Anti-Inflammatory Properties From Cannabis, Cannabinoids are well known to have anti-inflammatory effects in mammalians; however, the Cannabis plant also contains other compounds such as terpenoids, whose biological effects have not yet been characterized. The aim of this study was to compare the anti-inflammatory properties of terpenoids with those of cannabidiol (CBD).
Materials and Methods:
Essential oils prepared from three monoecious non psychoactive chemotypes of Cannabis were analyzed for their terpenoid content and subsequently studied pharmacologically for their anti-inflammatory properties in vitro and in vivo.
In vitro, the three essential oils rich in terpenoids partly inhibited reactive oxygen intermediate and nitric oxide radical (NO•) production in RAW 264.7 stimulated macrophages. The three terpenoid-rich oils exerted moderate anti-inflammatory activities in an in vivo anti-inflammatory model without affecting tumor necrosis factor alpha (TNFα) serum levels.
The different Cannabis chemotypes showed distinct compositions of terpenoids. The terpenoid-rich essential oils exert anti-inflammatory and antinociceptive activities in vitro and in vivo, which vary according to their composition. Their effects seem to act independent of TNFα. None of the essential oils was as effective as purified CBD. In contrast to CBD that exerts prolonged immunosuppression and might be used in chronic inflammation, the terpenoids showed only a transient immunosuppression and might thus be used to relieve acute inflammation.
Surgeon General Jerome Adams participated in a discussion about opioid addiction and treatment policy. He talked about what he said were improvements made by the Trump administration to address the opioid epidemic from the federal level, and suggested additional steps that could be taken in order to help those living with or seeking treatment for addiction.
Prior preclinical studies show that acute cannabinoid injections impair cognition.
Here, effects of cannabis smoke on working memory were tested in rats.
Cannabis smoke improved working memory accuracy.
Placebo smoke did not affect working memory accuracy.
Enhancing effects are likely due to THC dose and/or route of administration.
Numerous preclinical studies show that acute cannabinoid administration impairs cognitive performance. Almost all of this research has employed cannabinoid injections, however, whereas smoking is the preferred route of cannabis administration in humans.
The goal of these experiments was to systematically determine how acute exposure to cannabis smoke affects working memory performance in a rat model. Adult male (n = 15) and female (n = 16) Long-Evans rats were trained in a food-motivated delayed response working memory task. Prior to test sessions, rats were exposed to smoke generated by burning different numbers of cannabis or placebo cigarettes, using a within-subjects design.
Exposure to cannabis smoke had no effect on male rats’ performance, but surprisingly, enhanced working memory accuracy in females, which tended to perform less accurately than males under baseline conditions. In addition, cannabis smoke enhanced working memory accuracy in a subgroup of male rats that performed comparably to the worst-performing females.
Exposure to placebo smoke had no effect on performance, suggesting that the cannabinoid content of cannabis smoke was critical for its effects on working memory. Follow-up experiments showed that acute administration of either Δ9-tetrahydrocannabinol (0.0, 0.3, 1.0, 3.0 mg/kg) or the cannabinoid receptor type 1 antagonist rimonabant (0.0, 0.2, 0.6, 2.0 mg/kg) impaired working memory performance.
These results indicate that differences in the route, timing, or dose of cannabinoid administration can yield distinct cognitive outcomes, and highlight the need for further investigation of this topic.
Cannabidiol Treatment In Osteoarthritic Dogs, The objectives of this study were to determine basic oral pharmacokinetics, and assess safety and analgesic efficacy of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA).
Single-dose pharmacokinetics was performed using two different doses of CBD enriched (2 and 8 mg/kg) oil. Thereafter, a randomized placebo-controlled, veterinarian, and owner blinded, cross-over study was conducted. Dogs received each of two treatments: CBD oil (2 mg/kg) or placebo oil every 12 h. Each treatment lasted for 4 weeks with a 2-week washout period. Baseline veterinary assessment and owner questionnaires were completed before initiating each treatment and at weeks 2 and 4. Hematology, serum chemistry and physical examinations were performed at each visit. A mixed model analysis, analyzing the change from enrollment baseline for all other time points was utilized for all variables of interest, with a p ≤ 0.05 defined as significant.
Pharmacokinetics revealed an elimination half-life of 4.2 h at both doses and no observable side effects. Clinically, canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and increase in activity (p < 0.01) with CBD oil. Veterinary assessment showed decreased pain during CBD treatment (p < 0.02). No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).
This pharmacokinetic and clinical study suggests that 2 mg/kg of CBD twice daily can help increase comfort and activity in dogs with OA.
Premature Deaths Reduced By Cannabis, Adverse effects of moderate Cannabis use on physical health are subtle and rarely fatal, while Cannabis use is associated with decreased rates of obesity, diabetes mellitus, mortality from traumatic brain injury, use of alcohol and prescription drugs, driving fatalities, and opioid overdose deaths.
These data suggest that Cannabis use may decrease premature deaths. To date, no studies have attempted to estimate impacts of Cannabis use on premature death that include both adverse and beneficial effects on physical health. Marijuana use is estimated to reduce premature deaths from diabetes mellitus, cancer, and traumatic brain injury by 989 to 2,511 deaths for each 1% of the population using Cannabis.
The analysis predicts an estimated 23,500 to 47,500 deaths prevented annually if medical marijuana were legal nationwide. A number of other potential causes of reduced mortality due to Cannabis use were revealed, but were excluded from the analysis because quantitative data were lacking. These estimates thus substantially underestimate the actual impact of Cannabis use on premature death.
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.
Association of State Marijuana Legalization Policies for Medical and Recreational Use With Vaping Associated Lung Disease.
From June 2019 to January 2020, over 2500 cases of electronic cigarette (e-cigarette)– or vaping–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention (CDC). The specific cause of EVALI is unknown, but most patients report using e-cigarettes to consume tetrahydrocannabinol (THC), the primary psychoactive component of marijuana. The CDC and others have hypothesized that black-market THC products may cause EVALI.1,2
Some states have legalized marijuana and THC-containing products for recreational use. Many other states allow purchases for qualifying medical purposes. In remaining states, all forms of consumption and distribution are illegal, and individuals who use THC likely obtain it from the black market. If black-market THC products are responsible for EVALI, then case rates may be lower in recreational marijuana states. The goal of this cross-sectional study was to measure whether states where marijuana is legal have lower rates of EVALI compared with states where it is illegal.
We conducted a cross-sectional analysis at the state level plus Washington, DC (n = 51). We obtained data on the number of reported EVALI cases for each state in 2019 from the CDC,2 estimates of the prevalence of e-cigarette use in each state in 2017 from the Behavioral Risk Factor Surveillance System,3 and estimates of state populations in 2017 from the Surveillance, Epidemiology, and End Results database.4 This study was deemed exempt from approval by Indiana University’s Institutional Review Board as it used publicly available, aggregate state-level data. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
We defined the EVALI case rate in each state as the midpoint of the CDC-reported range of cases per million population. We classified states as medical marijuana states if the state had a medical marijuana law by January 1, 2019, but no recreational dispensaries. We coded states as recreational marijuana states if the state had a recreational marijuana law and there was at least 1 recreational dispensary open in the state by January 1, 2019.
Throughout, the unit of analysis was the state, and all analyses are unweighted. We estimated a linear regression of the state EVALI case rate per 1 million people on indicator variables for recreational and medical marijuana states, leaving prohibition states as the reference group. The coefficients on the marijuana law variables are estimates of the difference in mean unadjusted EVALI case rates in recreational compared with prohibition states and medical compared with prohibition states.
Differences in e-cigarette use might confound the estimated association between EVALI and state marijuana laws if (1) the prevalence of e-cigarette use differed across states with recreational, medical, and prohibition laws and (2) the prevalence of e-cigarette use was correlated with EVALI rates. We investigated this possibility by fitting linear regressions of the state-level prevalence of e-cigarette use on indicator variables for recreational and medical marijuana laws. We also fit an augmented regression of EVALI case rates on the indicators for state marijuana laws and e-cigarette prevalence. All regressions used heteroskedasticity robust standard errors. We used 2-tailed t tests to assess the null hypotheses of no effect and rejected the null if the P value was less than .05.
Post-traumatic stress disorder sharply increases the risk of depression and suicide. Individuals living with post-traumatic stress disorder frequently use cannabis to treat associated symptoms. We sought to investigate whether cannabis use modifies the association between post-traumatic stress disorder and experiencing a major depressive episode or suicidal ideation.
We used data from the 2012 Canadian Community Health Survey-Mental Health, a nationally representative cross-sectional survey of non-institutionalized Canadians aged ⩾15 years. The relationship between post-traumatic stress disorder and each outcome was modelled using logistic regression with an interaction term for cannabis and post-traumatic stress disorder, controlling for demographic characteristics, mental health, and substance use comorbidities. The ratio of odds ratios and relative excess risk due to interaction was calculated to measure interaction on the multiplicative and additive scales, respectively.
Among 24,089 eligible respondents, 420 (1.7%) reported a current clinical diagnosis of post-traumatic stress disorder. In total, 106 (28.2%) people with post-traumatic stress disorder reported past-year cannabis use, compared to 11.2% of those without post-traumatic stress disorder (p < 0.001). In multivariable analyses, post-traumatic stress disorder was significantly associated with recent major depressive episode (adjusted odds ratio = 7.18, 95% confidence interval: 4.32–11.91) and suicidal ideation (adjusted odds ratio = 4.76, 95% confidence interval: 2.39–9.47) among cannabis non-users. post-traumatic stress disorder was not associated with either outcome among cannabis-using respondents (both p > 0.05).
This study provides preliminary epidemiological evidence that cannabis use may contribute to reducing the association between post-traumatic stress disorder and severe depressive and suicidal states. There is an emerging need for high-quality experimental investigation of the efficacy of cannabis/cannabinoids for the treatment of post-traumatic stress disorder.
Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.
Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain.
Methods and findings
This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3–54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34–0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration.
We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.
This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014.
We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores’ sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (−0.33 percentage points, 95% CI −0.43 to −0.24, p < 0.01) from a mean market share growth of 0.14 ± 0.97.
The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law.
Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.
The Impact Of Cannabis Access Laws On Opioid Prescribing.
While recent research has shown that cannabis access laws can reduce the use of prescription opioids, the effect of these laws on opioid use is not well understood for all dimensions of use and for the general United States population.
Analyzing a dataset of over 1.5 billion individual opioid prescriptions between 2011 and 2018, which were aggregated to the individual provider-year level, we find that recreational and medical cannabis access laws reduce the number of morphine milligram equivalents prescribed each year by 11.8 and 4.2 percent, respectively.
These laws also reduce the total days’ supply of opioids prescribed, the total number of patients receiving opioids, and the probability a provider prescribes any opioids net of any offsetting effects. Additionally, we find consistent evidence that cannabis access laws have different effects across types of providers, physician specialties, and payers.
One policy option that has the potential to reduce opioid prescriptions and opioid-related deaths is the passage of cannabis access laws. These state laws facilitate access to cannabis by removing state legal barriers—though possession of cannabis remains illegal under federal law. Recreational cannabis laws (RCLs) allow adults over 21 to possess and consume a limited amount of cannabis. Medical cannabis laws (MCLs) allow patients with eligible conditions, which are listed in the law and often include some form of intractable pain, to obtain cannabis upon the recommendation or certification of a healthcare provider.