ALSUntangled # 69: astaxanthin.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review astaxanthin which has plausible mechanisms for slowing ALS progression including antioxidant, anti-inflammatory, and anti-apoptotic effects. While there are no ALS-specific pre-clinical studies, one verified "ALS reversal" occurred in a person using a combination of alternative therapies which included astaxanthin. There have been no trials of astaxanthin in people living with ALS. Natural astaxanthin appears to be safe and inexpensive. Based on the above information, we support further pre-clinical and/or clinical trials of astaxanthin in disease models and PALS, respectively, to further elucidate efficacy.

ALSUntangled #68: ozone therapy.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review ozone therapy. Ozone therapy has possible mechanisms for slowing ALS progression based on its antioxidant, anti-inflammatory, and mitochondrial effects. A non-peer-reviewed report suggests that ozone treatment may slow progression in a mTDP-43 mouse model of ALS. One verified "ALS reversal" occurred on a cocktail of alternative treatments including ozone. There are no ALS trials using ozone to treat PALS. There can be potentially serious side effects associated with ozone therapy, depending on the dose. Based on the above information, we support an investigation of ozone therapy in ALS cell or animal models but cannot yet recommend it as a treatment in PALS.

Medicinal Cannabis: A Survey Among Health Care Providers in Washington State

INTRODUCTION: Washington State allows marijuana use for medical (since 1998) and recreational (since 2012) purposes. The benefits of medicinal cannabis (MC) can be maximized if clinicians educate patients about dosing, routes of administration, side effects, and plant composition. However, little is known about clinicians' knowledge and practices in Washington State. METHODS: An anonymous online survey assessed providers' MC knowledge, beliefs, clinical practices, and training needs. The survey was disseminated through health care providers' professional organizations in Washington State. Descriptive analysis compared providers who had and had not authorized MC for patients. Survey results informed the approach and content of an online training on best clinical practices of MC. RESULTS: Four hundred ninety-four health care providers responded to the survey. Approximately two-third were women, aged 30 to 60 years, and working in family or internal medicine. More than half of the respondents were legally allowed to write MC authorizations per Washington State law, and 27% of those had issued written MC authorizations. Overall, respondents reported low knowledge and comfort level related to recommending MC. Respondents rated MC knowledge as important and supported inclusion of MC training in medical/health provider curriculum. Most Washington State providers have not received education on scientific basis of MC or training on best clinical practices of MC. Clinicians who had issued MC authorizations were more likely to have received MC training than those who had not issued MC authorization. DISCUSSION: The potential of MCs to benefit some patients is hindered by the lack of comfort of clinicians to recommend it. Training opportunities are badly needed to address these issues.

Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis.

Given the severity of their illness and lack of effective disease-modifying agents, it is not surprising that most patients with amyotrophic lateral sclerosis (ALS) consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation, and energy healing. This article reviews these in detail. The authors also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy, and shared decision making. Finally, the authors review a program called ALSUntangled, which uses shared decision making to review alternative therapies for ALS.

Pilot Randomized Trial Comparing Intersession Scheduling of Biofeedback Results to Individuals with Chronic Pain: Influence on Psychologic Function and Pain Intensity.

OBJECTIVE: The objective of this study was to compare the effectiveness of two biofeedback schedules on long-term improvement in physical and psychologic reactivity to chronic nonmalignant pain. DESIGN: This study is a prospective, randomized pilot trial. METHODS: Twenty adults with chronic pain engaged in heart rate variability (HRV) biofeedback training for nine sessions with HRV presented visually. Two groups, formed by random assignment, were compared: The faded feedback group received concurrent visual HRV biofeedback in session 1, with the amount of biofeedback systematically reduced for ensuing sessions so that, by session 9, the participants were controlling HRV without external feedback. The full feedback group received visual HRV biofeedback continuously across all sessions. Outcome measures assessed at baseline, immediately after the program, and 3 mos after the program included pain intensity, fear-avoidance beliefs, and self-report physical functioning. Use of biofeedback skills was also assessed 3 mos after the program. Nominal variables were analyzed with χ. Continuous measures were analyzed with repeated-measures analyses of variance. RESULTS: The faded feedback schedule resulted in greater use of biofeedback skills at 3 mos and improved pain intensity and fear-avoidance beliefs after the program and at 3 mos. Physical functioning did not differ between groups. CONCLUSIONS: Systematically reducing the frequency of external visual feedback during HRV biofeedback training was associated with reduced reactivity to chronic pain. Results of this pilot study should be confirmed with a larger randomized study.

Re-branding cannabis: the next generation of chronic pain medicine?

The field of pain medicine is at a crossroads given the epidemic of addiction and overdose deaths from prescription opioids. Cannabis and its active ingredients, cannabinoids, are a much safer therapeutic option. Despite being slowed by legal restrictions and stigma, research continues to show that when used appropriately, cannabis is safe and effective for many forms of chronic pain and other conditions, and has no overdose levels. Current literature indicates many chronic pain patients could be treated with cannabis alone or with lower doses of opioids. To make progress, cannabis needs to be re-branded as a legitimate medicine and rescheduled to a more pharmacologically justifiable class of compounds. This paper discusses the data supporting re-branding and rescheduling of cannabis.

Pain location and functioning in persons with spinal cord injury.

BACKGROUND: The influence of pain location and extent on functioning in persons with spinal cord injury (SCI) and chronic pain is not well understood. OBJECTIVE: To investigate the correlations between pain location and extent to determine which pain domains may be important to assess and potentially target in treating chronic pain in SCI populations. DESIGN: Prospective, observational study. SETTING: University medical center. PARTICIPANTS: A total of 259 persons with an SCI and chronic pain. METHODS: Postal mail survey questionnaire. MAIN OUTCOME MEASUREMENTS: Pain sites, pain extent (number of sites), pain intensity in specific body locations, pain interference, and physical and psychological functioning. RESULTS: A positive association between pain extent and intensity with pain interference (r = 0.33, P < .01) and a negative association with psychological functioning were noted in the study sample (r = -0.21, P < .01). Pain intensity in the lower back and legs (r = 0.55, P < .01) and a number of other sites showed strong associations with patient functioning. Correlation with psychological functioning was significant but weaker (r = -0.22, P < .01 for the lower back and legs). Ambulatory status had only a small moderating effect on the associations between pain intensity in specific sites and pain interference and no effect on psychological functioning. CONCLUSIONS: The findings support the importance of assessing pain intensity at specific locations as a part of a thorough evaluation of chronic pain, as well as the importance of addressing pain at multiple sites, when managing pain in persons with an SCI.

From 32 ounces to zero: a medical geographic study of dispensing a cultivated batch of "plum" cannabis flowers to medical marijuana patients in Washington State.

The medicinal use of cannabis is a growing phenomenon in the U.S. predicated on the success of overcoming specific spatial challenges and establishing particular human-environment relationships. This article takes a medical geographic "snapshot" of an urban site in Washington State where qualifying chronically ill and debilitated patients are delivered locally produced botanical cannabis for medical use. Using interview, survey, and observation, this medical geographic research project collected information on the social space of the particular delivery site and tracked the production cost, reach, and health value of a 32-ounce batch of strain-specific medical cannabis named "Plum" dispensed over a four-day period. A convenience sample of 37 qualifying patients delivered this batch of cannabis botanical medicine was recruited and prospectively studied with survey instruments. Results provide insight into patients' self-rated health, human-plant relationships, and travel-to-clinic distances. An overall systematic geographic understanding of the medical cannabis delivery system gives a grounded understanding of the lengths that patients and care providers go, despite multiple hurdles, to receive and deliver treatment with botanical cannabis that relieves diverse symptoms and improves health-related quality-of-life.

Considerations for neuropathic pain conditions in life care planning.

Significant progress has been made in assessing and managing neuropathic pain. Newer, more effective treatments with minimal side effects are available. Despite advances in treatments, neuropathic pain remains a multifaceted phenomenon that can be difficult to alleviate. Diagnosis, mechanisms of injury, and treatment recommendations are critical components of life care plans for patients with neuropathic pain. A clear understanding of the underlying issues and careful coordination with neurologists and other treatment providers are key to providing optimal life care plans. Understanding that pain treatments vary over time and by individual patient is integral to comprehensive life care planning.

Cannabis in palliative medicine: improving care and reducing opioid-related morbidity.

Unlike hospice, long-term drug safety is an important issue in palliative medicine. Opioids may produce significant morbidity. Cannabis is a safer alternative with broad applicability for palliative care. Yet the Drug Enforcement Agency (DEA) classifies cannabis as Schedule I (dangerous, without medical uses). Dronabinol, a Schedule III prescription drug, is 100% tetrahydrocannabinol (THC), the most psychoactive ingredient in cannabis. Cannabis contains 20% THC or less but has other therapeutic cannabinoids, all working together to produce therapeutic effects. As palliative medicine grows, so does the need to reclassify cannabis. This article provides an evidence-based overview and comparison of cannabis and opioids. Using this foundation, an argument is made for reclassifying cannabis in the context of improving palliative care and reducing opioid-related morbidity.

Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials.

Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS), yet this has not translated into any greatly effective therapies. It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen, including glutamate antagonists, antioxidants, a centrally acting anti-inflammatory agent, microglial cell modulators (including tumor necrosis factor alpha [TNF-alpha] inhibitors), an antiapoptotic agent, 1 or more neurotrophic growth factors, and a mitochondrial function-enhancing agent would be required to comprehensively address the known pathophysiology of ALS. Remarkably, cannabis appears to have activity in all of those areas. Preclinical data indicate that cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 ALS mouse, this has translated to prolonged neuronal cell survival, delayed onset, and slower progression of the disease. Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction. With respect to the treatment of ALS, from both a disease modifying and symptom management viewpoint, clinical trials with cannabis are the next logical step. Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending life expectancy and substantially reducing the overall burden of the disease.

Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State.

OBJECTIVES: This study was conducted to better understand the characteristics of chronic pain patients seeking treatment with medicinal cannabis (MC). DESIGN: Retrospective chart reviews of 139 patients (87 males, median age 47 years; 52 females, median age 48 years); all were legally qualified for MC use in Washington State. SETTING: Regional pain clinic staffed by university faculty. INCLUSION CRITERIA: age 18 years and older; having legally accessed MC treatment, with valid documentation in their medical records. All data were de-identified. MAIN OUTCOME MEASURES: Records were scored for multiple indicators, including time since initial MC authorization, qualifying condition(s), McGill Pain score, functional status, use of other analgesic modalities, including opioids, and patterns of use over time. RESULTS: Of 139 patients, 15 (11 percent) had prior authorizations for MC before seeking care in this clinic. The sample contained 236.4 patient-years of authorized MC use. Time of authorized use ranged from 11 days to 8.31 years (median of 1.12 years). Most patients were male (63 percent) yet female patients averaged 0.18 years longer authorized use. There were no other gender-specific trends or factors. Most patients (n = 123, 88 percent) had more than one pain syndrome present. Myofascial pain syndrome was the most common diagnosis (n = 114, 82 percent), followed by neuropathic pain (n = 89, 64 percent), discogenic back pain (n = 72, 51.7 percent), and osteoarthritis (n = 37, 26.6 percent). Other diagnoses included diabetic neuropathy, central pain syndrome, phantom pain, spinal cord injury, fibromyalgia, rheumatoid arthritis, HIV neuropathy, visceral pain, and malignant pain. In 51 (37 percent) patients, there were documented instances of major hurdles related to accessing MC, including prior physicians unwilling to authorize use, legal problems related to MC use, and difficulties in finding an affordable and consistent supply of MC. CONCLUSIONS: Data indicate that males and females access MC at approximately the same rate, with similar median authorization times. Although the majority of patient records documented significant symptom alleviation with MC, major treatment access and delivery barriers remain.

Medicinal use of cannabis in the United States: historical perspectives, current trends, and future directions.

Cannabis (marijuana) has been used for medicinal purposes for millennia, said to be first noted by the Chinese in c. 2737 BCE. Medicinal cannabis arrived in the United States much later, burdened with a remarkably checkered, yet colorful, history. Despite early robust use, after the advent of opioids and aspirin, medicinal cannabis use faded. Cannabis was criminalized in the United States in 1937, against the advice of the American Medical Association submitted on record to Congress. The past few decades have seen renewed interest in medicinal cannabis, with the National Institutes of Health, the Institute of Medicine, and the American College of Physicians, all issuing statements of support for further research and development. The recently discovered endocannabinoid system has greatly increased our understanding of the actions of exogenous cannabis. Endocannabinoids appear to control pain, muscle tone, mood state, appetite, and inflammation, among other effects. Cannabis contains more than 100 different cannabinoids and has the capacity for analgesia through neuromodulation in ascending and descending pain pathways, neuroprotection, and anti-inflammatory mechanisms. This article reviews the current and emerging research on the physiological mechanisms of cannabinoids and their applications in managing chronic pain, muscle spasticity, cachexia, and other debilitating problems.

Charcot-Marie-Tooth disease.

The family of hereditary peripheral neuropathies that makes up Charcot-Marie-Tooth disease (CMT) comprises some of the most common neuromuscular disorders. Over the past decade, understanding of the molecular basis of CMT has increased enormously. In addition, the neurophysiologic deficits and clinical problems associated with CMT are more clearly delineated, and the precise genetic cause of many types of CMT has now been determined. Advances in molecular biology and genetic manipulation techniques have allowed the development of animal models of some of these CMT types, allowing more productive scientific exploration of possible treatments. Recent treatment advances that have been effective in animal models include oral supplementation with curcumin and vitamin C (ascorbic acid), and the use of onapristone, a progesterone antagonist. Human trials with vitamin C are currently in progress. While ongoing molecular genetic research continues to identify more of the mutant genes and proteins that cause the various disease subtypes, clinical research should continue to focus on developing pharmaceutical and rehabilitative therapies to ameliorate nerve degeneration and ultimately improve function for patients with CMT. These patients optimally should be managed in a comprehensive, multidisciplinary setting involving neurologists, physiatrists, orthopedic surgeons, physical and occupational therapists, and orthotists. Treatment should be aimed at maximizing independence and quality of life.

Iatrogenic axillary neuropathy after intramuscular injection of the deltoid muscle.

A previously healthy 26-yr-old male presented for an electrodiagnostic evaluation with complaints of significant right deltoid muscle atrophy and shoulder abduction weakness after receiving an intramuscular (IM) deltoid injection of an antiemetic 4 wk earlier. Electrodiagnostic evaluation confirmed an acute axillary neuropathy. We hypothesize that direct mechanical trauma to the anterior branch of the axillary nerve resulted in axillary mononeuropathy with axonal loss, although chemically induced nerve injury cannot be excluded. Injections in and about the shoulder complex are performed routinely for the purposes of vaccination, IM medication administration, deltoid trigger-point injections, and intra-articular and bursal steroid injections. Although such injections are considered routine office procedures, there is increased risk of neurovascular injury if they are performed incorrectly. The purpose of this brief report is to make practitioners aware of the potential for axillary neuropathy with such procedures, to review the salient anatomy, and to propose a potential guideline for clinical practice to minimize iatrogenic axillary neuropathy.