The Polypharmacological Effects of Cannabidiol

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs of abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge of the neuro-molecular mechanisms of CBD is limited, and its pharmacology, which appears to be complex, has not yet been fully elucidated. The study of the pharmacological effects of CBD has grown exponentially in recent years, making it necessary to generate frequently updated reports on this important metabolite. In this article, a rationalized integration of the mechanisms of action of CBD on molecular targets and pharmacological implications in animal models and human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer’s disease, and inflammatory diseases, are presented. We identify around 56 different molecular targets for CBD, including enzymes and ion channels/metabotropic receptors involved in neurologic conditions. Herein, we compiled the knowledge found in the scientific literature on the multiple mechanisms of actions of CBD. The in vitro and in vivo findings are essential for fully understanding the polypharmacological nature of this natural product.

Cannabidiol goes nuclear: The role of PPARγ

Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD’s effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ.

Cannabis sativa and Cannabidiol: A Therapeutic Strategy for the Treatment of Neurodegenerative Diseases?

This work is a literature review, presenting the current state of the use of cannabinoids on neurodegenerative diseases. The emphasis is on Parkinson’s (PD) and Alzheimer’s (AD) diseases, the two most prevalent neurological diseases. The review goes from Cannabis sativa and its hundreds of bioactive compounds to Δ9-tetrahydrocannabinol (THC) and mainly cannabidiol (CBD) and their interactions with the endocannabinoid receptors (CB1 and CB2).

Cannabidiol for neurodegenerative disorders: A comprehensive review

This review briefly discusses the role of inflammation and oxidative stress in neurodegeneration and demonstrates the neuroprotective effect of cannabidiol, highlighting its general mechanism of action and disease-specific pathways in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Furthermore, we have summarized the preclinical and clinical findings on the therapeutic promise of CBD in PD and AD, shed light on the importance of determining its therapeutic window, and provide insights into identifying promising new research directions.

Effects of rich cannabidiol oil on behavioral disturbances in patients with dementia: A placebo controlled randomized clinical trial

Almost 90% of patients with dementia suffer from some type of neurobehavioral symptom, and there are no approved medications to address these symptoms. To evaluate the safety and efficacy of the medical cannabis oil “Avidekel” for the reduction of behavioral disturbances among patients with dementia.

Cannabidiol in the treatment and prevention of Alzheimer’s disease – a comprehensive

Dementia is a major public health problem. Alzheimer’s disease (AD) accounts for 60% of dementia cases. However, AD is currently considered as an incurable disorder and the only few drugs available for its treatment are mostly symptomatic. In the quest for novel drugs for this devastating disease, cannabidiol (CBD) has been recently gaining attention due to its multiple properties, such as an ability to interact with various receptors, anti-inflammatory and antioxidative effects and many more. The aim of this review article was to summarize findings on the effect of CBD on AD with a focus on molecular mechanisms of CBD’s action and therapeutic effects which it exerts.

Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report

Cannabinoid-based therapy has been shown to be promising and is emerging as crucial for the treatment of cognitive deficits, mental illnesses, and many diseases considered incurable. There is a need to find an appropriate therapy for Alzheimer’s disease, and cannabinoid-based therapy appears to be a feasible possibility.

Understanding the Modulatory Effects of Cannabidiol on Alzheimer’s Disease

Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by progressive cognitive impairment. The deposition of amyloid beta (Aβ) and hyperphosphorylated tau is considered the hallmark of AD pathology. Many therapeutic approaches such as Food and Drug Administration-approved cholinesterase inhibitors and N–methyl–D–aspartate receptor antagonists have been used to intervene in AD pathology. However, current therapies only provide limited symptomatic relief and are ineffective in preventing AD progression. Cannabidiol (CBD), a phytocannabinoid devoid of psychoactive responses, provides neuroprotective effects through both cannabinoid and noncannabinoid receptors. Recent studies using an AD mouse model have suggested that CBD can reverse cognitive deficits along with Aβ-induced neuroinflammatory, oxidative responses, and neuronal death.

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

This randomized, double-blind, placebo-controlled, cross-over study was conducted to evaluate the safety and efficacy of two-weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥three months).

Medical cannabis and cognitive performance in middle to old adults treated for chronic pain

Authors: Sharon R Sznitman, Simon Vulfsons, David Meiri, Galit Weinstein Published in Drug and Alcohol Review September 2020 Abstract Introduction and aims: Cannabis exposure is becoming more common in older…

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Authors: Luigia Cristino, Tiziana Bisogno, Vincenzo Di Marzo
Nature Reviews Neurology, January 2020

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, es…

An update on the advancements in the treatment of agitation in Alzheimer’s disease

Authors: Assaf Shelef, Yoram Barak, Uri Berger, Diana Paleacu, Shelly Tadger, Igor Plopsky, Yehuda Baruch
Expert Opinion on Pharmacotherapy, April 2017

Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are s…