Weekly Cannabis News
July 8th – July 15th, 2022
Cannabidiol Derivative & Traumatic Brain Injury (TBI)
VCE-004.8 demonstrated anti-inflammatory and protective effects, suggesting that this compound could open new therapeutic avenues for the treatment of TBI.
According to the Centers for Disease Control and Prevention, it is estimated that 1.5 million Americans sustain a traumatic brain injury (TBI) each year making it the leading cause of injury-related death and disability among children and young adults.  TBI is defined as damage sustained to the brain after the application of external physical force which can cause temporary or permanent functional or structural damage to the brain.  This can trigger a series of response over a period of days-months and promotes disruption of the blood-brain barrier (BBB) integrity, a network of blood vessels and tissue that helps keeping harmful substances from entering the brain.  It is known that TBI is an important risk factor for neurodegeneration and dementia such as chronic traumatic encephalopathy (CTE), sharing similar mechanistic pathological features (e.g., PP2A/B55a expression play a role in the development of neurodegenerative diseases).
Emerald Health Pharmaceuticals, headquartered in San Diego, California, is focused on the development of a new class of drugs with precise mechanisms of action aimed at bringing innovative therapies to patients, specifically for neurodegenerative and autoimmune diseases.  One of their main compound in their pipeline, VCE-004.8 or EHP-101, a cannabidiol aminoquinone, is currently enrolling patients for its Phase II clinical trials for systemic sclerosis and multiple sclerosis. ,
In this article, Navarrete et al., aimed to investigate VCE-004.8’s potential role in the treatment of TBI.  Using in vitro and vivo assays, the group showed that the compound was able to induce angiogenesis (i.e., formation of new blood vessels), prevented BBB disruption, ameliorated early motor deficits, and preserved BBB integrity after TBI. They also showed that VCE-004.8 attenuated neuroinflammation and reduced neuronal death and apoptosis in the damaged area, suggesting this compound could be an interesting molecule to mediate TBI-associated effects.
The authors concluded: “Herein we provide evidence that the treatment with VCE-004.8…ameliorated BBB disruption and neuroinfammation, provided neuroprotection and improved neurological function after TBI… Therefore, identifying new strategies to alleviate neuroinfammatory responses and to protect from vascular endothelial cells damage might be crucial for the treatment of TBI and perhaps other neurological diseases cursing with neuroinfammation and BBB disruption.”
Towards Legalization of Medical Cannabis and Industrial Hemp Export in Albania?
Albania may join other European countries in legalizing the export of medical cannabis.
Albania, located on the Southeastern European Balkan Peninsula, is a small country bordered by Greece, North Macedonia, Montenegro, and Kosovo, known its beautiful mountains and lakes. In addition, it is one of the top countries for cannabis cultivation and distribution, according to the World Drug Report 2022 from the United Nations Office on Drugs and Crime, despite being cannabis being an illegal substance. 
In addition, cannabis smuggling to other European countries has been become a major crime issue in Albania over the last decades. To reduce this, a draft law was published on June 30th, 2022, titled “control of the cultivation and processing of the cannabis plant and the production of its by-products for medical and industrial purposes”, with the hopes to license private production of cannabis to up to 150 hectares of land starting in 2023. 
However, this does not mean that patients will have access to medical cannabis treatment, and we may need to wait a few more years before Albanians can obtain medical cannabis products.
Microdosing a Cannabinoid Extract to Treat Alzheimer’s Disease (AD): Report from Single Case Report
While encouraging, placebo-controlled trials are needed to validate the benefits of cannabinoid microdosing in the treatment of AD.
Alzheimer’s disease (AD) is the most common type of dementia, defined by the slowly progressive appearance of neuritic plaques and neurofibrillary tangles due to the accumulation of amyloid-beta peptide in key areas of the brain involved in memory, thought, and language (e.g., medical temporal lobes and neocortical structures).  According to the Centers for Disease Control and Prevention, it was estimated that as many as 5.8 million Americans were living with AD as of 2020.  While young individuals may get AD, it is more common in older population, specifically beyond age 65. Unfortunately, scientific experts are anticipating that AD will be the next global epidemic by 2050. As of today, two categories of medications are approved (e.g., acetylcholinesterase inhibitors and N-methyl-D-aspartate (NDMA) blockers) which can help slow down disease progression but cannot cure the disease. 
Emerging evidence indicate that the endocannabinoid system (ECS), one of the most interesting and fascinating biological system in our bodies, can play a key role during AD progression when it is not properly regulated.  Along those lines, the cannabis plant, containing more than 100 phytocannabinoids, has been of great interest over the last years due to its potential anti-inflammatory properties and its use in the treatment of mental illnesses. However, its role in treating AD is not clear in human studies.
A study published in the Journal of Medical Case Reports by Ruver-Martins et al. aimed to investigate whether treatment of orally administered micro dose phytocannabinoids extract (8:1 tetrahydrocannabinol (THC): cannabidiol (CBD)) can help improve symptoms in a 75-year-old patient with AD.  The patient was diagnosed with AD two years prior the start of the experimental paradigm and presented with symptoms including memory deficit, spatial and temporal disorientation. This trial was carried out for 22 months and evaluated the effects of this cannabis extract using cognitive and mental state scales.
The group found that cannabinoid microdosing was able to improve the patient’s cognitive function as noted by his caregiver who reported a substantial improvement in his quality of life. Additionally, the patient himself described the experience as “I used to find myself lost on the streets, I could not leave home unassisted; today, I took the bus by myself to perform my clinical evaluation.”
The authors concluded: “Our results are unprecedented and very encouraging… Data presented in this case report suggest that cannabinoid microdosing is a potential therapeutic for AD, with no significant side effects, although placebo-controlled clinical trials are needed to confirm and extend these data.”
Anger Rumination (AR) and Cannabis Use
This study was the first to examine the construct of anger rumination (AR) in the context of cannabis use.
While potentially associated with therapeutic benefits, over-consumption of the cannabis plant is a real phenomenon. This is known as cannabis dependence, characterized by symptoms of impaired control of cannabis use which can lead to an increase in withdrawal and craving characteristics.  According to the World Mental Health Survey, 9% and 3% of cannabis consumers display harmful use and dependence.  Additionally, numerous studies have shown that increased cannabis use often leads to higher levels of anger/hostility. , However, the association between the anger rumination (AR), a cognitive-emotional process that refers to the tendency to dwell on frustrating experiences and to recall past anger experiences is not well defined.
A group of researchers from Hungary aimed to investigate to potential role of AR and cannabis use motives on the relationship between hostility and problematic cannabis use.  Using standardized and online questionnaires measuring the frequency of hostility, AR symptoms, motives for cannabis use, and the level of problematic cannabis use, they were able to obtain information from 764 respondents, the majority being males (70%), with a median age of 29 years.
They found that a positive effect of hostility on cannabis use problems which was significantly mediated by coping motives, by AR, AR and coping motives, and AR and conformity motives. However, the group noted a few study limitations including possible over-representation of regular cannabis consumption in the sample population, causal associations and bidirectional relationships were not explored, or the lack of influence effect of outlier cases.
The authors concluded: “The present study was the first that examined the construct of AR in the context of cannabis use… Future research should consider using longitudinal research design (e.g., ecological momentary assessment) to explore the directional associations between the variables.”
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 https://clinicaltrials.gov/ct2/show/NCT04166552?term=Emerald+Health+Pharmaceuticals&rank=2, assessed on July 15th, 2022
 https://clinicaltrials.gov/ct2/show/NCT04909502?term=Emerald+Health+Pharmaceuticals&rank=3, assessed on July 15th, 2022
 Navarrete C, Garcia-Martin A, Correa-Saez A, et al. A cannabidiol aminoquinone derivative activates the PP2A/B55alpha/HIF pathway and shows protective effects in a murine model of traumatic brain injury. J Neuroinflammation 2022;19(1):177. DOI: 10.1186/s12974-022-02540-9.
 https://konsultimipublik.gov.al/Konsultime/Detaje/484, assessed on July 15th, 2022
 De-Paula, V.J.; Radanovic, M.; Diniz, B.S.; Forlenza, O.V. Alzheimer’s disease. Sub-Cell. Biochem. 2012, 65, 329–352.
https://www.cdc.gov/aging/aginginfo/alzheimers.htm#:~:text=In%202020%2C%20as%20many%20as,were%20living%20with%20Alzheimer’s%20disease.&text=Younger%20people%20may%20get%20Alzheimer’s,14%20million%20people%20by%202060, assessed on July 15th, 2022
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 Ruver-Martins AC, Bicca MA, de Araujo FS, et al. Cannabinoid extract in microdoses ameliorates mnemonic and nonmnemonic Alzheimer’s disease symptoms: a case report. J Med Case Rep 2022;16(1):277. DOI: 10.1186/s13256-022-03457-w.
 World Health Organization. (2018). International classification of diseases for mortality and morbidity statistics (11th Revision). https://icd.who.int/browse11/l-m/en
 Degenhardt L, Bharat C, Bruno R, et al. Concordance between the diagnostic guidelines for alcohol and cannabis use disorders in the draft ICD-11 and other classification systems: analysis of data from the WHO’s World Mental Health Surveys. Addiction 2019;114(3):534-552. DOI: 10.1111/add.14482.
 Dillon KH, Van Voorhees EE, Elbogen EB, Beckham JC, Workgroup VAM-AM, Calhoun PS. Cannabis use disorder, anger, and violence in Iraq/Afghanistan-era veterans. J Psychiatr Res 2021;138:375-379. DOI: 10.1016/j.jpsychires.2021.04.018.
 Wycoff AM, Metrik J, Trull TJ. Affect and cannabis use in daily life: a review and recommendations for future research. Drug Alcohol Depend 2018;191:223-233. DOI: 10.1016/j.drugalcdep.2018.07.001.
 Horvath Z, Kokonyei G, Sarosi P, Koos M, Demetrovics Z, Urban R. The mediating effect of anger rumination, coping and conformity motives on the association between hostility and problematic cannabis use. Addict Behav Rep 2022;16:100447. DOI: 10.1016/j.abrep.2022.100447.