Canadians' use of cannabis for therapeutic purposes since legalization of recreational cannabis: a cross-sectional analysis by medical authorization status.

BACKGROUND: There has been a precipitous decline in authorizations for medical cannabis since non-medical cannabis was legalized in Canada in 2018. This study examines the demographic and health- and medical cannabis-related factors associated with authorization as well as the differences in medical cannabis use, side effects, and sources of medical cannabis and information by authorization status. METHODS: Individuals who were taking cannabis for therapeutic purposes completed an online survey in early 2022. Multivariable logistic regression was used to determine odds ratios (OR) and 95% confidence intervals (CI) of demographic and health- and medical cannabis-related variables associated with holding medical cannabis authorization. The differences in medical cannabis use, side effects, and sources of information by authorization status were determined via t-tests and chi-squared analysis. RESULTS: A total of 5433 individuals who were currently taking cannabis for therapeutic purposes completed the study, of which 2941 (54.1%) currently held medical authorization. Individuals with authorization were more likely to be older (OR ≥ 70 years vs. < 30 years, 4.85 (95% CI, 3.49-6.76)), identify as a man (OR man vs. woman, 1.53 (1.34-1.74)), have a higher income (OR > $100,000/year vs. < $50,000 year, 1.55 (1.30-1.84)), and less likely to live in a small town (OR small town/rural vs. large city, 0.69 (0.59-0.81)). They were significantly more likely to report not experiencing any side effects (29.9% vs. 23.4%; p < 0.001), knowing the amount of cannabis they were taking (32.1% vs. 17.7%; p < 0.001), obtaining cannabis from regulated sources (74.1% vs. 47.5%; p < 0.001), and seeking information about medical cannabis from healthcare professionals (67.8% vs. 48.2%; p < 0.01) than individuals without authorization. CONCLUSIONS: These findings offer insight into the possible issues regarding equitable access to medical cannabis and how authorization may support and influence individuals in a jurisdiction where recreational cannabis is legalized, highlighting the value of a formal medical cannabis authorization process.

Medical cannabis authorization patterns, safety, and associated effects in older adults.

BACKGROUND: Use of medical cannabis is increasing among older adults. However, few investigations have examined cannabis use in this population. METHODS: We assessed the authorization patterns, safety, and effects of medical cannabis in a sub-analysis of 201 older adults (aged ≥ 65 years) who completed a 3-month follow-up during this observational study of patients who were legally authorized a medical cannabis product (N = 67). Cannabis authorization patterns, adverse events (AEs), Edmonton Symptom Assessment Scale-revised (ESAS-r), and Brief Pain Inventory Short Form (BPI-SF) data were collected. RESULTS: The most common symptoms for which medical cannabis was authorized were pain (159, 85.0%) and insomnia (9, 4.8%). At baseline and at the 3-month follow-up, cannabidiol (CBD)-dominant products were authorized most frequently (99, 54%), followed by balanced products (76, 42%), and then delta-9-tetrahydrocannabinol (THC)-dominant products (8, 4.4%). The most frequent AEs were dizziness (18.2%), nausea (9.1%), dry mouth (9.1%), and tinnitus (9.1%). Significant reductions in ESAS-r scores were observed over time in the domains of drowsiness (p = .013) and tiredness (p = .031), but not pain (p = .106) or well-being (p = .274). Significant reductions in BPI-SF scores over time were observed for worst pain (p = .010), average pain (p = .012), and overall pain severity (p = 0.009), but not pain right now (p = .052) or least pain (p = .141). CONCLUSIONS: Overall, results suggest medical cannabis was safe, well-tolerated, and associated with clinically meaningful reductions in pain in this sample of older adults. However, the potential bias introduced by the high subject attrition rate means that all findings should be interpreted cautiously and confirmed by more rigorous studies.

Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic.

BACKGROUND: Cannabidiol (CBD) is a primary component in the cannabis plant; however, in recent years, interest in CBD treatments has outpaced scientific research and regulatory advancement resulting in a confusing landscape of misinformation and unsubstantiated health claims. Within the limited results from randomized controlled trials, and lack of trust in product quality and known clinical guidelines and dosages, real-world evidence (RWE) from countries with robust regulatory frameworks may fill a critical need for patients and healthcare professionals. Despite growing evidence and interest, no real-world data (RWD) studies have yet investigated patients' reports of CBD impact on symptom control in the common expression of pain, anxiety, depression, and poor wellbeing. The objective of this study is to assess the impact of CBD-rich treatment on symptom burden, as measured with a specific symptom assessment scale (ESAS-r). METHODS: This retrospective observational study examined pain, anxiety, depression symptoms, and wellbeing in 279 participants over 18 years old, prescribed with CBD-rich treatment at a network of clinics dedicated to medical cannabis in Quebec, Canada. Data were collected at baseline, 3 (FUP1), and 6 (FUP2) month after treatment initiation. Groups were formed based on symptom severity (mild vs moderate/severe) and based on changes to treatment plan at FUP1 (CBD vs THC:CBD). Two-way mixed ANOVAs were used to assess ESAS-r scores differences between groups and between visits. RESULTS: All average ESAS-r scores decreased between baseline and FUP1 (all ps < 0.003). The addition of delta-9-tetrahydrocannabinol (THC) during the first follow-up had no effect on symptom changes. Patients with moderate/severe symptoms experienced important improvement at FUP1 (all ps < 0.001), whereas scores on pain, anxiety, and wellbeing of those with mild symptoms actually increased. Differences in ESAS-r scores between FUP1 and FUP2 were not statistically different. CONCLUSION: This retrospective observational study suggests CBD-rich treatment has a beneficial impact on pain, anxiety, and depression symptoms as well as overall wellbeing only for patients with moderate to severe symptoms; however, no observed effect on mild symptoms. The results of this study contribute to address the myths and misinformation about CBD treatment and demand further investigation.

The model of care at a leading medical cannabis clinic in Canada.

Medical cannabis access has been legalized in more than 30 countries worldwide and popularity among patients is increasing rapidly. Cannabinoid-based treatments have been shown to be beneficial for several symptoms such as chemotherapy-induced nausea and vomiting, spasticity, chronic pain, intractable seizures and insomnia, yet high-quality clinical trials are still limited. As millions of patients now have legal access to medical cannabis, little information is available about the development of best clinical practices and an effective medical cannabis clinic model. A medical cannabis clinic is an innovative and emergent practice model that may be necessary to bridge the gap between patient and healthcare provider interest and existing barriers to the prescription of medical cannabis treatments, such as limited medical education, lack of high-quality clinical research and challenging or evolving regulatory frameworks. In this paper, we describe the model of care and organization of a dedicated medical cannabis clinic operating in Quebec, Canada since 2014. We share the principles of medical cannabis practice, including the structure of its medical and support team, clinic organisation and procedure guidelines. Key clinic statistics and patient demographics are shared with year by year comparison. Operating since 2014, the clinic has endured a rapidly changing regulatory landscape in Canada, overcoming numerous challenges including medical and social stigma, limited funding, resources and institutional support combined with a high demand for services. To support medical cannabis leaders globally, an important knowledge-sharing is required. The clinic has expanded to a network of four clinic sites across Quebec and offers continuing education and preceptorships to health care providers and trainees as well as research services to both academic and industry partners. The description of the clinic offers guidance on medical cannabis treatment and care and discusses possible solutions to associated challenges. The clinic model of care can be adapted to different healthcare settings and regulatory frameworks; it may assist physicians and health care providers in the development of medical cannabis clinics or the implementation of best practices as medical cannabis access continues to evolve.

Authorization Patterns, Safety, and Effectiveness of Medical Cannabis in Quebec.

Introduction: Despite increasing demand for data, little is known about the authorization patterns, safety, and effectiveness of medical cannabis products. Materials and Methods: We conducted a 2 year observational study of adult patients who were legally authorized a medical cannabis product from a single licensed producer; we captured and analyzed authorized cannabis use patterns by cannabinoid profile (tetrahydrocannabinol [THC]-dominant; cannabidiol [CBD]-dominant; and balanced (THC:CBD) and clinical outcomes using standardized outcome measures every 3 months for 12 months at a network of medical cannabis clinics in Quebec, Canada. Results: We recruited 585 patients (average age 56.5 years), of whom 61% identified as female and 85% reported pain as their primary complaint. Over 12 months, there was a significant increase in the number of products authorized (Z=2.59, p=0.01). The proportion of authorizations for a THC-dominant or CBD-dominant product increased relative to the proportion of authorizations for a balanced (THC:CBD) product (all p<0.01). Symptom improvement over time was observed for pain, tiredness, drowsiness, anxiety, and well-being. Patients authorized THC-dominant products exhibited less symptom improvement for anxiety and well-being relative to those authorized CBD-dominant or balanced (THC:CBD) products. Medical cannabis was well tolerated across all product profiles. Conclusion: These real-world data reveal changes in medical cannabis authorization patterns and suggest that symptom improvement may vary by cannabinoid profile over 12 months of follow-up.

The ConDialInt Model: Condensation, Dialogality, and Intentionality Dimensions of Inner Speech Within a Hierarchical Predictive Control Framework.

Inner speech has been shown to vary in form along several dimensions. Along condensation, condensed inner speech forms have been described, that are supposed to be deprived of acoustic, phonological and even syntactic qualities. Expanded forms, on the other extreme, display articulatory and auditory properties. Along dialogality, inner speech can be monologal, when we engage in internal soliloquy, or dialogal, when we recall past conversations or imagine future dialogs involving our own voice as well as that of others addressing us. Along intentionality, it can be intentional (when we deliberately rehearse material in short-term memory) or it can arise unintentionally (during mind wandering). We introduce the ConDialInt model, a neurocognitive predictive control model of inner speech that accounts for its varieties along these three dimensions. ConDialInt spells out the condensation dimension by including inhibitory control at the conceptualization, formulation or articulatory planning stage. It accounts for dialogality, by assuming internal model adaptations and by speculating on neural processes underlying perspective switching. It explains the differences between intentional and spontaneous varieties in terms of monitoring. We present an fMRI study in which we probed varieties of inner speech along dialogality and intentionality, to examine the validity of the neuroanatomical correlates posited in ConDialInt. Condensation was also informally tackled. Our data support the hypothesis that expanded inner speech recruits speech production processes down to articulatory planning, resulting in a predicted signal, the inner voice, with auditory qualities. Along dialogality, covertly using an avatar's voice resulted in the activation of right hemisphere homologs of the regions involved in internal own-voice soliloquy and in reduced cerebellar activation, consistent with internal model adaptation. Switching from first-person to third-person perspective resulted in activations in precuneus and parietal lobules. Along intentionality, compared with intentional inner speech, mind wandering with inner speech episodes was associated with greater bilateral inferior frontal activation and decreased activation in left temporal regions. This is consistent with the reported subjective evanescence and presumably reflects condensation processes. Our results provide neuroanatomical evidence compatible with predictive control and in favor of the assumptions made in the ConDialInt model.

The Frontotemporal Dementia versus Primary Psychiatric Disorder (FTD versus PPD) Checklist: A Bedside Clinical Tool to Identify Behavioral Variant FTD in Patients with Late-Onset Behavioral Changes.

BACKGROUND: Differentiating early behavioral variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is complex and biomarkers have limited accuracy, leading to inaccurate diagnoses. OBJECTIVES: Develop a simple bedside clinical tool to differentiate bvFTD from PPD. METHODS: A checklist of clinical features differentiating bvFTD from PPD was developed based on literature and clinical experience. The checklist was filled prospectively for 29 consecutive patients (Montreal Neurological Hospital) with late-onset (≥ age 40) behavioral changes suggestive of bvFTD. The checklist was subsequently retrospectively completed on the baseline visit (N = 137) of the Late-Onset Frontal Lobe study (Amsterdam). In both cohorts, patients were followed 2 years to establish a final best clinical diagnosis, categorizing patients into Probable FTD (N = 46), Possible FTD (N = 8), Other Cognitive Disorder (N = 36), Other Neurological Disorder (N = 10), or PPD (N = 66). RESULTS: All items distinguished the two groups except "duration more than 5 years", which was removed to create a final 17-item version. Mean checklist scores were significantly different across all groups (Oneway ANOVA F(4,161) = 27.462, p < 0.001). The PPD group had lower scores than all other dementia categories, with the largest difference between Probable FTD (X¯= 12.04) and PPD (X¯= 7.48). A score ≥11 was found to be strongly indicative of bvFTD (specificity 93.9%, sensitivity 71.1%, PPV 89.2%). Scores ≤8 were strongly indicative of a PPD (specificity 91.3%, sensitivity 77.3%, PPV 92.7%). Patient with scores of 9-10 are considered indeterminate. CONCLUSIONS: Although further prospective validation is required, the "FTD vs PPD Checklist" could provide a simple tool to improve diagnostic accuracy, particularly in non-specialized settings.

Atypical Activations of Fronto-Cerebellar Regions During Forethought in Parents of Children With ADHD.

OBJECTIVE: Although several studies suggest heritability of ADHD, only a few investigations of possible associations between people at risk and neural abnormalities in ADHD exist. In this study, we tested whether parents of children with ADHD would show atypical patterns of cerebral activations during forethought, a feature of working memory. METHOD: Using Functional Magnetic Resonance Imaging (fMRI), we compared 12 parents of children with ADHD and 9 parents of control children during a forethought task. RESULTS: Parents of children with ADHD exhibited significantly increased neural activations in the posterior lobes of the cerebellum and in the left inferior frontal gyrus, relative to parents of control children. CONCLUSION: These findings are consistent with previous reports in children and suggest the fronto-cerebellar circuit's abnormalities during forethought in parents of children with ADHD. Future studies of people at risk of ADHD are needed to fully understand the extent of the fronto-cerebellar heritability.

Left-dominant temporal-frontal hypercoupling in schizophrenia patients with hallucinations during speech perception.

BACKGROUND: Task-based functional neuroimaging studies of schizophrenia have not yet replicated the increased coordinated hyperactivity in speech-related brain regions that is reported with symptom-capture and resting-state studies of hallucinations. This may be due to suboptimal selection of cognitive tasks. METHODS: In the current study, we used a task that allowed experimental manipulation of control over verbal material and compared brain activity between 23 schizophrenia patients (10 hallucinators, 13 nonhallucinators), 22 psychiatric (bipolar), and 27 healthy controls. Two conditions were presented, one involving inner verbal thought (in which control over verbal material was required) and another involving speech perception (SP; in which control verbal material was not required). RESULTS: A functional connectivity analysis resulted in a left-dominant temporal-frontal network that included speech-related auditory and motor regions and showed hypercoupling in past-week hallucinating schizophrenia patients (relative to nonhallucinating patients) during SP only. CONCLUSIONS: These findings replicate our previous work showing generalized speech-related functional network hypercoupling in schizophrenia during inner verbal thought and SP, but extend them by suggesting that hypercoupling is related to past-week hallucination severity scores during SP only, when control over verbal material is not required. This result opens the possibility that practicing control over inner verbal thought processes may decrease the likelihood or severity of hallucinations.

Intergenerational transmission of fronto-parietal dysfunction during forethought in attention deficit/hyperactivity disorder: a pilot study.

There are only a few published reports of neural abnormalities within the families of children with attention deficit/hyperactivity disorder (ADHD). Functional magnetic resonance imaging was used to compare cerebral activation of ADHD and control biological parent-child dyads during forethought, a prospective function of working memory. Reduced activations in ADHD dyads were found in the inferior frontal gyrus, right superior parietal lobule and left inferior parietal lobule. This suggests that fronto-parietal abnormalities are shared within ADHD families.

An EMG study of the lip muscles during covert auditory verbal hallucinations in schizophrenia.

PURPOSE: Auditory verbal hallucinations (AVHs) are speech perceptions in the absence of external stimulation. According to an influential theoretical account of AVHs in schizophrenia, a deficit in inner-speech monitoring may cause the patients' verbal thoughts to be perceived as external voices. The account is based on a predictive control model, in which individuals implement verbal self-monitoring. The authors examined lip muscle activity during AVHs in patients with schizophrenia to check whether inner speech occurred. METHOD: Lip muscle activity was recorded during covert AVHs (without articulation) and rest. Surface electromyography (EMG) was used on 11 patients with schizophrenia. RESULTS: Results showed an increase in EMG activity in the orbicularis oris inferior muscle during covert AVHs relative to rest. This increase was not due to general muscular tension because there was no increase of muscular activity in the forearm muscle. CONCLUSION: This evidence that AVHs might be self-generated inner speech is discussed in the framework of a predictive control model. Further work is needed to better describe how inner speech is controlled and monitored and the nature of inner-speech-monitoring-dysfunction. This will lead to a better understanding of how AVHs occur.

[Not Available]. / Facteurs de risque dans le trouble déficitaire de l'attention et de l'hyperactivité: étude familiale.

OBJECTIVE: This study aims at examining risk factors associated with attention-deficit/hyperactivity disorder (ADHD) such as comorbidities and adversity factors in members of a family with ADHD. METHODS: 137 parents of 104 children with ADHD and 40 parents of 34 typically developing (TD) children filled a questionnaire. Chi-square tests and Student tests measured the association between each group and items of the questionnaire as well as the differences between the groups. RESULTS: Statistical analysis revealed overall decreased academic performances in children with ADHD compared to the TD children. Furthermore, ADHD was substantially more associated with learning, conduct, anxiety and oppositional disorders relative to TD children. Learning difficulties were more frequently reported by fathers of children with ADHD. Mothers of children with ADHD suffered more from depression and anxious disorder and were taking more medication than their TD correspondents. CONCLUSION: The results revealed a link between parents and children, namely depression and anxious disorder in mothers and learning difficulties in fathers of children with ADHD, suggesting a familial component to the disorder. The low report of ADHD diagnosis in fathers of children with ADHD is discussed.

Hyperintensity of functional networks involving voice-selective cortical regions during silent thought in schizophrenia.

An important aspect of schizophrenia symptomatology is inner-outer confusion, or blurring of ego boundaries, which is linked to symptoms such as hallucinations and Schneiderian delusions. Dysfunction in the cognitive processes involved in the generation of private thoughts may contribute to blurring of the ego boundaries through increased activation in functional networks including speech- and voice-selective cortical regions. In the present study, the neural underpinnings of silent verbal thought generation and speech perception were investigated using functional magnetic resonance imaging (fMRI). Functional connectivity analysis was performed using constrained principal component analysis for fMRI (fMRI-CPCA). Group differences were observable on two functional networks: one reflecting hyperactivity in speech- and voice-selective cortical regions (e.g., bilateral superior temporal gyri (STG)) during both speech perception and silent verbal thought generation, and another involving hyperactivity in a multiple demands (i.e., task-positive) network that included Wernicke's area, during silent verbal thought generation. This set of preliminary results suggests that hyperintensity of functional networks involving voice-selective cortical regions may contribute to the blurring of ego boundaries characteristic of schizophrenia.