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IACM-Bulletin of 11 February 2024

Science/Human: CBD reduces brain temperature in the seizure onset zone of patients with epilepsy

Investigators of the Department of Neurology at the University of Alabama at Birmingham, USA investigated 25 participants with magnetic resonance spectroscopic imaging approximately 12-weeks apart. Eight patients with treatment resistant epilepsy were imaged before receiving Epidiolex, a CBD rich cannabis extract, and after 12 weeks of CBD therapy. Treatment was started at a daily dose of 5 mg/kg, with bi-weekly titration based on response and tolerability. Seventeen healthy controls were also imaged twice.

Participants with treatment resistant epilepsy had abnormally high peak brain temperatures within their seizure onset zone that decreased after CBD initiation. Seizure severity scores also improved after CBD initiation. Authors noted these “findings provide insights into the possible neural effects of CBD”, and further demonstrate the potential of magnetic resonance spectroscopic imaging as a tool for delineating the seizure onset zone.

Sharma AA, Szaflarski JP. The longitudinal effects of cannabidiol on brain temperature in patients with treatment-resistant epilepsy. Epilepsy Behav. 2024;151:109606.

Science/Human: CBD reduces inflammation of the gingiva in a placebo-controlled study

According to a placebo-controlled study CBD (cannabidiol) in a dental gel and toothpaste reduced gingival inflammation. Investigators of the Faculty of Medicine and Dentistry at the Palacky University in Olomouc, Czech Republic, first demonstrated that cells of the gingiva express the CB2 receptor. The clinical study was conducted for 56 days in 90 participants divided into three groups using dental gel without CBD (group A) and with 1% CBD (group B) and corresponding toothpaste for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate and toothpaste without CBD.

The basic research showed that CBD exerts anti-inflammatory and antimicrobial effects. In the clinical part, significant improvement was found for gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. Authors concluded that CBD “reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application.”

Jirasek P, Jusku A, Frankova J, Urbankova M, Diabelko D, Ruzicka F, Papouskova B, Chytilova K, Vrba J, Havlasek J, Langova K, Storch J, Voborna I, Simanek V, Vacek J. Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol. J Periodontal Res. 2024 Feb 5. [in press]

Science/Cells: Increase of the concentration of anandamide may improve treatment results against melanoma

In a study with melanoma cells an increase of anandamide concentrations induced by a synthetic compound (AM1172) increased the anti-cancer effects of the chemotherapeutic agents docetaxel, mitoxantrone and cisplatin. The anti-cancer effects of paclitaxel were also improved in most melanoma cell lines.

Department of Occupational Medicine, Medical University of Lublin, Poland.

Marzęda P, et al. Pharmacol Rep. 2024;76(1):154-170.

Science/Cells: Cannabinoid glycosides show anti-cancer effects in several cancer cell lines

Scientists were able to produce cannabinoid glycosides from a cannabis extract. “These glycosides exhibit improved anti-proliferative and anti-metastatic effects against numerous cancer cell lines in vitro and are more water-soluble and stable than their parent cannabinoids.”

Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.

Nalli Y, et al. Bioorg Chem. 2024;143:107030.

Science/Cells: Spirochetes are resistant to CBD

Oral spirochetes, unlike some other periodontal bacteria, are resistant to physiological doses of CBD. Authors noted that these “findings should be considered in the context of the reported enhanced susceptibility to periodontitis in cannabis users.”

Department of Oral Immunology and Infectious Diseases, University of Louisville, USA.

Tan J, et al. J Clin Periodontol. 2024;51(2):222-232.

Science: Development of a dual agonist to the CB2 and 5-HT(1A) receptors for the treatment of depression

Scientists developed a synthetic derivative of CBD, which acts as a dual agonist and activates both the CB2 receptor and the 5-HT(1A) receptor. Behavioral experiments in mice showed that the substance “elicits significant antidepressant-like and anxiolytic-like effects while maintaining a good safety profile.”

Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, China.

Yang W, et al. Eur J Med Chem. 2024;265:116048.

Science/Animal: Mulberry extracts may influence the endocannabinoid system

Studies with mice showed that Mulberry (Morus alba L.) leaf water extract attenuates type 2 diabetes mellitus by regulating gut microbiota dysbiosis, lipopolysaccharide elevation and endocannabinoid system disorder.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

Du Y, et al. J Ethnopharmacol. 2024;323:117681.

Science/Animal: Many Danish dog owners use CBD for the treatment of their pets and a few use THC

The total number of respondents to an online survey was 2,002, of which 38% indicated using or having administered cannabinoids to their dog. The majority of the respondents confirming the use of cannabinoids (93%) had used cannabidiol drops/oil and only few (4%) reported using THC products.

Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Holst P, Kristensen AT, Arendt ML. PLoS One. 2024;19(1):e0296698.

Science/Animal: CBD exerts sedative effects through activation of the 5-HT(1A) receptor

In a study with mice “results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD.”

Shenyang Pharmaceutical University, Shenyang, China.

Liu YM, et al. Neurochem Res. 2024 Jan 31. [in press]

Science/Human: THC impairs 20-minute cycling time trial performance

“Cannabis containing THC alters the physiological response to maximal and submaximal exercise, largely independent of the inhalation method. THC-containing cannabis negatively impacts vigorous exercise performance during a sustained 20-min effort, likely due to physiological and psychotropic effects. Inhalation of cannabis devoid of THC and primarily containing CBD has little physiological effect on the exercise response or performance.”

Human Health and Nutritional Sciences, University of Guelph, Canada.

Cheung CP, et al. J Appl Physiol (1985). 2024 Feb 1. [in press]

Science/Human: CBD did not affect disease progression or survival in advanced cancer

Investigators reviewed the clinical records of all advanced cancer patients enrolled in the MEDCAN-1 Study (CBD vs placebo) at days 14, 28 and 56 of study follow-up, for evidence of disease progression. They started with 50 mg CBD once daily, which was increased up to 200 mg of CBD thrice daily. “CBD oil did not affect disease progression or survival over the course of 56 days in patients with advanced cancer.”

Oncology, Mater Cancer Care Centre, South Brisbane, Australia.

O'Leary C, et al. BMJ Support Palliat Care. 2024:spcare-2023-004746.

Science/Human: Regular cannabis users have only minor deficits in psychomotor performance

In this study 23 occasional cannabis users, 31 daily users and 32 non-users completed a tablet-based test battery before and about 60 minutes after cannabis smoking. The occasional use group exhibited decrements in reaction time and short-term memory from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change.

Injury and Violence Prevention Center, Colorado School of Public Health, University of Colorado, Aurora, USA.

Brooks-Russell A, et al. J Cannabis Res. 2024;6(1):3.

Science/Human: THC may not improve dyspnoea and exercise capacity in COPD

In a placebo-controlled trial with 8 patients suffering from COPD isolated THC or “dronabinol did not significantly improve dyspnea or exercise capacity compared with placebo.”

Pulmonary-Critical Care, Loma Linda University Medical Center, Loma Linda, USA.

Zaid AH, et al. Chronic Obstr Pulm Dis. 2024 Feb 2. [in press]

Science/Human: A majority of French psychiatrists are in favor of cannabis legalization

According to a survey with 413 French psychiatrists “253 (61.3%) declared being in favor of recreational cannabis, and 349 (84.4%) of medical cannabis. (…) Most respondents were concerned about the development of psychotic disorders. The most frequent pro-legalization arguments were improved prevention, better control of product content, and better protection of youth, respectively.”

Service universitaire d'addictologie de Lyon (SUAL), hospices civils de Lyon, France.

Leclerc L, et al. Encephale. 2024:S0013-7006(23)00215-4.

Science/Animal: Increased concentrations of endocannabinoids exhibit anxiolytic effects

In a study with mice a synthetic inhibitor of endocannabinoid degradation (both of anandamide and 2-AG) exhibited anxiolytic effects. They received “JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase.” Authors concluded that these “results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.”

Key Laboratory of Modern Teaching Technology, Ministry of Education, Shaanxi Normal University, Xi'an, China.

Zhang J, et al. iScience. 2024;27(2):108919.

Science/Cells: Antiviral effects of CBD and terpenes against the influenza A virus and the coronavirus

Scientists investigated the activity of terpenes and CBD in human lung fibroblasts. They tested preparations exhibiting both anti-inflammatory effects in peripheral blood mononuclear cells and antiviral effects against influenza A virus and the new human corona virus.

Eybna Technologies Ltd., Kfar Saba, Israel.

Chatow L, et al. Biotechnol Rep (Amst). 2024;41:e00829.

Science/Animal: CBD may be helpful in ulcerative colitis

In a mouse model of ulcerative colitis (UC) nanoparticles of CBD “significantly improved the species composition, abundance and amount of short chain fatty acids of intestinal flora in UC mice, thus effectively maintaining the balance of intestinal flora. The dual-targeted and glutathione-responsive nanoparticles prepared in this study provide a promising idea for achieving targeted delivery of CBD for effective treatment of UC.”

College of Food Science and Engineering, Hainan University, Haikou, China.

Zhang X, et al. Mater Today Bio. 2024;25:100965.

Science/Human: Cancer patients who use opioids and cannabis my experience stigma

According to interviews with 25 participants, cancer survivors experienced addiction fears, stigma and access challenges for opioids and cannabis. “Opioids were often perceived as critical for severe pain. Cannabis reduced pain and anxiety for many survivors, suggesting that anxiety screening, as recommended in guidelines, would improve traditional pain assessment.”

Memorial Sloan Kettering Cancer Center, Department of Epidemiology & Biostatistics, New York, USA.

Salz T, et al. Pain Manag. 2024 Feb 6. [in press]

Science/Animal: Cannabinoids may mitigate burn progression

In a study with pigs suffering from burns topical application of a cannabis extract with very low THC and CBD concentrations “decreased and mitigated burn wound progression in comparison to control treatments.”

Metis Foundation, San Antonio, Texas, USA.

Christy S, et al. J Surg Res. 2024;296:447-455.

Science/Animal: CBD may reduce anxiety in healthy dogs upon temporary separation from caregivers

In a study with 10 dogs there was increased vocal activity after separation from their caregivers. “Following the CBD administration, however, the degree of such increase was significantly less robust than that following the placebo administration (p < 0.01). As one of the possible explanations for the results the author hypothesizes anxiolytic effects of CBD in healthy domestic dogs, as has been reported in humans.”

Center for Research of Developmental Disorders, Kyoto, Japan.

Masataka N. Heliyon. 2024;10(3):e25548.

Science/Review: The sleep-wake cycle is modulated by the endocannabinoid system

The sleep-wake cycle and circadian rhythms “are both likely modulated” by the endocannabinoid system.

Department of Psychiatry, University of California San Diego, USA.

Miranda A, et al. Behav Sleep Med. 2024;22(2):217-233.