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  • ∆9-tetrahydrocannabinol (THC), synthetic cannabinoids, WIN55212-2
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Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

Abstract Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2...
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Inhaled Cannabis Suppresses Chemotherapy-Induced Neuropathic Nociception by Decoupling the Raphe Nucleus: A Functional Imaging Study in Rats

Abstract Background Efficacy of inhaled cannabis for treating pain is controversial. Effective treatment for chemotherapy-induced neuropathy represents an unmet medical need. We hypothesized that cannabis reduces neuropathic pain by reducing functional coupling in the raphe nuclei. Methods We assessed the impact of inhalation of vaporized cannabis plant (containing 10.3% Δ9-tetrahydrocannabinol/0.05% cannabidiol) or placebo cannabis on brain resting-state blood oxygen level–dependent functional connectivity and pain behavior induced by paclitaxel in rats. Rats received paclitaxel to produce chemotherapy-induced peripheral neuropathy or its vehicle. Behavioral and imaging experiments were performed after neuropathy was established and stable. Images were registered to, and analyzed using, a 3D magnetic resonance imaging rat atlas providing site-specific data on more than 168 different brain areas. Results Prior to vaporization, paclitaxel...
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The Role of Cannabidiol in Neurological Disorders

Abstract Cannabis has been used for both recreational and medicinal purposes for more than 4 millennia. Cannabis has been studied in various medical disorders including neurological disorders. There are well-known risks of long-term use of cannabis, including low motivation, lowered cognitive capabilities, and diminished IQ and brain mass. Cannabinoids are compounds in cannabis that are known to have therapeutic potential. The most abundant chemicals in cannabinoids are delta-9-tetrahydrocannabinol and cannabidiol. Delta-9-tetrahydrocannabinol has psychotropic effects that limits its use as a pharmacotherapeutic agent. Cannabidiol is a nonpsychotropic chemical and therefore has become a compound of interest for clinical researchers to study its therapeutic potential. This...
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∆9-tetrahydrocannabinol self-administration induces cell-type specific adaptations in the nucleus accumbens core

Abstract Drugs of abuse induce cell type specific adaptations in D1- and D2-medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), that can bias signaling towards D1-MSNs and enhance relapse vulnerability. Whether ∆9-tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC+cannabidiol (THC+CBD). After extinction training spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC+CBD induced a loss of large spine heads in D1- but not D2-MSNs and commensurate reductions in glutamate synaptic transmission. Also, presynaptic CB1R function was impaired selectively at...
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Cannabis-Based Medicines and Pain: A Review of Potential Synergistic and Entourage Effects

Abstract The recent legalization of medicinal cannabis in several jurisdictions has spurred the development of therapeutic formulations for chronic pain. Unlike pure delta-9-tetrahydrocannabinol (THC), full-spectrum products contain naturally occurring cannabinoids and have been reported to show improved efficacy or tolerability, attributed to synergy between cannabinoids and other components in the cannabis plant. Although ‘synergy’ indicates that two or more active compounds may produce an additive or combined effect greater than their individual analgesic effect, potentiation of the biological effect of a compound by related but inactive compounds, in combination, was termed the ‘entourage effect’. Here, we review current evidence for potential synergistic and entourage...
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The Effects of Cannabis Use on Cognitive Function in Healthy Aging: A Systematic Scoping Review

Abstract Background Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on cognition in healthy aging. Objective This systematic scoping review used preferred reporting items for systematic reviews and meta-analyses guidelines to critically examine the extent of literature on this topic and highlight areas for future research. Method A search of six databases (PubMed, EMBASE, PsycINFO, Web of Science, Family and Society Studies Worldwide, and...
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Cannabis in Parkinson’s Disease: The Patients’ View

Please use this link to access this publication. Abstract: Background: Little is known about the patients’ view on treatment with medical cannabis (MC) for Parkinson’s disease (PD). Objective:To assess the PD community’s perception of MC and patients’ experience with MC. Methods:Applying a questionnaire-based survey, we evaluated general knowledge and interest in MC as well as the frequency, modalities, efficacy, and tolerability of application. Questionnaires were distributed nationwide via the membership journal of the German Parkinson Association and locally in our clinic to control for report bias. Results:Overall, 1.348 questionnaires (1.123 nationwide, 225 local) were analysed. 51% of participants were aware of the legality of MC...
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Dronabinol Prescribing and Exposure Among Children and Young Adults Diagnosed with Cancer

Abstract Purpose: The therapeutic utility of Cannabis in cancer is a topic of intense interest. Dronabinol is synthetic Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of Cannabis sativa, and is approved for treating refractory chemotherapy-induced nausea and vomiting. Little is known about dronabinol prescribing in children and young adults, and no published concentration data are available. This study evaluated national level dronabinol use and assessed concentrations of THC and its primary metabolites in patients with cancer <27 years of age prescribed dronabinol. Methods: Observational review of records from the Pediatric Health Information System (PHIS) and a regional network of hospitals in the Intermountain West, including a tertiary care children's hospital, Primary...
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A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice

Please use this link to access this publication. Abstract The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we...
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Assessment of Cannabidiol and Δ9-Tetrahydrocannabiol in Mouse Models of Medulloblastoma and Ependymoma

Simple Summary Phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been demonstrated to exhibit anti-cancer activity in preclinical models of brain cancer leading to new clinical trials for adults with glioblastoma. We describe here the first report that has investigated a role for THC and CBD in pediatric brain cancer. Cannabinoids had cytotoxic activity against medulloblastoma and ependymoma cells in vitro, functioning in part through the inhibition of cell cycle progression and the induction of autophagy. Despite these effects in vitro, when tested in orthotopic mouse models of medulloblastoma or ependymoma, no impact on animal survival was observed. Furthermore, cannabinoids neither enhanced nor impaired conventional...
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