Tag Archives: medicinal

L-Theanine Prevents Long-Term Affective and Cognitive Side-Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry

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Journal of Neuroscience“Chronic adolescent exposure to Δ-9-Tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioural abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathological alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations.

L-theanine is an amino acid analogue of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-theanine has previously been shown to modulate levels of GABA, DA and glutamate in various neural regions and to possess neuroprotective properties.

Using a pre-clinical model of adolescent THC exposure in male rats, we report that L-theanine pre-treatment prior to adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect which persists into adulthood. In addition, pre-treatment with L-theanine blocked THC-induced downregulation of local GSK-3 and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and sub-cortical DAergic dysregulation.

Finally, L-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of L-theanine in the mesocorticolimbic system.

SIGNIFICANCE STATEMENT With the increasing trend of cannabis legalization and consumption during adolescence, it is essential to expand knowledge on the potential effects of adolescent cannabis exposure on brain development and identify potential pharmacological strategies to minimize THC-induced neuropathology. Previous evidence demonstrates that adolescent THC exposure induces long-lasting affective and cognitive abnormalities, mesocorticolimbic dysregulation and schizophrenia-like molecular biomarkers that persist into adulthood.

We demonstrate for the first time that L-theanine, an amino acid analogue of L-glutamate and L-glutamine, is capable of preventing long-term THC side-effects. L-theanine prevented development of THC-induced behavioral aberrations, blocked cortical downregulation of local GSK-3 and Akt signaling pathways and normalized dysregulation of both PFC and VTA DAergic activity, demonstrating powerful and functional neuroprotective effects against THC-induced developmental neuropathology.”

https://pubmed.ncbi.nlm.nih.gov/33268546/

https://www.jneurosci.org/content/early/2020/11/24/JNEUROSCI.1050-20.2020

Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A new Route to Fight against COVID-19?

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 “Cannabis sativa is a well-known plant which has been of benefit since ancient times in several medicinal systems, including Chinese, Indian, Greek and Egyptian ones.

Although C. sativa is one of the most investigated medicinal plants in the world, it faces the most controversial of issues for its legalization as a medication. C. sativa contains several hundreds of phytoconstituents including the infamous «cannabinoid.” It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where it’s still facing legal complexities.

The current review is focusing on most recent literature pertaining to the various applications of cannabinoids with a special focus on medicinal aspect of the phytochemicals. Peer reviewed articles focusing on the importance of cannabis and cannabinoids were the target of this review. Articles were selected based on the relevance to the general scope of the work i.e. application of cannabinoids.

Cannabinoids can truly be regarded as wonder drug keeping their immense diversity of usage but unfortunately, many of the mares never researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizons for the explicit use of these natural drugs in medicines such as Epidiolex® (cannabidiol used for the treatment of severe forms of epilepsy) and Sativex®(‘Δ9 -tetrahydrocannabinol and cannabidiol’ used for the treatment of spasticity caused by multiple sclerosis, aka: MS.)

Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9 -tetrahydrocannabinol (Δ9 -THC), a psychoactive component. This review addresses the most important application or current utilization of cannabinoids in a variety of treatments such as: chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicative diseases, glaucoma and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, this plant has a myriad of bioactive compounds which have the potential to increase the list of approved cannabinoids suitable for therapy.”

https://pubmed.ncbi.nlm.nih.gov/33267756/

https://www.eurekaselect.com/188617/article

Perioperative Cannabis as a Potential Solution for Reducing Opioid and Benzodiazepine Dependence

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See the source image“Cannabis is increasingly being used for medicinal purposes but remains outside Western medical practice. Data on perioperative use and outcomes are scarce. Few surgeons receive training regarding legal endorsement, reported medicinal benefits, and potential risks, making it difficult to advise patients. Guidelines and additional research are needed.

Observations: It is legal to recommend cannabis, which can be obtained in states with medical cannabis programs. There are many methods of consumption, oral being the safest. Activity is primarily through Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) via cannabinoid receptors, which may be potentiated when taken together in the plant or plant extract. The known effects of cannabis on inflammation and malignancy are largely limited to laboratory experiments. However, there are higher-quality data to support adjunctive use of cannabis for relief of pain, nausea, and insomnia, which may be useful postoperatively and could potentially decrease reliance on opiates and benzodiazepines. There are prospective trials in surgical patients, but no reported data regarding surgical complications or other surgical outcomes. Currently, cannabis is regulated differently than other controlled substances, and there are issues with purity/homogeneity, making it difficult for surgeons to accept or significantly explore its medical benefits.

Conclusions and relevance: Recommendations are made for surgeons advising patients who use cannabis based on the limited existing data. While cannabis likely has some therapeutic benefits, it must be treated as other medical controlled substances to truly elucidate its role in surgical patient care.”

https://pubmed.ncbi.nlm.nih.gov/33263719/

https://jamanetwork.com/journals/jamasurgery/article-abstract/2773526

The Therapeutic Potential of Cannabinoids for Integumentary Wound Management

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“The increasing legalization of Cannabis for recreational and medicinal purposes in the United States has spurred renewed interest in the therapeutic potential of cannabinoids (CBs) for human disease.

The skin has its own endocannabinoid system (eCS) which is a key regulator of various homeostatic processes, including those necessary for normal physiologic wound healing.

Data on the use of CBs for wound healing is scarce. Compelling pre-clinical evidence supporting the therapeutic potential of CBs to improve wound healing by modulating key molecular pathways is herein reviewed.

These findings merit further exploration in basic science, translational and clinical studies.”

https://pubmed.ncbi.nlm.nih.gov/33205468/

https://onlinelibrary.wiley.com/doi/10.1111/exd.14241

Cannabis Use May Reduce Healthcare Utilization and Improve Hospital Outcomes in Patients with Cirrhosis

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Cover image Annals of Hepatology“Introduction and objectives: Previous studies reveal conflicting data on the effect of cannabis use in patients with cirrhosis. This research evaluates the impact of cannabis on hepatic decompensation, health care utilization, and mortality in patients with cirrhosis.

Results: Cannabis use was detected in 370 (2.1%) of 17,520 cirrhotics admitted in 2011 and in 1,162 (5.3%) of 21,917 cirrhotics in 2015 (p-value <0.001). On multivariable analysis, cirrhotics utilizing cannabis after its legalization experienced a decreased rate of admissions related to hepatorenal syndrome (Odds Ratio (OR): 0.51; 95% Confidence Interval (CI): 0.34-0.78) and ascites (OR: 0.73; 95% CI: 0.63-0.84). Cirrhotics with an etiology of disease other than alcohol and hepatitis C had a higher risk of admission for hepatic encephalopathy if they utilized cannabis [OR: 1.57; 95% CI: 1.16-2.13]. Decreased length of stay (-1.15 days; 95% CI: -1.62, -0.68), total charges (-$15,852; 95% CI: -$21,009, -$10,694), and inpatient mortality (OR: 0.68; 95% CI: 0.51-0.91) were also observed in cirrhotics utilizing cannabis after legalization compared to cirrhotics not utilizing cannabis or utilizing cannabis prior to legalization.

Conclusion: Cannabis use in patients with cirrhosis resulted in mixed outcomes regarding hospital admissions with hepatic decompensation. A trend towards decreased hospital utilization and mortality was noted in cannabis users after legalization. These observations need to be confirmed with a longitudinal randomized study.”

https://pubmed.ncbi.nlm.nih.gov/33157269/

“The effectiveness of medicinal cannabis has been noted for many digestive system diseases including cirrhosis. Medicinal cannabis is associated with improved patient and hospital outcomes in cirrhotics”

https://www.sciencedirect.com/science/article/pii/S1665268120302052?via%3Dihub

Cannabis sativa extracts protect LDL from Cu 2+-mediated oxidation

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See the source image“Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile.

Objectives: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation.

Results: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2-3.5 per μg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7-4.6 μg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 μg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 μg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per μg, while for the propagation phase showed an IC50 ≤ 1 μg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 μg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase.

Conclusion: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of cannabis sativa whole extracts on the initial phase of atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/33123676/

“Our findings support the beneficial effects of Cannabis sativa extracts on the initial phase of atherosclerosis. Since isolated cannabinoids were less effective preventing the oxidation of LDL, a synergistic effect between the diverse arrange of phytochemicals present in complex extracts is supported, reinforcing the entourage hypothesis and the use of whole medicinal cannabis extracts for therapeutic purposes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00042-0

A Literature Analysis on Medicinal Use and Research of Cannabis in the Meiji Era of Japan

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 Journal of Pharmacopuncture“Cannabis is a historical plant which has been used as a medicine in East Asia.

 

Cannabis was prescribed in Meiji era of Japan to alleviate pain and cure the digestive, respiratory, urinary, and nervous system diseases such as indigestion, asthma, tuberculosis, gonorrhea and its complications, insomnia, and nervous prostration.

Cannabis was medically used in Meiji era of Japan and the reporting and sharing of its clinical effect was published on the medical journals like present days.

There were already Cannabis regulations in that era, but its medicinal use was more liberated than nowadays.

It may be a chance to reconsider the current legal system, which strictly controls the use of Cannabis.”

https://pubmed.ncbi.nlm.nih.gov/33072412/

http://www.journal-jop.org/journal/view.html?doi=10.3831/KPI.2020.23.3.142

Cancer patients’ experiences with medicinal cannabis-related care

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 “Background: Little is known about medical cannabis (MC)-related care for patients with cancer using MC.

Methods: Semistructured telephone interviews were conducted in a convenience sample of individuals (n = 24) with physician-confirmed oncologic diagnoses and state/district authorization to use MC (Arizona, California, Florida, Illinois, Massachusetts, Oregon, New York, and Washington, DC) from April 2017 to March 2019. Standard qualitative techniques were used to assess the degree of MC-related health care oversight, MC practices, and key information sources.

Results: Among 24 participants (median age, 57 years; range, 30-71 years; 16 women [67%]), MC certifications were typically issued by a professional new to a patient’s care after a brief, perfunctory consultation. Patients disclosed MCuse to their established medical teams but received little medical advice about whether and how to use MC. Patients with cancer used MC products as multipurpose symptom management and as cancer-directed therapy, sometimes in lieu of standard-of-care treatments. Personal experimentation, including methodical self-monitoring, was an important source of MC know-how. Absent formal advice from medical professionals, patients relied on nonmedical sources for MC information.

Conclusions: Patients with cancer used MC with minimal medical oversight. Most received MC certifications through brief meetings with unfamiliar professionals. Participants desired but were often unable to access high-quality clinical information about MC from their established medical teams. Because many patients are committed to using MC, a product sustained by a growing industry, medical providers should familiarize themselves with the existing data for MM and its limitations to address a poorly met clinical need.”

https://pubmed.ncbi.nlm.nih.gov/32986266/

“Notably, oncology patients reported using medical cannabis (MC) for symptom management and as cancer‐directed therapy, sometimes instead of traditional treatments.”

https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.33202

Development of cannabidiol as a treatment for severe childhood epilepsies

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“In recent years there has been a growing appreciation by regulatory authorities that cannabis-based medicines can play a useful role in disease therapy.

Although often conflagrated by proponents of recreational use, the legislative rescheduling of cannabis-derived compounds, such as cannabidiol (CBD), has been associated with the steady increase in the pursuit of use of medicinal cannabis.

One key driver in this interest has been the scientific demonstration of efficacy and safety of CBD in randomised, placebo-controlled clinical trials in children and young adults with difficult-to-treat epilepsies, which has encouraged increasing numbers of human trials of CBD for other indications and in other populations.

The introduction of CBD as the medicine Epidiolex in the US (in 2018) and as Epidyolex in the EU (in 2019) as the first cannabis-derived therapeutic for the treatment for seizures was underpinned by preclinical research performed at the University of Reading.

This work was awarded the British Pharmacological Society Sir James Black Award for Contributions to Drug Discovery 2019 and is discussed in the following review article.”

https://pubmed.ncbi.nlm.nih.gov/32986848/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.15274

Medicinal Cannabis and Synthetic Cannabinoid Use

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medicina-logo“Cannabis products have been used for centuries by humans for recreational and medical purposes. Resent research, proposed the promising therapeutic potential of cannabis and related cannabinoids for a wide range of medical conditions, including psychiatric and neurological diseases.

This Special Issue presents the latest updates on medicinal cannabis and synthetic cannabinoids pharmacology, toxicology and new analytical methods to identify and quantify these compounds in conventional and non-conventional biological matrices. Moreover, it provides current data regarding their adverse effects, safety, application for medical purposes and their harmful effects.”

https://pubmed.ncbi.nlm.nih.gov/32906770/

https://www.mdpi.com/1010-660X/56/9/453