of the plant. But through scientific evidence and measuring patients’ experiences many doctors and other health professionals had recognized that prohibition was ineffective and harmful. One of the most egregious outcomes of cannabis prohibition was  that many sick people could not  legally  access the medicine that could work best for them. At the same time, the prohibition  had not  prevented children from accessing the drug and  it had led to the proliferation of  more dangerous synthetic cannabinoids.

This  presentation will not offer clear-cut answers to many of the ethical issues raised. However, it will provide public with many perspectives on the role of public health concerning  medical cannabis . For example: What is the meaning of the most common  concepts in public health, such as:  population,  risk, harm, and benefit in the context of medical cannabis ? How does the population perspective differ from the individual perspective? When it is necessary and appropriate to intervene to protect human rights? And when it is necessary and appropriate to intervene to protect the public’s health? Are factors such as risk, effectiveness, cost, burdens and  fairness  the best ways to evaluate public health interventions ? To what extent should social justice be an advocating value in public health? It is essential to recognize that scientific and ethical arguments about the cannabis prohibition and access to medical cannabis have to be joined to political solutions. This may help us think more clearly and constructively about the medical cannabis challenge that will affect many types of health and social issues common with many people and life in communities.

The  presentation will provide many thoughts by both  authors and some conclusions by first autor with which not everyone will necessarily agree but which can open dialogue with others.