Skip to main content
SpringerLink
Log in
Book cover

Cannabinoids pp 691–717Cite as

Cannabinoid Tolerance and Dependence

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 168))

Abstract

The use of marijuana for recreational and medicinal purposes has resulted in a large prevalence of chronic marijuana users. Consequences of chronic cannabinoid administration include profound behavioral tolerance and withdrawal symptoms upon drug cessation. A marijuana withdrawal syndrome is only recently gaining acceptance as being clinically significant. Similarly, laboratory animals exhibit both tolerance and dependence following chronic administration of cannabinoids. These animal models are being used to evaluate the high degree of plasticity that occurs at the molecular level in various brain regions following chronic cannabinoid exposure. In this review, we describe recent advances that have increased our understanding of the impact of chronic cannabinoid administration on cannabinoid receptors and their signal transduction pathways. Additionally, we discuss several potential pharmacotherapies that have been examined to treat marijuana dependence.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   629.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   799.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aceto M, Scates S, Lowe J, Martin B (1995) Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. Eur J Pharmacol 282:R1–R2

    Article  PubMed  CAS  Google Scholar 

  • Aceto M, Scates S, Lowe J, Martin B (1996) Dependence on ⊲9-tetrahydrocannabinol: studies on precipitated and abrupt withdrawal. J Pharmacol Exp Ther 278:1290–1295

    PubMed  CAS  Google Scholar 

  • Aceto MD, Scates SM, Razdan RK, Martin BR (1998) Anandamide, an endogenous cannabinoid, has a very low physical dependence potential. J Pharmacol Exp Ther 287:598–605

    PubMed  CAS  Google Scholar 

  • Aceto MD, Scates SM, Martin BB (2001) Spontaneous and precipitated withdrawal with a synthetic cannabinoid, WIN 55212-2. Eur J Pharmacol 416:75–81

    Article  PubMed  CAS  Google Scholar 

  • Anthony J, Warner L, Kessler R (1994) Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbidity Survey. Exp Clin Psychopharmacol 2:244–268

    Google Scholar 

  • Bass C, Welch S, Martin B (2004) Reversal of delta(9)-tetrahydrocannabinol-induced tolerance by specific kinase inhibitors. Eur J Pharmacol 496:99–108

    Article  PubMed  CAS  Google Scholar 

  • Bass CE, Martin BR (2000) Time course for the induction and maintenance of tolerance to delta(9)-tetrahydrocannabinol in mice. Drug Alcohol Depend 60:113–119

    PubMed  CAS  Google Scholar 

  • Beardsley PM, Martin BR (2000) Effects of the cannabinoid CB(1) receptor antagonist, SR141716A, after delta(9)-tetrahydrocannabinol withdrawal. Eur J Pharmacol 387:47–53

    Article  PubMed  CAS  Google Scholar 

  • Beardsley PM, Balster RL, Harris LS (1986) Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther 239:311–319

    PubMed  CAS  Google Scholar 

  • Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, Le Fur G, Casellas P (1995) Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 312:637–641

    PubMed  CAS  Google Scholar 

  • Braida D, Pozzi M, Cavallini R, Sala M (2001a) Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system. Neuroscience 104:923–926

    Article  PubMed  CAS  Google Scholar 

  • Braida D, Pozzi M, Parolaro D, Sala M (2001b) Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system. Eur J Pharmacol 413:227–234

    Article  PubMed  CAS  Google Scholar 

  • Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Vogt LJ, Sim-Selley LJ (1999) Chronic delta9-tetrahydrocannabinol treatment produces a time-dependent loss of cannabinoid receptors and cannabinoid receptor-activated G proteins in rat brain. J Neurochem 73:2447–2459

    Article  PubMed  CAS  Google Scholar 

  • Budney AJ, Novy PL, Hughes JR (1999) Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction 94:1311–1322

    Article  PubMed  CAS  Google Scholar 

  • Budney AJ, Hughes JR, Moore BA, Novy PL (2001) Marijuana abstinence effects in marijuana smokers maintained in their home environment. Arch Gen Psychiatry 58:917–924

    PubMed  CAS  Google Scholar 

  • Budney AJ, Moore BA, Vandrey RG, Hughes JR (2003) The time course and significance of cannabis withdrawal. J Abnorm Psychol 112:393–402

    Article  PubMed  Google Scholar 

  • Burkey TH, Quock RM, Consroe P, Roeske WR, Yamamura HI (1997) Δ9-TetraHydro-Cannabinol is a partial agonist of cannabinoid receptors in mouse brain.Eur J Pharmacol 323:R3–R4

    Article  PubMed  CAS  Google Scholar 

  • Caberlotto L, Rimondini R, Hansson A, Eriksson S, Heilig M (2004) Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift? Neuropsychopharmacology 29:15–22

    Article  PubMed  CAS  Google Scholar 

  • Castane A, Robledo P, Matifas A, Kieffer BL, Maldonado R (2003) Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice. Eur J Neurosci 17:155–159

    Article  PubMed  Google Scholar 

  • Castane A, Maldonado R, Valverde O (2004) Role of different brain structures in the behavioural expression of WIN 55,212-2 withdrawal in mice. Br J Pharmacol

    Google Scholar 

  • Chaperon F, Thiebot MH (1999) Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 13:243–281

    PubMed  CAS  Google Scholar 

  • Cook SA, Lowe JA, Martin BR (1998) CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol. J Pharmacol Exp Ther 285:1150–1156

    PubMed  CAS  Google Scholar 

  • Cornelius JR, Salloum IM, Haskett RF, Ehler JG, Jarrett PJ, Thase ME, Perel JM (1999) Fluoxetine versus placebo for the marijuana use of depressed alcoholics. Addict Behav 24:111–114

    Article  PubMed  CAS  Google Scholar 

  • Costa B, Giagnoni G, Colleoni M (2000) Precipitated and spontaneous withdrawal in rats tolerant to anandamide. Psychopharmacology (Berl) 149:121–128

    Article  PubMed  CAS  Google Scholar 

  • Coutts AA, Anavi-Goffer S, Ross RA, MacEwan DJ, Mackie K, Pertwee RG, Irving AJ (2001) Agonist-induced internalization and trafficking of cannabinoid CB1 receptors in hippocampal neurons. J Neurosci 21:2425–2433

    PubMed  CAS  Google Scholar 

  • Cravatt BF, Demarest K, Patricelli MP, Bracey MH, Giang DK, Martin BR, Lichtman AH (2001) Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci U S A 98:9371–9376

    Article  PubMed  CAS  Google Scholar 

  • Darmani NA, Pandya DK (2000) Involvement of other neurotransmitters in behaviors induced by the cannabinoid CB1 receptor antagonist SR 141716A in naïve mice. J Neural Transm 107:931–945

    Article  PubMed  CAS  Google Scholar 

  • Davis MI, Ronesi J, Lovinger DM (2003) A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells. J Biol Chem 278:48973–48980

    PubMed  CAS  Google Scholar 

  • De Vry J, Jentzsch KR, Kuhl E, Eckel G (2004) Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. Behav Pharmacol 15:1–12

    PubMed  Google Scholar 

  • Derkinderen P, Toutant M, Burgaya F, Le Bert M, Siciliano JC, de Franciscis V, Gelman M, Girault JA (1996) Regulation of a neuronal form of focal adhesion kinase by anandamide. Science 273:1719–1722

    PubMed  CAS  Google Scholar 

  • Derkinderen P, Ledent C, Parmentier M, Girault JA (2001a) Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus. J Neurochem 77:957–960

    Article  PubMed  CAS  Google Scholar 

  • Derkinderen P, Toutant M, Kadare G, Ledent C, Parmentier M, Girault JA (2001b) Dual role of Fyn in the regulation of FAK+6,7 by cannabinoids in hippocampus. J Biol Chem 276:38289–38296

    PubMed  CAS  Google Scholar 

  • Derkinderen P, Valjent E, Toutant M, Corvol JC, Enslen H, Ledent C, Trzaskos J, Caboche J, Girault JA (2003) Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus. J Neurosci 23:2371–2382

    PubMed  CAS  Google Scholar 

  • Dewey WL, Jenkins J, Rourke T, Harris LS (1972) The effects of chronic administration of trans-⊲9-tetrahydrocannabinol on behavior and the cardiovascular system. Arch Int Pharmacodyn Ther 198:118–131

    PubMed  CAS  Google Scholar 

  • Di Marzo V, Berrendero F, Bisogno T, Gonzalez S, Cavaliere P, Romero J, Cebeira M, Ramos JA, Fernandez-Ruiz JJ (2000) Enhancement of anandamide formation in the limbic forebrain and reduction of endocannabinoid contents in the striatum of delta-9-tetrahydrocannabinol-tolerant rats. J Neurochem 74:1627–1635

    PubMed  Google Scholar 

  • DSM-IV (1994) Diagnostic and statistical manual of mental disorders: DSM-IV. American Psychiatric Association, Washington

    Google Scholar 

  • Fan F, Compton DR, Ward S, Melvin L, Martin BR (1994) Development of cross-tolerance between delta 9-tetrahydrocannabinol, CP 55,940 and WIN 55,212. J Pharmacol Exp Ther 271:1383–1390

    PubMed  CAS  Google Scholar 

  • Fan F, Tao Q, Abood M, Martin BR (1996) Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice. Brain Res 706:13–20

    Article  PubMed  CAS  Google Scholar 

  • Fattore L, Cossu G, Martellotta CM, Fratta W (2001) Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats. Psychopharmacology (Berl) 156:410–416

    Article  PubMed  CAS  Google Scholar 

  • FDA (2004) http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm serzone. Cited 12 September (2004)

    Google Scholar 

  • Ferguson SS, Caron MG (1998) G protein-coupled receptor adaptation mechanisms. Semin Cell Dev Biol 9:119–127

    Article  PubMed  CAS  Google Scholar 

  • Ferry L, Johnston JA (2003) Efficacy and safety of bupropion SR for smoking cessation: data from clinical trials and five years of postmarketing experience. Int J Clin Pract 57:224–230

    PubMed  CAS  Google Scholar 

  • Fielding S, Wilker J, Hynes M, Szewczak M, Novick WJ Jr, Lal H (1978) A comparison of clonidine with morphine for antinociceptive and antiwithdrawal actions. J Pharmacol Exp Ther 207:899–905

    PubMed  CAS  Google Scholar 

  • Fraser JD (1949) Withdrawal symptoms in cannabis-indica addicts. Lancet 257:747–748

    Google Scholar 

  • Freedland CS, Whitlow CT, Miller MD, Porrino LJ (2002) Dose-dependent effects of delta9-tetrahydrocannabinol on rates of local cerebral glucose utilization in rat. Synapse 45:134–142

    Article  PubMed  CAS  Google Scholar 

  • Freedland CS, Whitlow CT, Smith HR, Porrino LJ (2003) Functional consequences of the acute administration of the cannabinoid receptor antagonist, SR141716A, in cannabinoid-naïve and-tolerant animals: a quantitative 2-[14C]deoxyglucose study. Brain Res 962:169–179

    Article  PubMed  CAS  Google Scholar 

  • Galve-Roperh I, Rueda D, Gomez del Pulgar T, Velasco G, Guzman M (2002) Mechanism of extracellular signal-regulated kinase activation by the CB(1) cannabinoid receptor. Mol Pharmacol 62:1385–1392

    Article  PubMed  CAS  Google Scholar 

  • Garcia DE, Brown S, Hille B, Mackie K (1998) Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor. J Neurosci 18:2834–2841

    PubMed  CAS  Google Scholar 

  • Gardner EL (2002) Addictive potential of cannabinoids: the underlying neurobiology. Chem Phys Lipids 121:267–290

    Article  PubMed  CAS  Google Scholar 

  • Gardner EL, Lowinson JH (1991) Marijuana’s interaction with brain reward systems—update 1991. Pharmacol Biochem Behav 40:571–580

    Article  PubMed  CAS  Google Scholar 

  • Gardner EL, Paredes W, Smith D, Donner A, Milling C, Cohen A, Morrison D (1988) Facilitation of brain stimulation reward by D9-tetrahydrocannabinol. Psychopharmacology (Berl) 96:142–144

    PubMed  CAS  Google Scholar 

  • Gardner EL, Paredes W, Smith D, Zukin RS (1989) Facilitation of brain stimulation reward by D9-tetrahydrocannabinol is mediated by an endogenous opioid mechanism. Adv Biosci 75:671–674

    CAS  Google Scholar 

  • Ghozland S, Matthes HW, Simonin F, Filliol D, Kieffer BL, Maldonado R (2002) Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors. J Neurosci 22:1146–1154

    PubMed  CAS  Google Scholar 

  • Gold MS, Redmond DE Jr, Kleber HD (1978) Clonidine blocks acute opiate-withdrawal symptoms. Lancet 2:599–602

    PubMed  CAS  Google Scholar 

  • Gomez del Pulgar T, Velasco G, Guzman M (2000) The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt. Biochem J 347:369–373

    Google Scholar 

  • Gonzalez S, Fernandez-Ruiz J, Marzo VD, Hernandez M, Arevalo C, Nicanor C, Cascio MG, Ambrosio E, Ramos JA (2004) Behavioral and molecular changes elicited by acute administration of SR141716 to Delta9-tetrahydrocannabinol-tolerant rats: an experimental model of cannabinoid abstinence. Drug Alcohol Depend 74:159–170

    PubMed  CAS  Google Scholar 

  • Gossop M (1988) Clonidine and the treatment of the opiate withdrawal syndrome. Drug Alcohol Depend 21:253–259

    PubMed  CAS  Google Scholar 

  • Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999a) Abstinence symptoms following oral THC administration to humans. Psychopharmacology (Berl) 141:385–394

    PubMed  CAS  Google Scholar 

  • Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999b) Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl) 141:395–404

    PubMed  CAS  Google Scholar 

  • Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001) Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology (Berl) 155:171–179

    Article  PubMed  CAS  Google Scholar 

  • Haney M, Bisaga A, Foltin RW (2003a) Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology (Berl) 166:77–85

    PubMed  CAS  Google Scholar 

  • Haney M, Hart CL, Ward AS, Foltin RW (2003b) Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology (Berl) 165:157–165

    PubMed  CAS  Google Scholar 

  • Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, Foltin RW (2004) Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology 29:158–170

    Article  PubMed  CAS  Google Scholar 

  • Hill MN, Gorzalka BB, Choi JW (2004) Augmentation of the development of behavioral tolerance to cannabinoid administration through pavlovian conditioning. Neuropsychobiology 49:94–100

    Article  PubMed  CAS  Google Scholar 

  • Hirschhorn ID, Rosecrans JA (1974) Morphine and Δ9-tetrahydrocannabinol: tolerance to the stimulus effects. Psychopharmacologia 36:243–253

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

    Article  PubMed  CAS  Google Scholar 

  • Hsieh C, Brown S, Derleth C, Mackie K (1999) Internalization and recycling of the CB1 cannabinoid receptor. J Neurochem 73:493–501

    Article  PubMed  CAS  Google Scholar 

  • Hutcheson DM, Tzavara ET, Smadja C, Valjent E, Roques BP, Hanoune J, Maldonado R (1998) Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol. Br J Pharmacol 125:1567–1577

    Article  PubMed  CAS  Google Scholar 

  • Jin W, Brown S, Roche JP, Hsieh C, Celver JP, Kovoor A, Chavkin C, Mackie K (1999) Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization. J Neurosci 19:3773–3780

    PubMed  CAS  Google Scholar 

  • Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE (2004) Monitoring the Future national results on adolescent drug use: overview of key findings, 2003. National Institute on Drug Abuse, Bethdesda

    Google Scholar 

  • Jones RT, Benowitz N (1976) The 30-day trip—clinical studies of cannabis tolerance and dependence. In: Braude MC, Szara S, (eds) Pharmacology of Marihuana. Raven Press, New York, 627–642

    Google Scholar 

  • Jones RT, Benowitz N, Bachman J (1976) Clinical studies of cannabis tolerance and dependence. Ann NY Acad Sci 282:221–239

    PubMed  CAS  Google Scholar 

  • Jones RT, Benowitz NL, Herning RI (1981) Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol 21:143S–152S

    PubMed  CAS  Google Scholar 

  • Justinova Z, Tanda G, Redhi GH, Goldberg SR (2003) Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology (Berl) 169:135–140

    Article  PubMed  CAS  Google Scholar 

  • Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, Mor M, Tarzia G, Rana GL, Calignano A, Giustino A, Tattoli M, Palmery M, Cuomo V, Piomelli D (2003) Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 9:76–81

    Article  PubMed  CAS  Google Scholar 

  • Kaymakcalan K, Ayhan IH, Tulunay FC (1977) Naloxone-induced or postwithdrawal abstinence signs in Δ9-tetrahydrocannabinol-tolerant rats. Psychopharmacology (Berl) 55:243–249

    PubMed  CAS  Google Scholar 

  • Kaymakcalan S, Deneau GA (1972) Some pharmacologic properties of synthetic Δ9-tetrahydrocannabinol. Acta Medica Turcica Suppl 1:5

    Google Scholar 

  • Kouznetsova M, Kelley B, Shen M, Thayer SA (2002) Desensitization of cannabinoid-mediated presynaptic inhibition of neurotransmission between rat hippocampal neurons in culture. Mol Pharmacol 61:477–485

    Article  PubMed  CAS  Google Scholar 

  • Krupnick JG, Benovic JL (1998) The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol 38:289–319

    Article  PubMed  CAS  Google Scholar 

  • Landsman RS, Burkey TH, Consroe P, Roeske WR, Yamamura HI (1997) SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur J Pharmacol 334:R1–2

    Article  PubMed  CAS  Google Scholar 

  • Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmentier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283:401–404

    Article  PubMed  CAS  Google Scholar 

  • Lee MC, Smith FL, Stevens DL, Welch SP (2003) The role of several kinases in mice tolerant to delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther 305:593–599

    PubMed  CAS  Google Scholar 

  • Leite JR, Carlini EA (1974) Failure to obtain “cannabis-directed behavior” and abstinence syndrome in rats chronically treated with cannabis sativa extracts. Psychopharmacologia 36:133–145

    Article  PubMed  CAS  Google Scholar 

  • Lepore M, Vorel SR, Lowinson J, Gardner EL (1995) Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci 56:2073–2080

    Article  PubMed  CAS  Google Scholar 

  • Lepore M, Liu X, Savage V, Matalon D, Gardner EL (1996) Genetric differences in D9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains. Life Sci 58:365–0372

    Article  Google Scholar 

  • Lichtman AH, Wiley JL, LaVecchia KL, Neviaser ST, Arthrur DB, Wilson DM, Martin BR (1998) Acute and chronic cannabinoid effects: characterization of precipitated withdrawal in dogs. Eur J Pharmacol 357:139–148

    Article  PubMed  CAS  Google Scholar 

  • Lichtman AH, Fisher J, Martin BR (2001a) Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. Pharmacol Biochem Behav 69:181–188

    Article  PubMed  CAS  Google Scholar 

  • Lichtman AH, Sheikh SM, Loh HH, Martin BR (2001b) Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298:1007–1014

    PubMed  CAS  Google Scholar 

  • Lichtman AH, Varvel SA, Martin BR (2002) Endocannabinoids in cognition and dependence. Prostaglandins Leukot Essent Fatty Acids 66:269–285

    Article  PubMed  CAS  Google Scholar 

  • Lichtman AH, Leung D, Shelton C, Saghatelian A, Hardouin C, Boger D, Cravatt BF (2004) Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity. J Pharmacol Exp Ther

    Google Scholar 

  • Liu J, Gao B, Mirshahi F, Sanyal AJ, Khanolkar AD, Makriyannis A, Kunos G (2000) Functional CB1 cannabinoid receptors in human vascular endothelial cells. Biochem J 346:835–840

    PubMed  CAS  Google Scholar 

  • Maldonado R (2002) Study of cannabinoid dependence in animals. Pharmacol Ther 95:153–164

    Article  PubMed  CAS  Google Scholar 

  • Maldonado R, Rodriguez de Fonseca F (2002) Cannabinoid addiction: behavioral models and neural correlates. J Neurosci 22:3326–3331

    PubMed  CAS  Google Scholar 

  • Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W (1998) Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice. Neuroscience 85:327–330

    Article  PubMed  CAS  Google Scholar 

  • Martin BR (2002) Identification of the endogenous cannabinoid system through integrative pharmacological approaches. J Pharmacol Exp Ther 301:790–796

    PubMed  CAS  Google Scholar 

  • Martin BR, Sim-Selley LJ, Selley DE (2004) Signaling pathways involved in the development of cannabinoid tolerance. Trends Pharmacol Sci 25:325–330

    Article  PubMed  CAS  Google Scholar 

  • McMillan DE, Dewey WL, Harris LS (1971) Characteristics of tetrahydrocannabinol tolerance. Ann NY Acad Sci 191:83–99

    CAS  Google Scholar 

  • McRae AL, Budney AJ, Brady KT (2003) Treatment of marijuana dependence: a review of the literature. J Subst Abuse Treat 24:369–376

    Article  PubMed  Google Scholar 

  • Navarro M, Chowen J, Carrera MRA, del Arco I, Vallanua MA, Martin Y, Roberts AJ, Koob GF, Rodriguez de Fonseca F (1998) CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats. Neuroreport 9:3397–3402

    PubMed  CAS  Google Scholar 

  • Oliva JM, Ortiz S, Palomo T, Manzanares J (2004) Spontaneous cannabinoid withdrawal produces a differential time-related responsiveness in cannabinoid CB1 receptor gene expression in the mouse brain. J Psychopharmacol 18:59–65

    Article  PubMed  CAS  Google Scholar 

  • Oviedo A, Glowa J, Herkenham M (1993) Chronic cannabinoid administration alters cannabinoid receptor binding in rat brain: a quantitative autoradiographic study. Brain Res 616:293–302

    Article  PubMed  CAS  Google Scholar 

  • Pan X, Ikeda SR, Lewis DL (1998) SR 141716A acts as an inverse agonist to increase neuronal voltage-dependent Ca2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Mol Pharmacol 54:1064–1072

    PubMed  CAS  Google Scholar 

  • Richmond R, Zwar N (2003) Review of bupropion for smoking cessation. Drug Alcohol Rev 22:203–220

    PubMed  Google Scholar 

  • Rinaldi-Carmona M, Barth F, Hèaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Néliat G, Caput D, Ferrara P, Soubrié P, Breliére JC, Le Fur G (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240–244

    Article  PubMed  CAS  Google Scholar 

  • Rinaldi-Carmona M, Le Duigou A, Oustric D, Barth F, Bouaboula M, Carayon P, Casellas P, Le Fur G (1998) Modulation of CB1 cannabinoid receptor functions after a long-term exposure to agonist or inverse agonist in the Chinese hamster ovary cell expression system. J Pharmacol Exp Ther 287:1038–1047

    PubMed  CAS  Google Scholar 

  • Rodriguez de Fonseca F, Carrera M, Navarro M, Koob K, Weiss F (1997) Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 276:2050–2054

    Google Scholar 

  • Romero J, Garcia-Palomero E, Castro JG, Garcia-Gil L, Ramos JA, Fernandez-Ruiz JJ (1997) Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Brain Res Mol Brain Res 46:100–108

    PubMed  CAS  Google Scholar 

  • Romero J, Berrendero F, Garcia-Gil L, DeLa Cruz P, Ramos A, Fernandez-Ruiz JJ (1998a) Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist stimulated [35 s]guanylyl-5’-O-(thio)-triphosphate binding in the basal ganglia of rats. Neuroscience 84:1075–1083

    Article  PubMed  CAS  Google Scholar 

  • Romero J, Berrendero F, Manzanares J, Perez A, Corchero J, Fuentes JA, Fernandez-Ruiz JJ, Ramos JA (1998b) Time-course of the cannabinoid receptor down-regulation in the adult rat brain caused by repeated exposure to delta9-tetrahydrocannabinol. Synapse 30:298–308

    Article  PubMed  CAS  Google Scholar 

  • Rubino T, Massi P, Patrini G, Venier I, Giagnoni G, Parolaro D (1994) Chronic CP-55,940 alters cannabinoid receptor mRNA in the rat brain: An in situ hybridization study. NeuroReport 5:2493–2496

    PubMed  CAS  Google Scholar 

  • Rubino T, Patrini G, Parenti M, Massi P, Parolaro D (1997) Chronic treatment with a synthetic cannabinoid CP-55,940 alters G-protein expression in the rat central nervous system. Brain Res Mol Brain Res 44:191–197

    PubMed  CAS  Google Scholar 

  • Rubino T, Patrini G, Massi P, Fuzio D, Vigano D, Giagnoni G, Parolaro D (1998) Cannabinoid precipitated withdrawal: a time-course study of the behavioral aspect and its correlation with cannabinoid receptors and G protein expression. J Pharmacol Exp Ther 285:813–819

    PubMed  CAS  Google Scholar 

  • Rubino T, Vigano D, Costa B, Colleoni M, Parolaro D (2000a) Loss of cannabinoid-stimulated guanosine 5′-O-(3-[(35)S]thiotriphosphate) binding without receptor down-regulation in brain regions of anandamide-tolerant rats. J Neurochem 75:2478–2484

    PubMed  CAS  Google Scholar 

  • Rubino T, Vigano D, Massi P, Spinello M, Zagato E, Giagnoni G, Parolaro D (2000b) Chronic delta-9-tetrahydrocannabinol treatment increases cAMP levels and cAMP-dependent protein kinase activity in some rat brain regions. Neuropharmacology 39:1331–1336

    Article  PubMed  CAS  Google Scholar 

  • Rubino T, Vigano D, Zagato E, Sala M, Parolaro D (2000c) In vivo characterization of the specific cannabinoid receptor antagonist, SR141716A: behavioral and cellular responses after acute and chronic treatments. Synapse 35:8–14

    Article  PubMed  CAS  Google Scholar 

  • Rueda D, Galve-Roperh I, Haro A, Guzman M (2000) The CB(1) cannabinoid receptor is coupled to the activation of c-Jun N-terminal kinase. Mol Pharmacol 58:814–820

    PubMed  CAS  Google Scholar 

  • Sanchez C, Galve-Roperh I, Rueda D, Guzman M (1998) Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. Mol Pharmacol 54:834–843

    PubMed  CAS  Google Scholar 

  • Sanudo-Pena MC, Tsou K, Delay ER, Hohman AG, Force M, Walker JM (1997) Endogenous cannabinoids as an aversive or counter-rewarding system in the rat. Neurosci Lett 223:125–128

    PubMed  CAS  Google Scholar 

  • Siegel S, Ramos BM (2002) Applying laboratory research: drug anticipation and the treatment of drug addiction. Exp Clin Psychopharmacol 10:162–183

    PubMed  Google Scholar 

  • Sim LJ, Hampson RE, Deadwyler SA, Childers SR (1996a) Effects of chronic treatment with Δ9-tetrahydrocannabinol on cannabinoid-stimulated [35]GTPγS autoradiography in rat brain. J Neurosci 16:8057–8066

    PubMed  CAS  Google Scholar 

  • Sim LJ, Selley DE, Xiao R, Childers SR (1996b) Differences in G-protein activation by µ-and ´-opioid, and cannabinoid, receptors in rat striatum. Eur J Pharmacol 307:97–105

    Article  PubMed  CAS  Google Scholar 

  • Sim-Selley LJ (2003) Regulation of cannabinoid CB1 receptors in the central nervous system by chronic cannabinoids. Crit Rev Neurobiol 15:91–119

    Article  PubMed  CAS  Google Scholar 

  • Sim-Selley LJ, Martin BR (2002) Effect of chronic administration of R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-b enzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2) or delta(9)-tetrahydrocannabinol on cannabinoid receptor adaptation in mice. J Pharmacol Exp Ther 303:36–44

    Article  PubMed  CAS  Google Scholar 

  • Sim-Selley LJ, Brunk LK, Selley DE (2001) Inhibitory effects of SR141716A on G-protein activation in rat brain. Eur J Pharmacol 414:135–143

    Article  PubMed  CAS  Google Scholar 

  • Sipe JC, Chiang K, Gerber AL, Beutler E, Cravatt BF (2002) A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proc Natl Acad Sci U S A 99:8394–8399

    Article  PubMed  CAS  Google Scholar 

  • Smith NT (2002) A review of the published literature into cannabis withdrawal symptoms in human users. Addiction 97:621–632

    PubMed  Google Scholar 

  • Takahashi RN, Singer G (1979) Self-administration of D9-tetrahydrocannabinol by rats. Pharmacol Biochem Behav 11:737–740

    Article  PubMed  CAS  Google Scholar 

  • Takahashi RN, Singer G (1980) Effects of body weight levels on cannabis self-injection. Pharmacol Biochem Behav 13:877–881

    PubMed  CAS  Google Scholar 

  • Tanda G, Goldberg SR (2003) Cannabinoids: reward, dependence, and underlying neurochemical mechanisms—a review of recent preclinical data. Psychopharmacology (Berl) 169:115–134

    Article  PubMed  CAS  Google Scholar 

  • Tanda G, Munzar P, Goldberg SR (2000) Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci 3:1073–1074

    PubMed  CAS  Google Scholar 

  • Tsou K, Patrick S, Walker JM (1995) Physical withdrawal in rats tolerant to Δ9-tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist. Eur J Pharmacol 280:R13–R15

    Article  PubMed  CAS  Google Scholar 

  • Tzavara ET, Valjent E, Firmo C, Mas M, Beslot F, Defer N, Roques BP, Hanoune J, Maldonado R (2000) Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum. Eur J Neurosci 12:1038–1046

    Article  PubMed  CAS  Google Scholar 

  • Valjent E, Maldonado R (2000) A behavioural model to reveal place preference to delta9-tetrahydrocannabinol in mice. Psychopharmacology (Berl) 147:436–438

    Article  PubMed  CAS  Google Scholar 

  • Valverde O, Maldonado R, Valjent E, Zimmer AM, Zimmer A (2000) Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice. J Neurosci 20:9284–9289

    PubMed  CAS  Google Scholar 

  • Varvel SA, Cichewicz DL, Lichtman AH (2004) Interactions between cannabinoids and opioids. In: Wenger T (ed) Recent advances on pharmacology and physiology of cannabinoids research. Signpost, Keraka, 157–182

    Google Scholar 

  • Weiss F, Ciccocioppo R, Parsons LH, Katner S, Liu X, Zorrilla EP, Valdez GR, Ben-Shahar O, Angeletti S, Richter RR (2001) Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors. Ann N Y Acad Sci 937:1–26

    PubMed  CAS  Google Scholar 

  • Whitlow CT, Freedland CS, Porrino LJ (2003) Functional consequences of the repeated administration of delta9-tetrahydrocannabinol in the rat. Drug Alcohol Depend 71:169–177

    PubMed  CAS  Google Scholar 

  • Wiesbeck GA, Schuckit MA, Kalmijn JA, Tipp JE, Bucholz KK, Smith TL (1996) An evaluation of the history of a marijuana withdrawal syndrome in a large population. Addiction 91:1469–1478

    Article  PubMed  CAS  Google Scholar 

  • Wikler A (1976) Aspects of tolerance to and dependence on cannabis. Ann N Y Acad Sci 282:126–147

    PubMed  CAS  Google Scholar 

  • Willoughby KA, Moore SF, Martin BR, Ellis EF (1997) The biodisposition and metabolism of anandamide in mice. J Pharmacol Exp Ther 282:243–247

    PubMed  CAS  Google Scholar 

  • Wise RA (1996) Addictive drugs and brain stimulation reward. Annu Rev Neurosci 19:319–340

    Article  PubMed  CAS  Google Scholar 

  • Zhuang S, Kittler J, Grigorenko EV, Kirby MT, Sim LJ, Hampson RE, Childers SR, Deadwyler SA (1998) Effects of long-term exposure to delta9-THC on expression of cannabinoid receptor (CB1) mRNA in different rat brain regions. Brain Res Mol Brain Res 62:141–149

    PubMed  CAS  Google Scholar 

  • Zimmer A, Valjent E, Konig M, Zimmer AM, Robledo P, Hahn H, Valverde O, Maldonado R (2001) Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphind-deficient mice. J Neurosci 21:9499–9505

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. A. H. Lichtman

    Present address: Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA, 23298-0613, USA

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980613, Richmond, VA, 23298-0613, USA

    B. R. Martin

Authors
  1. A. H. Lichtman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. R. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Medical Sciences, Institute of Medical Science, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK

    Roger G. Pertwee

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag

About this chapter

Cite this chapter

Lichtman, A.H., Martin, B.R. (2005). Cannabinoid Tolerance and Dependence. In: Pertwee, R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26573-2_24

Download citation

Publish with us

Policies and ethics

Search

Navigation