Change We Can Believe In? Not for Medical Marijuana Research

by Paul Armentano

It was nearly two years ago that the Obama White House issued its "Scientific Integrity" memorandum stating, "Science and the scientific process must inform and guide decisions of my Administration."

Those of us involved in marijuana law reform welcomed the memo -- which came just months after the American Medical Association called for "facilitating ... clinical research and [the] development of cannabinoid-based medicines" -- and we hoped that it would stimulate the commencement of long-overdue human studies into the safety and efficacy of medical cannabis.

Those hopes were snuffed, however, when a representative from the U.S. National Institute on Drug Abuse (NIDA), the agency that oversees 85 percent of the world's research on controlled substances, reaffirmed its longstanding "no medi-pot" policy to The New York Times. "As the National Institute on Drug Abuse, our focus is primarily on the negative consequences of marijuana use," a spokesperson told the paper in 2010. "We generally do not fund research focused on the potential beneficial medical effects of marijuana."

A review of the U.S. National Institute of Health website clinicaltrials.gov shows that NIDA's kibosh on medical marijuana trials continues unabated. Though an online search of ongoing FDA-approved clinical trials using the keyword "cannabinoids" (the active components in marijuana) yielded me 65 worldwide hits, only six involved subjects's use of actual cannabis. (The others involved the use of synthetic cannabinoid agonists like dronabinol or nabilone, the commercially marketed marijuana extract Sativex, or the cannabinoid receptor blocking agent Rimonabant).

Of the six, two of the studies have already been completed: "Opioid and Cannabinoid Pharmacokinetic Interactions" and "Vaporization as a Smokeless Cannabis Delivery System," both of which were spearheaded by researchers (primarily Dr. Donald Abrams) at the University of California at San Francisco.

The four remaining studies are still in the "recruitment" phase. Of these, only two pertain to the potential medical use of cannabis: "Cannabis for Spasticity of Multiple Sclerosis," which is taking place at the University of California at Davis and is likely the final clinical trial associated with the soon-to-be-defunct and defunded California Center for Medicinal Cannabis Research and "Cannabis for Inflammatory Bowel Disease," led by researchers at the Meir Medical Center in Israel.

Of the remaining studies, one focuses on the detection of cannabinoids and their metabolites on drug screens, while the other, entitled "Effects of Smoked Marijuana on Risk Taking and Decision Making Tasks," seeks to establish pot-related harms, hypothesizing that subjects "demonstrate poorer decision-making abilities and increased risk-taking behaviors" after smoking marijuana.

So much for the AMA's demand for clinical cannabis research.

By contrast, preclinical (animal) trials assessing the therapeutic efficacy of cannabinoids are occurring at a record pace. A keyword search on the search engine PubMed using the term "cannabinoids" yielded over 1,300 published papers in 2008, some 1,700 papers in 2009 and another 1,200 published last year.

While many of these studies highlight the ability of cannabinoids to manage a wide range of symptoms, even more intriguing are the results indicating the potential of cannabinoid intervention to halt the development of serious diseases, such as cancer, diabetes, Lou Gehrig's disease and multiple sclerosis. Nevertheless, without abrupt changes at the highest levels of government -- changes that do not appear to be forthcoming despite this administration's public demand for "scientific integrity" -- scientists will indefinitely lack the human follow-up data necessary to adequately answer societal questions regarding cannabis safety, efficacy and proper dosage.

"Change we can believe in?" Not when it comes to studying pot.

Source: The Huffington Post

NEWS: How cannabis dampens the immune system

CANNABIS is a double-edged sword: by dampening the immune system, it provides relief from inflammatory diseases, but this also increase the risk of infections. Now we know how it does this: its active ingredient targets a newly discovered type of cell that lowers the immune response.

Prakash Nagarkatti at the University of South Carolina School of Medicine and colleagues injected the main active ingredient of cannabis, delta-9-tetrahydrocannabinol (THC), into mice. THC activated two types of cannabinoid receptor on immune cells, called CB1 and CB2. Activation of these receptors led to a "massive mobilisation" of myeloid-derived suppressor cells (MDSCs), which play a crucial role in lowering the immune system response back down to normal levels (European Journal of Immunology, DOI: 10.1002/eji.201040667).

The discovery offers a possible explanation of why cannabis smokers have a higher risk of getting infections, says Nagarkatti. It may also mean THC could be used when there is a need to suppress the immune system - after an organ transplant, for example.

Source: New Scientist

NEWS: Study In Monkeys Suggests Marijuana Does Not Lead To Faster HIV Disease Progression

A small study of monkeys infected with the monkey version of HIV, Simian Immunodeficiency Virus, found that regular administration of tetrahydrocannabinol – the active compound in marijuana – was not associated with faster SIV disease progression.

In fact, the monkeys were less likely to die early, experienced small reductions in their viral loads, and had slightly better retention of body mass. However, the study authors stated that the results are too preliminary to suggest marijuana might slow the progression of HIV.

“In terms of viral replication, disease progression, and immunological parameters, chronic use of cannabinoids may not be detrimental to the infection,” said Dr. Patricia Molina, lead author on the study.

However, she added, “It is too premature to claim that this also reflects protection or improvement of disease in HIV-positive [patients], or how this would play out in the presence of antiretroviral therapy.”

Studies have estimated that about a quarter to a third of people with HIV use marijuana to ease symptoms from HIV infection or antiretroviral therapy. Tetrahydrocannabinol (THC), the primary drug in marijuana, is available in two forms: the marijuana plant itself and two different pills, which are available by prescription.

Marijuana, which is usually smoked, is not approved by the United States Food and Drug Administration (FDA) and is illegal according to federal law. However, 15 states and Washington, D.C. have legalized use of marijuana for people with HIV.

In addition, Marinol (dronabinol), which contains THC, and Cesamet (nabilone), which contains a synthetic version of THC, are available by prescription. Marinol is approved by the FDA for the treatment of HIV-associated anorexia, while Cesamet is approved for use in treatment of anorexia and wasting in people with HIV.

Most research has shown that using marijuana or prescription THC can help ease common symptoms and side effects of antiretroviral therapy in people with HIV (see related AIDS Beacon news). However, some research has suggested that marijuana and THC may have harmful effects on the immune system, which could lead to more illnesses and faster HIV disease progression.

In this study, researchers set out to determine whether regular THC use causes faster disease progression in monkeys infected with SIV, the monkey equivalent of HIV.

Four monkeys were injected twice daily with THC starting approximately one month prior to being infected with SIV. Another four monkeys were infected with SIV but did not receive THC.

After infection, the researchers monitored immune system markers, CD4 (white blood cell) counts, and viral loads (amount of virus in the blood) over the course of 6 months. The monkeys receiving THC continued to receive the drug twice daily throughout the study period.

Contrary to the researchers’ expectations, results showed that regular THC administration did not increase viral load or lead to faster disease progression.

In fact, infected monkeys receiving THC had slightly lower viral loads than infected monkeys that did not receive THC, although the difference was too small to be significant. CD4 counts also dropped more slowly in monkeys receiving THC.

In addition, among the infected monkeys receiving THC, the first death did not occur until 11 months after infection. In that time, three of the four infected monkeys not receiving THC died: two about 5 months after infection and a third after 7 months.

Results also showed that monkeys receiving THC lost less weight 3 to 6 months after infection than monkeys not receiving THC, although the difference was too small to be significant.

The authors noted that their study was small, which means individual differences between monkeys could have played a role. Nonetheless, they concluded that THC does not increase disease progression and, in fact, regular administration of THC may actually delay SIV disease progression, possibly by reducing inflammation and weight loss.

Dr. Molina stated that additional follow-up studies on the monkeys are planned. “There are many things we are interested in pursuing, such as what happens with a longer period of exposure to THC prior to infection, can we eliminate the psychoactive effects of THC and still see protection, does THC interfere directly with viral entry into the cell, etc.,” said Dr. Molina.

The authors also plan to study the effects of THC in female monkeys (all the monkeys in this study were male) and what the biological mechanism of THC’s effects on disease progression might be.

Dr. Molina stated that they would like to replicate the results in human studies, but that this presents some challenges.

“These are difficult studies, and finding the right cohort of patients is quite complex,” said Dr. Molina. “Questions arise as to whom do we study? People on antiretroviral therapy plus cannabinoids? Do we add cannabinoids to the therapy? Do we study cannabinoid users?”

“We are interested in pursuing it, just not at that stage yet,” she added.

For more information on the study, please see the article in AIDS Research and Human Retroviruses.

Source: AIDS Beacon

NEWS: First NIDA Avant-Garde Awards for medications development research

Awards support novel approaches for treating tobacco and cocaine addiction

A potential immunotherapy, a new gene therapy, an enzyme inhibitor, and a compound originally isolated from a Chinese herb are among the latest approaches scientists are proposing to treat addiction. The recipients of the first-ever Avant-Garde Awards for Innovative Medication Development Research by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, will receive $500,000 per year for five years to support their research.

"Science has clearly shown that drug addiction results from profound disruptions in brain structure and function, presenting numerous potential targets for medications development—yet, few medications have come to fruition," said NIDA Director Nora D. Volkow, M.D. "The array of creative problem-solving approaches submitted by the awardees could help us quicken the pace to find urgently needed medications for addiction."

Awardees are listed below:

Awardee: Andrew Norman, Ph.D., University of Cincinnati
Project: A Human Antibody as an Immunotherapy for Cocaine Abuse

Dr. Norman will move forward with the development of a human monoclonal antibody against cocaine, designated h2E2, which when injected into the bloodstream will attach to cocaine, preventing it from entering the brain and thereby limiting its behavioral effects. A similar mouse-human antibody, 2E2, has been shown to reduce cocaine's effects in a rat model of relapse.

Awardee: William Brimijoin, Ph.D., Mayo Clinic, Rochester, Minn.
Project: Cocaine hydrolase gene therapy for cocaine abuse

Dr. Brimijoin's lab is developing a gene therapy to prevent relapse to cocaine abuse. Their strategy is to use gene transfer to produce high and sustained levels of a modified version of the enzyme butyrylcholinesterase (BChE), which efficiently degrades cocaine in the bloodstream before it reaches the brain.

Awardee: Jia Bei Wang, M.D., Ph.D., University of Maryland at Baltimore
Project: Development of l-THP as New Medication for Drug Addiction

Dr. Wang and colleagues will perform preclinical and small-scale human safety and efficacy studies of the compound l-tetrahydropalmatine (l-THP), a molecule originally discovered in the extract of Chinese herbs, as a treatment for cocaine addiction. Recent animal studies have shown that l-THP can reduce cocaine reward and self-administration.

Awardee: Daniele Piomelli, Ph. D., University of California Irvine
Project: Optimization and preclinical development of FAAH inhibitors for smoking cessation

Dr. Piomelli and his team of researchers are pursuing a medication for smoking cessation using a novel approach of targeting the endogenous cannabinoid system. They will identify and optimize compounds that inhibit an enzyme called fatty acid amide hydrolase (FAAH), which degrades the endocannabinoid anandamide. Animal studies have shown that blocking FAAH reduces nicotine self-administration and prevents nicotine-induced reinstatement, a model of relapse.

"The pharmaceutical industry has been reluctant to invest in medications development for addiction due to stigma and perceived financial disincentives," said Dr. Volkow. "These studies could lay the foundation to encourage greater pharmaceutical industry involvement, further helping to achieve our public health mandate to stop the devastation caused by drug abuse and addiction in this country."

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The newly launched research competition is an extension of NIDA's successful Avant-Garde Award for Innovative HIV/AIDS Research, now in its third year. For further information about the Avant-Garde Award, please visit the NIDA Avant-Garde Award Web site at http://drugabuse.gov/avgp.html. Information about applications for the 2011 Avant-Garde Awards will be posted on this site soon.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to inform policy and improve practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at www.drugabuse.gov. To order publications in English or Spanish, call NIDA's new DrugPubs research dissemination center at 1-877-NIDA-NIH or 240-645-0228 (TDD) or fax or email requests to 240-645-0227 or drugpubs@nida.nih.gov. Online ordering is available at http://drugpubs.drugabuse.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NEWS: Is Big Pharma Courting Widescale Cannabis Distribution?

When Professor Roger Pertwee announced to the world 'cannabis should be sold in shops ' it was quickly the talk of social networks facebook and twitter.

Here, was a respected academic in his field, promoting the harm recuction possibilities of doing away with the prohibition of cannabis, and in doing so he was also rubbishing the 'public health' message behind government generated anti-cannabis propoganda.

Not only a respected academic, but THE respected academic in cannabis research.

Professor Pertwee is said to be a 50 percent share in the partnership which actually discovered THC, the active component in cannabis. But maybe '50% share' was a bad use of verbage? Or was it?

All of a sudden the realisation of what looks like a clumsily implemented PR campaign becomes apparent.

The mist clears..and the reasons an educated and wholly qualified academic was stumbling and bumbling over his lines (it might work, it won't work) is clear for all to see.
In 2003 Professor Roger Pertwee was appointed as 'Head of Pharmacology' at UK cannabis pioneers GW Pharmaceuticals.

GW Pharmaceuticals manufacture the cannabis based medicine 'Sativex' which is commanding so many column inch's in today's press, (its a licensed medicine, although no-one on the NHS is allowed to have it - weird huh?).

They are also the only commercial enterprise in the United Kingdom which is ideally positioned to take advantage of a relaxation in the UK's frankly ridiculous cannabis laws as they are already geared up with tens of thousands of cannabis plants already growing, today, under glass.

In an announcement dripping with platitudes for Professor Pertwee's work , GW Pharma announced to the world, "Professor Pertwee is one of the world's leading cannabinoid scientists, having researched this area for over 30 years, and is the author of over 220 publications. He is a Past President of the International Cannabinoid Research Society and is frequently consulted about the therapeutic potential of cannabis and cannabinoids by parliamentary committees as well as leading medical organisations.

So no one is doubting Professor Pertwee's credentials, and at the time the good prof himself was clearly on a scientific mission. But has the professor made a deal with the devil in securing funding for further cannabinoid research?

Professor Pertwee said of the appointment, "The prospect of exploring the pharmacological actions of individual plant cannabinoids, separately and in combination, is exciting for both scientific and clinical reasons. The setting up of the Institute [Cannabinoid Research Institute] will greatly facilitate fundamental research into the pharmacology of plant cannabinoids and the exploitation of these constituents of cannabis as medicines."

Exploitation?

Thats right. No one is going to spend millions of pounds researching something without there being some form of payback on the horizon. Thats called enterprise.

Dr Geoffrey Guy, Executive Chairman of GW, commented, "It is our aim that GW should occupy the centre ground of cannabinoid science. We are therefore building a bridge between commercial enterprise and academia by establishing the Cannabinoid Research Institute .

So it would seem as far back as 2003 (coincidentally the year Labour Home Secretary David Blunkett decided to declassify cannabis from B to C), GW Pharmaceuticals were already looking towards a day in the not too distant future when democracy (remember that Mr Cameron?) would force cannabis onto the ballot.

Well that day has come. Proposition 19 hits the voting booth's in California come November 2010, when Governor Arnold Schwarzenegger will allow the electorate to decide how cannabis stands in the eyes of the law.

Here in the UK the blue-print for a mass-production facility already exists.

The only question which remains, is whether or not the average British toker is going to support a mass-produced product over something they can grow themselves for a few pounds invested at the local garden centre.

One would suspect not.

Source: PR Cannazine

NEWS: Smoking even low doses of cannabis helps patients, study shows

LOS ANGELES -- Stick to the pipe, medical marijuana users: that's the message from Canadian researchers who found that smoking even relatively low doses of cannabis can help reduce chronic pain, ease sleep and reduce anxiety.

The findings were published Monday in the Canadian Medical Association Journal.

For the study, 21 participants experiencing chronic neuropathic pain for at least three months smoked different preparations of marijuana three times a day for five days each, and stayed smoke-free for nine days as a buffer in between treatments. The most potent concentration was 9.4 percent tetrahydrocannabinol (the active ingredient in cannabis), followed by one of 6 percent, one of 2.5 percent and one with no THC at all.

Patients who inhaled the highest THC concentration felt pain less intensely and slept better than patients who did not inhale THC-laced smoke. Those taking the highest dose reported a pain level of 5.4 on a scale of 1 to 11 - lower than the 6.1 reported by those taking the THC-free dose.

The study's authors concede that a 0.7-point reduction in pain is pretty modest compared with the improvements seen from other drugs - but they also point out that the patients they were testing had suffered from pain that had resisted other forms of treatment. Smoking cannabis, then, could provide at least some relief to those who can find none.

As University of Oxford professor Henry McQuay wrote in a commentary accompanying the study, "Existing treatments are far from perfect. In the meantime, the current trial adds to the trickle of evidence that cannabis may help some of the patients who are struggling at present."

Source: Kentucky.com

NEWS: Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse.

The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors.

We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors.

Results: Our results show that both Delta9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice.

Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway.

We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2.

Conclusions: Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

Author: Maria CaffarelClara AndradasEmilia MiraEduardo Perez-GomezCamilla CeruttiGema Moreno-BuenoJuana FloresIsabel Garcia-RealJose PalaciosSantos ManesManuel GuzmanCristina Sanchez
Credits/Source: Molecular Cancer 2010, 9:196

Source: 7th Space Interactive