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IACM-Bulletin of 01 August 2021

Science: Large-scale genetic analyses confirms the assumption that cannabis was first domesticated in East Asia

A research team from Switzerland, China, the UK and India investigated its domestication history using whole-genome resequencing of 110 accessions from worldwide origins. They show that cannabis was first domesticated in early Neolithic times in East Asia and that all current hemp and drug cultivars diverged from an ancestral gene pool currently represented by feral plants and landraces in China.

The investigators identified candidate genes associated with traits differentiating hemp and drug cultivars, including branching pattern and cellulose/lignin biosynthesis. They also found evidence for loss of function of genes involved in the synthesis of the two major biochemically competing cannabinoids THC and CBD during selection for increased fiber production or psychoactive properties.

Ren G, Zhang X, Li Y, Ridout K, Serrano-Serrano ML, Yang Y, Liu A, Ravikanth G, Nawaz MA, Mumtaz AS, Salamin N, Fumagalli L. Large-scale whole-genome resequencing unravels the domestication history of Cannabis sativa. Sci Adv. 2021;7(29):eabg2286.

Science/Human: Cannabis improves stuttering according to case report

According to a case report presented by investigators of the Medical University of Warsaw, Poland, and the Medical School of Hannover, Germany, the use of cannabis may be helpful in the treatment of stuttering. They presented the case of a 20-year-old male with treatment-resistant stuttering, who markedly improved after treatment with medicinal cannabis.

Besides improved speech fluency as assessed by several phoniatric tests, the investigators observed remission of (social) anxiety, improved mood, and reduced stress, resulting in an overall improvement of quality of life after cannabis therapy. The patient, in addition, reported improved attention, concentration, and sleep, increased self-confidence, and better social life. Over a time period of more than a year, treatment was equally effective.

Szejko N, Fremer C, Baacke F, Ptok M, Müller-Vahl KR. Cannabis Improves Stuttering: Case Report and Interview with the Patient. Cannabis Cannabinoid Res. 2021 Jul 26. [in press]

Science/Human: CBD is effective in epilepsy due to Lennox-Gastaut syndrome for at least 3 years

In a long-term open extension trial of CBD in patients with Lennox-Gastautsyndrome (LGS ) the plant cannabinoid was effective in reducing seizure frequency for up to 156 weeks. Patients received plant-derived highly purified CBD (Epidiolex in the United States; Epidyolex in the EURopean Union; 100 mg/ml oral solution), titrated to a target maintenance dose of 20 mg/kg/day over 2 weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30 mg/kg/day.

Of 368 patients with LGS who completed several randomised controlled trials at several hospitals and universities in Poland, the Netherlands, the UK and the USA 366 (99.5%) enrolled in this long-term observational study. Mean treatment duration were 826 days with a mean daily dose of 24 mg/kg/day. Common adverse effects were convulsion (39%), diarrhoea (38%), fever (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal. Median percent reductions from baseline ranged 48%-71% for drop seizures and 48%-68% for total seizures through 156 weeks. Authors concluded that their study is “demonstrating long-term benefits of CBD treatment for patients with LGS.”

Patel AD, Mazurkiewicz-Bełdzińska M, Chin RF, Gil-Nagel A, Gunning B, Halford JJ, Mitchell W, Scott Perry M, Thiele EA, Weinstock A, Dunayevich E, Checketts D, Devinsky O. Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial. Epilepsia. 2021 Jul 20. [in press]

Science/Human: Exercise may improve post-traumatic stress disorder by increasing endocannabinoid levels

In a study with 35 women, who did moderate-intensity aerobic exercise, the blood levels of the endocannabinoid anandamide increased and fear decreased. The study was conducted by investigators of several institutions in the USA. Participant completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise or a light-intensity control condition following extinction training (day 2).

Circulating concentrations of anandamide and BDNF (brain-derived neurotrophic factor) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement. Authors concluded that exercise induced increases of these 2 substances “appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD” (post-traumatic stress disorder).

Crombie KM, Sartin-Tarm A, Sellnow K, Ahrenholtz R, Lee S, Matalamaki M, Almassi NE, Hillard CJ, Koltyn KF, Adams TG, Cisler JM. Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial. Psychoneuroendocrinology. 2021;132:105355.

Science/Human: An increasing number of adults with rheumatic diseases used cannabis

According to a large survey conducted in the US the number of patients suffering from rheumatic diseases tripled between 2014 in 2019. The study included participants in FORWARD, The National Databank for Rheumatic Diseases in Wichita, USA. Participants were asked in 2014 and 2019 about their past and current cannabis use.

Among 11,006 respondents, cannabis use increased from 6% in 2014 to 18% in 2019, with the greatest prevalence of use in states where cannabis use is legal. Most users (74% in 2014; 62% in 2019) reported that cannabis was effective for relief of arthritis symptoms.

Wipfler K, Simon TA, Katz P, Wolfe F, Michaud K. Increase in Cannabis Use Among Adults with Rheumatic Diseases: Results from a 2014-2019 US Observational Study. Arthritis Care Res (Hoboken). 2021 Jul 15. [in press]

Science/Human: Cannabis use is not associated with reduced motivation

Reduced motivation is often noted as a consequence of cannabis use. A study from the Florida International University in Miami demonstrates that this is not the case. Participants in their study were 401 adolescents aged 14-17 at baseline who completed five bi-annual assessments. Researchers assessed motivation at three timepoints using two self-report questionnaires.

On average, adolescent cannabis use frequency increased significantly over time. The disengagement and planning facets of motivation also increased significantly over time, whereas other aspects of motivation remained stable. After controlling for the effect of sex, age, depression, and use of alcohol and nicotine, only a baseline association between cannabis use and valuing school remained significant. Authors concluded there “results do not support a prospective link between cannabis use and reduced motivation among adolescents.”

Pacheco-Colón I, Hawes SW, Duperrouzel JC, Gonzalez R. Evidence Lacking for Cannabis Users Slacking: A Longitudinal Analysis of Escalating Cannabis Use and Motivation among Adolescents. J Int Neuropsychol Soc. 2021;27(6):637-647.

Science/Human: CBD reduced pain in patients with diabetic peripheral neuropath

In a placebo-controlled study with 51 patients suffering from painful diabetic peripheral neuropathy of the feet CBD showed a stronger analgesic effect than the placebo. The study was conducted by Pure Green Pharmaceuticals in Bloomfield, USA. Participants received either a water-soluble CBD preparation, 3 times daily 20 mg, or a corresponding placebo for 28 days

Patients taking the CBD tablets reported clinically significant pain reduction from baseline as compared with placebo. Average pain on a numerical rating scale between 0 and 10 decreased by 3.4 points in the CBD group compared to 1.7 points in the placebo group. Subjects in the CBD group also had improved sleep and reduced anxiety.

Kimless D, Caloura MK, Goldner S. Cannabidiol (CBD) For the Treatment of Painful Diabetic Peripheral Neuropathy of the Feet: A Placebo-Controlled, Double-Blind, Randomized Trial. J Diabetes Metab. 2021;12(5):1-9.

News in brief

Columbia: Companies may export cannabis for medical use
On 23 July Colombia gave the green light for exports of dried cannabis for medical and other industries, as the Andean country took another step to develop its cannabis industry, where progress has been slow despite high potential.
Reuters of 23 July 2021

Argentina: A laboratory to produce cannabis oil will be set up at an Argentine university
The National University of Lanús plans to develop an infrastructure to work on the production of clinical, ethnographic and epidemiological trials to increase scientific knowledge and validate popular knowledge. There are several university campuses in Argentina that have been interested in researching cannabis in the medical field, and now one of these institutions is ready to set up an experimental laboratory.
Ciudad Cannabis News of 13 July 2021

Peru: Government enacts medical cannabis law regulating cultivation
In Peru, Congress passed a bill that will allow for the cultivation of medicinal cannabis and state-regulated cultivation. Thus, with 100 votes in favour, zero against and four abstentions, lawmakers extended the scope of Law 30681, which has regulated medical cannabis since 2017.
El Planteo of 16 July 2021

Sports: World Athletics President questions cannabis use is doping
The rules on the use of cannabis by athletes should be reviewed, World Athletics President Sebastian Coe said on 27 July, after rising track and field star Sha'Carri Richardson will miss the Tokyo Games following a positive test for the substance.
Reuters of 27 July 2021

Science/Cells: Hemp extracts exert anti-cancer effects in ovarian cancer cells
In a study with human ovarian cancer cells hemp extracts and pure CBD induced programmed cell death (apoptosis).
Pharmaceutical Sciences, Sullivan University College of Pharmacy, Louisville, USA.
Wasana K, et al. The FASEB Journ. 2021 April 1. [in press]

Science/Animal: CBD reduced withdrawal symptoms after nicotine cessation
In a study with rats injections with CBD reduced withdrawal symptoms after cessation of nicotine use.
Department of Neuroscience, The Scripps Research Institute, La Jolla, USA.
Smith, et al. Psychopharmacology 238, 2201–2211 (2021).

Science/Cells: CBD may increase the anti-cancer effects of doxorubicin in breast cancer
The treatment of cells from triple negative breast cancer increased the sensitivity to the anti-cancer agent doxorubicin. Authors noted that CBD may increase the therapeutic efficacy of doxorubicin in triple negative breast cancer.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, USA.
Patel N, et al. Int J Pharm. 2021:120943.

Science/Animal: Microinjection of CBD in a certain brain region reduced pain
In a study with rats the injection of very low doses of CBD into the nucleus accumbens, a certain brain region, reduced pain.
Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.
Razavi Y, et al. Neurosci Lett. 2021:136141.

Science/Human: Pain related to Ehlers-Danlos syndrome was reduced by cannabis
Scientists presented the case of a 18-year-old woman, who suffered from pain due to Ehlers-Danlos syndrome, which did not respond to standard medication. They wrote that on “initiating cannabinoid-based treatment, her pain was drastically reduced, immediately enhancing the patient's quality of life.”
University College London Medical School, London, UK.
Dar S, et al. BMJ Case Rep. 2021;14(7):e242568.

Science/Animal: Exposure to THC as a foetus was associated with disturbances of fat metabolism in the liver
In a study with rats, whose mothers were given THC during pregnancy, this treatment had negative effects on liver metabolism during adulthood. Investigators noted that these results indicate that THC exposure before birth may result “in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.”
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, London, Canada.
Oke SL, et al. Int J Mol Sci. 2021;22(14):7502.

Science/Animal: The endocannabinoid system protects nerve cells against damage by kainic acid
Activation of the endocannabinoid system induced by intracerebral injection of URB597, an inhibitor of degradation of endocannabinoid anandamide, protected the normal structure of the hippocampus and prevented neuronal damage and death induced by KA” (kainic acid).
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia.
Gordon RY, et al. Bull Exp Biol Med. 2021 Jul 23. [in press]

Science/Animal: Increase of 2-AG reduces alcohol consumption
In different models of alcohol use disorder in mice the increase of the endocannabinoid 2-AG by inhibition of its degradation resulted in reduced alcohol consumption.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, USA.
Winters ND, et al. J Clin Invest. 2021:146861.

Science/Animal: CBD stabilised the blood-brain barrier after traumatic brain injury
In a rat model of traumatic brain injury CBD stabilised the blood-brain barrier. Authors wrote that “cannabidiol administration improved the integrity and permeability of the blood-brain barrier and reduced edema in the brain after TBI” (traumatic brain injury).
Department of Anatomy and Histology/Embryology, Faculty of Basic Medical Sciences, Kunming Medical University, China.
Jiang H, et al. Brain Res. 2021:147586.

Science/Human: Anxiety and depression did not significantly increase after cessation of cannabis use
In a study with 179 adolescents, who wanted to stop cannabis use, researchers did not find relevant effects on anxiety and depression. They concluded that among “adolescents who use cannabis at least weekly, 4 weeks of cannabis abstinence was not associated with a significant change in anxiety or depressive symptoms compared to continued use.”
Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, USA.
Cooke ME, et al. Front Psychiatry. 2021;12:689957.

Science/Animal: The anxiolytic effects of metamizole are mediated by the CB 1 receptor
A study with mice showed that the antidepressant and anxiolytic effects of metamizole (dipyrone) are mediated by the type 1 cannabinoid receptor.
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.
Topuz RD, et al. EUR J Pharmacol. 2021;908:174315.

Science/Animal: CBD promotes healing of ulcers in the mouth
Oral ulcer is a common inflammatory lesion in the mouth accompanied by severe pain but with few effective treatments. New research shows that CBD is promoting the healing of oral ulcers in mice.
West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Qi X, et al. J Dent Res. 2021:220345211024528.

Science/Human: The likelihood to start opiate use is threefold higher in cannabis users compared to non-cannabis users
Data from large databases from the USA, Australia and New Zealand in the years 1977 to 2017 with
102,461 participants shows, that the risk for the use of opiates is 2.8 times higher in cannabis users compared to non-cannabis users.
The Matilda Centre for Research in Mental Health and Substance Use, The University of Sydney, Australia.
Wilson J, et al. Addiction. 2021 Jul 15. [in press]

Science/Human: Cannabis use is common among patients with colorectal cancer
According to a survey with 1433 patients diagnosed with colorectal cancer 24% were cannabis users. Patients with lower quality of life and advanced-stage cancer were more likely to use cannabis.
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, USA.
Newcomb PA, et al. Cancer Causes Control. 2021 Jul 14. [in press]

Science/Human: Cannabis use may be associated with greater effort allocation during effort--based decision-making
In a study, where participants were asked to undergo tasks of different severity,
cannabis users (mean age: 24.6 years) selected hard trials significantly more than the 45 nonusers (mean age: 23.9 years) regardless of win probability or reward level. Cannabis users were abstinent for at least 24 hours.
Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, USA.
Taylor MB, et al. J Int Neuropsychol Soc. 2021;27(6):559-569.


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