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IACM-Bulletin of May 07 2023

USA: Delaware will become the 22nd state to legalise recreational cannabis

Delaware will become the 22nd state to legalize recreational cannabis after its governor allowed two bills already passed by the legislature to become law. Governor John Carney said he would not veto a bill that will allow private citizens over the age of 21 to possess up to one ounce (about 28 g)  of cannabis for personal consumption, and a second bill that would see the state issue 30 retail business licenses over the next 16 months through a bidding process.

The legislation also has provisions for amounts of concentrated cannabis and products containing 750 milligrams or less of THC. Delaware lawmakers passed the two pieces of legislation in March 2023.

UPI of 22 April 2023

Science/Human: Cannabis may be helpful in sleep disorders according to a survey

According to a survey from Australia called CAMS-20 cannabis was shown to be helpful in sleeping disorders. The study was led by investigators of the University of Sydney, Lambert Initiative for Cannabinoid Therapeutics. When asked to specify up to seven different conditions they were treating with medical cannabis, a total of 1030 (64%) respondents selected a sleep disorder, with insomnia disorder (85.5%), sleep-related movement disorders (26%) and sleep-related breathing disorders (11.1%) the most common subtypes. Only 165 (16.8%) respondents selected a self-reported sleep disorder as the main health condition being treated.

Most respondents reported a reduction in the use of benzodiazepines and alcohol since starting medical cannabis. Statistical analyses showed that respondents who predominantly used inhaled routes of administration, and concomitant use of medical cannabis for pain, mental health and/or substance use disorder, or a gastrointestinal disorder, were significantly more likely to also use medical cannabis to treat a self-reported sleep disorder.

Suraev A, Mills L, Abelev SV, Arkell TR, Lintzeris N, McGregor IS. Medical Cannabis Use Patterns for Sleep Disorders in Australia: Results of the Cross-Sectional CAMS-20 Survey. Nat Sci Sleep. 2023;15:245-255.

Cannabis may reduce chronic pain according to an observational study

An interim analysis of the CA Clinics Observational Study by the School of Pharmacy of the Faculty of Medicine and Health at The University of Sydney, Australia, found that cannabis may reduce chronic otherwise treatment refractory pain. Patients were prescribed medicinal cannabis by a medical practitioner, containing various ratios of THC and CBD.

The overall chronic pain cohort, and specifically the balanced CBD:THC products, were associated with significantly reduced pain intensity scores, with 22% of patients reporting a clinically meaningful reduction in pain intensity. Patients in the arthritis subset (n = 199) reported significantly reduced pain intensity scores overall, and specifically for those taking CBD-only and balanced products. Other quality of life outcomes, including pain interference and pain impact scores were significantly improved.

Schubert EA, Johnstone MT, Benson MJ, Alffenaar JC, Wheate NJ. Medicinal cannabis for Australian patients with chronic refractory pain including arthritis. Br J Pain. 2023;17(2):206-217.

Science/Human: Cannabis may be effective in the treatment of cancer-related pain

According to an analysis of data of 358 cancer patients collected from patients who were part of the Quebec Cannabis Registry. Participants filled in questionnaires before the start of medical cannabis, and at 3-month, 6-month, 9-month and 12-month follow-ups.

Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up for worst pain, average pain, overall pain severity and pain interference. THC:CBD balanced strains were associated with better pain relief as compared with THC-dominant and CBD-dominant strains.

Aprikian S, Kasvis P, Vigano M, Hachem Y, Canac-Marquis M, Vigano A. Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results. BMJ Support Palliat Care. 2023 May 2:spcare-2022-004003.

Science/Human: CBD had no relevant effect on inhaled THC according to a placebo controlled study

In a study from the UK with 46 healthy infrequent cannabis users different doses of inhaled CBD had no relevant effect on psychological and cognitive effects of inhaled THC. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The research was led by investigators of the National Addiction Centre of the Institute of Psychiatry, Psychology and Neuroscience at King's College London.

THC (0:1) was associated with impaired delayed verbal recall and induced positive psychotic symptoms on the PANSS (Positive and Negative Syndrome Scale). Authors noted that these “effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures.” They stated that they “found no evidence that CBD protects against the acute adverse effects of cannabis.”

Englund A, Oliver D, Chesney E, Chester L, Wilson J, Sovi S, De Micheli A, Hodsoll J, Fusar-Poli P, Strang J, Murray RM, Freeman TP, McGuire P. Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios. Neuropsychopharmacology. 2023;48(6):869-876.

Science/Human: About one third of patients with chronic pain in California use cannabis after general legalisation

About 35% of patients with chronic pain in California use cannabis after legalisation, compared to 23% of patients without chronic pain. Researchers of Kaiser Permanente Northern California, Division of Research, Oakland, and the University of California compared patients with and without chronic pain on measures for medical, non-medical, pain-related, and mental health-related cannabis use based on self-reported symptoms.

Patients with chronic pain (CP) reported higher past year medical use (35%) compared to patients without CP (23%), past year pain-related use (30% vs 16%), and past year mental health-related use (25% vs 19%). Authors concluded that “compared to patients without CP, patients with CP were more likely to use cannabis for reasons related to medical and pain symptoms in the past year. Use for past year mental health symptoms did not differ between these two groups.”

Karmali R, Does MB, Gordon N, Sterling SA, Young-Wolff K, Sidney S, Campbell CI. Cannabis use for medical reasons among patients in a large California health care system after legalization of non-medical use. J Stud Alcohol Drugs. 2023 Apr 20 [in press].

Science/Human: High doses of CBD may influence blood anandamide levels

According to a placebo controlled study by UK investigators led by the Addiction and Mental Health Group of the Department of Psychology at the University of Bath high doses of CBD may have an influence on anandamide levels in blood plasma. Individuals meeting criteria for cannabis use disorder and attempting cannabis cessation were randomised to 28-day administration with placebo (n = 23), 400 mg CBD daily (n = 24) or 800 mg CBD daily (n = 23).

They noted an effect of 800 mg CBD compared to placebo on anandamide levels from baseline to day 28 after adjusting for cannabis use. Pairwise comparisons indicated that anandamide levels unexpectedly reduced from baseline to day 28 in the placebo group, but did not change in the 800 mg CBD group. There was no evidence for an effect of 400 mg CBD compared to placebo. Changes in anandamide levels were not associated with clinical outcomes of cannabis use disorder.

Hua DY, Hindocha C, Baio G, Lees R, Shaban N, Morgan CJ, Mofeez A, Curran HV, Freeman TP. Effects of cannabidiol on anandamide levels in individuals with cannabis use disorder: findings from a randomised clinical trial for the treatment of cannabis use disorder. Transl Psychiatry. 2023 ;13(1):131.

Science/Human: CBD may reduce blood pressure in hypertension

In a placebo-controlled crossover study with 70 patients with mild or moderate primary hypertension, who were untreated or receiving standard medication, CBD was shown to reduce blood pressure. Investigators of the University Hospital of Split, Croatia assigned participants to receive either 5 weeks of oral CBD or placebo. Following a washout period, patients were crossed over to the alternate therapy.

Administration of CBD reduced average 24 h mean (mean reduction of about 3 mmHg), systolic (mean reduction of about 5 mmHg), and diastolic blood pressure (reduction of 2 mmHg) after 2.5 weeks. There were no changes in liver enzymes or serious adverse events. Authors concluded that administration of CBD reduces blood pressure in those with untreated and treated hypertension.

Dujic G, Kumric M, Vrdoljak J, Dujic Z, Bozic J. Chronic Effects of Oral Cannabidiol Delivery on 24-h Ambulatory Blood Pressure in Patients with Hypertension (HYPER-H21-4): A Randomized, Placebo-Controlled, and Crossover Study. Cannabis Cannabinoid Res. 2023 Apr 21 [in press].

Science/Human: Low doses of oral THC may may have a positive effect on fear learning in adults with trauma-exposure

In a placebo controlled study from the USA with 19 trauma exposed adults with post-traumatic stress disorder (PTSD), 26 trauma exposed adults without PTSD and 26 non-trauma exposed healthy controls low doses of THC affected neural indices of fear recall and fear renewal. This research was led by scientists of the Translational Neuroscience Program of Wayne State University School of Medicine in Detroit, USA. They used a Pavlovian fear conditioning and extinction paradigm, where they measured concurrent functional magnetic resonance imaging and behavioral responses. Of the 71 participants 33 received a placebo and 34 THC before extinction learning.

During early extinction learning, individuals with PTSD given THC had greater activation of a certain brain region (ventrlmedial prefrontal cortex) than the trauma exposed controls without PTSD. During a test of the return of fear, healthy controls and individuals with PTSD given THC had greater activation of this brain region compared to the trauma exposed controls without PTSD. Individuals with PTSD given THC also had greater amygdala activation compared to those given placebo. Authors concluded that these “data suggest that low dose, oral THC can affect neural indices of fear learning and memory in adults with trauma-exposure; this may be beneficial for future therapeutic interventions seeking to improve fear extinction learning and memory.”

Zabik NL, Rabinak CA, Peters CA, Iadipaolo A. Cannabinoid modulation of corticolimbic activation during extinction learning and fear renewal in adults with posttraumatic stress disorder. Neurobiol Learn Mem. 2023;201:107758.

News in Brief

Science/Human: Cannabis may be helpful in hyperhidrosis

According to a case report cannabis was helpful in hyperhidrosis. Researchers found “a remarkable reduction in the volume of sweat and an improvement to the patient's quality of life using this novel low-cost and low-impact approach.”

Department of Dermatology and Allergy, University Hospital, LMU Munich, Germany.

Kaemmerer T, et al. J Dermatolog Treat. 2023;34(1):2127308.

Luxembourg Publishes Plan to Legalize Recreational Cannabis

An expert group appointed by the Luxembourg government has unveiled plans for an experimental cannabis legalization program in the country. The report recommends allowing the possession of up to 3 grams of cannabis, the cultivation of a maximum of 4 plants at home, and the development of a legal framework for a retail market where residents will be able to buy up to 5 grams per day, but no more than 30 grams per month.

Born2Invest of 3 May 2023

Science/Human: A study on a cannabis extract in cancer started in the UK

Researchers have just recruited their first patient who will receive the cannabis extract Sativex for the treatment of glioblastoma, an aggressive brain tumour. During the second phase of the trial, which is funded by The Brain Tumour Charity, researchers will aim to find out whether combining cannabis and chemotherapy can extend the lives of people diagnosed with recurrent glioblastoma.

Yorkshire Post of 3 May 2023

Science/Animal: The combination of FAAH inhibition and activation of the melatonin receptor provides nerve protection

In a study with rats a synthetic molecule (UCM1341), which both inhibits the degradation of endocannabinoids by FAAH inhibition and activation of the melatonin receptor, promoted neuroprotection and reduced inflammation.

Division of Pharmacology, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, Federico II University of Naples, Italy.

Cammarota M, et al. Br J Pharmacol. 2023;180(10):1316-1338.

Science/Human: Cannabis users may need higher doses of anaesthetics

In an observational study with 53 patients, of whom 27 patients were cannabis users and 26 non-users the cannabis positive group required on average a somewhat higher dose of fentanyl and propofol compared to non-users. But there were no differences in vital signs or anaesthetic requirements between both groups.

Department of Oral and Maxillofacial Pathology, Medicine, Surgery, Temple University Kornberg School of Dentistry, Philadelphia, USA.

Gangwani P, et al. J Oral Maxillofac Surg. 2023;81(5):527-535.

Science/Human: Genetic differences between cannabinoid receptors may influence cannabis effects in psychosis

An analysis of 40 patients with a first episode of psychosis, of whom 20 were cannabis users researchers found a combined effect of cannabis receptor genotypes and cannabis use on brain activity in different brain areas.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

Oscoz-Irurozqui M, et al. Int J Mol Sci. 2023;24(8):7501.

Science/Cells: Some terpenes may increase the effects of THC at the CB1 receptor

In a cell study with 16 cannabis terpenes all terpenes activated CB1 receptors, at about 10-50% of the activation by THC alone. The combination of some of these terpenes with THC significantly increased the activity of the CB1 receptor, compared to THC alone.

Bazelet Medical Cannabis Group, Or Akiva, Israel.

Raz N, et al. Biochem Pharmacol. 2023:115548.

Science/Human: Many cannabis patients are not allowed to continue a treatment with cannabis during a hospital stay

According to a survey with 811 nurse leaders working in acute care inpatient settings in US states that had legalized medical cannabis “only a small percentage reported that inpatients had some access to their medical marijuana: 5.8% reported that the drug was kept in the pharmacy and dispensed like other prescriptions; another 3.4% indicated that patients kept the medical marijuana in their rooms and took it, as needed.” Most were switched to other medications.

Health Administration, Edward J. Bloustein School of Planning and Public Policy, Rutgers University, New Brunswick, USA.

Kurtzman ET, Greene J. Policy Polit Nurs Pract. 2023:15271544231168607.

Science/Animal: CBD prevents osteoporosis and increases proliferation of human skeletal stem cells

In a study with mice CBD prevented osteoporosis and increased cell viability, proliferation and osteogenic gene expression in human skeletal stem and progenitor cells. Authors concluded that these findings “indicate that CBD usage in an osteoporotic population may positively impact bone morphology.”

Department of Orthopaedic Surgery, NYU Langone Orthopedics, NYU Grossman School of Medicine, New York, USA.

Ihejirika-Lomedico R, et al. Calcif Tissue Int. 2023 Apr 24 [in press].

Science/Animal: CB1 receptors on mitochondria are involved in corticosterone effects

Corticosteroid-mediated stress responses require the activation of complex brain circuits involving mitochondrial activity. New research shows that the impairing effect of corticosterone in the novel object recognition task in mice requires CB1 receptors on mitochondria and the regulation of mitochondrial calcium levels in nerve cells.

INSERM, U1215 NeuroCentre Magendie, Bordeaux, France.

Skupio U, et al. Neuron. 2023:S0896-6273(23)00263-5.

Science/Animal: Activation of the CB2 receptor may ameliorate chronic alcohol exposure-induced anxiety

Activation of the CB2 receptor ameliorated adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing inflammation in the nervous system.

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

Li J, et al. Brain Behav Immun. 2023;110:60-79.

Science/Animal: Treatment of obese rats with a CB2 receptor agonist reduced the levels of leptin in adipose tissue

Treatment of diet-induced obese rats with a synthetic CB2 receptor agonist (AM1241) or a CB2 antagonist (AM630) reduced leptin levels in adipose tissue without effecting weight.

Institute for Health and Sport, Victoria University,  Melbourne, Australia.

O'Keefe L, et al. Int J Mol Sci. 2023;24(8):7601

Science/Animal: Activation of the CB1 receptor alleviates central sensitisation in chronic migraine

In a rat model of chronic migraine, activation of the CB1 receptor alleviated central sensitization by regulating hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2).

Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.

Zeng X, et al. J Headache Pain. 2023;24(1):44.

Science/Animal: THC may reduce cancer cachexia through modulation of inflammation

In a study with mice THC was protective against colorectal cancer cachexia through modulation of inflammation and immune responses.

Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Ng SK, et al. Biomed Pharmacother. 2023;161:114467.

Science/Animal: CBD may impede lung cancer growth

Researchers implanted human lung cancer cells in nude mice and treated the mice with inhalant CBD or placebo. CBD decreased tumor growth rate and suppressed expression of CD44 and the angiogenic factors VEGF and P-selectin.

Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, USA.

Salles ÉL, et al. Hum Cell. 2023 May;36(3):1204-1210.

Science/Animal: CBD may be helpful in prostate cancer

The growth of prostate cancer in mouse models was reduced following treatment with cisplatin and CBD.

Department of Biochemistry, University of Johannesburg, South Africa.

Motadi LR, et al. Mol Biol Rep. 2023;50(5):4039-4047.

Science/Animal: The analgesic effects of CBD neuropathic pain may involve serotonin receptors

Results of a mouse model of neuropathic pain suggest that CBD produces peripheral antinociception during acute treatment of neuropathic pain and it partially involved the participation of the 5-HT1A (serotonin) and TRPV1 (vanilloid) receptors.

Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.

Aguiar DD, et al. Biochem Biophys Res Commun. 2023;660:58-64.

Science/Cells: Cannabinoids might reduce the efficacy of platinum cancer drugs

Cell experiments with human cells demonstrate, that CBD may reduce intracellular accumulation of platinum drugs (cisplatin, oxaliplatin, carboplatin). Authors noted that their “study raises the possibility that the desirable effect of counteracting adverse effects of chemotherapy might, at least for some cannabinoids, reflect impaired cellular availability, and consequently attenuation of the anticancer effects of platinum drugs.”

Faculty of Medicine and Dentistry, Institute of Molecular and Translational Medicine, Palacký University, Olomouc, Czech Republic.

Buchtova T, et al. Biomed Pharmacother. 2023;163:114801.

Science/Human: CBD may increase the blood concentration of everolimus

In a study with healthy humans, who received the immunosuppressant medication everolimus, a dose of 12.5 mg CBD per kg bodyweight significantly increased blood concentration of everolimus. Authors noted that “everolimus blood concentration monitoring should be strongly advised with appropriate dose reduction when coadministered with CBD.”

GW Research Ltd, Cambridge, UK.

Wray L, et al. Clin Pharmacol Drug Dev. 2023 May 3 [in press].

Science/Human: A selective activator of the CB2 receptor was not effective in reducing abdominal pain in patients with irritable bowel syndrome

Olorinab is a synthetic highly selective, peripherally acting, full agonist of the CB2 receptor. In a placebo-controlled study with 273 participants olorinab did not reduce average abdominal pain scores. However, in participants with moderate-to-severe pain at baseline the medication showed some effect.

David Geffen School of Medicine, UCLA, Los Angeles, USA.

Chang L, et al. Neurogastroenterol Motil. 2023;35(5):e14539.

Science/Human: Activation of the CB2 receptor was not effective in cutaneous systemic sclerosis

Lenabasum, a cannabinoid type 2 receptor agonist, was tested in a phase 3 randomized placebo-controlled trial in 365 patients with diffuse cutaneous systemic sclerosis. A benefit of lenabasum could not be demonstrated.

Weill Cornell Medical College, New York City, USA.

Spiera R, et al. Arthritis Rheumatol. 2023 Apr 26 [in press].

Science/Animal: CBD may reduce the rewarding properties of methamphetamine

According to a study with rats CBD may inhibit the rewarding properties of methamphetamine and this was in part mediated by interaction with dopamine receptors in a certain brain region (hippocampus).

Department of Physiology, Faculty of Veterinary Science, Islamic Azad niversity, Sanandaj, Iran.

Mohammadi M, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2023;126:110778.

Science/Human: Activation of the CB1 receptor in the hippocampus inhibits ketamine-induced anxiety

In a study with mice activation of the CB1 receptor in the hippocampus, a certain brain region, by a synthetic cannabinoid (ACPA) was able to inhibit ketamine-induced anxiogenic-like behaviour.

Department of Biology, Faculty of Science, Gonbad Kavous University, Iran.

Alijanpour S, Rezayof A. Brain Res. 2023:148378.

Science/Animal: A CBD-rich cannabis extract induced programmed cell death in a certain form of leukaemia

In T-cell acute lymphoblastic leukemia (T-ALL) more than 50% of cases show NOTCH1-driven transformation. Using a mouse model investigators demonstrated that a CBD-rich extract selectively induced apoptosis (programmed cell death) in NOTCH1-mutated T-ALL cells. Authors wrote that “although CBD by itself was able to induce cell death, the whole extract was more effective, suggesting that other metabolites from the plant are required to achieve full potency.”

The Laboratory of Cancer Biology and Cannabinoid Research, Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.

Besser E, et al. Cancer Commun (Lond). 2023 Apr 21 [in press].

Science/Cells: Tetrahydrocannabivarin may be helpful in diabetes

Investigators evaluated the protective effects of THCV (tetrahydrocannabivarin) against endoplasmic reticulum (ER) stress in adipose-derived mesenchymal stem cells. They concluded that “our study shows that the cannabinoid THCV is a promising compound that counters the harmful effects triggered by ER stress in the adipose tissue. This work paves the way for the development of new therapeutic means based on THCV and its regenerative properties to create a favorable environment for the development of healthy mature adipocyte tissue and to reduce the incidence and clinical outcome of metabolic diseases such as diabetes.”

National Medicines Institute, Warsaw, Poland.

Kowalczuk A, et al. Int J Mol Sci. 2023;24(8):7120.