Entries by Michelle Smith

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The Impact Of Cannabidiol In Patients With Early Psychosis: A Randomized Controlled Trial

We aimed to study the effects of cannabidiol (CBD) in out-patients with early psychosis on clinical metrics of psychosis and cognition and on psychophysiological electroencephalogram (EEG) metrics of psychosis. Adult outpatient subjects with a primary psychotic disorder within approximately five years of psychosis onset were enrolled in a four-week, two-period, randomized, placebo-controlled crossover trial (clinicaltrials.gov NCT02504151). Subjects were randomized in a one-to-one ratio to receive either CBD (oral 800 mg/day) or placebo in the first of two treatment periods in a randomized, double-blind manner. Primary outcome measures assessed were psychosis symptoms measured using the Positive and Negative Syndrome Scale (PANSS); and cognition measured using the MATRICS Consensus Cognitive Battery (MCCB). Secondary clinical outcomes included Clinical Global Impression of Severity or of Improvement (CGI-S, CGI-I) and Quality of Life Scale (QLS). Statistical analyses were conducted using linear mixed models and nonparametric tests.

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Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

Self-reported Medicinal Cannabis Use as an Alternative to Prescription and Over-the-counter Medication Use Among US Military Veterans

Mental and other physical health concerns and substance use disorder are common and co-occurring events experienced by US veterans. Treatment with medicinal cannabis is a potential alternative to unwanted medication use for veterans, but more clinical and epidemiologic research is needed to understand the risks and benefits. Data were collected from a cross-sectional, self-reported, anonymous survey asking US veterans about their health conditions, medical treatments, demographics, and medicinal cannabis use along with its self-reported effectiveness. In addition to descriptive statistics, logistic regression models were run to examine correlates of the use of cannabis as a substitution for prescription or over-the-counter medications.

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Effects of CBD supplementation on ambulatory blood pressure and serum urotensin-II concentrations in Caucasian patients with essential hypertension: A sub-analysis of the HYPER-H21-4 trial

HYPER-H21–4 was a randomized crossover trial that aimed to determine if cannabidiol (CBD), a non-intoxicating constituent of cannabis, has relevant effects on blood pressure and vascular health in patients with essential hypertension. In the present sub-analysis, we aimed to elucidate whether serum urotensin-II concentrations may reflect hemodynamic changes caused by oral supplementation with CBD. The sub-analysis of this randomized crossover study included 51 patients with mild to moderate hypertension that received CBD for five weeks, and placebo for five weeks. After five weeks of oral CBD supplementation, but not placebo, serum urotensin concentrations reduced significantly in comparison to baseline (3.31 ± 1.46 ng/mL vs. 2.08 ± 0.91 ng/mL, P < 0.001). Following the five weeks of CBD supplementation, the magnitude of reduction in 24 h mean arterial pressure (MAP) positively correlated with the extent of change in serum urotensin levels (r = 0.412, P = 0.003); this association was independent of age, sex, BMI and previous antihypertensive treatment (β ± standard error, 0.023 ± 0.009, P = 0.009). No correlation was present in the placebo condition (r = −0.132, P = 0.357). In summary, potent vasoconstrictor urotensin seems to be implicated in CBD-mediated reduction in blood pressure, although further research is needed to confirm these notions.

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The modulatory role of cannabis use in subconcussive neural injury

Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

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Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry

Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety. This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs. A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0.

Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios

As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = −4.709, d = 0.69, p = 2.41 × 10–5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.

Cannabinoids in hyperhidrosis

Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient’s quality of life using this novel low-cost and low-impact approach.

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Integrative Oncology’s 30-Year Anniversary: What Have We Achieved? A North American Naturopathic Oncology Perspective

In 1991 the U.S. Congress mandated that the National Institutes of Health (NIH) form the Office of Alternative Medicine to study alternative medical therapies, especially in oncology care. Shortly after, the National Cancer Institute (NCI) created its own division of complementary and alternative medicine (Office of Complementary and Alternative Medicine). At the genesis of the field 30 years ago, what were we hoping to see accomplished by now? In this article we take a look back at milestones, shortfalls and future directions. Exciting opportunities exist to direct our established subspeciality’s future directions and we have made valuable advances the field of integrative oncology over the last 30 years: 1, IV high dose ascorbate has clinical research-based applications when used concurrently with some chemotherapeutic agents. 2. Whole body, extracorporeal and locoregional hyperthermia are being applied in treating solid tumors, including brain tumors. 3. PDL-1 tumor microenvironment testing and PDL-1 inhibitor immunotherapies have surprisingly excellent outcomes in a subgroup of cancer patients. 4. Tumor DNA sequencing (resected tumor and circulating tumor DNA in blood) has led to personalized precision targeted treatments. 5. Glucose metabolism’s role in cancer progression is better understood and better therapies are available (e.g., intermittent fasting, metformin). 6. Medical cannabis has a larger role in treating chemotherapy-related side effects and shows promise for anti-proliferative effects.

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Tetrahydrocannabinol and Cannabidiol in Tourette Syndrome

Tourette syndrome is characterized by chronic motor and vocal tics. There is preliminary evidence of benefit from cannabis products containing D9-tetrahydrocannabi- nol (THC) and that coadministration of cannabidiol (CBD) improves the side-effect profile and safety.In this double-blind, crossover trial, participants with severe Tourette syndrome were randomly assigned to a 6-week treatment period with escalating doses of an oral oil containing 5 mg/ml of THC and 5 mg/ml of CBD, followed by a 6-week course of placebo, or vice versa, separated by a 4-week washout period. The primary outcome was the total tic score on the Yale Global Tic Severity Scale (YGTSS; range, 0 to 50 [higher scores indicate greater severity of symptoms]). Secondary outcomes included video-based assessment of tics, global impairment, anxiety, depression, and obsessive-compulsive symptoms. Out- comes were correlated with plasma levels of cannabinoid metabolites. A computerized cogni- tive battery was administered at the beginning and the end of each treatment period.

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Neuronal Cannabinoid CB1 Receptors Suppress the Growth of Melanoma Brain Metastases by Inhibiting Glutamatergic Signalling

An estimated 60% of melanoma patients develop melanoma brain metastases (MBMs). However, the molecular factors that govern the growth of MBMs are still unknown. The excitatory neurotransmitter glutamate has been shown to control the proliferation of various types of cancer cells within the brain parenchyma, but the cellular sources and molecular mechanisms involved in this process remain unclear. By their well-known role in inhibiting synaptic glutamate release, cannabinoid CB1 receptors (CB1Rs) located on glutamatergic nerve terminals are conceivably well-positioned to control the growth of MBMs. In silico data mining in cancer-genome atlases and in vitro studies with melanoma cell lines supported that a glutamate-NMDA receptor axis drives melanoma cell proliferation. Strikingly, grafting melanoma cells into the brain of mice lacking CB1Rs selectively in glutamatergic neurons increased tumour size and concomitantly activated NMDA receptors on tumour cells. Altogether, our findings reveal an unprecedented role of neuronal CB1Rs in controlling MBMs.

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Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population

Patients diagnosed as having multiple sclerosis (MS) experience a wide range of symptoms requiring pharmacologic management, and many do not achieve adequate symptom control. The purpose of this study was to evaluate the role of medical cannabis (MC) as part of a comprehensive treatment plan for patients with MS. A retrospective medical record review of 141 patients with MS receiving MC for symptom management was conducted. Data were collected for up to 4 follow-up appointments after initiation of MC. Outcomes included changes in MS symptoms, medication changes, adverse events, and changes in cognition and mobility.