Sunil K. Aggarwal

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-α] 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.

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.

Prospectively Surveying Health-Related Quality of Life and Symptom Relief in a Lot- Based Sample of Medical Cannabis-Using Patients in Urban Washington State Reveals Managed Chronic Illness and Debility

Objectives: To characterize health-related quality of life (HRQoL) in medical cannabis patients. Methods: Short Form 36 (SF-36) Physical Health Component Score and Mental Health Component Score (MCS) surveys as well has CDC (Centers for Disease Control) HRQoL-14 surveys were completed by 37 qualified patients. Results: Mean SF-36 PCS and MCS, normalized at 50, were 37.4 and 44.2, respectively. Eighty percent of participants reported activity/functional limitations secondary to impairments or health problems. Patients reported using medical cannabis to treat a wide array of symptoms across multiple body systems with relief ratings consistently in the 7-10/10 range. Conclusion: The HRQoL results in this sample of medical cannabis-using patients are comparable with published norms in other chronically ill populations. Data presented provide insight into medical cannabis-using patients’ self-rated health, HRQoL, disease incidences, and cannabis-related symptom relief.

Clearing the air: What the latest Supreme Court decision regarding medical marijuana really means

handed down its 6-3 decision against Angel Raich and Diane Monson.1 The Court ruled that the federal government can prohibit even intrastate and noncommercial marijuana possession and cultivation under the rubric of “interstate commerce.” In the prior Supreme Court ruling, United States vs. the Oakland Cannabis Buyers’ Cooperative,2 the Court ruled that “medical necessity” is not a legal defense for the possession, manufacture, or distribution of marijuana, and that the federal law classifying marijuana as illegal has no exemption for ill patients. Although the latest decision did not address medical necessity or due process arguments, Justice Stevens, who wrote the majority opinion, did add at the end of Section I, “The case is made difficult by respondents’ strong arguments that they will suffer irreparable harm because, despite a congressional finding to the contrary, marijuana does have valid therapeutic purposes.”3 One week after the Supreme Court ruling, the US House of Representatives rejected an amendment prohibiting the federal government from undermining state medical marijuana laws. However, the bill received 13 more votes than last year, indicating growing support for patients. The Supreme Court ruling and the subsequent defeat in Congress brought much angst to many ill people currently using medical marijuana. Fortunately, for those living in states that allow the use of medical marijuana, this ruling does not overturn state law. Nearly all of the roughly 750,000 annual marijuana arrests in the United States are made by state and local officials. States are not required to have laws that are identical to federal law nor are they required to enforce federal laws. California Attorney General Bill Lockyer plainly stated this in a recent statement from his office: “The federal government cannot force state officials to enforce federal laws.”4 Although federal authorities retain the power to target patients and providers, state lawmakers should redouble their efforts to move forward with legislation to protect patients from arrest and jail. In addition, states without medical marijuana laws are still free to enact them. Following the

Distress, Coping, and Drug Law Enforcement in a Series of Patients Using Medical Cannabis

Abstract Patients using medical cannabis in the United States inhabit a conflicting medicolegal space. This study presents data from a dispensary-based survey of patients using medical cannabis in the state of Washington regarding cannabis-specific health behaviors, levels of psychological distress, stress regarding marijuana criminality, past experiences with drug law enforcement, and coping behaviors. Thirty-seven subjects were enrolled in this study, and all but three completed survey materials. The median index of psychological distress, as measured by the Behavioral Symptom Inventory, was nearly 2.5 times higher than that found in a general population sample but one third less than that found in an outpatient sample. The subjects reported a moderate amount of stress related to the criminality of marijuana, with 76% reporting previous exposure to 119 separate drug law enforcement tactics in total. The subjects reported a wide range of coping methods, and their responses to a modified standardized survey showed the confounding influence of legality in assessing substance-related disorders.

Medical marijuana for failed back surgical syndrome: a viable option for pain control or an uncontrolled narcotic?

M.J. is a 54-year-old woman with diffuse low back and bilateral leg pain. She has had 4 spinal surgeries over the past 12 years for her pain, including 2 laminectomies at L4-L5 and L5-S1, a fusion from L4-L5 to the sacrum, and a subsequent revision from L3 to the sacrum. The first surgery provided her 4 years of relief, but all other surgeries resulted in no measurable relief. Various interventional treatments have failed to help, including a spinal cord stimulator trial. She has no focal weakness on lower limb examination but has some subjective numbness in her lower extremities bilaterally and is areflexic in the Achilles tendon bilaterally. She sees a pain psychologist weekly for sessions that include pain coping skills and biofeedback. She denies any depression and scores well on standardized depression inventories. The apparent lack of depression may be due to the psychoaffective effects of opioids; she currently takes scheduled sustained release oxycodone 40 mg every 12 hours, with occasional oxycodone for breakthrough pain control. However, she believes that thesemedications only partially control her pain. She has had routine urine drug screens that show compliance with the treatment regimen. She has heard of people taking medical marijuana for pain control and wonders if that will be a viable option for her instead of escalating the dose of opioids. Sunil K. Aggarwal, MD, PhD, and Gregory Carter, MD, MS, will argue that medical marijuana is an appropriate treatment for this patient, and Sanjog Pangarkar, MD, Mark Miedema, MD, and Bianca Tribuzio, DO, will argue that medical marijuana is not a viable option for this patient.

Medicalization of marijuana.

Medicalization of Marijuana To the Editor In their Viewpoint, Drs Wilkinson and D’Souza1 expressed their opinion that cannabis should not be allowed for medical use. Their overarching argument was that cannabis has not been adequately studied or approved by the US Food and Drug Administration and is not administered like other drugs manufactured by pharmaceutical companies. We disagree with their claims about the investigations into the safety and efficacy of cannabis. Wilkinson and D’Souza claimed that “the relative lack of controlled clinical trial data makes finding the appropriate dose even more challenging.”1 However, to date, there have been more than 110 controlled clinical trials of cannabis and cannabinoids assessing more than 6100 patients,2 including clinical trials conducted by the Center for Medicinal Cannabis Research at the University of California. Summarizing their findings, Director Igor Grant, MD, concluded that “it is not accurate that cannabis has no medical value, or that information on safety is lacking.”3 Cannabis is one of the most studied biologically active substances. A search on PubMed using the term marijuana yields nearly 20 000 scientific articles referencing the plant or its constituents. In comparison, a key word search using the term Tylenol yields 17 495 publications; Ritalin, 7061; and hydrocodone, 645. Wilkinson and D’Souza also claimed that “there is an increasing perception, paralleling trends in legalization, that marijuana is not associated with significant or lasting harm.”1 However, examining one often-cited potential harm, a study of more than 5000 men and women followed up for 20 years concluded that “occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.”4 The opinions of Wilkinson and D’Souza do not reflect the modern view of cannabis therapeutics. Indeed, thanks to medicalization, research is progressing, patients are finding relief, and, increasingly, physicians are looking to cannabis as a viable treatment option.5