Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential

First Published May 1, 2005 Research Article Find in PubMed

Authors

,
,
,
Department of Psychiatry, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, UK
by this author
First Published Online: July 2, 2016

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: 2143
Google Scholar | Medline
Alger B E (2004) Endocannabinoids: getting the message across . Proc Natl Acad Sci 101: 85128513
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: 147162
Google Scholar | Crossref | Medline
Ameri A (1999) The effects of cannabinoids on the brain . Prog Neurobiol 58: 315348
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: 110117
Google Scholar | Crossref | Medline
Ashton H (1999a) Cannabis in palliative care . CME Bull Palliat Med 1: 7377
Google Scholar
Ashton H (1999b) Adverse effects of cannabis and cannabinoids . Br J Anaesth 83: 637649
Google Scholar | Crossref | Medline
Ashton H , Young A H (2003) GABA-ergic drugs: exit stage left, enter stage right . J Psychopharmacol 17: 174178
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: 705720
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: 845852
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: 105115
Google Scholar | Crossref | Medline
Carlini E A , Cunha J M (1981) Hypnotic and antiepileptic effects of cannabidiol . J Clin Pharmacol 21: 417S427S
Google Scholar | Crossref | Medline
Cassidy F , Ahearn E P , Carroll B J (2001) Substance abuse in bipolardisorder . Bipolar Disord 3: 181188
Google Scholar | Crossref | Medline
Christie M J , Vaughan C W (2001) Cannabinoids act backwards . Nature 410: 527530
Google Scholar | Crossref | Medline
Committee on Safety of Medicines (2003) Current Problems in Pharmacovigilance 29: 66
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. 459524
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. 2149
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: 175185
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: 5861
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. 205231
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: 822825
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: 521528
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: 15581572
Google Scholar | Crossref | Medline | ISI
Drevets W C , Price J L , Simpson J R (1997) Subgenual prefrontal cortex abnormalities in mood disorders . Nature 386: 824827
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: 7987
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: 3740
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: 293295
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: 377S382S
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. 187205
Google Scholar | Crossref
Geddes J R , Carney S M , Davies C (2003) Relapse prevention with antidepressant treatment in depressive disorders . Lancet 361: 643651
Google Scholar
Geddes J , Goodwin G (2001) Bipolar disorder: clinical uncertainty, evidence-based medicine and large-scale randomised trials . Br J Psychiatry 41 (Suppl): S191S194
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): 192192
Google Scholar
Gieringer D H (2003) The acceptance of medicinal marijuana in the US . J Cannabis Ther 3: 5365
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: 137142
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. 117131
Google Scholar
Goodwin G M (2003) Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association of Psychopharmacology . J Psychopharmacol 17: 149173
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: 171177
Google Scholar | Crossref | Medline
Grotenhermen F (2003) Clinical pharmacokinetics . J Cannabis Ther 3: 351
Google Scholar | Crossref
Gruber A J , Pope H G , Brown M E (1996) Do patients use marijuana as an antidepressant? Depression 4: 7780
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: 558559
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. 145166
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. 167204
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: 943949
Google Scholar
Johns A (2001) The psychiatric effects of cannabis . Br J Psychiatry 178: 116122
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: 230233
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: 15791588
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: 201205
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. 2168
Google Scholar
Martyn C N , Illis L S , Thom J (1995) Nabilone in the treatment of multiple sclerosis . Lancet 345: 579579
Google Scholar | Crossref | Medline
Maykutt M O (1985) Health consequences of acute and chronic marihuana use . Prog Neuropsychopharmacol Biol Psychiatry 9: 209238
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: 103132
Google Scholar | Crossref
Mechoulam R , Parker L A , Gallily R (2002) Cannabidiol: an overview of some pharmacological aspects . Clin Pharmacol 42: 11S19S
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. 385392
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: 291295
Google Scholar | Crossref | Medline
Mishra A , Moore P B , Hobbs R (2004) Does quetiapine have moodaltering properties? J Psychopharmacol 18: 281284
Google Scholar | SAGE Journals
Monti J M (1997) Hypnotic-like effects of cannabidiol in the rat . Psychopharmacology 55: 263265
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: 105114
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: 19331940
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. 671682
Google Scholar | Crossref
Notcutt W , Price M , Chapman G (1997) Clinical experience with nabilone for chronic pain . Pharmaceutical Sci 3: 551555
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. 735738
Google Scholar
Pertwee R G (1997) Pharmacology of cannabinoid CB1 and CB2 receptors . Pharmacol Ther 74: 129180
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. 177185
Google Scholar | Crossref
Pertwee R G (1999b) Pharmacology of cannabinoid receptor ligands . Curr Med Chem 6: 635664
Google Scholar | Medline
Pertwee R G (2001) Cannabinoid receptors and pain . Prog Neurobiol 63: 569611
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: 515528
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: 218224
Google Scholar | Crossref | Medline
Porter R , Ferrier N , Ashton H (1999) Anticonvulsants as mood stabilisers . Adv Psychiatr Treat 5: 96103
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: 5558
Google Scholar | Crossref | Medline
Ratey J J , Ciraulo D A , Shader R I (1981) Lithium and marijuana . J Clin Psychopharmacol 1: 3233
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. 763776
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: 25112518
Google Scholar | Crossref
Rottanburg D , Robins A H , Ben-Arie O , Teggin A , Elk R (1982) Cannabis-associated psychosis with hypomanic features . Lancet 2: 13641366
Google Scholar | Crossref | Medline
Russo E (2003) Cannabis: from pariah to prescription . J Cannabis Ther 3: 129
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: 1104
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: 349352
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: 529538
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: 107114
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: 254260
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: 477485
Google Scholar | Crossref | Medline
Sulcova E , Mechoulam R , Fride E (1998) Biphasic effects of anandamide . Pharmacol Biochem Behav 59: 347353
Google Scholar | Crossref | Medline
Surguladze S , Keedwell P , Phillips M (2003) Neural systems underlying affective disorders . Adv Psychiatr Treat 9: 446455
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: 253258
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: 576579
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: 165172
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: 133150
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: 1826
Google Scholar | SAGE Journals
Whittle B A , Guy G W , Robson P (2001) Prospects for new cannabis-based prescription medicines . J Cannabis Ther 1: 183205
Google Scholar | Crossref
Williams C M , Kukham T C (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors . Psychopharmacology 143: 315317
Google Scholar | Crossref | Medline
Williamson E M , Evans F J (2000) Cannabinoids in clinical practice . Drugs 60: 13031314
Google Scholar | Crossref | Medline
Wilson R I , Nicol R A (2001) Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses . Nature 410: 558559
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: 8189
Google Scholar | Crossref | Medline
Wylie A S , Scott R T A , Burnett S J (1995) Psychosis due to ‘skunk’ , Br Med J 311: 125125
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. 133141
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: 245259
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: 260264
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: 485486
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: 141143
Google Scholar | Crossref | Medline

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.
  • Access Options

    My Account

    Welcome
    You do not have access to this content.

    Chinese Institutions / 中国用户

    Click the button below for the full-text content

    请点击以下获取该全文

    Institutional Login

    Purchase Content

    24 hours online access to download content

    Added to Cart

    Cart is full

    There is currently no price available for this item in your region.

    Research off-campus without worrying about access issues. Find out about Lean Library here


Purchase

JOP-article-ppv for GBP32.00
JOP-article-ppv for $41.50
Single Issue 24 hour E-access for GBP330.74
Single Issue 24 hour E-access for $403.83