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Weekly Cannabis News

January 28th to February 4th 2022

Does ∆9-Tetrahydrocannabinol (∆9-THC) Affect Motivational Behavior in Women?

A new study suggests that oral ∆9-THC administration decreases willingness to exert motivational effort for rewards in women.

The use of cannabis has long been associated with a lack of motivation, commonly referred to as “amotivational syndrome”, term first coined by Smith, denoting the diminished desire to work or to complete among young individuals who consumed cannabis frequently. [1] While several studies aimed to determine the direct effect of ∆9-THC on motivated behavior on humans, separating drug effects on motor performance from the effects on motivation has been difficult.

To correct this, Wardle et al. examined the effects of two doses of acute ∆9-THC compared to placebo on a task measuring willingness to exert effort for rewards in 40 women. [2] The authors found a THC dose-dependence decrease in hard task choices, especially at moderate to high expected values of reward, compared to placebo treated women. While this study did not look at the effects of CBD administration on willingness to exert effort, it does seem to support a dose-dependent detrimental effect of ∆9-THC alone on effort.

The authors concluded: “we found that oral administration of THC decreased willingness to exert effort for rewards compared to placebo… The information that cannabis seems to have acute impacts on motivation, particularly at higher doses, is important for providers who are counseling individuals with cannabis use disorder about potential problems associated with their use, and for individuals who are considering either abstaining from cannabis or changing their use to reduce associated harms.”

Can Cannabidiol (CBD) Be a Potential Candidate for Future Cancer Therapies?

CBD-rich extracts may represent an alternative therapy against myeloproliferative cancers, a new study suggests.

Cancer is a multifactorial disease, characterized by proliferation of cells that have managed to evade central endogenous control mechanisms. [3] It is the second leading cause of death in the United States and the leading cause of death in some western countries. [4] While there is no cure for the disease due to intrinsic cancer features, the development of novel anti-cancer therapies is on the rise. One of which is the potential use of cannabis extracts, shown to have molecular properties which may inhibit cancer molecular pathways. As such, previous studies have shown that CBD, a non-psychoactive molecule in the cannabis plant, can modulate the tumorigenesis in different cancer types and may represent a powerful source for complementary therapeutics of cancer disease. [5],[6]

Anceshi et al. aimed to further assess the properties of different cannabis extracts by characterizing their antiproliferative activities in chronic myelogenous leukemia cancer cells. [7]They found that CBD-rich extract inhibited cell proliferation in a dose-dependent manner and induced mechanisms of cell death in a cancer cell line.

The authors concluded: “this hemp extract and its pure component CBD deserve further investigation for a possible application against myeloproliferative diseases, also in association with other anticancer drugs… Further investigation by proteomics will be necessary to unveil the specific molecular targets of CBD-rich hemp extracts.”

Will Israel Be the Next Country to Legalize Cannabis?

Cannabis legalization in Israel: the next step towards exportation profits?

Israel is widely known for its historical and religious sites as well as for its technological and medical advancements. It is also one of the world leaders in medical cannabis consumption and hopes to become a pioneer in cannabis research, production, and exportation. It has been at the forefront of cannabis research since the 1960’s when Professor Raphael Mechoulam, an Israeli Professor at the Hebrew University of Jerusalem, first isolated the phytocannabinoid ∆9-THC tetrahydrocannabinol (∆9-THC) in 1964 as well as the endogenous cannabinoids (cannabinoids made in the body) anandamide and 2-arachidonoylglycerol and is considered the “father of cannabis research”. [8],[9]

While medical use was authorized for specific medical conditions (e.g., chronic pain, cancer, PTSD…) and cannabis possession decriminalized in 1999 and 2019, respectively, recreational use is still illegal. [10] However, this may change in the next coming years. Former Israeli Prime Minister Ehud Olmert is pushing towards cannabis legalization in hope not only to bring additional income in the local market but also to expand its cultivation and exportation. He told The Associated Press: “everything will change dramatically overnight if there will be legalization… the market would be unlimited. It would be huge. I really think that there is not a reason, except for some fears and obsessions and prejudices, that keeps (away) the complete legalization of cannabis.” This may bring huge growth in a fast-expanding sector where an increasing number of cannabis start-ups are being developed.

Subjective, Cognitive, Cardiovascular and Behavioral Measures in Adolescents vs Adults After ∆9-Tetrahydrocannabinol (∆9-THC) Use

Adolescents might be prone to more behavioral and cognitive impairments compared to adults following ∆9-THC consumption.

As more and more US states are legalizing cannabis for recreational use, understanding how it affects both adults and adolescents is critical. Along those lines, past year cannabis use in adults in the US has increased from 7.0 to 15.2 % but there are limited studies available to assess potential adverse effects associated with cannabis administration. [11] The cannabis plant contains more than 500 known compounds including cannabidiol (CBD) and ∆9-THC, interacting with many different types of receptors in the human body. Notably, ∆9-THC binds to cannabinoid receptor 1 (CB1R), in which its expression is higher during adolescence than any other period of life. [12] Preclinical evidence also suggests that there are greater acute effects of ∆9-THC during adolescence but limited studies are available.

To solve this, Murray et al. investigated the effects of ∆9-THC administration vs. placebo in both adolescents (n=12) and adults (n=12) (who reported less than 20 total lifetime uses of cannabis and no cannabis use in the 30 days) using a wide array of different physiological and behavioral measures. [13]  They found that adolescents in the THC group were more sensitive to performance impairing effects including reaction time, response accuracy, and time perception, as well as behavioral and cognitive effects. No differences on cardiovascular and subjective measures were noted between adolescents and adults. Some of the reported limitations were the low sample size, which was insufficient to detect sex differences, differences in the ability to identify the drug each group received, and restricted demographic characteristics.

Overall, the authors concluded: “our findings indicate that adolescents are more sensitive than adults to the effects of THC on cognitive performance and on measures of neural function, but not to cardiovascular effects or subjective measures… compared to adults, adolescents may exhibit greater behavioral or neural impairment at doses that produce similar feelings of intoxication.”

References

[1] Smith DE. Acute and chronic toxicity of marijuana. Journal of Psychoactive Drugs. 1968;2(1):37–48.

[2] Wardle MC, Pabon E, Webber HE, de Wit H. Delta-9-tetrahydrocannabinol reduces willingness to exert effort in women. Psychopharmacology (Berl) 2022. DOI: 10.1007/s00213-021-06032-1.

[3] Krieghoff-Henning E, Folkerts J, Penzkofer A, Weg-Remers S. Cancer – an overview. Med Monatsschr Pharm 2017;40(2):48-54.

[4] Dagenais GR, Leong DP, Rangarajan S, et al. Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet 2020;395(10226):785-794. DOI: 10.1016/S0140-6736(19)32007-0.

[5] Kis B, Ifrim FC, Buda V, et al. Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer. Int J Mol Sci 2019;20(23). DOI: 10.3390/ijms20235905

[6] Luca Roncati, Maria Vadalà, Veronica Corazzari, Beniamino Palmieri. Immunohistochemical expression of cannabinoid receptors in women’s cancers: what’s new?. Eur. J. Gynaecol. Oncol. 2021, 42(2), 193–195https://doi.org/10.31083/j.ejgo.2021.02.5463

[7] Anceschi L, Codeluppi A, Brighenti V, et al. Chemical characterization of non-psychoactive Cannabis sativa L. extracts, in vitro antiproliferative activity and induction of apoptosis in chronic myelogenous leukaemia cancer cells. Phytother Res 2022. DOI: 10.1002/ptr.7357.

[8] Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258(5090):1946-9. DOI: 10.1126/science.1470919.

[9] Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995;50(1):83-90. DOI: 10.1016/0006-2952(95)00109-d.

[10] https://www.haaretz.com/israel-news/.premium-marijuana-decriminalization-goes-into-effect-in-israel-what-does-that-mean-1.7069271

[11] U.S. Department of Health and Human Services SAaMHSA, Center for Behavioral Health Statistics and Quality. (2019).

[12] Meyer HC, Lee FS, Gee DG. The role of the endocannabinoid system and genetic variation in adolescent brain development. Neuropsychopharmacology. 2018;43:21–33

[13] Murray CH, Huang Z, Lee R, de Wit H. Adolescents are more sensitive than adults to acute behavioral and cognitive effects of THC. Neuropsychopharmacology 2022. DOI: 10.1038/s41386-022-01281-w.

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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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