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IACM-Bulletin of February 13, 2022


USA — Mississippi becomes the 37th state to legalise the medical use of cannabis

Mississippi joined 36 other U.S. states in legalizing cannabis for medical use on 2 February, as the governor signed legislation permitting cannabis for treatment of severe health conditions such as cancer, AIDS and Alzheimer's disease. Announcing enactment of the bill, Governor Tate Reeves said the final version passed last week by the Republican-controlled legislature was designed to curb recreational cannabis use, such as by allowing patients to obtain no more than 3 ounces of cannabis per month, or 3.5 grams a day.

Under it, an individual can legally obtain medical marijuana only if diagnosed with one of approximately two dozen qualifying conditions, including cancer, Parkinson's disease, Huntington's disease, muscular dystrophy, Alzheimer's, autism, post-traumatic stress disorder and severe injury. The measure also permits cannabis to be prescribed for any "pain state in which the cause of the pain cannot be removed or otherwise treated ... and which no relief or cure of the cause of the pain is possible."

Reuters of 3 February 2022

Science/Human — Cannabis may be helpful in the treatment of chronic migraine according to a retrospective study

Investigators of the Department of Biomedical, Metabolic and Neural Sciences at the University of Modena and Reggio Emilia, Italy, compared 3 oral preparations made from 3 different cannabis strains (FM2, Bedrocan, Bediol) in the treatment of chronic migraine. The number of migraine days per month, pain intensity, and other parameters were recorded at baseline and at 3 months and 6 months after the start of treatment.

The number of migraine days did not change significantly after the third month or the sixth month when compared with baseline. The pain intensity, the acute medication consumption, and the number of days per month in which patients took at least one acute medication significantly decreased when compared with baseline. Different oral cannabinoid preparations displayed similar levels of effectiveness. The adverse events were mostly mild and occurred in 44% of patients.

Baraldi C, Lo Castro F, Negro A, Ferrari A, Cainazzo MM, Pani L, Guerzoni S. Oral Cannabinoid Preparations for the Treatment of Chronic Migraine: A Retrospective Study. Pain Med. 2022;23(2):396-402.

Science/Human — A cannabis extract and pure THC reduce pain according to two analyses from the German Pain e-Registry

Researchers of the Center of Excellence in Health Care Research of the German Pain Association in Nuernberg, Germany, analysed data from the German Pain e-Registry. In the first analysis they compared 337 patients treated with the cannabis extract Sativex, containing about equal amounts of THC and CBD, and 337 patients treated with THC. Mean THC dose over the 24-week evaluation period was 16.6 mg for Sativex and 17.2 mg for THC. Median improvement relative to baseline was 55% for Sativex and 41% for THC. More Sativex- than THC-treated patients were able to discontinue other pain medications.

Another analysis with 1145 patients with refractory chronic pain receiving pure THC showed that average pain intensity decreased from 46 to 27 on a visual analogue scale. Average daily THC dose was 16 mg. Authors concluded that “add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.” DRO was used as abbreviation for dronabinol/THC

Ueberall MA, Horlemann J, Schuermann N, Kalaba M, Ware MA. Effectiveness and tolerability of dronabinol use in patients with chronic pain - a retrospective analysis of 12-week open-label real-world data provided by the german pain e-registry. Pain Med. 2022:pnac010.

Ueberall MA, Essner U, Vila Silván C, Mueller-Schwefe GHH. Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry. J Pain Res. 2022;15:267-286.

Science/Human — Patients with neuropathic pain may benefit from a treatment with cannabis

Cannabis-based medicines may be beneficial in patients with neuropathic pain. Investigators of the Mental Health Center of Copenhagen University Hospital, Denmark, used nationwide data of a medical cannabis program with 1817 patients, who suffered from neuropathic pain, and 924 patients suffering from other pain disorders.

Among both patient groups, users of THC used more opioids during follow-up than controls. Among patients with neuropathic pain, however, users of either CBD, THC, or combined CBD + THC used less gabapentin than controls. Users of all three classes of cannabis-based medicines were hospitalized fewer days than controls among neuropathic-pain patients but not among patients with other or unspecified pain disorders.

Hjorthøj C, La Cour P, Nordentoft M, Posselt CM. Cannabis-based medicines and medical cannabis for patients with neuropathic pain and other pain disorders: Nationwide register-based pharmacoepidemiologic comparison with propensity score matched controls. Eur J Pain. 2022;26(2):480-491.

Science/Human — Cannabis use is associated with decreased mortality in trauma patients

The 2017 Trauma Quality Improvement Program database was used by investigators of the Department of Surgery of the University of California in Irvine, USA, to compare trauma patients with and without cannabis use. Cannabis users were younger but had a similar median injury severity score compared to patients without cannabis use.

Multivariable analysis of data showed, that mortality risk was 21% lower in cannabis users (OR 0.79) and this effect was highly significant (P < .001). Authors concluded that cannabis users “had decreased associated risk of mortality compared to” non-cannabis users. They wrote that these “findings require corroboration with future prospective clinical study and basic science evaluation to ascertain the exact pathophysiologic basis and thereby target potential interventions.”

Bloom SR, Grigorian A, Schubl S, Thangathurai D, Kuza CM, Swentek L, Nahmias J. Title: Marijuana Use Associated with Decreased Mortality in Trauma Patients. Am Surg. 2022 Feb 3:31348211069789.

News in brief

Science/Human — Cannabis use may reduce the intake of opioids in patients with chronic back pain

In a study with 186 patients with chronic back pain, who were allowed to use cannabis there was a significant reduction in opioid use within 6 months after start of the cannabis treatment as well as improved quality of life.

Department of Physical Medicine and Rehabilitation, Rothman Orthopedic Institute at Thomas Jefferson University, Pennsylvania, USA.

Greis A, et al. Cureus 2022;14(1): e21452.

Science/Human — Cannabis may reduce the need for opioids in pain patients

In a study with 115 pain patients, who received opioids, the use of cannabis led to a 67% decrease of opiate use on average.

Allegheny Health Network/West Penn Hospital, Institute for Pain Medicine, Pittsburgh, USA.

Benedict G, et al. Pain Physician. 2022 ;25(1):E113-E119.

Science/Human — Cannabis reduces intraocular pressure by an average of 16%

In a study with 11 healthy people a single dose of inhaled cannabis reduced intraocular pressure within one hour by 16 % on average. Reduction of intraocular pressure was negatively correlated with THC plasma concentrations up to a plasma level of 20 ng/mL.

Gavin Herbert Eye Institute, University of California, Irvine, USA.

Mosaed S, et al. Front Med (Lausanne). 2022;8:736792.

Thailand — All parts of the cannabis plant are legal if they contain less than 0.2% THC

Thailand on 8 February moved one step closer toward being the first Asian nation to decriminalize cannabis, after its health minister signed a measure officially dropping cannabis from a list of controlled drugs. The delisting will mean all parts of cannabis, including flowers and seeds, are allowed to be used in Thailand. However, products remain illegal if they contain more than 0.2% THC.

AP NEWS of 8 February 2022

Botswana — High Court rules that cannabis may be legally grown for medicinal purposes

In an unprecedented ruling on 21 January the High Court in Gaberone gave the company Fresh Standard Ltd the exclusive license to produce hemp and cannabis for industrial and medical purposes in the country.

Cannabiz Africa of January 2022

Science/Human — Psychomotor impairment following cannabis use decreases significantly within one hour in regular users

Findings of a study with 70 frequent cannabis users “demonstrate that psychomotor impairment emerges immediately after acute cannabis use even in regular users, but decreases significantly 1 h postuse.”

Institute for Cognitive Science, University of Colorado, Boulder, USA.

Karoly HC, et al. Cannabis Cannabinoid Res. 2022;7(1):107-115.

Science/Human — Inhaled cannabis use reduces self-reported pain severity

Using an app data from 131 582 sessions, in which inhaled cannabis was used to treat muscle pain, joint pain or nerve pain the drug was shown to reduce pain severity by about 42 to 49%.

Department of Psychology, Washington State University, Pullman, Washington, USA.

Cuttler C, et al. . Cannabis Cannabinoid Res. 2022;7(1):93-99.

Science/Cells — Cannabinoids influence several enzymes of the cytochrome P450 complex in the liver resulting in interactions with several medicinal drugs

Researchers provide “for the first time a comprehensive analysis of the potential for cannabidiol, delta-9-tetrahydrocannabinol, and their metabolites to inhibit cytochrome P450 enzymes in a reversible or time-dependent manner. These analyses enabled us to predict the potential of these cannabinoids to produce drug interactions in vivo at clinical or recreational doses.”

Department of Pharmaceutics, University of Washington, USA.

Bansal S, et al. Drug Metab Dispos. 2022:DMD-AR-2021-000734.

Science/Animal — CBD reduced consequences of stroke

In a study with rats CBD reduced infarct size volume after stroke. Authors wrote that “CBD played the anti-apoptosis and anti-oxidant roles in cerebral ischemia by affecting the pathways of intrinsic apoptosis, endogenous antioxidant enzymes, and lipid peroxidation.”

Department of Plant Sciences, Faculty of biological Sciences, Alzahra University, Tehran, Iran.

Khaksar S, et al. Brain Res Bull. 2022;180:118-130.

Science/Human — CBD was beneficial in patients with post-concussion syndrome

Results from a case series with 4 females suffering from post-concussion syndrome “suggest that CBD can help to improve the altered autonomic dysfunction in those with post-concussion syndrome, and that responses to the drug administration was individualized.”

Faculty of Kinesiology & Health Studies, University of Regina, Canada.

Singh J, et al. Can J Physiol Pharmacol. 2022;100(2):192-196.

Science — Kynurenine is found in cannabis and shows anti-inflammatory properties

Kynurenine is a product of the metabolism of L-tryptophan in the central nervous system of animals, but it is not commonly found in plants, but is present in cannabis. It has anti-oxidative, anti-inflammatory, hypolipidemic, and neuroprotective properties.

Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Italy.

Russo F, et al. J Pharm Biomed Anal. 2022;211:114636. [in press]

Canada — The price of cannabis flowers decreased within 2 years after legalisation

Two years after legalization in Canada, the price of dried flower from legal sources decreased, along with a greater percentage of consumers purchasing from legal sources than after one year.

School of Public Health Sciences, University of Waterloo, Canada.

Wadsworth E, et al. Drug Alcohol Depend. 2022;231:109262.

Science/Human — After legalisation of cannabis in US states less patients are enrolled in medical cannabis programs

An analysis of data from the US suggests “that recreational cannabis legalization is associated with decreasing enrolment in medical cannabis programs, particularly for males.”

Arizona State University, Department of Psychology, Tempe, USA.

Okey SA, et al. Int J Drug Policy. 2022;100:103531.

Science/Animal — CBD reduces the rewarding effects of methamphetamine

A study with rats shows that CBD reduces the rewarding effects of methamphetamine partly through the dopaminergic system in the nucleus accumbens, a structure in the brain.

Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Sharifi A, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 8;113:110458.

Science/Human — A high obesity risk is associated with a reduced number of CB1 receptors

In a study with 41 young non-obese males those with a higher risk for obesity had a decreased availability of the CB1 receptor.

Turku PET Centre, University of Turku, Finland.

Kantonen T, et al. Int J Obes (Lond). 2022;46(2):400-407.

Science — Free available CBD products may contain residual solvents and pesticides

Tests of 78 samples of cannabis products collected from families of children with epilepsy found residual solvents in 29% and most samples contained pesticides.

The University of Sydney, Lambert Initiative for Cannabinoid Therapeutics, Sydney, Australia.

Suraev A, et al. Epilepsy Behav. 2022;127:108496.

Science/Human — About one third of children with epilepsy experience reduced seizure frequency with CBD

Interviews with 23 parents or caregivers of children with refectory epilepsy revealed that CBD reduced “the severity and frequency of seizure activity for almost a third of patients experiencing refractory epilepsy. Participants described other benefits including „improved social engagement, wakefulness and a reduction of side effects related to a reduction of conventional medication dosage.”

The University of Queensland, School of Medicine, Brisbane, Australia.

Harte S, et al. BMC Health Serv Res. 2022;22(1):173.

Science/Animal — Some effects of CBD are mediated by the CB1 receptor

A study with mice showed that “cue-induced reinstatement of cocaine seeking was attenuated by cannabidiol” and this effect was mediated by the CB1 receptor.

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

Luján MÁ, et al. Prog Neuropsychopharmacol Biol Psychiatry. 2022;113:110462.

Science/Animal — Activation of the CB2 receptor ameliorates liver fibrosis

In a study with liver cells and mice the activation of the CB2 receptor with schisandrin B ameliorates liver fibrosis.

Department of Traditional Chinese Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Wang HQ, et al. Phytomedicine. 2022;98:153960.

Science/Cells — CBD-rich hemp extracts show anti-cancer effects

In a study with leukaemia cells a hemp extract rich in CBD showed antiproliferative effects.

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

Anceschi L, et al. Phytother Res. 2022 Feb 2. [in press]

Science/Animal — CBD may attenuate THC-induced nausea

In some people THC may induce nausea and vomiting. A study with rats shows, that this effect may be reduced by CBD mediated by the 5-HT1A receptor.

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Canada.

DeVuono MV, et al. Cannabis Cannabinoid Res. 2022;7(1):58-64.

Science/Animal — Oleoyl glycine reduces vomiting

The fatty acid amide oleoyl glycine and its more stable methylated form oleoyl alanine reduce vomiting in shrews or vomiting -like behaviour in rats.

Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Canada.

Rock EM, et al. Psychopharmacology (Berl). 2022;239(2):377-383.

Science — CBD products may not be labelled correctly

Analysis of commercial CBD products showed, that some may not be labelled correctly, especially beverages.

University of Wisconsin, School of Pharmacy, Madison, USA.

Miller OS, et al. Epilepsy Behav. 2022;127:108514.

Science/Human — Cannabis abstinence may be associated with decreased glutamine concentrations

20 cannabis users, who underwent abstinence, experienced maximal abstinence symptoms on day 7. This effect was accompanied by increases of glutamine and GABA in the striatum, a structure of the brain.

McLean Imaging Center, McLean Hospital, Harvard Medical School, Belmont, USA.

Zuo CS, et al. J Psychiatr Res. 2022;146:192-200.

Science/Human — Effort -related decision making is not hampered by cannabis use

In a test with 25 cannabis using 22 non-cannabis using college students “past-month cannabis days and cannabis use disorder symptoms predicted the likelihood of selecting a high-effort trial.” This speaks against the thesis of the induction of an amotivation syndrome by cannabis.

Department of Psychology, University of Memphis, USA.

Acuff SF, et al. Exp Clin Psychopharmacol. 2022 Jan 27. [in press]