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Association of State Marijuana Legalization Policies for Medical and Recreational Use With Vaping-Associated Lung Disease

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Author Insights: Bariatric Surgery May Lead to Increases in ...“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).

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.

Recreational marijuana states had among the lowest EVALI rates of all states.

The data suggest that EVALI cases were concentrated in states where consumers do not have legal access to recreational marijuana dispensaries. This association was not driven by state-level differences in e-cigarette use, and EVALI case rates were not associated with state-level prevalence of e-cigarette use.

One possible inference from our results is that the presence of legal markets for marijuana has helped mitigate or may be protective against EVALI.”

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2763966

“Legal Marijuana Tied to Lower Rates of Vaping Illness”  https://www.medpagetoday.com/pulmonology/smoking/85807

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MyD88-dependent and -independent signalling via TLR3 and TLR4 are differentially modulated by Δ9-tetrahydrocannabinol and cannabidiol in human macrophages.

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Journal of Neuroimmunology“Toll-like receptors (TLRs) are sensors of pathogen-associated molecules that trigger inflammatory signalling in innate immune cells including macrophages. All TLRs, with the exception of TLR3, promote intracellular signalling via recruitment of the myeloid differentiation factor 88 (MyD88) adaptor, while TLR3 signals via Toll-Interleukin-1 Receptor (TIR)-domain-containing adaptor-inducing interferon (IFN)-β (TRIF) adaptor to induce MyD88-independent signalling. Furthermore, TLR4 can activate both MyD88-dependent and -independent signalling (via TRIF).

The study aim was to decipher the impact of the highly purified plant-derived (phyto) cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), when delivered in isolation and in combination (1:1), on MyD88-dependent and -independent signalling in macrophages.

TLRs are attractive therapeutic targets given their role in inflammation and initiation of adaptive immunity, and data herein indicate that both CBD and THC preferentially modulate TLR3 and TLR4 signalling via MyD88-independent mechanisms in macrophages. This offers mechanistic insight into the role of phytocannabinoids in modulating cellular inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/32244040

https://www.jni-journal.com/article/S0165-5728(20)30057-6/pdf

“Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. Δ9-Tetrahydrocannabinol (THC) is a major constituent of Cannabis. The second major constituent of Cannabis extract is cannabidiol (CBD). Both THC and CBD have been shown to exert anti-inflammatory properties and to modulate the function of immune cells. In summary, our results show that although both THC and CBD exert anti-inflammatory effects, the two compounds engage different, although to some extent overlapping, intracellular pathways. Both THC and CBD decrease the activation of proinflammatory signaling.”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804319/

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Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant.

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molecules-logo “Medicinal use of Cannabis sativa L. has an extensive history and it was essential in the discovery of phytocannabinoids, including the Cannabis major psychoactive compound-Δ9-tetrahydrocannabinol (Δ9-THC)-as well as the G-protein-coupled cannabinoid receptors (CBR), named cannabinoid receptor type-1 (CB1R) and cannabinoid receptor type-2 (CB2R), both part of the now known endocannabinoid system (ECS).

Cannabinoids is a vast term that defines several compounds that have been characterized in three categories: (i) endogenous, (ii) synthetic, and (iii) phytocannabinoids, and are able to modulate the CBR and ECS. Particularly, phytocannabinoids are natural terpenoids or phenolic compounds derived from Cannabis sativa.

However, these terpenoids and phenolic compounds can also be derived from other plants (non-cannabinoids) and still induce cannabinoid-like properties. Cannabimimetic ligands, beyond the Cannabis plant, can act as CBR agonists or antagonists, or ECS enzyme inhibitors, besides being able of playing a role in immune-mediated inflammatory and infectious diseases, neuroinflammatory, neurological, and neurodegenerative diseases, as well as in cancer, and autoimmunity by itself.

In this review, we summarize and critically highlight past, present, and future progress on the understanding of the role of cannabinoid-like molecules, mainly terpenes, as prospective therapeutics for different pathological conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/32235333

https://www.mdpi.com/1420-3049/25/7/1567

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The effect of attitudes, subjective norms and stigma on health-care providers’ intention to recommend medicinal cannabis to patients.

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International Journal of Nursing Practice“The aim of this study was to explore the effect of health-care providers’ attitudes towards the medical use of cannabis, subjective norms and perceived stigma towards medicinal cannabis users on health-care providers’ intention to recommend medicinal cannabis for patients with qualifying conditions.

RESULTS:

More positive attitudes towards the medical use of cannabis were associated with lower stigma towards medicinal cannabis users, which, in turn, was associated with a higher intention of recommending medicinal cannabis for patients with qualifying conditions. The relationship between attitudes towards the medical use of cannabis and the intention to recommend medicinal cannabis varies according to subjective norms.

CONCLUSIONS:

Among nurses and physicians, stigma towards medicinal cannabis users mediated the relationship between attitudes towards the medical use of cannabis and the intention to recommend medicinal cannabis for patients with qualifying conditions, whereas subjective norms moderated this relationship.

Effective treatment with medicinal cannabis might be compromised by health-care providers’ negative attitudes, stigma and subjective norms.”

https://www.ncbi.nlm.nih.gov/pubmed/32237017

https://onlinelibrary.wiley.com/doi/abs/10.1111/ijn.12836

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Adolescent treatment admissions for marijuana following recreational legalization in Colorado and Washington.

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Drug and Alcohol Dependence“There is concern that recreational marijuana legalization (RML) may lead to increased cannabis use disorder (CUD) among youth due to increased marijuana use.

This study investigates whether adolescent substance use disorder treatment admissions for marijuana use increased in Colorado and Washington following RML.

RESULTS:

Over all states in the analysis, the rate of adolescent treatment admissions for marijuana use declined significantly over the study period (β=-3.375, 95 % CI=-4.842, -1.907), with the mean rate falling nearly in half. The decline in admissions rate was greater in Colorado and Washington compared to non-RML states following RML, though this difference was not significant (β=-7.671, 95 % CI=-38.798, 23.456).

CONCLUSION:

Adolescent treatment admissions for marijuana use did not increase in Colorado and Washington following RML. This may be because youth marijuana use did not increase, CUD did not increase (even if use did increase), or treatment seeking behaviors changed due to shifts in attitudes and perceptions of risk towards marijuana use.”

https://www.ncbi.nlm.nih.gov/pubmed/32222560

“Youth treatment admissions in Colorado and Washington did not increase after RML. Admissions for 2008–2017 declined in both Colorado/Washington and non-RML states.”

https://www.sciencedirect.com/science/article/abs/pii/S0376871620301253?via%3Dihub

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Δ9-Tetrahydrocannabinol (THC) Impairs CD8+ T Cell-Mediated Activation of Astrocytes.

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“CD8+ T cells can contribute to neuroinflammation by secretion of inflammatory cytokines like interferon γ (IFNγ) and tumor necrosis factor α (TNFα). Astrocytes, a glial cell in the brain, can be stimulated by IFNγ and TNFα to secrete the inflammatory cytokines, monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and interferon-γ inducible protein 10 (IP-10).

Δ9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in Cannabis sativa, possesses potent anti-inflammatory activity.

The objective of this investigation was to assess the effects of THC treatment on CD8+ T cell-mediated activation of astrocytes.

The results suggest that cannabinoid treatment can selectively reduce certain CD8+ T cell responses that contribute to stimulation of astrocytes. Treatment with THC can abate CD8+ T cell-dependent neuroinflammatory processes by inhibiting CD8+ cell differentiation into effector cells, suppressing CD8+ effector cell function, and reducing activation of astrocytes by CD8+ T cell-derived inflammatory cytokines.”

https://www.ncbi.nlm.nih.gov/pubmed/32215844

https://link.springer.com/article/10.1007%2Fs11481-020-09912-z

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Cannabidiol alleviates hemorrhagic shock-induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway.

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Publication cover image“Recently, several studies have reported that the pharmacological effects exerted by cannabidiol (CBD) are partially related to the regulation of autophagy. Increasing evidence indicates that autophagy provides protection against ischemia-induced brain injury. However, the protective effect of CBD against mitochondrial-dependent apoptosis in hemorrhagic shock (HS)-induced brain injury has not been studied.

In the present study, we observed the protective effects of CBD against neural mitochondrial-dependent apoptosis in a rat model of HS. In addition, CBD increased Beclin-1 and LC3II expression and reduced P62 expression, which were indicative of autophagy. CBD treatment attenuated the neural apoptosis induced by HS, as reflected by restoring mitochondrial dysfunction, downregulation of BAX, neuro-apoptosis ratio and NF-κB signaling activation, and upregulation of BCL2 in the cerebral cortex.

Such protective effects were reversed by 3-Methyladenine, a specific autophagy inhibitor, indicating that the protective effects of CBD treatment involved autophagy. LY294002, a PI3K inhibitor, significantly inhibited CBD-induced autophagy, demonstrating that PI3K/AKT signaling is involved in the CBD’s regulation of autophagy. Furthermore, we found that CBD treatment upregulated PI3K/AKT signaling via cannabinoid receptor 1.

Therefore, these findings suggested that CBD treatment protects against cerebral injury induced by HS-mediated mitochondrial-dependent apoptosis by activating the PI3K/AKT signaling pathway to reinforce autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/32215966

https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12557

“Hemorrhagic shock occurs when the body begins to shut down due to large amounts of blood loss.” https://www.healthline.com/health/hemorrhagic-shock

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Cannabidiol in sport : ergogenic or else?

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Pharmacological Research“In the sports domain, cannabis is prohibited by the World Anti-Doping Agency (WADA) across all sports in competition since 2004. The few studies on physical exercise and cannabis focused on the main compound i.e. Δ9-tetrahydrocannabinol. Cannabidiol (CBD) is another well-known phytocannabinoid present in dried or heated preparations of cannabis. Unlike Δ9-tetrahydrocannabinol, CBD is non-intoxicating but exhibits pharmacological properties that are interesting for medical use.

The worldwide regulatory status of CBD is complex and this compound is still a controlled substance in many countries. Interestingly, however, the World Anti-Doping Agency removed CBD from the list of prohibited substances – in or out of competition – since 2018. This recent decision by the WADA leaves the door open for CBD use by athletes.

In the present opinion article we wish to expose the different CBD properties discovered in preclinical studies that could be further tested in the sport domain to ascertain its utility. Preclinical studies suggest that CBD could be useful to athletes due to its anti-inflammatory, analgesic, anxiolytic, neuroprotective properties and its influence on the sleep-wake cycle. Unfortunately, almost no clinical data are available on CBD in the context of exercise, which makes its use in this context still premature.”

https://www.ncbi.nlm.nih.gov/pubmed/32205233

“Athletes could benefit from CBD to manage pain, inflammation and the swelling processes associated with injury. CBD could be useful to manage anxiety, fear memory process, sleep and sleepiness in athletes. CBD could be interesting for the management of mild traumatic brain injury and chronic traumatic encephalopathy.”

https://www.sciencedirect.com/science/article/abs/pii/S1043661819326143?via%3Dihub

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Effects of dietary hemp seed oil to sows on fatty acid profiles, nutritional and immune status of piglets.

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Image result for journal of animal science and biotechnology“The oil from industrial hemp seeds (Cannabis sativa) is an ideal source of stearidonic acid, which is a precursor fatty acid for the long-chained n-3 polyunsaturated fatty acids. These fatty acids are important for neonatal development, health and immunity.

Hemp seed oil has been investigated for the influence on human health, but research on the impact in pig nutrition is scarce. The aim of our research was to study the effect of dietary hemp seed oil relative to soybean oil to lactating sows on the transfer of fatty acids to the off-spring and the effect on piglets’ immune and nutritional status.

The hemp seed oil resulted in direct maternal supply with n-3 long-chain polyunsaturated fatty acids (LCPUFA), especially ALA and SDA, and piglets were able to convert these fatty acids obtained via the sow milk intake to C20:5n-3 and C22:5n-3. Furthermore, some interesting effects of the 5% hemp seed oil was obtained with regard to piglet initial body weight gain and glucose, which could be of interest for further research, i.e., the capability of hemp seed oil to benefit piglets during early life.”

https://www.ncbi.nlm.nih.gov/pubmed/32206310

“Our research demonstrated that colostrum and milk fatty acid composition and immunoglobulin concentration, as well as fatty acid profile of sows’ and piglets’ plasma, were influenced by the fatty acid composition of the maternal diets provided during late gestation and lactation. The hemp seed oil resulted in direct maternal supply with n-3 LCPUFAs, especially ALA and SDA, and piglets were able to convert these fatty acids obtained via the sow milk intake to C20:5n-3 and C22:5n-3.”

https://jasbsci.biomedcentral.com/articles/10.1186/s40104-020-0429-3

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CSF levels of the endocannabinoid anandamide are reduced in patients with untreated narcolepsy type 1: a pilot study.

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“The endocannabinoid system (ECs) is involved in excitatory/inhibitory balance mechanisms within the CNS.

Growing evidence shows that endocannabinoids may influence both hypothalamic orexinergic and histaminergic neurons involved in narcolepsy physiopathology, thus indicating that endocannabinoids may play an intrinsic role modulating sleep and wake.

We hypothesize that the endocannabinoid system is dysregulated in narcolepsy type 1 (NT1).”

https://www.ncbi.nlm.nih.gov/pubmed/32148204

http://www.eurekaselect.com/180033/article

“Taking together, these findings suggest that CBD might prevent sleepiness in narcolepsy.” https://www.ncbi.nlm.nih.gov/pubmed/31642794

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