Some two-thirds of Israeli cancer patients authorized to use cannabis report long-term, symptomatic improvement from the plant, according to clinical data presented in late January at a conference of the Israeli Oncologists Union and reported this week in several international media outlets.

Investigators at the Sheba Medical Center in Tel Aviv, in conjunction with the Israeli Cancer Association, assessed the efficacy of cannabis therapy over the course of one year in 264 patients with cancer. Israeli media reported the findings:

“Some 61 percent of the respondents reported a significant improvement in their quality of life as a result of the medical marijuana, while 56 percent noted an improvement in their ability to manage pain. In general, 67 percent were in favor of the treatment, while 65 percent said they would recommend it to other patients.”

The study concluded that cannabis is an “effective” treatment for certain symptoms of the disease cancer and recommended, “The treatment should be offered to the patients in earlier stages of cancer.”

In the trial, the most common types of cancer for which medical marijuana was authorized was lung cancer (21 percent ), breast cancer (12 percent ) and pancreatic cancer (10 percent ).

The study focused primarily on the use of cannabis to relieve various symptoms of cancer or cancer treatment, such as pain and nausea, but did not evaluate whether marijuana therapy could potentially suppress the proliferation of the disease. In preclinical trials, various cannabinoids – including THC and CBD (cannabidiol) – have been shown to selectively target and eliminate malignant cells and cancerous tumors.

To date, some 6,000 Israelis possess government authorization to use cannabis therapeutically. Patients authorized by the federal program may either cultivate cannabis at home or they may obtain marijuana from one of the nation’s 12 licensed cannabis farms.

Last summer, the Israeli Health Ministry formally acknowledged the therapeutic utility of cannabis and announced newly amended guidelines to more effectively govern the state-sponsored production and distribution of medical marijuana. The Ministry estimates that as many as 40,000 patients will eventually have access to medicinal cannabis once the Israeli program is fully implemented.

NORML’s literature review of the anti-cancer properties of cannabis and cannabinoids is available here.

Physicians who prescribe opioid drugs to patients with neuropathy (nerve pain) ought to consider recommending cannabis as an alternative therapy, according to a peer-reviewed paper published online this week in the Harm Reduction Journal.

“There is sufficient evidence of safety and efficacy for the use of (cannabis/cannabinoids) in the treatment of nerve pain relative to opioids,” the commentary states. “In states where medicinal cannabis is legal, physicians who treat neuropathic pain with opioids should evaluate their patients for a trial of cannabis and prescribe it when appropriate prior to using opioids. … Prescribing cannabis in place of opioids for neuropathic pain may reduce the morbidity and mortality rates associated with prescription pain medications and may be an effective harm reduction strategy.”

The author notes that between the years 1999 and 2006, “approximately 65,000 people died from opioid analgesic overdose.” By contrast, he writes “[N]o one has ever died from an overdose of cannabis.”

In clinical trials, inhaled cannabis has been consistently shown to reduce neuropathic pain of diverse causes in subjects unresponsive to standard pain therapies.

In November, clinical investigators at the University of California, San Francisco reported that vaporized cannabis augments the analgesic effects of opiates in subjects prescribed morphine or oxycodone. Authors of the study surmised that cannabis-specific interventions “may allow for opioid treatment at lower doses with fewer [patient] side effects.”

Neuropathy affects between five percent and 10 percent of the US population. The condition is often unresponsive to conventional analgesic medications such as opiates and non-steroidal anti-inflammatory drugs.

Full text of the paper, “Prescribing cannabis for harm reduction” is available online here.

Cannabis inhalation and the administration of cannabinoids are both associated with “significant analgesic effects” in the treatment of chronic non-cancer pain, according to a systemic review of randomized controlled trials to be published in the British Journal of Clinical Pharmacology.

Investigators from the University of Toronto, Hospital for Sick Children, conducted a literature review regarding the efficacy of cannabinoids in the treatment of chronic pain, including neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Eighteen randomized controlled trials published between 2003 and 2010 involving a total of 766 participants met inclusion criteria. Four of the trials assessed inhaled cannabis, while other studies assessed the analgesic properties of either plant-derived cannabinoids or synthetic cannabinoids.

“Overall the quality of trials was excellent,” authors wrote. “Fifteen of the eighteen trials that met inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared to placebo, several reported significant improvements in sleep. There were no serious adverse effects.”

Researchers noted that all four trials involving inhaled cannabis “found a positive effect with no serious adverse side effects.” They added: “Of special importance is the fact that two of the trials examining smoked cannabis demonstrated a significant analgesic effect in HIV neuropathy, a type of pain that has been notoriously resistant to other treatments normally used for neuropathic pain. In the trial examining cannabis based medicines in rheumatoid arthritis a significant reduction in disease activity was also noted, this is consistent with pre-clinical work demonstrating that cannabinoids are anti-inflammatory.”

Investigators concluded, “[C]annabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large-scale trials of longer duration reporting on pain and level of function are required.”

NORML has additional information on the analgesic properties of cannabinoids in its handbook, Emerging Clinical Applications for Cannabis and Cannabinoids, here.

Inhaled cannabis reduces pain and improves sleep compared to placebo, and is well tolerated by patients with chronic neuropathy, according to clinical trial data published this week in the Journal of the Canadian Medical Association (CMAJ).

Investigators at McGill University in Montreal assessed the efficacy of inhaled cannabis on pain intensity in 23 subjects with chronic post-traumatic or post-surgical neuropathic pain in a randomized, double-blind, placebo-controlled crossover trial. Participants in the study received a single inhalation of 25 mg of 9.4 percent herbal cannabis or placebo three times daily. All of the volunteers in the study suffered from refractory pain for which conventional therapies had proven ineffective.

Researchers reported: “[H]erbal cannabis … significantly reduced average pain scores compared with … cannabis placebo in adult participants. … We found significant improvement in measures of sleep quality and anxiety. … Our results support the claim that smoked cannabis reduces pain, improves mood, and helps sleep.”

Speaking to Web MD online, the study’s lead researcher Mark Ware said: “We’ve shown again that cannabis is an analgesic. Clearly it has medical value.”

In February, investigators from the California Center for Medicinal Cannabis Research summarized the results of four separate FDA ‘gold standard’ designed clinical trials demonstrating that inhaled marijuana was safe and effective for the treatment of neuropathy.

An estimated one to two percent of the population suffers from some form of neuropathic pain, which typically goes untreated by standard analgesics.

Listen to NORML Executive Director Allen St. Pierre and NORML Advisory Board member Lester Grinspoon discuss this trial, and other subjects related to the medical use of cannabis, on NPR’s The Diane Rehm show here.

Like many medical marijuana users, Kristin Redeen needed additional prescription medications for her severe chronic pain. For seven years she had been treated at a private pain clinic in the Central Valley, where a doctor maintained her on Percocet, a semi-synthetic opioid. One day Kristin was unexpectedly asked to submit a urine sample.  

“They already knew about my medical marijuana use,” says Kristin, who contacted California NORML. “I didn’t think I was doing anything wrong.”

When the test  came back, Kristin was informed that the clinic would no longer renew her prescription because she had tested positive for an illegal controlled substance. Her doctor at the clinic cited legal concerns, claiming –falsely– that DEA regulations forbid giving prescription narcotics to users of marijuana or other illegal drugs.

Kristin was cut off from her Percocet and began suffering seizures. She finally found a physician who was willing to prescribe her another opioid, Vicodin, but only at low doses insufficient to relieve her constant pain.

Kristin is one of a growing number of medical marijuana patients discriminated against by pain clinics. “I must have heard of 25 cases this year,” says Doug Hiatt, an attorney in Washington state. “It’s Jim Crow medicine.”

NORML has received a surge of complaints within the last six months.  Many medical marijuana users report that they can’t find a clinic willing to take them on.  Others, like Kristin, have been abandoned by clinics that suddenly adopted aggressive drug-screening policies.

Clinics say they are legally compelled to drug-test chronic pain patients so as to avoid liability for overdoses and diversion of prescription drugs, particularly opioids such as oxycontin –which have nothing to do with cannabis.

Chronic pain patients have good reason to object to being denied medical access to cannabis. Chronic pain is the leading indication for medical cannabis use, accounting for 90% of the patients in Oregon’s medical marijuana program.   More than 60 studies have shown cannabinoids to be effective in pain relief, according to a compilation by the International Association of Cannabis Medicine which includes four controlled studies of smoked marijuana by California’s Center for Medicinal Cannabis Research.

Studies indicate that cannabis interacts synergistically with opioids in such a way as to improve pain relief [1, 2].    California medical cannabis specialists consistently report that patients are able to reduce use of opioids –typically by 50%– when they add cannabis to their regimen.  Cannabis can therefore be seen as a gateway drug leading away from opioid addiction.  Nevertheless, patients are being pressured to stop using cannabis if they want to get prescription opioids.

To their dismay, patients have to pay for the drug tests at their own (or their insurers’) expense.   Carol, a chronic pain patient who had been treated for seven years by the same clinic without any testing, reports that she was billed $325 for a urine screen. The balance of the bill, which totaled $1,601, was paid by her insurer.

Carol says her doctor told her that “the DEA requires him to drug test all his clients, that he has no choice, it is the law.”

In fact, there is no law requiring clinics to drug screen patients for marijuana.   “It’s BS,” says Hiatt.  Not a single case is known in which pain doctors have been sued or prosecuted for allowing medical marijuana use along with opiates.

Prosecutors have argued that marijuana might be obtained on the illicit market in trade for  prescription drugs, though such a scenario seems implausible in medical cannabis states. “It’s unwarranted paranoia,” says Gregory Carter, MD, one of the few practicing pain experts who recommend marijuana in Washington.

Given that cannabis is notably less toxic and addictive than other prescription narcotics,  it seems highly ironic that pain clinics are discouraging its use.  The prejudice against marijuana has nothing to do with medical science, but rather with political and legal pressures to crack down on prescription drug use. Non-medical use of prescription drugs has recently emerged as the nation’s number-one drug problem du jour.

A new government report, ominously entitled the “National Prescription Drug Threat Assessment,” reported 8,500 deaths in 2005 from prescription pain relievers (mainly opioids), more than double the 2001 total. “Diversion and abuse of prescription drugs are a threat to our public health and safety – similar to the threat posed by illicit drugs such as heroin and cocaine,” warned Drug Czar Gil Kerlikowske.

The Pain Specialists’ Meeting
The 2009 American Pain Society Convention in San Diego included a panel on “Cannabinoids in Pain Management,” chaired by Dr. Mark Ware of McGill University. Dr. Andrea Hohmann, an expert on stress-level analgesia from the University of Georgia, presented evidence from rodent studies which showed that cannabinoids suppress nociceptive processing through both the CB1 and CB2 receptors, and that endocannabinoids, including 2-AG and anandamide, help suppress pain.

Donald Abrams, MD, of the University of California at San Francisco, discussed his studies showing that inhaled marijuana significantly reduced neuropathic pain experienced by HIV patients.  Cannabinoids and opioids interact synergistically on separate but parallel pain receptors, Abrams said. He is conducting another study on combined use of cannabinoids and opioids, preliminary results of which appear promising.

Dr. Ware discussed studies involving the variety of cannabinoid medicines available in Canada, which include dronabinol, Sativex, Nabilone, and herbal THC. All of them have demonstrated efficacy in pain relief.  Cannabis is now recognized as a “third line” agent for neuropathic pain in Canada.  Noting that that its adverse effects are mild to moderate, Ware concluded that “cannabinoid analgesia is the real thing.”

During the question session, your correspondent asked why it was that, in light of evidence that cannabis was so useful in pain therapy, there appeared to be an upsurge in drug testing to prevent its use.  The panelists could offer no explanation.

We moved on to the exhibition hall, where drug testing companies were conspicuously displaying their wares.  Their exhibits showed how well their products could monitor usage of opiates.  The exhibitors seemed surprised when we told them that their products were being used against medical marijuana.

One of the more sophisticated exhibitors was Ameritox, which boasted panels for distinguishing a dozen different opioids plus numerous sedatives, tricyclic anti-depressants, barbiturates, and stimulants as well as “drugs of abuse,” among them marijuana.  Their saleswoman seemed surprised to hear that the Ameritox test was being used to screen out medical marijuana patients.  She said that clinics could easily order the screens without the marijuana if they wanted.
Another company boasted how their test could be administered at the doctor’s office, thereby allowing the doctor rather than the lab to collect the bill.

Finally, we spoke to a legal expert on pain medication, Ms. Jennifer Bolen, a former prosecutor turned defense attorney, who has a useful website devoted to the subject:
www.legalsideofpain.com.

Ms Bolen pointed to three recent developments that have increased the pressure to conduct drug screening of pain patients.  First,  pain doctors have suffered a string of stinging legal judgments for over-prescribing opioids to patients who subsequently overdosed. One notable example involved Dr. Thomas Merrill of Florida,  whose life sentence was sustained by the Eleventh Circuit Court of Appeals last year.

This February, a prestigious panel of the American Pain Society issued “New Guidelines for Prescribing Opioid Pain Drugs” which counsels that “diligent monitoring of patients is essential. “ The report specifically recommends periodic drug screens for chronic opioid patients at risk for aberrant drug behavior, though it doesn’t mention cannabis.

Lastly,  under  legislation that took effect this year, the FDA has new authority to require pharmaceutical companies to implement “risk management” programs to prevent consumer drug misuse.

Medical cannabis patients have no easy remedy to the current drug testing onslaught. In the absence of dire bodily harm, malpractice suits are of no avail.  In general, pain clinics have no legal obligation to treat anyone.  They commonly require patients to sign contracts allowing them to conduct drug screening at will.  Nonetheless, patients may have good grounds to complain to their state medical boards.  This is particularly the case where they have been abandoned by their doctors after being made dependent on prescription narcotics.

The ultimate recourse is to educate doctors, many of whom remain woefully ignorant of the literature on medical marijuana and chronic pain.  At the APS convention we encountered a distinguished pain specialist from San Diego, who joked about having enjoyed the marijuana muchies with his son,  but averred that he wouldn’t let his patients use it, on the grounds that it wouldn’t be useful, and anyway smoked medicine is bad for the lungs. Like most convention attendees, he had missed the panel on medical cannabis, where Dr. Abrams had discussed the use of smokeless vaporizers.

Still,  good physicians should be open to persuasion from patients. Cynthia, a severe chronic pain patient. had frequented the same clinic for 10 years when she was confronted with a surprise urine test.  In addition to prescription opiates, she had been using medical marijuana, though her recommendation was four years out of date.   The test cost her $100  and her insurer $500 more.

On finding her positive for marijuana, her doctor informed her that she would have to reduce her cannabinoid level to zero.  After a heart-to-heart  talk, in which she explained to him how she had been able to reduce her opiate use to minimal levels thanks to medical cannabis, her doctor relented. “I feel really lucky,’ says Cynthia,  “You have to feel out the doctor. We have a special relationship.  I don’t think he plans to do this with all his patients.”

REFERENCES
[1] Lynch and Clark, “Cannabis reduces opioid dose in the treatment of chronic non-cancer pain,” Journal Pain Symptom Management, (2003) 25(6) 496-8.

[2[ Narang et al., 2008 Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy, J Pain. Mar;9(3):254-64.

From O’Shaughnessy’s, Summer 2009
To order this 52-page, all-content, no-jive publication, send $5 to p.o. box 490, Alameda, CA 94501. O’S is available in bulk to physicians, collectives, cooperatives and reform groups for $1/copy for free distribution to patients and interested citizens.