Today's post from the ever-reliable sciencedaily.com (see link below) provides yet more evidence that inhaled cannabis can be one of the few genuinely effective means of quietening neuropathic symptoms. Of course, smoking a joint is also inhaling cannabis (or at least the THC component) but many people quite understandably, can't take the smoking aspect of it and inhaling via vaporizers is for them, a better solution. The argument drags on but the more studies like this one, the more the relevant authorities will be convinced that it doesn't lead to a path of depravity and ruin. Meanwhile, savvy neuropathy patients have known this for years and regularly control their pain by means of inhaled cannabis, with no ill effects. When the moral and law-giving forces catch up we may get sensible legislation rolled out across the world.
Inhaled cannabis shown effective for diabetic neuropathy pain Date: July 20, 2015 Source: American Pain Society Summary:
Inhaled cannabis reduces diabetic neuropathy and the analgesic effect is dose-dependent, new research suggests. Researchers conducted a randomized, double-blind study evaluating 16 subjects to assess the efficacy and tolerability of inhaled cannabis for treating pain caused by diabetic peripheral neuropathy (DPN).
FULL STORY
New research reported in The Journal of Pain, published by the American Pain Society, shows that inhaled cannabis reduces diabetic neuropathy and the analgesic effect is dose-dependent.
Researchers at the University of California San Diego conducted a randomized, double-blind study evaluating 16 subjects to assess the efficacy and tolerability of inhaled cannabis for treating pain caused by diabetic peripheral neuropathy (DPN). They studied the effects of low, medium and high doses of inhaled cannabis on DPN pain and hyperalgesia. Subjects participated in four outpatient treatment sessions, separated by two weeks, in which they were exposed to placebo or three different doses of aerosol 1% THC, the most abundant and psychoactive compound in cannabis. As a drug delivery method for marijuana research, inhalation is preferred because the pharmacokinetics of inhalation are superior to smoking, as peak effects occur quickly and are more easily titrated.
DPN occurs in half of diabetes patients and 15 percent have pain, especially in the feet. Many patients do not achieve satisfactory relief from two FDA-approved treatments. Animal research in models of neuropathic pain suggest that cannabinoids may be effective in reducing pain, but no studies have focused specifically on painful DPN.
"We hypothesized that inhaled cannabis would result in a dose-dependent reduction in spontaneous and evoked pain with a concomitant effect on cognitive function," said lead author Mark S. Wallace, M.D., professor of anesthesiology, University of California San Diego School of Medicine.
Results showed there was a dose-dependent reduction in pain intensity from inhaled cannabis, which the authors noted is consistent with results of other trials of the drug for diverse neuropathic pain syndromes.
"The dose dependent analgesic effect was evident for both spontaneous and evoked pain in the trial subjects, but it was more consistent on spontaneous pain," said Wallace.
The also authors reported that all subjects experienced either euphoria or somnolence, which may limit the acceptability of cannabis as an analgesic. However, in measuring the impact of inhaled cannabis impact on cognition (attention and memory), they found modest effects with no dramatic declines or impairments.
"These findings along with previous studies suggest that cannabis might have analgesic benefit in neuropathic pain syndromes, including treatment-refractory DPN," said Wallace.
Story Source:
The above post is reprinted from materials provided by American Pain Society. Note: Materials may be edited for content and length.
Journal Reference:
Mark S. Wallace, Thomas D. Marcotte, Anya Umlauf, Ben Gouaux, Joseph H. Atkinson. Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. The Journal of Pain, 2015; 16 (7): 616 DOI: 10.1016/j.jpain.2015.03.008
http://www.sciencedaily.com/releases/2015/07/150720115147.htm
Today's post from cochrane.org (see link below) looks at the evidence supporting the use of amitriptyline as a treatment for neuropathic pain and as many other serious investigations in the past have done; has found that the drug is of very little benefit to neuropathy sufferers. Or at least, there's just not enough research and evidence to prove otherwise. Yet it is drug number one on the lists of standard treatments for nerve pain...why? It's more of a 'following the logic' sort of reasoning; you begin small and build up. Basically that predicts a trajectory ending with opiates but is of little benefit to patients. Apart from the associated side effects of taking anti-depressants, amitriptyline has not been proved to be of any significant benefit in reducing neuropathy symptoms, yet doctors routinely begin with it, in the hope that what they see as, only a very mild drug, will be enough to quell the symptoms. It's been the standard start-up drug of choice for decades; isn't it about time that the industry looked at the evidence and stopped putting us at risk from unnecessary side effects? The evidence suggests that other drugs are far better for the task but unfortunately we still have to go through the hope and ultimate failure of amitriptyline before any relief can be found by moving on to more effective treatments.
Neuropathic pain is pain coming from damaged nerves, and can have a variety of different names. Some of the more common are painful diabetic neuropathy, postherpetic neuralgia, or post-stroke pain. It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines to those used for pain from damaged tissue. Medicines such as paracetamol or ibuprofen are not usually effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain.
Amitriptyline is an antidepressant, and antidepressants are widely recommended for treating neuropathic pain. Amitriptyline is commonly used to treat neuropathic pain conditions, but an earlier review found no good quality evidence to support its use. Most studies were small, relatively old, and used methods or reported results that we now recognise as making benefits seem better than they are.
In March 2015 we performed searches to look for new studies in adults with neuropathic pain of at least moderate intensity. We found only two additional small studies that did not provide any good quality evidence for either benefit or harm. This is disappointing, but we can still make useful comments about the drug.
Amitriptyline probably does not work in neuropathic pain associated with human immunodeficiency virus (HIV) or treatments for cancer. Amitriptyline probably does work in other types of neuropathic pain, though we cannot be certain of this. Our best guess is that amitriptyline provides pain relief in about 1 in 4 (25%) more people than does placebo, and about 1 in 4 (25%) more people than placebo report having at least one adverse event, which may be troublesome, but probably not serious. We cannot trust either figure based on the information available.
The most important message is that amitriptyline probably does give really good pain relief to some people with neuropathic pain, but only a minority of them; amitriptyline will not work for most people.
Authors' conclusions:
Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all. Background:
This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.
Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.
Objectives:
To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials.
Search strategy:
We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies.
Selection criteria:
We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions.
Data collection and analysis:
We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.
Main results:
We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.
There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).
More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence).
http://www.cochrane.org/CD008242/SYMPT_amitriptyline-neuropathic-pain-adults
We've mentioned the subject of today's post from endocrinologyadvisor.com (see link below) several times already but this article explains this exciting new development in terms that almost everybody can understand. Certainly worth talking over with your doctor or specialist and maybe even getting your name onto some trial lists in your area (you may have to fight for that one). However, the idea of 8 injections per year taking away most of our pain, is a very attractive one - let's hope this is a development with real substance. Well worth a read.
Can Gene Therapy Reverse Diabetic Neuropathy?
John Schieszer, MA July 24, 2015 A nonviral gene therapy may relieve symptoms of painful diabetic neuropathy.
Gene therapy in the form of a plasmid containing two human hepatocyte growth factor isoforms administered via intramuscular injection may alleviate symptoms and improve quality of life in patients with painful diabetic neuropathy.
In addition, the plasmid —VM202 — may be particularly beneficial in those patients not taking gabapentin or pregabalin, according to researchers at Northwestern University.
In a recently completed double-blind, placebo-controlled study, 84 patients were randomly assigned to receive injections of 8 mg or 16 mg of VM202 per leg (calf muscles and lower leg) or placebo, with doses administered on days 0 and 14.
At 3 months, patients in the low-dose group experienced a significant reduction in pain compared with the placebo group, the researchers found.1
“I am very excited about it. This is an enormous problem, and it has a huge impact on people's lives. [These patients] spend so much time in agony,” said study investigator Jack Kessler, MD, who is a professor in the department of neurology at Northwestern University Feinberg School of Medicine in Chicago.
“The data are very, very strong. One issue that remains to be resolved is if we are modifying the disease, and at this time, the jury is still out. In our last study, we had some improvement in patients to feel light stimuli, but we need additional data to say we are altering the course of the disease. If our phase 3 study gives us the same results, then this treatment will be the best option for treating diabetic neuropathy.”
Study Results
The primary outcome for this current study was change in the mean pain score measured by a 7-day pain diary. The analysis also included quality of life and pain measures, and measurement of intraepidermal nerve fiber density, according to Kessler.
The study showed that patients receiving 8 mg of VM202 per leg improved the most in all efficacy measures, including a significant reduction at 3 months in the mean pain score. The reductions in pain continued but were not statistically significant at 6 and 9 months.
“We would probably inject patients four times a year. If it turns out that we are actually making the neuropathy better, then it is reason to think patients would graduate from this, but if it turns out we are just treating the symptoms and not the disease, then we would see injecting the patients four times a year,” Kessler said in an interview with Endocrinology Advisor.
The mean age of the patients in this study was 60 years (approximately 75% men), and the mean duration of diabetes was 15 to 16 years.
The researchers found that 48% of the patients experienced at least a 50% reduction in pain in the treated group compared with 17% in the placebo group. The study also demonstrated significant improvements in the brief pain inventory and the questionnaire portion of the Michigan Neuropathy Screening Instrument.
The researchers noted that the largest reductions in pain were found among patients not on pregabalin or gabapentin.
There were no significant adverse events attributable to VM202 and this treatment was deemed safe and well tolerated.
More to Learn
It is hoped that VM202, which contains a human hepatocyte growth factor gene, will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and subsequently reduce the pain.
“We believe we are getting a two-for-one treatment. We are supplying nourishment to the nerves, but we are also helping to improve blood vessel function,” said Kessler. “The most remarkable thing is that we pushed the dose up and we had literally not one serious side effect in the entire trial, only [injection] site soreness.”
A large trial is now planned, and the researchers hope to enroll 475 patients at 20 sites across the United States starting in December.
Amanda Peltier, MD, who is an assistant professor of neurology at Vanderbilt University in Nashville, Tennessee, said these study findings are interesting, and this approach could represent a new way of treating diabetic neuropathy with fewer treatment-related adverse effects.
“There is a huge unmet need for diabetic neuropathy as the current medicines have side effects and do nothing to improve or retard the progression of the underlying neuropathy, only treat the pain. In addition, our understanding of diabetic neuropathy has improved for type 1 diabetes, but there has been little headway in improving neuropathy for patients with type 2 diabetes,” Peltier told Endocrinology Advisor.
Looking Ahead
According to M. Sue Kirkman, MD, who is a clinical professor of medicine and the medical director of the Diabetes Care Center Clinical Trials Unit at the University of North Carolina School of Medicine in Chapel Hill, this is a quality of life issue.
Although there are several medications that may help symptoms, they are not effective in all patients and may come with significant side effects, Kirkman said.
“This trial showed promising results, but was relatively small and short-term. Larger and longer-term trials will be important to see if the benefits pan out, and also to get a better feel for potential adverse events. Up to now, treatments for diabetic neuropathy have been purely palliative, with no interventions that seem capable of actually improving nerve function,” Kirkman told Endocrinology Advisor.
“There are some hints from this study that this agent could actually improve nerve function. If that pans out in larger trials, it would be very exciting, since lack of feeling in the feet from advanced diabetic neuropathy is a risk factor for foot ulcers and amputations.”
Reference
Kessler JA et al. Ann Clin Transl Neurol. 2015;2(5):465-478.
http://www.endocrinologyadvisor.com/diabetes/painful-diabetic-neuropathy-gene-therapy/article/428342/
