Hypothesizing that marijuana smokers are at a significantly lower risk of carcinogenicity relative to tobacco-non-marijuana smokers: evidenced based on statistical reevaluation of current literature.

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“A hypothetical link between marijuana smoking and cancer has been established based on a number of misleading assumptions. However, recent studies tend to suggest, if anything, an inverse association between marijuana use and cancers.

To test the hypothesis that marijuana smoking significantly lowers the risk of developing cancer in humans, we analyzed published data from a prospective cohort study on cancer incidence among nonsmokers (NS), marijuana-only smokers (MS), tobacco-only smokers (TS), and marijuana and tobacco smokers (MTS).

Using the log linear model to calculate the probability of developing each cancer form as a function of the interaction between marijuana and tobacco smoking, as well as functions of marijuana and tobacco smoking main effects whereby chi square statistics were calculated for the interaction and main effect estimates, we found that in all cases tested there was a significantly lower risk for MS compared to TS. Male and female TS had a greater probability of developing lung cancer than did MS. Males and females TS had a greater probability of developing lung cancer compared with NS. Males and female MTS had a slightly higher probability of developing lung cancer than did MS.

This difference was statistically significant: chi2 = 30.51, p < .00001, with a correlation coefficient of -0.75, Z = -7.84, p < .05. Male and female MTS had a lower probability of developing lung cancer than did TS. This difference was statistically significant: chi2 = 71.61, p = .00003, with a correlation coefficient of 0.61, Z = 5.06, p < .05.”

https://www.ncbi.nlm.nih.gov/pubmed/19004418

http://www.tandfonline.com/doi/abs/10.1080/02791072.2008.10400641

 

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Cannabidiol reduced frequency of convulsive seizures in drug resistant Dravet syndrome.

BMJ Journals

“Study design

Design: Multinational double-blinded placebo-controlled trial. Patients randomised in 1:1 ratio to receive cannabidiol or placebo, in addition to stable antiepileptic treatment regime.

Study question

Setting: Twenty-three centres in Europe and USA.

 Patients: Patients aged 2 years to 18 years with established diagnosis of Dravet syndrome having at least four convulsive seizures during the 28-day baseline period despite regular antiepileptic medication.

Intervention: Adjunctive cannabidiol or placebo oral solution at 20 mg per kilogram of body weight per day.

Primary outcome: Percentage change in median frequency of convulsive seizures per month.

Follow-up period: Outcome measured over a 14-week treatment period in comparison to a 4-week baseline period.

Patient follow-up: One hundred and eight (90%) completed the trial: 85% (52/61) in the cannabidiol group and …”

http://ep.bmj.com/content/early/2017/09/22/archdischild-2017-313700

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Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury.

“Cannabidiol (CBD) is a non-psychoactive component of marijuana, which has anti-inflammatory effects. It has also been approved by FDA for various orphan diseases for exploratory trials. Herein, we investigated the effects of CBD on liver injury induced by chronic plus binge alcohol feeding in mice. CBD may have therapeutic potential in the treatment of alcoholic liver diseases associated with inflammation, oxidative stress and steatosis, which deserves exploration in human trials.”  https://www.ncbi.nlm.nih.gov/pubmed/28935932

“Cannabidiol (CBD) is the most abundant non-psychoactive constituent of marijuana plant (Cannabis Sativa) with excellent safety profile in humans even after chronic use. In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis.” https://www.nature.com/articles/s41598-017-10924-8

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Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats.

Neurotoxicity Research

“Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis.

Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured.

Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective.

Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”

https://www.ncbi.nlm.nih.gov/pubmed/28933048

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Medical marijuana for the treatment of vismodegib-related muscle spasm

JAAD Case Reports

“Basal cell carcinoma (BCC) arises from loss-of-function mutations in tumor suppressor patched homologue 1, which normally inhibits smoothened homologue in the sonic hedgehog signaling pathway. Vismodegib, a smoothened homologue inhibitor, is US Food and Drug Administration (FDA) approved for metastatic or locally advanced BCC that has recurred after surgery or for patients who are not candidates for surgery and radiation. Common adverse effects of vismodegib are muscle spasms, alopecia, dysgeusia, nausea, and weight loss. Muscle spasms worsen with duration of drug administration and may lead to drug discontinuation.

We report a case of vismodegib-related muscle spasm that was successfully treated with medical marijuana (MM).

During the first week of vismodegib and radiation, the patient started MM, having heard of its indication in the treatment of muscle cramps. She smoked 3 to 4 joints daily of Trainwreck strain, containing 18.6% tetrahydrocannabinol (THC), 0.0% cannabidiol (CBD), and 0.0% cannabinol. Her muscle spasms resolved immediately. She continued MM for 3.5 weeks, until the cost of MM became prohibitive. She reported no adverse effects from MM. Complete resolution of muscle spasms was sustained through the remaining 3.5 weeks of vismodegib. Complete blood count, comprehensive metabolic panel, and lactate dehydrogenase level were monitored throughout the study with no significant changes. As of 18 months posttreatment, the patient had a complete clinical response of her BCC.

One marijuana joint contains, on average, 0.66 g of marijuana, although the definition of a joint is highly variable. With any MM formulation, patients should start at a low dose and gradually titrate to effect. Additional studies could confirm safety and efficacy and better specify the optimal cannabinoid subtypes, preparations, and dosages that may be most beneficial for vismodegib-induced muscle spasms.”

http://www.jaadcasereports.org/article/S2352-5126(17)30124-8/fulltext

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Efficacy of Cannabis-Based Medicines for Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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“The management of chronic pain is a complex challenge worldwide. Cannabis-based medicines (CBMs) have proven to be efficient in reducing chronic pain, although the topic remains highly controversial in this field.

OBJECTIVES:

This study’s aim is to conduct a conclusive review and meta-analysis, which incorporates all randomized controlled trials (RCTs) in order to update clinicians’ and researchers’ knowledge regarding the efficacy and adverse events (AEs) of CBMs for chronic and postoperative pain treatment.

CONCLUSIONS:

The current systematic review suggests that CBMs might be effective for chronic pain treatment, based on limited evidence, primarily for neuropathic pain (NP) patients. Additionally, GI AEs occurred more frequently when CBMs were administered via oral/oromucosal routes than by inhalation.”

https://www.ncbi.nlm.nih.gov/pubmed/28934780

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Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.

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“There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing.

RESULTS:

Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism.

CONCLUSIONS:

Dronabinol’s effects on apneas were dependent on CB1 receptor activation, while dronabinol’s effects on REM sleep were CB receptor-independent.”

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Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy.

European Respiratory Society

“Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.

Primary vagal ganglia neurons, tissue bioassay, in vivoelectrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents. FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels.

These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.”

https://www.ncbi.nlm.nih.gov/pubmed/28931663

http://erj.ersjournals.com/content/50/3/1700782

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[Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience].

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“Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient’s quality of life. Its treatment is complex and sometimes the outcome is insufficient.

Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.

AIM:

To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations.

RESULTS:

Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001).

CONCLUSIONS:

Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28929471

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Medical marijuana in pediatric oncology: A review of the evidence and implications for practice.

Pediatric Blood & Cancer

“Medical marijuana (MM) has become increasingly legal at the state level and accessible to children with serious illness. Pediatric patients with cancer may be particularly receptive to MM, given purported benefits in managing cancer-related symptoms. In this review, we examine the evidence for MM as a supportive care agent in pediatric oncology. We describe the current legal status of MM, mechanism of action, common formulations, and potential benefits versus risks for pediatric oncology patients. We offer suggestions for how providers might approach MM requests. Throughout, we comment on avenues for future investigation on this growing trend in supportive care.”

https://www.ncbi.nlm.nih.gov/pubmed/28926679

http://onlinelibrary.wiley.com/doi/10.1002/pbc.26826/abstract

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