Cannabis: pharmacology and toxicology in animals and humans

Cannabis: pharmacology and toxicology in animals and humans Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, δ9‐tetrahydrocannabinol (δ9‐THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to δ9‐THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty‐acid derived compound that possesses pharmacological properties similar to δ9‐THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid‐derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Addiction Wiley

Cannabis: pharmacology and toxicology in animals and humans

ADAMS, IRMA B.; MARTIN, BILLY R.
Addiction, Volume 91 (11) – Nov 1, 1996
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Publisher
Wiley
Copyright
Copyright © 1996 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0965-2140
eISSN
1360-0443
DOI
10.1046/j.1360-0443.1996.911115852.x
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Abstract

Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, δ9‐tetrahydrocannabinol (δ9‐THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to δ9‐THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty‐acid derived compound that possesses pharmacological properties similar to δ9‐THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid‐derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids.

Journal

Addiction – Wiley

Published: Nov 1, 1996

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    Little, Little; Compton, Compton; Johnson, Johnson; Melvin, Melvin; Martin, Martin
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  • Regional cerebral blood flow after marijuana smoking
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  • Structure of a cannabinoid receptor and functional expression of the cloned cDNA
    Matsuda, Matsuda; Lolait, Lolait; Brownstein, Brownstein; Young, Young; Bonner, Bonner
  • Characteristics of tetrahydrocannabinol tolerance
    McMillan, McMillan; Dewey, Dewey; Harris, Harris
  • L‐Δ 9 Transt etrahydrocannabinol in pigeons: tolerance to the behavioral effects
    McMillan, McMillan; Harris, Harris; Frankenheim, Frankenheim; Kennedy, Kennedy
  • Cannabimimetic activity of novel enantiomeric, benzofuran cannabinoids
    Mechoulam, Mechoulam; Breuer, Breuer; Jarbe, Jarbe; Hiltunen, Hiltunen; Glaser, Glaser
  • Towards cannabinoid drugs
    Mechoulam, Mechoulam; Feigenbaum, Feigenbaum
  • Enantiomeric cannabinoids: stereospecificity of psychotropic activity
    Mechoulam, Mechoulam; Feigenbaum, Feigenbaum; Lander, Lander
  • The search for endogenous ligands of the cannabinoid receptor
    Mechoulam, Mechoulam; Hanus, Hanus; Martin, Martin
  • Marihuana and temporal disintegration
    Melges, Melges; Tinklenberg, Tinklenberg; Hollister, Hollister; Gillespie, Gillespie
  • A cannabinoid derived prototypical analgesic
    Melvin, Melvin; Johnson, Johnson; Harbert, Harbert; Milne, Milne; Weissman, Weissman
  • Effects of marihuana on intraocular and blood pressure in glaucoma
    Merritt, Merritt; Crawford, Crawford; Alexander, Alexander; Anduze, Anduze; Gelbart, Gelbart
  • Behavioral and biochemical effects of chronic Δ 9 ‐tetrahyrocannabinol in rats
    Miczek, Miczek; Dihit, Dihit
  • Effects of cannabinoids on host resistance to Listeria monocytogenes and Herpes simplex virus
    Morahan, Morahan; Klykken, Klykken; Smith, Smith; Harris, Harris; Munson, Munson
  • The cloning of a family of genes that encode the melanocortin receptors
    Mountjoy, Mountjoy; Robbins, Robbins; Mortrud, Mortrud; Cone, Cone
  • Molecular characterization of a peripheral receptor for cannabinoids
    Munro, Munro; Thomas, Thomas; Abu‐Shaar, Abu‐Shaar
  • Inhibition of cellular mediated immunity in marihuana smokers
    Nahas, Nahas; Sucio‐Foca, Sucio‐Foca; Armand, Armand; Morishima, Morishima
  • Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes
    Nahas, Nahas; Morishima, Morishima; Desoize, Desoize
  • Reversible effects of acute and long‐term administration of Δ 9 ‐tetrahydrocannabinol (THC) on memory in the rat
    Nakamura, Nakamura; Da Silva, Da Silva; Concilio, Concilio; Wilkinson, Wilkinson; Masur, Masur
  • Plasma δ 9 ‐tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking
    Ohlsson, Ohlsson; Lindgren, Lindgren; Wahlen, Wahlen; Agurell, Agurell; Hollister, Hollister; Gillespie, Gillespie
  • Single dose kinetics of deuterium labeled Δ 9 ‐tetrahydrocannabinol in heavy and light cannabis users
    Ohlsson, Ohlsson; Lindgren, Lindgren; Wahlen, Wahlen; Agurell, Agurell; Holuster, Holuster; Gillespie, Gillespie
  • Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study
    Oviedo, Oviedo; Glowa, Glowa; Herkenham, Herkenham
  • Identification of cannabinoid receptors in cultures of rat cerebellar granule cells
    Pacheco, Pacheco; Ward, Ward; Childers, Childers
  • Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism
    Paton, Paton; Pertwee, Pertwee
    Bookmark
  • Interaction between marihuana and ethanol: effects on psycho‐motor performance
    Perez‐Reyes, Perez‐Reyes; Hicks, Hicks; Bumberry, Bumberry; Jeff‐Coat, Jeff‐Coat; Cook, Cook
  • The clinical pharmacology and dynamics of marijuana cigarette smoking
    Perez‐Reyes, Perez‐Reyes; Owens, Owens; Guiseppis, Guiseppis
  • Tolerance to the effect of Δ 1 ‐tetrahydrocannabinol on corticosterone levels in mouse plasma produced by repeated administration of cannabis extract or Δ 1 ‐tetrahydrocannabinol
    Pertwee, Pertwee
  • The central neuropharmacology of psychorropic cannabinoids
    Pertwee, Pertwee
  • Cross‐tolerance between δ 9 ‐tetrahydro‐cannabinol and the cannabimimetic agents, CP 55,940, WIN 55, 212‐2 and anandamide
    Pertwee, Pertwee; Stevenson, Stevenson; Griffin, Griffin
  • Enhancement by chlordiazepoxide of catalepsy induced in rats by intravenous or intrapallidal injections of enantiomeric cannabinoids
    Pertwee, Pertwee; Wickens, Wickens
  • Recent clinical experience with Dronabinol
    Plasse, Plasse; Gorter, Gorter; Krasnow, Krasnow; Lane, Lane; Shepard, Shepard; Wadleigh, Wadleigh
  • Drug findings in ‘Driving Under the Influence of Drugs’ cases: a problem of illicit drug use
    Poklis, Poklis; Maginn, Maginn; Barr, Barr
  • The residual neuropsychological effects of cannabis: the current status of research
    Pope, Pope; Gruber, Gruber; Yurgelun‐Todd, Yurgelun‐Todd
  • Differing effects of δ 9 tetrahydrocannabinol CTHC) on murine spleen cell populations dependent upon stimulators
    Pross, Pross; Nakano, Nakano; Widen, Widen
  • Intact humoral and cell‐mediated immunity in chronic marijuana smoking
    Rachelefsky, Rachelefsky; Opelz, Opelz; Mickey, Mickey
  • Structure‐activity relationships in cannabinoids
    Razdan, Razdan
    Bookmark
  • SR141716A, a potent and selective antagonist of the brain cannabinoid receptor
    Rinaldi‐Carmona, Rinaldi‐Carmona; Barth, Barth; Héaulme, Héaulme
  • Down‐regulation of rat brain cannabinoid binding sites after chronic Δ 9 tetrahydrocannabinol treatment
    Rodriguez, Rodriguez; Fonseca, Fonseca; Gorriti, Gorriti; Fernandez‐Ruiz, Fernandez‐Ruiz; Palomo, Palomo; Ramos, Ramos
  • Changes in rat brain cannabinoid binding sites after acute or chronic exposure to their endogenous agonist, anan‐damide, or to Δ 9 ‐tetrahydrocannabinol
    Romero, Romero; Garcia, Garcia; Fernandez‐Ruiz, Fernandez‐Ruiz; Cebeira, Cebeira; Ramos, Ramos
  • Decreased platelet aggregation following marihuana smoking in man
    Schaefer, Schaefer; Brackett, Brackett; Gunn, Gunn; Dubowski, Dubowski
  • Dose‐related inhibition of leukocyte migration by marijuana and δ 9 tetrahydrocannabinol (THC) in vitro
    Schwartzfare, Schwartzfare; Needle, Needle; Chavez‐Chase, Chavez‐Chase
  • Marijuana smoking, pulmonary function, and lung macrophage oxidant release
    Sherman, Sherman; Roth, Roth; Gong, Gong; Tashkin, Tashkin
  • Δ 9 ‐Tetrahydrocannabinol (THC) modulates IL‐1 bioactivity in human monocyte/macrophage cell lines
    Shivers, Shivers; Newton, Newton; Friedman, Friedman; Klein, Klein
  • Metabolism of Δ 1 ‐tetrahydrocannabinol by rats tolerant to cannabis
    Siemens, Siemens; Kalant, Kalant
  • Response of rhesus monkey lymphocytes to short‐term administration of THC
    Silverman, Silverman; Darnell, Darnell; Montiel, Montiel; Smith, Smith; Asch, Asch
  • Normal skin test response in chronic marijuana users
    Sllverstein, Sllverstein; Lessin, Lessin
  • The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice
    Smith, Smith; Compton, Compton; Welch, Welch; Razdan, Razdan; Mechoulam, Mechoulam; Martin, Martin
  • Interactions between Δ 9 ‐tetrahydrocannabinol and Kappa opioids in mice
    Smith, Smith; Welch, Welch; Marten, Marten
  • Suppression of human macrophage function in vitro by Δ 9 ‐tetrahydrocannabinol
    Spector, Spector; Lancz, Lancz
  • State‐dependent (dissociative) effects of marihuana on human memory
    Stillman, Stillman; Weingartner, Weingartner; Wyatt, Wyatt; Gillin, Gillin; Eich, Eich
  • Electroen‐cephalographic and evoked potential methods in human marihuana research: historical review and future trends
    Struve, Struve; Straumanis, Straumanis
  • Persistent topographic quantitative EEG sequelae of chronic marijuana use: a replication study and initial discriminant function analysis
    Struve, Struve; Straumanis, Straumanis; Patrick, Patrick
  • Marihuana Psychosis
    Talbott, Talbott; Teague, Teague
  • Psychopathology and differential diagnosis of so‐called cannabis psychoses
    Taschner, Taschner
  • Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using ( 3 H)11–OH‐Δ 9 ‐THC‐DMH
    Thomas, Thomas; Wei, Wei; Martin, Martin
  • Oral and intravenous toxicity of Δ 9 ‐tetrahydrocannabinol in rhesus monkeys
    Thompson, Thompson; Fleischman, Fleischman; Rosenkrantz, Rosenkrantz; Braude, Braude
  • Cannabis and psychosis: is there epidemiological evidence for an association
    Thoknicroft, Thoknicroft
  • Physical withdrawal in rats tolerant to Δ 9 ‐tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist
    Tsou, Tsou; Patrick, Patrick; Walker, Walker
  • Novel antagonist implicates the CB 1 cannabinoid receptor in the hypotensive action of anandamide
    Varga, Varga; Lake, Lake; Martin, Martin; Kunos, Kunos
    Bookmark
  • Metabolism, disposition, and kinetics of Δ 9 ‐tetrahydrocannabinol in men and women
    Wall, Wall; Sadler, Sadler; Brine, Brine; Taylor, Taylor; Perez‐Reyes, Perez‐Reyes
  • Peripheral blood lymphocyte sub‐populations and mitogen responsiveness in tobacco and marijuana smokers
    Wallace, Wallace; Tashkin, Tashkin; Oishi, Oishi; Barbers, Barbers
  • Pravadoline: profile in isolated tissue preparations
    Ward, Ward; Mastriani, Mastriani; Casiano, Casiano; Arnold, Arnold
  • Development of tolerance and cross‐tolerance to the cataleptogenic effects of Δ 8 ‐tetrahydrocannabinol and ii‐hydroxy‐Δ 8 ‐tetrahydrocannabinol in mice
    Watanabe, Watanabe; Yamamoto, Yamamoto; Yoshimura, Yoshimura
  • Alcohol and other drug use and automobile safety: a survey of Boston‐area teen‐agers
    Wechsler, Wechsler; Rohman, Rohman; Kotch, Kotch; Idelson, Idelson
    Bookmark
  • The effect of the brain constituent anandamide. a cannabinoid receptor agonist, on the hypotholamo‐piruitary‐adrenal axis in the rat
    Weidenfeld, Weidenfeld; Feldman, Feldman; Mechoulam, Mechoulam
  • Modulation of cannabinoid‐induced antinociception following intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine
    Welch, Welch; Thomas, Thomas; Patrick, Patrick
  • The chronic cerebral effects of cannabis use. II. Psychological findings and conclusions
    Wert, Wert; Raulin, Raulin
  • Chronic exposure to Δ 9 ‐tetrahydrocannabinol fails to irreversibly alter brain cannabinoid receptors
    Westlake, Westlake; Howlett, Howlett; Ali, Ali; Paule, Paule; Scallet, Scallet; Slikker, Slikker
  • Aspects of tolerance to and dependence on cannabis
    Wikler, Wikler
  • Antagonism of the discriminative stimulus effects of Δ 9 ‐tetrahydrocannabinol in rats and rhesus monkeys
    Wiley, Wiley; Lowe, Lowe; Balster, Balster; Martin, Martin
  • Drugs in fatally injured young male drivers
    Williams, Williams; Peat, Peat; Crouch, Crouch; Wells, Wells; Finkle, Finkle
  • Inhibition by Δ 9 ‐tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages
    Zheng, Zheng; Specter, Specter; Friedman, Friedman
  • Effects on variable‐interval performance in rats of delta 9–tetrahydrocannabinol and cannabidiol. separately and in combination
    Zuardi, Zuardi; Karniol, Karniol

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