Craig Goldie

(1) Background: Despite widespread use of medical cannabinoids for cancer-related symptom management, systematic reviews consistently call for more clinical trial evidence. (2) Methods: An aggregate N-of-1 study of symptomatic but clinically stable outpatients from 8 Canadian cancer centres compared three blinded sublingual extracts (THC; CBD; Combined) with placebo, self-titrated within a prescribed schedule for four consecutive days each, in randomized sequence for up to three cycles. The primary outcome was the frequency of reporting a ≥1.4-point (20%) improvement in a 7-point Patient Global Impression of Change (PGIC) for at least one extract over placebo. (3) Results: The primary outcome was achieved in 50/89 (56%) participants, with no significant preference of one extract over another on average, but a clear preference between extracts for most individuals. Changes in a modified Edmonton Symptom Assessment score and blinded preference confirmed the findings. Improved sleep, tiredness, and anxiety contributed most to overall improvement regardless of primary symptom. Mild side-effects were common with all extracts and placebo but resolved rapidly on dose reduction. Moderate or severe adverse effects were rare but associated with higher doses of THC. (4) Conclusions: Medical cannabis extracts can be meaningfully beneficial for cancer-related symptoms in at least half of eligible patients. A starting dose of 2.5mg of THC/CBD up to three times a day is recommended. Personalization of treatment is required to optimize response.

PURPOSE: At our institution's cancer palliative care (PC) clinic, new referrals from oncologists were scheduled for consultation and ongoing follow-up by PC physicians without input from the patients' family physicians (FPs). FPs reported that they felt out of the loop. We implemented a quality improvement (QI) initiative aimed at systematically facilitating care coordination between FPs and PC physicians. METHODS: A coordination toolkit was sent from the PC physician to the FP whenever the PC physician received a consultation request from an oncologist. The toolkit included an introduction to the PC physician team; an opportunity for the FP to choose how best to collaborate with PC physicians to meet the patient's PC needs; and contact information for access to 24/7 PC physician support. Responses from FPs regarding their preferred level of engagement with PC determined further care planning in the clinic. We measured feasibility, response rate, and qualitative surveys of FPs about the usefulness of the intervention. RESULTS: Two hundred fourteen new consultations were eligible for a standardized letter over the 6-month implementation period. Feasibility for sending the toolkit was 90.0% and response rate for collaborative care preference from FPs was 86.0%, with median response time of 3-4 days. 78.9% of FPs indicated they would prefer ongoing consultative care by the PC physician, while 18.6% indicated that PC physician consultation was not needed, or that the FP would provide primary PC after a one-time PC physician consultation. CONCLUSION: We successfully implemented a QI initiative to improve care coordination between FPs and PC physicians for patients with cancer. The coordination toolkit can protect the patient-FP primary PC relationship and optimize specialist PC resource utilization for complex patients.

Background and Aims Psilocybin is a psychedelic drug that may hold promise for a wide range of human health conditions, yet the identification of therapeutic processes and mechanisms of action remains exploratory. We conducted a scoping review on pre-clinical behavioural investigations of psilocybin in non-human animals to help determine the behavioural effects of psilocybin in non-human animals, to identify studies completed, behavioural tests employed, and what dosing modalities had been studied. Methods A librarian-conducted literature search was performed using predefined key terms and search criteria and additional searching was conducted by reviewers, using electronic databases, grey literature sources, and reference lists of relevant articles or reviews. The final search updated occurred in October, 2021. Studies were reviewed, screened and selected against an a priori protocol using Covidence software by multiple reviewers with results plotted across the Research Domains Criteria construct. Results From 4124 records identified by database searching, 260 publications were subjected to full-text review with 77 studies included in this scoping review, published between 1962-2021. The preponderance of studies (n=64) investigated behavioural outcomes in rodents. Only 43 studies (55.8%) reported on housing conditions, and seventeen studies (22.1%) failed to report sample size. All studies reported behavioural outcomes following drug administration, with fifty-one studies (66.2%) using psilocybin, thirty studies (42.9%) psilocin, four studies (5.2%) administering whole mushroom extracts (WME), and a further eight studies investigating both psilocybin and psilocin and one study reporting the effects of both psilocin and WME. One hundred and thirty distinct behavioural investigations using fifty different behavioral paradigms were identified. Few adverse events were reported, and even exceedingly high doses were apparently well tolerated. Conclusion With seventy-seven publications spanning close to sixty years, there is huge variation in study design and quality. Overall psilocybin presents a unique and strong safety profile with no evidence of biological toxicity, is characterized by unique time and dose-dependent effects, and its pattern of drug action is significantly context and training-sensitive. Data suggest putative effects of psilocybin include acute arousal, dose-dependent sedation, reductions in fear conditioning at low doses, reduced aggression, improved valence, acute disruption of working memory, the rescuing of deficits from chronic stress, and improved learning when combined with repeated environmental exposure after resolution of drug effect.

Ensuring high quality end of life (EOL) care is necessary for people with advanced non-small-cell lung cancer (NSCLC), given its high incidence, mortality and symptom burden. Aggressive EOL care can adversely affect the quality of life of NSCLC patients without providing meaningful oncologic benefit. Objectives: (1) To describe EOL health services quality indicators and timing of palliative care consultation provided to patients dying of NSCLC. (2) To examine associations between aggressive and supportive care and patient, disease and treatment characteristics. Methods: This retrospective population-based cohort study describes those who died of NSCLC in Ontario, Canada from 2009–2017. Socio-demographic, patient, disease and treatment characteristics as well as EOL health service quality and use of palliative care consultation were investigated. Multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. Results: Aggressive care quality indicators were present in 50.3% and supportive care indicators in 60.3% of the cohort (N = 37,203). Aggressive care indicators decreased between 2009 and 2017 (57.4% to 45.3%) and increased for supportive care (54.2% to 67.5%). Benchmarks were not met by 2017 in 3 of 4 cases. Male sex and greater comorbidity were associated with more aggressive EOL care and less supportive care. Older age was negatively associated and rurality positively associated with aggressive care. No palliative care consultation occurred in 56.0%. Conclusions: While improvements in the use of supportive rather than aggressive care were noted, established Canadian benchmarks were not met. Moreover, there is variation in EOL quality between groups and use of earlier palliative care must improve.

We conducted a scoping review on psilocybin-assisted therapy for addiction, depression, anxiety and post-traumatic stress disorder. Psilocybin is a naturally-occurring tryptophan derivative found in species of mushroom with psycho-active properties. From 2022 records identified by database searching, 40 publications were included in the qualitative synthesis from which we identified 9 clinical trials with a total of 169 participants. Trials used a peak-psychedelic model of therapy, emphasizing inward journey through the use of eyeshades, set musical scores and with medium to high doses of psilocybin. No serious adverse effects were reported; mild adverse effects included transient anxiety, nausea and post-treatment headaches. Overall, the 9 trials all demonstrated safety, tolerability and preliminary efficacy in the treatments of obsessive-compulsive disorder, substance use disorder, treatment-resistant unipolar depression, anxiety or depression in patients with life-threatening cancer and demoralization among long-term AIDS survivors.The literature was found to be early and exploratory, with several limitations: only 5 were randomized controlled trials, small and homogenous patient sample size, difficulties in blinding, and the confounding influence of psychological supports provided. Further research is indicated to establish effectiveness for these and other indications, with a more diverse range of patients, and with differing program and dosing modalities.