Cannabis: An Emerging Treatment for Common Symptoms in Older Adults

Journal of the American Geriatrics Society “Background/objectives: Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist.

Design: Anonymous survey.

Setting: Geriatrics clinic.

Participants: A total of 568 adults 65 years and older.

Intervention: Not applicable.

Measurements: Survey assessing characteristics of cannabis use.

Results: Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%).

The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis “somewhat” or “extremely” helpful in managing one of these conditions, with few adverse effects.

Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking).

Conclusion: Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.”

https://pubmed.ncbi.nlm.nih.gov/33026117/

https://onlinelibrary.wiley.com/doi/10.1111/jgs.16833

“Study Finds Older Adults Using Cannabis to Treat Common Health Conditions”  https://health.ucsd.edu/news/releases/Pages/2020-10-07-study-finds-older-adults-using-cannabis-to-treat-common-health-conditions.aspx

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

Frontiers in Pharmacology (@FrontPharmacol) | Twitter “Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.”

https://pubmed.ncbi.nlm.nih.gov/32792944/

“Cannabinoids act by targeting several signaling processes, such as pain, abnormal processing of Aβ and tau, neuroinflammation, excitotoxicity, oxidative stress, and mitochondrial dysfunction, which play a pivotal role in the management of AD. Cannabinoids also ameliorate behavioral and cognitive dysfunctions. Therefore, due to these extensive medical uses of cannabinoid compounds, it can be said that targeting the endocannabinoid system can be a promising strategy to develop an effective therapy for the management of AD. Furthermore, cannabinoids may demonstrate a safe and reliable low-cost therapy, with limited side effects.”

https://www.frontiersin.org/articles/10.3389/fphar.2020.01097/full

Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

 “In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present a state of art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.”

https://pubmed.ncbi.nlm.nih.gov/32691712/

https://www.eurekaselect.com/183955/article

Use of Cannabis for Agitation in Patients With Dementia

 logo“Studies have reported changes in the endocannabinoid system in the brain of patients with Alzheimer’s disease (AD), playing a role in the pathophysiology of AD. Cannabinoids have been shown to have neuroprotective properties, reduce neuroinflammation, and enhance neurogenesis. Evidence suggests that the utilization of marijuana products containing both tetrahydrocannabinol (THC) and cannabidiol (CBD) or CBD alone have been effective and safe for use in older people with agitation associated with dementia.

A review in 2017 summarized positive findings for therapeutic benefits of cannabinoids in agitation of AD and dementia, but there was no definitive conclusion because of varying cannabinoid products. Cannabinoids were shown to be well tolerated, with few short-term side effects. This differs from first-line medications utilized for dementia behaviors, which can have unwanted side effects. Further research regarding the safety, efficacy, and variability of these products in older people is needed.”

https://pubmed.ncbi.nlm.nih.gov/32600509/

https://www.ingentaconnect.com/content/ascp/tscp/2020/00000035/00000007/art00006;jsessionid=1ivcuvrvy4g1s.x-ic-live-03

Cannabinoid as Beneficial Replacement Therapy for Psychotropics to Treat Neuropsychiatric Symptoms in Severe Alzheimer’s Dementia: A Clinical Case Report

CrossFit | 190629“Alzheimer’s Dementia (AD) is a devastating neurodegenerative disease that affects approximately 17% of people aged 75-84. Neuropsychiatric symptoms (NPS) such as delusions, agitation, anxiety, and hallucinations are present in up to 95% of patients in all stages of dementia. To date, any approved and effective pharmacological interventions for the treatment of NPS are still not available.

We describe a clinical case of a female patient diagnosed with AD with continuous cognitive decline and dementia-related behavioral symptoms. Between 2008 and 2019, the patient was examined half-yearly at the memory clinic of the Medical University of Innsbruck. At each visit, cognitive state and pharmacological treatment were evaluated. In addition, NPs were assessed by using the neuropsychiatric inventory (NPI). In 2018, the patient progressed to severe AD stage and presented with progressive NPs (anxiety, suspected delusions, agitation, aggressive behavior, and suspected pain due to long immobility).

Consequently, off-label treatment with low-dose dronabinol was initiated, which facilitated a reduction of psychopharmacological treatment from six to three psychotropics. At the same time, the patient’s emotional state improved, while disruptive behavior, aggression, and sedation decreased significantly. This case report underpins the need for randomized, controlled trials to explore the effect of cannabinoid receptor agonists on behavioral and psychological symptoms in patients with severe AD.”

https://pubmed.ncbi.nlm.nih.gov/32477187/

“Cannabinoids have a distinct pharmacologic profile that may offer an alternative pharmacologic approach to antipsychotics and sedatives for treating NPs in patients with AD. In addition, the beneficial effect on appetite and pain may significantly improve quality of life of AD-patients and their caregivers.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00413/full

Possible therapeutic applications of cannabis in the neuropsychopharmacology field.

European Neuropsychopharmacology“Cannabis use induces a plethora of actions on the CNS via its active chemical ingredients, the so-called phytocannabinoids.

These compounds have been frequently associated with the intoxicating properties of cannabis preparations. However, not all phytocannabinoids are psychotropic, and, irrespective of whether they are psychotropic or not, they have also shown numerous therapeutic properties.

These properties are mostly associated with their ability to modulate the activity of an intercellular communication system, the so-called endocannabinoid system, which is highly active in the CNS and has been found altered in many neurological disorders.

Specifically, this includes the neuropsychopharmacology field, with diseases such as schizophrenia and related psychoses, anxiety-related disorders, mood disorders, addiction, sleep disorders, post-traumatic stress disorder, anorexia nervosa and other feeding-related disorders, dementia, epileptic syndromes, as well as autism, fragile X syndrome and other neurodevelopment-related disorders.

Here, we gather, from a pharmacological and biochemical standpoint, the recent advances in the study of the therapeutic relevance of the endocannabinoid system in the CNS, with especial emphasis on the neuropsychopharmacology field. We also illustrate the efforts that are currently being made to investigate at the clinical level the potential therapeutic benefits derived from elevating or inhibiting endocannabinoid signaling in animal models of neuropsychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32057592

https://www.sciencedirect.com/science/article/abs/pii/S0924977X20300365?via%3Dihub

Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer’s disease?

Cellular Signalling“Alzheimer’s disease (AD) is a neurodegenerative disorder which accounts for 60-70% of the 50 million worldwide cases of dementia and is characterised by cognitive impairments, many of which have long been associated with dysfunction of the cholinergic system.

Although the M1 muscarinic acetylcholine receptor (mAChR) is considered a promising drug target for AD, ligands targeting this receptor have so far been unsuccessful in clinical trials.

As modulatory receptors to cholinergic transmission, the endocannabinoid system may be a promising drug target to allow fine tuning of the cholinergic system. Furthermore, disease-related changes have been found in the endocannabinoid system during AD progression and indeed targeting the endocannabinoid system at specific disease stages alleviates cognitive symptoms in numerous mouse models of AD.

Here we review the role of the endocannabinoid system in AD, and its crosstalk with mAChRs as a potential drug target for cholinergic dysfunction.”

https://www.ncbi.nlm.nih.gov/pubmed/31978506

“Targeting the endocannabinoid system could fine tune the cholinergic system”

https://www.sciencedirect.com/science/article/abs/pii/S089865682030022X?via%3Dihub

A Review on Studies of Marijuana for Alzheimer’s Disease – Focusing on CBD, THC.

book “This study was to discuss the research trend of dementia treatment using cannabis for the purpose of providing the basis of cannabis use for medical purposes in the future.

RESULTS:

These results implied that the CBD components of cannabis might be useful to treat and prevent AD because CBD components could suppress the main causal factors of AD.

Moreover, it was suggested that using CBD and THC together could be more useful than using CBD or THC alone.

CONCLUSION:

We hope that there will be a solid foundation to use cannabis for medical use by continuously evaluating the possibility of using cannabis for clinical purposes as a dementia treatment substance and cannabis can be used as a positive tool.”

https://www.ncbi.nlm.nih.gov/pubmed/31970019

“The ideal treatment for Alzheimer’s disease (AD) should be able to modulate the disease through multiple mechanisms rather than targeting a single dysregulated pathway.” http://www.ncbi.nlm.nih.gov/pubmed/25147120                                                             

THC could be a potential therapeutic treatment option for Alzheimer’s disease through multiple functions and pathways.” http://www.ncbi.nlm.nih.gov/pubmed/25024327

 CBD treatment would be in line with preventative, multimodal drug strategies targeting a combination of pathological symptoms, which might be ideal for AD #therapy.” http://www.ncbi.nlm.nih.gov/pubmed/27471947
“Combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD.” http://www.ncbi.nlm.nih.gov/pubmed/25125475

Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis.

 Image result for The Canadian Journal of Psychiatry“In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth.
Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have driven  the search for safer pharmacotherapies-including cannabinoids.

AIM:

To assess the efficacy and acceptability of cannabinoids for the treatment of NPS in individuals with dementia.

FINDINGS:

Cannabinoids led to significant improvements across NPS instruments, including the Cohen Mansfield Agitation Inventory (SMD = -0.80; 95% confidence interval [CI], -1.45 to -0.16), the Neuropsychiatric Inventory (SMD = -0.61; CI, -1.07 to -0.15), and nocturnal actigraphy (SMD = -1.05; CI, -1.56 to -0.54h). Cannabinoids were well-tolerated, with an overall trial completion rate of 93% (193/205) and no serious treatment-related adverse events. Treatment efficacy was associated with baseline dementia severity and dose, but not dementia subtype, age, or sex. The overall study quality was rated as low.

CONCLUSIONS:

There is preliminary evidence for the efficacy and tolerability of cannabinoids as treatments for NPS. Population-based studies are needed to characterize their real-world effectiveness and acceptability.”

https://www.ncbi.nlm.nih.gov/pubmed/31835954

https://journals.sagepub.com/doi/abs/10.1177/0706743719892717?journalCode=cpab

The Cannabinoid Receptor Agonist WIN55,212-2 Ameliorates Hippocampal Neuronal Damage After Chronic Cerebral Hypoperfusion Possibly Through Inhibiting Oxidative Stress and ASK1-p38 Signaling.

 “Chronic cerebral hypoperfusion (CCH) is a major contributor to cognitive decline and degenerative processes leading to Alzheimer’s disease, vascular dementia, and aging. However, the delicate mechanism of CCH-induced neuronal damage, and therefore proper treatment, remains unclear.

WIN55,212-2 (WIN) is a nonselective cannabinoid receptor agonist that has been shown to have effects on hippocampal neuron survival. In this study, we investigated the potential roles of WIN, as well as its underlying mechanism in a rat CCH model of bilateral common carotid artery occlusion.

These findings indicated that WIN may be a potential therapeutic agent for ischemic neuronal damage, involving a mechanism associated with the suppression of oxidative stress and ASK1-p38 signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31808139

https://link.springer.com/article/10.1007%2Fs12640-019-00141-8