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IACM-Bulletin of 18 July 2021

Germany: Medical cannabis grown by German companies is now available to patients for the first time

Aphria, a wholly-owned subsidiary of Canadian pharmaceutical and cannabis company Tilray, has become the first of the three licensed German producers to achieve this significant milestone. The medical cannabis crop is the first grown under EURopean Good Manufacturing Practice (EU-GMP) standard in Tilray’s 6,000sq m indoor growing facility in Neumünster, about 40 miles from Hamburg.

Aphria was one of three companies, along with Aurora and Demecan, to be granted a permit by the Federal Institute for Drugs and Medical Devices (BfArM), in spring 2019, to cultivate medicinal cannabis. Distribution of Aphria’s harvest to Germany’s pharmacies will be carried out by Frankfurt-based Cansativa. It won the the four-year contract year to become the sole distributor of all cannabis grown in Germany. Until now, Germany has had to rely on imports primarily from the Netherlands and Canada since the Narcotics Drugs Act was amended in March 2017 to allow doctors to prescribe cannabis-based medicines.

Business Cann of 8 July 2021

USA: U.S. Senate Democrats roll out draft bill to legalize cannabis

On 14 July three top U.S. Democratic senators unveiled a discussion draft of a bill that aims to legalize cannabis, a move that would allow adult Americans to buy and possess up to 10 ounces (about 280 g) of cannabis without facing criminal penalties. The Cannabis Administration and Opportunity Act floated by Senate majority leader Chuck Schumer, Finance Chairman Ron Wyden and New Jersey Senator Cory Booker, would expunge federal non-violent cannabis crimes, further medical research and allow cannabis companies access to essential financial services.

While adult use of cannabis is legal in 18 states, and allowed medically in 37 states, it remains illegal under U.S. federal law, deterring banks and others from dealing with companies that sell cannabis or related products. A final legislative draft will be introduced later and feedback on the discussion draft can be provided until 1 September. To become a law, the measure will have to pass both the Democratic-controlled Senate and House of Representatives and be signed by President Joe Biden.

Reuters of 14 July 2021

Science/Human: Cannabis use has no effect on cognitive functioning in adolescents according to large study

In 804 adolescents (441 females and 363 males) investigators of the Department of Psychiatry and Psychotherapy of the Charité Hospital in Berlin, Germany, did not find any negative effect on cognitive abilities by cannabis use. Participants were investigated at the age of 14 and 5 years later at the age of 19.

They concluded from their data that “decision making is not impaired when cannabis is used in moderation, and onset of use occurs after the age of 15.” They further wrote that “cross-sectionally, we detected no significant neurocognitive differences before initiation of drug use. However, after controlling for confounders, light cannabis use as well as late-onset thereof was associated with increased decision-making skills both cross-sectionally at follow-up as well as longitudinally compared to non-using controls. (…) We find no evidence to support the presumption that cannabis consumption leads to a decline in neurocognitive ability.”

Wendel LK, Daedelow L, Kaminski J, Banaschewski T, Millenet S, Bokde ALW, Burke Quinlan E, Desrivières S, Flore H, Grigis A, Garavan H, Gowland P, Heinz A, Brühl R, Martinotk JL, Artigeskl E, Neesbe F, Papadopoulos Orfanos D, Walter H. Residual effects of cannabis-use on neuropsychological functioning.2021;59.

Science/Human: Cannabis is helpful in the treatment of nausea and vomiting due to cancer chemotherapy

In a study with 81 patients, who experienced nausea and vomiting during cancer chemotherapy despite standard medication, a cannabis extract improved the symptoms. The study was conducted at several sites in Australia. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design.

A total of 81 participants were randomised and 72 completing two cycles were included in the efficacy analyses. Complete response was improved with cannabis from 14% to 25% with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. Authors concluded that the “addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects.”

Grimison P, Mersiades A, Kirby A, Lintzeris N, Morton R, Haber P, Olver I, Walsh A, McGregor I, Cheung Y, Tognela A, Hahn C, Briscoe K, Aghmesheh M, Fox P), Abdi E, Clarke S, Della-Fiorentina S, Shannon J, Gedye C, Begbie S, Simes J, Stockler M. Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial. Ann Oncol. 2020;31(11):1553-1560.

Science/Human: The use of cannabis for medicinal purposes may improve complex cognitive abilities over the course of 12 months

According to a study of investigators of the Department of Psychiatry at Harvard Medical School, Boston, and McLean Hospital Imaging Centre in Belmont, USA, the medical use cannabis may improve cognitive functioning. As part of an ongoing study, medical cannabis (MC) patients completed a baseline visit prior to initiating cannabis and evaluations following 3, 6, and 12 months of treatment.

Authors wrote that “relative to baseline, MC patients demonstrated significant improvements on measures of executive function and clinical state over the course of 12 months; verbal learning/memory performance generally remained stable. Improved cognitive performance was not correlated with MC use.” Authors concluded that “study results extend previous pilot findings, indicating that MC patients may exhibit enhanced rather than impaired executive function over time.”

Sagar KA, Dahlgren MK, Lambros AM, Smith RT, El-Abboud C, Gruber SA. An Observational, Longitudinal Study of Cognition in Medical Cannabis Patients over the Course of 12 Months of Treatment: Preliminary Results. J Int Neuropsychol Soc. 2021;27(6):648-660.

Science/Human: Cannabis use is associated with lower brain inflammation in people with HIV

According to a study at the University of California in San Diego, USA, with 263 participants daily cannabis use was associated with reduced inflammation of the brain. They analysed data of 4 groups: HIV negative non-cannabis users (n = 65), HIV positive non-cannabis users (n = 105), HIV positive moderate cannabis users (n = 62), and HIV positive daily cannabis users (n = 31).

HIV positive daily cannabis users showed significant lower amounts of markers for inflammation in the cerebral spinal fluid compared to HIV positive non-cannabis users. Blood biomarkers showed no differences by cannabis use. Authors concluded that “current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning.”

Watson CW, Campbell LM, Sun-Suslow N, Hong S, Umlauf A, Ellis RJ, Iudicello JE, Letendre S, Marcotte TD, Heaton RK, Morgan EE, Grant I. Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV. J Int Neuropsychol Soc. 2021;27(6):661-672.

Science/Human: Cannabis hyperemesis syndrome is associated with certain gene mutations

According to research from the USA published in Cannabis and Cannabinoid Research with 205 participants, who suffered from Cannabinoid hyperemesis syndrome (CHS), and 54 healthy controls changes in certain genes may be responsible for this rare syndrome. A reduced pool of 28 patients and 12 controls ultimately completed genomic testing.

88% of patients improved after cannabis cessation, most suffering recurrence rapidly after resumption. Findings in patients included mutations in genes COMT, transient receptor potential vanilloid receptor 1, CYP2C9, gene coding dopamine-2 receptor and ATP-binding cassette transporter gene. Authors wrote that “this is the largest patient cohort of CHS examined to date, and first to note associated mutations in genes affecting neurotransmitters, the endocannabinoid system, and the cytochrome P450 complex associated with cannabinoid metabolism.” Cannabinoid hyperemesis syndrome (CHS) is a diagnosis of exclusion with intractable nausea, cyclic vomiting, abdominal pain, and hot bathing behaviour associated with ongoing THC exposure.

Russo EB, Spooner C, May L, Leslie R, Whiteley VL. Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation. Cannabis Cannabinoid Res, 2021 Jul 5. [in press]

Science/Human: People may draw spiritual benefit from cannabis use

Results of a survey with 1087 participants show that cannabis use may be associated with spiritual benefits. The study was conducted by investigators of the California School of Professional Psychology at Alliant International University in Emeryville, USA.

Spiritual benefit from cannabis was reported by 66.1% of the sample, and 5.5% reported it had sometimes been a spiritual hindrance. Authors wrote that “the majority of the sample (63%) was free of cannabis use disorder. Compared to disordered groups, the non-disordered group was significantly older and scored lower on experiential avoidance, psychological distress, and several motives for use. Results suggest that spiritual motives for cannabis use may be widespread.”

Heide FJ, Chang T, Porter N, Edelson E, Walloch JC. Spiritual Benefit from Cannabis. J Psychoactive Drugs. 2021 Jul 5:1-9.

Science/Human: Cannabis is often used to substitute other medications

An anonymous survey with 2841 participants conducted by investigators of Aarhus University, Denmark, confirms previous research that cannabis is often used as substitution for other medications. The sample was recruited through social media, public media, and patient organizations. Cannabis was prescribed or non-prescribed and used with medicinal purposes. More than a half (55%) had used cannabis with the purpose of replacing a prescribed drug.

Compared to non-substitution users, substitution users were more likely to be women and to use cannabis in the treatment of chronic pain and other somatic conditions. Pain medication (67%), antidepressants (25%), and arthritis medication (21%) were the most common types of drugs replaced with cannabis. Authors wrote that “more than half (65.8%) found CaM much more effective compared to prescription drugs, and 85.5% that the side effects associated with prescription drug use were much worse compared to use of CaM.”

Kvamme Sl, Pedersen MM, Rømer Thomsen K, Thylstrup B. Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample. Harm Red J 2021;18(72).

News in brief

USA: White House recommends review of anti-doping rules after Richardson ban
The White House on 7 July said it may be worthwhile to review anti-doping rules in sport after American sprinter Sha'Carri Richardson tested positive for cannabis use. USA Track & Field declined to select Richardson to the relay team for the 2021 Olympics in Tokyo after she accepted a one-month ban for the prohibited substance. She stated that she had used cannabis to cope with the death of her mother.
Reuters of 7 July 2021

Switzerland: Majority of Swiss support the legalisation of cannabis
Most Swiss accept the idea of legalising cannabis for recreational purposes provided there are rules to protect minors, according to a survey. Nearly two-thirds of people surveyed want the minimum age of consumption to be set at 18, the Federal Office of Public Health (FOPH) said. Two-thirds are in favour of conducting pilot tests on the controlled distribution of cannabis for recreational purposes.
Swiss Info of 1 July 2021

Science/Human: Depression in adolescence is a risk factor for cannabis use
In a study with 1606 adolescents from Canada depressive symptoms were a risk factor for cannabis use.
Douglas Mental Health University Institute, Department of Psychiatry, Montreal, Canada.
Bolanis D, et al. J Affect Disord. 2020;274:1076-1083.

Science/Animal: Activation of the CB2 receptor may improve microcirculation in the cochlea
Activation of the CB2 receptor by a synthetic cannabinoid (JWH-133) improved microcirculation in the cochlea, a part of the inner ear.
Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University of Munich, Germany.
Weiss BG, et al. Otol Neurotol. 2021 Jul 9. [in press]

Science/Human: The therapeutic effects of CBD in Dravet syndrome may start within 2 weeks
In a placebo-controlled study with 124 patients suffering from Dravet syndrome differences between placebo and CBD became apparent by day 12 and day 13.
Department of Pediatrics, Division of Neurology at Connecticut Children's, University of Connecticut, Hartford, USA.
Madan Cohen J, Epilepsia. 2021 Jul 15. [In press]

Science/Human: Cannabis use was not associated with length of a hospital stay of patients with schizophrenia
In a comparison of 55 cannabis-only users and 462 non-substance users there was no difference between the length of hospital stay in the 2 groups of schizophrenic patients.
Department of Psychiatry, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.
Williams SR et al. Subst Use Misuse. 2021 Jul 15:1-4.

Science/Human: Regular cannabis use may have different consequences on cognitive performance in men and women
In a study with 110 regular cannabis users, of whom 72% were male, females exhibited better verbal learning and memory and males demonstrated better attention and cognitive flexibility.
Department of Psychology, Palo Alto University, USA.
Hirst R, et al. J Int Neuropsychol Soc. 2021;27(6):581-591.

Science/Animal: The cannabinoid receptor GPR55 may influence wound healing after a heart attack
A study with mice shows that the cannabinoid-sensitive receptor GPR55 “regulates cardiac homeostasis and ischaemia responses” after myocardial infarction. Mice without the GPR55 presented with infarct expansion.
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität (LMU) Munich, Germany.
Puhl SL, et al. Sci Rep. 2021;13;11(1):14385.

Science/Animal: The endocannabinoid system plays a critical role in depression after chronic pain
New research with rats demonstrates, that the endocannabinoid system plays a crucial role in the development of depression following chronic pain.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
Mecca CM, et al. J Neurosci. 2021 Jul 9 [In press]

Science/Human: A treatment with capsaicin may be helpful in cannabis hyperemesis syndrome
In a study with 201 patients suffering from cannabis hyperemesis syndrome some were treated with topical capsaicin to the abdomen. Authors wrote that “time to discharge after administration of the reference agent was shorter for those who received capsaicin compared to patients who did not.”
University of Michigan Health System, Ann Arbor, USA.
Kum V, et al. Am J Emerg Med. 2021;49:343-351. [In press]

Science/Animal: CBD reduced sickness behaviour, a measure of depressive-like response
In a study with mice, which suffered from inflammation, CBD reduced sickness behaviour, which according to the authors “reinforces its potential use as an antidepressant which modulates neuroinflammation.”
Neuroscience Program, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Tito PAL, et al. Pharmacol Rep. 2021 Jul 3:1-14.

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