“An improved understanding of the endocannabinoid system has provided new avenues of drug discovery and development toward the management of pain and other behavioral maladies. Exogenous cannabinoid type-1 (CB1) receptor agonists such as Δ9-tetrahydrocannabinol are increasingly utilized for their medicinal actions; however, their utility is constrained by concern regarding abuse-related subjective effects. This has led to growing interest in the clinical benefit of indirectly enhancing the activity of the highly labile endocannabinoids N-arachidonoylethanolamine (anandamide; AEA) and/or 2-arachidonoylglycerol (2-AG) via catabolic enzyme inhibition. The present studies were conducted to determine whether such actions can lead to CB1 agonist-like subjective effects, as reflected in the presence or absence of CB1-related discriminative-stimulus effects in laboratory subjects. Squirrel monkeys (n=8) that discriminated the CB1 full agonist AM4054 (0.01 mg/kg) from vehicle were used to study, first, inhibitors of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MGL) alone or in combination [FAAH (URB597, AM4303); MGL (AM4301); FAAH/MGL (AM4302)] and, second, the ability of the endocannabinoids AEA and 2-AG to produce CB1 agonist-like effects when administered alone or after enzyme inhibition. Results indicate that CB1-related discriminative-stimulus effects were produced by combined, but not selective, inhibition of FAAH and MGL, and that these effects were non-surmountably antagonized by low doses of rimonabant. Additionally, FAAH- or MGL-inhibition revealed CB1-like subjective effects produced by AEA, but not 2-AG. Taken together, the present data suggest that therapeutic effects of combined, but not selective, enhancement of AEA or 2-AG activity via enzyme inhibition may be accompanied by CB1 receptor-mediated subjective effects.” https://www.ncbi.nlm.nih.gov/pubmed/28947487 http://jpet.aspetjournals.org/content/early/2017/09/25/jpet.117.244392]]>
Category Archives: Uncategorized
Do Medical Marijuana Laws Reduce Addictions and Deaths Related to Pain Killers?
“Many medical marijuana patients report using marijuana to alleviate chronic pain from musculoskeletal problems and other sources. If marijuana is used as a substitute for powerful and addictive pain relievers in medical marijuana states, a potential overlooked positive impact of medical marijuana laws may be a reduction in harms associated with opioid pain relievers, a far more addictive and potentially deadly substance. To assess this issue, we study the impact of medical marijuana laws on problematic opioid use. We use two measures of problematic use: treatment admissions for opioid pain reliever addiction from the Treatment Episode Data Set (TEDS) and state-level opioid overdose deaths in the National Vital Statistics System (NVSS). Using both standard differences-in-differences models as well as synthetic control models, we find that states permitting medical marijuana dispensaries experience a relative decrease in both opioid addictions and opioid overdose deaths compared to states that do not. We find no impact of medical marijuana laws more broadly; the mitigating effect of medical marijuana laws is specific to states that permit dispensaries. We evaluate potential mechanisms. Our findings suggest that providing broader access to medical marijuana may have the potential benefit of reducing abuse of highly addictive painkillers.” http://www.nber.org/papers/w21345.pdf “Cannabis use is associated with a substantial reduction in premature deaths in the United States. These data suggest that Cannabis use may decrease premature deaths. Overall, prohibition is estimated to lead to similar numbers of premature deaths as drunk driving, homicide, or fatal opioid overdose. Cannabis use prevents thousands of premature deaths each year, and Cannabis prohibition is revealed as a major cause of premature death in the U.S.” https://scholarworks.iu.edu/dspace/handle/2022/21632]]>
Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use.
“Cannabis is purported to alleviate symptoms related to cancer treatment, although the patterns of use among cancer patients are not well known. This study was designed to determine the prevalence and methods of use among cancer patients, the perceived benefits, and the sources of information in a state with legalized cannabis.
METHODS:
A cross-sectional, anonymous survey of adult cancer patients was performed at a National Cancer Institute-designated cancer center in Washington State. Random urine samples for tetrahydrocannabinol provided survey validation.RESULTS:
Nine hundred twenty-six of 2737 eligible patients (34%) completed the survey, and the median age was 58 years (interquartile range [IQR], 46-66 years). Most had a strong interest in learning about cannabis during treatment (6 on a 1-10 scale; IQR, 3-10) and wanted information from cancer providers (677 of 911 [74%]). Previous use was common (607 of 926 [66%]); 24% (222 of 926) used cannabis in the last year, and 21% (192 of 926) used cannabis in the last month. Random urine samples found similar percentages of users who reported weekly use (27 of 193 [14%] vs 164 of 926 [18%]). Active users inhaled (153 of 220 [70%]) or consumed edibles (154 of 220 [70%]); 89 (40%) used both modalities. Cannabis was used primarily for physical (165 of 219 [75%]) and neuropsychiatric symptoms (139 of 219 [63%]). Legalization significantly increased the likelihood of use in more than half of the respondents.CONCLUSIONS:
This study of cancer patients in a state with legalized cannabis found high rates of active use across broad subgroups, and legalization was reported to be important in patients’ decision to use. Cancer patients desire but are not receiving information about cannabis use during their treatment from oncology providers.” https://www.ncbi.nlm.nih.gov/pubmed/28944449 http://onlinelibrary.wiley.com/doi/10.1002/cncr.30879/abstract;jsessionid=793E288AAC342234D14BA7C96AEEDB74.f02t04?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+7th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+08.00+EDT+%2F+13.00+BST+%2F+17%3A30+IST+%2F+20.00+SGT+and+Sunday+8th+Oct+from+03.00+EDT+%2F+08%3A00+BST+%2F+12%3A30+IST+%2F+15.00+SGT+to+06.00+EDT+%2F+11.00+BST+%2F+15%3A30+IST+%2F+18.00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience+caused+.“Study finds up to one-quarter of cancer patients use marijuana” https://medicalxpress.com/news/2017-09-one-quarter-cancer-patients-marijuana.html
“Up to one-quarter of cancer patients use marijuana” https://www.sciencedaily.com/releases/2017/09/170925095431.htm
“Cancer Patients Want to Use Marijuana, and with Good Reason” https://www.inverse.com/article/36751-cancer-patients-want-to-use-marijuana-study-fred-hutchinson-cancer-research-center
“The use of Cannabis for medicinal purposes dates back to ancient times. Cannabis has been shown to kill cancer cells in the laboratory.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all “Marijuana has been used in herbal remedies for centuries. More recently, scientists reported that THC and other cannabinoids such as CBD slow growth and/or cause death in certain types of cancer cells.” http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/chemotherapyeffects/marijuana-and-cancer http://www.thctotalhealthcare.com/category/cancer/]]>Hypothesizing that marijuana smokers are at a significantly lower risk of carcinogenicity relative to tobacco-non-marijuana smokers: evidenced based on statistical reevaluation of current literature.
“A hypothetical link between marijuana smoking and cancer has been established based on a number of misleading assumptions. However, recent studies tend to suggest, if anything, an inverse association between marijuana use and cancers. To test the hypothesis that marijuana smoking significantly lowers the risk of developing cancer in humans, we analyzed published data from a prospective cohort study on cancer incidence among nonsmokers (NS), marijuana-only smokers (MS), tobacco-only smokers (TS), and marijuana and tobacco smokers (MTS). Using the log linear model to calculate the probability of developing each cancer form as a function of the interaction between marijuana and tobacco smoking, as well as functions of marijuana and tobacco smoking main effects whereby chi square statistics were calculated for the interaction and main effect estimates, we found that in all cases tested there was a significantly lower risk for MS compared to TS. Male and female TS had a greater probability of developing lung cancer than did MS. Males and females TS had a greater probability of developing lung cancer compared with NS. Males and female MTS had a slightly higher probability of developing lung cancer than did MS. This difference was statistically significant: chi2 = 30.51, p < .00001, with a correlation coefficient of -0.75, Z = -7.84, p < .05. Male and female MTS had a lower probability of developing lung cancer than did TS. This difference was statistically significant: chi2 = 71.61, p = .00003, with a correlation coefficient of 0.61, Z = 5.06, p < .05.” https://www.ncbi.nlm.nih.gov/pubmed/19004418 http://www.tandfonline.com/doi/abs/10.1080/02791072.2008.10400641 ]]>
Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats.
“Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory. This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis.
Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured.
Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective.
Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”
https://www.ncbi.nlm.nih.gov/pubmed/28933048
Targeting fatty acid amide hydrolase as a therapeutic strategy for antitussive therapy.
“Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids. Primary vagal ganglia neurons, tissue bioassay, in vivoelectrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents. FAAH inhibition produced antitussive activity in guinea pigs with concomitant plasma elevation of the fatty acid amides N-arachidonoylethanolamide (anandamide), palmitoylethanolamide, N-oleoylethanolamide and linoleoylethanolamide. Palmitoylethanolamide inhibited tussive stimulus-induced activation of guinea pig airway innervating vagal ganglia neurons, depolarisation of guinea pig and human vagus, and firing of C-fibre afferents. These effects were mediated via a cannabinoid CB2/Gi/o-coupled pathway and activation of protein phosphatase 2A, resulting in increased calcium sensitivity of calcium-activated potassium channels. These findings identify FAAH inhibition as a target for the development of novel, antitussive agents without the undesirable side-effects of direct cannabinoid receptor agonists.” https://www.ncbi.nlm.nih.gov/pubmed/28931663 http://erj.ersjournals.com/content/50/3/1700782]]>
[Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience].
:
“Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient’s quality of life. Its treatment is complex and sometimes the outcome is insufficient.
Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.
AIM:
To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations.RESULTS:
Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001).CONCLUSIONS:
Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.” https://www.ncbi.nlm.nih.gov/pubmed/28929471]]>Crash Fatality Rates After Recreational Marijuana Legalization in Washington and Colorado
“Objectives. To evaluate motor vehicle crash fatality rates in the first 2 states with recreational marijuana legalization and compare them with motor vehicle crash fatality rates in similar states without recreational marijuana legalization. Methods. We used the US Fatality Analysis Reporting System to determine the annual numbers of motor vehicle crash fatalities between 2009 and 2015 in Washington, Colorado, and 8 control states. We compared year-over-year changes in motor vehicle crash fatality rates (per billion vehicle miles traveled) before and after recreational marijuana legalization with a difference-in-differences approach that controlled for underlying time trends and state-specific population, economic, and traffic characteristics. Results. Pre–recreational marijuana legalization annual changes in motor vehicle crash fatality rates for Washington and Colorado were similar to those for the control states. Post–recreational marijuana legalization changes in motor vehicle crash fatality rates for Washington and Colorado also did not significantly differ from those for the control states (adjusted difference-in-differences coefficient = +0.2 fatalities/billion vehicle miles traveled; 95% confidence interval = −0.4, +0.9). Conclusions. Three years after recreational marijuana legalization, changes in motor vehicle crash fatality rates for Washington and Colorado were not statistically different from those in similar states without recreational marijuana legalization. Future studies over a longer time remain warranted.” http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2017.303848
“Study: Marijuana not linked to rise in auto fatalities” http://www.ktvu.com/news/study-marijuana-not-linked-to-rise-in-auto-crash-rates
]]>Maternal and infant outcomes following third trimester exposure to marijuana in opioid dependent pregnant women maintained on buprenorphine.
“Analyses failed to support any significant relationship between marijuana use in the third trimester and a variety of maternal and infant outcomes. Preliminary results indicate that marijuana exposure in the third trimester does not complicate the pregnancy or the delivery process.” https://www.ncbi.nlm.nih.gov/pubmed/28917206 http://www.drugandalcoholdependence.com/article/S0376-8716(17)30443-X/fulltext]]>
What's the harm? Alcohol and marijuana use and perceived risks of unprotected sex among adolescents and young adults.
“The link between substance use and risky sexual behavior, particularly unprotected sex, among adolescents and young adults has been well established in the literature; however, less is known regarding how different patterns and types of substance use differentially relate to unprotected sex and perceived risks of unprotected sex. The current study examined perceived risks and unprotected sex among adolescents and young adults, and examined whether marijuana use, alcohol use, and dual marijuana and alcohol use were differentially linked to unprotected sex and perceived risks of unprotected sex.