Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological Characteristics of the Patient Population: A Prospective Study

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“Background: Despite the absence of rigorous prospective studies, there has been an increase in the use of cannabis-based medicinal products. During the study period, the use of medical cannabis in Israel was tightly regulated by national policy. Through a prospective study of approximately 10,000 patients, we aimed to characterize the medical cannabis patient population as well as to identify treatment adherence, safety, and effectiveness.

Methods and findings: In this study of prescribed medical cannabis patients, adherence, safety, and effectiveness were assessed at 6 months. Treatment adherence was assessed by the proportion of patients purchasing the medication out of the total number of patients (excluding deceased cases and patients transferred to another cannabis clinic). Safety was assessed by the frequency of the side-effects, while effectiveness was defined as at least moderate improvement in the patient condition without treatment cessation or serious side-effects. The most frequent primary indications requiring therapy were cancer (49.1%), followed by non-specific pain (29.3%). The average age was 54.6 ± 20.9 years, 51.1% males; 30.2% of the patients reported prior experience with cannabis. During the study follow-up, 1,938 patients died (19.4%) and 1,735 stopped treatment (17.3%). Common side-effects, reported by 1,675 patients (34.2%), were: dizziness (8.2%), dry mouth (6.7%), increased appetite (4.7%), sleepiness (4.4%), and psychoactive effect (4.3%). Overall, 70.6% patients had treatment success at 6 months. Multivariable logistic regression analysis revealed that the following factors were associated with treatment success: cigarette smoking, prior experience with cannabis, active driving, working, and a young age. The main limitation of this study was the lack of data on safety and effectiveness of the treatment for patients who refused to undergo medical assessment even at baseline or died within the first 6 months.

Conclusions: We observed that supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events.”

https://pubmed.ncbi.nlm.nih.gov/35223923/


“This is a large study describing certain characteristics of medical cannabis users in a tightly regulated environment. The treatment appears to be safe and efficacious.”

https://www.frontiersin.org/articles/10.3389/fmed.2022.827849/full

Medical Cannabis for Gilles de la Tourette Syndrome: An Open-Label Prospective Study

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“Objectives: Assessing the effectiveness and tolerability of medical cannabis (MC) treatment on Gilles de la Tourette syndrome (GTS) patients.

Methods: We report on an open-label, prospective study on the effect of MC on adult GTS patients. MC mode of use was decided by the treating neurologist and the patient. Δ9-Tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) content within MC product and monthly dose were titrated during the study. Following treatment initiation, patients were assessed after 4 and 12 weeks for efficacy, tolerability, and side effects.

Results: Eighteen patients entered the study. Baseline Yale Global Tic Severity Scale- (YGTSS) Total (range 0-100) was 60.3 ± 17.1. Three patients did not reach the end of follow-up period. The most common mode of administration was smoking (80%). Following twelve weeks of treatment, a significant 38% average reduction (p = 0.002) of YGTSS-Total and a 20% reduction (p = 0.043) of Premonitory Urge for Tic Scale (PUTS) were observed. Common side effects were dry mouth (66.7%), fatigue (53.3%), and dizziness (46.7%). Three patients suffered from psychiatric side effects including worsening of obsessive compulsive disorder (stopped treatment), panic attack, and anxiety (resolved with treatment modification). Six patients (40%) reported cognitive side effects regarding time perception, visuospatial disorientation, confusion, slow processing speed, and attention.

Conclusions: MC treatment demonstrates good efficacy and tolerability in adult GTS patients. Predilection for smoking rather than using oil drops requires further comparative studies to evaluate the efficacy of each. Cognitive and psychiatric side effects have to be monitored and addressed.”

https://pubmed.ncbi.nlm.nih.gov/35310886/

“Our results are in line with a number of other studies suggesting that MC is effective and well tolerated in adults with GTS. From our data, it is suggested that MC might be a treatment option for resistant TS patients, and MC has a significant effect on tics, premonitory urges, and patients’ overall quality of life. In our sample, patients favored THC-rich cannabis strands and smoking/inhaling MC over sublingual oil.”

https://www.hindawi.com/journals/bn/2022/5141773/

Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer’s disease

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“Given that neuronal degeneration in Alzheimer’s disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile of cannabinoid compounds. In this work, molecular docking has been used to design some cannabinoid analogues with such multitarget properties, based on the similarities of donepezil and Δ9-tetrahydrocannabinol. The analogues synthesized, compounds 1 and 2, demonstrated to have two interesting characteristics in different in vitro assays: competitive inhibition of AChE and competitive antagonism at the CB1/CB2 receptors. They are highly lipophilic, highlighting that they could easily reach the CNS, and apparently presented a low toxicity. These results open the door to the synthesis of new compounds for a more effective treatment of AD.”

https://pubmed.ncbi.nlm.nih.gov/33460612/

https://www.sciencedirect.com/science/article/abs/pii/S0014299921000285?via%3Dihub

Neuroprotection of retinal ganglion cells in vivo using the activation of the endogenous cannabinoid signaling system in mammalian eyes

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“Cannabinoid and glutamatergic signaling systems in the human retina coexist and greatly influence one another. Under glaucomatous conditions, excess levels of glutamate accrete in the retinal ganglion cell (RGC) layer. The present study tests the putative neuroprotective effect mediated by cannabinoids at the CB1 and CB2 receptors. In the first experiment, mice were given intravitreal injections of 160 nmol N-methyl-d-aspartic acid (NMDA) in one eye and saline in the paired eye. In the second experiment, both eyes were given NMDA, while one of the two was additionally given the cannabinoid agonist WIN 55,212-2. Ten days later, animals were perfused and the retinae were dissected as wholemounts and stained with Cresyl Violet. Quantitative analysis revealed that 70% of the neurons in the retinal ganglion cell (RGC) layer exposed to NMDA underwent cell death. The addition of the cannabinoid CB1/CB2 agonist doubled the number of neurons surviving the NMDA treatment. These data provide evidence that cannabinoids, either exogenous or endogenous, may be harnessed to provide protection from neurodegenerative diseases, including glaucoma, and from glutamate-induced, and potentially other forms of neurotoxicity, under chronic or acute conditions.”

https://pubmed.ncbi.nlm.nih.gov/35233292/

“In summary, we have demonstrated that the cannabimimetic drug, the CB1 and CB2 receptor agonist WIN55,212-2, acts to protect RGCs from NMDA-induced excitotoxicity in an in vivo mouse model. This further indicates the potential for therapeutic applications of cannabinoids in neurodegenerative diseases, including glaucoma.”

https://portlandpress.com/neuronalsignal/article/6/1/NS20210038/230703/Neuroprotection-of-retinal-ganglion-cells-in-vivo

Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study

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“Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.

Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC.

Results: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse.

Conclusion: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.”

“Our analysis revealed that cannabis users were 55% less likely to have HCC compared to non-cannabis users.”

https://www.cureus.com/articles/90568-lower-rates-of-hepatocellular-carcinoma-observed-among-cannabis-users-a-population-based-study

Cannabis sativa L. protects against oxidative injury in kidney (vero) cells by mitigating perturbed metabolic activities linked to chronic kidney diseases

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“Ethnopharmacological relevance: Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases.

Aims: The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines.

Methods: Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO4 for 30 minutes, following pretreatment with C. sativa extracts for 25 minutes. Normal control consisted of Vero cells not treated with the extracts and/or FeSO4, while untreated (negative) control consisted of cells treated with only FeSO4.

Results: MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 μg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts.

Conclusion: These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.”

https://pubmed.ncbi.nlm.nih.gov/35476933/

An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample

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“Background: Little is known about cannabis use for insomnia in individuals with depression, anxiety, and comorbid depression and anxiety. To develop a better understanding of distinct profiles of cannabis use for insomnia management, a retrospective cohort study was conducted on a large naturalistic sample.

Methods: Data were collected using the medicinal cannabis tracking app, Strainprint®, which allows users to monitor and track cannabis use for therapeutic purposes. The current study examined users managing insomnia symptoms in depression (n = 100), anxiety (n = 463), and comorbid depression and anxiety (n = 114), for a total of 8476 recorded sessions. Inferential analyses used linear mixed effects modeling to examine self-perceived improvement across demographic variables and cannabis product variables.

Results: Overall, cannabis was perceived to be efficacious across all groups, regardless of age and gender. Dried flower and oral oil were reported as the most used and most efficacious product forms. In the depression group, all strains were perceived to be efficacious and comparisons between strains revealed indica-dominant (Mdiff = 1.81, 95% CI 1.26-2.36, Padj < .001), indica hybrid (Mdiff = 1.34, 95% CI 0.46-2.22, Padj = .045), and sativa-dominant (Mdiff = 1.83, 95% CI 0.68-2.99, Padj = .028) strains were significantly more efficacious than CBD-dominant strains. In anxiety and comorbid conditions, all strain categories were perceived to be efficacious with no significant differences between strains.

Conclusions: In terms of perceptions, individuals with depression, anxiety, and both conditions who use cannabis for insomnia report significant improvements in symptom severity after cannabis use. The current study highlights the need for placebo-controlled trials investigating symptom improvement and the safety of cannabinoids for sleep in individuals with mood and anxiety disorders.”

https://pubmed.ncbi.nlm.nih.gov/35484520/

Medical cannabis oil for benign essential blepharospasm: a prospective, randomized controlled pilot study

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“Objective: To examine the efficacy and safety of medical cannabis in benign essential blepharospasm (BEB).

Methods: This is a prospective, double-blind, placebo-controlled study. All consecutive adult BEB patients who had been treated with BTX-A injections without success between 3/2019 and 2/2020 were recruited. The study patients were randomly allocated into a treatment and a control (placebo) group in a 1:1 ratio. The treatment group used cannabis drops and the control group used cannabis oil drops during the first 6 weeks of the study, and both groups were treated with the medical cannabis drops during the second 6 weeks. The cannabis dose was gradually increased for each patient depending upon effect and tolerability.

Results: Three patients were included in each group (treatment and control groups). The mean duration of spasm attack during the first 6 weeks was 4.29 min in the treatment group and 73.9 min in the placebo group (P < 0.01). During the last 6 weeks, the treatment group used an average of 6.27 drops and the placebo group used an average of 5.36 drops (P = 0.478). There were 61 spasm events in the treatment group and 94 spasm events in the placebo group (P = 0.05). The mean duration of spasm attack was 1.77 and 8.96 min, respectively (P < 0.01). The side effects were mild, and they included general fatigue, dry mouth, and insomnia.

Conclusions: Medical cannabis can be an effective and safe treatment for BEB as a second line after BTX-A injections when used for 3 months. No significant ocular or systemic side effects was associated with the treatment.”

https://pubmed.ncbi.nlm.nih.gov/35067772/

The Effects of Consuming Cannabis Flower for Treatment of Fatigue

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“Objectives: We measure for the first time how commercially available Cannabis flower products affect feelings of fatigue. Results: On average, 91.94% of people experienced decreased fatigue following consumption with an average symptom intensity reduction of 3.48 points on a 0–10 visual analog scale (SD = 2.70, d = 1.60, p < 0.001). While labeled plant phenotypes (“C. indica,” “C. sativa,” or “hybrid”) did not differ in symptom relief, people that used joints to combust the flower reported greater symptom relief than pipe or vaporizer users. Across cannabinoid levels, tetrahydrocannabinol, and cannabidiol levels were generally not associated with changes in symptom intensity levels. Cannabis use was associated with several negative side effects that correspond to increased feelings of fatigue (e.g., feeling unmotivated, couch-locked) among a minority of users (<24% of users), with slightly more users (up to 37%) experiencing a positive side effect that corresponds to increased energy (e.g., feeling active, energetic, frisky, or productive). Conclusions: The findings suggest that the majority of patients experience decreased fatigue from consumption of Cannabis flower consumed in vivo, although the magnitude of the effect and extent of side effects experienced likely vary with individuals’ metabolic states and the synergistic chemotypic properties of the plant.”

https://www.karger.com/Article/FullText/524057

Δ 9-Tetrahydrocannabinol (Δ 9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment

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“Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury.

Methods: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters.

Results: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3-6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 μM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6-9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria-were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 μM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6-9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6-9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6-8), confirming oxidative stress, while administration of 10 μM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6-8).

Conclusions: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.”

https://pubmed.ncbi.nlm.nih.gov/35468673/