Dronabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.Receptors, Cannabinoid: A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Receptor, Cannabinoid, CB2: A subclass of cannabinoid receptor found primarily on immune cells where it may play a role modulating release of CYTOKINES.Benzoxazines: OXAZINES with a fused BENZENE ring.Cannabidiol: Compound isolated from Cannabis sativa extract.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Cannabis: The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber.Cannabinoid Receptor Modulators: Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.Endocannabinoids: Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.Cyclohexanols: Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers.MorpholinesPolyunsaturated Alkamides: Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Cannabinol: A physiologically inactive constituent of Cannabis sativa L.Piperidines: A family of hexahydropyridines.Arachidonic AcidsReceptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Designer Drugs: Drugs designed and synthesized, often for illegal street use, by modification of existing drug structures (e.g., amphetamines). Of special interest are MPTP (a reverse ester of meperidine), MDA (3,4-methylenedioxyamphetamine), and MDMA (3,4-methylenedioxymethamphetamine). Many drugs act on the aminergic system, the physiologically active biogenic amines.BornanesSubstance Abuse Detection: Detection of drugs that have been abused, overused, or misused, including legal and illegal drugs. Urine screening is the usual method of detection.Glycerides: GLYCEROL esterified with FATTY ACIDS.Monoacylglycerol Lipases: An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.Marijuana Smoking: Inhaling and exhaling the smoke from CANNABIS.Street Drugs: Drugs obtained and often manufactured illegally for the subjective effects they are said to produce. They are often distributed in urban areas, but are also available in suburban and rural areas, and tend to be grossly impure and may cause unexpected toxicity.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents).Enzyme Multiplied Immunoassay Technique: An immunoenzyme test for the presence of drugs and other substances in urine and blood. The test uses enzyme linked antibodies that react only with the particular drug for which the sample is being tested.Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.Forensic Toxicology: The application of TOXICOLOGY knowledge to questions of law.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.TRPV Cation Channels: A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.AmidohydrolasesCatalepsy: A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.Hypothermia: Lower than normal body temperature, especially in warm-blooded animals.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Controlled Substances: Drugs or chemical agents whose manufacture, possession, or use are regulated by government. This may include narcotics and prescription medications.Fluorescence Polarization Immunoassay: Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations.Benzodioxoles: Compounds based on benzene fused to oxole. They can be formed from methylated CATECHOLS such as EUGENOL.Limit of Detection: Concentration or quantity that is derived from the smallest measure that can be detected with reasonable certainty for a given analytical procedure.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.Appetite Stimulants: Agents that are used to stimulate appetite. These drugs are frequently used to treat anorexia associated with cancer and AIDS.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.ShrewsSynaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Periaqueductal Gray: Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.Drug and Narcotic Control: Control of drug and narcotic use by international agreement, or by institutional systems for handling prescribed drugs. This includes regulations concerned with the manufacturing, dispensing, approval (DRUG APPROVAL), and marketing of drugs.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Behavior, Animal: The observable response an animal makes to any situation.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Mononeuropathies: Disease or trauma involving a single peripheral nerve in isolation, or out of proportion to evidence of diffuse peripheral nerve dysfunction. Mononeuropathy multiplex refers to a condition characterized by multiple isolated nerve injuries. Mononeuropathies may result from a wide variety of causes, including ISCHEMIA; traumatic injury; compression; CONNECTIVE TISSUE DISEASES; CUMULATIVE TRAUMA DISORDERS; and other conditions.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Legislation, Drug: Laws concerned with manufacturing, dispensing, and marketing of drugs.ResorcinolsNeural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Vomiting: The forcible expulsion of the contents of the STOMACH through the MOUTH.Antiemetics: Drugs used to prevent NAUSEA or VOMITING.Carbamates: Derivatives of carbamic acid, H2NC(=O)OH. Included under this heading are N-substituted and O-substituted carbamic acids. In general carbamate esters are referred to as urethanes, and polymers that include repeating units of carbamate are referred to as POLYURETHANES. Note however that polyurethanes are derived from the polymerization of ISOCYANATES and the singular term URETHANE refers to the ethyl ester of carbamic acid.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Mice, Inbred ICRBody Temperature: The measure of the level of heat of a human or animal.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating): An NAD-dependent glyceraldehyde-3-phosphate dehydrogenase found in the cytosol of eucaryotes. It catalyses the dehydrogenation and phosphorylation of GLYCERALDEHYDE 3-PHOSPHATE to 3-phospho-D-glyceroyl phosphate, which is an important step in the GLYCOLYSIS pathway.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Substance-Related Disorders: Disorders related to substance abuse.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Ceramides: Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.Mice, Inbred C57BLReceptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Solid Phase Extraction: An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.Psychoses, Substance-Induced: Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Analgesia: Methods of PAIN relief that may be used with or in place of ANALGESICS.Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Saliva: The clear, viscous fluid secreted by the SALIVARY GLANDS and mucous glands of the mouth. It contains MUCINS, water, organic salts, and ptylin.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.PyransSignal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.CA3 Region, Hippocampal: A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA2 FIELD and the DENTATE GYRUS.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Transient Receptor Potential Channels: A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cardiovascular System: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.AnilidesTime Factors: Elements of limited time intervals, contributing to particular results or situations.Nociceptors: Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Pyramidal Cells: Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Rats, Long-Evans: An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Purkinje Cells: The output neurons of the cerebellar cortex.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.Injections, Intraventricular: Injections into the cerebral ventricles.Glioma: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Chronic Pain: Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Gastrointestinal Motility: The motor activity of the GASTROINTESTINAL TRACT.Acetonitriles: Compounds in which a methyl group is attached to the cyano moiety.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.Palmitic Acids: A group of 16-carbon fatty acids that contain no double bonds.Amphetamines: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.Muscle Tonus: The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. (Stedman, 25th ed)Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Ethanolamines: AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.Reinforcement (Psychology): The strengthening of a conditioned response.Receptors, Glycine: Cell surface receptors that bind GLYCINE with high affinity and trigger intracellular changes which influence the behavior of cells. Glycine receptors in the CENTRAL NERVOUS SYSTEM have an intrinsic chloride channel and are usually inhibitory.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Anti-Anxiety Agents: Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Benzodiazepines: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.Plant Oils: Oils derived from plants or plant products.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Conditioning, Operant: Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.Hypothalamus: Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Discrimination Learning: Learning that is manifested in the ability to respond differentially to various stimuli.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Amygdala: Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Glucuronides: Glycosides of GLUCURONIC ACID formed by the reaction of URIDINE DIPHOSPHATE GLUCURONIC ACID with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and BILIRUBIN metabolism to a more water-soluble compound that can be eliminated in the URINE and BILE.Pain Threshold: Amount of stimulation required before the sensation of pain is experienced.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Tandem Mass Spectrometry: A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.Reference Standards: A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.CA1 Region, Hippocampal: One of four subsections of the hippocampus described by Lorente de No, located furthest from the DENTATE GYRUS.Anticonvulsants: Drugs used to prevent SEIZURES or reduce their severity.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Cell Line, Tumor: A cell line derived from cultured tumor cells.Peroxisome Proliferator-Activated Receptors: TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.False Negative Reactions: Negative test results in subjects who possess the attribute for which the test is conducted. The labeling of diseased persons as healthy when screening in the detection of disease. (Last, A Dictionary of Epidemiology, 2d ed)Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Ghrelin: A 28-amino acid, acylated, orexigenic peptide that is a ligand for GROWTH HORMONE SECRETAGOGUE RECEPTORS. Ghrelin is widely expressed but primarily in the stomach in the adults. Ghrelin acts centrally to stimulate growth hormone secretion and food intake, and peripherally to regulate energy homeostasis. Its large precursor protein, known as appetite-regulating hormone or motilin-related peptide, contains ghrelin and obestatin.Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency or other output.Epilepsy: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Anxiety: Feeling or emotion of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Ganglia, Spinal: Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Benzamides: BENZOIC ACID amides.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Receptors, Glutamate: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Tetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)

Solid-phase microextraction for cannabinoids analysis in hair and its possible application to other drugs. (1/1123)

This paper describes the application of solid-phase microextraction (SPME) to cannabis testing in hair. Fifty milligrams of hair was washed with petroleum ether, hydrolyzed with NaOH, neutralized, deuterated internal standard was added and directly submitted to SPME. The SPME was analyzed by GC-MS. The limit of detection was 0.1 ng/mg for cannabinol (CBN) and delta9-tetrahydrocannabinol (THC) and 0.2 ng/mg for cannabidiol (CBD). THC was detected in a range spanning from 0.1 to 0.7 ng/mg. CBD concentrations ranged from 0.7 to 14.1 ng/mg, and CBN concentrations ranged from 0.4 to 0.7 ng/mg. The effectiveness of different decontamination procedures was also studied on passively contaminated hair. The proposed method is also suitable for the analysis of methadone in hair; cocaine and cocaethylene can be detected in hair with SPME extraction after enzymatic hydrolysis.  (+info)

Toxicological findings in a fatal ingestion of methamphetamine. (2/1123)

This paper presents the case history of a fatality caused by the complications brought about by the presence of methamphetamine and ethanol. Drug concentrations are reported from samples obtained approximately 15 min after the subject was last observed to be chewing what was then believed to be gum, 3 h after the initial toxic symptoms were displayed, 6, 11, and 22 h later. The subjects conditions deteriorated over the course of this time, and he was declared dead 33 h after the initial display of toxic symptoms. The toxicological findings and concentration levels of the reported biological specimens concurred with the expected findings in a case of methamphetamine toxicity.  (+info)

The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells. (3/1123)

Upon activation, brain microglial cells release proinflammatory mediators, such as nitric oxide (NO), which may play an important role in the central nervous system antibacterial, antiviral, and antitumor activities. However, excessive release of NO has been postulated to elicit immune-mediated neurodegenerative inflammatory processes and to cause brain injury. In the present study, the effect of cannabinoids on the release of NO from endotoxin/cytokine-activated rat cortical microglial cells was evaluated. A drug dose-dependent (0.1 microM-8 microM) inhibition of NO release from rat microglial cells was exerted by the cannabinoid receptor high-affinity binding enantiomer (-)-CP55940. In contrast, a minimal inhibitory effect was exerted by the lower affinity binding paired enantiomer (+)-CP56667. Pretreatment of microglial cells with the Galphai/Galphao protein inactivator pertussis toxin, cyclic AMP reconstitution with the cell-permeable analog dibutyryl-cAMP, or treatment of cells with the Galphas activator cholera toxin, resulted in reversal of the (-)-CP55940-mediated inhibition of NO release. A similar reversal in (-)-CP55940-mediated inhibition of NO release was effected when microglial cells were pretreated with the central cannabinoid receptor (CB1) selective antagonist SR141716A. Mutagenic reverse transcription-polymerase chain reaction, Western immunoblot assay using a CB1 receptor amine terminal domain-specific antibody, and cellular colocalization of CB1 and the microglial marker Griffonia simplicifolia isolectin B4 confirmed the expression of the CB1 receptor in rat microglial cells. Collectively, these results indicate a functional linkage between the CB1 receptor and cannabinoid-mediated inhibition of NO production by rat microglial cells.  (+info)

Cannabinoid suppression of noxious heat-evoked activity in wide dynamic range neurons in the lumbar dorsal horn of the rat. (4/1123)

The effects of cannabinoid agonists on noxious heat-evoked firing of 62 spinal wide dynamic range (WDR) neurons were examined in urethan-anesthetized rats (1 cell/animal). Noxious thermal stimulation was applied with a Peltier device to the receptive fields in the ipsilateral hindpaw of isolated WDR neurons. To assess the site of action, cannabinoids were administered systemically in intact and spinally transected rats and intraventricularly. Both the aminoalkylindole cannabinoid WIN55,212-2 (125 microg/kg iv) and the bicyclic cannabinoid CP55,940 (125 microg/kg iv) suppressed noxious heat-evoked activity. Responses evoked by mild pressure in nonnociceptive neurons were not altered by CP55,940 (125 microg/kg iv), consistent with previous observations with another cannabinoid agonist, WIN55,212-2. The cannabinoid induced-suppression of noxious heat-evoked activity was blocked by pretreatment with SR141716A (1 mg/kg iv), a competitive antagonist for central cannabinoid CB1 receptors. By contrast, intravenous administration of either vehicle or the receptor-inactive enantiomer WIN55,212-3 (125 microg/kg) failed to alter noxious heat-evoked activity. The suppression of noxious heat-evoked activity induced by WIN55,212-2 in the lumbar dorsal horn of intact animals was markedly attenuated in spinal rats. Moreover, intraventricular administration of WIN55,212-2 suppressed noxious heat-evoked activity in spinal WDR neurons. By contrast, both vehicle and enantiomer were inactive. These findings suggest that cannabinoids selectively modulate the activity of nociceptive neurons in the spinal dorsal horn by actions at CB1 receptors. This modulation represents a suppression of pain neurotransmission because the inhibitory effects are selective for pain-sensitive neurons and are observed with different modalities of noxious stimulation. The data also provide converging lines of evidence for a role for descending antinociceptive mechanisms in cannabinoid modulation of spinal nociceptive processing.  (+info)

Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation. (5/1123)

1. The aim of the present study was to analyse the cardiovascular actions of the synthetic CB1/CB2 cannabinoid receptor agonist WIN55212-2, and specifically to determine its sites of action on sympathetic cardiovascular regulation. 2. Pithed rabbits in which the sympathetic outflow was continuously stimulated electrically or which received a pressor infusion of noradrenaline were used to study peripheral prejunctional and direct vascular effects, respectively. For studying effects on brain stem cardiovascular regulatory centres, drugs were administered into the cisterna cerebellomedullaris in conscious rabbits. Overall cardiovascular effects of the cannabinoid were studied in conscious rabbits with intravenous drug administration. 3. In pithed rabbits in which the sympathetic outflow was continuously electrically stimulated, intravenous injection of WIN55212-2 (5, 50 and 500 microg kg(-1)) markedly reduced blood pressure, the spillover of noradrenaline into plasma and the plasma noradrenaline concentration, and these effects were antagonized by the CB1 cannabinoid receptor-selective antagonist SR141716A. The hypotensive and the sympathoinhibitory effect of WIN55212-2 was shared by CP55940, another mixed CB1/CB2 cannabinoid receptor agonist, but not by WIN55212-3, the enantiomer of WIN55212-2, which lacks affinity for cannabinoid binding sites. WIN55212-2 had no effect on vascular tone established by infusion of noradrenaline in pithed rabbits. 4. Intracisternal application of WIN55212-2 (0.1, 1 and 10 microg kg(-1)) in conscious rabbits increased blood pressure and the plasma noradrenaline concentration and elicited bradycardia; this latter effect was antagonized by atropine. 5. In conscious animals, intravenous injection of WIN55212-2 (5 and 50 microg kg(-1)) caused bradycardia, slight hypotension, no change in the plasma noradrenaline concentration, and an increase in renal sympathetic nerve firing. The highest dose of WIN55212-2 (500 microg kg(-1)) elicited hypotension and tachycardia, and sympathetic nerve activity and the plasma noradrenaline concentration declined. 6. The results obtained in pithed rabbits indicate that activation of CB1 cannabinoid receptors leads to marked peripheral prejunctional inhibition of noradrenaline release from postganglionic sympathetic axons. Intracisternal application of WIN55212-2 uncovered two effects on brain stem cardiovascular centres: sympathoexcitation and activation of cardiac vagal fibres. The highest dose of systemically administered WIN55212-2 produced central sympathoinhibition; the primary site of this action is not known.  (+info)

Stage-specific excitation of cannabinoid receptor exhibits differential effects on mouse embryonic development. (6/1123)

Anandamide (N-arachidonoylethanolamine), an arachidonic acid derivative, is an endogenous ligand for both the brain-type (CB1-R) and spleen-type (CB2-R) cannabinoid receptors. We have previously demonstrated that preimplantation mouse embryos express mRNA for these receptors and that the periimplantation uterus contains the highest level of anandamide yet discovered in a mammalian tissue. We further demonstrated that 2-cell mouse embryos exposed to low levels of anandamide (7 nM) or other known cannabinoid agonists in culture exhibit markedly compromised embryonic development to blastocysts and that this effect is mediated by CB1-R. In contrast, the present study demonstrates that blastocysts exposed in culture to the same low levels of cannabinoid agonists exhibited accelerated trophoblast differentiation with respect to fibronectin-binding activity and trophoblast outgrowth. Again, these effects resulted from activation of embryonic CB1-R. There was a differential concentration-dependent effect of cannabinoids on the trophoblast, with an observed inhibition of differentiation at higher doses. These results provide evidence for the first time that cannabinoid effects are differentially executed depending on the embryonic stage and cannabinoid levels in the environment. Since uterine anandamide levels are lowest at the sites of implantation and highest at the interimplantation sites, the new findings imply that site-specific levels of anandamide and/or other endogenous ligands in the uterus may regulate implantation spatially by promoting trophoblast differentiation at the sites of blastocyst implantation.  (+info)

A role for N-arachidonylethanolamine (anandamide) as the mediator of sensory nerve-dependent Ca2+-induced relaxation. (7/1123)

We tested the hypothesis that an endogenous cannabinoid (CB) receptor agonist, such as N-arachidonylethanolamine (anandamide), is the transmitter that mediates perivascular sensory nerve-dependent Ca2+-induced relaxation. Rat mesenteric branch arteries were studied using wire myography; relaxation was determined after inducing contraction with norepinephrine. Cumulative addition of Ca2+ caused dose-dependent relaxation (ED50 = 2.2 +/- 0.09 mM). The relaxation was inhibited by 10 mM TEA and 100 nM iberiotoxin, a blocker of large conductance Ca2+-activated K+ channels, but not by 5 microM glibenclamide, 1 mM 4-aminopyridine, or 30 nM apamin. Ca2+-induced relaxation was also blocked by the selective CB receptor antagonist SR141716A and was enhanced by pretreatment with 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (pefabloc; 30 microM), an inhibitor of anandamide metabolism. Anandamide also caused dose-dependent relaxation (ED50 =.72 +/- 0.3 microM). The relaxation was not inhibited by endothelial denudation, 10 microM indomethacin, or 1 microM miconazole, but was blocked by 3 microM SR141716A, 10 mM TEA, precontraction with 100 mM K+, and 100 nM iberiotoxin, and was enhanced by treatment with 30 microM pefabloc. Mesenteric branch arteries were 200-fold more sensitive to the relaxing action of anandamide than arachidonic acid (ED50 = 160 +/- 7 microM). These data show that: 1) Ca2+ and anandamide cause hyperpolarization-mediated relaxation of mesenteric branch arteries, which is dependent on an iberiotoxin-sensitive Ca2+-activated K+ channel, 2) relaxation induced by both Ca2+ and anandamide is inhibited by CB receptor blockade, and 3) relaxation induced by anandamide is not dependent on its breakdown to arachidonic acid and subsequent metabolism. These findings support the hypothesis that anandamide, or a similar cannabinoid receptor agonist, mediates nerve-dependent Ca2+-induced relaxation in the rat.  (+info)

Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630. (8/1123)

We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and also investigated whether L759633 and L759656, are CB2 receptor agonists. Binding assays with membranes from CHO cells stably transfected with human CB1 or CB2 receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and L759656 (CB2/CB1 affinity ratios = 163 and 414 respectively) and showed AM630 to have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165. In CB2-transfected cells, L759633 and L759656 were potent inhibitors of forskolin-stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively and CB1/CB2 EC50 ratios of > 1000 and > 3000 respectively. AM630 inhibited [35S]-GTPgammaS binding to CB2 receptor membranes (EC50 = 76.6 nM), enhanced forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 microM), and antagonized the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940. In CB1-transfected cells, forskolin-stimulated cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 microM and 45.9% at 10 microM) and by L759633 at 10 microM (48%) but not 1 microM. L759656 (10 microM) was not inhibitory. AM630 also produced a slight decrease in the mean inhibitory effect of CP55940 on cyclic AMP production which was not statistically significant. We conclude that AM630 is a CB2-selective ligand that behaves as an inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors. L759633 and L759656 are both potent CB2-selective agonists.  (+info)

  • For the first time ever, pharmaceutical companies will have access to a wide variety of patent protected, stable cannabinoid molecules synthesized to provide stability and consistency for use in developing new medicines, with numerous potential therapeutic applications," Reshef Swisa, the chief executive officer for EPM, said in a press release. (ganjapreneur.com)
  • The development is critical because cannabinoid acids are significantly more potent than typical cannabinoids (CBDA is about a thousand times more potent than CBD , for example), but the plant's naturally occurring acids are very unstable and had so far eluded chemical synthesis. (ganjapreneur.com)
  • The patient's response to cannabinoid treatment may have a genetic background, which depends on genes polymorphism involved in the action, metabolism, and the transport of these substances in the organism. (springer.com)
  • Cannabis is also home to its share of unique compounds, however, and these substances are called "cannabinoids" since they are only found in Cannabis sativa. (selfgrowth.com)
  • Missouri has become the latest state to ban products containing synthetic cannabinoids, with Gov. Jay Nixon signing into law this week a bill making them and products containing them controlled substances in the state. (stopthedrugwar.org)
  • The Administrator of the Drug Enforcement Administration (DEA) is issuing this final order to temporarily place five synthetic cannabinoids into the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions. (usdoj.gov)
  • As a result of this order, the full effect of the CSA and its implementing regulations including criminal, civil and administrative penalties, sanctions and regulatory controls of Schedule I substances will be imposed on the manufacture, distribution, possession, importation, and exportation of these synthetic cannabinoids. (usdoj.gov)
  • The Deputy Administrator of the Drug Enforcement Administration (DEA) is issuing this notice of intent to temporarily schedule three synthetic cannabinoids into the Controlled Substances Act (CSA) pursuant to the temporary scheduling provisions of 21 U.S.C. 811 (h). (usdoj.gov)
  • Any final order will impose the administrative, civil, and criminal sanctions and regulatory controls of Schedule I substances under the CSA on the manufacture, distribution, possession, importation, and exportation of these synthetic cannabinoids. (usdoj.gov)
  • These are the classical cannabinoids (THC and HU-210), as well as the non-classical cannabinoid (CP55940) and certain aminoalkylindoles. (news-medical.net)
  • The classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes . (wikipedia.org)
  • The classical cannabinoids are derived from their respective 2- carboxylic acids (2-COOH) by decarboxylation (catalyzed by heat, light, or alkaline conditions). (wikipedia.org)
  • Natural cannabinoids, also called herbal cannabinoids and classical cannabinoids , are nearly insoluble in water but soluble in lipids , alcohols , and other non-polar organic solvents . (wikidoc.org)
  • Although three clinical trials studied cannabinoids for the treatment of Parkinson's Disease , these studies "did not provide a clear answer whether cannabinoids modify the progression or the outcome of the disease," wrote Bilkei-Gorzo. (time.com)
  • Some clinical trials showed that cannabinoids help reduce pain in some people. (cancer.ca)
  • CNAB ) progress in initiating clinical trials to study its proprietary Prana Bio Medicinals cannabinoid compounds. (yahoo.com)
  • In order to do so, the company must undertake extensive clinical trials designed to prove both the safety and efficacy of cannabinoid-based compounds given that only a handful of synthetic compounds have been approved by government regulatory bodies thus far. (yahoo.com)
  • Advise patients that larger clinical trials would be necessary before cannabinoid activators could be used widely for conditions of the lower colon. (medpagetoday.com)
  • There is an urgent need for rigorous clinical trials to research the use of cannabinoids in pediatric patients. (cmaj.ca)
  • 3 , 5 The use of cannabinoids to treat some pediatric conditions has become so common that recruiting cannabinoid-naive children for clinical trials has become challenging. (cmaj.ca)
  • To guide the development of more clinical trials of cannabinoids in children with neurologic disorders, several aspects of study design must be considered. (cmaj.ca)
  • Retrieved on July 19, 2019 from https://www.news-medical.net/news/20190619/Metabolic-engineering-of-cannabinoids-are-we-there-yet.aspx. (news-medical.net)
  • There are conflicting interpretations of the evidence regarding the efficacy, tolerability, and safety of cannabinoids in pain management and palliative medicine. (nih.gov)
  • Some medical professionals and patients argue that cannabinoids have marked analgesic properties, while other physicians, who cite the still relatively scant literature supporting their use, are skeptical about their efficacy, especially in comparison with other currently available analgesics. (psychiatrictimes.com)
  • Although no cannabinoids are currently FDA-approved as analgesics, there is ongoing research on their efficacy. (psychiatrictimes.com)
  • Synthetic cannabinoids can affect brain function. (cdc.gov)
  • Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids. (nih.gov)
  • Determination and characterization of a cannabinoid receptor in rat brain. (springer.com)
  • Isolation and structure of a brain constituent that binds to the cannabinoid receptor. (springer.com)
  • Cannabinoids are active in areas of the brain known to be involved in migraine pathophysiology, including areas suspected of being involved in the generation of migraine. (medscape.com)
  • Cannabinoid receptors have been found in several areas of the brain identified as potential migraine generators. (medscape.com)
  • The latest review, published in Philosophical Transactions of the Royal Society B, suggests that activating the brain's cannabinoid system may trigger a sort of anti-oxidant cleanse, removing damaged cells and improving the efficiency of the mitochrondria, the energy source that powers cells, ultimately leading to a more robustly functioning brain. (time.com)
  • Previous studies have linked cannabinoids to increased amounts of brain-derived neurotrophic factor (BDNF), a substance that protects brain cells and promotes the growth of new ones. (time.com)
  • Andras Bilkei-Gorzo of the Institute of Molecular Psychiatry at the University of Bonn in Germany and an author of the study, is encouraged by the expanding knowledge of the brain's cannabinoid system and its potential for leading to new understanding of aging in the brain. (time.com)
  • Some cannabinoids are psychoactive (acting on the brain and changing mood or consciousness) (see Question 1 ). (cancer.gov)
  • The human brain has more cannabinoid receptors than any other G protein-coupled receptor (GPCR) type. (wikipedia.org)
  • However, with the passage of the 2018 Farm Bill, which made hemp-derived cannabinoids legal, it is expected that research restrictions will no longer inhibit progress and JC Pharma Inc. will be able to share their formulation within the scientific community. (prnewswire.com)
  • Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents. (nih.gov)
  • These findings highlight the potential for cannabinoids to provide a dual function by acting as anti-inflammatory agents as well as regulators of MSC biology in order to enhance tissue engineering strategies aimed at cartilage repair. (mdpi.com)
  • Nevertheless, the results suggest that "the potential for cannabinoids to modulate colonic motor function in disease deserves further study," the investigators concluded. (medpagetoday.com)
  • And for the most common form of dementia, "Despite the promising preclinical results, the detailed clinical evaluation of cannabinoids in [Alzheimer's] patients is missing," he said in the paper. (time.com)
  • In addition, we are interested in the evaluation of cannabinoids as anticancer agents, which can exhibit synergistic potential with conventional therapies. (up.pt)
  • Now, evidence has emerged that suggests an additional effect results from the cannabinoid pathway, according to a publication in Nature Medicine . (wired.com)
  • They found there was only moderate-quality evidence to suggest cannabinoids may alleviate chronic neuropathic or cancer pain and muscle contractions or involuntary movements due to multiple sclerosis. (bristol.ac.uk)
  • There was very low-quality evidence to indicate patients treated with cannabinoids showed improvement in anxiety, psychosis and depression. (bristol.ac.uk)
  • Current evidence for the existence of these new molecular targets for cannabinoids is summarized in this review. (ingentaconnect.com)
  • The use of cannabinoids to treat mental health conditions cannot be justified based on current evidence, according to new analysis published in The Lancet Psychiatry . (cosmosmagazine.com)
  • In countries where medicinal cannabinoids are already legal, doctors and patients must be aware of the limitations of existing evidence and the risks of cannabinoids," says lead author Louisa Degenhardt, from the National Drug and Alcohol Research Centre (NDARC) at Australia's University of NSW. (cosmosmagazine.com)
  • We provide experimental evidence to show that activation of the cannabinoid system enhances the survival, migration and chondrogenic differentiation of MSCs, which are three major tenets behind the success of a cell-based tissue-engineered cartilage repair strategy. (mdpi.com)
  • Based upon prior evidence showing how specific cannabinoids attach to different chemical configurations, researchers were able predict how these cannabinoids would fit into the three-dimensional CB1 model. (eurekalert.org)
  • 2 - 5 Without licensed products supported by high-quality evidence, unregulated use of cannabinoids in children will continue, particularly given the impending legalization of cannabis in Canada and parents' desperation for effective treatments. (cmaj.ca)
  • It is time to move away from the "era of the anecdote" and toward evidence-informed selection and dosing of cannabinoids in children. (cmaj.ca)
  • Marinol is a prescribed cannabinoid from my doctor - and I am going to test it against the herbal cannabinoids I have been baking into my brownies for five years now. (norml.org)
  • T]he '911 patent claims are novel and inventive because they are directed to never before made liquid formulations of highly enriched extracts of plant cannabinoids. (ipwatchdog.com)
  • If even a single piece is removed from this cannabinoid puzzle, the benefits of the remaining cannabinoids are reduced, and isolating single cannabinoids may considerably reduce their effectiveness. (selfgrowth.com)
  • One thing is for sure: synthetic cannabinoids do not look anything like herbal cannabinoids - the ones from the plant itself. (norml.org)
  • I have been self-medicating with herbal cannabinoids for five years to provide relief from MS, which I have had for 23 years. (norml.org)
  • There are today seventy known herbal cannabinoids. (wikidoc.org)
  • And while it contributes to everything from pain relief to building material , did you know that there are other plants that contain cannabinoids that are also extremely useful? (davidwolfe.com)
  • Can you think of any other helpful plants that contain cannabinoids? (davidwolfe.com)
  • Natural cannabinoids are only known to occur naturally in the cannabis plant, and are concentrated in a viscous resin that is produced in glandular structures known as trichomes . (wikidoc.org)
  • To the right the main classes of natural cannabinoids are shown. (wikidoc.org)