Monday, April 30, 2012

Monday Hepatitis C News Ticker-Research and Headlines

Most management decisions were relatively simple, and most patients could be followed primarily by nurse practitioners and physician assistants The field of HCV therapeutics is moving rapidly and much remains to be learned; thus, firm predictions are inherently risky. It is likely, however, that for the foreseeable future, management decisions will require much more thought than they did in the “easy” days of interferon alfa–based regimens.

Interferon-Associated Retinopathy and Non-HCV Related Eye Conditions
This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes

Coffee reduced HCV replication with regular coffee having a more pronounced effect. Coffee significantly reduced HCV replication at concentrations achievable by coffee consumption, while caffeine as well as caffeine degradation products interfered with HCV replication at high concentrations (about 100 µM or more).


Advances in the treatment of hepatitis C virus infection.
Thomas DL. Antivir Med. 2012 Apr;20(1):5-10.

The addition of a protease inhibitor (PI) to what has been the standard HCV therapy of peginterferon alfa and ribavirin dramatically improves sustained virologic response rates in treatment-naive patients with genotype 1 infection.

Similar results have been observed in some treatment-experienced patients in whom prior peginterferon alfa/ribavirin therapy has failed. The use of these new agents has also permitted response-guided therapy, wherein early sustained virologic response to treatment allows for a shortened treatment duration.

However, these new PIs add cost and adverse effects to HCV therapy. Boceprevir is associated with increased risk of anemia and dysgeusia, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal adverse effects. Early studies indicate that the addition of PIs results in high response rates in patients with HCV/HIV coinfection. Other studies suggest that combinations of PIs and other direct-acting antivirals may ultimately permit cure when used in interferon sparing regimens....


Analysis of long-term persistence of resistance mutations within the hepatitis C virus NS3 protease after treatment with telaprevir or boceprevir

Liz Highleyman
Adding GS-7977 to pegylated interferon and ribavirin for 12 weeks led to a sustained response rate of 90% for previously untreated chronic hepatitis C patients with difficult-to-treat genotype 1, researchers reported at the 47th International Liver ...Continue Reading...


Annals Of Hepatology
May-June, Vol. 11 Issue 3, 2012

Does the persistently normal aminotransferase levels in hepatitis C sitll have relevance?
Jorge Méndez-Navarro, Margarita Dehesa-Violante

Prevention of hepatocellular carcinoma: a concise review of contemporary issues
Vincent Wai-Sun Wong, Henry Lik-Yuen Chan

Treatment of recurrent genotype 4 hepatitis C after liver transplantation: early virological response is predictive of sustained virological response. An AISF RECOLT-C Group Study
Francesca Romana Ponziani, Alessandro Milani, Antonio Gasbarrini, Raffaella Zaccaria, Raffaella Viganò, Maria Francesca Donato, Maria Cristina Morelli, Lucia Miglioresi, Luisa Pasulo, Maria Rendina, Daniele Di Paolo, Maria Marino, Pierluigi Toniutto, Stefano Fagiuoli, Maurizio Pompili

In The News

Media Advisory - Interview Local Nurses Dedicated to the Hepatitis C Community: National Nursing
Week - May 7 to 13, 2012

TORONTO, April 30, 2012 /PRNewswire via COMTEX/ -- During National Nursing Week, Canadians will recognize and celebrate the important contributions nurses make daily to patient care in Canada. The role nurses play in the prevention and management of chronic hepatitis C, a potentially life-threatening virus, provides a powerful example of their impact as supporter, educator and counsellor.

Canadians living with chronic hepatitis C often fear the judgment of others because the virus infecting them is often associated with injection drug use. The reality is that people can contract the virus through a number of different ways including, body piercings, tattoos, blood transfusions or personal care items (razors).

Members of the Canadian Association of Hepatology Nurses (CAHN) build trusted relationships with patients by not focusing on how the hepatitis C virus was contracted, but rather on providing care and support that is beneficial, respectful and can lead to a cure.

The road to a cure is a difficult journey for patients living with chronic hepatitis C. While treatments can be very successful at getting rid of the virus, the stigma associated with the disease often requires patients to struggle through chemotherapy-like side effects in isolation.

CAHN wants to shatter the stigma for those people living with chronic hepatitis C by helping Canadians recognize that anyone, including someone they know and love, could be living with this virus. Stigma must not be a barrier to detection and treatment.

This National Nursing Week, celebrate the leadership provided by CAHN nurses in the prevention and management of chronic hepatitis C.

What: Interview opportunities with nurses and individuals living with chronic hepatitis C willing to share their stories Who: Cheryl Dale, President of the Canadian Association of Hepatology Nurses, CAHN members and individuals living with chronic hepatitis C Where: The following communities across Canada: Ontario (Toronto, Oakville, Mississauga, Guelph, Hamilton, Kitchener-Waterloo, Newmarket, Sutton, Sudbury, North Bay, and London), Quebec (Montreal), British Columbia (Vancouver, Kelowna, and Nanaimo), Alberta (Edmonton), Nova Scotia (Halifax), and Saskatchewan (Prince Albert) When: National Nursing Week (May 7-13, 2012)

SOURCE Canadian Association of Hepatology Nurses
Copyright (C) 2012 PR Newswire. All rights reserved

Hep C Bulletin: Medication Management
There are hundreds of medications that are metabolized by the liver - both prescription and over-the-counter drugs. In an ideal world, each person would have a physician who knows all about his or her medical history and monitors every pharmaceutical he or she takes. In the real world, many of us are left to fend for ourselves in this arena. Instead of turning one's well-being over to the medical system, being diagnosed with Hepatitis C should put those affected in the driver seat to control their fate:
• by making sure they know what kind of stress every drug taken places on the liver
• by instigating a dialogue with their primary healthcare provider about monitoring their liver's health when necessary

In the end, develop the patience to learn about your medications and the courage to speak up to a doctor about their effect on your liver. Being responsible for these two simple steps can help those with chronic Hepatitis C take an active role in receiving the best healthcare possible.
Continue Reading....

Gilead Sciences Looks For Hepatitis C Cure
Why the emphasis on hep c? While Gilead Sciences has branched out into treatments for cardiovascular diseases, its primary expertise in in anti-viral drugs, particularly for HIV infections, which lead to AIDS if untreated. Because of the effectiveness of its single-tablet, multi-drug combinations, Gilead dominates that market. Gilead also markets Viread for Hepatitis B. The past generation of Hepatitis C therapies have limited effectiveness, have a number of side effects, and cannot be administered orally.

Before the Pharmasset acquisition Gilead had four hepatitis drugs in phase II trials, and three in phase I, and said they would likely be made into a successful combination therapy. Pharmasset added Phase III candidate PSI-7977 (now GS7977), Phase II candidate Mericitabine, and Phase II candidate PSI-938, all for hep C. Pharmasset also brought candidates for HIV and hepatitis B treatment.

Thursday Gilead executives reviewed recent hep C data and clarified their strategy. The GS-7977 plus ribavirin hepatitis C (HCV) genotype 1 Phase 2 study showed no detectible virus after 12 weeks of treatment, but at end of treatment the majority of patients relapsed. GS-7977 plus BMS-790052 (owned by Bristol Myer BMY) showed high hepatitis C cure rates: >90% for genotype 2/3 and 100% for genotype 1.

Based on those and other results, Gilead is designing Phase III studies that could be fully enrolled by the end of May. Several paths are available to get therapies to market, but they need to talk more to regulators before the final trials are initiated. They would clearly prefer an all-Gilead single tablet regimen that cures most hep C, so working with Bristol Myer would be a fall back position. Given the number of drugs Gilead owns and could combine with 7977, it is a good, but not certain, bet that something will work.

At the same time it is a race, since other companies are also trying to break into the all-oral hepatitis market. It is a huge market. An estimated 150 million people have chronic hepatitis C, with the U.S. figure likely somewhere between 3 and 6 million (many people have undiagnosed hep c).

It is too early, I think, to put a number on the value of a hep c cure, but note that Gilead paid $11 billion for Pharmasset. They went through most of their cash and borrowed some $5.5 billion to do it. Gilead annual cash flow runs around $2 billion.

The main risk here is that a competitor (or multiple competitors) will also create an all-oral hepatitis c therapy, and might even gain FDA approval first. Even so, it is a big market and I don't think Gilead's present price reflects much of this opportunity.............
Read full article here

Stem Cells

Stem cell researchers map new knowledge about insulin production      
Monday, 30 April 2012   

Scientists from The Danish Stem Cell Center (DanStem) at the University of Copenhagen and Hagedorn Research Institute have gained new insight into the signaling paths that control the body's insulin production. This is important knowledge with respect to their final goal: the conversion of stem cells into insulin-producing beta cells that can be implanted into patients who need them. The research results have just been published in the journal PNAS.

Insulin is a hormone produced by beta cells in the pancreas. If these beta cells are defective, the body develops diabetes. Insulin is vital to life and therefore today the people who cannot produce their own in sufficient quantities, or at all, receive carefully measured doses – often via several daily injections. Scientists hope that in the not-so-distant future it will be possible to treat diabetes more effectively and prevent secondary diseases such as cardiac disease, blindness and nerve and kidney complications by offering diabetes patients implants of new, well-functioning, stem-cell-based beta cells.

"In order to get stem cells to develop into insulin-producing beta cells, it is necessary to know what signaling mechanisms normally control the creation of beta cells during fetal development. This is what our new research results can contribute," explains Professor Palle Serup from DanStem.
"When we know the signaling paths, we can copy them in test tubes and thus in time convert stem cells to beta cells," says Professor Serup.

The new research results were obtained in a cooperative effort between DanStem, the Danish Hagedorn Research Institute and international partners in Japan, Germany, Korea and the USA. The scientific paper has just been published in the well-respected international journal PNAS (Proceedings of the National Academy of Sciences of the United States of America) entitled Mind bomb 1 is required for pancreatic β-cell formation.

Better control of stem cells
The signaling mechanism that controls the first steps of the development from stem cells to beta cells has long been known.

"Our research contributes knowledge about the next step in development and the signaling involved in the communication between cells - an area that has not been extensively described. This new knowledge about the ability of the so-called Notch signaling first to inhibit and then to stimulate the creation of hormone-producing cells is crucially important to being able to control stem cells better when working with them in test tubes," explains Professor Palle Serup.

This new knowledge about the characteristics of the Notch signaling mechanism will enable scientists to design new experimental ways to cultivate stem cells so that they can be more effectively converted into insulin-producing beta cells.

David vs Goliath in stem cells: the global power of blogs
The conflict in Ireland over stem cells is still brewing and bubbling this week as I’ve been blogging it.

It is remarkable to me that as just one person I have in a few days been able to have a substantial impact in that dialogue via this blog.

There has been a rather large push lately, especially in the past week, by the “adult stem cells only” crowd in Ireland to advance their cause via press releases and use of traditional media.
For example, the Irish Times published a piece on stem cells in Ireland that almost entirely regurgitated verbatim verbiage from the Adult Stem Cell Foundation of Ireland (ASFI). Rather than a news piece, it was really a propaganda piece.

A more balanced piece was found in the Irish Examiner, presenting arguments from both ASFI, which only advocates use of adult stem cells, and also the Irish Stem Cell Foundation, which advocates the use of all stem cells.

What does the Internet “think” of this issue?
A Google search for Adult Stem Cell Foundation of Ireland yields some remarkable results. While the Irish Times propaganda piece pops up as #1 in the search results sadly, the Irish Examiner piece is #4. Strikingly, two of my blog pieces (here and here) from this week are sandwiched in between at #2 and #3. I also posted another piece that is I believe #12 in the search results.

Thus, in just a manner of 4 days the pieces just mentioning ASFI on this blog have generated enough traffic and interest to be of major importance by Google, impact that is essentially comparable to those of two major traditional newspapers in Ireland. The Times’ circulation in 2011 was almost 400,000 and the Examiner is about 60,000 I believe.

How is it that a blog written by me can compete with these relatively gargantuan media businesses? The reality is that highly read blogs written by a single person can vie with newspapers for influence on specific topics.

Perhaps my pieces will fade in Google’s view over time, but the impact now is surprising to me. I take this power in a very sober manner and consider this a big responsibility. At the same time this tells me that even one patient advocate or stem cell researcher can have a surprisingly powerful influence on the discourse on specific issues.

Of course this power can and is used effectively by people on the other side of the stem cell battlefront. Many examples of powerful “adult stem cells only” blogs are apparent on the Internet.
No matter one’s opinion on issues such as stem cells, an indisputable reality of today is that blogs are quite powerful tools.

Healthy You

Vitamin D supplements may protect against viral infections during the winter
New research published in the Journal of Leukocyte Biology suggests that the older population could benefit from vitamin D supplementation in autumn and winter to protect against viral infections
Vitamin D may be known as the sunshine vitamin, but a new research report appearing in the Journal of Leukocyte Biology shows that it is more than that.

According to the report, insufficient levels of vitamin D are related to a deficiency in our innate immune defenses that protect us from infections, neoplasias or autoimmune diseases. Since vitamin D levels decrease during autumn and winter when days are shorter and sunlight is relatively weak, this may explain why people are more prone to viral infection during these times. It also suggests that vitamin D supplementation, especially in older populations, could strengthen people's innate immunity against viral infections.

"There are numerous studies showing the benefits of maintaining adequate Vitamin D levels. As more and more research into Vitamin D is conducted, we are learning that it is extremely important for human health. Our study is no different, and vitamin D supplements should be considered one of many tools that might help when conventional therapies are not enough," said Victor Manuel Martinez-Taboada, M.D., a researcher involved in the work from the Division of Rheumatology at the Hospital Universitario "Marque's de Valdecilla," Facultad de Medicina at the Unversidad de Cantabria, in Santander, Spain.

To make this discovery, the researchers compared the changes in the blood levels of vitamin D among three groups of healthy subjects: young (age range: 20-30), middle (age range: 31-59), and elderly (age range: 60-86). They found decreased levels of vitamin D with aging, prompting researchers to compare whether such changes kept any relationship with toll-like receptor (TLR) expression measured on lymphocytes and monocytes and function after in vitro stimulation with specific ligands for each of the nine human TLRs and measurement of effector molecules, such as proinflammatory cytokines. Specifically, they found that the TRL most affected by a vitamin D insufficiency is TLR7, which regulates the immune response against viruses. Finally, scientists studied whether there was any difference in the three age groups depending on the season of the year since it is well known that a limited sun exposure during darker winter months is related with vitamin D deficiency.

"Any school teacher will tell you that people tend to be sicker during the winter than any other time of the year," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "There have been numerous studies showing several environmental factors during winter months may allow viruses to spread easier. This study shows that sunlight, or more precisely the lack of vitamin D, could have a role in the seasonally higher rates of infection. More extensive studies must be conducted for this link to be conclusive, but since vitamin D supplements are inexpensive and generally safe, this is a really exciting discovery."


The Journal of Leukocyte Biology publishes peer-reviewed manuscripts on original investigatins focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology

Details: Lorena Alvarez-Rodriguez, Marcos Lopez-Hoyos, Maite Garcia-Unzueta, Jose Antonio Amado, Pedro Muñoz Cacho, and Victor Manuel Martinez-Taboada. Age and low levels of circulating vitamin D are associated with impaired innate immune function. J Leukoc Biol May 2012 91:829-838; doi:10.1189/jlb.1011523 ;

Anxiety, Depression Often Go Hand-in-Hand With Arthritis

Mental health screening, treatment could improve quality of life for these patients, report suggests

MONDAY, April 30 (HealthDay News) -- Depression or anxiety affect one-third of Americans with arthritis who are aged 45 or older, a new study shows.

Researchers from the U.S. Centers for Disease Control and Prevention also found that even though anxiety is nearly twice as common as depression among people with arthritis, doctors tend to focus more on depression in these patients.

The study included nearly 1,800 people with arthritis or other rheumatic conditions who took part in the CDC's Arthritis Conditions and Health Effects Survey. Among the study participants, 31 percent reported anxiety and 18 percent reported depression.

One-third of the patients reported at least one of the two conditions and 84 percent of those with depression also had anxiety. Only half of those with anxiety or depression sought mental health treatment in the previous year, according to the study, which was published in the April 30 issue of the journal Arthritis Care & Research.

"Given their high prevalence and the effective treatment options that are available, we suggest that all people with arthritis be screened for anxiety and depression," study leader Dr. Louise Murphy, of the Arthritis Program at the CDC, said in a journal news release.

"With so many arthritis patients not seeking mental health treatment, health care providers are missing an intervention opportunity that could improve the quality of life for those with arthritis," she added.
In the United States, 27 million people age 25 and older have osteoarthritis, and 1.3 million adults have rheumatoid arthritis, according to the American College of Rheumatology.

More information
The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases offers advice on how to live with arthritis.
Copyright © 2012 HealthDay. All rights reserved.

Of Interest

Is Marijuana Medicinal?

POINT: Cannabis can relieve neuropathic pain.
As an oncologist, I treat cancer patients who have nausea, vomiting, weight loss, pain with and without opioids, insomnia, and depression. With cannabis, I can recommend that they try one medicine instead of five or six prescriptions that will interact either with one another or with their cancer chemotherapy.

Studies show that cannabis and cannabinoids are effective for peripheral neuropathic syndromes associated with HIV, multiple sclerosis, or posttraumatic or postsurgical causes. A study of diabetic neuropathy is ongoing; cannabis has not yet been studied for chemotherapy-induced neuropathy. Other data show that cannabis and cannabinoids may be synergistic with opioids in relief of chronic pain without altering pharmacokinetics.

We conducted a randomized, placebo-controlled study of cannabis for patients with HIV-related peripheral neuropathy at San Francisco General Hospital because preclinical studies and anecdotal patient reports said it was helpful. Average neuropathic pain scores in the week before being admitted to our research center were about 60 out of 100.

After a 2-day run-in period, patients were randomized to smoke cannabis or placebo three times a day for 5 days. Among 50 patients who completed the study, neuropathic pain decreased by about 34% with cannabis versus 17% with placebo. Our threshold for a positive response was at least a 30% reduction in pain; this was reported by 52% on cannabis and 24% on placebo (Neurology 2007;68:515-21).

We also used a more objective heat-capsaicin method to assess pain. An area on the forearm was heated to 40° C for half an hour and then capsaicin (the active ingredient in chili peppers) was applied. This creates an area of hypesthesia and allodynia that can be measured using a brush and a piece of foam while the patient looks in another direction.

On the heat-capsaicin tests, the area of hypesthesia or allodynia either increased or was the same after smoking placebo but decreased approximately 30% after smoking cannabis. We calculated that the number needed to treat to get a beneficial effect was 3.6, which is equivalent to that with gabapentin, the mainstay treatment for our patients with HIV-related peripheral neuropathy.

A crossover study in 28 patients with HIV-associated neuropathy at the University of California, San Diego found that pain decreased with cannabis versus placebo. The number needed to treat was 3.5. (Neuropsychopharmacology 2009;34:672-680).

Investigators at the University of California, Davis, randomized 38 patients with central and peripheral neuropathic pain to low- or high-dose cannabis or placebo. They found a linear analgesic dose response for both doses of cannabis, compared with placebo, and reported that the effect was not due to lysis of anxiety but to reduction of core nociception as well as emotional responses to pain. (J. Pain 2008;9:506-21).

Dr. Donald I. Abrams
A randomized, double-blind, four-period crossover study in Montreal looked at 23 participants with postsurgical neuropathic pain who inhaled increasing dosages of tetrahydrocannabinol (THC). Results showed that the average daily pain intensity was significantly lower and quality of sleep improved in the highest-dose THC group, compared with the placebo group (CMAJ 2010;182:e694-701).

We recently completed a study funded by the National Institute on Drug Abuse to look at effects of combined use of opioids and cannabis, in which
we also assessed effects on pain.

We saw a significant 26% reduction in pain with the addition of vaporized cannabis in the cohort as a whole. Pain reduction was greater in the morphine group (a 31% decrease) compared with the oxycodone group (a 23% decrease). We saw no adverse safety effects. Although we know quite well that the study was too small to make a definitive claim, this was a tantalizing demonstration of potential synergy between opioids and cannabinoids, (Clin. Pharmacotherapeutics 2011;90:844-51).

Every 10 years since cannabis was removed from the medical formulary in 1942, some august government body in the United States looks at cannabis in medicine. They all conclude the same thing – that it’s a valuable medicine, and should be available. That usually goes ignored, however. An Institute of Medicine report in 1999 said the accumulated data indicate a potential therapeutic value for cannabinoid drugs in the treatment of pain, control of nausea and vomiting, and appetite stimulation.

Dr. Donald I. Abrams is a professor of clinical medicine at the University of California, San Francisco. He declared having nothing to disclose except that he went to college in the 1960s. This debate took place at the annual meeting of the American Academy of Pain Medicine.

COUNTERPOINT: But chronic use is harmful.
Marijuana doesn’t meet standards to be considered a medicine.

There’s a massive lack of standardization in the product. Compounds have very different, in some cases opposing, effects. Potency varies depending on the strain and how it was prepared.

There’s also no standardization around administration. Smoking or inhaling marijuana – the most common routes speed drug uptake and the effects of cannabinoids on reward processing, which increases addictiveness.

Smoking marijuana is carcinogenic and causes lung damage. Yes, a study suggested twice-a-month use doesn’t really change your lung capacity, but that changed with daily, frequent use. The typical use pattern is about four times per day, daily, in medical patients.

Pain studies looked at acute use of cannabis for a week or so. They haven’t looked at chronic effects. We don’t know the impact of tolerance and dependence in patients with chronic pain, or the effect of constant activation of reward circuits by marijuana on new behavior patterns over time. That’s typically what you have trouble with in chronic pain patients – getting them up, getting them going, getting them back into life. Marijuana could make that more difficult.

Dr. Jodie Trafton
A meta-analysis of 18 randomized, double-blind, controlled trials of cannabis for chronic pain found a greater effect with cannabis than with placebo, but this was not huge. If a patient starts out with a pain score of 8 out of 10, it will drop to about 7.4 – a 7.5% reduction in score. We’re talking about going from severe to a little less severe pain. Patients on cannabis were much more likely to have alterations in perception, motor function, and cognitive function (Pain Med. 2009;10:1353-68).

In the crossover study of 23 patients that Dr. Abrams cites, low-dose and high-dose THC decreased pain, but there was no difference in the middle doses, compared with placebo. And look at the levels of pain scores: You’re going from an average of 6.1 to 5.4, from moderate pain to moderate pain. That’s less than 1 point on a 10-point scale, and you’re getting all of the adverse effects and behavioral changes in conjunction with that. Is that worth it?

The 28-patient crossover study he cites started with 34 patients. There were some serious cannabis-related issues, including acute psychosis and intractable cough, in the patients who didn’t complete it. One patient started using methamphetamine again. This is not a particularly low rate of problems.

We don’t have a lot of data to say what happens to patients with chronic pain who use marijuana over time. There are more data on what happens when people in the general population use marijuana chronically. The best characterized chronic effects include a motivational syndrome, poor concentration, attention and judgment, impaired social skills, introversion, deteriorating personal habits and depersonalization, mood disorders, anxiety disorders, insomnia, increased risk of schizophreniform illness and psychosis, more negative life events, and withdrawal.

Studies have found functional impairments related to chronic marijuana use. People who use marijuana over long periods of time develop at least partially persistent problems on neuropsychological tests – problems that don’t go away even if they stop using marijuana.

There’s also evidence of a relationship between cannabis and mood disorders. Cross-sectional studies show that people who use cannabis daily or near-daily are 3.4 times more likely to have major depression. Longitudinally, if you are diagnosed with cannabis dependence, you have a 6.4-fold increased chance of being diagnosed with major depression within a 12-month time period.

It appears that cannabis is inducing the mood disorders, not the mood disorders driving cannabis use. A Dutch study of 3,854 adults with no history of mood disorders found that cannabis use at baseline was associated with a doubling in risk for developing any mood disorder, a 60% increased risk for major depression, and a five-fold increased risk for bipolar disease (Addiction 2007;102:1251-60).

If cannabis use makes people tend toward mood disorders, and chronic pain patients tend toward mood disorders, how much harder are you making it by suggesting they try marijuana to get that 1-point decrease in pain?

Frequent marijuana use is associated with development of dependence. Withdrawal symptoms occur whenever drug levels start to decrease over time. Withdrawal starts within 2-4 hours, and symptoms last for weeks. Symptoms include irritability, anger or aggression, nervousness or anxiety, sleep difficulty, decreased appetite or weight loss, restlessness, depressed mood, and a variety of physical symptoms causing significant discomfort.

The main reasons that people say they want to use medical marijuana are to treat nervousness, anxiety, insomnia, and depressed mood. All of these potentially are withdrawal symptoms.

One study showed a vast majority of California patients seeking a physician’s recommendation for medical marijuana – well over 95% were already self-medicating with marijuana. We would expect that population to be dependent.

A separate study confirmed that 10 of the 15 "clinical benefits" reported by 1,746 medical marijuana users were the easing of problems that can be found on a list of withdrawal symptoms (J. Psychoactive Drugs 2011;43:128-35).

Chronic pain patients already have high comorbidity with depression, functional problems, and high rates of disability. Recommending medical marijuana increases risk in an already at-risk population.

Jodie Trafton, Ph.D., is director of the Program Evaluation and Resource Center in the Office of Mental Health Operations, Veterans Affairs Palo Alto (Calif.) Health Care System. The views expressed are those of Dr. Trafton and do not necessarily represent those of the Department of Veterans Affairs. She declared having no financial disclosures.

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