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

Posted on December 15, 2019 by David

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.

Posted on December 8, 2019 by David

“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

Kinetics of acetylcholinesterase inhibition by hemp seed protein-derived peptides.

Posted on October 21, 2019 by David

Journal of Food Biochemistry banner “The aim of this work was to enhance the acetylcholinesterase (AChE)-inhibitory activity of a pepsin-produced hemp seed protein hydrolysates (HPH) through reverse-phase HPLC separation followed by identification of peptide sequences present in the most active fraction. The HPH was separated into eight fractions (F1-F8) with F7 exhibiting significantly (p < 0.05) the strongest (97.5%) in vitro inhibition of electric eel AChE (eeAChE) activity in comparison to 53.8% for HPH. The HPH consisted mostly of low molecular weight peptides of < 11 amino acid residues and most contained at least one hydrophobic amino acid. Kinetics of enzyme inhibition revealed a mixed-type inhibition of eeAChE activity by HPH whereas F7 acted through an uncompetitive mode; in contrast inhibition of human AChE by HPH and F7 was uncompetitive. The stronger inhibitory potency of the F7 peptides fraction against both enzymes was confirmed through reduced maximal velocity, catalytic efficiency, and inhibition constant values when compared to the HPH.

PRACTICAL APPLICATIONS: The use of natural products for the prevention or treatment of human diseases continues to be an area of intense research activities. Food protein-derived peptides obtained through enzymatic hydrolysis of hemp seed proteins were shown in vitro to be strong inhibitors of activities of both the eel and human forms of acetylcholinesterase (AChE). AChE is an important therapeutic target because excessive activity of this enzyme is a causative factor of neurodegenerative diseases such as dementia and Alzheimer’s. This work showed that peptides in the most active fraction are small in sizes, which may favor their absorption into blood circulation and possible permeation of the blood-brain barrier. Therefore, the hemp seed peptides are potential agents that can be used to formulate functional foods and nutraceuticals against neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/31353736

https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.12897

Agitation, Oxidative Stress, and Cytokines in Alzheimer Disease: Biomarker Analyses From a Clinical Trial With Nabilone for Agitation.

Posted on September 25, 2019 by David

“The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation.

We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38).

These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31547752

https://journals.sagepub.com/doi/abs/10.1177/0891988719874118?journalCode=jgpb

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.

Posted on June 18, 2019 by David

“Neuropsychiatric symptoms (NPS) in dementia impact profoundly on the quality of life of people living with dementia and their care givers. Evidence for the effectiveness and safety of current therapeutic options is varied.

Cannabinoids have been proposed as an alternative therapy, mainly due to their activity on CB1 receptors in the central nervous system. However, little is known regarding the safety and effectiveness of cannabinoid therapy in people with dementia.

A literature review was undertaken to identify, describe and critically appraise studies investigating cannabinoid use in treating NPS in dementia.

RESULTS:

Twelve studies met the inclusion criteria. There was considerable variability across the studies with respect to study design (50% randomized controlled trials), intervention [dronabinol (33%), nabilone (25%) or delta-9 tetrahydrocannabinol (THC; 42%)] and outcome measures.

Dronabinol (three studies) and THC (one study) were associated with significant improvements in a range of neuropsychiatric scores.

The most common adverse drug event (ADE) reported was sedation. A high risk of bias was found in eight studies. The highest-quality trial found no significant improvement in symptoms or difference in ADE rate between treatment arms. Included studies used low doses of oral cannabinoids and this may have contributed to the lack of demonstrated efficacy.

CONCLUSION:

While the efficacy of cannabinoids was not proven in a robust randomized control trial, observational studies showed promising results, especially for patients whose symptoms were refractory. In addition, the safety profile is favourable as most of the ADEs reported were mild. Future trials may want to consider dose escalation and formulations with improved bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/31205674

https://journals.sagepub.com/doi/10.1177/2042098619846993

Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors.

Posted on May 6, 2019 by David

Progress in Neuro-Psychopharmacology and Biological Psychiatry

“Long-term single housing increases aggressive behavior in mice, a condition named isolation-induced aggression or territorial aggression, which can be attenuated by anxiolytic, antidepressant, and antipsychotic drugs.

Preclinical and clinical findings indicate that cannabidiol (CBD), a non-psychotomimetic compound from Cannabis sativa, has anxiolytic, antidepressant, and antipsychotic properties. Few studies, however, have investigated the effects of CBD on aggressive behaviors.

Here, we investigated whether CBD (5, 15, 30, and 60 mg/kg; i.p.) could attenuate social isolation-induced aggressive behavior in the resident-intruder test.

Taken together, our findings suggest that CBD may be therapeutically useful to treat aggressive behaviors that are usually associated with psychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31054943

https://www.sciencedirect.com/science/article/pii/S0278584618308340?via%3Dihub

“cannabidiol reduces aggressiveness, study concludes” https://globalhealthnewswire.com/2019/07/31/cannabidiol-reduces-aggressiveness-study-concludes/

Prescription of a THC/CBD-Based Medication to Patients with Dementia: A Pilot Study in Geneva

Posted on April 10, 2019 by David

Related image

“Dementia is increasing worldwide. No effective medication is currently available for the treatment of the underlying disease and accompanying behavioral symptoms. Cannabinoids might have a beneficial effect, but clinical studies with (low-dose) synthetic THC have not been conclusive.

Objective: To test the acceptability, practical aspects, and clinical outcomes of the introduction of a THC/CBD-based oral medication in severely demented patients in a specialized nursing home in Geneva.

Methods: This was a prospective observational study.

Results: Ten female demented patients with severe behavior problems received oral medication with on average 7.6 mg THC/13.2 mg CBD daily after 2 weeks, 8.8 mg THC/17.6 mg CBD after 1 month, and 9.0 mg THC/18.0 mg CBD after 2 months. The THC/CBD-based oil was preferred. Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory score, and a behavior problem visual analog scale decreased by 40% after 2 months, rigidity score by 50%. Half of the patients decreased or stopped other psychotropic medications. The staff appreciated the decrease in rigidity, making daily care and transfers easier, the improved direct contact with the patients, the improvement in behavior, and the decrease in constipation with less opioids. There was no withholding of the medication for reasons of side effects, and the effects persisted after 2 months.

Conclusions: An oral cannabis extract with THC/CBD, in higher dosages than in other studies, was well tolerated and greatly improved behavior problems, rigidity, and daily care in severely demented patients.”

https://www.karger.com/Article/Abstract/498924

Opposite effects of cannabinoid CB1 and CB2 receptors on antipsychotic clozapine-induced cardiotoxicity.

Posted on February 3, 2019 by David

Publication cover image

“Clozapine is an atypical antipsychotic drug that is very efficacious in treating psychosis but the risk of severe cardiotoxicity limits its clinical use.

The present study investigated the myocardial injury effects of clozapine and assessed the involvement of cannabinoid receptors in clozapine cardiotoxicity.

Our data provided evidence that cannabinoid CB1 and CB2 receptors had opposite effects and selective antagonists of CB1R or agonists of CB2R might confer protective effects against clozapine.”

https://www.ncbi.nlm.nih.gov/pubmed/30707759

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14591

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

Posted on February 3, 2019 by David

“We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders.

Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists.

THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30706168

https://link.springer.com/article/10.1007%2Fs00406-019-00984-4

Dark Classics in Chemical Neuroscience: Δ9-Tetrahydrocannabinol.

Posted on January 30, 2019 by David

ACS Chemical Neuroscience

“Cannabis (Cannabis sativa) is the most widely used illicit drug in the world, with an estimated 192 million users globally.

The main psychoactive component of cannabis is (-)-trans-Δ⁹-tetrahydrocannabinol (Δ⁹-THC), a molecule with a diverse range of pharmacological actions. The unique and distinctive intoxication caused by Δ⁹-THC primarily reflects partial agonist action at central cannabinoid type 1 (CB₁) receptors.

Δ⁹-THC is an approved therapeutic treatment for a range of conditions, including chronic pain, chemotherapy-induced nausea and vomiting, and is being investigated in indications such as anorexia nervosa, agitation in dementia, and Tourette’s syndrome.

It is available as a regulated pharmaceutical in products such as Marinol®, Sativex®, and Namisol®, as well as in an ever-increasing range of unregistered medicinal and recreational cannabis products.

While cannabis is an ancient medicament, contemporary use is embroiled in legal, scientific, and social controversy, much of which relates to the potential hazards and benefits of Δ⁹-THC itself.

Robust contemporary debate surrounds the therapeutic value of Δ⁹-THC in different diseases, its capacity to produce psychosis and cognitive impairment, and the addictive and “gateway” potential of the drug.

This review will provide a profile of the chemistry, pharmacology, toxicology, and recreational and therapeutic uses of Δ⁹-THC, as well as the historical and societal importance of this unique, distinctive, and ubiquitous psychoactive substance.”

https://www.ncbi.nlm.nih.gov/pubmed/30689342

https://pubs.acs.org/doi/10.1021/acschemneuro.8b00651

www.thctotalhealthcare.com

Category Archives: Dementia