The Use of Dispensary-Obtained Tetrahydrocannabinol as a Treatment for Neuropsychiatric Symptoms of Dementia

Posted on September 29, 2023 by David

“Objective: Neuropsychiatric symptoms (NPS) of dementia represent a large driver of health care costs, caregiver burden, and institutionalization of people with dementia. Management options are limited, and antipsychotics are often used, although they carry a significant side effect profile. One novel option is tetrahydrocannabinol (THC); however, in the US, to obtain THC for patients with dementia, caregivers have to go to a commercial dispensary. We evaluated the effectiveness of dispensary-obtained THC for patients with dementia and NPS.

Methods: Two independent reviewers reviewed charts of patients with diagnosed dementia (N = 50) seen in geriatric psychiatry between 2017 and 2021 for whom dispensary-obtained THC was recommended. The primary outcome was effectiveness in treating NPS; secondary outcomes were the proportion of caregivers who obtained and administered THC (uptake), post-THC antipsychotic use, and adverse reactions leading to treatment discontinuation.

Results: Caregiver uptake of dispensary-obtained THC was high (38/50, 76%). The majority of patients (30/38, 79%) who took THC had an improvement in NPS according to their caregivers. THC was recommended most often for the NPS of agitation, aggression, irritability, lability, anxiety, and insomnia. Among the 20 patients who were taking antipsychotics at baseline and took THC, over half (12/20, 60%) were able to decrease or discontinue the antipsychotic. Adverse reactions to THC included dizziness, worsening of agitation, and worsening of paranoia; two caregivers of patients who took THC reported adverse reactions that led to treatment discontinuation.

Conclusions: Our results suggest that dispensary-obtained THC can be effective in managing a subset of NPS in patients with dementia and may decrease the requirement for antipsychotics.”

https://pubmed.ncbi.nlm.nih.gov/37728481/

https://www.psychiatrist.com/jcp/neurologic/dementia/dispensary-obtained-tetrahydrocannabinol-treatment-neuropsychiatric-symptoms-dementia/

Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy

Posted on September 28, 2023 by David

“In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/37759788/

https://www.mdpi.com/2218-273X/13/9/1388

Synergetic effect of β-asarone and cannabidiol against Aβ aggregation in vitro and in vivo

Posted on August 23, 2023 by David

“Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer’s disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining β-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aβ) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aβ₄₀ aggregates in the presence of β-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like β-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.”

https://pubmed.ncbi.nlm.nih.gov/37602231/

https://www.csbj.org/article/S2001-0370(23)00262-3/fulltext

Cannabis reduces anxiety in dementia

Posted on August 13, 2023 by David

“Neuropsychiatric symptoms occur in almost 90% of people with dementia. Agitated and aggressive behavior significantly reduces the quality of life of those affected and those around them, but it is difficult to access therapy. One option could be medicinal cannabis. The results of a double-blind, placebo-controlled study indicate that a full-spectrum cannabis extract with a high content of cannabidiol (CBD) can reduce dementia-related agitation [1]. In the study, 60 patients with severe neurocognitive disorder and associated behavioral disorders received a full-spectrum cannabis extract with 1% tetrahydrocannabinol (THC) and 30% CBD (Re:cannis) or a placebo oil. After 16 weeks, sleep disturbances, Agitation and aggression significantly improved compared to the placebo group. Since the effects only became apparent in the 14th week, patience is required.”

https://www.springermedizin.de/agitiertheit/demenz/cannabis-daempft-die-unruhe-bei-demenz/25883850?fulltextView=true&doi=10.1007%2Fs15006-023-2867-2

Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

Posted on August 3, 2023 by David

“Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3-4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.”

https://pubmed.ncbi.nlm.nih.gov/37534036/

“Our findings imply that the THC microdose treatment alleviates age-dependent cognitive deficits by modulating multiple hallmarks of brain aging, supporting past hypotheses regarding the relation between aging and the endocannabinoid system.”

https://www.frontiersin.org/articles/10.3389/fnins.2023.1182932/full

The role of cannabidiol in aging

Posted on July 23, 2023 by David

“Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.”

https://pubmed.ncbi.nlm.nih.gov/37418976/

“CBD is a potential antiaging candidate. CBD possesses antioxidant, anti-inflammatory and autophagy-inducing properties. CBD has potentially beneficial therapeutic effects for several age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S075333222300865X?via%3Dihub

Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

Posted on July 12, 2023 by David

“Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

Herein, we discuss the current state-of-art regarding the contribution of the endocannabinoid system (ECS) in synaptic transmission processes, synapses plasticity and neurogenesis and consequently the use of exogenous cannabinoids in the treatment of depression and on delaying the progression of AD. Besides the well-known imbalance of neurotransmitter levels, including serotonin, noradrenaline, dopamine and glutamate, recent scientific evidence highlights aberrant spine density, neuroinflammation, dysregulation of neurotrophic factor levels and formation of amyloid beta (Aβ) peptides, as the main physiopathological mechanisms compromised in depression and AD. The contribution of the ECS in these mechanisms is herein specified as well as the pleiotropic effects of phytocannabinoids.

At the end, it became evident that Cannabinol, Cannabidiol, Cannabigerol, Cannabidivarin and Cannabichromene may act in novel therapeutic targets, presenting high potential in the pharmacotherapy of both diseases.”

https://pubmed.ncbi.nlm.nih.gov/37414155/

“Endocannabinoid system is dysregulated in depression and AD.

Cannabinoids have potential to modulate the physiopathological mechanisms common in both diseases.”

https://www.sciencedirect.com/science/article/pii/S1568163723001575?via%3Dihub

Cannabis sativa-based oils against aluminum-induced neurotoxicity

Posted on June 18, 2023 by David

“The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer’s and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.”

https://pubmed.ncbi.nlm.nih.gov/37330587/

“In our study, we observed that Al is responsible for neurotoxicity, especially causing AChE decrease. The main effect of Al is related to reduced social ability and anxiety-like patterns. The testes oil THC- and CBD-rich have an important role in AChE reestablishment and social ability reacquisition. In addition, both oils exert an outstanding effect on antioxidant enzyme modulations with the re-establishment of the SOD and CTL after Al exposition. The activity of GST was also well modulated indicating that the oils played a crucial role in cellular damage avoidance. However, the oils do not change the impaired anxiety-like behavior that looks to be linked to other central signaling pathways and needs to be well investigated in the next studies. Finally, the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance.”

https://www.nature.com/articles/s41598-023-36966-9

Examining the use of cannabidiol and delta-9-tetrahydrocannabinol-based medicine among individuals diagnosed with dementia living within residential aged care facilities: Results of a double-blind randomised crossover trial

Posted on June 16, 2023 by David

“Objective: Dementia affects individuals older than 65 years. Currently, residential aged care facilities (RACF) use psychotropic medications to manage behavioural and neuropsychiatric symptoms of dementia (BPSD), which are recommended for short-term use and have substantial side effects, including increased mortality. Cannabinoid-based medicines (CBM) have some benefits that inhibit BPSD and cause minimal adverse effects (AEs), yet limited research has been considered with this population. The study aimed to determine a tolerable CBM dose (3:2 delta-9-tetrahydrocannabinol:cannabidiol), and assessed its effect on BPSD, quality of life (QoL) and perceived pain.

Methods: An 18-week randomised, double-blinded, crossover trial was conducted. Four surveys, collected on seven occasions, were used to measure changes in BPSD, QoL and pain. Qualitative data helped to understand attitudes towards CBM. General linear mixed models were used in the analysis, and the qualitative data were synthesised.

Results: Twenty-one participants (77% female participants, mean age 85) took part in the trial. No significant differences were seen between the placebo and CBM for behaviour, QOL or pain, except a decrease in agitation at the end of treatment in favour of CBM. The qualitative findings suggested improved relaxation and sleep among some individuals. Post hoc estimates on the data collected suggested that 50 cases would draw stronger conclusions on the Neuropsychiatric Inventory.

Conclusions: The study design was robust, rigorous and informed by RACF. The medication appeared safe, with minimal AEs experienced with CBM. Further studies incorporating larger samples when considering CBM would allow researchers to investigate the sensitivity of detecting BPSD changes within the complexity of the disease and concomitant with medications.”

https://pubmed.ncbi.nlm.nih.gov/37321847/

https://onlinelibrary.wiley.com/doi/10.1111/ajag.13224

Therapeutic use of cannabinoids for the treatment of neurodegenerative disorders: a potential breakthrough

Posted on May 24, 2023 by David

“Marijuana, also known as cannabis, is a plant-based illicit drug notorious for its recreational purposes. However, in recent years its extracts are being extensively studied for their overall therapeutic effects. Active substances found in marijuana that interact with the endocannabinoid system are known as cannabinoids, the primary examples being 9-tetrahydrocannabinol (9-THC) and Cannabidiol (CBD). These cannabinoids ligand to receptors such as CB1 (found in CNS) and CB2 (found in immune system cells) to prevent the release of neurotransmitters and modulate immune cell migration as well as cytokine release, respectively (1). In recent years, there has been a surge of interest in the neuroprotective potential of marijuana; however, investigators could not make firm conclusions about the effectiveness of these treatments. A comprehensive review by Bahji A et al. (2022) found an evident link between cannabidiol-based products and relief from the motor as well as behavioural and psychological symptoms spanning Alzheimer’s disease (AD), Huntington’s disease (HD), and Parkinson’s disease (PD) (2). Here we discuss the effects of marijuana and its derivatives on the treating significant neurodegenerative disorders.

Dronabinol (2.5 mg) seemed to lessen the disordered behaviours as assessed by the Cohen-Mansfield Agitation Inventory in 12 patients of AD (p=0.05) (3). Sherman et al. (2018) reported the association of cannabis administration with weight and pain management in AD patients. The adverse effects are typically well tolerated at the levels supplied, even though cannabis is linked to an increased risk of euphoria, sleepiness and psychosis (1). On the other hand, for HD, nabilone (1 or 2 mg) had a substantial therapeutic benefit in a different 10-week placebo-controlled crossover experiment as determined by the overall motor and chorea score on the Unified Huntington’s Disease Rating Scale (UHDRS) (4). Available reviews revealed variable evidence suggesting the clinical benefits of cannabis in treating motor symptoms in patients with PD. A randomized trial found that compared to a placebo, giving a single dosage of 300 mg of CBD successfully decreased tremor amplitude (5).

Neurological diseases, including the neurodegenerative diseases, comprise 8.7% of the disease burden in lower- middle- income countries (such as Pakistan) (6). Currently, there is no real cure for neurodegenerative disorders, only symptomatic management, such as dopamine treatment for PD or cholinesterase inhibitors for dementia. Cannabinoids might be the lifeline all neurodegenerative disorder patients have been waiting for.”

https://pubmed.ncbi.nlm.nih.gov/37218269/

https://ojs.jpma.org.pk/index.php/public_html/article/view/7805

www.thctotalhealthcare.com

Category Archives: Alzheimer’s Disease (AD)