Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Inflammaging and Cannabinoids

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Ageing Research Reviews“Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging -a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/34662745/

“The beneficial effects of cannabinoids may be considered as alternative therapy in treating age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S1568163721002348?via%3Dihub

The potential of cannabinoids and inhibitors of endocannabinoid degradation in respiratory diseases

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European Journal of Pharmacology“The global incidence of respiratory diseases and complications is increasing. Therefore, new methods of treatment, as well as prevention, need to be investigated.

A group of compounds that should be considered for use in respiratory diseases is cannabinoids. There are three groups of cannabinoids – plant-derived phytocannabinoids, synthetic cannabinoids, and endogenous endocannabinoids including the enzymes responsible for their synthesis and degradation.

All cannabinoids exert their biological effects through either type 1 cannabinoid receptors (CB1) and/or type 2 cannabinoid receptors (CB2). In numerous studies (in vitro and in vivo), cannabinoids and inhibitors of endocannabinoid degradation have shown beneficial anti-inflammatory, antioxidant, anti-cancer, and anti-fibrotic properties.

Although in the respiratory system, most of the studies have focused on the positive properties of cannabinoids and inhibitors of endocannabinoid degradation. There are few research reports discussing the negative impact of these compounds. This review summarizes the properties and mechanisms of action of cannabinoids and inhibitors of endocannabinoid degradation in various models of respiratory diseases.

A short description of the effects selected cannabinoids have on the human respiratory system and their possible use in the fight against COVID-19 is also presented. Additionally, a brief summary is provided of cannabinoid receptors properties and their expression in the respiratory system and cells of the immune system.”

https://pubmed.ncbi.nlm.nih.gov/34648805/

“Phytocannabinoids are terpenophenolic compounds produced by specialized parts of the Cannabis sativa plant and are found in high concentrations in marijuana and hashish. In most of models, these compounds have shown positive biological properties. Anti-inflammatory, anti-oxidant, anti-cancer and anti-fibrotic actions are especially emphasized.”

https://www.sciencedirect.com/science/article/pii/S0014299921007160?via%3Dihub

Activity of THC, CBD, and CBN on Human ACE2 and SARS-CoV1/2 Main Protease to Understand Antiviral Defense Mechanism

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“THC, CBD, and CBN were reported as promising candidates against SARS-CoV2 infection, but the mechanism of action of these three cannabinoids is not understood.

This study aims to determine the mechanism of action of THC, CBD, and CBN by selecting two essential targets that directly affect the coronavirus infections as viral main proteases and human angiotensin-converting enzyme2.

Tested THC and CBD presented a dual-action action against both selected targets. Only CBD acted as a potent viral main protease inhibitor at the IC50 value of 1.86 ± 0.04 µM and exhibited only moderate activity against human angiotensin-converting enzyme2 at the IC50 value of 14.65 ± 0.47 µM.

THC acted as a moderate inhibitor against both viral main protease and human angiotensin-converting enzymes2 at the IC50 value of 16.23 ± 1.71 µM and 11.47 ± 3.60 µM, respectively.

Here, we discuss cannabinoid-associated antiviral activity mechanisms based on in silico docking studies and in vitro receptor binding studies.”

https://pubmed.ncbi.nlm.nih.gov/34638139/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-1581-3707

Inducing Effects of Illegal Drugs to Improve Mental Health by Self-Regulation Therapy: A Pilot Study

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ijerph-logo“This study consists of a brief psychological intervention, which uses Self-Regulation Therapy (SRT, procedure based on suggestion and classical conditioning), to improve coping with stress and emotionality by reproducing the positive effects of illegal drugs: cannabis, cocaine, ecstasy.

Results: SRT was superior to non-intervention for the 4 coping strategies (η2 = 0.829, 0.453, 0.411 and 0.606) and for positive (η2 = 0.371) and negative emotionality (η2 = 0.419). An improvement in scores was evidenced in the follow-up scores compared to the pre-intervention measures.

Conclusions: This study shows for the first time that it is possible to use illegal drugs, considered harmful to public health, to improve young people’s coping capacity and emotionality by reproducing their positive effects with SRT.”

https://pubmed.ncbi.nlm.nih.gov/34639687/

https://www.mdpi.com/1660-4601/18/19/10387

Antidepressant and Anxiolytic Effects of Medicinal Cannabis Use in an Observational Trial

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Archive of "Frontiers in Psychiatry".“Anxiety and depressive disorders are highly prevalent. Patients are increasingly using medicinal cannabis products to treat these disorders, but little is known about the effects of medicinal cannabis use on symptoms of anxiety and depression.

The aim of the present observational study was to assess general health in medicinal cannabis users and non-using controls with anxiety and/or depression. 

Results: Medicinal cannabis use was associated with lower self-reported depression, but not anxiety, at baseline. Medicinal cannabis users also reported superior sleep, quality of life, and less pain on average. Initiation of medicinal cannabis during the follow-up period was associated with significantly decreased anxiety and depressive symptoms, an effect that was not observed in Controls that never initiated cannabis use. 

Conclusions: Medicinal cannabis use may reduce anxiety and depressive symptoms in clinically anxious and depressed populations. Future placebo-controlled studies are necessary to replicate these findings and to determine the route of administration, dose, and product formulation characteristics to optimize clinical outcomes.”

https://pubmed.ncbi.nlm.nih.gov/34566726/

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.729800/full

“Johns Hopkins: New Study Backs Claims That Cannabis Can Reduce Anxiety And Depression”  https://finance.yahoo.com/news/johns-hopkins-study-backs-claims-145005658.html

“Report Shows Cannabis is Effective in Treating Anxiety, Depression”   https://www.legalreader.com/report-shows-cannabis-is-effective-in-treating-anxiety-depression/

Efficacy of Δ 9 -Tetrahydrocannabinol (THC) Alone or in Combination With a 1:1 Ratio of Cannabidiol (CBD) in Reversing the Spatial Learning Deficits in Old Mice

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Archive of "Frontiers in Aging Neuroscience".“Decline in cognitive performance, an aspect of the normal aging process, is influenced by the endocannabinoid system (ECS). Cannabinoid receptor 1 (CB1) signaling diminishes with advancing age in specific brain regions that regulate learning and memory and abolishing CB1 receptor signaling accelerates cognitive aging in mice.

We recently demonstrated that prolonged exposure to low dose (3 mg/kg/day) Δ9-tetrahydrocannabinol (THC) improved the cognitive performances in old mice on par with young untreated mice. Here we investigated the potential influence of cannabidiol (CBD) on this THC effect, because preclinical and clinical studies indicate that the combination of THC and CBD often exhibits an enhanced therapeutic effect compared to THC alone.

We first tested the effectiveness of a lower dose (1 mg/kg/day) THC, and then the efficacy of the combination of THC and CBD in 1:1 ratio, same as in the clinically approved medicine Sativex®. Our findings reveal that a 1 mg/kg/day THC dose still effectively improved spatial learning in aged mice. However, a 1:1 combination of THC and CBD failed to do so.

The presence of CBD induced temporal changes in THC metabolism ensuing in a transient elevation of blood THC levels. However, as CBD metabolizes, the inhibitory effect on THC metabolism was alleviated, causing a rapid clearance of THC. Thus, the beneficial effects of THC seemed to wane off more swiftly in the presence of CBD, due to these metabolic effects.

The findings indicate that THC-treatment alone is more efficient to improve spatial learning in aged mice than the 1:1 combination of THC and CBD.”

https://pubmed.ncbi.nlm.nih.gov/34526890/

“In conclusion, our observations indicate that 1 mg/kg/day THC dose is still effective in improving the spatial learning in aged mice. With regard to the efficacy, THC-alone has proved to be more efficient in improving spatial learning in aged mice than its 1:1 combination with CBD. However, the possibility of THC/CBD being efficient in other ratios or at the earliest time-points, like immediately after the treatment cease, cannot be negated. Possibly, reducing the dose of CBD may improve the efficacy of the THC/CBD combination.”

https://www.frontiersin.org/articles/10.3389/fnagi.2021.718850/full

Cannabinoid receptor 1 expression is higher in muscle of old vs. young males, and increases upon resistance exercise in older adults

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Scientific Reports“Aged skeletal muscle undergoes metabolic and structural alterations eventually resulting in a loss of muscle strength and mass, i.e. age-related sarcopenia. Therefore, novel targets for muscle growth purposes in elderly are needed.

Here, we explored the role of the cannabinoid system in muscle plasticity through the expression of muscle cannabinoid receptors (CBs) in young and old humans.

The CB1 expression was higher (+ 25%; p = 0.04) in muscle of old (≥ 65 years) vs. young adults (20-27 years), whereas CB2 was not differently expressed. Furthermore, resistance exercise tended to increase the CB1 (+ 11%; p = 0.055) and CB2 (+ 37%; p = 0.066) expression in muscle of older adults. Interestingly, increases in the expression of CB2 following resistance exercise positively correlated with changes in key mechanisms of muscle homeostasis, such as catabolism (FOXO3a) and regenerative capacity (Pax7, MyoD).

This study for the first time shows that CB1 is differentially expressed with aging and that changes in CB2 expression upon resistance exercise training correlate with changes in mediators that play a central role in muscle plasticity.

These data confirm earlier work in cells and mice showing that the cannabinoid system might orchestrate muscle growth, which is an incentive to further explore CB-based strategies that might counteract sarcopenia.”

https://pubmed.ncbi.nlm.nih.gov/34526596/

“In conclusion, cell culture and murine experiments suggested that CBs can be a promising target to treat cachexia and sarcopenia through modulation of the metabolism and muscle regenerative capacity. These data imply that CB modulation might be a promising tool to combat muscle degeneration. ”

https://www.nature.com/articles/s41598-021-97859-3

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

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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

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

 

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

The Pathophysiology and the Therapeutic Potential of Cannabinoids in Prostate Cancer

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cancers-logo“Prostate cancer is the second most frequently occurring cancer diagnosed among males. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation. In this review, we focused on studies that demonstrated anticancer effects of cannabinoids and their possible mechanisms of action in prostate cancer. Besides the palliative effects of cannabinoids, research from the past two decades has demonstrated their promising potential as antitumor agents in a wide variety of cancers. This analysis may provide pharmacological insights into the selection of specific cannabinoids for the development of antitumor drugs for the treatment of prostate cancer.”

https://pubmed.ncbi.nlm.nih.gov/34439262/

“Prostate cancer, after lung cancer, is the leading cause of death among men. Although the pathophysiological mechanisms and the etiological factors of prostate cancer development are still poorly understood, there are several factors associated with the risk of developing the disease such as age, family history, lifestyle-related factors (e.g., smoking, diet), and testosterone levels. Cannabinoids are an emerging class of pharmacological molecules that may exert their therapeutic effect against different cancers, including those from the prostate. Several studies have shown that various agonists are able to target cannabinoid receptors exhibited on prostate cancer cells.”

https://www.mdpi.com/2072-6694/13/16/4107