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IACM-Bulletin of 28 January 2024

Science/Human: CBD may reduce symptoms in infantile epileptic spasms syndrome

Pure CBD may be helpful in the treatment of about two thirds of children with treatment-resistant epileptic spasms syndrome. Investigators of several hospitals in Argentine conducted a retrospective analysis of clinical records of 28 children aged 6 to 21 months, who received CBD between 2021 and 2023. The cause was structural in 10, Down syndrome in seven, genetic in nine, and unknown in two. Initial CBD dose was 2 mg/kg/day, which was uptitrated to a median dose of 25 mg/kg/day.

Prior to CBD initiation, patients had a median of 69 epileptic spasms in clusters per day

and 10 focal seizures per week. After a mean follow-up of 15 months, seven patients were free of spasms and 12 had a reduction of more than 50%. Five of seven patients (71 %) with Down syndrome and 3/5 (60 %) with cerebral palsy responded well.

Reyes Valenzuela G0, Gallo A, Calvo A, Chacón S, Fasulo L, Galicchio S, Adi J, Fortini PS, Caraballo R. Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome. Seizure. 2024;115:94-99.

Science/Human: Many cancer patients use cannabis for pain management

According to a survey with 5523 cancer patients those suffering from pain were twice as likely to use cannabis compared to those without pain. The study was conducted by investigators of the Ohio State University College of Medicine in Columbus, USA.

Cannabis use was slightly more prevalent in those undergoing active treatment relative to those who were not undergoing active treatment (9% vs. 6%). Those under active treatment were more likely to use cannabis medicinally (72% vs. 50%). Relative to those without cancer-related pain, persons with pain under medical control or uncontrolled pain were twice as likely to use cannabis.

Krok-Schoen JL, Plascak JJ, Newton AM, Strassels SA, Adib A, Adley NC, Hays JL, Wagener TL, Stevens EE, Brasky TM. Current cannabis use and pain management among US cancer patients. Support Care Cancer. 2024;32(2):111.

Science/Human: CBD dominant cannabis may reduce tension in patients with anxiety

In a study by investigators of the Institute of Cognitive Science at the University of Colorado in Boulder, USA, 42 participants with anxiety symptoms who were not using cannabis were compared to 258 participants with anxiety symptoms who used cannabis flower about 3 to 4 times per week. Participants who used cannabis were randomly assigned to one of three legal market cannabis conditions; THC-dominant, THC+CBD, or CBD-dominant.

While all participants reported anxiety reductions over the 4-week study on several validated scales, ad libitum CBD-dominant cannabis use was associated with lower scores on an anxiety subscale compared to THC-dominant use. Similarly, acute CBD-dominant cannabis use was associated with lower scores on a tension and paranoia subscale. Participants in all cannabis conditions experienced acute changes in positive mood and subjective drug effects.

Bidwell LC, Martin-Willett R, Skrzynski C, Lisano J, Ortiz Torres M, Giordano G, Hutchison KE, Bryan AD. Acute and Extended Anxiolytic Effects of Cannabidiol in Cannabis Flower: A Quasi-Experimental ad libitum Use Study. Cannabis Cannabinoid Res. 2024 Jan 22. [in press]

Science/Human: Cannabis use in adolescence may not be associated with reduced educational attainment, while alcohol use may

In a large birth cohort study with a 17 year follow-up higher frequency of alcohol intoxication in adolescence was associated with poorer educational outcomes, while cannabis use was not. Investigators of the Department of Psychiatry at the University of Helsinki, Finland, examined prospective associations of drug use at age 15 to 16 years with subsequent educational attainment obtained from comprehensive registers until age 33 in Northern Finland Birth Cohort 1986 (6564 individuals).

Younger age at first intoxication, higher frequency of alcohol intoxication, and high self-reported alcohol tolerance at age 15/16 years were associated with poorer educational outcomes by the age of 33 years. The association between adolescent cannabis use and educational attainment in adulthood was no longer statistically significant after adjusting for confounders including frequency of alcohol intoxication at age 15/16.

Levola J, Alakokkare AE, Denissoff A, Mustonen A, Miettunen J, Niemelä S. Adolescent alcohol and cannabis use and early adulthood educational attainment in the 1986 Northern Finland birth cohort study. BMC Public Health. 2024;24(1):255.

Science/Human: The therapeutic use of cannabis extracts may improve driving ability in patients suffering from Tic disorders

According to results of the "Fitness to Drive" sub study of the CANNA-TICS trial, which investigated the effects of a cannabis extract (Sativex) on symptom severity in patients with tic disorders, cannabis treatment may improve driving ability in those, who were not able to drive at baseline. In the study by investigators of the Clinic of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany, the key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment with the cannabis extract or a placebo.

In the sub study, a total of 64 patients were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with cannabis, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. Authors concluded that “treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment.”

Müller-Vahl KR, Pisarenko A, Ringlstetter R, Cimpianu CL, Fremer C, Weidinger E, Jenz EB, Musil R, Brunnauer A, Großhennig A. The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial. Cannabis Cannabinoid Res. 2024 Jan 23. [in press]

News in brief

Australia: 50% of Australians would support a bill that legalizes growing cannabis for personal use

According to a poll, overall, Australian voters are more for, than against, a new bill that has been proposed in the Parliament of New South Wales. This bill is in favor of legalizing the cultivation of up to six cannabis plants at home for personal use. The proposed legalization would also allow growers to share the plants with their friends. In total, 50% of Australians supported the proposition, with only 31% opposing the motion. 19% were on the fence.

YouGov of 2 January 2024

USA: Cannabis use by teens fell significantly in King County and the reason may be legalization of cannabis

Researchers of the US Centers for Disease Control and Prevention reported that cannabis use fell 60 percent among male teens and 42 percent among female teens from 2012 to 2021 in Kings County, Washington, USA. Washington voters approved a ballot initiative legalizing the adult use market in 2012. The study’s authors suggested that legalization likely made it more difficult for teens to access cannabis. “The observed overall decreases in cannabis use among students in grades 8, 10, and 12 might be associated with changes in the availability of cannabis among persons aged ≥21 years as well as limited opportunities to engage in use,” they wrote.

CDC of 18 January 2024

Science/Animal: Cannabichromene (CBC) may reduce pain

Following tests with mice investigators concluded that their “results suggest that CBC targets receptors involved in nociceptive signaling and imparts antinociceptive properties that may benefit males and females afflicted with diverse forms of acute or chronic/persistent pain.”

Department of Pharmacology, Penn State College of Medicine, Hershey, USA.

Raup-Konsavage WM, et al. Biomedicines. 2023;12(1):83.

Science/Animal: THC rich extract may prevent weight gain

According to studies with mice “THC-enriched extract prevented weight gain by a high-fat diet and attenuated diet-induced liver steatosis concomitantly with reduced levels of the lipid mediators palmitoyl ethanolamide (PEA) and docosahexaenoyl ethanolamide (DHEA) in the liver. In contrast, CBD-enriched extract had no effect on weight gain, but, on the contrary, it even exacerbated liver steatosis.”

The Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel.

Eitan A, et al. Int J Mol Sci. 2024;25(2):1073.

Science/Animal: Essential oils of cannabis may reduce inflammation

Findings of mouse studies suggest a therapeutic value of cannabis essential oils “in the management of arthritis and inflammatory diseases while highlighting the need for further in-depth research to study the molecular mechanisms and validate their safety and efficacy for clinical applications.“

Laboratory of Pharmacology, Neurobiology, Anthropology and Environment, Department of Biology, Faculty of Sciences Semlalia, University Cadi Ayyad, Marrakech, Morocco.

Kabdy H, et al. Pharmaceuticals (Basel). 2023;17(1):20.

Science/Animal: CBD derivatives may be potent broad-spectrum antibacterial agents

A CBD derivative “showed potent in vivo antibacterial efficacy in murine corneal infection models caused by Staphylococcus aureus or Pseudomonas aeruginosa. These findings would provide a new design idea for the discovery of novel broad-spectrum antibacterial agents to overcome the antibiotic resistance crisis.”

The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.

Fang S. et al. Eur J Med Chem. 2024;266:116149.

Science/Human: The number of young adults with depression, who use cannabis, increased after legalization

Results of a new study from the US “suggest that the association between prevalence rates of young adult depression and cannabis use strengthened following recreational legalization in the U.S. This is potentially due to increases in cannabis accessibility and the acceptance of the health benefits of cannabis, which may enhance the use of cannabis as a coping mechanism among young adults with depression.”

Department of Geography and Urban Studies, Temple University, Philadelphia, USA.

Mennis J. Am J Prev Med. 2024;66(2):333-341.

Science/Human: Asthma in adolescents was higher among youth with cannabis use

Using a large US database researchers found that “asthma was greater among youth who reported more frequent cannabis use; asthma was highest among youth who reported having used cannabis "40 or more times" in the month.”

Department of Epidemiology and Biostatistics, Graduate School of Public Health and Health Policy, The City University of New York, USA.

Silverman KD, et al. Pediatr Pulmonol. 2024 Jan 19. [in press]

Science/Animal: CBD may reduce the consequences of sepsis

In a study with rats with sepsis “CBD alone improved the cognitive impairment, which was accompanied by restoration of BDNF, reduced neuroinflammation, and oxidative stress, mainly in the hippocampus. “

Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, Santa Catarina, Brazil.

Frederico Gava F, et al. Brain Res. 2024:148771.

Science/Human: Cannabis use had no effect on the outcome of cancer patients treated with PARPi

According to a study with 93 cancer patients medical cannabis usage in patients receiving treatment with PARPi (poly (ADP-ribose) polymerase inhibitors) “showed no association with duration of PARPi therapy, progression-free survival, or overall survival.”

Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Peleg Hasson S, et al. Int J Gynecol Cancer. 2024:ijgc-2023-004953.

Science/Human: Cannabis use is associated with reduced inflammation in tissues in men with HIV

In tissues of 20 men with HIV, taken from them after death, cannabis use was “associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs.”

School of Biological Sciences, University of Nebraska-Lincoln, USA.

Liu Z, et al. J Infect Dis. 2024:jiad575.

Science/Animal: CBD may reduce the stress level in dogs

“Daily dosing of cannabidiol (CBD) demonstrates a positive effect on measures of stress in dogs during repeated exposure to car travel.”

Waltham Petcare Science Institute, Waltham on the Wolds, United Kingdom.

Flint HE, et al. J Anim Sci. 2024:skad414.

Science/Animal: How CBD suppresses the secretion of the pro-inflammatory cytokine TNF-alpha

“The mechanism by which cannabidiol (CBD) suppresses TNF-α secretion involves inappropriate localization of TNF-α converting enzyme (TACE).”

Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, USA.

Frodella CM, et al. Cell Immunol. 2024;397-398:104812.

Science/Animal: THC during pregnancy reduces birth weight

In studies with pregnant rats vaporized THC “results in reduced birthweight, increased locomotion, and altered wake-cycle activity dependent on dose, sex, and diet in the offspring.”

Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, USA.

Roeder NM, et al. Life Sci. 2024:122447.

Science/Cells: CBD enhances photodynamic therapy effects on breast cancer cells

In studies with breast cancer cells the effects of photodynamic therapy were enhanced by a combination with cannabidiol and this caused programmed cell death (apoptosis).

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa.

Mokoena D, George BP, Abrahamse H. Cells. 2024;13(2):187.

Science/Human: Patients with cystic fibrosis often use cannabis

According to a survey with 226 participants suffering from cystic fibrosis, 29% used cannabis, 22% used CBD, 27% used e-cigarettes, and 22% used cigarettes in the last 12 months.

Department of Pediatrics, University of California San Francisco, USA.

Vaziri S, et al. Pediatr Pulmonol. 2024 Jan 22. [in press]

Science/Human: Cannabis and opioid codependence contribute to cognitive impairment

Investigators selected adult participants, who met the diagnosis of opioid dependence (N = 268), of opiate dependence and cannabis use (N = 58), and opioid dependence and cannabis dependence  (N = 115), who were investigated for cognitive abilities. They concluded: “Cannabis and opioid co-dependence contribute to cognitive impairments, especially in working memory and executive functions.”

Drug Deaddiction and Treatment Centre, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Ghosh A, et al. J Psychoactive Drugs. 2024:1-13.

Science/Human: CBD treatment is associated with anti-inflammatory effects in people with HIV

Researchers analyzed peripheral blood mononuclear cells of 3 patients living with HIV before and 27 to 60 days after CBD treatment. They “obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells.”

Department of Epidemiology, University of Florida, Gainesville, USA.

Marini S, et al. Cannabis Cannabinoid Res. 2024 Jan 22. [in press]

Science/Human: Cold exposure increases the levels of anandamide

Cold exposure activates brown adipose tissue and potentially improves cardio metabolic health through the secretion of signaling lipids. “Here, we show that 2 h of cold exposure in young adults increases the levels of omega-6 and omega-3 oxylipins, the endocannabinoids (eCBs) anandamide and docosahexaenoylethanolamine, and lysophospholipids containing polyunsaturated fatty acids.”

Department of Physical Education and Sports, Faculty of Sports Science, Sport and Health University Research Institute (iMUDS), University of Granada, Spain.

Jurado-Fasoli L, et al. Cell Rep Med. 2024:101387.

Science/Review: The therapeutic potential of CBD in psychiatric disorders

“Of the 150 articles identified, 54 publications were included, covering the effects of CBD on healthy subjects and various psychiatric conditions, such as schizophrenia, substance use disorders (SUDs), anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders.”

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.

Dammann I, Rohleder C, Leweke FM. Pharmacopsychiatry. 2024 Jan 24. [in press]

Science/Review: The pharmacokinetics of THC may be altered during pregnancy

“The clearance and distribution processes of THC and its metabolites likely change in pregnancy. Hepatic CYP2C9 and CYP3A4 are known to be induced in pregnant individuals and in vitro by pregnancy hormones. this induction of CYP2C9 and CYP3A4 is predicted to lead to altered THC and 11-OH-THC disposition and potential change in pharmacodynamic effect.”

Department of Pharmaceutics, School of Pharmacy, University of Washington, USA.

Authement AK, Isoherranen N. Expert Opin Drug Metab Toxicol. 2024 Jan 23. [in press]

Science/Review: Review on the interplay between the gut microbiome and cannabis

“This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.”

NICM Health Research Institute, Western Sydney University, Penrith, Australia.

Al-Khazaleh AK, et al. Int J Mol Sci. 2024;25(2):872.

Science/Review: The interplay of cannabis constituents

“This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.”

NICM Health Research Institute, Western Sydney University, Penrith, Australia.

Al-Khazaleh AK, et al. Molecules. 2024;29(2):410.