Category Archives: THC (Delta-9-Tetrahydrocannabinol)

Self-reported cannabis use is not associated with greater opioid use in elective hand surgery patients

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SpringerLink


“Background: The purpose of this study was to examine the influence of preoperative marijuana use on postoperative opioid use during the first three postoperative days (POD 1-3) after surgery, and on expectations of pain control, resiliency, and quality-of-life scores.

Methods: All patients presenting to a single institution undergoing elective hand or upper extremity outpatient surgery were asked to complete pre- and postoperative questionnaires. Preoperative questionnaires collected information on demographics, marijuana use, tobacco use, procedure type, self-assessed health, pain control expectations, and EuroQol-5D (EQ-5D) scores. At the first postoperative visit, patients self-reported opioid consumption from POD 1-3. Multivariate linear regression analysis was used to determine which patient characteristics were predictive of greater postoperative opioid consumption during POD 1-3.

Results: Self-reported marijuana users were younger, less healthy, and more likely to use tobacco compared to non-users. Marijuana users and non-users were comparable in their use of pain medication (including non-opioids), rates of chronic pain diagnoses, and self-reported pain tolerance. EQ-5D scores were lower in marijuana users than non-users (0.64 vs. 0.72). Marijuana users and non-users were prescribed comparable quantities of opioids during the first 14 days after surgery (176 ± 148 vs 115 ± 87). Multiple linear regression analysis revealed that lower preoperative EQ-5D scores, rather than marijuana use, were associated with increased opioid consumption during POD 1-3.

Conclusions: Preoperative marijuana use was not independently associated with increased opioid use during POD 1-3 after elective hand and upper extremity surgery; instead, an association with lower preoperative EQ-5D scores was identified.”

https://pubmed.ncbi.nlm.nih.gov/35986814/

“Given the increasing prevalence of marijuana use in the USA, it is imperative that surgeons be able to counsel their patients on the effect of marijuana use on their postoperative recovery. The effect of marijuana use on hand surgery patients certainly merits further research.”

https://link.springer.com/article/10.1007/s00590-022-03321-z

Benefits and Concerns Regarding Use of Cannabis for Therapeutic Purposes Among People Living with Chronic Pain: A Qualitative Research Study

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Pain Medicine

“Objective: Although there is growing interest in medically authorized cannabis for chronic pain, little is known about patients’ perspectives. We explored perceptions of people living with chronic pain regarding benefits and concerns surrounding their use of cannabis for therapeutic purposes.

Setting: A hospital-based clinic in Hamilton and two community-based interdisciplinary pain clinics in Burlington, Ontario, Canada.

Methods: In this qualitative descriptive study, we conducted semi-structured interviews with 13 people living with chronic pain who used cannabis therapeutically, living in Ontario, Canada. We used thematic analysis, with data collection, coding, and analysis occurring concurrently.

Results: People living with chronic pain reported important benefits associated with use of cannabis for therapeutic purposes, including reduced pain, improved functionality, and less risk of harms compared to prescription opioids. Most patients also acknowledged harms, such as grogginess and coughing, and there was considerable variability in patient experiences. Financial costs and stigma were identified as important barriers to use of cannabis.

Conclusion: Evidence-based guidance that incorporates patients’ values and preferences may be helpful to inform the role of cannabis in the management of chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/35652734/

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnac085/6598805?redirectedFrom=fulltext&login=false


Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications

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BMC Medicine logo

“Background: Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events.

Results: In total, 152 RCTs (12,123 participants) were analysed according to the type of the cannabinoid, outcome and comparator used, resulting in 84 comparisons. Significant therapeutic effects of medical cannabinoids show a large variability in the grade of evidence that depends on the type of cannabinoid. CBD has a significant therapeutic effect for epilepsy (SMD – 0.5[CI – 0.62, – 0.38] high grade) and Parkinsonism (- 0.41[CI – 0.75, – 0.08] moderate grade). There is moderate evidence for dronabinol for chronic pain (- 0.31[CI – 0.46, – 0.15]), appetite (- 0.51[CI – 0.87, – 0.15]) and Tourette (- 1.01[CI – 1.58, – 0.44]) and moderate evidence for nabiximols on chronic pain (- 0.25[- 0.37, – 0.14]), spasticity (- 0.36[CI – 0.54, – 0.19]), sleep (- 0.24[CI – 0.35, – 0.14]) and SUDs (- 0.48[CI – 0.92, – 0.04]). All other significant therapeutic effects have either low, very low, or even no grade of evidence. Cannabinoids produce different adverse events, and there is low to moderate grade of evidence for this conclusion depending on the type of cannabinoid.

Conclusions: Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.”

https://pubmed.ncbi.nlm.nih.gov/35982439/

“Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.”

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02459-1

Cannabinoid modulation of brain activation during volitional regulation of negative affect in trauma-exposed adults

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Neuropharmacology

“Emotion dysregulation is considered a core component of posttraumatic stress disorder (PTSD). Cognitive reappraisal is one therapeutic emotion regulation strategy that has been widely studied among individuals with mood and anxiety disorders, and numerous differences in brain activation patterns have been shown between individuals with and without PTSD during tasks of cognitive reappraisal.

Prior research among healthy subjects suggests that an acute, low dose of Δ9-tetrahydrocannabinol (THC) could attenuate the neurophysiological discrepancies that exist between individuals with and without PTSD during tasks of emotional processing; however, the effect of an acute, low dose of THC on corticolimbic activity during emotion regulation among individuals with PTSD has not yet been studied.

The present study aimed to investigate the effect of THC on negative affect and brain activation in a priori regions of interest during cognitive reappraisal among trauma-exposed individuals with and without PTSD.

Using a double-blind design, 51 individuals were randomized to receive THC or placebo (PBO) before participating in a well-established emotion regulation task during functional magnetic resonance imaging (fMRI).

THC but not PBO reduced negative affect during reappraisal, and THC increased dorsomedial prefrontal cortex (dmPFC) activation in response to neutral images. Individuals with PTSD displayed less activation in the angular gyrus, overall, compared to the trauma-exposed control (TEC) group, however THC increased angular gyrus activation in the PTSD group so that there was no significant difference in angular gyrus activation between the TEC and PTSD groups that received THC.

Compared to PBO, THC also increased cerebellar activation during exposure to neutral images in individuals with PTSD. Lastly, in participants that received THC, greater posterior cingulate cortex (PCC)/precuneus activation during reappraisal was associated with less self-reported negative affect following reappraisal blocks.

Together these findings suggest that THC may prove to be a beneficial pharmacological adjunct to cognitive reappraisal therapy in the treatment of PTSD.”

https://pubmed.ncbi.nlm.nih.gov/35981598/

“Δ9-tetrahydrocannabinol (THC) reduced negative affect during reappraisal.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390822002817?via%3Dihub

Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs

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Nature Communications

“Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging.

While it has been known that cannabinoids such as Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood.

Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The GlyR-THC complexes are captured in multiple conformational states that reveal the basis for THC-mediated potentiation, manifested as different extents of opening at the level of the channel pore.

Taken together, these structural findings, combined with molecular dynamics simulations and functional analysis, provide insights into the potential THC binding site and the allosteric coupling to the channel pore.”

https://pubmed.ncbi.nlm.nih.gov/35982060/

https://www.nature.com/articles/s41467-022-32594-5

Anticancer activity of Δ9-tetrahydrocannabinol and cannabinol in vitro and in human lung cancer xenograft

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Asian Pacific Journal of Tropical Biomedicine

“Objective: To investigate the effects of Δ9-tetrahydrocannabinol, the principal psychoactive compound of Cannabis sativa, and cannabinol, a Δ9-tetrahydrocannabinol degradative product, on human non-small cell lung cancer cells.
Methods: Δ9-Tetrahydrocannabinol and cannabinol were tested for anticancer activity in human non-small cell lung cancer (A549) cells. The effects on cell proliferation, apoptosis, and phosphorylation profiles were examined. The effects of Δ9-tetrahydrocannabinol and cannabinol on tumor growth were also investigated using a xenograft nude mouse model. Apoptosis and targeted phosphorylation were verified by immunohistochemistry.
Results: Δ9-Tetrahydrocannabinol and cannabinol significantly inhibited cell proliferation and increased the number of apoptotic cells in a concentration-dependent manner. The Δ9-tetrahydrocannabinol- and cannabinol-treated cells had lower levels of phosphorylated protein kinase B [AKT (S473)], glycogen synthase kinase 3 alpha/beta, and endothelial nitric oxide synthase compared to the controls. The study of xenograft mice revealed that tumors treated with 15 mg/kg Δ9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly smaller than those of the control mice. The tumor progression rates in mice treated with 15 mg/kg Δ9-tetrahydrocannabinol or 40 mg/kg cannabinol were significantly slower than in the control group.
Conclusions: These findings indicate that Δ9-tetrahydrocannabinol and cannabinol inhibit lung cancer cell growth by inhibiting AKT and its signaling pathways, which include glycogen synthase kinase 3 alpha/beta and endothelial nitric oxide synthase.”

https://journals.lww.com/aptb/fulltext/2022/12080/anticancer_activity_of__9_tetrahydrocannabinol_and.1.aspx

In Vitro Anti-Proliferative Activity of Cannabis Extract on Human Cancer Cell Lines

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“Background: Cannabis is classified as a Schedule 5 substance under the Narcotics Act B.E. 2522. Among with various modulatory effects of cannabinoids on body functions, two major cannabinoids are known to be used as medicines. They are a psychoactive delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). Currently, THC and CBD are advised to be used for treatment of a variety of medical conditions. Such as cell growth inhibition, anti-inflammatory effects and tumor regression. Although, potential benefit can be found in the medical condition above mentioned. The use of cannabis in some disease states such as cancer remain to be clinically evaluated in both efficacy and safety aspects through systematic research before being generalized for routine use.

Objective: The purpose of this study to investigate the In vitro effects of cannabis extracts on 10 types of human cancer cell line.

Methods: Two cannabis extracts (high THC level and high CBD level) were kept in sterile bottles, in refrigerator, until further use when it was dissolved in DMSO to give a stock solution, filtered and stored at 4 °C. The small percentage of DMSO present in the wells (maximal 0.1%) was found not to affect the experiment. The anti-proliferative activities of cannabis extract on cancer cell lines was determined by MTT assay.

Results: To evaluate the anti-proliferative activity of the cannabis extracts on 10 types of cancer cell line (lung cancer, breast cancer, colorectal cancer, gastric cancer, cervical cancer, ovarian cancer, liver cancer, pancreatic cancer, cholangiocarcinoma cancer, lymphoma cancer), the cells were treated with different concentrations of high THC level and high CBD level for 72h and cell viability was determined using MTT assay.

The results showed that all of cancer cell lines viability significantly reduced in concentration and time dependent manner following treatment with the extract. The IC50 of the high THC level values ranging from 10.80 ±1.03 to 54.60±1.27 μg/mL, and exhibited very strong activity against RBE with IC50 values of 10.80±1.03 μg/mL. The IC50 of the high CBD level values ranging from 6.00±1.16 to 26.00±1.37 μg/mL, and exhibited very strong activity against NCI-N87 with IC50 values of 6.00±1.16 μg/mL.

Conclusions: The results suggest that high THC level and high CBD level is a potent human cancer cells proliferation. Further investigations are needed to elucidate the mechanism of anticancer actions.”

https://he02.tci-thaijo.org/index.php/JDMS/article/view/255013

Association between cannabis use with urological cancers: A population-based cohort study and a mendelian randomization study in the UK biobank

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“Background: Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers.

Methods: We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age-standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis.

Results: Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR = 0.61, 95%CI:0.40-0.93, p = 0.021) and prostate cancer (HR = 0.82, 95%CI:0.73-0.93, p = 0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC = 0.42, 95%CI:0.19-0.94, p = 0.034; HRBCa = 0.43, 95%CI:0.21-0.86, p = 0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma.

Conclusions: Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.”

https://pubmed.ncbi.nlm.nih.gov/35975633/

“Cannabis, also known as marijuana, is the most used substance derived from Cannabis Sativa which can be used for recreational or medical purposes. Some evidence also suggested that cannabinoids might induce apoptosis of cancer cells and inhibit oncogenesis, indicating a potential treatment effect”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.5132

“Previous Cannabis Use Linked to Lower Risk of Some Genitourinary Cancers”

https://www.cancertherapyadvisor.com/home/cancer-topics/urologic-cancers/genitourinary-cancers-previous-cannabis-use-lower-risk/

Incidence and Predictors of Cannabis-Related Poisoning and Mental and Behavioral Disorders among Patients with Medical Cannabis Authorization: A Cohort Study

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“Objective: As medical cannabis use increases in North America, establishing its safety profile is a priority. The objective of this study was to assess rates of emergency department (ED) visits and hospitalizations due to poisoning by cannabis, and cannabis-related mental health disorders among medically authorized cannabis patients in Ontario, Canada, between 2014 and 2017.

Methods: This is a retrospective cohort study of patients who received medical cannabis authorization in Ontario, Canada, using data collected in participating cannabis clinics. Outcomes included ED visit/hospitalization with a main diagnosis code for: cannabis/cannabinoid poisoning; and mental/behavioral disorders due to cannabis use. Cox proportional hazard regressions were utilized to analyze the data.

Results: From 29,153 patients who received medical authorization, 23,091 satisfied the inclusion criteria. During a median follow-up of 240 days, 14 patients visited the ED or were hospitalized for cannabis poisoning-with an incidence rate of 8.06 per 10,000 person-years (95% CI: 4.8-13.6). A total of 26 patients visited the ED or were hospitalized for mental and behavioral disorders due to cannabis use-with an incidence rate of 15.0 per 10,000 person-years (95% CI: 10.2-22.0). Predictors of cannabis-related mental and behavioral disorders include prior substance use disorders, other mental disorders, age, diabetes, and chronic obstructive pulmonary disease.

Conclusions: The results suggest that the incidence of cannabis poisoning or cannabis-related mental and behavioral disorders was low among patients who were authorized to use cannabis for medical care. Identified predictors can help to target patients with potential risk of the studied outcomes.”

https://pubmed.ncbi.nlm.nih.gov/35866679/

https://www.tandfonline.com/doi/abs/10.1080/10826084.2022.2102193?journalCode=isum20

Antifungal and anti-aflatoxigenic properties of organs of Cannabis sativa L.: relation to phenolic content and antioxidant capacities

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SpringerLink

“Aflatoxin B1 is a carcinogenic mycotoxin that frequently contaminates crops worldwide.

Current research indicates that the use of natural extracts to combat mycotoxin contamination may represent an eco-friendly, sustainable strategy to ensure food safety. Although Cannabis sativa L. has long been known for its psychoactive cannabinoids, it is also rich in many other bioactive molecules.

This study examines extracts from various organs of Cannabis sativa L. to determine their ability to limit aflatoxin production and growth of Aspergillus flavus.

The results indicate that flower extract is most effective for limiting the synthesis of aflatoxin B1, leading to an almost-complete inhibition of toxin production at a concentration of 0.225 mg dry matter per gram of culture medium. Since flower extract is rich in phenolic compounds, its total antioxidant ability and radical-scavenging capacity are determined.

Compared with other anti-aflatoxigenic extracts, the anti-oxidative potential of Cannabis sativa L. flower extract appears moderate, suggesting that its anti-mycotoxin effect may be related to other bioactive compounds.”

https://pubmed.ncbi.nlm.nih.gov/34143269/

https://link.springer.com/article/10.1007/s00203-021-02444-x