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Weekly Cannabis News

January 14th – 21st, 2022

Cannabis Use May be Linked to Defects in Cognitive Function

Results from a meta-analysis suggest that cannabis consumption may lead to cognitive impairments.

Despite an increasing number of US states legalizing cannabis for medical and recreational purposes, the long-term effects associated with its use are not entirely understood. While it may provide therapeutic effects in a wide range of conditions, exaggerated cannabis consumption can lead to cannabis use disorder (CUD), broadly defined as the inability to stop consuming cannabis even when it is causing physical or psychological harm. [1]

Moreover, the cannabis plant contains more than 500 known compounds including the non-psychoactive molecule, cannabidiol (CBD) and the psychoactive molecule, ∆9-tetrahydrocannabinol (∆9-THC).  Both molecules interact with the endocannabinoid system (ECS) in humans, with ∆9-THC partially activating both cannabinoid receptor 1 and 2 (CB1R, CB2R) while CBD blocks CB1R and inhibits signaling from CB2R. [2],[3]  Previous studies have shown that CB1R are expressed in the central nervous system (CNS), most specifically in areas of the brain responsible for learning and memory as well as cognitive and psychomotor functions. As such, understanding the potential impact that cannabis may have on cognitive impairment is critical.

Canadian researchers performed a meta-analysis, a research process used to synthesize and merge findings from single independent studies, to investigate the magnitude of acute and residual effects of cannabis on cognitive function.[4] They extracted information from 10 independent studies and divided the findings into executive functions, learning and memory, complex attention, processing speed, perceptual motor function, and language. From this analysis, they found that verbal learning and memory were the most impaired by acute cannabis intoxication and persisted beyond intoxication as well as reported some deficits in inhibitory processes and working memory.

They concluded: “meta-analytical data on the acute effects of cannabis use on neurocognitive function have shown that cannabis intoxication leads to small to moderate deficits in numerous cognitive domains, most notably executive functions, verbal learning and memory and processing speed. These acute impairments accord with documented residual effects, suggesting that the detrimental effects of cannabis persist beyond acute intake.”

One drawback of this study is the lack of information on the type of cannabis products as well as the route of administration used by the participants.

Will Mississippi be the Next State to Legalize Medical Cannabis?

The Mississippi House of Representatives passed a new bill with amendments which would legalize the use of medical cannabis for patients with specific medical conditions.

Despite being decriminalized since 1978, the progress towards cannabis legalization for both medical and recreational purposes have been slow.  In 2014, Mississippi Governor Phil Bryant signed the “Harper Grace’s Law”, authorizing the use of low THC: CBD oils for specific medical conditions. [5]  In November 2020, medical cannabis use was legalized as measure 65 but was overturned by the Supreme Court of Mississippi in May 2021.[6] However, exciting news arrived this week with the Mississippi House of Representatives passing a new medical bill (MS SB2095) allowing legalization of medical cannabis.[7] As such, consumers with specific medical conditions (i.e., cancer, sickle cell disease, glaucoma, or dementia) would be able to obtain up to 3.5 g of cannabis per day, up to six days a week.

Increase in Calls to Illinois Poison Control (IPC) Among the Pediatric Population Following Cannabis Exposure

Legalization of recreational cannabis in Illinois led to an increase in the number of cannabis exposure calls to IPC.

Consuming cannabis via ingestion using edibles, candies, or drinks have increased over the last years, especially among adolescents. [8] This method is difficult to get the appropriate dosage due to a slower absorption rate and as such, may result in larger than expected quantity ingested and may cause delusions, hallucinations, and confusions. [9]

Consequently, over-consumption of these products led to an increase in the rates of acute cannabinoid intoxication (ACI) with US poison control centers reporting a dramatic increase in the number of reports involving edibles, rising from 8.3% to 31.2% from 2017 to 2019. [10]

A study published last week in the Journal JAMA Network Open found a significant increase in the proportion of cannabis-related ED visits with hospitalization during periods following legalization of commercially edible products in Ontario, Canada. [11] New reports from the IPC indicate that there is an increase in the numbers of calls since the legalization of recreational cannabis on January 1st, 2020, specifically linked to the consumption of edibles ranging from 80 calls in 2019 to 347 in 2020 and 450 in 2021. More specifically, a similar increase was reported among children ranging from 81 calls in 2019 to 202 calls in 2020 and 278 calls in 2021. [12]

 As a warning, the IPC posted on their website that cannabis edibles are toxic to children with symptoms including drowsiness, loss of muscle coordination or control, and increase heart rate and coma. [13]

Can Cannabidiol (CBD) Prevent SARS-CoV-2 Infections?

CBD may have the potential to fight prevent SARS-CoV-2 infections and deserves additional attention, a new study suggests.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) or COVID-19 is the most recent and currently occurring viral epidemic, first reported in December 2019 in Wuhan, China before spreading worldwide. [14]

While the FDA has authorized COVID-19 vaccines, their limited availability and the increased rate of virus mutation have led to a search for additional therapeutics which may help prevent entry of the virus.

SARS-CoV-2 is expelled in respiratory droplets from an infected individual and subsequently inhaled by another non-infected individual.  Common symptoms including cough, fever, respiratory distress, muscle pain, sore throat, loss of taste and/or smell, which may lead to severe illness and death. [15]

The cannabis plant contains more than 500 known compounds including phytocannabinoids, terpenes and flavonoids, with as many as 140 different phytocannabinoids present including the non-psychoactive molecule, cannabidiol (CBD) and the psychoactive molecule, ∆9-tetrahydrocannabinol (∆9-THC). Both molecules interact with the endocannabinoid system (ECS) in humans, with ∆9-THC partially activating both cannabinoid receptor 1 and 2 (CB1R, CB2R) while CBD blocks CB1R and inhibits signaling from CB2R. [16],[17]  A study published last week in the Journal of Natural Products showed that the cannabinoid compounds cannabigerolic acid (CBGA) and cannabidiolic acid (CBDA) inhibited the SARS-CoV-2 cell entry in human cells incubated with the live SARS-CoV-2 virus and other variants. [18] 

Researchers at the University of Chicago aimed to determine whether CBD use may be an important agent to prevent entry of the SARS-CoV-2 virus in human cells and mice. [19]  They found that CBD was a potent inhibitor of SARS-CoV-2 infection as well as inhibited viral expression in human cells.  Furthermore, mice who were injected twice daily for seven days with CBD prior to SARS-CoV-2 administration (and for four additional days following) showed an inhibition of viral replication in lungs and nasal turbinates at day 5 post-infection with no signs of clinical disease and weight change reported. Finally, they report that in a matched group of human patients, CBD usage is negatively associated with indications of SARS-CoV-2 infections in patients and as such, they recommend the start of CBD-based clinical trials.

They concluded: “this study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials.  However, we strongly caution against the temptation to take CBD in presently available formulations including edibles, inhalants or topicals as a preventative or treatment therapy at this time, especially without the knowledge of a rigorous randomized clinical trial with this natural product.”

References

[1] Connor JP, Stjepanovic D, Le Foll B, Hoch E, Budney AJ, Hall WD. Cannabis use and cannabis use disorder. Nat Rev Dis Primers 2021;7(1):16. DOI: 10.1038/s41572-021-00247-4

[2] Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008;153(2):199-215. DOI: 10.1038/sj.bjp.0707442

[3] Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol 2007;150(5):613-23. DOI: 10.1038/sj.bjp.0707133

[4] Dellazizzo L, Potvin S, Giguere S, Dumais A. Evidence on the acute and residual neurocognitive effects of cannabis use in adolescents and adults: a systematic meta-review of meta-analyses. Addiction 2022. DOI: 10.1111/add.15764.

[5] https://law.justia.com/codes/mississippi/2014/title-41/chapter-29/article-3/section-41-29-136

[6] https://courts.ms.gov/Images/Opinions/CO154253.pdf

[7] https://legiscan.com/MS/bill/SB2095/2022

[8] Knapp AA, Lee DC, Borodovsky JT, Auty SG, Gabrielli J, Budney AJ. Emerging Trends in Cannabis Administration Among Adolescent Cannabis Users. J Adolesc Health 2019;64(4):487-493. DOI: 10.1016/j.jadohealth.2018.07.012.

[9] MacCoun RJ, Mello MM. Half-baked–the retail promotion of marijuana edibles. N Engl J Med

2015;372(11):989-91. DOI: 10.1056/NEJMp1416014.

[10] Dilley JA, Graves JM, Brooks-Russell A, Whitehill JM, Liebelt EL. Trends and Characteristics of Manufactured Cannabis Product and Cannabis Plant Product Exposures Reported to US Poison Control Centers, 2017-2019. JAMA Netw Open 2021;4(5):e2110925. DOI: 10.1001/jamanetworkopen.2021.10925

[11] Myran DT, Cantor N, Finkelstein Y, et al. Unintentional Pediatric Cannabis Exposures After Legalization of Recreational Cannabis in Canada. JAMA Netw Open 2022;5(1):e2142521. DOI: 10.1001/jamanetworkopen.2021.42521

[12] https://newschannel20.com/news/local/pediatric-cannabis-exposure-calls-to-il-poison-control-have-increased-243-since-2019

[13] https://stage.illinoispoisoncenter.org/my-child-ate/cannabis-edibles

[14] Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020;382(8):727-733. DOI: 10.1056/NEJMoa2001017

[15] Lovato A, de Filippis C, Marioni G. Upper airway symptoms in coronavirus disease 2019 (COVID-19). Am J Otolaryngol 2020;41(3):102474. DOI: 10.1016/j.amjoto.2020.102474

[16] Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008;153(2):199-215. DOI: 10.1038/sj.bjp.0707442

[17] Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol 2007;150(5):613-23. DOI: 10.1038/sj.bjp.0707133

[18] van Breemen RB, Muchiri RN, Bates TA, et al. Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants. J Nat Prod 2022. DOI: 10.1021/acs.jnatprod.1c00946

[19] Nguyen LC, Yang D, Nicolaescu V, et al. Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response. Sci. Adv 2022 eabi61000

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Author Yoel H. Sitbon

Yoel is a Medical Writer in the Medical Content division at Csequence. His scientific expertise is in Neuroscience (neural mechanisms behind drug addiction) and Molecular & Cellular Pharmacology (molecular mechanisms behind mutations induced cardiovascular diseases). Yoel has over five years of scientific writing experience as evidenced by 8 peer-reviewed publications in scientific journals. He is an effective oral communicator having presented his PhD thesis work at many biomedical conferences nationally. He also has strong mentorship and leadership experience. Yoel has a B.S in Neuroscience at the University of California, Los Angeles and a Ph.D. in Molecular & Cellular Pharmacology at the University of Miami, Miller School of Medicine.

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