Effects of β-caryophyllene, A dDietary Cannabinoid, in Animal Models of Drug Addiction

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“Background: β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in Cannabis and other plants. BCP is currently used as a food additive, although pharmacological studies suggest its potential therapeutic application for the treatment of certain brain disorders. The mechanisms of action of BCP remain uncertain, possibly including full agonism at the cannabinoid CB 2 receptor (CB 2 R).

Objective: The study aims to investigate the BCP’s potential as a new drug for the treatment of substance use disorders, by reviewing preclinical studies with animal models.

Results: BCP has been investigated in behavioral paradigms, including drug self-administration, conditioned place preference, and intracranial self-stimulation; the drugs tested were cocaine, nicotine, alcohol, and methamphetamine. Remarkably, BCP prevented or reversed behavioral changes resulting from drug exposure. As expected, the mechanism of action entails CB 2 R activation, although this is unlikely to constitute the only molecular target to explain such effects. Another potential target is the peroxisome proliferator-activated receptor.

Conclusion: Preclinical studies report promising results with BCP in animal models of substance use disorders. Further research, including studies in humans, are warranted to establish its therapeutic potential and its mechanisms of action.”

https://pubmed.ncbi.nlm.nih.gov/36173065/

https://www.eurekaselect.com/article/126579

Natural vs. artificial cannabinoid oils: the comparison of their antioxidant activities

SpringerLink

“In the wide range of products containing hemp ingredients, cannabinoid oils are the most popular. They have gained popularity not only among people struggling with various health ailments, but also those who search for a neutral way of taking care of their body and mind.

The antioxidant activities of cannabinoid oils differing in the type of their main cannabinoid [i.e., Cannabigerol (CBG), Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (Δ9-THC), Cannabigerolic acid (CBGA), Cannabidiolic acid (CBDA) or Δ9-Tetrahydrocannabinolic acid (Δ9-THCA)] are compared and discussed in the paper. The oils with the same concentration of their main cannabinoid but prepared in different ways were applied in the experiments.

Following the presented results, cannabinoid oils obtained from the plant extracts are characterized by evidently greater antioxidant activity than those prepared from pure cannabinoids. The essential difference in the antioxidant activity of the oils containing the neutral or acidic form of a given cannabinoid is observed only in the case of THC and THCA oils.”

https://pubmed.ncbi.nlm.nih.gov/36164439/

“Cannabinoid oils obtained from the plant extracts have the greatest antioxidant activity.”

https://link.springer.com/article/10.1007/s00217-022-04121-9

Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents

Frontiers announces first journal acquisition: Oncology Reviews – STM  Publishing News

“Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide. In particular, the polar fraction of hemp including many phenolic compounds has been overlooked when compared with the more lipophilic fraction containing cannabinoids. Therefore, the aim of this study was to assess two extracts of industrial hemp (C. sativa) of different polarity (aqueous and hexane) by evaluating their antioxidant profile and their neuroprotective potential on pharmacological targets in the central nervous system (CNS). Several assays on in vitro antioxidant capacity (DPPH, superoxide radical, FRAP, ORAC), as well as inhibition of physiological enzymes such as acetylcholinesterase (AChE) and monoaminooxidase A (MAO-A) were carried out in order to find out how these extracts may be helpful to prevent neurodegenerative disorders. Neuro-2a cell line was selected to test the cytotoxic and neuroprotective potential of these extracts. Both extracts showed striking antioxidant capacity in the FRAP and ORAC assays, particularly the hexane extract, and interesting results for the DPPH and superoxide radical uptake assays, with the aqueous extract standing out especially in the latter. In enzyme inhibition assays, the aqueous extract showed AChE and MAO-A inhibitory activity, while the hexane extract only reached IC50 value for AChE inhibitory bioassay. Neuro-2a assays demonstrated that polyphenolic extract was not cytotoxic and exhibited cytoprotective properties against hydrogen peroxide and antioxidant response decreasing reactive oxygen species (ROS) production. These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/36176449/

“In conclusion, this study provided new insights into the biological activities of two different extracts of C. sativa. It was revealed that these extracts constitute a valuable and interesting natural source of bioactive molecules with great antioxidant properties, potentially capable of preventing neurodegenerative diseases.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1009868/full

The role of cannabinoids in neurodevelopmental disorders of children and adolescents

PubMed | MIT Libraries News

“Introduction: Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field.

Development: Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder.

Conclusions: This review hopefully draws attention to an emerging body of evidence concerning cannabidiol’s significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.”

https://pubmed.ncbi.nlm.nih.gov/36169325/

Cannabidiol in Treatment of Autism Spectrum Disorder: A Case Study

Archive of "Cureus". - PMC

“This case study aims to demonstrate the use of cannabidiol (CBD) with low-dose tetrahydrocannabinol (THC) in managing symptoms associated with autism spectrum disorder (ASD) to increase the overall quality of life for these individuals and their families.

ASD is a neurodevelopmental disorder affecting cognitive development, behavior, social communication, and motor skills. Despite the increasing awareness of ASD, there is still a lack of safe and effective treatment options.

The study includes a nine-year-old male patient who was diagnosed with nonverbal ASD. He exhibited emotional outbursts, inappropriate behaviors, and social deficits including challenges in communicating his needs with others. Since the patient was unable to attain independence at school and at home, his condition was a significant burden to his caregivers.

The patient was treated with full-spectrum high CBD and low THC oil formulation, with each milliliter containing 20 mg of CBD and <1 mg of THC. CBD oil starting dose was 0.1ml twice daily, increased every three to four days to 0.5ml twice daily.

Overall, the patient experienced a reduction in negative behaviors, including violent outbursts, self-injurious behaviors, and sleep disruptions. There was an improvement in social interactions, concentration, and emotional stability.

A combination of high CBD and low-dose THC oil was demonstrated to be an effective treatment option for managing symptoms associated with autism, leading to a better quality of life for both the patient and the caregivers.”

https://pubmed.ncbi.nlm.nih.gov/36176817/

“In this case, the child patient responded positively to the introduction of CBD oil treatment with reduced negative behaviors, better sleep, and improved communication. With the increasing clinical studies on the use of cannabidiol in treating patients with mood disorders, anxiety, chronic pain conditions, and other behavioral problems, it should be considered as a treatment option in managing symptoms related to autism. In the case study presented, the child patient has shown behavioral and cognitive improvements with no side effects reported. Altogether, this study presents a case that motivates further research and clinical studies to understand the molecular mechanism of CBD as well as the dosing regimes for pediatric populations, the etiology of ASD, and how various dosing affect different demographics.”

https://www.cureus.com/articles/109585-cannabidiol-in-treatment-of-autism-spectrum-disorder-a-case-study


Cannabidiol counters the effects of a dominant-negative pathogenic Kv7.2 variant

iScience journal (@iScience_CP) / Twitter

“Epilepsy and neurodevelopmental disorders can arise from pathogenic variants of KCNQ (Kv7) channels. A patient with developmental and epileptic encephalopathy exhibited an in-frame deletion of histidine 260 on Kv7.2. Coexpression of Kv7.2 mutant (mut) subunits with Kv7.3 invoked a decrease in current density, a depolarizing shift in voltage for activation, and a decrease in membrane conductance. Biotinylation revealed an increased level of surface Kv7.2mut compared to Kv7.3 with no change in total membrane protein expression. Super-resolution and FRET imaging confirmed heteromeric channel formation and a higher expression density of Kv7.2mut. Cannabidiol (1 μM) offset the effects of Kv7.2mut by inducing a hyperpolarizing shift in voltage for activation independent of CB1 or CB2 receptors. These data reveal that the ability for cannabidiol to reduce the effects of a pathogenic Kv7.2 variant supports its use as a potential therapeutic to reduce seizure activity.”

https://pubmed.ncbi.nlm.nih.gov/36157585/

“Control of seizure activity has been increasingly gained through use of cannabinoids, with cannabidiol (CBD) specifically approved for clinical use.”

https://www.cell.com/iscience/fulltext/S2589-0042(22)01364-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2589004222013645%3Fshowall%3Dtrue