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IACM-Bulletin of March 29, 2020


🌐 Expert Opinion — Claims on infeasibility of cannabis with high THC concentrations for medical use are not supported by science

In March 2020 the IACM Board of Directors decided to install a new category in the IACM-Bulletin, which allows the publication of opinions and statements by researchers on current scientific reports and statements by colleagues. These opinions are meant to encourage the discussion on controversial issues. Today’s opinion is by Dr Franjo Grotenhermen, Executive Director of the IACM, who is running a medical practice in Germany focused on cannabis-based treatments. It is about a claim on cannabis potency for pain relief made by Dr Alfonso Edgar Romero-Sandoval from the Department of Anesthesiology, Wake Forest University School of Medicine in Winston-Salem, USA, and colleagues.

According to the report of a press agency Dr Romero-Sandoval stated: "We know that high-potency products should not have a place in the medical realm because of the high risk of developing cannabis-use disorders, which are related to exposure to high THC-content products." Dr Romero-Sandoval and colleagues analysed cannabis potency in 8505 cannabis samples from 653 legal dispensaries in the US. About 70% of samples for medicinal use were advertised to have more than 15% of THC. In the research article published in Plos One authors claim that “patients consuming these products may be at risk of acute intoxication or long-term side effects.” Romero-Sandoval stated, that multiple studies have shown that cannabis products containing up to 5% of THC are sufficient to reduce chronic pain with minimal side effects.

“In German pharmacies more than 30 varieties of cannabis flowers are available, the majority of which exceed THC concentrations of 15% and often 20%. This makes sense, since with high THC concentrations you need lower doses of cannabis flowers, which reduces the costs for the patients. They should of course continue to have their place in modern treatment with cannabis-based medicines. In a medical context there is no scientific basis, that products with a higher THC content are more dangerous than those with lower THC content,” Dr Grotenhermen stated. “I’ve never seen a patient, whose cannabis product was too potent. You should start with very low doses and then titrate until the tolerated and necessary dose, whatever product you use. If you start too high even a product with 2% THC may be too much in inexperienced patients. We should have a relevant number of varieties of cannabis flowers with different contents of THC, CBD and other cannabis constituents in pharmacies and dispensaries.”

Cash MC , Cunnane K, Fan C, Romero-Sandoval EA. Mapping cannabis potency in medical and recreational programs in the United States. PLoS ONE 15(3): e0230167.

UPI of 26 March 2020

🏷️ Science/Human — THC may be helpful in post-traumatic stress disorder

In a placebo-controlled study study with 71 participants, consisting of 3 groups (25 healthy controls, 27 trauma-exposed adults without post-traumatic stress disorder, and 19 patients with post-traumatic stress disorder) low doses of THC lowered threat-related reactivity in a certain brain region, the so-called amygdala. After intake of placebo or THC all participants underwent a well-established threat processing procedure during functional magnetic resonance imaging (fMRI). The study involved researchers from different departments Wayne State University in Detroit, USA.

THC lowered threat-related amygdala reactivity. Authors concluded that “these preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.”

Rabinak CA, Blanchette A, Zabik NL, Peters C, Marusak HA, Iadipaolo A, Elrahal F. Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study. Psychopharmacology (Berl). 2020 Mar 11. [in press]

🏷️ Science/Human — Exercise in patients with fibromyalgia increases anandamide levels and decreases pain and depression

In a study with 37 women with fibromyalgia and 33 healthy controls a 15-week exercise program resulted in reduced pain and increased anandamide levels. The study was conducted by scientists of the Pain and Rehabilitation Centre of the Department of Health, Medicine and Caring Sciences of Linköping University, Sweden.

After the 15 weeks exercise program anandamide levels were significantly increased in fibromyalgia patients. Pain intensity and depression scorings decreased and muscle strength increased. Authors wrote that the “increased anandamide and decreased SEA [stearoylethanolamide] in women with fibromyalgia after the 15 weeks program might point to a chronic effect of resistance exercise.”

Stensson N, Gerdle B, Ernberg M, Mannerkorpi K, Kosek E, Ghafouri B. Increased Anandamide and Decreased Pain and Depression after Exercise in Fibromyalgia. Med Sci Sports Exerc. 2020 Mar 10. [in press]

🏷️ Science/Human — Cannabis, ondansetron, and promethazine are perceived as most effective in treatments for nausea according to a survey

According to a survey with 153 patients with gastrointestinal chronic nausea cannabis and the standard medication ondansetron and promethazine were rated as most effective to reduce symptoms. The study was conducted at the Division of Gastroenterology and Hepatology of Stanford University School of Medicine in Redwood City, USA. Patients were asked to rate anti-nausea efficacy on a scale of 0 (no efficacy) to 5 (very effective) of 29 commonly used anti-nausea treatments.

The mean efficacy score of all anti-nausea treatments evaluated was 1.7. After adjustment, three treatments had scores statically higher than the mean, including cannabis (2.8), ondansetron (2.6), and promethazine (2.5). Patients with more severe nausea responded better to cannabis and diphenhydramine and less so to metoclopramide. Authors wrote that when “treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, (…)”

Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Zikos TA, Nguyen L, Kamal A, Fernandez-Becker N, Regalia K, Nandwani M, Sonu I, Garcia M, Okafor P, Neshatian L, Grewal D, Garcia P, Triadafilopoulos G, Clarke JO. Dig Dis Sci. 2020 Mar 17. [in press]

🏷️ Science/Human — CBD reduces inflammatory reactions in humans

In a double-blind study with 10 healthy adults researchers of the Food and Nutrition Clinical Research Laboratory, Department of Food Science and Human Nutrition, Colorado State University in Fort Collins, USA, found anti-inflammatory effects of CBD. Participants consumed a single 30 mg dose, which is within the range of typical commercial supplement doses, and blood samples were collected over 6 hr and analyzed for CBD concentrations. Peripheral blood mononuclear cells were collected at baseline and after 90 min, cultured and stimulated with bacterial lipopolysaccharide to induce an inflammatory response.

The pro-inflammatory cytokine TNF-alpha was decreased in LPS-stimulated in the blood cells collected 90 min after CBD exposure relative to cells collected at baseline. authors wrote that this “study provides pilot data for designing and powering future studies to establish the anti-inflammatory potential and bioavailability of a larger variety of commercial CBD products consumed by humans.”

Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman KE, Wei Y, Woelfel KA, Arnold OR, Wolfe LM, Johnson SA, Weir TL. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res. 2020 Mar 8. [in press]

🏷️ Science/Human — CBD may be effective in refractory epileptic spasms

In an open clinical study with 9 patients with refractory childhood-onset epileptic spasms CBD was shown to be effective. The study was conducted by US researchers from Yale University in New Haven and Massachusetts General Hospital in Boston. Patients received plant-derived highly purified CBD in oral solution in addition to their baseline medications at an initial dosage of 5 mg/kg/day, which was increased by 5 mg/kg/day every week to an initial target dosage of 25 mg/kg/day.

Overall, the responder rates in 9 patients were about 75 to 80% after 4 weeks of treatment. In detail they were 67%, 78%, 67%, 56%, 78%, 78%, and 78% after 2 weeks and 1, 2, 3, 6, 9, and 12 months of CBD treatment, respectively. Three out of nine patients (33%) were free of epileptic spasms after two months of treatment. Parents reported subjective improvements in cognitive and behavioral domains. Side effects, primarily drowsiness, were seen in 89% of patients.

Herlopian A, Hess EJ, Barnett J, Geffrey AL, Pollack SF, Skirvin L, Bruno P, Sourbron J, Thiele EA. 2020;106:106988.

News in brief

🏷️ Science — Cannabidiol for Viral Diseases: Hype or Hope?

An article in the official Journal of the IACM “Cannabis and Cannabinoid Research” discusses the use of CBD in viral diseases.

Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy.

Tagne AM, et al. Cannabidiol for Viral Diseases: Hype or Hope? Cannabis Cannabinoid Res. 2020 Jan 15. [in press]

🏷️ Science/Human — Replacement of opiate treatment by cannabis in a pain patient

This report describes a case of 43-year-old female with a traumatic brain injury who developed chronic pain and opioid dependence. Authors wrote that “medical cannabis has risks associated with administration but is safer than opioids. Our patient was successfully weaned off her opioid medications with the help of medical cannabis and pain remained well controlled.”

Hospital of the University of Pennsylvania, Philadelphia, USA.

Caldera FE. SAGE Open Med Case Rep. 2020;8:2050313X20907015.

🌐 Australia — Trial on the efficacy of a cannabis-based medicine in the treatment of dementia has begun

MGC Pharmaceuticals has teamed up with the University of Notre Dame in Perth to commence a new clinical trial for its cannabis extract containing THC and CBD, called “CogniCann”.. The trial will involve a total of 50 patients with dementia or Alzheimer’s disease over the age of 65 at various aged care facilities across Perth. The specific aim is to evaluate the potential behavioural benefits of CogniCann on those patients.

The West Australian of 9 March 2020

🌐 Paraguay — Twelve companies can now produce medical cannabis, which patients will get for free

Paraguay issued its first-ever medical cannabis licenses this February, marking a major shift for the cannabis producing country while raising questions about its approach to fighting illegal cultivation. Twelve pharmaceutical companies received licenses to import seeds for the domestic cultivation and sale of cannabis products with medical benefits, which eligible patients will be able to obtain for free.

Inside Crime of 16 March 2020

🏷️ Science/Animal — Hemp seed oil fed to sows improved fatty acid profiles in piglets

Feeding of hemp seed oil resulted in direct maternal supply with n-3 long-chain polyunsaturated fatty acids, and piglets were able to convert these fatty acids obtained via the sow milk intake higher long-chain fatty acids.

Department of Animal Science, Faculty of Technical Sciences, Aarhus University, Tjele, Denmark.

Vodolazska D, et al. J Anim Sci Biotechnol. 2020 Mar 18;11:28.

🏷️ Science/Animal — Piperine increases bioavailability of CBD by more than twofold

In a study with freely moving rats addition of piperine increased the bioavailability by 2.5-fold in comparison to a control group without piperine.

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel.

Izgelov D, et al. Eur J Pharm Sci. 2020 Mar 17:105313.

🏷️ Science/Animal — Agonists of the GPR55 and the GPR18 cannabinoid receptors improved bladder overactivity

In a study with female rats the synthetic cannabinoid O-1602, which activates the new cannabis receptors GPR55 and GPR18, was shown to improve improve overactivity of the bladder muscle, and according to the authors “may serve as a promising novel substance for the pharmacotherapy of bladder diseases.”

Second Department of Gynecology, Medical University of Lublin, Poland.

Wróbel A, et al. Molecules 2020;25(6).

🏷️ Science/Human — A variant of the gene which encodes the CB1 receptor is associated with Tourette syndrome

New findings suggest that a certain variant of the CNR1, the gene which encodes the CB1 receptor may be a risk factor for the development of Tourette syndrome. They wrote that the “variant can be potentially associated with abnormal endocannabinoid transmission,” which is suspected to be one of the causes of Tourette syndrome.

Department of Neurology, Medical University of Warsaw, Poland.

Szejko N(, et al. Front Genet. 2020 Mar 4;11:125.

🏷️ Science/Cells — CBD may be protective in a model of Parkinson’s disease

In cells cannabidiol was shown to exert preventive and protective effects in Parkinson's disease activating a certain pathway within cells.

IRCCS Centro Neurolesi "Bonino Pulejo", Messina, Italy.

Gugliandolo A, et al. Fitoterapia. 2020 Mar 14:104553.

🏷️ Science/Human — THC improves gastrointestinal symptoms in a patient with a rare chronic intestinal disease (CIPO)

Researchers reported of a 19 year old female with chronic intestinal pseudo-obstruction (CIPO, responded well to low doses of THC. CIPO is a rare cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life.

Pediatric Gastroenterology-Hepatology-Nutrition Unit, Necker-Enfants-Malades Hospital, Paris, France.

Zemrani B, et al. JPEN J Parenter Enteral Nutr. 2020 Mar 17. [in press]

🏷️ Science/Human — Cannabis use was not associated with drug use disorder after 16 years

In a study, which used survey data collected in 1998 to 2000 with 10,345 participants aged 20 to 64 years, were followed for 16 years “there was no independent association between cannabis use and subsequent drug use disorders. The association with subsequent drug use disorders was rather explained by other illicit drug use, which cannabis users were at higher risk of at the three-year follow-up.”

Karolinska Institutet, Department of Public Health Sciences, Stockholm, Sweden.

Rabiee R, et al. Addict Behav. 2020;106:106390.

🏷️ Science — High number of conflicts of interests among authors of published articles on CBD

In a study researchers found that of 99 human CBD studies done since 2014, about 62 percent had some conflict of interest, including industry funding, or a study author employed by a company that markets CBD products.

Wellesley College, USA.

Deary EC, et al. Ann Intern Med. 2020 Mar 17. [in press]

🏷️ Science/Human — Higher levels of anandamide in seminal fluid were associate with lower sperm motility

In a study with 200 men anandamide concentrations in seminal fluid and oleoylethanolamide (OEA) concentrations in blood serum appeared inversely correlated with sperm motility, while semen palmytoylethanolamide (PEA) was positively linked to sperm concentration.

Service of Clinical Chemistry & Toxicology, Central Institute of Hospitals, Hospital of Valais, Sion, Switzerland.

Zufferey F, et al. Andrology. 2020 Mar 13. [in press]

🏷️ Science/Human — Cannabis use does not influence gastric surgery against obesity

According to an analysis of 1176 patients, who underwent weight loss surgery, there was no negative effect of cannabis use on its outcome. Authors concluded that cannabis use “should not be a contraindication to bariatric surgery.”

University of Maryland School of Medicine, USA.

Shockcor N, et al. Surg Endosc. 2020 Mar 12. [in press]

🏷️ Science/Animal — CBD reduces changes in a mouse model of schizophrenia through serotonin receptors

According to a mouse model CBD induces antipsychotic-like effects by activating 5-HT1A receptors (or serotonin receptors). Authors wrote that the investigations “indicate that this compound could be an interesting alternative for the treatment of negative and cognitive symptoms of schizophrenia.”

Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.

da Silva NR, et al. Pharmacol Res. 2020 Mar 6:104749. [in press]

🏷️ Science/Human — Levels of anandamide are reduced in cerebral fluid in patients with narcolepsy

Scientists investigated the endocannabinoid system in patients with narcolepsy to type 1 (6 patients) and type 2 (6 patients) compared to healthy controls. No differences were found between the levels the endocannabinoid anandamide in cerebrospinal fluid in type 2 patients (NT2) versus controls and between 2-AG levels in all groups, although a trend toward a decrease in type 1 patients (NT1) was evident. Authors “hypothesize that the endocannabinoid system is dysregulated in NT1.”

IRCCS Neuromed, Sleep Medicine Center, Italy.Romigi A, et al. CNS Neurol Disord Drug Targets. 2020 Mar 9. [in press]