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IACM-Bulletin of January 5, 2020

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Italy — Growing small amounts of cannabis at home is not a crime, the High Court rules

Growing small amounts of cannabis at home for private use is not a crime, Italy’s top court has ruled, putting an end to a yearlong legal dispute. A 1990s law prohibits the cultivation and sale of cannabis in Italy, but conflicting court decisions created confusion over how it should be interpreted. The country’s highest court appears to have settled at least part of the question, writing in a statement of its findings that “at home, small-scale cultivation activities are to be considered excluded from the application of the penal code.”

The judges produced the document on 19 December. A full, detailed ruling remains weeks or months away, so the court’s complete reasoning has not been made public. Among the unanswered questions is how much cannabis qualifies as “small-scale cultivation,” but the ruling stemmed from a case in which the defendant had two plants. The court appears to have stopped short of outright legalizing cannabis, but has decriminalized small-scale, private cultivation, meaning that while it might still be technically illegal, it is not treated as a serious crime and carries only light penalties.

New York Times of 27 December 2019

Science/Human — The oral intake together with fat may increase the systemic bioavailability of THC by two-fold

In a controlled 4-way crossover investigation with 28 healthy adults researchers demonstrated, that the intake of oral THC together with a high-fat meal increased systemic bioavailability of THC and its primary metabolite 11-hydroxy-THC by twofold or more. The study was conducted by 3 Canadian institutions, Aurora cannabis in Leduc, MedReleaf in Markham, and the Faculty of Medicine and Dentistry of the University of Alberta in Edmonton and published in Cannabis and Cannabinoid Research. THC capsules (1 or 2×5 mg) were either administered under a fasted condition or after a high-fat meal.

The presence of high-fat food, which included 57 g of fat (mainly through eggs, milk and butter), significantly enhanced time to peak plasma concentration (T max) and area under the curve, an expression of systemic bioavailability, for both THC and 11-OH-THC. Females had a significantly greater peak plasma concentration compared with males after 5 mg THC in a fasted state. Systemic bioavailability increased by 2.7 for the 5 mg THC condition and by 2.0 for the 10 mg THC condition.

Lunn S, Diaz P, O'Hearn S, Cahill SP, Blake A, Narine K, Dyck JRB. Human pharmacokinetic parameters of orally administered δ9-tetrahydrocannabinol capsules are altered by fed versus fasted conditions and sex differences. Cannabis Cannabinoid Res. 2019;4(4):255-264.

Science/Human — Exercise reduced headache attacks and anandamide levels in migraine sufferers in controlled study

In a study at the hospital São Paulo, Brazil, a 12-week aerobic exercise intervention reduced the number of headache attacks and blood concentration of the endocannabinoid anandamide in migraine sufferers. The study included 4 groups, one group of migraine sufferers, who underwent the exercise program (completed by 13 participants), a group of migraine sufferers without exercise (completed by 12), a control group of healthy people without exercise (completed by 13) and a group of healthy subjects, who participated in the aerobic exercise intervention (completed by 12 participants). The research was recently published in the Journal of the IACM, Cannabis and Cannabinoid Research.

The blood anandamide (AEA) levels were significantly reduced in patients with migraine in the exercise group and in the control exercise groups. The number of days with migraine, migraine attacks, and medication used reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups. Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group. Authors wrote that this study “suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients.”

Oliveira AB, Ribeiro RT, Mello MT, Tufik S, Peres MFP. Anandamide is related to clinical and cardiorespiratory benefits of aerobic exercise training in migraine patients: a randomized controlled clinical trial. Cannabis Cannabinoid Res. 2019;4(4):275-284.

Science/Human — Patients with Tourette syndrome prefer medicinal cannabis over pure THC and Sativex according to a survey

According to an online survey conducted by researchers of the Medical School of Hannover, Germany, and the Medical University of Warsaw, Poland, cannabis-based medicines may be an effective treatment against symptoms of Tourette syndrome. The survey included all patients seen at some time at the Clinic of Psychiatry, Social Psychiatry and Psychotherapy of the Medical School of Hannover, who had used cannabis-based medicines for the treatment of Tourette syndrome. 98 patients were identified.

Of the 38 patients whose data have been analysed, 66% preferred treatment with medicinal cannabis, 18% dronabinol, 11% Sativex, and 5% street cannabis. Altogether, cannabis-based medicines resulted in a subjective improvement of tics and comorbidities. Most comorbidities were obsessive compulsive disorder, ADHD and sleeping disorders. Dosages of cannabis-based medicines varied considerably.

Milosev LM, Psathakis N, Szejko N, Jakubovski E, Müller-Vahl KR. Retrospective analysis and online survey. Cannabis Cannabinoid Res. 2019;4(4):265-274.

News in brief

USA — Cannabis becomes legal for use by adults in Illinois

Starting New Year’s Day, people 21 and older are able to legally buy up to 30 grams of cannabis flower, 5 grams of cannabis concentrate, or 500 grams of THC-infused products such as edibles at licensed commercial dealers throughout the state.

Reuters of 24 December 2019

Peru — Legal sale of medicinal cannabis oil started in the country

On 12 December began the legal sale of medicinal cannabis oil. Currently it is only available in one pharmacy in the district of San Miguel. The 10 ml bottle of the product has a price of 47.70 soles (about 13 Euros).

Voces of 14 December 2019

Zambia — Approval to export cannabis

Zambia has legalized the production and export of cannabis for economic and medicinal purposes, the government’s chief spokeswoman said on 16 December, becoming the latest country to change its position on the drug to give its finances a boost. The approval for the export of cannabis was granted at a special cabinet meeting on 4 December, spokeswoman Dora Siliya said in a statement.

Reuters of 16 December 2019

Israel — An Israeli company imports cannabis from Portugal

Israel’s InterCure said on 2 January its subsidiary Canndoc has signed a strategic cooperation agreement with Tilray for the import and export of medical cannabis. Canndoc has an option to import 2.5 tons of high quality cannabis from Tilray’s facilities in Portugal, with a first shipment of 250 kilograms already on its way to Israel. Canndoc said to its knowledge this is the first medical cannabis imported commercially to Israel.

Reuters of 2 January 2020

Science/Animal — THC exposure during adolescence has no effect on interest for nicotine in adults

According to a study with mice the exposure to THC during adolescence (during days 35 to 49 after birth) had no effect on nicotine self-administration or nicotine seeking behaviour during adulthood (day 70)

Department of Experimental and Health Sciences, Universidad Pompeu Fabra, Barcelona, Spain.

Flores Á. Psychopharmacology (Berl). 2019 Dec 19. [in press]

Science/Animal — Beta-caryophyllene reduces neuropathic pain

Beta-caryophyllene, a terpene which binds to the CB2 receptor, was shown to reduce neuropathic pain, which was induced by antiretroviral medication

Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.

Aly E. Molecules. 2019 Dec 27;25(1).

Science — New cannabinoids have been detected in cannabis

In two articles 3 new cannabinoids have been presented by Italian researchers. One is delta-9-tetrahydrocannabutol (THCB), the butyl derivative of delta-9-THC, which is a partial agonist of the CB1 receptor. The second is canabidibutol (CBDB), the butyl derivative of cannabidiol (CBD). The third is delta-9-tetrahydrocannabiphorol (THCP), which is a full agonist at the CB1 receptor and “could account for the pharmacological properties of some cannabis varieties difficult to explain by the presence of the sole delta-9-THC.”

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

National Council of Research (CNR), Lecce, Italy.

Linciano P. J Nat Prod. 2019 Dec 31. [in press]

Citti C. Sci Rep. 2019 Dec 30;9(1):20335.

Science/Human — 2-AG is increased in acute coronary syndrome

In a study with 83 patients undergoing coronary angiography there was large variation in the concentration of the endocannabinoid 2-AG (2-arachidonoylglycerol) in the blood of coronary arteries. It was lowest in patients without coronary artery disease and highest in patients with myocardial infarction.

Department of Internal Medicine II Cardiology, Pneumology, Angiology, University Hospital Bonn, Germany.

Jehle J. PLoS One. 2019;14(12):e0227142.

Science/Animal — PEA stimulates the production of 2-AG

The endocannabinoid palmitoylethanolamide (PEA) was shown to stimulate the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG).

Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.

Petrosino S. J Neuroinflammation. 2019;16(1):274.

Science/Cells — The endocannabinoid 2-linoleoylglycerol modulates the effects of other endocannabinoids

The endocannabinoid 2-linoleoylglycerol was shown to be a partial agonist at the CB1 receptor and capable of modulating the activity of the well-known endocannabinoids anandamide and 2-AG.

Wolfson Centre for Age-Related Diseases, King's College London, UK.

Lu L. Cannabis Cannabinoid Res. 2019;4(4):231-239.

Science/Human — Higher risk of stroke in cannabis users

In a large US sample of more than 3 million hospitalisations among young adults with current or previous cannabis use researchers identified a higher risk (16% higher of overall young-onset stroke) of stroke-related hospitalizations and worse outcomes among cannabis users aged 18-49 years from 2007 to 2014. It is unclear whether cannabis components or toxic components of smoke are responsible for this.

Division of Cardiology, Atlanta VA Medical Center, Decatur, USA.

Desai R. Int J Stroke. 2019 Dec 23:1747493019895651.

Science/Human — Cannabis laws reduce the use of opioids

According to an analysis of 1.5 billion opioids prescriptions between 2011 and 2018 researchers found that recreational and medical cannabis access laws reduce the number of morphine milligram equivalents prescribed each year by 11.8 for a legalisation of recreational use and 4.2 percent for medical cannabis use, respectively. These laws also reduce the total days' supply of opioids prescribed and the total number of patients receiving opioids.

University of Alabama School of Law, Tuscaloosa, USA.

McMichael BJ. J Health Econ. 2019;69:102273.

Science/Human — Recreational cannabis use may change the structure of the heart

According to MRI scans of 3407 individuals cannabis use may be associated with a larger left ventricle. However, the study is limited due to the low number of regular users among the scanned individuals. And it remains unclear, whether smoked toxins or cannabis compounds may be responsible for the observations.

Queen Mary University in London, UK.

Khanji MY. JACC Cardiovasc Imaging. 2019 Dec 18. [in press]

Science/Animal — Beta-caryophyllene shows antidepressant-like effects

In stressed animals the administration of beta-caryophyllene improved chronic stress related behaviour. Authors quote that these results “suggest that BCP may be effective in treating depression and stress related mental illnesses.”

Kyung Hee University, Yongin, Republic of Korea.

Hwang ES. Behav Brain Res. 2019;380:112439