Acute Effects of Smoked Marijuana and Oral Δ9-Tetrahydrocannabinol on Specific Airway Conductance in Asthmatic Subjects

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“The acute effects of smoked 2 per cent natural marijuana (7 mg per kg) and 15 mg of oral Δ9-tetrahydrocannabinol (THC) on plethysmographically determined airway resistance (Raw) and specific airway conductance (SGaw) were compared with those of placebo in 10 subjects with stable bronchial asthma using a double-blind crossover technique.

After smoked marijuana, SGaw increased immediately and remained significantly elevated (33 to 48 per cent above initial control values) for at least 2 hours, whereas SGaw did not change after placebo. The peak bronchodilator effect of 1,250 µg of isoproterenol was more pronounced than that of marijuana, but the effect of marijuana lasted longer.

After ingestion of 15 mg of THC, SGaw was elevated significantly at 1 and 2 hours, and Raw was reduced significantly at 1 to 4 hours, whereas no changes were noted after placebo.

These findings indicated that in the asthmatic subjects, both smoked marijuana and oral THC caused significant bronchodilation of at least 2 hours’ duration.”  http://www.atsjournals.org/doi/abs/10.1164/arrd.1974.109.4.420?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

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Effects of smoked marijuana in experimentally induced asthma.

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“After experimental induction of acute bronchospasm in 8 subjects with clinically stable bronchial asthma, effects of 500 mg of smoked marijuana (2.0 per cent delta9-tetrahydrocannabinol) on specific airway conductance and thoracic gas volume were compared with those of 500 mg of smoked placebo marijuana (0.0 per cent delta9-tetrahydrocannabinol), 0.25 ml of aerosolized saline, and 0.25 ml of aerosolized isoproterenol (1,250 mug).

After methacholine-induced bronchospasm, placebo marijuana and saline inhalation produced minimal changes in specific airway conductance and thoracic gas volume, whereas 2.0 per cent marijuana and isoproterenol each caused a prompt correction of the bronchospasm and associated hyperinflation. After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.”  https://www.ncbi.nlm.nih.gov/pubmed/1099949

“After exercise-induced bronchospasm, placebo marijuana and saline were followed by gradual recovery during 30 to 60 min, whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation.”
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Cannabis for restless legs syndrome: a report of six patients

Sleep Medicine
“Restless legs syndrome (RLS) is a chronic and sometimes severe sensorimotor disorder of still unclear pathophysiology. Usually symptoms respond well to dopamine agonists (DA), opiates, or anticonvulsants, used either alone or in combination. However, a subset of patients remains refractory to medical therapy, and serious side effects such as augmentation and impulse control disorder have been observed with DA. We present six patients’ spontaneous reports of a remarkable and total remission of RLS symptoms following cannabis use.”
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Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Related image“The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.” https://www.ncbi.nlm.nih.gov/pubmed/28653665

https://www.nature.com/npp/journal/vaop/naam/abs/npp2017130a.html

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Pharmaceutical and biomedical analysis of cannabinoids: A critical review

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“Cannabis products have recently regained much attention due to the high pharmacological potential of their cannabinoid content. In this review, the most widely used sample preparation strategies for the extraction of cannabinoids are described for the specific application to either plant materials or biological matrices. Several analytical techniques are described pointing out their respective advantages and drawbacks. In particular, chromatographic methods, such as TLC, GC and HPLC, are discussed and compared in terms of selectivity and sensitivity. Various detection methods are also presented based on the specific aim of the cannabinoids analysis. Lastly, critical considerations are mentioned with the aim to deliver useful suggestions for the selection of the optimal and most suitable method of analysis of cannabinoids in either biomedical or cannabis derived samples.” https://www.ncbi.nlm.nih.gov/pubmed/28641906   http://www.sciencedirect.com/science/article/pii/S0731708517311895

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The case for cannabinoid CB1 receptors as a target for bronchodilator therapy for β-agonist resistant asthma.

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“Although b2-receceptor agonists are powerful bronchodilators and are at the forefront of asthma symptom relief, patients who use them frequently develop partial resistance to them. This can be a particularly serious problem during severe attacks, where high dose b2-agonist treatment is the front line therapy.

Alternative bronchodilators are urgently needed. In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanism of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation.

Specifically, clinical trials testing the bronchodilator effects of THC in b2 agonist resistant asthmatic patients would show whether THC could fill the role of rescue bronchodilator in cases of b2 agonist resistance.”  https://www.ncbi.nlm.nih.gov/pubmed/28641517

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Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

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“The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC.

Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day).

Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment.

Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.” https://www.ncbi.nlm.nih.gov/pubmed/28641496   http://neuro.psychiatryonline.org/doi/10.1176/appi.neuropsych.16120328

“Guanfacine (brand name EstulicTenex and the extended release Intuniv; not to be confused with guaifenesin, an expectorant) is a sympatholytic drug used in the treatment of attention deficit hyperactivity disorder (ADHD), anxiety, and hypertension. It is a selective α2A receptor agonist https://en.wikipedia.org/wiki/Guanfacine

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Cannabinoids in Pediatrics.

“Despite its controversial nature, the use of medical marijuana and cannabis-derived medicinal products grows more popular with each passing year. As of November 2016, over 40 states have passed legislation regarding the use of either medical marijuana or cannabidiol products. Many providers have started encountering patients experimenting with cannabis products for a wide range of conditions. While the debate continues regarding these agents for both medicinal and recreational use in the general population, special consideration needs to be made for pediatric use. This review will deliver the history of marijuana use and legislation in the United States in addition to the currently available medical literature to equip pediatric health care providers with resources to provide patients and their parents the best recommendation for safe and appropriate use of cannabis-containing compounds.” https://www.ncbi.nlm.nih.gov/pubmed/28638299     http://www.jppt.org/doi/10.5863/1551-6776-22.3.176?code=ppag-site

“Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.” https://www.ncbi.nlm.nih.gov/pubmed/24237632

“The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law.”  https://www.ncbi.nlm.nih.gov/pubmed/28169144

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The cannabinoid ligand LH-21 reduces anxiety and improves glucose handling in diet-induced obese pre-diabetic mice.

“LH-21 is a triazol derivative that has been described as a low-permeant neutral CB1 antagonist, though its pharmacology is still unclear. It has been associated with anti-obesity actions in obese rats. However, its role in preventing type 2 diabetes (T2D) onset have not been studied yet. Given CB1 receptors remain as potential pharmacological targets to fight against obesity and T2D, we wanted to explore the metabolic impact of this compound in an animal model of obesity and pre-diabetes as well as the lack of relevant actions in related central processes such as anxiety. These results suggest that LH-21 can be a new candidate to fight against diabetes onset. Indeed, this compound shows potential in counteracting obesity-related anxiety.” https://www.ncbi.nlm.nih.gov/pubmed/28638091   https://www.nature.com/articles/s41598-017-03292-w

“Anti-obesity efficacy of LH-21, a cannabinoid CB(1) receptor antagonist with poor brain penetration, in diet-induced obese rats.”  https://www.ncbi.nlm.nih.gov/pubmed/21951309

“Antiobesity effects of the novel in vivo neutral cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole–LH 21.”  https://www.ncbi.nlm.nih.gov/pubmed/16750544

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Is cannabis treatment for anxiety, mood, and related disorders ready for prime time?

Depression and Anxiety

“Anxiety and related disorders are the most common mental conditions affecting the North American population. Despite their established efficacy, first-line antidepressant treatments are associated with significant side effects, leading many afflicted individuals to seek alternative treatments. Cannabis is commonly viewed as a natural alternative for a variety of medical and mental health conditions. Currently, anxiety ranks among the top five medical symptoms for which North Americans report using medical marijuana. However, upon careful review of the extant treatment literature, the anxiolytic effects of cannabis in clinical populations are surprisingly not well-documented. The effects of cannabis on anxiety and mood symptoms have been examined in healthy populations and in several small studies of synthetic cannabinoid agents but there are currently no studies which have examined the effects of the cannabis plant on anxiety and related disorders. In light of the rapidly shifting landscape regarding the legalization of cannabis for medical and recreational purposes, it is important to highlight the significant disconnect between the scientific literature, public opinion, and related policies. The aim of this article is to provide a comprehensive review of the current cannabis treatment literature, and to identify the potential for cannabis to be used as a therapeutic intervention for anxiety, mood, and related disorders. Searches of five electronic databases were conducted (PubMed, MEDLINE, Web of Science, PsychINFO, and Google Scholar), with the most recent in February 2017. The effects of cannabis on healthy populations and clinical psychiatric samples will be discussed, focusing primarily on anxiety and mood disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/28636769   http://onlinelibrary.wiley.com/doi/10.1002/da.22664/abstract

“The endocannabinoid system and the treatment of mood and anxiety disorders. Collectively, both clinical and preclinical data argue that cannabinoid receptor signalling may be a realistic target in the development of a novel class of agent for the pharmacotherapy of mood and anxiety disorders.”  https://www.ncbi.nlm.nih.gov/pubmed/19839936

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