Cannabidiol Exposure During the Mouse Adolescent Period Is Without Harmful Behavioral Effects on Locomotor Activity, Anxiety, and Spatial Memory

Archive of "Frontiers in Behavioral Neuroscience".“Cannabidiol (CBD) is a non-intoxicating phytocannabinoid whose purported therapeutic benefits and impression of a high safety profile has promoted its increasing popularity.

CBD’s popularity is also increasing among children and adolescents who are being administered CBD, off label, for the treatment of numerous symptoms associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, and depression. The relative recency of its use in the adolescent population has precluded investigation of its impact on the developing brain and the potential consequences that may present in adulthood. Therefore, there’s an urgency to identify whether prolonged adolescent CBD exposure has substantive impacts on the developing brain that impact behavioral and cognitive processes in adulthood.

Here, we tested the effect of twice-daily intraperitoneal administrations of CBD (20 mg/kg) in male and female C57BL/6J mice during the adolescent period of 25-45 days on weight gain, and assays for locomotor behavior, anxiety, and spatial memory. Prolonged adolescent CBD exposure had no detrimental effects on locomotor activity in the open field, anxiety behavior on the elevated plus maze, or spatial memory in the Barnes Maze compared to vehicle-treated mice. Interestingly, CBD-treated mice had a faster rate of learning in the Barnes Maze. However, CBD-treated females had reduced weight gain during the exposure period.

We conclude that prolonged adolescent CBD exposure in mice does not have substantive negative impacts on a range of behaviors in adulthood, may improve the rate of learning under certain conditions, and impacts weight gain in a sex-specific manner.”

https://pubmed.ncbi.nlm.nih.gov/34512286/

“Cannabidiol (CBD) is one of the most abundant cannabinoids naturally produced by the plant, Cannabis sativa, and the dominant phytocannabinoid produced by the hemp variety. We report that multiple daily doses of a moderate CBD dose throughout the adolescent developmental period does not negatively impact locomotor behavior, anxiety, and spatial learning in healthy C57BL/6J mice. Further, the faster acquisition rate of a spatial learning task may highlight CBD’s potential protective benefits against stressors.”

https://www.frontiersin.org/articles/10.3389/fnbeh.2021.711639/full

Targeting of Protein’s Messenger RNA for Viral Replication, Assembly and Release in SARS-CoV-2 Using Whole Genomic Data From South Africa: Therapeutic Potentials of Cannabis Sativa L

frontiers in pharmacology – Retraction Watch“The possible evolutionary trend of COVID-19 in South Africa was investigated by comparing the genome of SARS-CoV-2 isolated from a patient in KwaZulu-Natal, South Africa with those isolated from China, Spain, Italy, and United States, as well as the genomes of Bat SARS CoV, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Mouse Hepatitis Virus (MHV), and Infectious Bronchitis Virus (IBV). Phylogenetic analysis revealed a strong homology (96%) between the genomes of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from the study countries as well as those isolated from bat SARS CoV, MERS-CoV, MHV and IBV.

The ability of phytocannabinoids from Cannabis sativa infusion to interact with gene segments (mRNAs) coding for proteins implicated in viral replication, assembly and release were also investiagted using computational tools. Hot water infusion of C. sativa leaves was freeze-dried and subjected to Gas Chromatography-Mass Spectroscopy analysis which revealed the presence of tetrahydrocannabivarin, cannabispiran, cannabidiol tetrahydrocannabinol, cannabigerol, and cannabinol. Molecular docking analysis revealed strong binding affinities and interactions between the phytocannabinoids and codon mRNAs for ORF1ab, Surface glycoprotein, Envelope protein and Nucleocapsid phosphoprotein from SARS-CoV-2 whole genome which may be due to chemico-biological interactions as a result of nucleophilic/electrophilic attacks between viral nucleotides and cannabinoids.

These results depict the spread of SARS-CoV-2 is intercontinental and might have evolved from other coronaviruses. The results also portray the phytocannabinoids of C. sativa infusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2. However, further studies are needed to verify these activities in pre-clinical and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/34539415/

“Taken together, the results from this study indicates a homology between the genome of SARS-CoV-2 isolated from KwaZulu-Natal, South Africa and those isolated from Europe, Asia and North America, as well as those isolated from bat SARS COV, MERS-CoV, MHV and IBV. Thus, depicting the spread of the virus is intercontinental and might have evolved from other coronaviruses. The results also indicate the phytocannabinoids of C. sativa infusion as potential therapies against COVID-19 as depicted by their ability to molecularly interact with codon mRNAs of proteins implicated in the replication, translation, assembly, and release of SARS-CoV-2.”

https://www.frontiersin.org/articles/10.3389/fphar.2021.736511/full

Green Hope: Perspectives on Cannabis from People who Use Opioids

Sociological Inquiry“While states are implementing policies to legalize cannabis for medical or recreational purposes, it remains a Schedule 1 controlled substance with no medical uses according to US federal law. The perception of cannabis depends on social and cultural norms that impact political institutions involved in implementing policy. Because of negative social constructions, such as the “gateway hypothesis,” legalization of cannabis has been slow and contentious.

Recent studies suggest that cannabis can help combat the opioid epidemic.

This paper fills a gap in our understanding of how cannabis is viewed by people who are actively misusing opioids and not in treatment. Using ethnographic methods to recruit participants living in a state that legalized cannabis and a state where cannabis was illegal, survey and interview data were analyzed informed by a social constructionist lens.

Findings from their “insider perspective” suggest that for some people struggling with problematic opioid use, cannabis can be beneficial.”

https://pubmed.ncbi.nlm.nih.gov/34538961/

https://onlinelibrary.wiley.com/doi/10.1111/soin.12359

Cannabinoids induce functional Tregs by promoting tolerogenic DCs via autophagy and metabolic reprograming

Mucosal Immunology“The generation of functional regulatory T cells (Tregs) is essential to keep tissue homeostasis and restore healthy immune responses in many biological and inflammatory contexts.

Cannabinoids have been pointed out as potential therapeutic tools for several diseases.

Dendritic cells (DCs) express the endocannabinoid system, including the cannabinoid receptors CB1 and CB2. However, how cannabinoids might regulate functional properties of DCs is not completely understood.

We uncover that the triggering of cannabinoid receptors promote human tolerogenic DCs that are able to prime functional FOXP3+ Tregs in the context of different inflammatory diseases. Mechanistically, cannabinoids imprint tolerogenicity in human DCs by inhibiting NF-κB, MAPK and mTOR signalling pathways while inducing AMPK and functional autophagy flux via CB1- and PPARα-mediated activation, which drives metabolic rewiring towards increased mitochondrial activity and oxidative phosphorylation.

Cannabinoids exhibit in vivo protective and anti-inflammatory effects in LPS-induced sepsis and also promote the generation of FOXP3+ Tregs. In addition, immediate anaphylactic reactions are decreased in peanut allergic mice and the generation of allergen-specific FOXP3+ Tregs are promoted, demonstrating that these immunomodulatory effects take place in both type 1- and type 2-mediated inflammatory diseases.

Our findings might open new avenues for novel cannabinoid-based interventions in different inflammatory and immune-mediated diseases.”

https://pubmed.ncbi.nlm.nih.gov/34548620/

“Cannabinoids have been pointed out as potential therapeutic tools for several diseases. Our results might well contribute to pave the way for the future development of novel cannabinoid-based strategies for different inflammatory and immune-mediated diseases.”

https://www.nature.com/articles/s41385-021-00455-x

The Effect of Medical Cannabis on Pain Level and Quality of Sleep among Rheumatology Clinic Outpatients

logo“Introduction: Medical cannabis (MC) is becoming increasingly popular for the treatment of chronic pain conditions.

In this study, we evaluated the effect of MC treatment on pain level and quality of sleep of patients with different medical conditions at the rheumatology clinic.

Conclusions: MC had a favorable effect on pain level and quality of sleep among all spectrums of problems at the rheumatology clinic.”

https://pubmed.ncbi.nlm.nih.gov/34531934/

“MC has a favorable effect on pain level and sleep quality among nearly the entire spectrum of resistant “chronic pain syndromes” seen or referred to rheumatology clinics, including inflammatory diseases resistant to biological treatment, although the effect of MC on synovitis was relatively mild.

Cannabis should be seriously considered in every “chronic pain condition” whenever the accepted modalities of treatment are insufficient for alleviating patient’s pain and sleep problems.”

https://www.hindawi.com/journals/prm/2021/1756588/

Endocannabinoid Levels in Ulcerative Colitis Patients Correlate With Clinical Parameters and Are Affected by Cannabis Consumption

Logo of frontendo“Inflammatory bowel diseases (IBDs) are chronic, idiopathic, inflammatory, gastrointestinal disorders.

The endocannabinoid system may have a role in the pathogenesis of IBD.

We aimed to assess whether cannabis treatment influences endocannabinoids (eCBs) level and clinical symptoms of IBD patients.

Conclusion

Our study supports the notion that cannabis use affects eCB “tone” in UC patients and may have beneficial effects on disease symptoms in UC patients.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438407/

“In conclusion, our study suggests that cannabis use may affect eCBs tone in UC patients. This affect has a beneficial effect on UC symptoms.”

https://www.frontiersin.org/articles/10.3389/fendo.2021.685289/full

A Review of the Potential Use of Pinene and Linalool as Terpene-Based Medicines for Brain Health: Discovering Novel Therapeutics in the Flavours and Fragrances of Cannabis

Archive of "Frontiers in Psychiatry".“”Medicinal cannabis” is defined as the use of cannabis-based products for the treatment of an illness. Investigations of cannabis compounds in psychiatric and neurological illnesses primarily focus on the major cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), which are hypothesised to benefit multiple illnesses manifesting cognitive impairment, neurodegeneration and neuro-inflammation, as well as chronic pain, epilepsy and post-traumatic stress disorder, respectively.

The cannabis plant contains >500 compounds, including terpenes responsible for the flavour and fragrance profiles of plants. Recently, research has begun providing evidence on the potential use of certain plant-derived terpenes in modern medicine, demonstrating anti-oxidant, anti-inflammatory, and neuroprotective effects of these compounds.

This review examined the effects of two key terpenes, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, highlighting gaps in the literature and recommendations for future research into terpene therapeutics.

Overall, evidence is mostly limited to preclinical studies and well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer’s disease and ageing), insomnia, anxiety, and depression.

Linalool and pinene influence multiple neurotransmitter, inflammatory and neurotrophic signals as well as behaviour, demonstrating psycho-activity (albeit non-intoxicating).   Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes and cannabinoids, such as linalool, pinene and CBD, could present a unique opportunity to discover novel medicines to treat psychiatric and neurological illnesses; however, further research is needed.”

https://pubmed.ncbi.nlm.nih.gov/34512404/

“Overall, it appears that the importance of the terpene profile of plants to humans extends further than mere olfactory and gustatory delight. Rather, these compounds have the potential for use as treatments for serious chronic neurological and psychiatric illnesses.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.583211/full

Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

pharmaceutics-logo“Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers.

However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported.

Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death.

In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.

We believe that our study makes a significant contribution to the field because these results can be developed as a promising strategy for a safer and more efficient anticancer therapy.”

https://www.mdpi.com/1999-4923/13/9/1415/htm

Cannabinoids and Cancer

cancers-logo“Cannabinoids, active components of the plant Cannabis sativa, had been used for centuries in ancient medicine as therapeutic remedies for a variety of conditions, before becoming stigmatized due to their psychoactive effects.

In the second half of the 19th century, phyto-cannabinoids have been re-evaluated after the discovery of the chemical structure and isolation of different substances, and the subsequent development of cannabinoid-based drugs that have been FDA approved mainly to treat chemotherapy-induced nausea, insomnia and appetite, epilepsy, spasticity, and pain management.

Then, the elucidation of the endocannabinoid system, from the initial type 1 and type 2 (CB1 and CB2) cannabinoid receptors and their endogenous ligands (especially N-arachidonoylethanolamine, or anandamide, and 2-arachidonoylglycerol) to the emerging complexity of a wider system made up of additional putative receptors, ligands and enzymes, altogether termed endocannabinoidome, has further boosted research into the therapeutic potential of phyto-, endo- and even syntho-(synthetic) cannabinoids, cancer treatment included.”

https://pubmed.ncbi.nlm.nih.gov/34503268/

https://www.mdpi.com/2072-6694/13/17/4458/htm

Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer

cancers-logo“Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world’s disease and mortality rates. The development of novel therapy is in critical need, and based on recent experimental data, cannabinoids could become excellent candidates. This review covered known experimental studies regarding the effects of cannabinoids on intestinal inflammation and colorectal cancer. In our opinion, because colorectal cancer is a heterogeneous disease with different genomic landscapes, the choice of cannabinoids for tumor prevention and treatment depends on the type of the disease, its etiology, driver mutations, and the expression levels of cannabinoid receptors. In this review, we describe the molecular changes of the endocannabinoid system in the pathologies of the large intestine, focusing on inflammation and cancer.”

https://pubmed.ncbi.nlm.nih.gov/34503163/

“In recent years, multiple preclinical studies have shown that changes in endocannabinoid system signaling may have various effects on intestinal inflammation and colorectal cancer. However, not all tumors can respond to cannabinoid therapy in the same manner. Given that colorectal cancer is a heterogeneous disease with different genomic landscapes, experiments with cannabinoids should involve different molecular subtypes, emerging mutations, and various stages of the disease. We hope that this review can help researchers form a comprehensive understanding of cannabinoid interactions in colorectal cancer and intestinal bowel diseases. We believe that selecting a particular experimental model based on the disease’s genetic landscape is a crucial step in the drug discovery, which eventually may tremendously benefit patient’s treatment outcomes and bring us one step closer to individualized medicine.”

https://www.mdpi.com/2072-6694/13/17/4353