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IACM-Bulletin of 12 February 2023

Science/Human: Treatment of childhood epilepsy with a combination of THC and CBD may be much more effective than treatment with CBD alone

A case series of 35 children (<18 years old) with treatment resistant epilepsy from the UK Medical Cannabis Registry was analysed. Data were presented by investigators of the Department of Surgery & Cancer of Imperial College London, UK. Patients received either CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/THC combination therapy (n = 17).  

Twenty-three (65.7%) patients achieved a reduction in seizure frequency of 50% or more. 94% of patients treated with CBD and THC observed a 50% or higher reduction in seizure frequency compared to 32 % and 18 % of patients treated with CBD isolates and broad-spectrum CBD products, respectively. Authors concluded that these results “demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products.”

Erridge S, Holvey C, Coomber R, Hoare J, Khan S, Platt MW, Rucker JJ, Weatherall MW, Beri S, Sodergren MH. Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy - Analysis from the UK Medical Cannabis Registry. Neuropediatrics. 2023 Jan 30 [in press].

Science/Human: Cannabis improves symptoms of post-traumatic stress disorder in observational study

In an observational study 14 patients (age range: 32 to 68 years) with treatment-resistant chronic combat post-traumatic stress disorder symptoms were considerably improved. Investigators of Clalit Health Services Community Division of the Ramat-Chen Brull Mental Health Center in Tel Aviv-Yafo, Israel, reported that patients had been treated without success “with many lines of conventional treatment prior to receiving medicinal cannabis.”

Total sleep score, subjective sleep quality, and sleep duration significantly improved. Total post-traumatic stress disorder symptom score and its subdomains (intrusiveness, avoidance, and alertness) showed improvement. However, there was no improvement in the frequency of nightmares. The mean follow-up time was 1.1 years (range of 0.5 to 3 years).  

Nacasch N, Avni C, Toren P. Medical cannabis for treatment-resistant combat PTSD. Front Psychiatry. 2023;13:1014630.

Science/Human: Cannabis use was associated with reduced SARS-CoV-2 infection among pregnant women

According to a retrospective analysis of data from 58,114 pregnancies current cannabis use was associated with a reduced risk of coronavirus-2 infection. Investigators of the Division of Research, Kaiser Permanente Northern California in Oakland, USA, used data of outcomes from 5 March 2020 to 30 September 2021 of pregnant women, who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (a health-care system) and had not tested positive for COVID-19 prior to pregnancy onset.  

They observed 348 810 person-months of follow-up time in their cohort with 41 064 SARS-CoV-2 PCR tests and 6% of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection (adjusted hazard ratio = 0.60) than non-use. Those who had recently quit did not differ from non-cannabis users.

Young-Wolff KC, Ray GT, Alexeeff SE, Benowitz N, Adams SR, Does MB, Goler N, Ansley D, Conway A, Avalos LA. Association of cannabis use during pregnancy with severe acute respiratory syndrome coronavirus 2 infection: a retrospective cohort study. Addiction. 2023;118(2):317-326.

Science/Human: Legalisation of cannabis for medical and recreational use in the USA was not associated with any psychosis diagnoses

Commercial and Medicare Advantage claims data for about 64 million beneficiaries aged 16 years and older in all 50 US states and the District of Columbia between 2003 to 2017 were used to analyse the relationship between cannabis legalisation and psychosis. State cannabis legalization policies were measured for each state and month based on law type (medical or recreational) and degree of commercialization (presence or absence of retail outlets).  

Authors concluded from the main results that in their “retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes.”

Elser H, Humphreys K, Kiang MV, Mehta S, Yoon JH, Faustman WO, Matthay EC. State Cannabis Legalization and Psychosis-Related Health Care Utilization. JAMA Netw Open. 2023;6(1):e2252689.  

Science/Human: The medical use of cannabis reduced opiate use in large clinical study

In a study with 8165 pain patients, who received long-term opioid therapy, the medical use of cannabis reduced opioid dosages. Investigators of the New York State Department of Health Albany, USA, divided the cohort into 2 groups. The nonexposure group (4124 patients) received cannabis for 30 days or fewer, and the exposure group (4041 patients) received cannabis for more than 30 days. Opioid dosage was measured as mean daily morphine milligrams equivalent (MME). Analyses were conducted for 3 strata by opioid dosage prior to receiving cannabis: MME less than 50, MME of 50 to less than 90, and MME of 90 or greater.  

During follow-up, significantly greater reductions in opioid dosage were observed among the exposure group. The daily MME for the last month of the follow-up period among patients receiving longer cannabis treatment was reduced by 48% in the lowest stratum, 47% in the middle stratum, and 51% in the highest stratum compared with the baseline dosages. Among individuals in the nonexposure group, daily MME was reduced by only 4% in the lowest stratum, 9% in the middle stratum, and 14% in the highest stratum. Authors concluded that longer cannabis use was “associated with reductions in opioid dosages, which may lower their risk of opioid-related morbidity and mortality. “

Nguyen T, Li Y, Greene D, Stancliff S, Quackenbush N. Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019. JAMA Netw Open. 2023;6(1):e2254573.

Science/Human: THC does not enhance oxycodone-induced respiratory depression

In a placebo-controlled crossover study with 18 healthy volunteers the inhalation of 100 mg THC-rich cannabis of the variety Bedrocan had no effect on ventilatory control following the intake of 20 mg oxycodone. Investigators of the Department of Anesthesiology at Leiden University Medical Center, Netherlands administered cannabis 1.5 and 4.5 hours after placebo or oxycodone intake.  

Oxycodone produced a 30% decrease in in a measure of ventilation (VE55), whereas placebo was without effect on VE55. The first cannabis inhalation resulted in VE55 changing from 20.3 to 23.8 L min-1 after placebo, and from 11.8 to 13.0 L min-1 after oxycodone. The second cannabis inhalation also had no effect on VE55. Authors concluded that “THC has no effect on ventilatory control after placebo or oxycodone pretreatment.”

van Dam CJ, van der Schrier R, van Velzen M, van Lemmen M, Simons P, Kuijpers KWK, Jansen S, Kowal MA, Olofsen E, Kramers C, Dahan A, Niesters M. Inhaled Δ(9)-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers. Br J Anaesth. 2023:S0007-0912(22)00743-7.

Science/Human: Cannabis may be helpful in fibromyalgia according to a prospective study

According to a prospective cohort study involving 30 woman aged 18 to 70 years diagnosed with fibromyalgia cannabis may improve quality of life. Researchers of the Department of Orthopedic Surgery at the Wolfson Medical Center in Tel Aviv, Israel, investigated participants before initiation of cannabis treatment and one month later.

Cannabis treatment for 30 days showed a marked improvement in general quality of life, general health, physical health, and psychological domain. Authors concluded that these results “suggest a potentially significant role of Cannabis in treatment-resistant Fibromyalgia women. Early Cannabis treatment may result in a beneficial short-term effect on the quality of life through its influence on pain, sleep, and physical and psychological domains.”

Hershkovich O, Hayun Y, Oscar N, Shtein A, Lotan R. The role of cannabis in treatment-resistant fibromyalgia women. Pain Pract. 2023;23(2):180-184.

Science/Human: CBD may improve quality of life in patients with Sturge-Weber Syndrome

In an open-label prospective study with 10 patients suffering from Sturge-Weber Syndrome CBD improved anxiety and motor impairments. Investigators of the Department of Neurology and Developmental Medicine at Hugo Moser Kennedy Krieger Research Institute in Baltimore, USA, administered CBD (cannabidiol) for 6 months in doses ranging from 5 to 20 mg/kg bodyweight/day.

Significant improvements in Sturge-Weber syndrome neuroscore, patient-reported quality of life, anxiety and emotional regulation, and bimanual ability use were noted. Migraine scores were high at baseline in these subjects, and remained high. Neuropsychologic and other quality of life and motor outcomes remained stable, with some within-subject improvements noted.  

Smegal LF, Vedmurthy P, Ryan M, Eagen M, Andrejow NW, Sweeney K, Reidy TG, Yeom S, Lin DD, Suskauer SJ, Kalb LG, Salpekar JA, Zabel TA, Comi AM. Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome. . Pediatr Neurol. 2023;139:24-34.

Science/Human: Cannabis alters the subjective experience of cocaine

In a double-blind, placebo-controlled study with 9 subjects, who reported smoking both cocaine and cannabis treatment with cannabis altered the subjective experience of smoked cocaine and reduced peak plasma levels of cocaine. Participants completed a 13-day inpatient protocol by investigators of UCLA Center for Cannabis and Cannabinoids at the David Geffen School of Medicine of the University of California in Los Angeles, USA. On session days, cannabis with 5.6% THC or placebo cannabis with no THC was administered 28 min prior to 3 different cocaine doses.

Active cannabis increased plasma levels of THC and subjective ratings of cannabis effects. Cocaine dose-dependently increased plasma cocaine and subjective ratings of cocaine effects. Active cannabis pre-treatment decreased plasma levels of cocaine and metabolites. Furthermore, active cannabis attenuated cocaine-related reductions in 'Hunger' and 'Calm.'  

Murray CH, Haney M, Foltin RW, Manubay J, Bedi G, Cooper ZD. Smoked cannabis reduces peak cocaine plasma levels and subjective effects in a controlled drug administration study of polysubstance use in men. Drug Alcohol Depend. 2023;243:109757.

Science/Human: Cannabis may be helpful in headache disorders

A case series of 97 patients with headache disorders of the UK Medical Cannabis Registry was conducted. They filled in questionnaires before the start of treatment with a cannabis-based medication as well as 1-, 3-, and 6-months follow-up. Data were analysed by investigators of the Imperial College Medical Cannabis Research Group of the Imperial College London, UK.  

Improvements were observed in the Headache Impact Test-6, the Migraine Disability Assessment and quality of life scores at 1-, 3-, and 6-months follow-up. Anxiety disorder scores improved at 1- and 3-months. Seventeen (17.5%) patients experienced adverse events.

Nicholas M, Erridge S, Bapir L, Pillai M, Dalavaye N, Holvey C, Coomber R, Rucker JJ, Weatherall MW, Sodergren MH. UK medical cannabis registry: assessment of clinical outcomes in patients with headache disorders. Expert Rev Neurother. 2023:1-12.

Science/Human: Cannabis had no negative effect on the outcome in lung cancer treated with immunotherapy

In a study with 201 patients with non-small cell lung cancer cannabis had no negative effect on the efficacy of pembrolizumab. In this investigation by researchers of the Oncology Institute of Tel Aviv Medical Center, Israel, 102 patients received licence for cannabis within the first month of treatment. The most common indication for cannabis was pain (71%) followed by loss of appetite (34%).  

Time to tumour progression was similar for cannabis-naive and cannabis-treated patients (6.1 versus 5.6 months, respectively), while overall survival was numerically higher in the cannabis-naive group (54.9 versus 23.6 months) but did not reach statistical significance. Authors wrote that “in multivariate analyses, we did not identify cannabis use as an independent predictor factor for mortality.”

Waissengrin B, Leshem Y, Taya M, Meiri D, Merimsky O, Shamai S, Wolf I, Rubinek T.The use of medical cannabis concomitantly with immune checkpoint inhibitors in non-small cell lung cancer: A sigh of relief? Eur J Cancer. 2023;180:52-61.

News in brief

Science/Cells: CBD may protect against amyloid beta induced senescence of astrocytes

In human astrocytes treatment with amyloid beta, an endogenous pathogenic agent of Alzheimer’s disease, induces senescence features. CBD treatment protected against this form of senescence and authors wrote that their findings “support the new therapeutic avenues of CBD for the treatment of AD patients.”

Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, Australia.

Wang Z, et al. Cannabis Cannabinoid Res. 2023 Jan 24 [in press].

Science/Animal: The number of CB1 receptors in the brain of female mice varies with age

In female mice the number of brain cells with CB1 receptors changes with age. During life it increased in some brain regions and decreased in others.

Shenzhen Key Lab of Translational Research for Brain Diseases, China.

Li X, et al. J Comp Neurol. 2023;531(2):294-313.

Science/Human: Depressive symptoms are associated with reduced levels of anandamide in hair

In a study with 128 subjects depressive symptoms as well as hair endocannabinoids were measured annually over 4 years. Authors found that higher depressive symptomatology was associated with reduced levels of the endocannabinoid anandamide.

Clinical Psychology and Psychotherapy, University of Zurich, Switzerland.

Walther A, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2023;121:110658.

Science: THC binds to the glycine receptor

Researchers demonstrated that THC binds to the glycine receptor, an ion channel involved in peripheral pain.

Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.

Alvarez LD, Alves NRC. Proteins. 2023;91(3):400-411.

Science/Animal: Both opioids and cannabinoids exert comparable analgesic effects in rhesus monkeys

Results of a study with rhesus monkeys “demonstrate that in nonhuman primates, both opioids and cannabinoids exert comparable antinociception; however, physical dependence on opioids, but not cannabinoids, at their antinociceptive doses, occurs following short-term exposures.”

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, USA.

Ding H, et al. Neuropharmacology. 2023 Feb 1;223:109328.

Science/Animal: Cannabis sativa and indica strains had different effects on cognition in rats

Scientists detected some differences in cognition of rats following cannabis oils prepared with sativa and Indica strains. They noted that “these results support the suggestion that products marketed as different cannabis cultivars have dissociable cognitive effects that may not resemble pure THC”.

Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Canada.

Brodie HG, et al. Behav Neurosci. 2023;137(1):41-51.

Science/Human: The medical use of cannabis reduced alcohol sales in Canada

New research “suggests that medical cannabis was an economic substitute for alcohol in Canada, and that the country's 2017-2018 alcohol sales were roughly 1.8% lower than they would have been without legal medical cannabis.”

FOIS, Brock University, St. Catharines, ON, Canada.

Armstrong MJ. Health Policy. 2023;128:28-33.

Science/Animal: 2-AG is important for maintaining integrity of synopses in nerve cells of the hippocampus

An animal study “provides evidence that 2-AG signalling in astrocytes plays an important role in maintaining the functional integrity of synapses in the hippocampus”, a certain brain region.

Department of Cellular and Integrative Physiology, University of Texas Health San Antonio, USA.

Zhu D, et al. Exp Neurol. 2023;361:114292.

Science/Animal: Oleoylethanolamide prevents calcification of blood vessels

In a study with rats researchers demonstrated that oleoylethanolamide “serves as a prospective candidate for the prevention and treatment of vascular calcification in metabolic abnormality syndromes.”

Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, PR China.

Chen Z, et al. Biochem Pharmacol. 2023;208:115379.

Science/Animal: Abnormal cannabidiol may be helpful in the treatment of obesity and dyslipidaemia in type-2-diabetes

According to a study with mice a treatment with abnormal CBD may be “a novel and effective approach for bodyweight control and the treatment of glucose intolerance and dyslipidaemia in type-2-diabetes.”

School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.

McCloskey AG, et al. Biochem Pharmacol. 2023;208:115398.

Science/Animal: The endocannabinoid system is important for the integrity of the blood-cerebral spinal fluid barrier (BCB)

Results of a study with mice suggest endocannabinoids and their metabolizing enzymes play an important role in the brain and BCB integrity and highlight the need for more extensive studies on these mechanisms.”

Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, USA.

Ahluwalia M, et al. Exp Neurol. 2023;361:114320.

Science/Human: CBD did not influence neural reward anticipation in adolescents

In a placebo-controlled crossover trial with 47 adolescent “cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.”

Department of Psychiatry, University of Cambridge, United Kingdom.

Skumlien M, et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023;8(2):219-229.

Science/Human: Cannabis use has no effect on the risk of adenomyosis

In a study with 386 patients suffering from adenomyosis and 323 healthy controls no association was observed between cannabis use and at the risk of adenomyosis, while tobacco use increased this risk.

Department of Microbiology and Molecular Genetics, Lyman Briggs College, Michigan State University, East Lansing, USA.

Joachim GE, et al. Fertil Steril. 2023:S0015-0282(23)00071-7.

Science/Animal: CBD and transcutaneous electrical nerve stimulation act synergistically against neuropathic pain

Combined, cannabidiol and TENS (transcutaneous electrical nerve stimulation) potentiate pain reduction in neuropathic pain of mice, “potentially associated with spinal IL-10 upregulation.”

Postgraduate Program in Physiological Sciences, Institute of Motricity Sciences, Federal University of Alfenas, Brazil.

Malta I, et al. Neuroreport. 2023;34(3):165-169.

Science/Animal: CBD triggers cell death in hormone-refractory prostate cancer.

In studies with mice cannabidiol alters mitochondrial bioenergetics and triggers cell death in hormone-refractory prostate cancer.

National Research Council of Italy, Institute of Biomolecular Chemistry, Pozzuoli, Italy.

Mahmoud AM, et al. Pharmacol Res. 2023;189:106683.

Science/Animal: CBD reduces lung cancer growth

In mice transplanted human lung cancer cells “inhalant CBD can impede lung cancer growth by suppressing CD44 and angiogenesis.”

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

Salles ÉL, et al. Hum Cell. 2023 Feb 3 [in press].