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IACM-Bulletin of 25 September 2022

Science/Human: Cannabis may improve autism symptoms

In a study with a cannabis extract containing a ratio of THC to CBD of 1 to 20 children with autism spectrum disorder showed significant improvement. The study was conducted by investigators of Azrieli National Centre for Autism and Neurodevelopment Research at Ben Gurion University in Beer Sheva, Israel, and other Israelian universities. “Parents were instructed to start with one drop daily (each drop contains: 0.3 mg THC and 5.7 mg CBD) and increase the dosage gradually until they perceived improvements in their child’s behavior such as decreased irritability, aggressiveness, hyperactivity, and/or sleep disturbances.” Patients received the extract for 6 months in an open study, which was completed by 82 participants.

The final dose did not exceed 400 mg/day of CBD and 20 mg/day of THC. There were overall significant improvements in social communication abilities with larger improvements in participants who had more severe initial symptoms. Since the extract contained rather high doses of THC it is unclear from the study, whether the effect was mainly due to THC, since previous studies with pure CBD only showed minor effects on autism.

Hacohen M, Stolar OE, Berkovitch M, Elkana O, Kohn E, Hazan A, Heyman E, Sobol Y, Waissengreen D, Gal E, Dinstein I. Children and adolescents with ASD treated with CBD-rich cannabis exhibit significant improvements particularly in social symptoms: an open label study. Transl Psychiatry. 2022;12(1):375.

Science/Human: A CBD-rich cannabis extract improved symptoms in drug-resistant epilepsy

In an open study by investigators of the National University of Colombia in Bogotá, Colombia, with 44 adult patients with drug-resistant focal epilepsy CBD-rich cannabis improved symptoms. All participants were on stable doses of antiepileptic medication and in addition received a cannabis based preparation containing 100 mg/mL CBD and less than 1.9 mg/mL THC. The extract was administered every 12 hours for 12 weeks.

The median daily dose of CBD was 200 mg that of THC was 4 mg. The median number of seizures per month before CBD treatment was 11 and after CBD treatment significantly reduced to 2.5. A reduction in seizures of more than 50% at 12 week was achieved in 79.5% of the patients. Authors concluded that this cannabis extract is “a highly effective and safety therapy to treat adult patients with DRFE [drug-resistant focal epilepsy]. The reduction in seizures frequency is maintained over time.”

Navarro CE. Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study. Neurol Sci. 2022 Sep 21. [in press].

Science/Human: Oleoylethanolamide may improve clinical outcome in stroke patients according to a controlled study

In a study with 60 patients, who were admitted to hospital within 12 hours after start of stroke symptoms, the addition of the endocannabinoid-like substance oleoylethanolamide (OEA) to the standard treatment improved the outcome. They either received 300 mg or 600 mg per day of the medication or a placebo for 3 days. The investigation was conducted by researchers of Hamadan University of Medical Sciences, Iran.

Results show that the medium dose of 300 mg OEA improves short-term inflammatory, lipid, and biochemical parameters. There was a statistically significant difference between patients receiving the endocannabinoid and placebo in terms of interleukin-6, a pro-inflammatory mediator in the immune system.

Sabahi M, Ahmadi SA, Kazemi A, Mehrpooya M, Khazaei M, Ranjbar A, Mowla A. The Effect of Oleoylethanolamide (OEA) Add-On Treatment on Inflammatory, Oxidative Stress, Lipid, and Biochemical Parameters in the Acute Ischemic Stroke Patients: Randomized Double-Blind Placebo-Controlled Study. Oxid Med Cell Longev. 2022;2022:5721167.

Science/Human: Palmitoylethanolamide may improve negative symptoms in patients with schizophrenia

In a study by investigators of Tehran University of Medical, Sciences, Iran, with 50 patients suffering from schizophrenia the endocannabinoid-like substance palmitoylethanolamide (PEA) reduced negative symptoms. Participants received either the standard medication risperidone and palmitoylethanolamide in a dose of 600 mg twice daily or risperidone and placebo for 8 weeks.

There was a significant effect on negative symptoms in the PEA group. In contrast, the longitudinal changes in positive symptoms and depressive symptoms were similar between groups. Authors concluded that “adjunctive therapy with PEA and risperidone alleviates schizophrenia-related primary negative symptoms in a safe manner. “

Salehi A, Namaei P, TaghaviZanjani F, Bagheri S, Moradi K, Khodaei Ardakani MR, Akhondzadeh S. Adjuvant palmitoylethanolamide therapy with risperidone improves negative symptoms in patients with schizophrenia: A randomized, double-blinded, placebo-controlled trial. Psychiatry Res. 2022;316:114737.

News in brief

Malaysia: The government aims to learn from Thailand in push for medical use of cannabis
Malaysia plans to learn from the cannabis policy of neighbouring Thailand in its effort to legalise use of the drug for medical purposes, a health ministry official said, in a country where possession can bring the death penalty now.
Reuters of 17 August 2022

Germany: Large majority of citizens supports government plans to legalise cannabis
The majority of German citizens, especially younger people, support the plans of the traffic light coalition for a general legalization of cannabis for adults. A recent survey by the market and opinion research institute Ipsos now shows that more than half of Germans welcome this step. 61 percent of respondents say they would support the controlled dispensing of cannabis in licensed stores.
Presseportal of 8 September 2022

Uruguay: Legalisation of cannabis has reduced illegal traffic of the drug
The legalisation of cannabis has helped to take drug traffickers out of the market, but the legal supply of the drug is still insufficient and of low potency, which leads most consumers to turn to the illegal market. The 2021 data show that 27% of drug users buy cannabis legally. In 2013, Uruguay became the first country in the world to legalize and regulate the production and consumption of cannabis.
Play Crazy Game of 21 September 2022

Science/Cells: CBD protects nerve cells against damage from lack of oxygen supply
CBD was shown to protect nerve cells against damage in case of reduced oxygen supply. Authors noted that these “results reinforce the potential of CBD for the therapy of the hypoxia of the neonate” during birth.
CiberNed, Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, Madrid, Spain.
Lillo J, et al. Int J Mol Sci. 2022;23(17):9695.

Science/Animal: CBD may be helpful against prostate cancer
The growth of prostate cancers in “mouse models were reduced following treatment with cisplatin and cannabidiol.”
University of Johannesburg, Department of Biochemistry, Gauteng, South Africa.
Motadi LR, et al. AACR; Cancer Res 2022;82.

Science/Animal: CBD decreases motor impairment in a model of Parkinson’s disease
In a rat model of Parkinson’s disease CBD improved motor function and this effect was mediated by inhibitory effects of the cannabinoid on the GPR55 receptor.
Laboratorio de Neurofarmacología, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Mexico.
Patricio F, et al. Front Pharmacol. 2022;13:945836.

Science/Animal: Isoflavonoids may increase endocannabinoid levels and act as antidepressants
Isoflavonoids, which are present in many plants, including cannabis may act as inhibitors of fatty acid amide hydrolase (FAAH), which degrades anandamide thus increasing its levels. They showed antidepressant effects in mice.
Department of Pharmacy, COMSATS University Islamabad, Khyber Pakhtunkhwa, Pakistan.
Zada W, et al. Pharmacol Res Perspect. 2022;10(5):e00999.

Science/Animal: Inhibition of FAAH protects against kidney damage
In a mouse model of reduced blood supply to the kidneys inhibition of the enzyme FAAH (fatty acid amide hydrolase), which is responsible for anandamide degradation, protects kidney cells against fibrogenesis and reduced function.
Department of Pharmacology & Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, USA.
Chen C, et al. Biochim Biophys Acta Mol Basis Dis. 2022;1868(10):166456.

Science/Animal: 2-AG reduces hypersensitivity in alcohol withdrawal
In mice, which underwent alcohol withdrawal, increase of the endocannabinoid 2-AG (2-arachidonoylglycerol) reduces mechanical hypersensitivity due to withdrawal.
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, USA.
Morgan A, et al. Alcohol Clin Exp Res. 2022 Sep 20. [in press].

Science/Animal: Cannabis oil ameliorates pain in a fibromyalgia model
In a mouse model of fibromyalgia “repeated cannabis oil administration, given daily for 14 days, markedly mitigated the mechanical and thermal sensitivity during the FM model, and its reduced depressive-like behavior.”
Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Araranguá, Universidade Federal de Santa Catarina, Brazil.
Ferrarini EG, et al. Biomed Pharmacother. 2022;154:113552.

Science/Animal: Endocannabinoids ameliorate allergic airway inflammation
Inhibition of the degradation of both endocannabinoids anandamide and 2-AG in guinea pigs can “be a promising strategy for bronchial hyperreactivity and airway inflammation in allergic asthma.”
Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey.
Abohalaka R, et al. Life Sci. 2022 Oct 1;306:120808.

Science/Animal: CBG attenuates pain in peripheral neuropathy
In a mouse model of cisplatin-induced neuropathy CBG (cannabigerol) reduced pain. It did not reduce other forms of pain.
Department of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
Sepulveda DE, et al. EUR J Pain. 2022;26(9):1950-1966.

Science/Animal: CBD attenuates symptoms of traumatic spinal cord injury
In a study with rats CBD reduced pain after traumatic spinal-cord injury and the “antinociceptive effect induced by CBD is regulated by reducing oxidative stress by decreasing the LP [lipid peroxidation] and increasing the concentration of antioxidant (GSH) defenses.”
Laboratorio de Neurofarmacología Molecular, Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico.
Baron-Flores V, et al. Neurosci Lett. 2022;788:136855.

Science/Animal: The development of an antiglaucoma eyedrop
In a study with rabbits researchers developed eyedrops based on an inhibitor of MAGL (monoacylglycerol lipase), thus increasing the level of 2-AG.
Department of Pharmacy, University of Pisa, Italy.
Chetoni P, et al. Int J Pharm. 2022;625:122078.

Science/Animal: Anandamide and 2-AG modulate autistic -like traits in rats
In a rat model of autism spectrum disorder the two endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) had different effects on symptoms.
Department of Science, Roma Tre University, Rome, Italy.
Schiavi S, et al. Neuropsychopharmacology. 2022 Sep 16. [in press].

Science/Animal: CBD enhances analgesic effects of morphine
In a rat model of nerve damage CBD was able to enhance analgesic effects of morphine and attenuated opioid-induced tolerance.
Department of Pharmacology, Biological Sciences Sector, Federal University of Paraná, Curitiba, Paraná, Brazil.
Jesus CHA, et al. Behav Brain Res. 2022;435:114076.

Science/Animal: Development of a CBD nanoemulsion for application through the nose mucosa
Scientists achieved good nasal permeability of a CBD nanoemulsion for direct nose to brain delivery.
Jamia Hamdard Faculty of Pharmacy, Dept. of Pharmaceutics, SPER, New Delhi, India.
Hameed B, et al. Biomed Mater. 2022 Sep 15. [in press].

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