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Micronutrients for Improved Management of Huntington’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Cannabinoid receptors CB1 and CB2 are reduced in the key areas of the HD brain, such as the striatum and cortex. Loss of CB1 receptors was observed at the early stage of HD in the autopsied brain samples of patients with HD.25 This was confirmed by the PET, using a novel CB1 ligand N- [2-(3-cyano-phenyl)-3-(4-(2-18F-fluorethoxy)phenyl)-1-methylpropyl-2-(5-methyl-2-pyridyloxyl)-2-methylproponamide in 20 symptomatic HD patients and 14 healthy subjects. Levels of CB1 receptors decreased throughout the gray matter of the cerebellum, cerebellum, and brainstem.26 Thus, upregulation of CB1 receptors may be of protective value. Indeed, upregulation of CB1 receptors slowed progression of the disease in transgenic R6/1 HD mice.27 Deletion of CB1 receptors aggravated the symptoms and caused neurodegeneration in transgenic HD mice.28 Furthermore, administration of an endogenous cannabinoid receptor agonist delta-9-tetrahydrocannabinol prevented the effect of deletion of CB1 receptors in these mice. Therefore agonists of CB1 receptors may be useful in improving the symptoms of HD. Indeed, administration of CB1 agonist WIN 55,212-2 prevented the development of HD phenotype in quinolinate rat model of HD. This effect of a CB1 receptor agonist was blocked by the corresponding antagonist AM251.29
Central Nervous System Effects of Essential Oil Compounds
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
Elaine Elisabetsky, Domingos S. Nunes
Oleamide 34 is part of a brain lipid family that induces sleep (Cravatt et al., 1995). Systemic and icv administration of 34 to rats and mice markedly decreased sleep latency without changing other sleep parameters (Basile et al., 1999; Mendelson, 2001). When the major metabolizing enzyme for 34 (fatty acyl amide hydrolase, type I) is administered intraventricularly, sleep latency is reduced and total sleep is increased (Mendelson, 2001). In one study, acute and the subchronic (15 days) centrally administered oleamide increased REMS in rats, without affecting waking and NREM sleep. No abstinence effects on the sleep–waking cycle were observe after drug cessation (Herrera-Solís et al., 2010). Another study found that 50 administered systemically increased slow-wave sleep and decreased wakefulness and sleep latency, with no effects on REM sleep. The oleamide-induced increase in slow-wave sleep was prevented by 5-HT reuptake inhibitors (Yang et al., 2003). Research has found that 34 acts as a full cannabinoid receptor agonist (Leggett et al., 2004), and at least part of its hypnotic action involves the CB1 receptor system (Mendelson and Basile, 1999). A very well thought of and elegant series of experiments generated data to show that the cis isomer of oleamide is a stereoselective modulator of voltage-gated Na+ channel and GABAA receptor complex (Verdon et al., 2000). The mechanism is consistent with the hypno-sedative effects observed in vivo for cis-oleamide and its anticonvulsant effects (Verdon et al., 2000). Therefore, 34 effects on CB1 are compounded with other properties, such as the allosteric modulation of other receptors and fatty acid amide hydrolase inhibition.
An overview of the pharmacotherapeutics for dystonia: advances over the past decade
Published in Expert Opinion on Pharmacotherapy, 2022
O. Abu-hadid, J. Jimenez-Shahed
A systematic review assessing two DB-RCT described one study evaluating the effect of nabilone, a synthetic cannabinoid receptor agonist, in 15 patients with generalized or segmental dystonia, and another study evaluating the effect of dronabinol, a synthetic tetrahydrocannabinol, on nine patients with cervical dystonia [137]. Both studies show no significant improvement in outcome measures when compared to placebo [137]. A cross-sectional case series evaluated the use of tetrahydrocannbinol/cannabidiol mixtures in 12 patients with focal/segmental or hemidystonia. Efficacy of dystonia improvement was measured using a 1–5 point Likert scale, on which patients gave treatment an average score of 3.16 [138]. In addition, a case series of seven patients with juvenile onset Huntington disease had a significant improvement in the unified Huntington’s disease rating scale, dystonia subscale from 12.3 to 8.0 (p = 0.018) [139]. Finally, a case report of a patient with CD showed improvement in pain and TWSTRS while smoking cannabis, with the patient relapsing after discontinuing the cannabis and remitting after restarting it [140].
The rise of global research trends on cathinones during 1994-2018: lessons from a systematic bibliometric analysis
Published in Journal of Substance Use, 2022
Kang Wang, Yijie Duan, Haihong Chen, Jin Hu, Man Liang
The US has been the most productive country regarding research on cathinones, as well as research on similar substances, such as cocaine (Zyoud et al., 2017) and tramadol (Maassen, 2016; Sweileh et al., 2016). Possible reasons for the rich research output include relatively abundant research budgets for substance use and the sharp increase in reported cathinone-use cases – from 34 in 2009 to 628 in 2010 – by the National Forensic Laboratory Information System (NFLIS, 2012). In 2011, 6137 poisonings were related to the use of “bath salts” in the US (Palamar, Salomone, Vincenti, & Cleland, 2016). From 2011 to 2014, the reported prevalence of NPS accounted for 7.7% (n = 423) of total intentional synthetic cannabinoid receptor agonist (SCRA) and other drug use reported to the New York City Poison Control Center (Palamar, Su, & Hoffman, 2016). Currently, phenethylamines/synthetic cathinones (10.2%) are the second most prevalent class of NPS in the US (Palamar, Su, et al., 2016). However, many ecstasy-using nightclub/festival attendees may be using “bath salts” or other NPS unintentionally, suggesting that the rate of NPS use in the US may be much higher than that reported (Palamar, Salomone, et al., 2016). In addition, there are some indications that US researchers tend to cite publications from their own country more often than from researchers in other countries, which may have contributed to even more influences from with this citations preference also possibly impacting the high publication production (Khelfaoui et al., 2020).
Emerging role of nanomedicine in the treatment of neuropathic pain
Published in Journal of Drug Targeting, 2020
Pankaj Bidve, Namrata Prajapati, Kiran Kalia, Rakesh Tekade, Vinod Tiwari
Several studies have suggested that psychotic effect of CB1 agonist limits its therapeutic use, this problem can be solved by targeting the CB1 receptors in the peripheral nervous system (PNS) thus reducing its psychotic effect, but these peripherally acting drugs failed to relieve acute pain in humans at a tolerable dose. However, if these cannabinoid receptor agonist, if targeted to specific nociceptor in peripheral nervous system, could have a potent analgesic effect [38,46,47]. In 2014, Linsell and colleagues evaluated the effect of styrene maleic acid micelles encapsulating WIN55,212–2 in rats with CCI induced NeP. These micelles have a unique property of restricting the formulation in peripheral nervous system because of the presence of styrene core which encapsulates the lipophilic drug through hydrophobic bond and maleic acid shell for increasing its hydrophilicity. Also, these micelles provided prolongrelease of drug in a controlled manner thus making it different from the convectional formulation and a good candidate for clinical use too [48,49].