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IACM-Bulletin of 10 September 2023

Science/Human: Cannabis may be helpful in Parkinson’s disease according to observational study

In a study with 15 patients suffering from Parkinson’s disease profited from different CBD/THC products by reducing pain and improving sleep. Investigators of the Osteopathic Manipulative Medicine of the New York Institute of Technology College of Osteopathic Medicine in Old Westbury, USA, compared 8 patients, who were prescribed CBD/THC treatments and 7 who were not prescribed cannabis.

Authors wrote: “We found a wide range of prescribed products and methods as well as variability in perceived benefits and untoward effects, even in our small sample. (…) Qualitatively, some participants with PD who were taking CBD/THC reported improved pain levels, sleep, and reductions in anxiety. A few negative effects were endorsed, including sleepiness, concentration difficulties, and forgetfulness.”

Sousa A, DiFrancisco-Donoghue J. Cannabidiol and Tetrahydrocannabinol Use in Parkinson's Disease: An Observational Pilot Study. Cureus. 2023;15(7):e42391.

Science/Human: Cannabis did not increase the risk for psychosis in adolescents at high risk

In a study by investigators of the Division of Psychiatry Research at the Zucker Hillside Hospital in Glen Oaks, USA, cannabis usage was tracked over a 2-year period. They examined the association with clinical and neurocognitive outcomes along with medication rates. Authors found that “youth who continuously used cannabis had higher neurocognition and social functioning over time, and decreased medication usage, relative to non-users. Surprisingly, clinical symptoms improved over time despite the medication decreases.”

They concluded that “continuous cannabis use over 2-years of follow-up was not associated with an increased psychosis transition rate, and did not worsen clinical symptoms, functioning levels, or overall neurocognition (…) indicating that CHR [clinical high risk] youngsters are not negatively impacted by cannabis.”

Carrión RE, Auther AM, McLaughlin D, Adelsheim S, Burton CZ, Carter CS, Niendam T, Ragland JD, Sale TG, Taylor SF, Tso IF, McFarlane WR, Cornblatt BA. Recreational cannabis use over time in individuals at clinical high risk for psychosis: Lack of associations with symptom, neurocognitive, functioning, and treatment patterns. Psychiatry Res. 2023;328:115420.

Science/Human: Cannabis may alleviate chronic neuropathic pain according to a retrospective analysis

According to a retrospective analysis of data from 99 cases by investigators of the Department of Neurology at the University Medical Center Hamburg-Eppendorf, Germany, cannabis may reduce neuropathic pain without severe side effects. Patients with chronic neuropathic pain received medical cannabis by means of inhaling dried cannabis flowers at daily doses between 0.15 to 1 g. They were up to 6 follow-ups at intervals of 4 to 6 weeks.

Within 6 weeks on the therapy, median pain scores decreased significantly from 7.5 to 4.0 and

the proportion of patients with severe pain (score >6) decreased from 96% to 16%. Sleep disturbance was significantly improved. Improvement was sustained over a period of up to 6 months.

Kluwe L, Scholze C, Schmidberg LM, Wichmann JL, Gemkov M,Keller MJ,Farschtschi SC. Medical Cannabis Alleviates Chronic Neuropathic Pain Effectively and Sustainably without Severe Adverse Effect: A Retrospective Study on 99 Cases. Med Cannabis Cannabinoids (2023) 6 (1): 89–96.

Science/Human: Cannabis extracts may improve symptoms of autism according to a retrospective analysis

Investigators of several scientific institutions in Brazil analysed data of 20 patients with autistic symptoms who were treated with full-spectrum cannabis extracts in a response-based, individually-tailored dosage regimen. The daily dosage and relative proportions of CBD and THC were adjusted based on treatment results following periodic clinical evaluation. Most patients (80%) were treated for a minimum of 6 months.

Eighteen patients started with a CBD-rich extract, and in three of them, the CBD-rich (CBD-dominant) extract was gradually complemented with low doses of a THC-rich extract based on observed effects. Two other patients have used throughout treatment a blend of two extracts, one CBD-rich and the other THC-rich. The outcomes were mainly positive for most symptoms. Authors summarised their observations that “18 out of 20 patients showed improvement in most core and comorbid symptoms of autism, and in quality of life for patients and their families.” Other medications were reduced or completely discontinued in most cases.

Montagner PSS, Medeiros W, da Silva LCR, Borges CN, Brasil-Neto J, de Deus Silva Barbosa V, Caixeta FV, Malcher-Lopes R. Individually tailored dosage regimen of full-spectrum Cannabis extracts for autistic core and comorbid symptoms: a real-life report of multi-symptomatic benefits. Front Psychiatry. 2023;14:1210155.

Science/Human: CBD may be effective in half of patients suffering from epilepsy according to real-life data

Investigators of the Regional Center for Epilepsy- Sleep Medicine, ASST Santi Paolo e Carlo in Milan, Italy, presented data of 18 patients with drug-resistant epilepsy (12 adults and 6 children), who received treatment with CBD and were followed for a median of 9 months.

At the last follow-up, nine patients (50%) were considered CBD responders with at least a 50% decrease in seizure frequency. No serious adverse effects were found. No statistically significant differences were found concerning sleep, including daytime sleepiness, and no statistically significant effect was found on parental stress. An improvement was found for social interaction in quality of life for all patients.

Ferrera G, Ricci E, Vignoli A, Savini MN, Viganò I, Chiesa V, Caputo D, Zambrelli E, La Briola F, Turner K, Canevini MP. Highly purified cannabidiol in the treatment of drug-resistant epilepsies: A real-life impact on seizure frequency, quality of life, behavior, and sleep patterns from a single Italian center. Epilepsy Behav. 2023;147:109409

Science/Human: Cannabis may improve quality of life according to a large observational study

The QUEST Initiative is a large prospective multicenter study of patients with any chronic health condition newly prescribed medicinal cannabis between November 2020 and December 2021. Investigators of several Australian universities participated in this study. Eligible patients were identified by 120 clinicians at medical centers across six Australian states and followed for 3 months.

Of the 2762 consenting participants, 2327 completed baseline and at least one follow-up questionnaire. Ages ranged between 18-97 years, 62.8% were female. The most commonly treated conditions were chronic pain, insomnia, generalized anxiety, and mixed anxiety and depression. Across the whole cohort both quality of life scores showed clinically meaningful improvements.

Tait MA, Costa DSJ, Campbell R, Norman R, Warne LN, Schug S, Rutherford C. Health-related quality of life in patients accessing medicinal cannabis in Australia: The QUEST initiative results of a 3-month follow-up observational study. PLoS One. 2023;18(9):e0290549.

Science/Human: Physicians Use THC to reduce psychological distress in critically ill patients

Altogether 662 physicians working in intensive care units throughout Germany were surveyed with regard to their use of cannabinoids and 67 participated. The frequency and regimen of cannabinoid therapy initiated by the participating physicians in the last 2 years at the time of the survey were characterized. According to the investigators of the Pain Clinic at Hannover Medical School, Germany, 22 had used cannabis in some patients during the 2-year period studied, with dronabinol in doses between 1 and 20 mg being their cannabinoid of choice.

Metabolic and psychological distress and medication savings, followed by pain and nausea/vomiting, were the most frequently cited indications for cannabinoid therapy. No relevant safety issues arrived. Lack of personal experience, limited evidence, and gaps in knowledge were the most commonly cited reservations about cannabinoid use.

Foadi N, Dos Santos Teixeira L, Fitzner F, Dieck T, Rhein M, Karst M. Therapeutic Use of Cannabinoids in Critically Ill Patients: A Survey of Intensive Care Physicians in Germany. Cannabis Cannabinoid Res. 2023 Sep 4. [in press]

Science/Human: Almost a third of cancer patients used cannabis according to a survey and most of them don’t inform their doctors

Among 1258 surveyed cancer patients, 31% used cannabis after diagnosis, ranging from 25% for lung cancer to 59% for testicular cancer. This is the result of research by investigators of the Memorial Sloan Kettering Cancer Center in New York, USA.

Among users, reasons for use included difficulty sleeping (48%), stress, anxiety, or depression (46%), and pain (42%). Among respondents who used cannabis to improve symptoms, 70-90% reported improvement. Less than 5% reported that any symptom worsened. Only 25% discussed cannabis with healthcare providers

Salz T, Meza AM, Chino F, Mao JJ, Raghunathan NJ, Jinna S, Brens J, Furberg H, Korenstein D. Cannabis use among recently treated cancer patients: perceptions and experiences. Support Care Cancer. 2023;31(9):545.

Science/Human: THC relates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder

Scientists of the Department of Psychiatry at Yale University School of Medicine in New Haven, USA, and other scientific institutions from the US conducted an experimental study to investigate the acute effects of THC among persons receiving methadone therapy for opioid use disorder. Using a within-subject, crossover design, 25 persons were randomly assigned to receive single oral doses of THC (10 or 20 mg) or placebo, during three separate 5-h test sessions.

Results demonstrated that, for self-reported rather than experimental pain sensitivity measures, 10 mg THC provided greater relief than 20 mg THC, with no substantial evidence of abuse potential, and inconsistent dose-dependent cognitive adverse effects. There was no indication of any interaction between THC and methadone doses.

De Aquino JP, Meyerovich J, Xie CZ, Ranganathan M, Compton P, Pittman B, Rogan M, Sofuoglu M. Delta-9-tetrahydrocannabinol modulates pain sensitivity among persons receiving opioid agonist therapy for opioid use disorder: A within-subject, randomized, placebo-controlled laboratory study. Addict Biol. 2023;28(9):e13317.

News in brief

USA: Health officials look to move cannabis to lower-risk drug category

The U.S. Department of Health and Human Services has recommended easing restrictions on marijuana, a department spokesperson said, following a review request from the Biden Administration last year. Nearly 40 U.S. states have legalized cannabis use in some form, but it remains completely illegal in some states and at the federal level.

Reuters of 30 August 2023

Science/Human: Cannabis use linked to higher levels of toxic metals in blood and urine

Cannabis users may be building up high levels of toxic metals in their blood, a new study suggests. "Like the tobacco plant, the cannabis plant is a hyper-accumulator of metals," said lead author Katlyn McGraw, a post-doctoral researcher at Columbia University Mailman School of Public Health in New York City. "The plant absorbs metals from the soil and then deposits them in the leaves and the stems and the buds, so when the marijuana is smoked or inhaled people might be inhaling those metals." The metals include cadmium and lead.

Health News of 30 August 2023

Science/Cells: Cannabinoids induce programmed cell death in breast cancer cells

THC and CBD as well as standardized cannabis extracts inhibit migration, invasion, and induce apoptosis (programmed cell death) in certain breast cancer cells (MCF-7 cells).

Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Thailand.

Suttithumsatid W, et al. Toxicol In Vitro. 2023;93:105667.

Science/Human: CBD rich cannabis products had no effect on driving ability

In a placebo-controlled study “pairwise comparison of driving-related ability revealed no significant differences between low-THC/CBD-rich products (...) and placebo.”

Institute of Forensic Medicine, Department of Biomedical Engineering, University of Basel, Switzerland.

Egloff L, et al. Int J Legal Med. 2023 Aug 26. [in press]

Science/Cells: CBD may decrease viral load in certain blood cells

Both CBD and a synthetic cannabinoid (HU308) decreased viral load in myeloid cells as well as pro-inflammatory cytokines, such as TNF-alpha and interleukin-1 beta.

Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, USA.

Williams A, et al. Pharmaceuticals (Basel). 2023;16(8):1147.

Science/Cells: CBD reduces the levels of pro-inflammatory molecules in small intestine cells

Investigators “showed that high-CBD cannabis extracts (…) suppressed the levels of expression of proinflammatory cyclooxygenase 2 (COX2) and increased the expression of the anti-inflammatory suppressor of cytokine signalling 3 (SOCS3) in human small intestinal epithelial cells.”

Department of Biological Sciences, University of Lethbridge, Canada.

Wang B, et al. Heliyon. 2023;9(8):e18817.

Science/Human: The number of adolescents referred to a treatment of cannabis use disorder declined after legalisation in the USA

“Nationwide, the number and proportion of adolescent and young adult criminal justice referrals to CUD [cannabis use disorder] treatment declined over the study period. The proportion of young adult criminal justice referrals declined significantly more rapidly after recreational legalization as compared with before.”

Temple University, Philadelphia, USA.

Mennis J, Stahler GJ, McKeon TP. J Addict Med. 2023 Aug 30. [in press]

Science/Human: Cannabis involvement in traffic injury increased after legalisation of cannabis in Canada

A “cross-sectional study found large increases in cannabis involvement in ED [emergency department] visits for traffic injury over time, which may have accelerated following nonmedical cannabis commercialization. Although the frequency of visits was rare, they may reflect broader changes in cannabis-impaired driving.”

Department of Family Medicine, University of Ottawa, Canada.

Myran DT, et al. JAMA Netw Open. 2023;6(9):e2331551.

Science/Animal: Topical CBD gel shows analgesic and anti-inflammatory effects in mice

“The anti-inflammatory effects in vivo after inflammation induction, represented by decreased times of paw licking, degree of paw edema, and decreased writhing response, showed that 1% of tropical CBD use had significantly comparable or better anti-inflammatory effects when compared with tropical diclofenac, an anti-inflammatory agent.” Investigators used a mouse model.

Center of Excellence in Stroke, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.

Bunman S, et al. Cannabis Cannabinoid Res. 2023 Sep 5. [in press]

Science/Human: CBD had no effect on the need of emergency healthcare service in patients with epilepsy

There were 136 patients included in a 12 month study of CBD treatment. Authors concluded from their research that “despite potential benefits of prescription CBD, many patients utilize EHSs [emergency healthcare service] in the first 12 months of treatment with minimal changes in concomitant ASM [anti-seizure medication] use.”

Vanderbilt Specialty Pharmacy, Vanderbilt Health System, Nashville, USA.

Johnson K, et al. Epilepsy Behav. 2023;147:109412.

Science/Cells: Skin cells may be protected from UVA -induced changes by a combination of CBG and ascorbic acid

A study with keratinocytes (skin cells) showed that the combined protective effects of CBG (cannabigerol) on protein structure and of 3-O-ethyl ascorbic acid on protein expression profile allowed to obtain a wider protection of cells against UVA radiation.

Medical University of Białystok, Poland.

Gęgotek A, et al. J Pharmacol Exp Ther. 2023:JPET-AR-2023-001731.

Science/Cells: CBD increases the proliferation of gingival cells

Using a wound healing assay CBD at non-toxic doses promoted proliferation and migration of human gingival cells.

Department of Restorative Dentistry and Periodontology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.

Montreekachon P, et al. J Periodontal Res. 2023 Aug 28. [in press]

Science/Human: Patient-reported cannabis use to treat post-operative pain was associated with increased opioid use

In an analysis of 11,314 patients, 581 reported using cannabis to treat pain after surgery. In adjusted models, patients who used cannabis consumed an additional 1.0 opioid pills after surgery. Patients who used cannabis were more likely to report moderate-to-severe surgical site pain at 1 week and 1 month after surgery.

Department of Anesthesiology, University of Michigan, Ann Arbor, USA.

Bicket MC, et al. Ann Surg. 2023 Aug 28. [in press]