Medical Marijuana and Dementia-Associated Agitation: Stirring the Pot

From the Group for the Advancement of Psychiatry, Committee on Aging

My 79-year-old memory clinic patient arrived with her daughter, whose first question caught me off guard: “Can you prescribe medical marijuana for my mother? I think it might help her agitation better than the medication you gave her last visit.” When I asked her why she thought that marijuana might help, she blushed and turned her eyes briefly away. “Well, the other night she was really bad . . . and we gave her a joint. She really calmed down.”

This dialogue will become familiar as baby boomers-many of whom are comfortable with marijuana use-age into caretaking roles, assisting parents who have Alzheimer disease and other conditions that combine cognitive decline with behavioral symptoms.

The spread of medical and recreational marijuana use in the US is accelerating. Medical use of marijuana is now legalized in 28 states plus Washington, DC.¹ Twelve additional states allow medical use of isolated cannabidiol, one of the many active alkaloids contained in marijuana.¹ Although marijuana remains a Schedule I substance and has not been legalized under federal law, the Obama administration refrained from interfering with its medical use in states where it is approved and appropriately regulated.² Whether this federal permissiveness will continue under President-Elect Trump’s leadership is uncertain, despite his remarks regarding the benefits of medical marijuana.³

Interest in medical and complementary treatments for agitation in people with dementia disorders, which are now under the umbrella of the DSM-5 major neurocognitive disorder category, has grown in part because of an increase in the prevalence of these disorders. Improved treatment of many chronic medical diseases has prolonged life expectancy. Because age is the chief risk factor for major neurocognitive disorders, greater longevity increases the prominence of cognitive impairment in the aging population. By 2050, barring significant treatment advances, nearly 14 million older adults in the US will live with Alzheimer disease-the most common of neurodegenerative disorders.⁴ The majority will display the behavioral disturbances that so often accompany cognitive decline, including agitation.

By 2050 nearly 14 million older adults in the US will live with Alzheimer disease-the most common of neurodegenerative disorders.

The most frequent of dementia-associated disruptive behaviors, agitation is known to increase caregiver burden and morbidity.⁵ Despite suggestive leads from case reports in peer-reviewed journals, no medication has yet achieved an FDA indication as a primary treatment for behavioral disturbances associated with major neurocognitive disorders.

As the desire for effective treatment grows in parallel with the increased availability of marijuana, it’s time to reconsider the evidence regarding risks and benefits of marijuana use in the care of those with cognitive decline and disruptive behaviors. In a recent review, Maust and colleagues⁶ tackled this question. They noted that “dementia” is a qualifying condition for medical marijuana use in 10 states, often specifically designated for treatment of agitation in Alzheimer disease, despite a lack of support for its efficacy in that usage. Their citation of the “only randomized, placebo-controlled trial of marijuana for dementia,” which did not significantly improve agitation, fails to note the difference between marijuana and the isolated alkaloid administered in that study, tetrahydrocannabinol (THC).⁷ A positive open-label trial of medical cannabis oil, also cited by Maust and colleagues, used a marijuana extract high in THC and low in other marijuana alkaloids.⁸

The more commonly used forms of marijuana appear to remain untested as treatments for agitation in Alzheimer disease. Agitation associated with non-Alzheimer dementias appears not to be a qualifying condition for marijuana use-an important consideration for clinicians given that cognitive impairment in many older adults has no etiologic diagnosis.

Treatment approaches

Marijuana, although it may be requested, is not the only available treatment alternative for addressing disruptive behaviors in cognitively impaired individuals. Behavioral approaches such as the DICE (Describe, Investigate, Create, and Evaluate) protocol are widely regarded as the first-line intervention, although agitation sometimes fails to respond to this nonpharmacological approach.⁹

Citalopram and other serotonergic antidepressants are beneficial in the management of agitation, although they are not without adverse effects.¹⁰ Antiadrenergic agents, analgesics, and a smattering of other pharmacological approaches are supported by a limited evidence base and are used in the absence of a more definitive or standardized approach.

Synthetic tetrahydrocannabinol, available as dronabinol, holds a credible position among these sometimes effective pharmacological approaches, although both positive and negative results have been reported.^11-13 Antipsychotic medications, still frequently prescribed, are recognized as potentially harmful and of limited clinical value for many agitated, cognitively impaired patients.¹⁴ The FDA-approved cognitive enhancers, memantine and the cholinesterase inhibitors, are not regarded as valuable treatments for acute agitation.

Marijuana: effective and safe?

The jury is still out on medical marijuana’s role in the treatment ofAlzheimer disease and other major neurocognitive disorders. Anorexia, nausea, anxiety, depression, or pain might be reasonable indications in selected patients. The benefits of such use must be weighed against potential risks. Some research suggests that marijuana’s active alkaloids, the cannabinoids, can mitigate Alzheimer disease progression through neuroprotective blockade of microglial activation.¹⁵

The more commonly used forms of marijuana appear to remain untested as treatments for agitation in Alzheimer disease.

Cannabis has been reported to have adverse acute and non-acute effects on cognitive functions, which might outweigh its therapeutic benefits.¹⁶ Furthermore, marijuana use has been associated with hallucinations and adverse effects on mood and memory as well as unpleasant physical symptoms, including blurred vision, dizziness, dry mouth and eyes, tachycardia, somnolence, urinary retention, and changes in blood pressure.

Marijuana interacts through pharmacokinetic and pharmacodynamic mechanisms with a large variety of prescribed psychiatric medications, including SSRIs, TCAs, and lithium. It has an additive effect when used in conjunction with other CNS depressants.¹⁷ One case report attributed increased bleeding risk to the combined use of marijuana and warfarin, and another case report attributed a man’s myocardial infarction to the concurrent use of marijuana with sildenafil.^18,19 Needless to say, these potential complications could seriously complicate the treatment of a person with dementia.

 MORE ABOUT JAMES M. ELLISON, MD, MPH

Formerly Director of Geriatric Psychiatry at McLean Hospital in Belmont, Massachusetts, I recently re-located to Wilmington, Delaware, where I am privileged to serve as the first Swank Foundation Endowed Chair in Memory Care and Geriatrics. In that capacity, I am consultant to a team of geriatricians who have helped me experience the great value of interdisciplinary and collaborative care.

I am the proud father of 2 teenage boys. I wish for them as much career satisfaction, whatever they choose to pursue, as I have found in psychiatry.

Disclosures:

Dr. Ellison is Professor of Psychiatry and Human Behavior, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; and Swank Foundation Endowed Chair in Memory Care and Geriatrics at Christiana Care in Wilmington, DE. He reports no conflicts of interest concerning the subject matter of this article.

Acknowledgment-This article is from the Committee on Aging of the Group for the Advancement of Psychiatry (GAP): Robert P. Roca, MD, Chair; James M. Ellison, MD; Warachal Faison, MD; Helen Kyomen, MD; Susan Lehman, MD; Ben Liptzin, MD; Marsden McGuire, MD; Keith Meador, MD; Robert Rohrbaugh, MD; and Ken Sakauye, MD. The GAP, American psychiatry’s think tank, informs and educates mental health professionals, policy makers, and the public at large.

References:

1. ProCon.org. 28 Medical Marijuana States and DC. November 2016. http://medicalmarijuana.procon.org/view.resource.php?resourceID=000881. Accessed December 6, 2016.

2. US Department of Justice. Guidance Regarding Marijuana Enforcement. August 2013. https://www.justice.gov/iso/opa/resources/3052013829132756857467.pdf. Accessed December 6, 2016.

3. Strauss M. Will the Trump Administration Weed Out Medical Marijuana? November 11, 2016. http://news.nationalgeographic.com/2016/11/medical-marijuana-cannabis-trump-election/. Accessed December 6, 2016.

4. Alzhemer Association. Changing the Trajectory of Alzheimer Disease: How a Treatment by 2015 Saved Lives and Dollars. 2015. https://www.alz.org/documents_custom/trajectory.pdf. Accessed December 6, 2016.

5. Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry. 2000;157:708-714.

6. Maust DT, Bonar EE, Ilgen MA, et al. Agitation in Alzheimer disease as a qualifying condition for medical marijuana in the United States. Am J Geriatr Psychiatry. 2016;24:1000-1003.

7. van den Elsen GAH, Ahmed AIA, Verkes RJ, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. Neurology. 2015;84:2338-2346.

8. Shelef A, Barak Y, Berger U, et al. Safety and efficacy of medical cannabis oil for behavioral and psychological symptoms of dementia: an open label, add-on, pilot study. J Alzheimer Dis. 2016;51:15-19.

9. Kales HC, Gitlin LN, Lyketsos CG, et al. Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc. 2014;62:762-769.

10. Leonpacher AK, Peters ME, Drye LT, et al. Effects of citalopram on neuropsychiatric symptoms in Alzheimer dementia: evidence from the CitADstudy. Am J Psychiatry. 2016;173:473-480.

11. Woodward MR, Harper DG, Stolyar A, et al. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry. 2014;22:415-419.

12. Volicer L, Stelly M, Morris J, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer disease. Int J Geriatr Psychiatry. 1997;12:913-919.

13. Antonsdottir IM, Makino KM, Porsteinsson AP. Dazed and confused: medical cannabis in Alzheimer disease. Am J Geriatr Psychiatry. 2016;24:1004-1006.

14. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer disease. N Engl J Med. 2006;355:1525-1538.

15. Ramirez BG, Blazquez C, Gomez del Pulgar T, et al. Prevention of Alzheimer disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005;25:1904-1913.

16. Crane NA, Schuster RM, Fusar-Poli P, et al. Effects of cannabis on neurocognitive functioning: recent advances, neurodevelopmental influences, and sex differences. Neuropsychol Rev. 2013;23:117-137.

17. Lindsey WT, Stewart D, Childress D. Drug interactions between common illicit drugs and prescription therapies. Am J Drug Alcohol Abuse. 2012;38:334-343.

18. Yamreudeewong W, Wong HK, Brausch LM, et al. Probable interaction between warfarin and marijuana smoking. Ann Pharmacother. 2009;43:1347-1353.

19. McLeod AL, McKenna CJ, Northridge DB. Myocardial infarction following the combined recreational use of Viagra and cannabis. Clin Cardiol. 2002;25:133-134.