“Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.” https://www.ncbi.nlm.nih.gov/pubmed/28549792 http://www.sciencedirect.com/science/article/pii/S0065128116303154]]>
Category Archives: THC (Delta-9-Tetrahydrocannabinol)
Single and combined effects of delta9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.
“It has been suggested that the non-psychoactive phytocannabinoid cannabidiol (CBD) can impact the pharmacological effects of delta-9-tetrahydrocannabinol (THC). We tested the hypothesis that CBD and THC would significantly mitigate mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain, and that CBD+THC combinations would produce synergistic effects. We also tested the hypothesis that CBD would attenuate oxaliplatin- and vincristine- induced mechanical sensitivity.
KEY RESULTS:
Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity.CONCLUSIONS AND IMPLICATIONS:
CBD may be potent and effective at preventing the development of CIPN, and its clinical utility may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of Cannabis-based pharmacotherapies.” https://www.ncbi.nlm.nih.gov/pubmed/28548225 http://onlinelibrary.wiley.com/doi/10.1111/bph.13887/abstract]]>Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis.
“There is a lack of consensus on the role of selective cannabinoids for the treatment of neuropathic pain (NP). Guidelines from national and international pain societies have provided contradictory recommendations. The primary objective of this systematic review and meta-analysis (SR-MA) was to determine the analgesic efficacy and safety of selective cannabinoids compared to conventional management or placebo for chronic NP.
METHODS:
We reviewed randomized controlled trials that compared selective cannabinoids (dronabinol, nabilone, nabiximols) with conventional treatments (eg, pharmacotherapy, physical therapy, or a combination of these) or placebo in patients with chronic NP because patients with NP may be on any of these therapies or none if all standard treatments have failed to provide analgesia and or if these treatments have been associated with adverse effects. MEDLINE, EMBASE, and other major databases up to March 11, 2016, were searched. Data on scores of numerical rating scale for NP and its subtypes, central and peripheral, were meta-analyzed. The certainty of evidence was classified using the Grade of Recommendations Assessment, Development, and Evaluation approach.RESULTS:
Eleven randomized controlled trials including 1219 patients (614 in selective cannabinoid and 605 in comparator groups) were included in this SR-MA. There was variability in the studies in quality of reporting, etiology of NP, type and dose of selective cannabinoids. Patients who received selective cannabinoids reported a significant, but clinically small, reduction in mean numerical rating scale pain scores (0-10 scale) compared with comparator groups (-0.65 points; 95% confidence interval, -1.06 to -0.23 points; P = .002, I = 60%; Grade of Recommendations Assessment, Development, and Evaluation: weak recommendation and moderate-quality evidence). Use of selective cannabinoids was also associated with improvements in quality of life and sleep with no major adverse effects.CONCLUSIONS:
Selective cannabinoids provide a small analgesic benefit in patients with chronic NP. There was a high degree of heterogeneity among publications included in this SR-MA. Well-designed, large, randomized studies are required to better evaluate specific dosage, duration of intervention, and the effect of this intervention on physical and psychologic function.”The Standard Joint Unit.
“Reliable data on cannabis quantities is required to improve assessment of cannabis consumption for epidemiological analysis and clinical assessment, consequently a Standard Joint Unit (SJU) based on quantity of 9-Tetrahydrocannabinol (9-THC) has been established.
METHODOLOGY:
Naturalistic study of a convenience sample recruited from February 2015-June 2016 in universities, leisure spaces, mental health services and cannabis clubs in Barcelona. Adults, reporting cannabis use in the last 60 days, without cognitive impairment or language barriers, answered a questionnaire on cannabis use and were asked to donate a joint to further determine their 9-THC and Cannabidiol (CBD) content.RESULTS:
492 participants donated 315 valid joints. Donators were on average 29 years old, mostly men (77%), single (75%), with at least secondary studies (73%) and in active employment (63%). Marijuana joints (N=232) contained a median of 6.56mg of 9-THC (Interquartile range-IQR=10,22) and 0.02mg of CBD (IQR=0.02); hashish joints (N=83) a median of 7.94mg of 9-THC (IQR=10,61) and 3.24mg of CBD (IQR=3.21). Participants rolled 4 joints per gram of cannabis and paid 5€ per gram (median values).CONCLUSION:
Consistent 9-THC-content in joints lead to a SJU of 7mg of 9-THC, the integer number closest to the median values shared by both cannabis types. Independently if marijuana or hashish, 1 SJU = 1 joint = 0.25 g of cannabis = 7 mg of 9-THC. For CBD, only hashish SJU contained relevant levels. Similarly to the Standard Drink Unit for alcohol, the SJU is useful for clinical, epidemiological and research purposes.” https://www.ncbi.nlm.nih.gov/pubmed/28531767 http://www.drugandalcoholdependence.com/article/S0376-8716(17)30194-1/fulltext]]>Modulation of CB1 cannabinoid receptor by allosteric ligands: Pharmacology and therapeutic opportunities.
“Cannabinoid pharmacology has been intensely studied because of cannabis’ pervasive medicinal and non-medicinal uses as well as for the therapeutic potential of cannabinoid-based drugs for the treatment of pain, anxiety, substance abuse, obesity, cancer and neurodegenerative disorders. The identification of allosteric modulators of the cannabinoid receptor 1 (CB1) has given a new direction to the development of cannabinoid-based therapeutics due to the many advantages offered by targeting allosteric site(s). Allosteric receptor modulators hold potential to develop subtype-specific and pathway-specific therapeutics. Here we briefly discuss the first-generation of allosteric modulators of CB1 receptor, their structure-activity relationships, signaling pathways and the allosteric binding site(s) on the CB1 receptor.” https://www.ncbi.nlm.nih.gov/pubmed/28527758 http://www.sciencedirect.com/science/article/pii/S0028390817302307]]>
A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice
“The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.” https://www.ncbi.nlm.nih.gov/pubmed/28481360 https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4311.html
“CAN MARIJUANA RESTORE MEMORY? NEW STUDY SHOWS CANNABIS CAN REVERSE COGNITIVE DECLINE IN MICE” http://www.newsweek.com/cannabis-marijuana-restores-memory-learning-cognitive-decline-596160
“A little cannabis every day might keep brain ageing at bay” https://www.newscientist.com/article/2130257-a-little-cannabis-every-day-might-keep-brain-ageing-at-bay/
“Low-dose cannabinoid THC restores memory and learning in old mice” http://www.medicalnewstoday.com/articles/317342.php
“Daily Dose Of Cannabis May Protect And Heal The Brain From Effects Of Aging” https://www.forbes.com/sites/janetwburns/2017/05/08/daily-dose-of-cannabis-may-protect-and-heal-the-brain-from-effects-of-aging/#70ef658f2e44
“Cannabis reverses aging processes in the brain” https://medicalxpress.com/news/2017-05-cannabis-reverses-aging-brain.html
“Future dementia cure – Chemical in cannabis could REVERSE the ageing process” http://www.express.co.uk/life-style/health/801827/dementia-cure-cannabis-THC-chemical-memory
]]>Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial.
“A double-blind study was performed comparing 5 mg delta-9-tetrahydrocannabinol (THC) p.o., 50 mg codeine p.o., and placebo in a patient with spasticity and pain due to spinal cord injury. The three conditions were applied 18 times each in a randomized and balanced order. Delta-9-THC and codeine both had an analgesic effect in comparison with placebo. Only delta-9-THC showed a significant beneficial effect on spasticity. In the dosage of THC used no altered consciousness occurred.”