Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Medical Marijuana Effects in Movement Disorders, Focus on Huntington Disease; A Literature Review

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“We aimed to comprehensively evaluate the effects of medical marijuana on symptoms that are relevant to movement disorders with a focus on Huntington disease (HD).

A systematic review by literature search through PubMed and EBSCO electronic databases was conducted for relevant studies reported after 2002 on the effects of medical marijuana or cannabis use on tremor, spasm, spasticity, chorea, sleep quality and HD-specific rating scales. Study selection, quality assessment and data extraction was performed by three reviewers. Outcome measures were changes in psychomotor, and sleep related symptoms. The methodological quality of the included studies was evaluated.

Results: A total of 22 studies were reviewed. There was strong evidence for significant improvement in the neurologic symptoms of spasms, tremors, spasticity, chorea, and quality of sleep following treatment with medical marijuana. Analysis of specific motor symptoms revealed significant improvement after treatment in tremors and rigidity. Furthermore, all pretreatment and post-treatment measures indicated a significant increase in average number of hours slept.

Conclusion: Larger scale studies are warranted to test the benefits of medical marijuana in HD patients. In the meanwhile, clinicians may consider prescribing medical marijuana as part of their strategy for better symptomatic treatment of patients with HD.”

https://pubmed.ncbi.nlm.nih.gov/33064979/

https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30967

Medical Cannabis Treatment for Chronic Pain: Outcomes and Prediction of Response

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“Although studied in a few randomized controlled trials (RCTs), the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicenter, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various etiologies and to identify predictors for MC treatment success.

Results: 1045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12 month follow-up. At one year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI= -2.13 to -1.81; p<0.001)]. All other parameters improved by 10-30% (p<0.001). A significant decrease of 42% [reduction of 27mg; (95%CI= -34.89 to -18.56, p<0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index (BMI) and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite.

Conclusions: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild to modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

Significance: This “real world” paper shows that MC mildly to modestly attenuates chronic pain and related symptoms. MC treatment can also cause frequent, but mostly non-serious adverse effects, although central nervous system (CNS)-related AEs that can impair the ability to drive vehicles are not uncommon. This study is novel in identifying possible predictors for treatment success, including normal to long sleep duration, lower BMI and lower depression scores. In contrast to current beliefs the diagnosis of neuropathic pain predicts a less favorable outcome. These findings provide physicians with new data to support decision making on recommendations for MC treatment.”

https://pubmed.ncbi.nlm.nih.gov/33065768/

https://onlinelibrary.wiley.com/doi/10.1002/ejp.1675

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

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molecules-logo“This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis.

The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis.

Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed.

The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/33066359/

https://www.mdpi.com/1420-3049/25/20/4682

Acute Effects of Cannabis on Symptoms of Obsessive-Compulsive Disorder

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Journal of Affective Disorders“Background: Little is known about the the acute effects of cannabis on symptoms of OCD in humans. Therefore, this study sought to: 1) examine whether symptoms of OCD are significantly reduced after inhaling cannabis, 2) examine predictors (gender, dose, cannabis constituents, time) of these symptom changes and 3) explore potential long-term consequences of repeatedly using cannabis to self-medicate for OCD symptoms, including changes in dose and baseline symptom severity over time.

Results: Patients reported a 60% reduction in compulsions, a 49% reduction in intrusions, and a 52% reduction in anxiety from before to after inhaling cannabis. Higher concentrations of CBD and higher doses predicted larger reductions in compulsions. The number of cannabis use sessions across time predicted changes in intrusions, such that later cannabis use sessions were associated with smaller reductions in intrusions. Baseline symptom severity and dose remained fairly constant over time.

Conclusions: Inhaled cannabis appears to have short-term beneficial effects on symptoms of OCD. However, tolerance to the effects on intrusions may develop over time.”

https://pubmed.ncbi.nlm.nih.gov/33049434/

“Inhaled cannabis reduced the severity of compulsions by 60% and intrusions by 49%.”

https://www.sciencedirect.com/science/article/abs/pii/S0165032720328202?via%3Dihub

Antioxidant and antimicrobial activity of two standardized extracts from a new Chinese accession of non-psychotropic Cannabis sativa L

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Phytotherapy Research “The purpose of this study was to evaluate the antioxidant and antimicrobial properties of two extracts from a new Chinese accession (G-309) of Cannabis sativa L. (Δ9 -tetrahydrocannabinol <0.2%) with high content of propyl side chain phytocannabinoids.

Dried flowering tops, as such and after hydrodistillation of the essential oil, were extracted with acidic hexane to produce the Cannabis Chinese hexane extract 1 (CChHE1) and 2 (CChHE2), respectively. The phytochemical profile of CChHE1 and CChHE2 was investigated by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-diode array detector-electrospray ionization-tandem mass spectrometry (LC-DAD-ESI-MS/MS) analyses. The antioxidant properties were assessed by several in vitro cell-free assays. The antimicrobial activity was evaluated against Gram-positive and Gram-negative bacteria and the yeast Candida albicans.

Phytochemical analyses highlighted a high content of cannabidivarinic acid (CBDVA) and tetraydrocannabivarinic acid (THCVA) in CChHE1, and cannabidivarin (CBDV) and tetraydrocannabivarin (THCV) in CChHE2. Both extracts showed remarkable antioxidant activity and strong antimicrobial properties (MIC 39.06 and MBC 39.06-78.13 μg/ml) against both ATCC and methicillin-resistant clinical strains of Staphylococcus aureus.

In conclusion, standardized extracts of C. sativa Chinese accession could be promising for their possible use as novel antibacterial agents for the treatment of widespread S. aureus infections.”

https://pubmed.ncbi.nlm.nih.gov/33034400/

https://onlinelibrary.wiley.com/doi/10.1002/ptr.6891

The immunosuppressive effect of the endocannabinoid system on the inflammatory phenotypes of macrophages and mesenchymal stromal cells: a comparative study

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SpringerLink “The inflammatory sequence is the first phase of wound healing. Macrophages (MPhs) and mesenchymal stromal cells (MSCs) respond to an inflammatory microenvironment by adapting their functional activity, which polarizes them into the pro-inflammatory phenotypes M1 and MSC1. Prolongation of the inflammatory phase results in the formation of chronic wounds. The endocannabinoid system (ECS) possesses immunomodulatory properties that may impede this cellular phenotypic switch.

Methods: We investigated the immunosuppressive influence of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) on the M1 and MSC1 cytokine secretion. Lipopolysaccharides (LPS) were used as inflammagen to stimulate MPhs and MSCs. Both inflammatory phenotypes were co-exposed to AEA or 2-AG, the specific cannabinoid receptor CB2 agonist JWH-133 served as reference. The inflammatory responses were detected by CD80/163 immuno-labelling and by ELISA measures of secreted IL-6, IL-8, MIF, TNF-α, TGF-β, and VEGF.

Results: M1 cells were found positive for CD80 expression and secreted less IL-6 and IL-8 than MSC1 cells, while both cell types produced similar amounts of MIF. TNF-α release was increased by M1, and growth factors were secreted by MSC1, only. Cannabinoid receptor ligands efficiently decreased the inflammatory response of M1, while their impact was less pronounced in MSC1.

Conclusions: The ECS down-regulated the inflammatory responses of MPhs and MSCs by decreasing the cytokine release upon LPS treatment, while CB2 appeared to be of particular importance. Hence, stimulating the ECS by manipulation of endo- or use of exogenous cannabinoids in vivo may constitute a potent therapeutic option against inflammatory disorders.”

https://pubmed.ncbi.nlm.nih.gov/33026642/

https://link.springer.com/article/10.1007%2Fs43440-020-00166-3

Signaling Through the Type 2 Cannabinoid Receptor Regulates the Severity of Acute and Chronic Graft versus Host Disease

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Blood“Graft versus host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments.

In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R) which is expressed on nearly all immune cells and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells, or administration of a selective CB2R pharmacological antagonist, exacerbated acute GVHD lethality. This was accompanied primarily by the expansion of proinflammatory CD8+ T cells indicating that constitutive CB2R expression on T cells preferentially regulated CD8+ T cell alloreactivity. Using a novel CB2R-EGFP reporter mouse, we observed significant loss of CB2R expression on T cells, but not macrophages, during acute GVHD, indicative of differential alterations in receptor expression under inflammatory conditions.

Therapeutic targeting of the CB2R with the agonists, tetrahydrocannabinol (THC) and JWH-133, revealed that only THC mitigated lethal T cell-mediated acute GVHD. Conversely, only JWH-133 was effective in a sclerodermatous chronic GVHD model where macrophages contribute to disease biology. In vitro, both THC and JWH-133 induced arrestin recruitment and ERK phosphorylation via CB2R, but THC had no effect on CB2R-mediated inhibition of adenylyl cyclase.

These studies demonstrate that the CB2R plays a critical role in the regulation of GVHD and suggest that effective therapeutic targeting is dependent upon agonist signaling characteristics and receptor selectivity in conjunction with the composition of pathogenic immune effector cells.”

https://pubmed.ncbi.nlm.nih.gov/33027805/

https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2020004871/464166/Signaling-Through-the-Type-2-Cannabinoid-Receptor?redirectedFrom=fulltext

The impact of cannabinoid type 2 receptors (CB2Rs) in neuroprotection against neurological disorders

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 Acta Pharmacologica Sinica“Cannabinoids have long been used for their psychotropic and possible medical properties of symptom relief. In the past few years, a vast literature shows that cannabinoids are neuroprotective under different pathological situations.

Most of the effects of cannabinoids are mediated by the well-characterized cannabinoid receptors, the cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Even though CB1Rs are highly expressed in the central nervous system (CNS), the adverse central side effects and the development of tolerance resulting from CB1R activation may ultimately limit the clinical utility of CB1R agonists. In contrast to the ubiquitous presence of CB1Rs, CB2Rs are less commonly expressed in the healthy CNS but highly upregulated in glial cells under neuropathological conditions.

Experimental studies have provided robust evidence that CB2Rs seem to be involved in the modulation of different neurological disorders. In this paper, we summarize the current knowledge regarding the protective effects of CB2R activation against the development of neurological diseases and provide a perspective on the future of this field. A better understanding of the fundamental pharmacology of CB2R activation is essential for the development of clinical applications and the design of novel therapeutic strategies.”

https://pubmed.ncbi.nlm.nih.gov/33024239/

https://www.nature.com/articles/s41401-020-00530-2

An Agathokakological tale of ∆9 -THC: Exploration of Possible Biological Targets

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“∆ 9 -Tetrahydrocannabinol (∆9 -THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system.

By interacting with G-protein-coupled receptors CB1 and CB2, ∆9 -THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities respectively.

∆ 9 -THC is effective in suppressing chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy.

∆ 9 -THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases.

∆9 -THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism.

Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. In this review, we represent the current pharmacological status of the phytocannabinoid, ∆ 9 -THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/33001012/

https://www.eurekaselect.com/186455/article

A Cannabinoid Type 2 (CB2) Receptor Agonist Augments NOS-Dependent Responses of Cerebral Arterioles during Type 1 Diabetes

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Microvascular Research “While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D).

Our goal was to test the hypothesis that administration of a CB2 agonist (JWH-133) would improve impaired endothelial (eNOS)- and neuronal (nNOS)- dependent dilation of cerebral arterioles during T1D.

In vivo diameter of cerebral arterioles in nondiabetic and T1D rats was measured in response to an eNOS-dependent agonist (adenosine 5′-diphosphate; ADP), an nNOS-dependent agonist (N-methyl-D-aspartate; NMDA), and an NOS-independent agonist (nitroglycerin) before and 1 hour following JWH-133 (1 mg/kg IP). Dilation of cerebral arterioles to ADP and NMDA was greater in nondiabetic than in T1D rats.

Treatment with JWH-133 increased responses of cerebral arterioles to ADP and NMDA in both nondiabetic and T1D rats. Responses of cerebral arterioles to nitroglycerin were similar between nondiabetic and T1D rats, and JWH-133 did not influence responses to nitroglycerin in either group. The restoration in responses to the agonists by JWH-133 could be inhibited by treatment with a specific inhibitor of CB2 receptors (AM-630; 3 mg/kg IP).

Thus, activation of CB2 receptors can potentiate reactivity of cerebral arterioles during physiologic and pathophysiologic states. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular diseases via a mechanism that can increase cerebral blood flow.”

https://pubmed.ncbi.nlm.nih.gov/32979391/

“Activation of CB2 receptors improves cerebral vascular function. Activation of CB2 receptors improves responses in type 1 diabetes. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular disease that can contribute to the pathogenesis of stroke.”

https://www.sciencedirect.com/science/article/pii/S0026286220301370?via%3Dihub