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Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study

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The BMJ (@bmj_latest) / Twitter

“Objective: To examine county level associations between the prevalence of medical and recreational cannabis stores (referred to as dispensaries) and opioid related mortality rates.

Participants: The study used US mortality data from the Centers for Disease Control and Prevention combined with US census data and data from Weedmaps.com on storefront dispensary operations. Data were analyzed at the county level by using panel regression methods.

Main outcome measure: The main outcome measures were the log transformed, age adjusted mortality rates associated with all opioid types combined, and with subcategories of prescription opioids, heroin, and synthetic opioids other than methadone. The associations of medical dispensary and recreational dispensary counts with age adjusted mortality rates were also analyzed.

Results: County level dispensary count (natural logarithm) is negatively related to the log transformed, age adjusted mortality rate associated with all opioid types (β=-0.17, 95% confidence interval -0.23 to -0.11). According to this estimate, an increase from one to two storefront dispensaries in a county is associated with an estimated 17% reduction in all opioid related mortality rates. Dispensary count has a particularly strong negative association with deaths caused by synthetic opioids other than methadone (β=-0.21, 95% confidence interval -0.27 to -0.14), with an estimated 21% reduction in mortality rates associated with an increase from one to two dispensaries. Similar associations were found for medical versus recreational storefront dispensary counts on synthetic (non-methadone) opioid related mortality rates.

Conclusions: Higher medical and recreational storefront dispensary counts are associated with reduced opioid related death rates, particularly deaths associated with synthetic opioids such as fentanyl. While the associations documented cannot be assumed to be causal, they suggest a potential association between increased prevalence of medical and recreational cannabis dispensaries and reduced opioid related mortality rates. This study highlights the importance of considering the complex supply side of related drug markets and how this shapes opioid use and misuse.”

https://pubmed.ncbi.nlm.nih.gov/33504472/

“We studied county level associations between cannabis storefront dispensaries and opioid related mortality rates in the US between 2014 and 2018. Our study found that increased medical and recreational storefront dispensary counts are associated with reduced opioid related mortality rates during the study period. These associations appear particularly strong for deaths related to synthetic opioids such as fentanyl.”

https://www.bmj.com/content/372/bmj.m4957

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

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“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

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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“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

The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts

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“Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial.

In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested.

We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001).

Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed.”

https://pubmed.ncbi.nlm.nih.gov/35955938/

“We, for the first time, show that application of TRSV in combination with CBD constitutes a very promising anti-aging and regenerative regimen that can potentially be used for treatment or/and prevention of appearance of aging spots and treating cutaneous wounds. Moreover, we found pCBs alone appeared to be highly efficacious as an anti-aging treatment. Further work should study and test pCBs alone, as well as TRSV in combination with CBD as anti-aging remedies.”

https://www.mdpi.com/1422-0067/23/15/8804/htm

Acyclic Diterpene Phytol from Hemp Seed Oil ( Cannabis sativa L.) Exerts Anti-Inflammatory Activity on Primary Human Monocytes-Macrophages

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“Seeds from non-drug varieties of hemp (Cannabis sativa L.) have been used for traditional medicine, food, and fiber production. Our study shows that phytol obtained from hemp seed oil (HSO) exerts anti-inflammatory activity in human monocyte-macrophages.

Fresh human monocytes and human macrophages derived from circulating monocytes were used to evaluate both plasticity and anti-inflammatory effects of phytol from HSO at 10-100 mM using FACS analysis, ELISA, and RT-qPCR methods. The quantitative study of the acyclic alcohol fraction isolated from HSO shows that phytol is the most abundant component (167.59 ± 1.81 mg/Kg of HSO).

Phytol was able to skew monocyte-macrophage plasticity toward the anti-inflammatory non-classical CD14+CD16++ monocyte phenotype and toward macrophage M2 (CD200Rhigh and MRC-1high), as well as to reduce the production of IL-1β, IL-6, and TNF-α, diminishing the inflammatory competence of mature human macrophages after lipopolysaccharide (LPS) treatment.

These findings point out for the first time the reprogramming and anti-inflammatory activity of phytol in human monocyte-macrophages. In addition, our study may help to understand the mechanisms by which phytol from HSO contributes to the constant and progressive plasticity of the human monocyte-macrophage linage.”

https://pubmed.ncbi.nlm.nih.gov/35954130/

“These results showed that phytol, which was isolated and identified for the first time in HSO, can help to better understand the specific mechanism by which this acyclic diterpene exerts beneficial effects on monocyte-macrophage plasticity. So far, HSO has already been demonstrated to include healthy polyunsaturated fatty acids, as well as antioxidant tocopherols and anti-inflammatory phytosterols in its unsaponifiable fraction. In recent years, inflammation has emerged as a leading pathophysiologic mechanism in atherosclerosis and other diseases, so the effects of phytol on different hallmarks of the inflammatory response contribute to the recommendation of HSO as an interesting source of functional compounds.”

https://www.mdpi.com/2304-8158/11/15/2366/htm

Neuroprotection of Cannabidiol, Its Synthetic Derivatives and Combination Preparations against Microglia-Mediated Neuroinflammation in Neurological Disorders

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“The lack of effective treatment for neurological disorders has encouraged the search for novel therapeutic strategies. Remarkably, neuroinflammation provoked by the activated microglia is emerging as an important therapeutic target for neurological dysfunction in the central nervous system. In the pathological context, the hyperactivation of microglia leads to neuroinflammation through the release of neurotoxic molecules, such as reactive oxygen species, proteinases, proinflammatory cytokines and chemokines.

Cannabidiol (CBD) is a major pharmacologically active phytocannabinoids derived from Cannabis sativa L. CBD has promising therapeutic effects based on mounting clinical and preclinical studies of neurological disorders, such as epilepsy, multiple sclerosis, ischemic brain injuries, neuropathic pain, schizophrenia and Alzheimer’s disease.

A number of preclinical studies suggested that CBD exhibited potent inhibitory effects of neurotoxic molecules and inflammatory modulators, highlighting its remarkable therapeutic potential for the treatment of numerous neurological disorders. However, the molecular mechanisms of action underpinning CBD’s effects on neuroinflammation appear to be complex and are poorly understood.

This review summarises the anti-neuroinflammatory activities of CBD against various neurological disorders with a particular focus on their main molecular mechanisms of action, which were related to the downregulation of NADPH oxidase-mediated ROS, TLR4-NFκB and IFN-β-JAK-STAT pathways. We also illustrate the pharmacological action of CBD’s derivatives focusing on their anti-neuroinflammatory and neuroprotective effects for neurological disorders. We included the studies that demonstrated synergistic enhanced anti-neuroinflammatory activity using CBD and other biomolecules.

The studies that are summarised in the review shed light on the development of CBD, including its derivatives and combination preparations as novel therapeutic options for the prevention and/or treatment of neurological disorders where neuroinflammation plays an important role in the pathological components.”

https://pubmed.ncbi.nlm.nih.gov/35956911/

“Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. The preclinical studies summarised in this review supported the therapeutic use of CBD in treating neurological disorders from its action in addressing microglia-mediated neuroinflammation. The findings of this review shed light on the development of CBD and relevant compounds as novel and more advantageous therapeutics to prevent or treat neurological disorders by targeting microglia-mediated neuroinflammation.”

https://www.mdpi.com/1420-3049/27/15/4961/htm


Phytochemical differences of hemp ( Cannabis sativa L.) leaves from different germplasms and their regulatory effects on lipopolysaccharide-induced inflammation in Matin-Darby canine kidney cell lines

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“The increasing demand of hemp (Cannabis sativa L.) has attracted more interest in exploring its phytochemical profile and bioactivities, such as anti-inflammatory effect. In this study, the phytochemicals of different hemp leaves were investigated, with the content order: total saponins content (TSC) > total alkaloids content (TAC) > total phenolics content (TPC) > total flavonoids content (TFC) > cannabinoids.

Hemp leaves from Shanxi accumulated higher flavonoids and cannabinoids (i.e., THC, CBD, and CBN), while phenolics were more abundant in those from Hunan. A lipopolysaccharide (LPS)-induced inflammatory Matin-Darby canine kidney (MDCK) cell model was established to evaluate the anti-inflammatory effects of hemp leaf extracts.

Hemp leaf extracts, especially the D129 and c7, significantly increased cell viability of LPS-induced inflammatory MDCK cells, and D132 significantly decreased the secretion of pro-inflammatory cytokines (TNF-α and IL-6) and the lactate dehydrogenase (LDH) activity. Except for c12, other hemp leaf extracts obviously decreased the cell morphological damage of LPS-induced inflammatory MDCK cells.

The correlation analysis revealed that cannabinol (CBN) and TPC showed the strongest correlation with anti-inflammatory activities, and hierarchical clustering analysis also showed that hemp germplasms from Shanxi might be good alternatives to the common cultivar Ym7 due to their better anti-inflammatory activities.

These results indicated that hemp leaves were effective in LPS-induced inflammatory MDCK cells, and flavonoids and cannabinoids were potential geographical markers for distinguishing them, which can provide new insights into the anti-inflammatory effect of hemp leaves and facilitate the application of hemp leaves as functional ingredients against inflammatory-related disorders.”

https://pubmed.ncbi.nlm.nih.gov/35938104/

“The current findings demonstrated that the contents of various phytochemicals in hemp leaves were generally descending from TSC > TAC > TPC > TFC > cannabinoids. In addition, hemp leaves (0.05 mg/mL), especially hemp leaves cultivated in Shanxi (D129, D130, D132, D134, D142, and D361), reduced the release of pro-inflammatory cytokines (TNF-α), reduced LDH levels, and inhibited the cell morphological changes and the membrane damage of LPS-induced inflammatory MDCK cells. Furthermore, correlation analysis indicated phenolics and CBN might be the leading contributors to protecting the MDCK cells from LPS-induced inflammation. Meanwhile, hierarchical clustering indicated hemp leaves from Shanxi performed a better anti-inflammatory activity than the common cultivar Ym7. Thus, it is suggested that these germplasms from Shanxi can be good alternatives to Ym7. Overall, the present study provides scientific evidence for the anti-inflammatory potential of hemp leaves, which can be used in nutraceuticals and functional foods.”

https://www.frontiersin.org/articles/10.3389/fnut.2022.902625/full


Synthetic cannabinoid poisonings and access to the legal cannabis market: findings from US national poison centre data 2016-2019

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“Aim: To investigate trends in synthetic cannabinoid exposures reported to United States (US) poison control centres, and their association with status of state cannabis legalisation.

Methods: A retrospective study of National Poison Data System (NPDS) data from 2016 to 2019 identified and associated synthetic poisoning reports with annual state cannabis law and market status. State status was categorised as restrictive (cannabis illegal or limited medical legalisation), medical (allowing THC-containing medical cannabis use) and permissive (allowing non-medical use of THC-containing cannabis by adults). We categorised a subset of states with permissive policies by their implementation of legal adult possession/use and opening retail markets, on a quarterly basis. Mixed-effects Poisson regression models assessed synthetic exposures associated with legal status, first among all states using annual counts, and then among states that implemented permissive law alone using quarterly counts.

Results: A total of 7600 exposures were reported during the study period. Overall, reported synthetic exposures declined over time. Most reported exposures (64.8%) required medical attention, and 61 deaths were documented. State implementation of medical cannabis law was associated with 13% fewer reported annual exposures. Adoption of permissive state cannabis policy was independently and significantly associated with 37% lower reported annual synthetic exposures, relative to restrictive policies (IRR: 0.63, 95% CI: 0.50-0.79). Among states with permissive law during the period, implementation of legal adult possession/use was associated with 22% fewer reported quarterly exposures. Opening of retail markets was associated with 36% fewer reported exposures, relative to states with medical cannabis only.

Conclusions: Adoption of permissive cannabis law was associated with significant reductions in reported synthetic cannabinoid exposures. More permissive cannabis law may have the unintended benefit of reducing both motivation and harms associated with use of synthetic cannabis products.”

https://pubmed.ncbi.nlm.nih.gov/35942512/

“The gradual reduction of prohibitions against plant-based cannabis offers an opportunity to study use of cannabis and powerful synthetic analogues that may have been used as natural cannabis substitutes. Our study identified an association between more liberal policies (legalisation) for natural cannabis and declines in reported synthetic cannabinoid poisonings. This finding suggests a potential effect of policy change on substance use behaviours that may have long-term public health implications.”

https://www.tandfonline.com/doi/full/10.1080/15563650.2022.2099887

Cannabis Use and Sinonasal Symptoms in US Adults

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Medflixs - JAMA Otolaryngology Formation

“Importance: Cannabis is the most commonly used illicit substance in the US and worldwide. Understanding the association between cannabis use and sinonasal symptoms may help clinicians and patients better understand the symptomatology associated with cannabis use.

Objective: To assess the association between frequency of cannabis use and presence of sinonasal symptoms in a nationally representative sample of US adults.

Design, setting, and participants: This population-based, retrospective cross-sectional study included adults aged 20 to 69 years who had completed data on sinonasal symptoms and substance use for the 2013 to 2014 National Health and Nutrition Examination Survey. The data were analyzed in February 2022.

Exposures: Cannabis use frequency.

Main outcomes and measures: Presence of sinonasal symptoms, demographic information, and medical history were obtained from National Health and Nutrition Examination Survey questionnaires. Presence of any sinonasal symptoms was defined as responding yes to any of a series of questions assessing rhinologic symptoms. Regular cannabis users were defined as using cannabis 15 or more times within the last 30 days. Nonregular users were defined as using cannabis fewer than 15 times within the last 30 days. Multivariable models were used to examine the association between frequency of cannabis use and presence of sinonasal symptoms while adjusting for demographic characteristics and medical comorbidities.

Results: The study included 2269 adults with a mean (SD) age of 36.5 (12.4) years (1207 women [53.2%]; 330 Asian [14.5%], 739 Black [32.6%], 461 Hispanic [20.3%], and 656 White [28.9%] individuals). The prevalence of sinonasal symptoms among regular cannabis users (45.0%; 95% Cl, 38.9%-51.1%) was lower than the prevalence among never users (64.5%; 95% Cl, 58.3%-68.8%). Compared with adults who had never used cannabis, regular cannabis users were less likely to have sinonasal symptoms (odds ratio, 0.22, 95% CI, 0.10-0.50). Current tobacco smokers were more likely to have sinonasal symptoms (odds ratio, 1.96; 95% CI, 1.17-3.28). The most common sinonasal symptoms reported were nasal congestion (62.8%; 95% Cl, 60.2%-65.4%) and change in smell (17.8%; 95% Cl, 15.2%-20.9%).

Conclusions and relevance: This cross-sectional study found that the prevalence of sinonasal symptoms was lower among regular cannabis users. Further research is needed to elucidate the mechanisms underlying the association between cannabis use and sinonasal symptoms.”

https://pubmed.ncbi.nlm.nih.gov/35900733/

https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2794662

“SINONASAL SYMPTOMS LESS COMMON IN REGULAR CANNABIS USERS”

https://www.physiciansweekly.com/sinonasal-symptoms-less-common-in-regular-cannabis-users