We’d all like to think that cannabis is a potential solution for specific, difficult-to-treat medical conditions – such as neuropathic pain or inflammatory disease – for which we lack ideal treatments. After all, it would be poetic if nature’s wisdom provided the ideal medicine we have not yet designed ourselves. That may be why the level of hype, hope, anger and backlash around medical cannabis in popular culture has reached a feverish pitch – but the truth is more prosaic than poetic.
Despite anecdotal reports otherwise, data from a growing number of peer-reviewed studies show that the whole-plant cannabis accessible to researchers does not perform consistently as a viable treatment for specific conditions. Furthermore, mainstream cannabis culture seems to proclaim the notion that cannabis is a panacea, pushing public perception of its efficacy far beyond what science has validated. Sorry to be buzzkills (pun intended), but the term herbal cannabis describes a class of plants, not a tailored therapy for a particular indication or a group of indications. This problem is compounded by the barriers patients and researchers face in accessing tailored cannabis varieties with diverse – and perhaps questionable – chemistry.
As we see it, there are two main paths that should be pursued in parallel by the research community to realize the full potential and promise of cannabinoids as legitimate medicine. Both will be productive as our understanding of the human endocannabinoid system (ECS) continues to grow through dedicated research. One is modifying isolated plant-derived and semi-synthetic cannabinoid compounds that can be developed into medicines to target the ECS. Another, which we’ll explore in more detail here, breeding whole plants for more precisely targeted combinations of compounds to increase their therapeutic utility.
Given the types of whole plant cannabis that are widely available around the world today, writing a prescription that reads “cannabis” is about as specific as writing a prescription for “pills”; yet, it doesn’t need to be this way. It’s possible to breed plants that yield tailored ratios of very diverse compounds and therefore, it’s possible to imagine a time when cannabis plants consistently produce material that synergistically serves as effective and safe medicines.
When it comes to adapting cannabis for medical use, it is important to distinguish the generic term from carefully-tailored and standardized “cultivars” (cultivated-varieties) or “chemovars” (chemical-varieties) with well-characterized and tested phytochemical profiles. Compared to other compounds, individual phytocannabinoids (cannabinoid compounds from plants) tend to act very differently on our bodies’ ECS. Some even cause seemingly opposite effects. Moreover, like many treatments, some phytocannabinoids may have a biphasic dosing effect, meaning their effects at higher doses may be the opposite of their effects at lower doses. This is true, for example, of two of the best-known cannabinoids. At low doses, THC may be a potent anti-depressant known to induce hyperphagia (over-eating or “munchies”), but at higher doses, it can exacerbate depression, may stimulate anxiety, and triggers hypophagia (loss of appetite). Like THC, CBD’s mode of operation is also often biphasic. To make matters even more complex, these compounds have been shown to work differently when combined than when isolated and tested individually.
Scientific inquiry in the cannabinoid field has consistently been motivated by asking “what if,” and we must continue to ask that question.
What if plants were bred such that they contained specific compounds in specific quantities and tailored ratios to hit the right disease targets with minimal adverse effects?
We’re now able to advance such targeting by enhancing our understanding of why our bodies respond to cannabinoids at all. Early studies of whole plant cannabis led to the 1964 discovery of tetrahydrocannabinol. That eventually helped us identify interactions with the ECS, which is present in every organ and affects nearly all physiological processes. These studies during the past 50+ years have laid the foundation for cannabinoid medicine.
Prominent scientists from the US National Institutes of Health focused on ECS function have summed up well what is so exciting about the system: “…modulating the ECS holds therapeutic promise for practically all human diseases.” To fully harness its potential, we must look beyond what we know from cannabis – building upon that foundation and knowledge – and identify the safest and most efficient means to modulate the ECS to achieve optimal therapeutic results.
Efforts to transform herbal cannabis into an effective medicine have taken significant strides in recent years, as evidenced by scientific publications highlighting the pharmacological properties of novel cannabis chemovars. This description of herbal cannabis as particular chemovars is critical if it is to be considered as legitimate therapy by physicians.
A group of Canadian doctors recently warned that there is little to no research supporting the efficacy of cannabis, which is very disturbing for those of us who know there is great value in modulating ECS activity to address specific diseases and other afflictions. Our disappointment is not directed at the physicians; rather, we are frustrated that the herbal cannabis used for almost all published studies has made such conclusions inevitable. We can unlock this potential phytochemical diversity through a directed breeding program. Fortunately, innovative breeding work is now taking place that will increase the likelihood that study results will align with the hopes and expectations of those looking for cannabis-derived treatment options.
However, the possibilities don’t stop with plants. While we breed specific, targeted cannabis chemovars, we should ask what if we also modified cannabis-derived compounds to more accurately and effectively hit challenging disease targets as has been done for centuries with other remarkable plants?
This article was co-authored by Gary Hiller, President and COO of Phytecs, Inc.
Joseph (Yossi) Tam, DMD, PhD is Director of the Multidisciplinary Center for Cannabinoid Research at Hebrew University of Jerusalem.
A higher calling: How Israeli marijuana research changed the world
As much of the world debates how to address marijuana use, the vast majority of American states have legalized it or allow it for medical purposes. Global pharmaceutical companies and hospitals seeking effective treatments using cannabis should look to Professor Raphael Mechoulam, a scientist at Hebrew University. Mechoulam, a pioneer in the field, was the first to isolate, analyze and synthesize the major psychoactive and non-psychoactive compounds in cannabis and has developed a number of revolutionary marijuana-related treatments.
Today, roughly 147 million people use medical marijuana for effective relief of various ailments, including AIDS, multiple sclerosis, Crohn’s disease, cancer treatment side effects and Parkinson’s. Experts believe these numbers will grow exponentially in the coming years, and Mechoulam is now widely recognized as the godfather of medical marijuana, the high priest of his field.
Mechoulam began studying marijuana as a young professor in 1964. He learned that researchers had isolated morphine from opium over 150 years ago and cocaine from coca leaves a century prior, yet no one had tried to understand cannabis and its psychoactive and non-psychoactive ingredients. Mechoulam and his colleagues became their own test subjects and after a few months not only understood marijuana’s ingredients, but found a way to test its medicinal properties.
Not long after Mechoulam’s human experiments with THC, the major psychoactive compound in cannabis, he applied for a grant with the US National Institutes of Health, but the response was not exactly welcoming. “Cannabis is not important to us,” he recalls an NIH official telling him. “When you have something relevant, call us… marijuana is not an American problem.” At the time, not a single US lab was working on it.
In 1965, the NIH changed its tune at the insistence of a member of Congress, who was concerned about his son’s recreational use. Mechoulam had just isolated THC for the first time and discovered its structure. Dan Efron, head of pharmacology at the National Institute of Mental Health, promised Mechoulam financial support for further research. In return, the professor sent the NIH the entire world supply of synthesized THC, about 10 grams, which the NIH used to conduct many of the original cannabis experiments in the United States.
Today, thanks to Mechoulam’s research over the past half century, doctors around the world prescribe marijuana for a variety of disorders. Mechoulam’s work catapulted Israel to the top of the field of medical marijuana testing.
“Israel is the marijuana research capital of the world,” says Dr. Sanjay Gupta, chief medical correspondent for the Health, Medical & Wellness unit at CNN.
Globally, there is an obstacle to wider acceptance of medical marijuana: doctors themselves. Mechoulam believes that use of the drug is not standard practice because most physicians are not yet familiar with it and because most doctors are uncomfortable with a medicine that can be consumed by inhaling its smoke. But Mechoulam has played a major role in dispelling misconceptions about cannabis.
“The problem is that for many years, marijuana was put on the [same] scale as cocaine and morphine,” Mechoulam says. “This is not fair. All drugs, starting from aspirin to valium, [have] side effects. One has to know how to use them.”
Until recently, pharmaceutical companies weren’t enthusiastic about applied research on the drug. The legal ambiguity around cannabis and the difficulty of filing patents on a plant that has existed forever limit their ability to make money.
“It is still widely believed that cannabinoids are drugs and they make you crazy, make you mad, that they don’t have therapeutic value and they are addictive,” says Manuel Guzman, a professor in the Department of Biochemistry and Molecular Biology at Complutense University in Madrid and one of the world’s leading scientists studying the effects of cannabis on cancer cells. But, according to Guzman, that’s “based on ignorance. Knowledge takes time to get absorbed by society and the clinical community.”
At the federal level, cannabis is still illegal in the United States, which prevents serious and ongoing research on THC and on CBD, the non-psychoactive compound in cannabis. But 23 states and the District of Columbia have legalized marijuana for some medical uses, and according to polling data, a majority of Americans now favor legalization for recreational purposes. Elsewhere in the world, there is even more momentum. Israel, Canada and the Netherlands all have medical marijuana programs. Uruguay has legalized pot and Portugal has decriminalized the drug.
All of this gives reason for optimism about the future of medical marijuana research, according to Mechoulam, who is now investigating the drug’s effects on asthma. It is clear that his groundbreaking life’s work and “never, ever give up” attitude are slowly changing the minds of his peers. “If a Nobel Prize was given on cannabis research,” Dr. Guzman says, “Rafi would be the leading candidate.”
The writer is the author of Thou Shalt Innovate: How Israeli Ingenuity Repairs the World (Gefen Publishing) and a senior fellow at the American Foreign Policy Council.
Throughout the world, Israel is known as the “startup nation,” where investors are increasingly drawn to the innovation and brainpower that are its greatest natural resources. Accordingly, philanthropists are starting to look at their Israel-related donations less as one-shot gifts and more as charitable contributions with characteristics more typically associated with venture investments.
An anonymous donor recently gave $1 million to the American Friends of Hebrew University (AFHU). The university invested the same sum of money in Agrinnovation, an Israeli agricultural investment fund partially owned by Yissum, HU’s technology commercialization company. Agrinnovation invests exclusively in cutting-edge agricultural technologies, food, plant and animal sciences originating from HU.
Rather than simply supporting a cause with a single gift, this sort of impact philanthropy seeks to create a virtuous cycle: Dollars are invested to do social good and create financial returns that can be reinvested in the same enterprise. It has become so widespread that in December, JLens, a network of more than 9,000 Jewish investors, held a summit in New York City on impact investing.
“The donation to Hebrew University assumed some characteristics of a typical venture investment, though it is purely philanthropic and the university will benefit from all the returns,” said AFHU board member Clive Kabatznik, “This is a new model for us, and we are meeting with potential donors about what they think is good for the world and coming up with bespoke investment ideas.”
HU has a long history of innovation. Mobileye, a vehicle collision warning and driver safety software system, was founded in 1999 by a researcher at the university; it was purchased by Intel last year for $15.3 billion. Blockbuster chemotherapy drug Doxil and Alzheimer’s disease medication Exelon also originated in HU’s laboratories. Among its agricultural advancements, the university is responsible for a cherry tomato variety with a long shelf life sold around the world.
Despite a difficult topography, Israel has been a pioneer in agriculture for decades, making the “desert bloom” and turning a water shortage problem into a surplus through desalination. The agriculture sector is appealing to investors because the time frame from patent to profit is relatively short: five years, on average.
There are currently six companies in the Agrinnovation fund’s portfolio. Among them, ChickP has invented a high-grade plant-based protein for food; Sufresca has created a safe-to-consume vegetable and fruit coating to increase the shelf life of such products. Gemma-Cert, a medical marijuana company, is developing an affordable device for the detection, analysis and sorting of medical cannabis flowers.
“If you are a donor and want to celebrate Israel’s economy and young democracy, then you can accomplish many different goals through an investment in Israel and its agriculture sector,” said Charlene Seidle, executive vice president of the Leichtag Foundation, who visited Hebrew University recently to discuss her foundation’s agricultural property in California.
While philanthropy in Israel was traditionally about Zionism and giving back to the Jewish nation, experts say that has become a tougher sell for younger donors from the tech and hedge fund worlds. Those reasons might be in the back of their minds, but they are increasingly motivated by economic considerations. They want to see their donations actually making a difference.
“What we are seeing among second- and third-generation donors is that they’re giving with their heads rather than their hearts,” said Jeff Solomon, president emeritus of the Andrea and Charles Bronfman philanthropies. “There’s an expectation that you will see a return on your charitable investment just as you would on a business investment.”
Diane Hess is a New York-based writer and alumna of Hebrew University of Jerusalem’s Rothberg International School.
Bill Nye’s new Netflix show explores Israel’s advances in medical marijuana, which are much more advanced than the United States.
People are getting high in the Holy Land for a good cause.
In a recent episode of “Bill Nye Saves the World” in which Nye explore medical marijuana, he sends a correspondent to Israel for a segment called “How is Israel healing the world with marijuana.”
The episode highlights the progress Israel has made in medical marijuana research, noting that there are significantly fewer regulatory hurdles than in the United States.
The company Tikun Olam operates the largest cannabis farm in Israel, and it’s licensed by the Israeli government. Tikkun Olam CEO Aharon Lutzky explains that the cooperation between the Israeli government and private industry fosters success in finding ways cannabis can help patients struggling with conditions such as cancer, Crohn’s and colitis, PTSD, epilepsy and Parkinson’s disease.
Nye notes that the situation is very different in the U.S. because the Drug Enforcement Agency doesn’t believe cannabis has medical value, and therefore classifies it as a Schedule 1 drug, making it illegal to grow it for the purpose of medical studies.
“It is literally easier to study meth,” Nye claimed.
Israeli organic chemist Raphael Mechoulam was the first to isolate marijuana’s THC compound for scientific study more than 50 years ago. In 1996, Israel began its national medical marijuana program, the first one in the world.
Attorney General Jeff Sessions unwittingly has become a key supporter of Israel’s thriving medical marijuana industry. Just ask cannabis researcher Yossi Tam.
Speaking in Palo Alto this week, the Israeli expert on cannabinoids — chemicals that give the cannabis plant its medical and recreational properties — said anti-pot politics in the United States have allowed Israel’s medical marijuana industry to thrive. Israel even has attracted some of the top American researchers, he said.
Israel even has attracted some of the top American researchers, he said. After all, in the U.S., marijuana remains a Schedule 1 drug, alongside heroin and ecstasy, meaning that research is stunted because such substances have “no currently accepted medical use and a high potential for abuse.”
However, in Israel, which is preparing to start issuing export licenses for cannabinoid-based products, cannabis research is flourishing. Tam is focused on how cannabinoids can help patients battle obesity, and he’s also part of a team seeking medicinal uses of cannabis in fighting everything from epilepsy to traumatic brain injury to cancer.
“Israel has become a leader because it was allowed to conduct research, whereas here [in the U.S.] it was stopped,” Tam told J. after his talk, which focused on the science of cannabinoids and how to use them to fight obesity. “Once it will be legal here, then the U.S. will take over like with every other thing.”
Tam is the managing director of the Multidisciplinary Center on Cannabinoid Research at the Hebrew University of Jerusalem, and he also heads the Obesity and Metabolism Laboratory there.
He spoke Jan. 16 in Palo Alto at the Morgan, Lewis and Bockius law firm, telling an audience of about 50 that medical marijuana was first used in China nearly 5,000 years ago and that synthetic cannabinoids could have an even wider range of curative powers. The talk was presented by the California Israel Chamber of Commerce, American Friends of the Hebrew University and WGD Partners, a Palo Alto-based financial advisory firm.
Recreational use of marijuana is banned in Israel, but medical marijuana is legal there — and Israeli researchers have been focused on the efficacy of cannabinoids in fighting pain and disease for more than 50 years. Meanwhile in the U.S., Sessions has spearheaded a federal drive to keep pot illegal, even as California this year became the eighth state to legalize recreational use of marijuana and more than half the states allow the use of medical marijuana.
Tam works at Hebrew University with Raphael Mechoulam, who in the 1960s first isolated CBD and THC, the two most prominent of the many cannabinoids found in marijuana.
A brochure available at his talk proclaimed: “Join the cannabis revolution: Cannabis is no longer just associated with getting high, but is now tantamount to getting healthy.”
Michael Mitgang, WGD’s managing director, gave a short presentation on the cannabis industry and its growth potential before Tam’s talk, predicting the $8.1 billion U.S. cannabis market in 2017 will balloon to more than $100 billion annually in a few years.
Tam, a former dentist who did postdoctoral work in the U.S. at the National Institutes of Health, said Israeli researchers know their place at the forefront of cannabinoid investigation will be threatened if the U.S. reclassifies marijuana.
“We have a window of opportunity now,” he said. “Let’s see what happens.”
13 of the biggest health breakthroughs in Israel in 2017
Compound kills energy generating system of cancer
An Israeli researcher devised a synthetic compound to disable the enzymes that allow cancer cells to metastasize. When cancer cells leave the primary tumor and spread to other organs, they reprogram their energy-generating system in order to survive in harsh conditions with a shortage of nutrients like glucose. Prof. Uri Nir of Bar-Ilan University identified an enzyme called FerT in the energy-generating mitochondria of metastatic cancer cells – an enzyme normally only found in sperm cells (which need to function outside the body they came from). When he targeted FerT in lab mice, the malignant cells soon died. Using advanced chemical and robotic approaches, Nir’s lab team developed a synthetic compound, E260, which can be administered orally or by injection, causing a complete collapse of the entire mitochondria “power station.” “We have treated mice with metastatic cancer and this compound completely cured them with no adverse or toxic affect that we can see,” reported Nir, adding that normal cells were not affected. Phase 1 clinical trials are planned over the next 18 months.
Personal menu to help avoid diabetes
In 2015, two researchers from the Weizmann Institute of Science in Israel released a groundbreaking study showing that specific foods and food combinations affect each individual’s blood-sugar level differently.
That discovery was incorporated into a made-in-Israel app, DayTwo, which helps pre-diabetics and diabetics who are not insulin dependent choose dishes that can best balance their individual blood-sugar levels. The algorithm predicts blood-glucose response to thousands of foods based on gut microbiome information and other personal parameters.
High blood sugar is linked to energy dips, excessive hunger and weight gain as well as increased risk of metabolic diseases such as diabetes and obesity.
To use the app, which went on sale in the US in 2017, users need to answer a questionnaire about their medical history, physical characteristics, lifestyle and diet. A stool-sample kit is then FedExed to the user, who sends it on to DayTwo’s lab. There the microbiome DNA is sequenced and the data is plugged into an advanced machine-learning algorithm.
In about six to eight weeks, users receive a microbiome report and a six-month plan of personalized meal recommendations to help balance blood sugar.
World’s first bone implants
In August and December, doctors at Emek Medical Center in Afula performed rare bone implants – one on a man missing part of his arm bone and the second on a man missing five centimeters of his shinbone, both as the result of car accidents. Normally, the human body cannot restore bone segments, but revolutionary tissue-engineering technology developed by Haifa-based Bonus BioGroup enables growing semi-solid live bone tissue from the patient’s own fat cells. The tissue is then injected back into the patient’s body in the expectation that the missing bone fragment will be regenerated in around six weeks without any danger of implant rejection or the complications of traditional bone transplants. “This surgery is truly science fiction; it changes the entire game in orthopedics,” said Dr. Nimrod Rozen, head of orthopedics at Emek, who carried out the experimental procedure. In the future, the Bonus BioGroup regeneration technology could be used for a variety of bone-loss conditions, including bone cancer, for which there is currently no solution.
An early-stage Israeli ophthalmic medical devices startup developed a revolutionary artificial cornea implant that holds out hope to millions of blind and visually impaired people. The nanotech-based synthetic cornea by CorNeat Vision of Ra’anana proved successful in initial tests on animals. The company plans human implantations in Israel in mid-2018, and a larger clinical trial in the United States. According to the World Health Organization, diseases of the cornea are the second leading cause of blindness worldwide, affecting as many as 30 million people. “Unlike previous devices, which attempt to integrate optics into the native cornea, CorNeat’s implant leverages a virtual space under the conjunctiva that is rich with fibroblast cells, heals quickly and provides robust long-term integration,” said CorNeat Vision’s Almog Aley-Raz. The surgical procedure takes just 30 minutes.
Hernia surgery just got simpler
In June, ISRAEL21c reported on a new tool developed by Via Surgical for attaching mesh to tissue, allowing surgeons to treat hernias with fewer complications, less pain and faster recovery. In the US alone, some five million people have a hernia – a protrusion of an organ or tissue through a weak spot in the abdomen or groin — according to the National Center for Health Statistics. Traditionally, open hernia-repair surgery involved stitching a mesh patch, or surrounding tissue, over the weak tissue. Today, many hernias are repaired laparoscopically, but because suturing through tiny laparoscopic incisions is difficult, most surgeons use a less ideal solution — screw-like tacks to secure the mesh to the abdominal wall or bone. Via Surgical’s unique FasTouch cartridge system, which received FDA approval in 2016, affixes prosthetic material to soft tissue. It is designed like sutures and delivered like tacks, with the goal of providing the best of both worlds for laparoscopic hernia repair. “Surgeons are very excited about it,” says Lena Levin, cofounder and CFO of Via Surgical. “Hernia repair is one of the most common surgeries.
Screening newborns for autism
Israeli engineer Raphael Rembrand developed a simple noninvasive way to screen newborns for signs of autism using the same instrument currently used to test infants’ hearing. The SensPD diagnostic test, now ready for clinical trials, uses optoacoustic emissions as an indicator of the baby’s overall sensory perception. It can be administered hours after birth, and because the inner-ear mechanism develops in the third trimester of pregnancy, one day it may even be possible to screen for autism spectrum disorders prenatally. Some three million children are diagnosed with autism every year. The earlier the condition is detected the better the possible outcome. Thirty years ago, Rembrand’s four-year-old son was diagnosed as autistic, but it was too late at this point for critical early-intervention therapies. “Applying interventions before the age of two results in better than 90% success rate in ingraining social skills for social integration,” says Rembrand.
Reversing cognitive decline with cannabis
In May, scientists from the Hebrew University of Jerusalem and from the University of Bonn in Germany announced that they had restored the memory performance of lab mice to a juvenile stage by administering a small quantity of THC, the active ingredient in cannabis. The report in Nature Medicine showed that after giving low doses of THC to mice over a four-week period, the cognitive functions of 12- to 18-month-old mice treated with cannabis were just as good as the functions of two-month-old mice in the control group. Clinical trials on humans are to follow. A study by Therapix Biosciences presented in September to the International Association for Cannabinoid Medicines’ Conference on Cannabinoids in Cologne, Germany, similarly suggested that THC can significantly reverse age-related cognitive impairment in old mice.
Early diagnostic test for Parkinson’s
This year, Hebrew University of Jerusalem Ph.D. student Suaad Abd-Elhadi won the Kaye Innovation Award for her diagnostic tool, ELISA, which detects Parkinson’s disease at a much earlier stage than existing tools, and better tracks progression of the disease and response to therapy. Parkinson’s disease, affecting seven to 10 million people worldwide, is characterized by stiffness, tremors and shaking. Medication to control symptoms is costly. Currently there are no standard diagnostic tests for Parkinson’s other than clinical information provided by the patient and the findings of a neurological exam. Once Parkinson’s is revealed, the neurodegenerative disease is usually already progressing. Abd-Elahdi’s diagnostic tool detects the alpha-synuclein protein closely associated with Parkinson’s disease, and could lead to a minimally invasive and cost-effective way to diagnose the disorder in time to improve the lives of patients. Abd-Elhadi has demonstrated a proof of concept and is analyzing a large cohort of samples as part of a clinical study. Through its Yissum technology transfer company, Hebrew University has signed an agreement with Integra Holdings for further development and commercialization.
Hip-Hope cushions falls in elderly
Each year, nearly 3 million seniors worldwide are hospitalized due to hip fractures – many experiencing a drastic deterioration in quality of life. The direct annual cost of treating hip fractures exceeds $15 billion in the US alone. Rather than focus on better ways to treat the broken bone, Israeli engineer Amatsia Raanan decided to use cutting-edge technology to avoid injury in the first place. He and three cofounders developed Hip-Hope, a smart wearable device designed as a belt. Once Hip-Hope’s multi-sensor detection system senses an impending collision with a ground surface, two large airbags are deployed instantly from each side of the belt to cushion the hips, and a connected smartphone app sends an automatic alert message to predetermined recipients. The 1-kilo (2.2-pound) device, due to go on sale shortly, even has a built-in emergency call button that the user can activate in any situation of distress. Hip-Hope is certified by the CE (Europe), FDA (United States), Health-Canada and AMAR (Israel). In studies carried out at a major Canadian lab, the Israeli device was proven to reduce impact by 90%.
An injection that melts fat
Jerusalem-based Raziel Therapeutics has developed an injection that melts fat cells and postpones the proliferation of new fat cells. The medication generates heat to use up some of the free fatty acid that’s produced by fat cells in the body, which in turn reduces fat tissue. Obesity has become a worldwide epidemic, and the World Obesity Federation predicts that by 2025, a third of the world’s population will be overweight or obese. Raziel’s technology, which targets specific areas in the body, is now in clinical trials in the US. Preliminary results show a 30 to 50 percent reduction in subcutaneous fat at the treated site after a single injection. Each treatment lasts between six and nine months, but treatment could be more effective in those who change their lifestyle in parallel. An audio-analysis technology developed at Ben-Gurion University can assess sleep disorders such as obstructive sleep apnea (OSA) while the user is awake, at home and not hooked up to machines or sensors. The American Sleep Apnea Association estimates that 22 million Americans suffer from the malady and that as many as 80% of moderate to severe OSA cases go undiagnosed. Currently, patients are diagnosed using overnight polysomnography (PSG) to record brain waves, blood oxygen level, heart rate, breathing, and eye and leg movements via electrodes and sensors. The new system, which does not require contact sensors, could be installed onto a smartphone or other device that utilizes ambient microphones. It analyzes speech during waking hours and records and evaluates overnight breathing sounds using new technology that is simpler and significantly less expensive than PSG. The researchers have tested the system on more than 350 subjects and are working toward commercialization.
First implant for heart failure
In July, a 72-year old Canadian man became the world’s first recipient of an Israeli-developed implant to treat diastolic heart failure – a fairly common condition for which there is no effective long-term treatment. The minimally invasive surgery was performed at Rambam Health Care Campus, a medical center in Haifa. The CORolla implant was developed by cardiologists at Israeli startup CorAssist Cardiovascular of Haifa. The elastic device is implanted inside the left ventricle and applies direct expansion force on the ventricle wall to help the heart fill with blood. The patient, Robert MacLachlan, had run out of treatment options in Canada for his diastolic heart failure. His wife read about CORolla on the Internet and contacted Rambam.
Renewing damaged cells
Researchers from the Weizmann Institute of Science discovered a molecule in newborn hearts that appears to control the process of renewing heart muscle. The findings, published in June in Nature, point to new directions for research on restoring the function of damaged cardiac cells. Heart disease is the leading cause of death worldwide. The Agrin molecule seems to “unlock” the renewal process and enable heart-muscle repair – never seen before outside the womb. Normally, after a heart attack the damaged muscle cells called cardiomyocytes are replaced by scar tissue, which cannot pump blood and therefore place a burden on the remaining cardiomyocytes. Following a single injection of Agrin, damaged mouse hearts were almost completely healed and fully functional. Scar tissue was dramatically reduced, and replaced by living heart tissue that restored the heart’s pumping function. The research team has begun pre-clinical studies in larger animals.
Therapix Biosciences Plans Preclinical Study to Evaluate Opioid-Sparing Effects of Two Innovative Synthetic Cannabinoids
/PRNewswire/ — Therapix Biosciences Ltd. (Nasdaq: TRPX), a specialty clinical-stage pharmaceutical company specializing in the development of cannabinoid-based treatments, executed a non-exclusive material transfer agreement with Yissum, the technology transfer company of The , for two synthetic cannabinoids synthesized by , Ph.D., Professor of medicinal chemistry at the university and Chairman of the Therapix Scientific Advisory Board. Therapix plans to initiate a preclinical study during the fourth quarter to evaluate the opioid-sparing effect of these compounds in a rat model. The opioid overuse epidemic in was recently declared a public health emergency by President . According to Medical Care, prescription opioid overdose, abuse and dependence carries high costs for society with an estimated total economic burden of alone. Nevertheless, for immediate relief of moderate-to-severe acute as well as chronic pain, opioids are frequently the treatment of choice due to their rapid onset and efficacy. However, due to their addictive nature and deleterious adverse events that may lead to lethal outcomes, there is a need to significantly reduce their effective therapeutic dose, Chief Technology Officer at Therapix, said, “To address the opioid issue, Therapix is collaborating with Professor Mechoulam to develop a therapy of innovative cannabinoids and opioids. The study builds upon the innovative work of Professor Mechoulam and seeks to reduce the use of opioids by combining them with proprietary cannabinoid molecules to alleviate pain.” “Based on our research surrounding the effects of the endocannabinoid system and how cannabinoids can play a role in pain relief, our group of research scientists has synthesized cannabinoids with improved binding affinity and target specificity, which do not cause the therapeutically undesirable cannabis psychoactivity,” stated Professor Mechoulam. “In view of their parallel actions in pain, cannabinoids and opioids together may allow the development of a novel therapy that could exhibit a synergistic effect that reduces the therapeutic effective dose of opioids.” , Chief Financial Officer at Therapix, said, “We are privileged to be working with Professor Mechoulam and the in paving the way forward to a potential new therapeutic that may one day help to address this deadly social and medical crisis.” About Therapix Biosciences Ltd.: Therapix Biosciences Ltd. is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. Our focus is creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on repurposing an FDA approved synthetic cannabinoid (dronabinol): THX-110 and THX-120 for the treatment of Tourette syndrome (TS) and Obstructive Sleep Apnea (OSA); THX-130 for the treatment of Mild Cognitive Impairment (MCI) and Traumatic Brain Injury (TBI); and THX-150 for the treatment of infectious diseases. Please visit our website for more information at www.therapixbio.com. About Yissum: Yissum is the technology transfer company of the Hebrew University . Founded in 1964, it is the third company of its kind to be established, and serves as a bridge between cutting-edge academic research and a global community of entrepreneurs, investors, and industry. Yissum’s mission is to benefit society by converting extraordinary innovations and transformational technologies into commercial solutions that address our most urgent global challenges. Yissum has registered over 10,000 patents covering 2,800 inventions; licensed over 900 technologies and has spun out more than 125 companies. Yissum’s business partners span the globe and include companies such as Boston Scientific, Google, ICL, Intel , Johnson & Johnson, Merck, Microsoft, Novartis and many more. For further information please visit www.yissum.co.il Forward-Looking Statements: This press release contains forward-looking statements about the Company’s expectations, beliefs, and intentions. Forward-looking statements can be identified by the use of forward-looking words such as “believe”, “expect”, “intend”, “plan”, “may”, “should”, “could”, “might”, “seek”, “target”, “will”, “project”, “forecast”, “continue” or “anticipate” or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. Such forward-looking statements used in this press release include, among other things, references to the clinical and commercial potential of the Company’s product candidates. Actual results could differ from those projected in any forward-looking statements due to numerous factors. Such factors include, among others, our ability to raise the additional funding needed to continue to pursue our business and product development plans, the inherent uncertainties associated with developing new products or technologies, our ability to obtain regulatory approval for our product candidates, our ability to commercialize our product candidates, competition in the industry in which we operate and overall market conditions. Any forward-looking statement in this press release speaks only as of the date of this press release. The Company undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. More detailed information about the risks and uncertainties affecting the Company is contained under the heading “Risk Factors” in Therapix Biosciences Ltd.’s annual report on Form 20-F dated filed with the SEC, which is available on the SEC’s website, www.sec.gov. For further information: Investor Contact: , CFO, Therapix Biosciences, [email protected] Therapix Biosciences Ltd. For further information: +972-3-616-7055 Media Contact: +1-212-825-3210 SOURCE Therapix Biosciences Ltd http://www.therapixbio.com
Dr. Yossi Tam, D.M.D, Ph.D., heads the Obesity and Metabolism Laboratory at the Hebrew University’s Institute for Drug Research and is Director of the Multidisciplinary Center on Cannabinoid Research. The Multidisciplinary Center is focused on developing cannabinoid-based therapies to alleviate pain, treat traumatic brain injuries, and to address a broad spectrum of diseases. Dr. Tam, who works closely with Hebrew University Professor Emeritus Raphael Mechoulam, a world leader in the field of cannabis research, serves on the scientific board of Kalytera Therapeutics. Kalytera is developing cannabinoid-like and endocannaboid-like medicines for conditions ranging from osteoporosis to Prader-Willi Syndrome, a genetic disease.
Dr. Tam earned his Ph.D. at Hebrew University and received his D.M.D. from the Faculty of Dental Medicine. He launched his research in the area of bone biology, pursuing this work under the auspices of the Faculty of Dental Medicine and the School of Pharmacy. Dr. Tam explored the clinical phenomenon whereby traumatic brain injury induces a systemic stimulation of bone formation, leading to excessive accumulation of bone. Dr. Tam demonstrated a critical role for the eCB system in regulating bone mass, identifying a novel brain-to-bone pathway. His work was recognized with the prestigious Young Investigator Award by the American Society for Bone and Mineral Research.
Dr. Tam conducted his postdoctoral research fellowship in the U.S. at the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (NIH), where he examined the biological mechanisms underlying obesity and metabolic syndrome. His research demonstrated the therapeutic potential of the first peripherally restricted, potent and selective CB1 blockers in biological models of obesity/metabolic syndrome. His preclinical findings showed that this class of compounds had strong clinical promise for treating obesity.
Dr. Tam joined the Hebrew University in 2014. His recent research investigates the peripheral eCB system in the development of obesity. His laboratory uses multidisciplinary approaches to study the molecular mechanisms involved in the development of metabolic syndrome. He has won numerous awards for his pioneering work, among these the Jacob Metzner’s Young Investigators Award and the FARE Award from the NIH.
CIITECH Sponsors Research Project on Cannabis-based Therapy for Asthma at the Multidisciplinary Center on Cannabinoid Research of the Hebrew University of Jerusalem
LONDON and TEL AVIV, Israel, October 24, 2017 /PRNewswire/
CIITECH, a UK-Israel cannabis biotech startup, announced today that it has selected to sponsor a research project with the Multidisciplinary Center on Cannabinoid Research of the Hebrew University of Jerusalem, focused on the therapeutic benefit of cannabis for the treatment of asthma.
CIITECH selected to award research funding, through a non-exclusive grant competition, to the collaborative work of Professor Raphael Mechoulam, a pioneer in the field of cannabis research credited for the discovery of the endocannabinoid system, and his colleague, Professor Francesca Levi-Schaffer, a global expert in asthma research. Together, these two Hebrew University scientists will embark on research to identify a possible inhibitory effect of a derivative of cannabidiol (CBD) on allergic airway inflammation.
CBD is the non-psychoactive ingredient or cannabinoid found in both hemp and regular cannabis strains. Last year, the UK Home Office reclassified cannabis, scheduling only the psychoactive compounds of the drug. CBD is now legal in the UK, available in retailers across the country and online.
“We know that CBD has anti-inflammatory properties and we’re looking forward to investigating whether this will be effective on treating asthma and related respiratory conditions,“ said Professor Raphael Mechoulam. “We‘re excited to further explore the therapeutic potential of cannabis.“
Asthma is a common allergic inflammatory disease both in children and in adults of the lungs airways causing a heavy health burden for patients. From 1990 to 2015, the number of asthma cases worldwide has doubled. According to Asthma UK, 5.4 million people here receive treatment for the condition including 1.1 million children, equating to one of the highest rates in Europe. Alongside asthma, other allergic diseases include allergic rhinitis, atopic dermatitis, and food allergy that affect approximately 20% of the global population and are continually increasing.
“Most of the symptoms of allergic disease patients are controlled by either symptomatic drugs or corticosteroids. However, some patients are steroid-resistant and allergic diseases such as severe asthma have been labelled as unmet clinical needs by the WHO,” adds Professor Francesca Levi-Schaffer. “We believe our research will provide a novel and effective solution to treating this condition.”
The Hebrew University of Jerusalem is globally recognized as the epicenter of cannabis scientific research. The Hebrew University’s recently established Multidisciplinary Center on Cannabis Research, headed by Dr. Joseph Tam, now serves as one of the world’s leading institutes on the plant. Israel’s supportive regulatory environment and collaborative healthcare ecosystem place the country at the vanguard of therapeutic cannabis. Prof. Francesca Levi-Schaffer’slaboratory at the University is focused on finding novel ways to treat allergy and recently started to study the effects of cannabis compounds on mast cells and eosinophils, the major effector cells in allergic diseases.
“We believe therapeutic,non-psychoactive, cannabis supplements provide consumers with a real alternative option for health and wellbeing,especially in countries such as the UK that have yet to legalise cannabis medicinally,“ says Clifton Flack, founder of CIITECH. “Cannabis could well become this century‘s wonder drug and we‘re honored to have the opportunity to support Professors Mechoulam and Levi-Schaffer on thispreclinical research project. Many of the plant‘s therapeutic benefits and compounds are yet to be explored and we‘re excited to take part in expanding and galvanizingthis new field of therapy.“
CIITECH is sponsoring the UK’s first medical cannabis conference Cannatech London on 26th October 2017, organized by iCan: Israel Cannabis.
CIITECH is a cannabis biotech company that focuses on discovering, developing and commercializing therapeutic cannabis products. By collaborating with leading research institutions in Israel and local suppliers in the UK & the EU, CIITECH leverages the full potential of Israel’s cutting-edge cannabis innovation. Through its UK based eCommerce shop EssentialCannabinoids.co.uk, Israeli cannabis products are available for the first time and exclusively overseas. Go to www.ciitech.co.uk for more info.
About the Multidisciplinary Center on Cannabinoid Research
The Multidisciplinary Center on Cannabinoid Research, staffed by leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, conducts and coordinates exciting new research about cannabinoids, endocannabinoids and medical Cannabis, while promoting collaboration and disseminating information. More info at http://cannabinoids.huji.ac.il/
In August, a joint feasibility committee of the Health and Finance ministries submitted a recommendation that Israel open its booming medical marijuana business to international exports. The market could be worth as much as $4 billion a year in revenue. In the expectation that the proposal will be approved by legislators, an Israel company – Breath of Life Pharma (BOL) – is positioning itself to become the world’s largest medical cannabis facility. BOL’s new production, research and development campus in central Israel has a 35,000-square-foot plant, an 8,000-square-foot storage room, 30,000 square feet of grow rooms and labs, and a million square feet of cultivation fields. BOL CEO Dr. Tamir Gedo says his firm can store enough medical marijuana to supply the entire United States. Gedo estimates that BOL will produce 80 tons of medical cannabis per year. “Just don’t call it ‘marijuana,’” Gedo told a group of visiting journalists under high security (marijuana is, after all, a controlled substance in much of the world, including Israel). The word “marijuana” was used by US drug enforcement agents in the 1930s to make it sound foreign and dangerous. Gedo, like most in his industry, prefers to use the plant’s real name, cannabis. He refers to BOL’s business as the growing, packaging and distribution of “medical-grade cannabis” (MGC for short). BOL has no interest in pushing the legalization of recreational cannabis, Gedo says. Rather, BOL works toward bringing pharmaceutical-grade quality and delivery systems to purified extracts of the plant. Because the chemical composition of cannabis flowers from different branches is not at all consistent, companies in the medical cannabis space don’t use the whole plant but instead isolate specific molecules and turn those into controlled, consistent drugs. That can be quite a challenge: Cannabis has 142 different cannabinoids – active components – and each targets different illnesses. The two best known cannabinoids are THC and CBD. The former is the psychoactive component responsible for marijuana’s “high.” It also helps with pain and nausea, which has made it a much sought-after medication for patients undergoing chemotherapy. CBD, on the other hand, works on the autoimmune system and acts as an anti-inflammatory. It is being tested on inflammatory bowel diseases (including Crohn’s and ulcerative colitis) and has shown to be effective with conditions as diverse as autism, epilepsy, diabetes and heart disease. Moreover, you can’t get high from CBD. In order to get FDA approval, a company like BOL, which was founded in 2007, must conduct the same kind of double-blind clinical trials any drug would go through. Some 120 trials are currently under way in Israel – more than in any other country. Gedo says that if even 10 percent of trials underway at his facility result in a patentable drug, BOL could be the Pfizer of MGC. BOL’s autism trial, under the supervision of Dr. Adi Aran, director of the neuropediatric unit of Shaare Zedek Medical Center in Jerusalem, will go to the FDA in 2018. If it’s approved, a commercial drug could be available as early as 2021. Medical cannabis drugs are delivered via pills you swallow, delayed-release gel capsules, sublingual tablets, drops, ointments, transdermal patches and metered inhalers. You don’t smoke MGC because that destroys the CBD and other components aside from THC. BOL is building on Israel’s reputation as one of the most cannabis-friendly countries in the world. Israel, which has the world’s highest ratio of cannabis users – 27 percent of the population aged 18-65 used marijuana in the last year – recently reduced penalties for recreational cannabis use to a fine. Prof. Raphael Mechoulam from the Weizmann Institute of Science was the first to successfully isolate THC. That was in 1964. Mechoulam, now 86, is still active in cannabis research at the Hebrew University in Jerusalem, and is on the board of directors of BOL. Testing medical cannabis on human patients has been part of the research landscape in Israel for years, but it’s nearly impossible to do in the United States. Only one facility, the University of Mississippi, is a licensed source for medical cannabis, and production is limited to just 650 kilograms per year. “We can produce that amount in half a day,” Gedo says. “Israel is a hotbed of quality cannabis research, because it has a much more favorable regulatory climate for doing serious scientific research on medical cannabis,” says Charles Pollack, director of the Lambert Center for the Study of Medicinal Cannabis at Thomas Jefferson University in Philadelphia. As a result, companies are increasingly turning to Israel to conduct their phase 1 and 2 clinical trials. If you can point to previous studies done overseas, the FDA is more likely to approve a phase 3 trial in US. Of the 15 companies signed up so far to conduct their R&D at BOL’s facility in Israel, at least six are American. And while importing cannabis into the United States remains illegal (even though 29 US states have legalized medical cannabis), if a product has FDA approval companies can circumvent that ban. Israel is also blessed with a climate conducive to growing cannabis, BOL’s Gedo said. “The many days of sunshine make it more suitable than many parts of the US and Europe.” BOL isn’t the only company in Israel to jump on the medical cannabis bandwagon. Tikun Olam was Israel’s first medical cannabis distributor and opened an American subsidiary in 2016. One World Cannabis Pharmaceuticals is working on a topical cannabis cream to treat psoriasis. NASDAQ-listed Therapix Biosciences is deploying THC to address Alzheimer’s and Tourette syndrome. And there are others. The Israeli firm iCAN sponsors CannaTech, a leading medical cannabis conference and trade show that started in Israel and is now on the road to London and Australia. While Israel’s medical cannabis industry is targeting the international market, big changes are afoot domestically. Last summer, 81 doctors completed a medical cannabis course from the Ministry of Health. And the number of licensed cultivators has increased from eight to 60, including several kibbutzim. The aim is to open up the Israeli market from just a few dispensaries serving the entire country to allowing doctors to prescribe MGC preparations that can be picked up at a local pharmacy. “There are 30,000 patients in Israel getting medical cannabis,” ICAN’s Saul Kaye told ISRAEL21c. “Most people know someone who’s getting it. The stigma is being removed.” Israel has gone so far as to publish a “Cannacopeia,” a guide to the use of MGC. “We call it the ‘Green Book,’” quipped Yuval Landschaft, director of the Medical Cannabis Unit in the Israeli Ministry of Health. Some 21 countries have requested a copy. In 2016, more than $250 million was invested in Israeli cannabis companies and about 50 American companies have established R&D operations in Israel or partnerships with Israeli companies like BOL. The medical cannabis industry in Israel may not eclipse high-tech, but the two share the common root of Israeli chutzpah and the belief that bucking the rules often yields the biggest payout. When Mechoulam first wanted to study cannabis, there was none to be had. So his boss at the Weizmann Institute called a buddy at the local police station and scored a confiscated stash of 11 pounds of Lebanese hashish (also from cannabis) that the cops were planning to burn. Mechoulam hopped on a bus to pick it up. This creative approach jump-started an entire industry. Now the only question is: how high can Israel leap? Four billion dollars in potential exports (and taxable revenue) certainly raises the bar. For more information, click here.
Marijuana was first comprehensively studied in Israel in the 1960s by Professor Raphael Mechoulam, considered “the father of medical marijuana.” Professor Mechoulam is with The Hebrew University of Jerusalem’s Department of Medicinal Chemistry and Natural Products at the Faculty of Medicine.
Mechoulam’s research team isolated some of the major compounds in marijuana, many of which had been previously unknown, including THC (Tetrahydrocannabinol) and CBD (Cannabidiol). THC is the psychoactive compound in marijuana that causes the typical “high” effect, and CBD is non-psychoactive. Both compounds have medicinal properties.
THC has proven valuable in helping to treat a multitude of issues such as pain, insomnia, depression, nausea and appetite loss. CBD has shown an ability to treat inflammation, nausea, diabetes, alcoholism, Posttraumatic stress disorder (PTSD), rheumatoid arthritis and cardiovascular disease. Hebrew University’s research on cannabinoids includes studying how different types and amounts of CBD treat various medical issues such as how it may help heal fractured bones, reduce or eliminate negative side effects from cancer treatment, anxiety, seizures, chronic pain and more.
Israel boasts one of the most advanced medical marijuana programs in the world. More than 20,000 Israeli patients use medical marijuana to alleviate various ailments, such as Crohn’s disease, Tourette’s syndrome, pediatric epilepsy, cancer side effects and PTSD.
In early 2015, Hebrew University ‘s technology transfer company, Yissum Research Development Co. Ltd., signed an exclusive licensing and collaboration agreement with PhytoTech Medical Ltd. for the development, manufacturing and marketing of a novel delivery system to enhance the bioavailability of cannabidiol (CBD) and/or THC. The novel formulations are based on oral and transbuccal delivery technologies developed by Professors Abraham Domb and Amnon Hoffman of The Hebrew University Faculty of Medicine, School of Pharmacy, Institute of Drug Research.
Hebrew University’s efforts in medical marijuana research have been featured in The New York Times, BBC News, Washington Post, National Geographic, The New Yorker, Bloomberg and more.
With more than 400 scientific papers and 35 patents to his name, Professor Mechoulam is so highly regarded that a documentary about him came out in 2015. Watch The Scientist below:
Israel’s ‘medical weed wonderland’ draws US pot developers
Standing on the rear balcony of a gray factory building off the side of a highway, Tamir Gedo shields his eyes from the blazing sun. He points to the 23 acres of agricultural fields spread out before him. “We’ll be able to produce more cannabis here than the entire state of Colorado,” he says. Minutes later, walking past the 8,000 square-foot storage room, he adds, “We can store enough in this warehouse to supply medical marijuana for the whole United States.”
With one million square feet of cultivation fields, a 35,000-square-foot production plant, and 30,000 square feet of grow rooms and labs, Gedo’s company, Breath of Life Pharma (BOL), is about to open the world’s largest medical marijuana production, research and development facility. According to Gedo’s estimates, BOL will produce 80 tons – more than 175,000 pounds – of cannabis per year.
A tour of BOL’s new facility feels like a walk through the medical-marijuanaversion of Willy Wonka’s Chocolate Factory. With its patented extraction and purification equipment, grow rooms and germination labs, BOL will be pumping out pharmaceutical-grade cannabis tablets, capsules, inhalers and oils that are customized to treat certain ailments, with specific and controlled consistencies.
And no, this isn’t happening in Colorado, California, or anywhere near America for that matter. This medical weed wonderland sits in what might be the last place you would imagine finding the world’s largest facility for medical marijuana: Israel.
Over the past 50 years, Israel has become the epicenter of medical pot. Home to Raphael Mechoulam, the pioneer of marijuana research, Israel is where THC and the endocannabinoid system were first discovered. And with the world’s largest number of clinical trials testing the benefits of medicinal cannabis, Israel has become the global destination for medical cannabis research and development. Now it is becoming the offshore greenhouse for American cannabis companies seeking to overcome the federal roadblocks standing in their way.
Israel was among the first countries to legalize medicinal use, and is one of just three countries with a government-supported medical cannabis program. Though recreational use remains illegal, support for legalization is a bipartisan issue, with some of the most outspoken proponents coming from the right. Until now, Israel’s role in this multi-billion dollar field has been limited to R&D. Yet now that the Israeli government has approved the export of medicinal cannabis products, companies there are hoping to gain a larger piece of the market. While importing cannabis into the United States is illegal under federal law, companies can get around that ban by receiving drug approval from the FDA – and that is exactly what Israeli companies hope to do. According to the FDA, nothing is stopping them, as long as they meet the agency’s arduous requirements for drug approval.
While the FDA has approved three drugs containing synthetic cannabinoids (Marinol, Syndros and Cesamet, which treat symptoms of AIDS and chemotherapy), it has never approved a product derived from botanical marijuana. According to the agency’s guidelines, “Study of marijuana in clinical trial settings is needed to assess the safety and effectiveness of marijuana for medical use.” Yet initiating clinical trials on U.S. soil is difficult to the point of being nearly impossible. So, American companies are increasingly taking a shortcut: beginning phases 1 and 2 of their clinical trials in Israel, after which they will complete phase 3 in the U.S., speeding up the process through which they can apply for FDA approval of the botanical cannabis drugs they are developing.
Though this level of American R&D in Israel is new, Israel’s impact on the American cannabis industry is not. The very fact that medical marijuana is now legal in 29 U.S. states and counting, is a direct result of Israeli research, which essentially legitimized the study of cannabis in the international scientific community that had long stigmatized it. Without this research, “We wouldn’t have the scientific interest we have now around the world,” says Paul Armentano, deputy director of the D.C.-based National Organization for the Reform of Marijuana Laws (NORML). “That really opened the door to making the study of cannabis and cannabinoids a legitimate avenue for more conventional scientists and researchers.”
Israel is becoming the offshore greenhouse for American cannabis companies seeking to overcome the federal roadblocks.
The Lambert Center is one of several American institutions that have partnered with BOL, collaborating on at least one of the more than 50 clinical trials the Israeli company will begin once its new facility is fully operational in late September. Of the 15 international companies that have already signed up to conduct their R&D at BOL’s facility, at least six are American, and Gedo is in talks with more.
BOL isn’t the only Israeli cannabis company benefitting from international interest. A growing number of American investors are getting on the Israeli cannabis wagon, which they see as the best vehicle for transforming the medical cannabis field, still in its infancy, into a pharmaceutical-level industry.
According to Saul Kaye, the founder of iCAN, an Israeli cannabis R&D firm, 2016 saw the investment of more than $250 million in Israeli cannabis companies and startups – half of that investment camefrom North America. Kaye predicts that investment will grow ten-fold over the next two years, reaching $1 billion. At least 50 American cannabis companies – and counting – have established R&D operations in Israel.
Israel’s journey to the forefront of the medical cannabis field began with 86-year-old Israeli chemist Raphael Mechoulam, known in the field as the Grandfather of Medical Marijuana. In 1963, as a young researcher, Mechoulam secured 11 pounds of Lebanese hashish, which had been confiscated by his friend at a police station in Tel Aviv. He used that hash to identify, isolate and synthesize THC, the psychoactive compound in cannabis, for the first time in history, and study its medical uses. He was also the first to decode the structure of CBD, the plant’s primary non-psychoactive ingredient. But Mechoulam’s most groundbreaking discovery came in 1992, when he and his team at Hebrew University in Jerusalem discovered the physical reason humans can get high.
“It turned out that the cannabinoids in the plant actually mimic the compounds that we form in our brain,” says Mechoulam, a professor and researcher at Hebrew University who works with several American cannabis companies. He and his team discovered that THC triggers the human body’s largest receptor system, now known as the endocannabinoid system, and that the human brain produces its own cannabinoids – compounds that stimulate the body almost exactly the way THC does.
While Mechoulam’s research is what first placed Israel on the medical marijuana map, the country’s progressive attitudes toward cannabis, coupled with the Israeli government’s liberal regulatory policies and the nation’s technological leadership, are what have maintained Israel’s status as the capital of medical marijuana research and development. It might also help that Israel has the world’s highest ratio of marijuana users, according to Israel’s Anti-Drug Authority, with 27 percent of the population aged 18-65 having used marijuana in the last year. That rate is followed by Iceland and the U.S., at 18 and 16 percent respectively.
“There are onerous restrictions on conducting this research in the U.S. that don’t exist in Israel,” says one expert.
Despite the fact that 95 percent of the U.S. population lives in states where cannabis is legal in some form, marijuana remains federally illegal. This policy makes conducting research into the medical benefits of marijuana notoriously difficult on U.S. soil. Researchers who wish to do so must go through the DEA, the FDA and the National Institute on Drug Abuse (NIDA). Even when American researchers are given approval, they have only one source for their material: a cannabis farm at the University of Mississippi, operated by NIDA. The process, if successful, can take years.
“There’s a lengthy and arduous regulatory process for getting approval for doing studies, and limited resources at these agencies for processing those requests,” says Pollack, of Thomas Jefferson University. “It’s deliberately made very difficult for us.” In Israel, on the other hand, a cannabis clinical trial can get off the ground in a matter of months.
“I think they have approached the issue in a more even-handed and genuine way than the U.S. government has,” says Armentano of NORML. “There are onerous restrictions on conducting this research in the U.S. that don’t exist in Israel.”
This is precisely why many American researchers from universities and private companies are using Israel as an offshore research hub. For example, Pollack, from Thomas Jefferson University, will be conducting clinical trials at BOL’s new facility. Since the trials haven’t begun, he won’t divulge details, but says they will focus on orphan drug indications, meaning they will be testing the benefits of cannabinoids on people with diseases that don’t afflict many people in the U.S. (It also means that the clinical studies are smaller – and go faster – given that fewer patients are needed for these trials.) For that reason, he said, “Big pharma companies tend not to pursue them because there’s not a big enough market for these drugs.”
Kalytera – a California-based company with a lab in northern Israel and Mechoulam on its scientific advisory board – is also focusing on orphan drug indications, conducting clinical trials at Israeli clinics and hospitals in order to bring to market a cannabinoid drug for the treatment of graft-versus-host-disease, which can happen after certain kinds of transplants.
What institutions like Kalytera and Thomas Jefferson University do is they conduct the initial phases of their clinical trials in Israel, since it’s much easier to get the process started here, and then they do the final stages in the U.S., since FDA approval requires that part of the study be done there. Once they reach the final stage (phase 3) it’s much easier to conduct the rest of their study in the U.S., because they’ve already amassed enough data to show that it’s safe. This is the ultimate goal for Kalytera, Pollack and other researchers in Israel: to speed track the process of conducting a clinical trial that meets FDA standards, thus shortening the journey toward FDA approval of their drugs.
In addition to Kalytera, Mechoulam works with two other American companies, helping them develop new cannabinoid drugs and delivery methods out of his lab in Jerusalem, where he tests the specific properties, compositions and combinations of the cannabis compounds that are best suited to alleviate a specific ailment. American companies then use that research and data to manufacture cannabinoid drugs in the U.S.
According to Saul Kaye of iCan, about 50 U.S. cannabis companies are conducting research in Israel through partnerships, joint ventures or by employing Israel-based researchers like Mechoulam. At least 15 American cannabis companies have set up their entire R&D operations on Israeli soil, conducting clinical trials, and developing the appropriate dosing forms and delivery systems for pharmaceutical-grade cannabis-based drugs. According to Michael Dor, senior medical advisor at the Health Ministry’s cannabis unit, at least 120clinicaltrials are currently under way in Israel to test the medicinal benefits of cannabis — more than any other country.
At least 15 American cannabis companies have set up their entire R&D operations on Israeli soil.
Cannabics, a Maryland-based, publicly-traded company, is conducting a clinical trial at an Israeli hospital in order to develop a capsule for cancer treatment. In 2015, One World Cannabis Pharmaceuticals, a public company based in Delaware, established an Israeli subsidiary overseen by Yehuda Baruch, the first head of the Israeli government’s medical cannabis program, established in 2007. They are now beginning phase 1 of a clinical trial to test the benefits of a topical cannabis cream to treat psoriasis. Their next trial will study the efficacy of a soluble pill for the treatment of chronic pain. They eventually plan to conduct clinical trials on patients with multiple myeloma.
Some Israeli companies have partnered with American companies to establish a presence in the U.S., where they sell products that were developed in Israel. For example, Tikun Olam, Israel’s first medical cannabis distributor, opened an American subsidiary in 2016. It now sells its proprietary medical-grade plant strains at 10 dispensaries in Delaware and Nevada and will soon be available at dispensaries in Oregon and California. Their most popular strain is Avidekel, a non-psychoactive CBD blend used to help children with seizures.
Some American researchers have even moved to Israel all together. Alan Shackelford, a Harvard-trained physician, was among the first American doctors to prescribe cannabis to a child. His eight-year-old epileptic patient Charlotte Figi sparked national interest in CBD after her miraculous story aired on CNN’s Weed documentary in 2013.
Yet after years of failed attempts to conduct clinical trials in the U.S., Shackelford recently established his own research entity in Israel because of his frustration with the American government’s stonewalling.
“The U.S. government has funded $1.4 billion in marijuana research since 2008,” says Schackelford. “Yet $1.1 billion of that went to studying addiction, withdrawal and drug abuse,” problems that barely exist with cannabis when compared to the effects of other legal medications, like prescription painkillers, which killed more than 17,000 Americans in 2016.
His research subjects in Israel will include the development of new delivery methods, he says, “because to date, most medical cannabis products no matter where you look in the world, are pot-culture derived. They’re things like brownies, cookies, candy and smoking. Even with advances to these things being much more consistent, they’re still not medically appropriate.”
While the U.S. government restricts American cannabis companies on U.S. soil, it does not prevent them from or penalize them for conducting their work in Israel. According to Robert Farrell, president of Kalytera, “The FDA has no problem with this work being done in Israel. When you file with the FDA, in the application you say, ‘Look we’ve done the previous studies in Israel, gave the drug to this many patients, the drug is safe, it works, now we want to conduct a larger study with patients in the U.S.’ If the FDA is satisfied with the data, they’ll say, ‘Go ahead, try it in the U.S.'”
The FDA will never get behind cannabis the plant as medicine, since it can’t be controlled as a consistent drug.
Even the National Institutes of Health (NIH) has funded cannabis research in Israel. Indeed, much of Professor Mechoulam’s groundbreaking research was funded by the American government. The NIH provided him with grants to the tune of $100,000 a year for over four decades, says Mechoulam.
There is also nothing preventing Israeli companies from receiving FDA approval for their cannabis-based drugs, as long as they meet FDA requirements. In order to do so, they will need to develop the kind of products that are more in line with pharmaceutical standards, such as the kinds of capsules and inhalers BOL is developing.
While that goal is feasible, Gedo and others admit that it will take time, perhaps several years, to achieve. The process of getting FDA approval is an arduous one, especially for a drug that has long been viewed with skepticism by the medical establishment. Yet it is these clinical trials that are taking place at a record pace in Israel, along with the advancement of pharmaceutical grade cannabinoid drugs, that will enable Israeli companies to eventually receive FDA approval for their drugs, or for the drugs thatthey are helping American companies to develop.
As Gedo notes, the FDA will never get behind cannabis the plant as medicine, since it can’t be controlled as a consistent drug that has the same effect day in and day out. After all, there are 140 active compounds in cannabis, and the composition of the flowers plucked from one branch can fluctuate wildly, by up to 300 percent. “The experience of a user will vary a lot with the same strain,” says Gedo. “So even if you have the best-grown product, it will never become a scientific pharmaceutical product.”
This is precisely why the FDA has never approved a botanical marijuana drug, a larger problem than scheduling when it comes to drug approval. According to Senate testimony by the FDA’s Douglas Throckmorton in 2016, who was citing a report from the Institute of Medicine, in order to obtain FDA approval, drug manufacturers “must demonstrate that they are able to consistently manufacture a high-quality drug product. This is an essential part of drug development and presents special challenges when the drug is derived from a botanical source, such as marijuana…. If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives.”
BOL and other Israeli companies are working to meet that challenge by developing cannabis-based drugs – the capsules, inhalers, creams and oils composed of isolated, controlled and consistent cannabinoids. Going this route, they could eventually receive FDA approval.
While Gedo is optimistic, he’s also realistic, knowing the complexity of the FDA’s drug approval process, and the skepticism that remains among many in the medical establishment.
Still, asked when Israeli companies might be exporting their cannabis medicine to the U.S., Michael Dor, of the Israeli Health Ministry says, “I believe it’s not far.”
The ICRS is the oldest scientific society dedicated to the research in the cannabis plant, cannabinoids, and their physiological and biochemical targets. The ICRS has nearly 400 members from all over the world. The members and guests of the ICRS gather yearly to present the ICRS Symposium.
Hundreds of participants from Israel and around the world will participate in the conference, at the International Convention Center (ICC) in Jerusalem, in cooperation with the Jerusalem Conventions & Visitors Bureau (JCVB), which operates under the Jerusalem Development Authority (JDA).
The event will be hosted by the Hebrew University’s Multidisciplinary Center on Cannabinoid Research (MCCR), which is the leading center in Israel for conducting and coordinating research on cannabinoids, endocannabinoids and medical Cannabis.
Over the last 50 years, Hebrew University research has spearheaded a new scientific era of Cannabis research. Professor Raphael Mechoulam, a Hebrew University researcher widely regarded as “the father of cannabinoid research,” and his colleagues isolated the active constituent of the Cannabis plant, tetrahydrocannabinol, elucidated its structure, and synthesized it. Later Professor Mechoulam identified the endogenous cannabinoids (formed in the mammalian body) and thus pioneered the field of cannabinoid research.
Professor Raphael Mechoulam
The International Symposium will mark Professor Mechoulam’s 90th birthday.
The Symposium will feature oral and poster presentations covering a wide range of topics germane to cannabinoid science and medicine. Past conferences have covered such topics as autoimmunity, epilepsy, pain, PTSD, drug development and medicinal chemistry, neuroprotection, metabolism, endocrine and obesity, cancer, and much more.
Professor Cecilia Hillard, Executive Director of the ICRS, said: “The board of directors of the International Cannabinoid Research Society is very pleased that our 31st annual meeting will be held in Jerusalem in 2021. Jerusalem holds a special place in the history of the science of cannabis and the endocannabinoids. Professor Raphael Mechoulam of Hebrew University was the first to publish the structure of the active principal of cannabis, THC, and was also the first to identify an endogenous cannabinoid, anandamide. Just as impressive is the current state of cannabinoid research in Jerusalem and Israel at large, including the Multidisciplinary Center on Cannabinoid Research led by Dr. Tam. We are looking forward to visiting Jerusalem and to an exciting and informative conference.”
Dr. Joseph (Yossi) Tam, Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research, said: “I’m excited that the International Cannabinoid Research Society has decided to hold its 31st conference in Jerusalem under the auspices of the Multidisciplinary Center on Cannabinoid Research. One of our first goals after establishing the Center was to host the ICRS conference in Jerusalem so that the international community of researchers can learn about the highly advanced work in the field of cannabinoids carried out in the Center and in Israel. I am certain that hosting this high-level conference will constitute another turning point in Israel’s position as a global leader in cannabinoid research and development.”
“Modulating endocannabinoid activity has therapeutic potential in a large number of human diseases, and research on cannabinoids may lead to very significant advances in basic science and therapeutics. We look forward to hosting the world’s top scientists working to discover new therapies based on cannabinoids,” said Professor Raphael Mechoulam, Head of the Academic Committee of the Multidisciplinary Center, and the Lionel Jacobson Professor Emeritus of Medicinal Chemistry in the Hebrew University’s Faculty of Medicine.
“Bringing this global symposium to Jerusalem emphasizes the ongoing collaboration between multiple institutions including the JCVB, ICC, and MCCR. This partnership was only possible with the shared vision in highlighting the city’s potential as a leading scientific conference destination. Jerusalem offers an ideal setting to host the over 400 global researchers to learn and promote the exchange of scientific information and gain new perspectives about Cannabis,” said Ilanit Melchior, Director of Tourism in Jerusalem.
“As the largest and leading conference center in Israel, the Jerusalem ICC looks forward to hosting this important conference aimed at bringing international researchers together to improve human health and well-being,” said Mira Altman, CEO of the International Convention Center (ICC) in Jerusalem.
The ICRS is a scientific association with hundreds of international members, all active researchers in the field of endogenous, plant-derived and synthetic cannabinoids and related bioactive lipids. The ICRS Symposium is considered the most important conference in the field of cannabinoids research. The conference brings together the leading researchers from the international scientific community and presents the latest and most up-to-date research in the field.
The Multidisciplinary Center on Cannabinoid Research, staffed by leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, conducts and coordinates exciting new research about cannabinoids, endocannabinoids, and medical Cannabis, while promoting collaboration and disseminating information. More info at http://cannabinoids.huji.ac.il/.
Hebrew University Looks for High Impact with New Cannabinoid Multidisciplinary Center
The Hebrew University announced the launch of a Multidisciplinary Center on Cannabinoid Research.The new Center will serve as one of the world’s leading institutes for conducting and coordinating research about cannabinoids, endocannabinoids, and medical Cannabis. In addition, it will promote collaboration and disseminate information.
Staffed by some of the world’s leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, the Multidisciplinary Center is already supporting exciting new research. In February 2017, the Center awarded funding to three research projects:
“The establishment in Israel of the Multidisciplinary Center on Cannabinoid Research is of great relevance at this time since both academic institutions and pharmaceutical companies worldwide are channeling enormous efforts to basic and clinical research in this field,” said Dr. Joseph (Yossi) Tam, Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research, and Head of the Obesity and Metabolism Laboratory at the Hebrew University’s Institute for Drug Research in the Faculty of Medicine.
Along with integrating the research activities of multiple Hebrew University research laboratories into interdisciplinary networks, the Center, which relies on the infrastructure of the Institute for Drug Research at the School of Pharmacy in the Faculty of Medicine, will also foster collaborations between its participating laboratories and other well-established research groups around the globe.
“We feel incredibly fortunate to team up with a vast number of scientists working together on this expanding field of medicine with the significant potential to discover new therapies based on cannabinoids,” said Dr. Tam.
Until very recently, the Cannabis plant and its extracts (popularly called marijuana, hashish, weed, and grass) were mostly frowned upon as purely recreational drugs. However, over the last 50 years, Professor Raphael Mechoulam at the Hebrew University has spearheaded a new scientific era of Cannabis research. Professor Mechoulam, along with his colleagues, isolated the active constituent of the Cannabis plant, tetrahydrocannabinol, elucidated its structure and synthesized it. Later he identified the endogenous cannabinoids (formed in the mammalian body) and thus pioneered the field of cannabinoid research.
“It has been shown that modulating endocannabinoid activity has therapeutic potential in a large number of human diseases, hence research on cannabinoids may lead to very significant advances, not only in basic science but also in therapeutics. Our Multidisciplinary Center addresses many aspects in this promising area, such as cancer, head injury, addiction, bone formation, obesity and others,” said Professor Raphael Mechoulam, Head of the Academic Committee of the Multidisciplinary Center, and the Lionel Jacobson Professor Emeritus of Medicinal Chemistry in the Hebrew University’s Faculty of Medicine.
The Center’s teams of highly qualified researchers comprise Heads of Labs and Research Groups ranging through Nano-Medicine & Nano Delivery Systems, Tumor Micro-environment, Neurobiology, Pain Relief & Plasticity, Molecular Modeling & Drug Design, Immuno-pharmacology, Free Radicals, Stress, and Plant Pathogen Interactions.
The Center’s informational resources include a World Calendar of Cannabinoids, featuring information about major upcoming events in the field of cannabinoid research.