Health Literacy and Demand for Medical Cannabis use among Colorectal Cancer Patients in Northern Thailand: A Cross-Sectional Study.

OBJECTIVE: This study aimed to explore health literacy and factors associated with demand for medical cannabis (MC) use among colorectal cancer (CRC) patients in Northern Thailand as a target group. METHODS: This cross-sectional analytical study administered multistage random sampling to recruit 439 CRC patients in northern Thailand. Ethical approval and signed written informed consents were obtained from the patients, prior to the study. A standardized, self-administered structured questionnaire was used to obtain the sociodemographic characteristics, clinical characteristics, social support, attitudes toward MC, knowledge about MC, health literacy about MC, and questions on demand for MC use. The scores from all questionnaires were converted to percentages before analysis. RESULTS: A total of 146 (33.26%) of patients with CRC reported demand to use MC. The multivariable analysis revealed that factors associated with demand for MC among CRC patients included: had high levels of health literacy about MC (adj.OR = 7.71; 95% CI: 4.28 to 13.87), aged less than 45 years (adj.OR =5.09; 95% CI: 2.78 to 9.34), positive attitudes toward MC use (adj.OR = 4.66; 95% CI: 2.68 to 8.10), and higher levels of social support (adj.OR =4.14; 95% CI: 2.39 to 7.17) when controlling effect of other covariates. CONCLUSIONS: Health literacy is an important factor affecting the demand for MC use of CRC patients. Therefore, improving health literacy, social support, and attitudes about MC especially among younger CRC patients, could help increase demand for MC as a complementary and alternative medicine alongside cancer treatment.

Predictors of effective therapy among individuals with Cannabis Use Disorder: a review of the literature.

Treatment demand for Cannabis Use Disorder (CUD) has increased in the past decade in almost all European countries, and CUD is currently the most common reason for first-time drug-related treatment admission in the European Union. Even though several therapeutic approaches have been shown to benefit individuals with CUD, there is a lack of knowledge regarding factors associated with effective therapy and the underlying mechanisms of change among individuals with CUD presenting for treatment. The aim of the present paper was to review current knowledge on factors that have been shown to contribute to positive outcomes in CUD treatment. A scoping methodology was used, focusing on empirically evaluated studies that used defined, cannabis-related outcome measures. In eligible studies, factors of investigation were categorized as either 'mediators', i.e., treatment-related factors associated with the processes or mechanisms through which patients benefit from therapy, or 'moderators' which are patient-related characteristics that predict his/her odds to benefit from treatment or patient-related (i.e., moderators). Factors categorized as mediators were then classified 'specific factors' if they were related to a certain technique or treatment modality or 'common factors' if they were assessed beyond treatment modalities. Findings suggest that in CUD treatment, specific mediators include treatment duration, addressing motivation to change, acquiring coping skills, enhancing self-efficacy, and integrating several therapeutic components. Common mediators include therapeutic alliance, empathy, expectations and cultural adaptation. Moderators in CUD treatment include sex, ethnicity, age-related factors and comorbid disorders.

Does medicinal cannabis affect depression, anxiety, and stress in people with cancer? A systematic review and meta-analysis of intervention studies.

INTRODUCTION: Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of medicinal cannabis, compared with any control, as an intervention for depression, anxiety, and stress symptoms in people living with cancer. A secondary aim was to examine the effect of low versus high Δ9-tetrahydrocannabinol (THC) dose on these outcomes. METHODS: Five databases were systematically searched, and complemented with a snowball search from inception to May 2023, for any type of interventional study that included humans of any age with any cancer type. Primary outcomes were incidence and severity of depression, anxiety, and stress symptoms. Secondary outcomes were mood, cognition, quality of life, appetite, nutrition status, gastrointestinal symptoms, and adverse events. Data were pooled using Review Manager. Evidence was appraised using Cochrane risk of bias tools. Confidence in the estimated effect of pooled outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen studies (n = 11 randomized trials, n = 4 non-randomized trials) of 18 interventions (N = 1898 total participants; 100 % ≥18 years of age) were included. Ten studies examined THC (70 % synthetic), two synthetic cannabidiol with or without THC, and six whole-plant extracts. No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher-dose synthetic THC compared with a lower dose (OR: 2.0; 95 % CI: 1.4, 2.9; p < 0.001; Confidence: very low). Medicinal cannabis (THC, cannabidiol, and whole-plant extract) increased the likelihood of improved appetite (OR: 12.3; 95 % CI: 3.5, 45.5; p < 0.001; n = 3 interventions; Confidence: moderate) and reduced severity of appetite loss (SMD: -0.4; 95 % CI: -0.8, -0.1; p = 0.009; Confidence: very low). There was very low confidence that higher doses of synthetic THC increased the likelihood of any adverse event (OR: 0.5; 95 % CI: 0.3, 0.7; p < 0.001). Medicinal cannabis had no effect on emotional functioning, mood changes, confusion, disorientation, quality of life, and gastrointestinal symptoms. Confidence in findings was limited by some studies having high or unclear risk of bias and imprecise pooled estimates. CONCLUSIONS: There was insufficient evidence to determine the efficacy and safety of medicinal cannabis as a therapeutic intervention for depression, anxiety, or stress in people with active cancer. Further research should explore whether medicinal cannabis might improve and maintain appetite and if high-dose synthetic THC might increase the incidence of side-effects, including anxiety. To inform clinical practice, well-powered and rigorously designed trials are warranted that evaluate the effects of medicinal cannabis prescribed to target anxiety, depression, and stress.

Cardiotoxic effects of common and emerging drugs: role of cannabinoid receptors.

Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public health and drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in the regulation of heart health and disease, with mounting evidence linking CBRs with the pathogenesis and progression of drug-induced cardiotoxicity. This review aims to summarize fundamental characteristics of two well-documented CBRs (CB1R and CB2R) from aspects of molecular structure, signaling and their functions in cardiovascular physiology and pathophysiology. Moreover, we describe the roles of CB1R and CB2R in the occurrence of cardiotoxicity induced by common drugs such as antipsychotics, anti-cancer drugs, marijuana, and some emerging synthetic cannabinoids. We highlight the 'yin-yang' relationship between CB1R and CB2R in drug-induced cardiotoxicity and propose future perspectives for CBR-based translational medicine toward cardiotoxicity curation and clinical monitoring.

A phase III multisite randomised controlled trial to compare the efficacy of cannabidiol to placebo in the treatment of cannabis use disorder: the CBD-CUD study protocol.

BACKGROUND: Cannabis use disorder (CUD) is increasingly common and contributes to a range of health and social problems. Cannabidiol (CBD) is a non-intoxicating cannabinoid recognised for its anticonvulsant, anxiolytic and antipsychotic effects with no habit-forming qualities. Results from a Phase IIa randomised clinical trial suggest that treatment with CBD for four weeks reduced non-prescribed cannabis use in people with CUD. This study examines the efficacy, safety and quality of life of longer-term CBD treatment for patients with moderate-to-severe CUD. METHODS/DESIGN: A phase III multi-site, randomised, double-blinded, placebo controlled parallel design of a 12-week course of CBD to placebo, with follow-up at 24 weeks after enrolment. Two hundred and fifty adults with moderate-to-severe CUD (target 20% Aboriginal), with no significant medical, psychiatric or other substance use disorders from seven drug and alcohol clinics across NSW and VIC, Australia will be enrolled. Participants will be administered a daily dose of either 4 mL (100 mg/mL) of CBD or a placebo dispensed every 3-weeks. All participants will receive four-sessions of Cognitive Behavioural Therapy (CBT) based counselling. Primary endpoints are self-reported cannabis use days and analysis of cannabis metabolites in urine. Secondary endpoints include severity of CUD, withdrawal severity, cravings, quantity of use, motivation to stop and abstinence, medication safety, quality of life, physical/mental health, cognitive functioning, and patient treatment satisfaction. Qualitative research interviews will be conducted with Aboriginal participants to explore their perspectives on treatment. DISCUSSION: Current psychosocial and behavioural treatments for CUD indicate that over 80% of patients relapse within 1-6 months of treatment. Pharmacological treatments are highly effective with other substance use disorders but there are no approved pharmacological treatments for CUD. CBD is a promising candidate for CUD treatment due to its potential efficacy for this indication and excellent safety profile. The anxiolytic, antipsychotic and neuroprotective effects of CBD may have added benefits by reducing many of the mental health and cognitive impairments reported in people with regular cannabis use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12623000526673 (Registered 19 May 2023).

Cannabis use and trauma-focused treatment for co-occurring posttraumatic stress disorder and substance use disorders: A meta-analysis of individual patient data.

High rates of cannabis use among people with posttraumatic stress disorder (PTSD) have raised questions about the efficacy of evidence-based PTSD treatments for individuals reporting cannabis use, particularly those with co-occurring alcohol or other substance use disorders (SUDs). Using a subset of four randomized clinical trials (RCTs) included in Project Harmony, an individual patient meta-analysis of 36 RCTs (total N = 4046) of treatments for co-occurring PTSD+SUD, we examined differences in trauma-focused (TF) and non-trauma-focused (non-TF) treatment outcomes for individuals who did and did not endorse baseline cannabis use (N = 410; 70% male; 33.2% endorsed cannabis use). Propensity score-weighted mixed effects modeling evaluated main and interactive effects of treatment assignment (TF versus non-TF) and baseline cannabis use (yes/no) on attendance rates and within-treatment changes in PTSD, alcohol, and non-cannabis drug use severity. Results revealed significant improvements across outcomes among participants in all conditions, with larger PTSD symptom reductions but lower attendance among individuals receiving TF versus non-TF treatment in both cannabis groups. Participants achieved similar reductions in alcohol and drug use across all conditions. TF outperformed non-TF treatments regardless of recent cannabis use, underscoring the importance of reducing barriers to accessing TF treatments for individuals reporting cannabis use.

Psychiatric and substance use disorders among adults over age 50 who use cannabis: A matched cohort study using electronic health record data.

INTRODUCTION: Adults over age 50 increasingly use cannabis, but few studies have examined co-occurring psychiatric and substance use disorders (SUDs) in this population. The current study utilized electronic health record (EHR) data to compare adults age 50 + with ICD-10 cannabis codes (cases) and matched controls on common psychiatric and SUDs from 2016 to 2020. METHOD: Patients age 50 + from an integrated healthcare system in Hawai'i were identified using ICD-10 codes for cannabis (use, abuse, and dependence) from 2016 to 2018. In a matched cohort design, we selected non-cannabis-using controls (matched on sex and age) from the EHR (n = 275) and compared them to cases (patients with an ICD-10 cannabis code; n = 275) on depressive and anxiety disorders and SUDs (i.e., tobacco, opioid, and alcohol use disorders) over a two-year follow-up period. RESULTS: Participants were 62.8 years (SD = 7.3) old on average; and were White (47.8 %), Asian American (24.4 %), Native Hawaiian or Pacific Islander (19.3 %), or Unknown (8.5 %) race/ethnicity. Conditional multiple logistic regression was used to estimate odds ratios comparing cases vs controls. Participants with an ICD-10 cannabis code had a significantly greater risk of major depressive disorder (OR = 10.68, p < 0.0001) and any anxiety disorder (OR = 6.45, p < 0.0001), as well as specific anxiety or trauma-related disorders (e.g., generalized anxiety disorder, PTSD) and SUDs (ORs 2.72 - 16.00, p < 0.01 for all). CONCLUSIONS: Over a two-year period, diverse adults age 50 + in Hawai'i with ICD-10 cannabis codes experienced higher rates of subsequent psychiatric and SUDs compared to controls. These findings can guide efforts to inform older adults about possible cannabis-related risks.

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder.

BACKGROUND: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. METHODS: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. RESULTS: There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02). CONCLUSIONS: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Prevalence, reasons for use, perceived benefits, and awareness of health risks of cannabis use among cancer survivors - implications for policy and interventions.

BACKGROUND: There is increasing discourse on the use of cannabis as a palliative for cancer/cancer-treatment-related symptoms. We described the prevalent reasons for use, perceived benefits, and awareness of health risks from cannabis use for cancer management among cancer survivors. METHODS: Cross-sectional survey of adult (≥ 18 years) cancer survivors from 41 US states receiving treatment at a comprehensive cancer center. RESULTS: Of 1,886 cancer survivors included, 17.4% were current users, 30.5% were former users, and 52.2% were never users of cannabis. Among survivors who currently or formerly used cannabis after their cancer diagnosis (n = 510), the reasons for cannabis use in cancer management were; sleep disturbance (60%), pain (51%), stress (44%), nausea (34%), and mood disorder/depression (32%). Also, about a fifth (91/510) of survivors used cannabis to treat their cancer. Across the different symptoms assessed, over half of the survivors who reported a reason for using cannabis currently or after their cancer diagnosis perceived that cannabis was helpful to a great extent in improving their symptoms. However, of the 167 survivors who reported awareness of potential health risks from cannabis use, the awareness of adverse health risks associated with cannabis use was low: suicidal thoughts (5%), intense nausea and vomiting (6%), depression (11%), anxiety (14%), breathing problems (31%), and interaction with cancer drugs (35%). CONCLUSION: Prevalence of cannabis use among survivors was notable, with most reporting a great degree of symptomatic improvement for the specified reason for use. However, only a few were aware of the health risks of cannabis use during cancer management. IMPLICATIONS FOR CANCER SURVIVORS: With more cancer survivors using cannabis as a palliative in managing their cancer-related symptoms, future guidelines and policies on cannabis use in cancer management should incorporate cannabis-based interventions to minimize the inadvertent harm from cannabis use during cancer treatment among survivors.

Cannabis Use among Cancer Survivors: Use Pattern, Product Type, and Timing of Use.

Despite growing interest in the use of cannabis for the treatment of cancer-related symptoms, there are limited studies that have assessed the use pattern, type, and mode of delivery of cannabis products used by cancer survivors. This study describes the current state of the use pattern, product type, and mode of delivery of cannabis used by cancer survivors. This was a cross-sectional study of cancer survivors from 41 U.S. states who received treatment at the largest NCI-designated comprehensive cancer center. The weighted prevalence of the use patterns, product types, and modes of delivery of cannabis used by cancer survivors was estimated. A total of 1886 cancer survivors were included in the study, with 915 (48% [95% CI: 45-51]) reporting ever using cannabis. Of survivors who had ever used cannabis, 36% (95% CI: 33-40) were current users. Among survivors who reported cannabis use after diagnosis, 40% used cannabis during and after cancer treatment, 35% used cannabis during treatment, and 25% used cannabis after completing their cancer treatment. Additionally, 48% of survivors reported an increase in cannabis use since cancer diagnosis. The commonest types of cannabis products used by cancer survivors were dry leaf cannabis (71%), cannabidiol (CBD) oil (46%), and cannabis candy (40%). Moreover, cancer survivors frequently used baked goods (32%), creams and gels (21%), and tinctures (18%). Furthermore, among ever users, the predominant mode of use was cannabis inhalation/smoking (69%) compared to eating/drinking (59%). More so, the common mode of inhalation/smoking of cannabis products were rolled cannabis cigarettes (79%), pipes (36%), water pipes (34%), vaporizers or vapes (14%), and e-cigarette devices (14%). A substantial number of cancer survivors use cannabis during cancer treatment, with increased use following cancer diagnosis. The forms and modes of delivery of cannabis varied among survivors, with most survivors inhaling or smoking cannabis. There is a need to educate healthcare providers (HCPs) and survivors on current evidence of cannabis use and strengthen cannabis regulatory frameworks to optimize benefits and minimize adverse events from cannabis use during cancer treatment.

Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis.

Background: Epilepsy is one of the most common chronic brain diseases. Almost one-third of patients have drug-resistant epilepsy (DRE). Cannabidiol is being considered as a potential novel drug for treating DRE. Objectives: To investigate long-term efficacy and safety of cannabidiol in treatment of DRE and the differences in cannabidiol treatment among patients with different characteristics. Design: Systematic review and meta-analysis. Data sources and methods: Medline, Embase, and CENTRAL were searched for literature. RevMan5.4 was used for meta-analysis. The Intention-to-treat set and the random effect were used as the main analysis. Subgroup analyses were performed according to age, dose, concomitant antiseizure medications (ASMs), epilepsy syndromes, and study designs. Results: Fifty studies were included in this systematic review. A total of 4791 participants were collected. The responder rates (seizure frequency reduced at least 50%) at 12-, 24-, 48-, 72-, 96-, and 144-week were 0.40 [0.36, 0.45], 0.39 [0.34, 0.44], 0.37 [0.30, 0.44], 0.27 [0.17, 0.37], 0.22 [0.14, 0.30], and 0.38 [0.23, 0.53]. Seizure-free rates were 0.04 [0.03, 0.06], 0.04 [0.03, 0.05], 0.03 [0.02, 0.05], 0.03 [0.02, 0.03], 0.02 [0.01, 0.03], and 0.04 [0.01, 0.06]. Proportion of adverse events were 0.72 [0.61, 0.83], 0.62 [0.42, 0.81], 0.60 [0.41, 0.79], 0.35 [0.14, 0.56], 0.83 [0.75, 0.90], and 0.96 [0.94, 0.99]. The pooled 12-, 24-, 48-, 96-, and 144-week proportion of serious adverse events were 0.15 [0.09, 0.21], 0.23 [0.14, 0.31], 0.10 [0.06, 0.15], 0.31 [0.24, 0.38], and 0.40 [0.35, 0.45]. Subgroup analyses showed that there was no significant difference on efficacy and safety among age subgroups and epilepsy syndromes subgroups. For most periods, there were no significant difference on efficacy among subgroups of dose and concomitant ASMs. However, higher doses and more concomitant ASMs were associated with higher proportion of adverse events. Conclusion: Cannabidiol treatment of DRE has stable efficacy and fewer adverse events in early period. Long-term use may have decreased efficacy and increased adverse events. Dose escalation may not increase efficacy, but may increase adverse events. Furthermore, cannabidiol use may reduce dosage of other ASMs without reducing efficacy, thereby reducing adverse effects. Cannabidiol may have similar effects in various epilepsy syndromes. Trial registration: PROSPERO (CRD42022351250).

Does sleep relate to next-day cannabis use during treatment? Findings from an adolescent and young adult motivational enhancement and cognitive behavioral therapy plus topiramate intervention.

BACKGROUND: Interventions for youth cannabis use have limited efficacy. Sleep is likely to affect treatment response, as sleep difficulties are cross-sectionally associated with use and common during treatment. This analysis examined how sleep duration and subjective trouble sleeping related to next-day cannabis use among youth during cannabis treatment. METHOD: Participants (N=64) received a psychosocial intervention plus topiramate versus placebo while completing a 6-week ecological momentary assessment study. Time-varying effect modeling (TVEM) examined within- and between-person associations between sleep and cannabis use and how the strength of within-person associations varied over the course of treatment. RESULTS: TVEM resvealed that, between-participants, youth with longer average sleep duration used cannabis less often controlling for baseline cannabis use, topiramate, and weekend status. Daily within-person fluctuations in sleep duration and trouble were not associated with use. CONCLUSIONS: Findings suggest regularly shorter sleep may impede treatment outcomes. Adolescents who regularly have insufficient sleep durations likely need additional intervention to improve sleep difficulties in tandem with cannabis use reduction.

Treatment of Adolescent Cannabis Use Disorders.

This review summarizes treatments for cannabis use disorder (CUD) in adolescents. The best supported CUD treatments are cognitive behavioral psychotherapies, including family-based models that facilitate environmental changes and youth-focused models that incorporate skills training, motivational interviewing, and contingency management to promote reductions in cannabis use. Some medications show promise in reducing cannabis craving and withdrawal symptoms. Further research is needed on the efficacy and implementation of existing treatments given the changes in cannabis use trends over time and on emerging technologies that may expand access to evidence-based CUD treatments.

Assessment of Online Marketing and Sales Practices Among Recreational Cannabis Retailers in Five U.S. Cities.

Background: With more states legalizing recreational cannabis, examining cannabis retail and marketing is crucial, as it may influence consumers' perceptions and behaviors. Particularly understudied is online cannabis retail. Methods: In Spring 2022, coders collected and analyzed data regarding retailer characteristics, age verification, and marketing strategies (e.g., product availability, health-related content, promotions, website imagery) among 195 cannabis retail websites in five U.S. cities (Denver, Colorado; Seattle, Washington; Portland, Oregon; Las Vegas, Nevada; Los Angeles, California). Descriptive analyses characterized the websites overall and across cities. Results: Overall, 80.5% verified age for website entry, and 92.8% offered online purchases (92.3% of retailers in Seattle, where prohibited). Of these, 82.9% required age verification for purchases, and 30.9% offered delivery. Almost all (>92%) offered flower/bud, concentrates, edibles, vaping devices, topicals, and tinctures. Health warnings were displayed on 38.3% of websites. Although all five states required health warnings regarding use during pregnancy, only 10.3% had these warnings. In addition, 59.0% posted some unsubstantiated health claims, most often indicating physical and mental health benefits (44.6%). Although Colorado, Washington, and Oregon prohibit health claims, 51.2-53.8% of these retailers posted them. Discounts, samples, or promotions were present on 90.8% of websites; 63.6% had subscription/membership programs. Subpopulations represented in website content included the following: 27.2% teens/young adults, 26.2% veterans, 7.2% sexual/gender minorities, and 5.6% racial/ethnic minorities. Imagery also targeted young people (e.g., 29.7% party/cool/popularity, 18.5% celebrity/influencer endorsement). Conclusions: Regulatory efforts are needed to better monitor promotional strategies and regulatory compliance (e.g., health claims, youth-oriented content, underage access) among online cannabis retailers.

Is Cannabis Effective in the Treatment of Chronic Back Pain?

Cannabis is commonly recognized as a recreational substance. It has been explored for its potential therapeutic applications in addressing various conditions, such as depression, anxiety, sleep disorders, neurological disorders, and chronic low back pain, which affect a significant portion of the population. In the United Kingdom, cannabis has been recognized and licensed for medical use since November 2018, with about 12 National Health Service prescriptions in circulation largely due to patient pressure, with support from media campaigns for its use when there was growing evidence of its use in intractable epilepsy. Cannabis is beginning to gain traction as an alternative or even a complementary drug to opiates with some pre-clinical studies showing opiate-sparing effects. Despite references to its therapeutic use, cannabis as a therapeutic drug has been controversial due to the negative perception of its use as a recreational drug. As a result, there have been challenges in changing the perception of healthcare authorities and clinicians on the use of cannabis as a therapeutic tool for pain relief. The stigma associated with cannabis could be responsible for the paucity of randomized controlled trials on the efficacy of medical cannabis, further decreasing the credibility of the few trials conducted.

Beneficio clínico del tratamiento con cannabinoides para el dolor crónico no oncológico / Clinical benefit of cannabinoids to treat chronic non-cancer pain / Benefício clínico do tratamento com canabinoide para dor crônica não oncológica

Introducción: los cannabinoides pueden ser una opción válida para el tratamiento del dolor crónico no oncológico de acuerdo a los estudios publicados hasta el momento y a nuestra experiencia clínica. Objetivo: valorar el beneficio clínico de preparados de cannabis medicinal (CM) para dolor crónico no oncológico en pacientes que consultaron en la Clínica de Endocannabinología del Uruguay (CEDU). Material y método: estudio descriptivo, observacional, longitudinal, de una población atendida en un centro privado de salud. Se trata de una cohorte de 438 pacientes que consultaron espontáneamente en CEDU desde septiembre de 2016 a marzo de 2020. El motivo de consulta fue dolor crónico no oncológico que no respondió al tratamiento estándar. Resultados: en la cohorte estudiada predominaron las mujeres (74%), promedio 69 años, que se asisten en el sistema privado de salud en el 95% de los casos, en su mayoría con instrucción secundaria. El tipo de dolor más frecuente fue el dolor osteoarticular. El quimiotipo de CM más usado fue cannabidiol (CBD) al 5%, con buena respuesta al tratamiento en el descenso del nivel del dolor y suspensión o disminución de uso de opioides (y derivados) y antiinflamatorios no esteroideos (AINES). Se observaron escasos y leves efectos adversos (EA) en la gran mayoría de los pacientes. Abandonaron el tratamiento 12 pacientes (menos del 3%). Conclusiones: esta investigación retrospectiva mostró una caída del nivel del dolor de 3,14 (valor p ≤ 0,0001), indicando que el CM puede ser una opción para el tratamiento del dolor crónico no oncológico. Se requieren más estudios para demostrar la efectividad y seguridad de los cannabinoides. Esto depende de muchos factores (leyes que faciliten la accesibilidad a variedad de productos de CM de grado médico, incentivos a la ciencia e investigación). De todas formas, podemos afirmar que los resultados presentados son prometedores en relación con su potencial terapéutico.

Introduction: Cannabinoids can be a valid option for the treatment of chronic non-cancer pain, according to the studies published to date and our clinical experience. Objectives: To evaluate the clinical benefit of medicinal cannabis preparations (MCPs) for chronic non-cancer pain in patients seen at the Endocannabinology Clinic of Uruguay (CEDU). Method: Descriptive, observational, longitudinal study of a population treated at a private healthcare center. This involves a cohort of 438 patients who spontaneously consulted at CEDU from September 2016 to March 2020. The reason for consultation was chronic non-cancer pain that did not respond to standard treatment. Results: in the studied cohort, women prevailed and accounted for 74% of patients. Average age was 69 years old and 95% of them sought care within the private healthcare system. Most women had completed secondary school education. The most frequent type of pain was osteoarticular pain. The most used chemovar of Medicinal Cannabis (MC) was 5% cannabidiol (CBD), showing a favorable treatment response in reducing pain levels and the discontinuation or reduction of opioid and non-steroidal anti-inflammatory drug (NSAID) usage. Few and mild adverse effects (AE) were observed in the vast majority of patients. Twelve patients (less than 3%) discontinued the treatment. Conclusions: This retrospective study demonstrated a reduction in pain level of 3.14 (p-value ≤ 0.0001) indicating that MC could be an option for the treatment of non-oncological chronic pain. Further studies are needed to demonstrate the effectiveness and safety of cannabinoids. This depends on many factors (laws facilitating accessibility to a variety of medical-grade MC products, incentives for science and research). Nevertheless, we can assert that the presented results are promising in consideration of their therapeutic potential.

Introdução: os canabinoides podem ser uma opção válida para o tratamento da dor crônica não oncológica de acordo com estudos publicados até o momento e nossa experiência clínica. Objetivos: avaliar o benefício clínico das preparações de Cannabis Medicinal (CM) para dor crônica não oncológica em pacientes que consultaram a Clínica de Endocanabinologia do Uruguai (CEDU). Método: estudo descritivo, observacional, longitudinal de uma população atendida em um centro de saúde privado. Esta é uma coorte de 438 pacientes que consultaram espontaneamente no CEDU no período setembro de 2016 - março de 2020. O motivo da consulta foi dor crônica não oncológica que não respondeu ao tratamento padrão. Resultados: na coorte estudada, 74% eram mulheres, a idade média foi 69 anos, 95% frequentam a rede privada de saúde e a maioria com ensino médio. O tipo de dor mais frequente foi a osteoarticular. O quimiotipo de MC mais utilizado foi o Canabidiol 5% (CBD), com boa resposta ao tratamento em termos de redução do nível de dor e suspensão ou redução do uso de opioides (e derivados) e anti-inflamatórios não esteroides (AINEs). A grande maioria dos pacientes apresentou poucos e leves efeitos adversos (EAs). Menos de 3% dos 12 pacientes abandonou o tratamento. Conclusões: Esta investigação retrospectiva mostrou uma queda no nível de dor de 3,14 (valor de p ≤ 0,0001), indicando que o MC pode ser uma opção para o tratamento da dor crônica não oncológica. São necessários mais estudos para demonstrar a eficácia e segurança dos canabinoides. Isso depende de muitos fatores (leis que facilitem o acesso a uma variedade de produtos CM de grau médico, incentivos para ciência e pesquisa). De qualquer forma, podemos afirmar que os resultados apresentados são promissores em relação ao seu potencial terapêutico.

Elicitation enhances the production of friedelin and epifriedelanol in hairy root cultures of Cannabis sativa L.

Cannabis sativa L. (hemp) has a global distribution and social impact, and it is widely used as a medicinal plant, food ingredient, and textile fiber. Its roots have received less attention than other parts, especially the inflorescence, leaves, and shoots. Triterpenoids, including friedelin and epifriedelanol, have been found in hemp roots, and their anti-inflammatory effects have been reported. In this study, the potential enhancement of triterpenoid accumulation in the roots of C. sativa by elicitation was examined. Hairy roots were successfully established, and they contained 2.02-fold higher triterpenoid levels than natural roots. Furthermore, hairy roots treated with 75 µM salicylic acid had 1.95-fold higher friedelin levels (0.963 mg/g DW) and 1.4-fold higher epifriedelanol levels (0.685 mg/g DW) than untreated hairy roots. These results suggested that the elucidation of hairy root cultures using an optimized elicitor could represent an alternative strategy to produce the valuable triterpenoids friedelin and epifriedelanol.

Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis.

BACKGROUND: Cannabis consumption exerts multiple effects on metabolism via various pathways, including glucose regulation and insulin secretion. Studies concerning the association between cannabis use and diabetes mellitus type 2 are discrepant. OBJECTIVE: This study was conducted to evaluate the association between cannabis use and type 2 diabetes mellitus (T2DM). SEARCH METHODS: We searched PubMed, Scopus, Embase, Proquest, Web of Science, and Cochrane Library with no time, language or study types restriction until July 1, 2022, using various forms of "cannabis" and "diabetes mellitus" search terms. SELECTION CRITERIA: Randomized control trials, cohort, and case-control studies investigating the relationship between cannabis consumption and diabetes mellitus type 2 were included. DATA COLLECTION AND ANALYSIS: The Newcastle-Ottawa scale was used to assess the quality of studies. We pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model, generic inverse variance method, DerSimonian and Laird approach. MAIN RESULTS: A meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing T2DM in individuals exposed to cannabis was 0.48 times (95% CI: 0.39 to 0.59) lower than in those without cannabis exposure. CONCLUSIONS: A protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested. Yet given the considerable interstudy heterogeneity, the upward trend of cannabis consumption and cannabis legalization is recommended to conduct studies with higher levels of evidence.

A Preliminary Investigation Of Repetitive Transcranial Magnetic Stimulation Applied To The Left Dorsolateral Prefrontal Cortex In Treatment Seeking Participants With Cannabis Use Disorder.

Background: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have a therapeutic clinical effect when applied in serial sessions. The present study sought to preliminarily determine whether serial sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. Methods: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post-treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. Results: There were no significant differences in craving between conditions. Participants who received active rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period (Active vs. Sham: -0.72; Z=-2.33, p=0.02). Conclusions: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.