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Implications of Cannabis Use on Attention Deficits Associated with Bipolar Disorder
  • CME
  • CE

Joseph F. Goldberg, MD
Released: October 7, 2021
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Key Research

The complex relationship between ADD and bipolar disorder is confounded by numerous overlapping or similar symptoms that present hurdles for accurate and timely diagnosis. However, according to several studies, the two disorders have significant differences at the functional and anatomical level despite common symptoms, such as cognitive deficits, and relatively frequent comorbidity, which affects diagnosis and effective treatment strategy. Frank ADD is considered a childhood-onset disorder that can persist into adulthood in up to two thirds of cases.1 There remains debate within the field as to whether ADD symptoms can arise de novo in adults with no childhood history of ADD.2 In adults with bipolar disorder, meta-analyses have reported prevalence rates for comorbid ADD/ADHD ranging from 9.5% to 21.2%,3 as compared with a rate of adult ADHD of approximately 4.4% in the general population.4 Both subjective cognitive complaints and objective cognitive deficits are common in people with bipolar disorder and are identifiable across all phases of illness including euthymia; they most often involve impairment in attention, verbal memory, and executive functioning.5,6 Up to 60% of adult patients with bipolar disorder have been shown to score from -0.5 to -1.0 standard deviation below the general population in measures of global cognitive functioning.7,8 When assessing cognitive complaints in adult patients with bipolar disorder, in addition to investigating a history of childhood ADD/ADHD symptoms, it is useful to differentiate complaints that reflect true cognitive deficits from affective or anxiety symptoms that can involve memory and attentional processing, since many patients with bipolar disorder who report subjective cognitive complaints may not demonstrate objective cognitive deficits but may instead misidentify affective or anxiety symptoms as signs of cognitive dysfunction.9

Subjective cognitive complaints are common in adults with bipolar disorder and do not necessarily reflect comorbid ADD. In fact, they may occur from a wide variety of causes that range from symptoms related to depression or anxiety to the aftereffects of substance use to medication adverse events. The differential diagnosis of attentional complaints also includes possible adverse cognitive effects from medications. Regarding the patient’s pharmacology, lamotrigine in the usual therapeutic dosing range for bipolar disorder (<200 mg/day) has not been associated with adverse cognitive events.10

Long-term lithium has been associated with small deficits in verbal learning and memory and psychomotor functioning but no negative effects on attention, executive functioning, or nonverbal memory.11 Aripiprazole is believed to have minimal adverse cognitive events because of its modest antihistaminergic effects and may confer some benefit on cognitive domains compared with other antipsychotics in patients with schizophrenia.12 Hence, it was felt to be unlikely that the patient’s current pharmacology was negatively affecting her cognitive functioning.

Bipolar disorder and cannabis use are highly comorbid and are each associated with cognitive impairment. Hence, it is important to evaluate the implications of cannabis use on cognition in people with bipolar disorder, as cannabis use in bipolar disorder may be associated with greater cognitive impairment. Regular cannabis use is notoriously associated with causing anxiety, paranoia, depression, and amotivation/apathy.13 In adults with bipolar disorder, a review of 5 studies found higher mood symptom severity levels in those using cannabis in the preceding 6 months.14 The prevalence of cannabis use disorder in patients with bipolar disorder ranges from 10% to 40%.15 Pharmacotherapy studies in patients with bipolar disorder collectively indicate that active cannabis use is a predictor of poorer treatment response.16 Despite some patients being convinced that cannabis use calms them, uplifts them, blunts their anxiety, enables them to sleep, and has other benefits, these short-term perceived benefits are contradicted by evidence that points to a clear association between cannabis usage and worsening course of bipolar disorder over time. In a study of 4915 participants, Henquet et al. found a strong increased risk of manic symptoms associated with cannabis over a 3-year follow-up (after controlling for possible covariates), an earlier age of onset of bipolar disorder, greater overall illness severity, more rapid cycling, poorer life functioning, and poorer adherence with prescribed treatments.17 Zorilla et al compared the clinical course and outcomes of patients with bipolar disorder who stopped cannabis use after an illness episode with those who had never used cannabis and those who continued cannabis use and reported that in a 2-year period, the continued users had significantly lower rates of recovery and greater work impairment.18

Since long-term cannabis use adversely affects attentional processing, learning, memory, and executive functioning, it poses a confounding factor for healthcare professionals faced with self-reported complaints of attention or cognitive deficits in patients with bipolar disorder. Differentiating the cognitive deficits of bipolar exacerbated by cannabis use from ADD or other conditions is key to effective diagnosis and treatment strategy.

References 

  1. Faraone SV, Biederman J, Mick E. The age-dependent decline of attention-deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36:159-165.
  2. Caye A, Rocha TB, Anselme L, et al. Attention-deficit/hyperactivity disorder trajectories from childhood to young adulthood: evidence from a birth cohort supporting a late-onset syndrome. JAMA Psychiatry. 2016;73:705-712.
  3. Wingo AP, Ghaemi SN. A systematic review of rates and diagnostic validity of comorbid adult attention-deficit/hyperactivity disorder and bipolar disorder. J Clin Psychiatry. 2007;68:1776-1784.
  4. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163:716-723.
  5. Martínez-Arán A, Vieta E, Reinares M, et al. Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. Am J Psychiatry. 2004;161:262-270
  6. Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord. 2009;113:1-20.
  7. Reichenberg A, Harvey PD, Bowie CR, et al. Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Schiz Bull. 2009;35:1022-1029.
  8. Burdick KE, Russo M, Frangou S, et al. Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychol Med. 2014;44:3083-3096.
  9. Burdick KE, Endick CJ, Goldberg JF. Assessing cognitive deficits in bipolar disorder: are self-reports valid? Psychiatry Res. 2005;136:43-50.
  10. Khan A, Ginsberg LD, Asnis GM, et al. Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder. J Clin Psychiatry. 2004;65:1483-1490.
  11. Wingo AP, Wingo TS, Harvey PD, et al. Effects of lithium on cognitive performance: a meta-analysis. J Clin Psychiatry. 2009;70:1588-1597.
  12. Kern RS, Green MF, Cornblatt BA, et al. The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology. 2006;187:312-320.
  13. Johns A. Psychiatric effects of cannabis. Br J Psychiatry. 2001;178:116-122.
  14. Mammen G, Rueda S, Roerecke M, et al. Association of cannabis with long-term clinical symptoms in anxiety and mood disorders: a systematic review of prospective studies. J Clin Psychiatry. 2018;79:17r11839.
  15. Cerullo MA, Strakowski SM. The prevalence and significance of substance use disorders in bipolar type I and type II disorder. Subst Abuse Treat Prev Policy. 2007;2:29.
  16. Coles AS, Sasiadek J, George TP. Pharmacotherapies for co-occurring substance use and bipolar disorders: a systematic review. Bipolar Disord. 2019;21:595-610.
  17. Henquet C, Krabbendam L, de Graaf R, et al. Cannabis use and expression of mania in the general population. J Affect Disord. 2006;95:103-110.
  18. Zorrilla I, Aguado J, Jaro JM, et al. Cannabis and bipolar disorder: does quitting cannabis use during manic/mixed episodes improve clinical/functional outcomes? Acta Psychiatrica Scand. 2015;131:100-110.
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