Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice.

“The use of cannabis for medical purposes has been recently legalised in many countries including the Czech Republic. As a result, there is increased interest on the part of physicians and patients in many aspects of its application. This mini review briefly covers the main active substances of the cannabis plant and mechanisms of action. It focuses on two conditions, cancer pain and spasticity in multiple sclerosis, where its effects are well-documented. A comprehensive overview of a few cannabis-based products and the basic pharmacokinetics of marijuana’s constituents follows. The review concludes with an outline for preparing cannabis (dried inflorescence) containing drug dosage forms that can be produced in a hospital pharmacy.”

Medical marijuana laws and adolescent marijuana use in the United States: A systematic review and meta‐analysis

Addiction banner

“Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. In summary, current evidence does not support the hypothesis that MML passage is associated with increased marijuana use prevalence among adolescents in states that have passed such laws up until 2014.”  https://onlinelibrary.wiley.com/doi/full/10.1111/add.14136

“Medical Marijuana Hasn’t Affected Teen Pot Use: Meta-Analysis. Medical marijuana laws have had little impact on recreational pot use among U.S. teens, according to a meta-analysis of 11 studies dating back to 1991. The findings appear to debunk claims by opponents of medical marijuana that the laws have led to greater cannabis use among adolescents, wrote researcher Deborah Hasin, PhD, of Columbia University’s Mailman School of Public Health, New York City, and colleagues in the journal Addiction.”  https://www.medpagetoday.com/psychiatry/addictions/71342

Marijuana use and mortality following orthopedic surgical procedures.

Publication Cover

“The association between marijuana use and surgical procedures is a matter of increasing societal relevance that has not been well studied in the literature.

The primary aim of this study is to evaluate the relationship between marijuana use and in-hospital mortality, as well as to assess associated comorbidities in patients undergoing commonly billed orthopedic surgeries.

METHODS:

The National Inpatient Sample (NIS) database from 2010 to 2014 was used to determine the odds ratios for the associations between marijuana use and in-hospital mortality, heart failure (HF), stroke, and cardiac disease (CD) in patients undergoing five common orthopedic procedures: hip (THA), knee (TKA), and shoulder arthroplasty (TSA), spinal fusion, and traumatic femur fracture fixation.

RESULTS:

Of 9,561,963 patients who underwent one of the five selected procedures in the four-year period, 26,416 (0.28%) were identified with a diagnosis of marijuana use disorder. In hip and knee arthroplasty patients, marijuana use was associated with decreased odds of mortality compared to no marijuana use (p<0.0001), and increased odds of HF (p = 0.018), stroke (p = 0.0068), and CD (p = 0.0123). Traumatic femur fixation patients had the highest prevalence of marijuana use (0.70%), which was associated with decreased odds of mortality (p = 0.0483), HF (p = 0.0076), and CD (p = 0.0003). For spinal fusions, marijuana use was associated with increased odds of stroke (p<0.0001) and CD (p<0.0001). Marijuana use in patients undergoing shoulder arthroplasty was associated with decreased odds of mortality (p<0.001) and stroke (p<0.001).

CONCLUSIONS:

In this study, marijuana use was associated with decreased mortality in patients undergoing THA, TKA, TSA and traumatic femur fixation, although the significance of these findings remains unclear. More research is needed to provide insight into these associations in a growing surgical population.”

https://www.ncbi.nlm.nih.gov/pubmed/29558287

https://www.tandfonline.com/doi/abs/10.1080/08897077.2018.1449054?journalCode=wsub20

Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System.

ijms-logo

“The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/29533978

http://www.mdpi.com/1422-0067/19/3/833

Clinical response to Nabiximols correlates with the down-regulation of immune pathways in Multiple Sclerosis.

European Journal of Neurology

“Nabiximols (Sativex® ) is a cannabinoid-based compound used for the treatment of moderate to severe spasticity in multiple sclerosis (MS).

The aim of the study is to investigate the effect of the administration of Nabiximols on blood transcriptome profile of MS patients and to interpret it in the context of pathways and networks.

Our findings support the immunomodulatory activity of cannabinoids in MS patients. Further studies in more specific cell types are needed to refine these results.”

https://www.ncbi.nlm.nih.gov/pubmed/29528549

http://onlinelibrary.wiley.com/doi/10.1111/ene.13623/abstract

Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29512125
Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/

Cannabis Vaporizer Combines Efficient Delivery of THC with Effective Suppression of Pyrolytic Compounds

Publication Cover

“Cannabis vaporization is a technology designed to deliver inhaled cannabinoids while avoiding the respiratory hazards of smoking by heating cannabis to a temperature where therapeutically active cannabinoid vapors are produced, but below the point of combustion where noxious pyrolytic byproducts are formed.

This study was designed to evaluate the efficacy of an herbal vaporizer known as the Volcano®, produced by Storz & Bickel GmbH&Co. KG, Tuttlingen, Germany. Three 200 mg samples of standard NIDA cannabis were vaporized at temperatures of 155°–218°C. For comparison, smoke from combusted samples was also tested.

The study consisted of two phases: (1) a quantitative analysis of the solid phase of the vapor using HPLC-DAD-MS (High Performance Liquid Chromatograph-Diode Array-Mass Spectrometry) to determine the amount of cannabinoids delivered; (2) a GC/MS (Gas Chromatograph/ Mass Spectrometer) analysis of the gas phase to analyze the vapor for a wide range of toxins, focusing on pyrene and other polynuculear aromatic hydrocarbons (PAHs).

The HPLC analysis of the vapor found that the Volcano delivered 36%–61% of the THC in the sample, a delivery efficiency that compares favorably to that of marijuana cigarettes.

The GC/MS analysis showed that the gas phase of the vapor consisted overwhelmingly of cannabinoids, with trace amounts of three other compounds. In contrast, over 111 compounds were identified in the combusted smoke, including several known PAHs.

The results indicate that vaporization can deliver therapeutic doses of cannabinoids with a drastic reduction in pyrolytic smoke compounds. Vaporization therefore appears to be an attractive alternative to smoked marijuana for future medical cannabis studies.”

https://www.tandfonline.com/doi/abs/10.1300/J175v04n01_02

Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

Current Protocols in Toxicology

“Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one’s ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE.”

https://www.ncbi.nlm.nih.gov/pubmed/29512125

http://onlinelibrary.wiley.com/doi/10.1002/cptx.43/abstract

Marijuana Use and Renal Function Among US Adults.

The American Journal of Medicine Home

“In recent years, the number of states that have legalized medical marijuana or retail sales has increased, bringing potential changes of marijuana use pattern among the general population. However, health effects of acute and chronic marijuana use on many relevant health outcomes, including renal function, remain largely unexamined.

In this study, we aimed to assess the association between recent and past marijuana use and renal function.

CONCLUSIONS:

We did not observe any clinically significant association between current or past self-reported marijuana use and measures of kidney function.”

https://www.ncbi.nlm.nih.gov/pubmed/29291894

http://www.amjmed.com/article/S0002-9343(17)31193-2/fulltext

“No link between current or previous marijuana use and kidney disease, say researchers” https://www.sciencedaily.com/releases/2018/03/180301125051.htm

“Marijuana Doesn’t Seem to Harm the Kidneys” https://www.webmd.com/mental-health/addiction/news/20180306/marijuana-doesnt-seem-to-harm-the-kidneys

“”Our research provides some reassuring evidence suggesting that there is no detrimental effect of infrequent, relatively light use of marijuana on kidney function among healthy adults under age 60,”” https://consumer.healthday.com/general-health-information-16/illicit-drugs-news-217/marijuana-doesn-t-seem-to-harm-the-kidneys-731632.html

“Pot Won’t Harm Healthy Young People’s Kidneys, Study Suggests”  https://www.medicinenet.com/script/main/art.asp?articlekey=206375

Toxicity, Cannabinoids.

Cover of StatPearls

“Cannabinoids are a collective group of compounds that act on cannabinoid receptors. They include plant-derived phytocannabinoids, synthetic cannabinoids, and endogenously-derived endocannabinoids. The primary source of cannabinoid toxicity is from plant-derived cannabinoids and synthetic cannabinoids. These agents act as cannabinoid receptor agonists. More than 60 naturally occurring cannabinoids are found in the Sativa and Indica species of Cannabis, with delta-9 tetrahydrocannabinol (THC) being the main psychoactive compound. Other naturally occurring cannabinoids include cannabidiol and cannabinol. Marijuana is the most common colloquial name for crushed, dried leaves and flowers of the Cannabis plant. In recent years, there have been many reports of marijuana toxicity, primarily in the pediatric population, as medical and recreational marijuana has been legalized. The terms phytocannabinoids, marijuana and cannabis are used interchangeably. Synthetic cannabinoids were created for therapeutic and research purposes; however, despite legal efforts to limit their availability, synthetic cannabinoids have become an increasingly common drug of abuse, sold under various street names such as K2, Spice, and Black Mamba. Synthetic cannabinoids are associated with much more morbidity and mortality than the phytocannabinoids. Prescription preparations for medical usage include dronabinol, or pure THC, nabilone, a synthetic cannabinoid, and cannabidiol (CBD). Pharmaceutical use of cannabinoids is an ongoing field of research.”

https://www.ncbi.nlm.nih.gov/pubmed/29489164

https://www.ncbi.nlm.nih.gov/books/NBK482175/

Effect of marijuana on Essential Tremor: A case report

MDS Abstracts

“Objective: Examine the effectiveness of THC marijuana versus non-THC marijuana on handwriting in Essential Tremor.

Background: Essential tremor (ET) is a chronic movement disorder which can be quite debilitating. ET is often progressive, beginning as a mild visible tremor with little or no impact on activities of daily living (ADLs) but tends to increase in severity over the course of years, often to the extent that people with ET may have extreme difficulty with task such as writing, drinking, eating, shaving, or putting on make-up. Unfortunately, a certain portion of people with ET are either intolerant or unresponsive to the currently recommended treatments. Patients occasionally report improvement in ET after marijuana use. While reports exist of THC effect on tremor in patients with Multiple Sclerosis (MS) and Parkinson’s disease (PD), the same is not true for ET.

Methods: Case Report.

Results: Patient JB, a retired psychologist, had long-standing severe familial tremor significantly interfering with ADLs. Standard treatments were tried. Primidone was partially effective, but resulted in erectile dysfunction and anorgasmia. Propranolol was mildly effective, but was switched to metoprolol by his cardiologist. Gabapentin was ineffective and caused GI distress. Topiramate was ineffective. Diazepam and alcohol were effective but used only occasionally due to sedating effects. While on a family vacation in a state with legalized marijuana, JB recorded his handwriting at baseline, after using an oral non-THC marijuana derivative, after using standard marijuana (oral), and after using alcohol. Handwriting was moderately improved after taking the THC preparation, as well as after taking alcohol; the improvement was roughly equivalent with these two treatments. It did not improve with the non-THC preparation.

Conclusions: This case report suggests 1) handwriting in ET may be improved with the use of THC, 2) handwriting in ET may not be improved with non-THC derivatives of marijuana, and 3) the effect of THC in this case was similar to that of alcohol. While there have been several small studies and case reports addressing the efficacy of marijuana in controlling tremor in PD and MS, no such studies have been conducted regarding ET and the use of marijuana and its derivatives for control of ET is currently considered category U due to insufficient evidence. Further investigation of the potential efficacy of marijuana for ET is clearly warranted.” http://www.mdsabstracts.org/abstract/effect-of-marijuana-on-essential-tremor-a-case-report/

Effect of marijuana on Essential Tremor: A case report

Marijuana May Improve Essential Tremor and Parkinson’s”  http://parkinsonsclinic.com/1/post/2016/05/marijuana-may-improve-essential-tremor-and-parkinsons.html