Cannabinoids in the Management of Frontotemporal Dementia: A Case Series

Gopalakrishna, Ganesh; Srivathsal, Yazhini; Kaur, Gurmehr

doi:10.2217/nmt-2020-0048

Cited by 8 publications

(3 citation statements)

References 13 publications

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“…Of these, five studies were controlled trials [17][18][19][20][21] , three were openlabel/observational studies, and seven were case reports. 16,[22][23][24][25][26][27][28][29][30] To facilitate description of the findings, the publications selected were grouped in the following subsections, according to the neuropsychiatric domains targeted by the intervention: (a) agitation; (b) sleep disturbances; (c) abnormal sexual behavior.…”

Section: Resultsmentioning

confidence: 99%

“…27 Favorable results were also observed in patients with FTD suffering from agitation and anxiety who were given CBD (medical marijuana). 30 Conversely, in two controlled trials (level of evidence 1), enrolling patients with severe AD, VD, and AD/ VD, who were suffering from agitation and other NPS, the authors found no significant differences between dronabinol and placebo. 19,20 Moreover, one of the patients ("B") with severe AD 25 who received dronabinol, achieved an improvement in nighttime agitation for only a very short period.…”

Section: Efficacymentioning

confidence: 97%

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Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review

Stella¹,

Valiengo²,

Paula³

et al. 2021

Trends Psychiatry Psychother

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Introduction: Neuropsychiatric symptoms are an integral component of the natural history of dementia, occurring from prodromal to advanced stages of the disease process and causing increased burden and morbidity. Clinical presentations are pleomorphic and clinical management often requires combinations of pharmacological and non-pharmacological interventions. However, limited efficacy and a non-negligible incidence of adverse psychotropic drug events emphasize the need for novel therapeutic options. Objectives: To review the evidence supporting use of medical cannabinoids for treatment of neuropsychiatric symptoms (NPS) of dementia. Methods: We conducted a systematic review of the medical literature to examine scientific publications reporting use of medical cannabinoids for treatment of NPS. Medical Subject Headings (MeSH) were used to search for relevant publications and only papers reporting original clinical information were included. A secondary search was performed within selected publications to capture relevant citations that were not retrieved by the systematic review. The papers selected were categorized according to the level of evidence generated by the studies in relation to this clinical application, i.e. (1) controlled clinical trials;(2) open-label or observational studies; and (3) case reports. Results: Fifteen publications with original clinical data were retrieved: five controlled clinical trials, three open-label/observational studies, and seven case reports. Most studies indicated that use of medical cannabinoids engendered favorable outcomes for treatment of NPS related to moderate and advanced stages of dementia, particularly agitation, aggressive behavior, sleep disorder, and sexual disinhibition. Conclusion: Medical cannabinoids constitute a promising pharmacological approach to treatment of NPS with preliminary evidence of benefit in at least moderate to severe dementia. Controlled trials with longitudinal designs and larger samples are required to examine the long-term efficacy of these drugs in different types and stages of dementia, in addition to their adverse events and risk of interactions with other drugs. Many pharmacological details are yet to be determined, such as dosing, treatment duration, and concentrations of active compounds (e.g., cannabidiol [CBD]/ Δ 9 -tetrahydrocannabinol [THC] ratio) in commercial preparations of medical cannabinoids.

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Section: Resultsmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 97%

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review

Stella¹,

Valiengo²,

Paula³

et al. 2021

Trends Psychiatry Psychother

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“…Such strategy is being investigated in different neurodegenerative disorders (e.g., Alzheimer’s disease, Parkinson’s disease, Huntington’s chorea, multiple sclerosis, ALS), mainly in preclinical studies with a few clinical trials already finalized or currently in progress [ 22 ]. Recent experimental evidence has related Tau-dependent FTD with dysregulation in the endocannabinoid signaling [ 25 ], which may support the pharmacological modulation of certain proteins of this system (e.g., CB 2 receptors) as a promising disease-modifying therapy in this form of FTD [ 10 , 25 , 30 ]. Such potential has not been investigated in TDP-43-dependent FTD yet, so that this has been the major objective of the present study, which has been conducted with a murine conditional TDP-43-dependent model of FTD that overexpress this protein exclusively in the forebrain (cortical and subcortical (e.g.…”

Section: Introductionmentioning

confidence: 99%

Preclinical investigation in FAAH inhibition as a neuroprotective therapy for frontotemporal dementia using TDP-43 transgenic male mice

Santos‐García

Rodríguez‐Cueto

Villegas

et al. 2023

J Neuroinflammation

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Background Frontotemporal dementia (FTD) is a heterogeneous group of early onset and progressive neurodegenerative disorders, characterized by degeneration in the frontal and temporal lobes, which causes deterioration in cognition, personality, social behavior and language. Around 45% of the cases are characterized by the presence of aggregates of the RNA-binding protein TDP-43. Methods In this study, we have used a murine model of FTD that overexpresses this protein exclusively in the forebrain (under the control of the CaMKIIα promoter) for several biochemical, histological and pharmacological studies focused on the endocannabinoid system. Results These mice exhibited at postnatal day 90 (PND90) important cognitive deficits, signs of emotional impairment and disinhibited social behaviour, which were, in most of cases, maintained during the first year of life of these animals. Motor activity was apparently normal, but FTD mice exhibited higher mortality. Their MRI imaging analysis and their ex-vivo histopathological evaluation proved changes compatible with atrophy (loss of specific groups of pyramidal neurons: Ctip2- and NeuN-positive cells) and inflammatory events (astroglial and microglial reactivities) in both cortical (medial prefrontal cortex) and subcortical (hippocampus) structures at PND90 and also at PND365. The analysis of the endocannabinoid system in these mice proved a decrease in the hydrolysing enzyme FAAH in the prefrontal cortex and the hippocampus, with an increase in the synthesizing enzyme NAPE-PLD only in the hippocampus, responses that were accompanied by modest elevations in anandamide and related N-acylethanolamines. The potentiation of these elevated levels of anandamide after the pharmacological inactivation of FAAH with URB597 resulted in a general improvement in behaviour, in particular in cognitive deterioration, associated with the preservation of pyramidal neurons of the medial prefrontal cortex and the CA1 layer of the hippocampus, and with the reduction of gliosis in both structures. Conclusions Our data confirmed the potential of elevating the endocannabinoid tone as a therapy against TDP-43-induced neuropathology in FTD, limiting glial reactivity, preserving neuronal integrity and improving cognitive, emotional and social deficits.

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Marijuana/memantine/valproic-acid

2021

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Cannabinoids in the Management of Frontotemporal Dementia: A Case Series

Cited by 8 publications

References 13 publications

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review

Medical cannabinoids for treatment of neuropsychiatric symptoms in dementia: a systematic review

Preclinical investigation in FAAH inhibition as a neuroprotective therapy for frontotemporal dementia using TDP-43 transgenic male mice

Marijuana/memantine/valproic-acid

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