scholarly journals Oleoylethanolamide: A Novel Potential Pharmacological Alternative to Cannabinoid Antagonists for the Control of Appetite

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Adele Romano ◽  
Roberto Coccurello ◽  
Giacomo Giacovazzo ◽  
Gaurav Bedse ◽  
Anna Moles ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Motor Activity ◽  
Endocannabinoid System ◽  
Temporary Increase ◽  
Similar Extent ◽  
Resting Time ◽  
Cb1 Antagonist ◽  
Satiety Sequence ◽  
Cannabinoid Antagonists

The initial pharmaceutical interest for the endocannabinoid system as a target for antiobesity therapies has been restricted by the severe adverse effects of the CB1 antagonist rimonabant. This study points at oleoylethanolamide (OEA), a monounsaturated analogue, and functional antagonist of anandamide, as a potential and safer antiobesity alternative to CB1 antagonism. Mice treated with equal doses (5 or 10 mg/kg, i.p.) of OEA or rimonabant were analyzed for the progressive expression of spontaneous behaviors (eating, grooming, rearing, locomotion, and resting) occurring during the development of satiety, according to the paradigm called behavioral satiety sequence (BSS). Both drugs reduced food (wet mash) intake to a similar extent. OEA treatment decreased eating activity within the first 30 min and caused a temporary increase of resting time that was not accompanied by any decline of horizontal, vertical and total motor activity. Besides decreasing eating activity, rimonabant caused a marked increase of the time spent grooming and decreased horizontal motor activity, alterations that might be indicative of aversive nonmotivational effects on feeding. These results support the idea that OEA suppresses appetite by stimulating satiety and that its profile of action might be predictive of safer effects in humans as a novel antiobesity treatment.

scholarly journals Efficacy of limited hippocampal radiofrequency thermocoagulation for mesial temporal lobe epilepsy

2019 ◽  
Vol 131 (3) ◽  
pp. 781-789 ◽  
Author(s):  
Ching-Yi Lee ◽  
Han-Tao Li ◽  
Tony Wu ◽  
Mei-Yun Cheng ◽  
Siew-Na Lim ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Seizure Frequency ◽  
Seizure Control ◽  
Mesial Temporal Lobe Epilepsy ◽  
Temporary Increase ◽  
Drug Resistant ◽  
Radiofrequency Thermocoagulation ◽  
Mesial Temporal Lobe

OBJECTIVERadiofrequency thermocoagulation (RFTC), which has been developed for drug-resistant epilepsy patients, involves less brain tissue loss due to surgery, fewer surgical adverse effects, and generally good seizure control. This study demonstrates the effectiveness of RFTC performed at limited hippocampal locations.METHODSDaily seizure diaries were prospectively maintained for at least 6 months by 9 patients (ages 30–59 years) with drug-resistant mesial temporal lobe epilepsy (MTLE) before treatment with RFTC. The limited target for stereotactic RFTC was chosen based on intraoperative electroencephalography (EEG) recording and was initially tested with a Radionics electrode at a low temperature, 45°C, for 60 seconds. The therapeutic RFTC heating parameters were 78°C–80°C for 90 seconds. All patients who received the RFTC treatment underwent both MRI and EEG recording immediately postoperatively and at the 3-month follow-up. Monthly outpatient clinic visits were arranged over 6 months to document seizure frequency and severity to clarify the changes noted in imaging studies and EEG patterns.RESULTSTwo patients were excluded from our analysis because one had undergone multiple seizure surgeries and the other had a poor recording of seizure frequency, before the RFTC surgery. Five and two patients underwent left-sided and right-sided RFTC, respectively. None of the patients had generalized tonic-clonic attacks postoperatively, and no adverse effects or complications occurred. According to MRI data, the effect of coagulation was limited to less than 1.0 cm in diameter and perifocal edema was also in limited range. The seizure frequency within 6 months decreased postoperatively with a mean reduction in seizures of 78% (range 36%–100%). Only two patients had a temporary increase in seizure frequency within 2 weeks of the surgery, and over 50% of all patients showed a decrease in average seizure frequency.CONCLUSIONSThe study results confirm that limited RFTC provides a more effective surgery with similar seizure control but fewer complications than resective surgery for drug-resistant MTLE patients.

scholarly journals Cannabinoids for clinicians: the rise and fall of the cannabinoid antagonists

2009 ◽  
Vol 161 (5) ◽  
pp. 655-662 ◽  
Author(s):  
Helen Butler ◽  
Márta Korbonits
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Side Effects ◽  
Endocannabinoid System ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Concise Review ◽  
Psychiatric Side Effects ◽  
Lipid Parameters ◽  
Cannabinoid Antagonists

The endocannabinoid system has emerged as a significant player in the control of energy balance and metabolism, through its direct central and peripheral effects, as well as via its interaction with other appetite-regulating pathways. There is mounting evidence that the endocannabinoid system is overactive in obesity and were it possible to safely dampen-down the elevated endocannabinoid tone, lipid and carbohydrate profiles could be improved and weight loss induced. The series of randomised clinical trials showed reproducible beneficial effects on weight, HbA1c and lipid parameters, in addition to other cardiovascular risk factors. However, to date, clinical developments have been halted because of psychiatric side effects. Although recent evidence has highlighted the importance of an appetite-independent, peripheral mode of action, it is still unclear whether selectively blocking the peripheral system could potentially solve the problem of the central side effects, which thus far has led to the demise of the cannabinoid antagonists as useful pharmaceuticals. In this concise review, we summarise the data on the metabolic effects of the cannabinoid pathway and its antagonists.

scholarly journals Cannabis “in utero”: the fetus as a compulsive consumer

2019 ◽  
Vol 6 (09) ◽  
pp. 4565-4569 ◽  
Author(s):  
Luiz Antonio Del Ciampo ◽  
Ieda Regina Lopes Del Ciampo
Keyword(s):  
Adverse Effects ◽  
Pregnant Women ◽  
Cannabis Sativa ◽  
Endocannabinoid System ◽  
In Utero ◽  
Fundamental Importance ◽  
Psychoactive Substances ◽  
Long Run ◽  
Adolescents And Adults

Cannabis sativa, a plant known for millennia for its hallucinogenic and medicinal effects, contains widely consumed psychoactive substances worldwide, with increasing numbers among adolescents and adults, including pregnant women. Due to its potential adverse effects on users, it is of fundamental importance to know and disseminate the harm caused to humans in order to reduce the consumption of this drug. This article presents a review of the physiological and pharmacological characteristics of psychoactive substances present in cannabis, their actions on the endocannabinoid system and the placenta. It also highlights the main clinical repercussions that can occur with the fetus and, in the long run, with children whose mothers used cannabis during pregnancy.

scholarly journals Phytocannabinoids use in Alzheimer’s disease

2021 ◽  
Author(s):  
Júlia Maia Seixas ◽  
Hygor Kleber Cabral Silva ◽  
Maria Alice Rocha Lopes ◽  
Kamila Castro Oliveira Camargos ◽  
Lara Silveira Marques ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Cognitive Deficits ◽  
Endocannabinoid System ◽  
In Vivo Studies ◽  
Publication Date ◽  
Β Amyloid

Background: Alzheimer’s disease (AD) is the most common cause of dementia among older adults impacting quality of life. Nowadays, four drugs are indicated to manage AD symptoms, however, none of them have shown effectiveness to prevent the disease’s progress, and they are associated with adverse effects. In this scenario, the endocannabinoid system has the attention of researchers and physicians, because of its relation with processes involved in the AD physiopathology. Therefore, in the last decade, studies that evaluate the use of Cannabidiol (CBD) and other phytocannabinoids, like tetrahydrocannabinol (THC) and cannabinol (CBN), as an alternative treatment to this illness, have multiplied. Objectives: To bring updated information about this new and promising therapeutic. Methods: A bibliographic research in PubMed with the terms “Cannabidiol and Alzheimer” was made, with the filters “Free full text” and “Publication Date 5 years”. The research obtained 31 results, from which were chosen 10. Results: In vivo studies with CBD, THC and CBN have shown their properties: anti-inflammatory, antioxidant, attenuation of toxic accumulation of β-amyloid protein and to reverse cognitive deficits, all AD physiopathological processes. It was also demonstrated that the combination between THC and CBD shows better efficiency and fewer adverse effects than CBD isolated use. Conclusions: Despite needing deeper and stronger studies with better conducted clinical trials, the researches about phytocannabinoids use in AD seem promising, and they might become the biggest ally in the treatment of this and other neurodegenerative conditions.

Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff

2020 ◽  
Vol 22 (10) ◽  
pp. 1757-1763
Author(s):  
Erik Lunell ◽  
Karl Fagerström ◽  
John Hughes ◽  
Robert Pendrill
Keyword(s):  
Single Dose ◽  
Adverse Effects ◽  
Blood Circulation ◽  
Crossover Design ◽  
Similar Extent ◽  
Systemic Blood ◽  
Moist Snuff ◽  
Higher Doses ◽  
Swedish Snus

Abstract Introduction The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes. Aims and Methods A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined. Results Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%). Results Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%). Conclusions The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.

scholarly journals Cannabis and Inflammation in HIV: A Review of Human and Animal Studies

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1521
Author(s):  
Ronald J. Ellis ◽  
Natalie Wilson ◽  
Scott Peterson
Keyword(s):  
Myocardial Infarction ◽  
Adverse Effects ◽  
Animal Studies ◽  
Endocannabinoid System ◽  
Cannabis Use ◽  
Review Of The Literature ◽  
Barrier Integrity ◽  
Persistent Inflammation ◽  
Anti Inflammatory ◽  
The Impact

Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut–blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.

scholarly journals FARMAKOLOGIJA KANABINOIDOV

2015 ◽  
Vol 84 (6) ◽  
Author(s):  
Ilonka Ferjan ◽  
Mojca Kržan ◽  
Metoda Lipnik-Štangelj ◽  
Lovro Žiberna ◽  
Lovro Stanovnik ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Adverse Effects ◽  
Cannabinoid Receptors ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Drug Candidate ◽  
Isolation And Identification ◽  
Increased Risk

The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."

scholarly journals Acute Immobilization Stress Modulate GABA Release from Rat Olfactory Bulb: Involvement of Endocannabinoids—Cannabinoids and Acute Stress Modulate GABA Release

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Alejandra Delgado ◽  
Erica H. Jaffé
Keyword(s):  
Olfactory Bulb ◽  
Immobilization Stress ◽  
Acute Stress ◽  
Endocannabinoid System ◽  
Gaba Release ◽  
Synaptic Function ◽  
The Other ◽  
Cb1 Antagonist ◽  
Per Se ◽  
Autocrine Mechanism

We studied the effects of cannabinoids and acute immobilization stress on the regulation of GABA release in the olfactory bulb. Glutamate-stimulated 3H-GABA release was measured in superfused slices. We report that cannabinoids as WIN55, 212-2, methanandamide, and 2-arachidonoylglycerol were able to inhibit glutamate- and KCl-stimulated 3H-GABA release. This effect was blocked by the CB1 antagonist AM281. On the other hand, acute stress was ableper seto increase endocannabinoid activity. This effect was evident since the inhibition of stimulated GABA release by acute stress was reversed with AM281 and tetrahydrolipstatin. Inhibition of the endocannabinoid transport or its catabolism showed reduction of GABA release, antagonized by AM281 in control and stressed animals. These results point to endocannabinoids as inhibitory modulators of GABA release in the olfactory bulb acting through an autocrine mechanism. Apparently, stress increases the endocannabinoid system, modulating GABAergic synaptic function in a primary sensory organ.

Interactions between the nitrergic and the endocannabinoid system in rats exposed to the elevated T maze

2021 ◽  
pp. 1-14
Author(s):  
L.A Batista ◽  
F.A Moreira ◽  
D.C Aguiar
Keyword(s):  
Nitric Oxide ◽  
Animal Model ◽  
Receptor Agonist ◽  
Wistar Rats ◽  
Endocannabinoid System ◽  
Cb1 Receptor ◽  
Cb1 Receptors ◽  
Male Wistar Rats ◽  
No Signaling ◽  
Cb1 Antagonist

Abstract Objective: the aim of this study was to test the hypothesis that synthesis of nitric oxide (NO) and activation of CB1 receptors have opposite effects in a behavioural animal model of panic and anxiety. Methods: to test the hypothesis male Wistar rats were exposed to the elevated T maze (ETM) model under the following treatments: L-Arginine (L-Arg) was administered before treatment withWIN55,212-2, a CB1 receptor agonist ; AM251, a CB1 antagonist, was administered before treatment with L-Arg. All treatments were by intraperitoneal route. Results: the CB1 receptor agonist, WIN55,212-2 (1 mg/kg), induced an anxiolytic-like effect which was prevented by pretreatment with an ineffective dose of L-Arg (1 mg/kg). Administration of AM251 (1 mg/kg), a CB1 antagonist before treatment with L-Arg (1 mg/kg) did not produce anxiogenic-like responses. Conclusion: altogether, this study suggests that the anxiolytic-like effect of cannabinoids may occur though modulation of NO signaling.

Implications of Cannabis Legalization: A Medical Perspective

2021 ◽  
Vol 11 ◽  
Author(s):  
John Calvin Chatlos ◽  
Theodore A. Petti
Keyword(s):  
Young Adults ◽  
Adverse Effects ◽  
Emerging Adults ◽  
Legal Status ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
The United States ◽  
Cannabis Use ◽  
Adolescents And Young Adults ◽  
Research Information

Background: Knowledge of the effects of cannabis and the endocannabinoid system (ECS) has significantly increased in recent years. This information has been brought into debates and decisions regarding the medical use of cannabis and recreational use of cannabis and cannabinoid products, often with non-science-based conclusions. Health-related effects, especially those related to children, adolescents, and young adults, must be a critical part of the decisions about the legalization of cannabis, and current knowledge is a necessity. The aim of this study was to provide an overview of cannabis use epidemiology in the United States. and provide current research information about the effects of cannabis use to be used in decisions about cannabis use and legalization, highlighting impacts on children, adolescents, and young adults. Method: Key features of cannabis-related to health benefits and adverse effects were identified to provide a representative collage detailing the knowledge base of health, disease, and public welfare. Emphasis is paid on to the most current research findings and adverse effects related to youth and young adults. Results: Helpful and harmful cannabis effects explain contradictory positions taken regarding further legalization of cannabis products. Federal research prohibition has handicapped a timely science-based informed discussion. Concerns are expressed for the protection of adolescents and emerging adults, regardless of cannabis’ legal status. Conclusion: The special vulnerabilities and needs of adolescents and emerging adults need to be considered in current and future discussions in public policy and legislation at all levels of government related to any further legalization of cannabis products. (N=247 words).

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