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IACM-Bulletin of 18 June 2023

Science/Human: Cannabis may be helpful in generalised anxiety disorder

According a prospective study with 302 patients suffering from generalised anxiety disorder from the UK Medical Cannabis Registry a treatment with cannabis may improve their symptoms. Primary outcomes of the study by investigators of the Imperial College Medical Cannabis Research Group in London, UK, were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline.

“Improvements in anxiety, sleep quality and quality of life were observed at each time point.” Thirty-nine participants (13%) reported 269 adverse events in the follow-up period. Authors concluded that the prescription of cannabis-based medicines in patients with generalised anxiety disorder “ is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting.”

Rifkin-Zybutz R, Erridge S, Holvey C, Coomber R, Gaffney J, Lawn W, Barros D, Bhoskar U, Mwimba G, Praveen K, Symeon C(, Sachdeva-Mohan S, Rucker JJ, Sodergren MH. Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry. Psychopharmacology (Berl). 2023 Jun 14 [in press].

Science/Human: Cannabis use during pregnancy may not have negative effects on cognitive abilities of children

According to a study with 2868 children exposition to cannabis by their mothers during pregnancy had no significant effect on neuro psychological test scores at the age of 10 years. Investigators of the Department of Anesthesiology at the Columbia University Vagelos College of Physicians and Surgeons in New York, USA, included children born between 1989 and 1992, whose mothers provided information on cannabis use during pregnancy.

Of the 2868 children in this cohort, 285 (10%) had prenatal cannabis exposure. Exposed children scored similarly as non-exposed children. In the primary outcome test, called CELF (Clinical Evaluation of Language Fundamentals). In addition, cannabis use was not associated with secondary outcomes or risks of clinical deficit in any neuro psychological assessments, the Peabody Picture Vocabulary Test (PPVT), Child Behaviour Checklist (CBCL), McCarron Assessment of Neuromuscular Development (MAND), Coloured Progressive Matrices (CPM), Symbol Digit Modality Test (SDMT) and Autism Spectrum Quotient (AQ) scores. Authors concluded that “after adjusting for sociodemographic and clinical covariates” prenatal cannabis exposure “was not associated with worse neuropsychological test scores at age 10 or autistic traits at 19-20.”

Isik OG, Guo L, Whitehouse AJO, Li G, Ing C. Neurodevelopmental outcomes in children after prenatal marijuana exposure. Paediatr Perinat Epidemiol. 2023 Jun 7 [in press].

Science/Human: Cannabis may reduce agitation in individuals diagnosed with dementia according to a placebo controlled study

In a placebo-controlled crossover study with 21 participants with a mean age of 85 years cannabis had no effect on behaviour and quality of life, but reduced agitation at the end of the treatment. Investigators of the Institute for Health Research of the University of Notre Dame Australia in Fremantle, USA, used a cannabis extract with a ratio of 3 to 2 for THC and CBD for 18 weeks and a placebo. Four surveys, collected on seven occasions, were used to measure changes in neuropsychiatric symptoms of dementia, quality of life and pain.

No significant differences were seen between the placebo and cannabis for behaviour, quality of life or pain, except a decrease in agitation at the end of treatment in favour of cannabis. The qualitative findings suggested improved relaxation and sleep among some individuals. There were only “minimal” side-effects.

Timler A, Bulsara C, Bulsara M, Vickery A, Jacques A, Codde J. Examining the use of cannabidiol and delta-9-tetrahydrocannabinol-based medicine among individuals diagnosed with dementia living within residential aged care facilities: Results of a double-blind randomised crossover trial. Australas J Ageing 2023 Jun 15 [in press].

Science/Human: Nabilone may be helpful in persistent vomiting due to gastrointestinal disorders according to a case series

According to a case series of 7 patients nabilone, a synthetic THC derivative, may be helpful in vomiting caused by gastrointestinal disorders. Patients prescribed nabilone at St. Mark's intestinal rehabilitation unit (January 2017 to September 2022) have been retrospectively reviewed by investigators of the Hospital Universitario 12 de Octubre in Madrid, Spain. Among the reasons for vomiting were gastroparesis, Crohn’s disease, adrenal insufficiency and intestinal dysmotility. All patients did not respond to standard medication. They received 1 or 2 mg of nabilone twice daily.

The median treatment duration was 9 days. Regarding the efficacy of nabilone, 3 of 7 had symptomatic improvement. In terms of side-effects 4 of 7 patients reported some incidence under the treatment such as headache, light-headedness, drowsiness, dizziness or hallucinations. Authors concluded that “nabilone improved symptoms in almost half of the patients although adverse effects appeared in more than 50%”.

Olmedo Moreno C, Holman R, Naghibi M, Donnelly S, Culkin A, Malcom L, Vernon N, Gabe S. Usefulness of nabilone as an antiemetic in persistent vomiting due to refractory gastrointestinal disorders. Rev Esp Enferm Dig 2023 Jun 14 [in press].

Science/Human: Cannabis may reduce anxiety according to self-reports by patients

Data of 184 patients collected through an app showed, that the inhalation of cannabis may reduce anxiety. Investigators of Aurora Cannabis Inc. in Edmonton, Canada, analyzed a dataset encompassing three of the most commonly utilized dried flower products in anxiety.

Cannabis consumption resulted in a significant decrease in anxiety scores among both males and females and efficacy was similar across the three cultivars. The overall optimal dosing for the entire cohort was 9 to 11 inhalations for males and 5 to 7 inhalations for females, with some variation in dosing across the different cultivars, genders and age groups.

Minhas M, Lunn SE. Naturalistic examination of the anxiolytic effects of medical cannabis and associated gender and age differences in a Canadian cohort. J Cannabis Res 2023;5(1):20.

Science/Human: CBD may reduce blood pressure in hypertension according to a placebo-controlled study

In a placebo-controlled study with 16 volunteers with untreated hypertension CBD in a dose of 150 mg thrice daily reduced blood pressure and arterial stiffness. Investigators of the Department of Integrative Physiology at the University of Split School of Medicine, Croatia, measured blood pressure, heart rate variability and arterial stiffness for 24 hours.

Although physical activity, sleep patterns and heart rate variability were comparable between the 2 groups , arterial stiffness, systolic blood pressure (5 mmHg), and mean arterial pressure (3 mmHg) were all significantly lower over 24 h on cannabidiol when compared to the placebo. These reductions were generally larger during sleep.

Dragun T, Brown CV, Tulppo MP, Obad A, Dujić Ž. The Influence of Oral Cannabidiol on 24-h Ambulatory Blood Pressure and Arterial Stiffness in Untreated Hypertension: A Double-Blind, Placebo-Controlled, Cross-Over Pilot Study. Adv Ther 2023 Jun 8 [in press].

Science/Human: THC may be helpful in the treatment of fibromyalgia

According to a chart review of 120 patients with fibromyalgia treated in a multimodal interdisciplinary setting the 62 participants receiving THC showed a greater symptom improvement than those not receiving THC. They were treated at the Schmerzzentrum Inn-Salzach in Burghausen, Germany.

“In the parameters of pain intensity, depression, and quality of life, there was a significant improvement in the entire group during the stay (p < 0.001), which was significantly greater through the use of THC”, authors noted. “The results provide indications that THC can be considered as a medical alternative in addition to the substances previously recommended in various guidelines.”

Bettstetter H, Schäfer A. [Tetrahydrocannabinol (THC) in patients with fibromyalgia syndrome (FMS) : A retrospective study of changes in pain, psychometric variables, and analgesic consumption during inpatient interdisciplinary multimodal pain therapy (IMPT)]. Schmerz 2023 Jun 8 [in press].

Science/Human: The Cytochrome P450-mediated interaction of cannabinoids with other medicinal drugs were investigated in healthy adults

Cannabis extracts were used to evaluate quantitatively potential pharmacokinetic cannabinoid-drug interactions in 18 healthy adults at the School of Pharmacy of the University of Washington, USA.

In a randomized cross-over manner (separated by at least 1 week), a brownie containing 1) no cannabis extract (ethanol/placebo), 2) CBD-dominant cannabis extract (640 mg CBD+20 mg THC), or 3)THC-dominant cannabis extract (20 mg THC and no CBD) was administered. After 30 min, participants consumed a cytochrome P450 (CYP) drug cocktail consisting of caffeine (metabolised in the liver by CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A).

The CBD+THC brownie inhibited CYP2C19>CYP2C9>CYP3A>CYP1A2 (but not CYP2D6) activity relative to placebo of omeprazole, losartan, midazolam, and caffeine by 207%, 77%, 56%, and 39%, respectively. In contrast, the THC brownie did not inhibit any of the CYPs. The CBD+THC brownie increased THC activity by 161%, consistent with CBD inhibiting CYP2C9-mediated oral THC clearance.

Bansal S, Zamarripa CA, Spindle TR, Weerts EM, Thummel KE, Vandrey R, Paine MF, Unadkat JD. Evaluation of Cytochrome P450-Mediated Cannabinoid-Drug Interactions in Healthy Adult Participants. Clin Pharmacol Ther 2023 Jun 14 [in press].

News in brief

Science/Human: Cancer patients would like to talk to their doctors about cannabis

According to a survey with 46 cancer patients, of whom 17 were current cannabis users the most common symptoms participants used cannabis for were pain (9 of 17), anxiety (9 of 17), and insomnia (9 of 17). Many participants using cannabis had not talked to their doctor about cannabis (9 of 17), but would like to do so.

Division of Gynecologic Oncology, University of Calgary, Canada.

Black KA, Bowden S, Thompson M, Ghatage P. Cannabis use in gynecologic cancer patients in a Canadian cancer center. Gynecol Oncol Rep 2023;47:101210.

Science/Animal: CBD may prevent episodic and chronic migraine like states

According to a mouse model of migraine CBD may be effective “in preventing episodic and chronic migraine-like states with reduced risk of causing medication overuse headache.”

Biomedical Science Department, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, USA .

Sturaro C, et al. Pain 2023 Jun 9 [in press].

Science/Animal: CBD and beta-caryophyllene may improve symptoms of Dravet syndrome

In a mouse model of Dravet syndrome treatment with beta-caryophyllene or CBD attenuated behavioural disturbances, “but, again and in general, superior results were obtained when both cannabinoids were combined.”

Instituto Universitario de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain.

Alonso C, et al. Neuropharmacology 2023:109602.

Science/Human: Baseline affective symptomatology influences acute subjective effects of cannabis concentrates

Results of a study with 54 cannabis users suggest “that baseline affect moderates the acute effects of ad libitum use of THC and CBD concentrates such that preexisting affective symptoms modulate the intensity of subjective drug experiences.”

Department of Psychology and Neuroscience, University of Colorado Boulder, USA.

Martin-Willett R, et al. Exp Clin Psychopharmacol 2023 Jun 8 [in press].

Science/Animal: Activation of the CB2 receptor may improve inflammatory pain

In a study with mice as synthetic cannabinoid-2 receptor agonist suppressed “inflammatory nociception in mice through a neuronal CB2-dependent mechanism that requires peripheral sensory neuron CB2 receptors.”

Program in Neuroscience, Indiana University, Bloomington, USA.

Guenther KG, et al. Neuropharmacology 2023:109601.

Science/Cells: A combination of a hops extract and CBD may reduce inflammation

A study with macrophages supports “the potential of CBD combined with phytomolecules from a non-cannabinoid source, such as hops, for the treatment of inflammatory diseases.”

Sanity Group GmbH, Berlin, Germany.

Dammann I, et al. Nat Prod Bioprospect 2023;13(1):19.

Science/Animal: The administration of THC during adolescence may have a lasting effect on the brain

A study with rats indicates “that mild THC exposure during adolescence leaves a lingering mark on brain structure and function in a sex-dependent manner. Some of the changes found here resemble those observed in human studies and highlight the importance of studying sex-specific effects in cannabinoid research.”

Department of Psychobiology, School of Psychology, National University for Distance Learning (UNED, Madrid, Spain.

Orihuel J, et al. Eur Neuropsychopharmacol 2023;74:47-63.

Science/Animal: THC alters the levels of the CB1 receptor in a dose-dependent manner

Results of a study with rats “demonstrate that chronic Δ9-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.”

Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, USA.

Freeman-Striegel L, et al. Life Sci 2023:121825

Science/Human: Drug use may not have an effect on the overall effectiveness of neuroleptics

A study with 144 patients with schizophrenia “showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.”

Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.

Alisauskiene R, et al. Gen Hosp Psychiatry 2023;83:185-193.

Science/Animal: Exercise may modulate the density of CB1 receptors in certain brain regions in Parkinson’s disease

According to a rat model of Parkinson’s disease regular exercise may reduce the detrimental effects of Parkinson’s disease on the density of CB1 receptors in certain brain regions (substantia nigra, hippocampus).

Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.

Binda KH, et al. Brain Res 2023;1814:148436.

Science/Animal: THC may show anti-allodynic effects in neuropathic rats

Findings of a study with rats “indicate that a single dose of THC produces antiallodynic effect in individuals with NP (neuropathic pain) who are tolerant to morphine, acting mostly on the ON cells of the descending pain pathways, but not on OFF cells.”

Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, Canada.

Pearl-Dowler L, et al. Prog Neuropsychopharmacol Biol Psychiatry 2023:110805.