Abstract
Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabisrelieves symptoms of mania and/or depression. The cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects. Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or amixture of the two in known concentrations, are available and can be delivered sublingually. Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.
|
Agurell A , Halldin M , Lindgren J E , Ohlsson A , Widman M , Gillespie H , Hollister L (1986) Pharmacokinetics and metabolism of Δ1-tetrahydrocannabinol and other cannabinoids with emphasis on man . Pharmacol Rev 38: 21–43 Google Scholar | Medline | |
|
Alger B E (2004) Endocannabinoids: getting the message across . Proc Natl Acad Sci 101: 8512–8513 Google Scholar | Crossref | Medline | |
|
Altshuler L L , Bartzokis G , Grieder T , Curran J , Jimenez T , Leight K , Wilkins J , Gerner R , Mintz J (2000) An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia . Biol Psychiatry 48: 147–162 Google Scholar | Crossref | Medline | |
|
Ameri A (1999) The effects of cannabinoids on the brain . Prog Neurobiol 58: 315–348 Google Scholar | Crossref | Medline | ISI | |
|
Arsenault L , Cannon M , Witton J , Murray R M (2004) Causal association between cannabis and psychosis: examination of the evidence . Br J Psychiatry 184: 110–117 Google Scholar | Crossref | Medline | |
|
Ashton H (1999a) Cannabis in palliative care . CME Bull Palliat Med 1: 73–77 Google Scholar | |
|
Ashton H (1999b) Adverse effects of cannabis and cannabinoids . Br J Anaesth 83: 637–649 Google Scholar | Crossref | Medline | |
|
Ashton H , Young A H (2003) GABA-ergic drugs: exit stage left, enter stage right . J Psychopharmacol 17: 174–178 Google Scholar | SAGE Journals | ISI | |
|
Ashton H , Golding J F , Marsh V R , Millman J E , Thompson J W (1981) The seed and the soil: effect of dosage, personality and starting state on the response to Δ9-tetrahydrocannabinol in man . Br J Clin Pharmacol 12: 705–720 Google Scholar | Crossref | Medline | |
|
Bisogno T , Hanus L , De Petrocellis L , Tchilibon S , Ponde D , Brandi I , Moriello A S , Davis J B , Mechoulam R , Di Marzo V (2001) Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide . Br J Pharmacol 134: 845–852 Google Scholar | Crossref | Medline | |
|
British Medical Association (1997) Therapeutic Uses of Cannabis. Harwood Publishers, London Google Scholar | |
|
Brown E , Suppes T , Adinoff B , Thomas NR (2001) Drug abuse and bipolar disorder: comorbidity or misdiagnosis? J Affect Dis 65: 105–115 Google Scholar | Crossref | Medline | |
|
Carlini E A , Cunha J M (1981) Hypnotic and antiepileptic effects of cannabidiol . J Clin Pharmacol 21: 417S–427S Google Scholar | Crossref | Medline | |
|
Cassidy F , Ahearn E P , Carroll B J (2001) Substance abuse in bipolardisorder . Bipolar Disord 3: 181–188 Google Scholar | Crossref | Medline | |
|
Christie M J , Vaughan C W (2001) Cannabinoids act backwards . Nature 410: 527–530 Google Scholar | Crossref | Medline | |
|
Committee on Safety of Medicines (2003) Current Problems in Pharmacovigilance 29: 6–6 Google Scholar | |
|
Consroe P , Sandyk R (1992) Potential role of cannabinoids for therapy of neurological disorders. In Murphy L , Bartke A (eds), Marijuana/Cannabinoids: Neurobiology and Neuropsychology. CRC Press, Boca Raton, FL , pp. 459–524 Google Scholar | |
|
Consroe P , Snyder S R (1986) Therapeutic potential of cannabinoids for therapy of neurological disorders. In Mechoulam R (ed.), Cannabinoids as Therapeutic Agents. CRC Press, Boca Raton, FL , pp. 21–49 Google Scholar | |
|
Cunha J M , Carlini E A , Pereira A E , Ramos O L , Pimentel G , Gagliardi R , Sanvito E L , Lander N , Mechoulam R (1980) Chronic administration of CBD to healthy volunteers and epileptic patients . Pharmacologia 21: 175–185 Google Scholar | Medline | |
|
Dalton E J , Cate-Carter T D , Mundo E , Parikh S V , Kennedy J L (2003) Suicide risk in bipolar patients: the role of co-morbid substance usedisorders . Bipolar Disord 3: 58–61 Google Scholar | Crossref | |
|
Deadwyler S A , Hampson R E , Childers S R (1995) Functional significance of cannabinoid recepters in brain. In Pertwee R G (ed.), Cannabinoid Receptors. Academic Press Ltd, London , pp. 205–231 Google Scholar | |
|
Di Marzo V , Goparaju S K , Wang L , Liu J , Batkai S , Jaral Z M , Fezza F , Miura G I , Palmiter R D , Sugiura T , Kunos G (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake . Nature 410: 822–825 Google Scholar | Crossref | Medline | ISI | |
|
Di Marzo V , Melck D , Brisogno T , De Petrocellos L (1998) Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action . Trends Neurosci 21: 521–528 Google Scholar | Crossref | Medline | ISI | |
|
D’Souza D C , Perry E , MacDougall L , Ammerman Y , Cooper T , Wu,Y , Braley G , Gueorguieva R , Krystal J H (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis . Neuropsychopharmacology 29: 1558–1572 Google Scholar | Crossref | Medline | ISI | |
|
Drevets W C , Price J L , Simpson J R (1997) Subgenual prefrontal cortex abnormalities in mood disorders . Nature 386: 824–827 Google Scholar | Crossref | Medline | ISI | |
|
El-Badri S M , Ashton C H , Moore P B , Marsh V R , Ferrier I N (2001) Electrophysiological and cognitive function in young euthymic patients with bipolar affective disorder . Bipolar Disord 3: 79–87 Google Scholar | Crossref | Medline | |
|
Estroff T W , Dackis C A , Golod M S , Pottash A L C (1985) Drug abuse and bipolar disorders . Int J Psychiatry Med 15: 37–40 Google Scholar | SAGE Journals | |
|
Ferrier I N , Thompson J M (2002) Cognitive impairment in bipolar affective disorder: implications for the bipolar diathesis . Br J Psychiatry 180: 293–295 Google Scholar | Crossref | Medline | |
|
Fabre L F , McLendon D (1981) The efficacy and safety of nabilone (asynthetic cannabinoid) in the treatment of anxiety . J Pharmacol Sci 21: 377S–382S Google Scholar | |
|
Gardner E L (1999) Cannabinoid interaction with reward systems. In Nahas G G , Sutin K M , Harvey D J , Agurell S (eds), Marihuana and Medicine. Humana Press, Totowa, New Jersey , pp. 187–205 Google Scholar | Crossref | |
|
Geddes J R , Carney S M , Davies C (2003) Relapse prevention with antidepressant treatment in depressive disorders . Lancet 361: 643–651 Google Scholar | |
|
Geddes J , Goodwin G (2001) Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials . Br J Psychiatry 41 (Suppl): S191–S194 Google Scholar | Crossref | |
|
Gerth C W , Schultze-Lutter F , Mauss C , Ruhrmann S , Klosterkotter J , Leweke F M (2002) B113: the natural cannabinoid cannabidiol in the treatment of acute schizophrenia . Schizophr Res 53 (Suppl): 192–192 Google Scholar | |
|
Gieringer D H (2003) The acceptance of medicinal marijuana in the US . J Cannabis Ther 3: 53–65 Google Scholar | Crossref | |
|
Glass R M , Uhlenhuth E H , Hartel F W , Schuster C R , Fischman M W (1980) A single dose study of nabilone, a synthetic cannabinoid . Psychopharmacology 71: 137–142 Google Scholar | Crossref | Medline | |
|
Gold M S (1992) Marihuana and hashish. In Winger G , Hoffman F G , Woods J H (eds). A Handbook of Drug and Alcohol Abuse. The Biological Aspects. Chapter 7. Oxford University Press, Oxford , pp. 117–131 Google Scholar | |
|
Goodwin G M (2003) Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association of Psychopharmacology . J Psychopharmacol 17: 149–173 Google Scholar | SAGE Journals | |
|
Goodwin G , Sachs G (2004) Definitions: Diagnosis and Comorbidity. Bipolar Disorder – Fast Facts. Health Press, Oxford Google Scholar | |
|
Grinspoon L , Bakalar J B (1998) The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research . J Psychoactive Drugs 30: 171–177 Google Scholar | Crossref | Medline | |
|
Grotenhermen F (2003) Clinical pharmacokinetics . J Cannabis Ther 3: 3–51 Google Scholar | Crossref | |
|
Gruber A J , Pope H G , Brown M E (1996) Do patients use marijuana as an antidepressant? Depression 4: 77–80 Google Scholar | Crossref | Medline | |
|
Guimaraes F S , Chiaretti T M , Graeff F G , Zuardi A W (1990) Antianxiety effect of cannabidiol in the elevated plus-maze . Psychopharmacology 100: 558–559 Google Scholar | Crossref | Medline | |
|
Herkenham M (1995) Localisation of cannabinoid receptors in brain and periphery. In Pertwee R G (ed.), Cannabinoid Receptors. Academic Press, London , pp. 145–166 Google Scholar | |
|
Hodges C (1993) I wish I could get it at the chemist’s. The Independent 23rd February 1993. Google Scholar | |
|
Howlett A C (1995) Cannabinoid compounds and signal transduction mechanisms. In Pertwee R G (ed.), Cannabinoid Receptors. Academic Press, London , pp. 167–204 Google Scholar | |
|
Ilaria R L , Thornby J I , Fann W E (1981) Nabilone, a cannabinol derivative, in the treatment of anxiety neurosis . Curr Ther Res 29: 943–949 Google Scholar | |
|
Johns A (2001) The psychiatric effects of cannabis . Br J Psychiatry 178: 116–122 Google Scholar | Crossref | Medline | |
|
Joy J E , Watson S J , Benson J A (eds) (1999) Marijuana and Medicine. National Academy Press, Washington, DC Google Scholar | |
|
Lloyd A J , Harrison C L , Ferrier I N , Young A H (2003) The pharmacological treatment of bipolar affective disorder: practice is improving but could be better . J Psychopharmacol 17: 230–233 Google Scholar | SAGE Journals | |
|
Macleod J , Oakes R , Copello A , Crome I , Egger M , Hickman M , Oppenkowski T , Stokes-Lampard H , Smith G D (2004) Psychological and social sequelae of cannabis and other illicit drug use by youngpeople: a systematic review of longitudinal, general population studies . Lancet 363: 1579–1588 Google Scholar | Crossref | Medline | |
|
Marken P A , Stanislav S W , Lacombe S , Pierce C , Horstra R , Sommi R W (1992) Profile of a sample of subjects admitted to an acute care psychiatric facility with manic symptoms . Psychopharmacol Bull 28: 201–205 Google Scholar | Medline | |
|
Martin B R , Cone E J (1999) Chemistry and pharmacology of cannabis. In Kalant H , Corrigal W A , Hall W , Smart R G (eds), The Health Effects of Cannabis. Centre for Addiction and Mental Health, Toronto , pp. 21–68 Google Scholar | |
|
Martyn C N , Illis L S , Thom J (1995) Nabilone in the treatment of multiple sclerosis . Lancet 345: 579–579 Google Scholar | Crossref | Medline | |
|
Maykutt M O (1985) Health consequences of acute and chronic marihuana use . Prog Neuropsychopharmacol Biol Psychiatry 9: 209–238 Google Scholar | Crossref | Medline | |
|
McPartland J M , Russo E B (2001) Cannabis and cannabis extracts: greater than the sum of their parts? J Cannabis Ther 1: 103–132 Google Scholar | Crossref | |
|
Mechoulam R , Parker L A , Gallily R (2002) Cannabidiol: an overview of some pharmacological aspects . Clin Pharmacol 42: 11S–19S Google Scholar | Crossref | |
|
Mendelson J H , Mello N K (1999) Marihuana effects on pituitary and gonadal hormones. In Nahas G G , Sutin K M , Harvey D , Agurell S (eds), Marihuana and Medicine. Humana Press, Totowa, NJ , pp. 385–392 Google Scholar | Crossref | |
|
Miller F T , Busch F , Tanenbaum J H (1989) Drug abuse in schizophrenia and bipolar disorder . Am J Drug Alcohol Abuse 15: 291–295 Google Scholar | Crossref | Medline | |
|
Mishra A , Moore P B , Hobbs R (2004) Does quetiapine have moodaltering properties? J Psychopharmacol 18: 281–284 Google Scholar | SAGE Journals | |
|
Monti J M (1997) Hypnotic-like effects of cannabidiol in the rat . Psychopharmacology 55: 263–265 Google Scholar | Crossref | |
|
Mueser K T , Yarnold P R , Bellack A S (1992) Diagnostic and demographic correlates of substance abuse in schizophrenia and major affective disorder . Acta Psychiatr Scand 85: 105–114 Google Scholar | Crossref | Medline | |
|
Musty R E , Reggio P , Consroe P (1995) A review of recent advances in cannabinoid research and the 1994 international symsposium on cannabis and the cannabinoids . Life Sci 56: 1933–1940 Google Scholar | Crossref | Medline | |
|
Negrete J C , Gill K (1999) Cannabis and schizophrenia: an overview of the evidence to day. In Nahas G G , Sutin K M , Harvey D , Agurell S (eds), Marihuana and Medicine. Humana Press, Totowa, NJ , pp. 671–682 Google Scholar | Crossref | |
|
Notcutt W , Price M , Chapman G (1997) Clinical experience with nabilone for chronic pain . Pharmaceutical Sci 3: 551–555 Google Scholar | |
|
Paton W D M , Pertwee R G (1973) The actions of cannabis in man. In Nahas G G , Paton W D M (eds), Marijuana: Chemistry, Pharmacology, Metabolism and Clinical Effects. Pergamon Press, Oxford , pp. 735–738 Google Scholar | |
|
Pertwee R G (1997) Pharmacology of cannabinoid CB1 and CB2 receptors . Pharmacol Ther 74: 129–180 Google Scholar | Crossref | Medline | |
|
Pertwee R G (1999a) Cannabinoid receptors and their ligands in brain and other tissues. In Nahas G G , Sutin K M , Harvey D , Agurell S (eds), Marihuana and Medicine. Humana Press, Totowa, NJ , pp. 177–185 Google Scholar | Crossref | |
|
Pertwee R G (1999b) Pharmacology of cannabinoid receptor ligands . Curr Med Chem 6: 635–664 Google Scholar | Medline | |
|
Pertwee R G (2001) Cannabinoid receptors and pain . Prog Neurobiol 63: 569–611 Google Scholar | Crossref | Medline | ISI | |
|
Phillips M L , Drevets W C , Rauch S L , Lane R (2003) Neurobiology of emotion perception II: Implications for major psychiatric disorders . Biol Psychiatry 54: 515–528 Google Scholar | Crossref | Medline | ISI | |
|
Piomelli D , Giuffrida A , Calignano A , de Fonseca F R (2000) The endocannabinoid system as a target for therapeutic drugs . Trends Pharm Sci 21: 218–224 Google Scholar | Crossref | Medline | |
|
Porter R , Ferrier N , Ashton H (1999) Anticonvulsants as mood stabilisers . Adv Psychiatr Treat 5: 96–103 Google Scholar | Crossref | |
|
Randall R (ed.) (1991) Muscle Spasm, Pain and Marijuana Therapy. Galen Press, Washington, DC Google Scholar | |
|
Randall M D , Kendall D A (1998) Endocannabinoids: a new class of vasoactive substances . Trends Pharm Sci. 19: 55–58 Google Scholar | Crossref | Medline | |
|
Ratey J J , Ciraulo D A , Shader R I (1981) Lithium and marijuana . J Clin Psychopharmacol 1: 32–33 Google Scholar | Crossref | Medline | |
|
Regelson W , Butler J R , Schulz J , Kirk T , Peek L , Green M L , Zalis M O (1976) Delta-9-THC as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In Braude M C , Szara S (eds), The Pharmacology of Marihuana. Raven Press, New York, NY , pp. 763–776 Google Scholar | |
|
Regier D A , Farmer M E , Rae D S , Locke B Z , Keith S J , Judd L L , Goodwin F K (1990) Comorbidity of mental disorders with alcohol and other drug abuse . J Am Med Assoc 264: 2511–2518 Google Scholar | Crossref | |
|
Rottanburg D , Robins A H , Ben-Arie O , Teggin A , Elk R (1982) Cannabis-associated psychosis with hypomanic features . Lancet 2: 1364–1366 Google Scholar | Crossref | Medline | |
|
Russo E (2003) Cannabis: from pariah to prescription . J Cannabis Ther 3: 1–29 Google Scholar | Crossref | |
|
Sachs G S , Printz D J , Kahn D A (2000) The Expert Consensus Guideline Series: Medication treatment of bipolar disorder. Postgrad Med Spec. No: 1–104 Google Scholar | |
|
Shiloh R , Nutt D , Weizman A (1999) Atlas of Psychiatric Chemotherapy. Martin Dunitz, London Google Scholar | |
|
Solowij N (1998) Cannabis and Cognitive Function. Cambridge University Press, Cambridge Google Scholar | Crossref | |
|
Sonne S C , Brady K T , Morton W A (1994) Substance abuse and bipolar affective disorder . J Nerv Ment Dis 182: 349–352 Google Scholar | Crossref | Medline | |
|
Steffens M , Feuerstein T J (2004) Receptor-independent depression of DA and 5-HT uptake by cannabinoids in rat neocortex – involvement of Na(+)/K(+)-ATPase . Neurochem Int 44: 529–538 Google Scholar | Crossref | Medline | |
|
Stein E A , Fuller S A , Edgemond W S , Campbell W B (1996) Physiological and behavioural effects of the endogenous cannabnoid, arachidonyl-ethanolamine (anandamide), in the rat . Br J Pharmacol 119: 107–114 Google Scholar | Crossref | Medline | |
|
Strakowski S M , DelBello M P , Sax K W (1999) Brain magnetic resonance imaging of structural abnormalities in bipolar disorder . Arch Gen Psychiatry 56: 254–260 Google Scholar | Crossref | Medline | |
|
Strakowski S M , DelBello M P , Fleck D E , Arndt S (2000) The impact of substance abuse on the course of bipolar disorder . Biol Psychiatry 48: 477–485 Google Scholar | Crossref | Medline | |
|
Sulcova E , Mechoulam R , Fride E (1998) Biphasic effects of anandamide . Pharmacol Biochem Behav 59: 347–353 Google Scholar | Crossref | Medline | |
|
Surguladze S , Keedwell P , Phillips M (2003) Neural systems underlying affective disorders . Adv Psychiatr Treat 9: 446–455 Google Scholar | Crossref | |
|
Svendsen K B , Jensen T S , Bach F W (2004) Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial . Br Med J 329: 253–258 Google Scholar | Crossref | Medline | |
|
Terranova J P , Michaud J D , Le Fur G , Soubrie P (1995) Inhibiting long-term potentiation in rat hippocampal slice by anandamide and WIN55, 212-2: Reversal by SR1411716A, a selective antagonist of CB1 canna-binoid receptors . Naunyn-Schmiedeberg’s Arch Pharmacol 352: 576–579 Google Scholar | Crossref | Medline | |
|
Terranova J P , Storme J J , Lafon N , Perio A , Rinaldi-Ca J , Le Fur G , Soubrie P (1996) Improvement in memory in rodents by selective CB1 cannabinoid receptor antagonist, SR141716 A . Psychopharmacology 126: 165–172 Google Scholar | Crossref | Medline | |
|
Van der Stelt M , Di Marzo V (2003) The endocannabinoid system in the basal ganglia and in the meslolimbic reward system: implications for neurological and psychiatric disorders . Eur J Pharmacol 480: 133–150 Google Scholar | Crossref | Medline | |
|
Wade D , Robson P , House H , Makela P , Aram J (2003) A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms . Clin Rehab 17: 18–26 Google Scholar | SAGE Journals | |
|
Whittle B A , Guy G W , Robson P (2001) Prospects for new cannabis-based prescription medicines . J Cannabis Ther 1: 183–205 Google Scholar | Crossref | |
|
Williams C M , Kukham T C (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors . Psychopharmacology 143: 315–317 Google Scholar | Crossref | Medline | |
|
Williamson E M , Evans F J (2000) Cannabinoids in clinical practice . Drugs 60: 1303–1314 Google Scholar | Crossref | Medline | |
|
Wilson R I , Nicol R A (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses . Nature 410: 558–559 Google Scholar | Crossref | |
|
Winokur G , Turvey C , Skiskal H , Coryell W , Solomon D , Leon A , Mueller T , Endicott J , Maser J , Keller M (1998) Alcoholism and drug abuse in three groups – bipolar I, unipolars and their acquaintances . J Affect Disord 50: 81–89 Google Scholar | Crossref | Medline | |
|
Wylie A S , Scott R T A , Burnett S J (1995) Psychosis due to ‘skunk’ , Br Med J 311: 125–125 Google Scholar | Crossref | Medline | |
|
Zuardi A W , Guimaraes F S (1997) Cannabidiol as an anxiolytic and antipsychotic. In Mathre M L (ed.), Cannabis in Medical Practice. McFarland & Company, Jefferson, NC , pp. 133–141 Google Scholar | |
|
Zuardi A W , Shirakawa I , Finkelfarb E , Karmol I G (1982) Action of cannabidiol on the anxiety and other effects produced by Δ9-THC in normal subjects . Psychopharmacology 76: 245–259 Google Scholar | Crossref | Medline | |
|
Zuardi A W , Rodrigues J A , Cunha J M (1991) Effects of cannabidiol in animal models predictive of antipsychotic activity . Psychopharmacology 104: 260–264 Google Scholar | Crossref | Medline | ISI | |
|
Zuardi A W , Morais S L , Guimaraes F S , Mechoulam R (1995) Antipsychotic effect of cannabidiol . J Clin Psychiatry 56: 485–486 Google Scholar | Medline | |
|
Zullino D F , Delessert D , Eap C B , Preisij M , Baumann P (2002) Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine . Int Clin Psychopharmacol 17: 141–143 Google Scholar | Crossref | Medline |
