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Dialogues in Clinical Neuroscience Sep 2020This article retraces the story of cannabis from the earliest contacts of humans with the plant to its subsequent global expansion, its medicinal uses, and the discovery... (Review)
Review
This article retraces the story of cannabis from the earliest contacts of humans with the plant to its subsequent global expansion, its medicinal uses, and the discovery of the endocannabinoid system in the 20 century. Cannabis was attested to around 12 000 years ago near the Altai Mountains in Central Asia, and since then, cannabis seeds have accompanied the migration of nomadic peoples. Records of the medicinal use of cannabis appear before the Common Era in China, Egypt, and Greece (Herodotus), and later in the Roman empire (Pliny the Elder, Dioscorides, Galen). In the 19 century, orientalists like Silvestre de Sacy, and Western physicians coming into contact with Muslim and Indian cultures, like O'Shaughnessy and Moreau de Tours, introduced the medicinal use of cannabis into Europe. The structure of the main psychoactive phytocannabinoid, tetrahydrocannabinol (THC), was determined in Israel by Mechoulam and Gaoni in 1964. This discovery opened the gate for many of the subsequent developments in the field of endocannabinoid system (ECS) research. The advances in the scientific knowledge of the ECS place the debate on cannabis liberalization in a new context. .
Topics: Cannabinoids; Cannabis; Endocannabinoids; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Medical Marijuana
PubMed: 33162765
DOI: 10.31887/DCNS.2020.22.3/mcrocq -
Biological Psychiatry. Cognitive... Jun 2021The endocannabinoid system (ECS) is a widespread neuromodulatory network involved in the developing central nervous system as well as playing a major role in tuning many... (Review)
Review
The endocannabinoid system (ECS) is a widespread neuromodulatory network involved in the developing central nervous system as well as playing a major role in tuning many cognitive and physiological processes. The ECS is composed of endogenous cannabinoids, cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of endocannabinoids. In addition to its endogenous roles, cannabinoid receptors are the primary target of Δ-tetrahydrocannabinol, the intoxicating component of cannabis. In this review, we summarize our current understanding of the ECS. We start with a description of ECS components and their role in synaptic plasticity and neurodevelopment, and then discuss how phytocannabinoids and other exogenous compounds may perturb the ECS, emphasizing examples relevant to psychosis.
Topics: Cannabis; Endocannabinoids; Humans; Neuronal Plasticity; Receptors, Cannabinoid
PubMed: 32980261
DOI: 10.1016/j.bpsc.2020.07.016 -
Neuron Oct 2012Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can... (Review)
Review
Endocannabinoids are key modulators of synaptic function. By activating cannabinoid receptors expressed in the central nervous system, these lipid messengers can regulate several neural functions and behaviors. As experimental tools advance, the repertoire of known endocannabinoid-mediated effects at the synapse, and their underlying mechanism, continues to expand. Retrograde signaling is the principal mode by which endocannabinoids mediate short- and long-term forms of plasticity at both excitatory and inhibitory synapses. However, growing evidence suggests that endocannabinoids can also signal in a nonretrograde manner. In addition to mediating synaptic plasticity, the endocannabinoid system is itself subject to plastic changes. Multiple points of interaction with other neuromodulatory and signaling systems have now been identified. In this Review, we focus on new advances in synaptic endocannabinoid signaling in the mammalian brain. The emerging picture not only reinforces endocannabinoids as potent regulators of synaptic function but also reveals that endocannabinoid signaling is mechanistically more complex and diverse than originally thought.
Topics: Animals; Brain; Endocannabinoids; Humans; Neuronal Plasticity; Receptors, Cannabinoid; Signal Transduction; Synaptic Transmission
PubMed: 23040807
DOI: 10.1016/j.neuron.2012.09.020 -
Neurotherapeutics : the Journal of the... Oct 2015The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ(9)-tetrahydrocannabinol (but not... (Review)
Review
The endocannabinoid system is currently defined as the ensemble of the two 7-transmembrane-domain and G protein-coupled receptors for Δ(9)-tetrahydrocannabinol (but not for most other plant cannabinoids or phytocannabinoids)-cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R); their two most studied endogenous ligands, the "endocannabinoids" N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG); and the enzymes responsible for endocannabinoid metabolism. However, anandamide and 2-AG, and also the phytocannabinoids, have more molecular targets than just CB1R and CB2R. Furthermore, the endocannabinoids, like most other lipid mediators, have more than just one set of biosynthetic and degrading pathways and enzymes, which they often share with "endocannabinoid-like" mediators that may or may not interact with the same proteins as Δ(9)-tetrahydrocannabinol and other phytocannabinoids. In some cases, these degrading pathways and enzymes lead to molecules that are not inactive and instead interact with other receptors. Finally, some of the metabolic enzymes may also participate in the chemical modification of molecules that have very little to do with endocannabinoid and cannabinoid targets. Here, we review the whole world of ligands, receptors, and enzymes, a true "endocannabinoidome", discovered after the cloning of CB1R and CB2R and the identification of anandamide and 2-AG, and its interactions with phytocannabinoids.
Topics: Animals; Cannabinoid Receptor Modulators; Endocannabinoids; Humans; Plant Extracts; Receptors, Cannabinoid
PubMed: 26271952
DOI: 10.1007/s13311-015-0374-6 -
International Journal of Molecular... May 2021All nations which have undergone a nutrition transition have experienced increased frequency and falling latency of chronic degenerative diseases, which are largely... (Review)
Review
All nations which have undergone a nutrition transition have experienced increased frequency and falling latency of chronic degenerative diseases, which are largely driven by chronic inflammatory stress. Dietary supplementation is a valid strategy to reduce the risk and severity of such disorders. Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator with extensively documented anti-inflammatory, analgesic, antimicrobial, immunomodulatory and neuroprotective effects. It is well tolerated and devoid of side effects in animals and humans. PEA's actions on multiple molecular targets while modulating multiple inflammatory mediators provide therapeutic benefits in many applications, including immunity, brain health, allergy, pain modulation, joint health, sleep and recovery. PEA's poor oral bioavailability, a major obstacle in early research, has been overcome by advanced delivery systems now licensed as food supplements. This review summarizes the functionality of PEA, supporting its use as an important dietary supplement for lifestyle management.
Topics: Amides; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Dietary Supplements; Endocannabinoids; Ethanolamines; Humans; Inflammation; Inflammation Mediators; Neuroprotective Agents; Pain; Palmitic Acids
PubMed: 34069940
DOI: 10.3390/ijms22105305 -
International Journal of Molecular... Mar 2018The biological effects of cannabinoids, the major constituents of the ancient medicinal plant (marijuana) are mediated by two members of the G-protein coupled receptor... (Review)
Review
The biological effects of cannabinoids, the major constituents of the ancient medicinal plant (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids.
Topics: Animals; Cannabinoid Receptor Agonists; Central Nervous System; Endocannabinoids; Humans; Receptors, Cannabinoid; Signal Transduction
PubMed: 29533978
DOI: 10.3390/ijms19030833 -
Dialogues in Clinical Neuroscience Sep 2020The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive... (Review)
Review
The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive behavior. Cannabis-derived psychoactive compounds such as Δ-tetrahydrocannabinol and synthetic cannabinoids directly interact with the reward system and thereby have addictive properties. Cannabinoids induce their reinforcing properties by an increase in tonic dopamine levels through a cannabinoid type 1 (CB) receptor-dependent mechanism within the ventral tegmental area. Cues that are conditioned to cannabis smoking can induce drug-seeking responses (ie, craving) by eliciting phasic dopamine events. A dopamine-independent mechanism involved in drug-seeking responses involves an endocannabinoid/glutamate interaction within the corticostriatal part of the reward system. In conclusion, pharmacological blockade of endocannabinoid signaling should lead to a reduction in drug craving and subsequently should reduce relapse behavior in addicted individuals. Indeed, there is increasing preclinical evidence that targeting the endocannabinoid system reduces craving and relapse, and allosteric modulators at CB receptors and fatty acid amide hydrolase inhibitors are in clinical development for cannabis use disorder. Cannabidiol, which mainly acts on CB and CB receptors, is currently being tested in patients with alcohol use disorder and opioid use disorder. .
Topics: Animals; Behavior, Addictive; Cannabinoids; Drug-Seeking Behavior; Endocannabinoids; Humans; Marijuana Abuse; Receptors, Cannabinoid; Reward
PubMed: 33162767
DOI: 10.31887/DCNS.2020.22.3/rspanagel -
International Journal of Molecular... Jan 2023The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation,... (Review)
Review
The endocannabinoid system (ECS) is involved in various processes, including brain plasticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions. Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endogenous cannabinoids. Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time. A runner's high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects. This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.
Topics: Humans; Endocannabinoids; Exercise; Running; Emotions; Pain; Receptor, Cannabinoid, CB1
PubMed: 36768332
DOI: 10.3390/ijms24031989 -
International Journal of Molecular... Aug 2021The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and... (Review)
Review
The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of L. (hereafter referred to as " L." or "medical cannabis"), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.
Topics: Anxiety; Cannabinoid Receptor Agonists; Cannabinoids; Cannabis; Cardiovascular Diseases; Depression; Endocannabinoids; Feeding Behavior; Homeostasis; Humans; Neurodegenerative Diseases; Neurogenesis; Pain; Receptors, Cannabinoid
PubMed: 34502379
DOI: 10.3390/ijms22179472 -
International Journal of Molecular... Jun 2020The plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system.... (Review)
Review
The plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.
Topics: Animals; Cannabinoid Receptor Modulators; Cannabis; Endocannabinoids; Humans; Immunity
PubMed: 32585801
DOI: 10.3390/ijms21124448