Trends in U.S. Medical Cannabis Registrations, Authorizing Clinicians, and Reasons for Use From 2020 to 2022.

BACKGROUND: As medical cannabis availability increases, up-to-date trends in medical cannabis licensure can inform clinical policy and care. OBJECTIVE: To describe current trends in medical cannabis licensure in the United States. DESIGN: Ecological study with repeated measures. SETTING: Publicly available state registry data from 2020 to 2022. PARTICIPANTS: People with medical cannabis licenses and clinicians authorizing cannabis licenses in the United States. MEASUREMENTS: Total patient volume and prevalence per 10 000 persons in the total population, symptoms or conditions qualifying patients for licensure (that is, patient-reported qualifying conditions), and number of authorizing clinicians. RESULTS: In 2022, of 39 jurisdictions allowing medical cannabis use, 34 reported patient numbers, 19 reported patient-reported qualifying conditions, and 29 reported authorizing clinician numbers. Enrolled patients increased 33.3% from 2020 (3 099 096) to 2022 (4 132 098), with a corresponding 23.0% increase in the population prevalence of patients (175.0 per 10 000 in 2020 to 215.2 per 10 000 in 2022). However, 13 of 15 jurisdictions with nonmedical adult-use laws had decreased enrollment from 2020 to 2022. The proportion of patient-reported qualifying conditions with substantial or conclusive evidence of therapeutic value decreased from 70.4% (2020) to 53.8% (2022). Chronic pain was the most common patient-reported qualifying condition in 2022 (48.4%), followed by anxiety (14.2%) and posttraumatic stress disorder (13.0%). In 2022, the United States had 29 500 authorizing clinicians (7.7 per 1000 patients), 53.5% of whom were physicians. The most common specialties reported were internal or family medicine (63.4%), physical medicine and rehabilitation (9.1%), and anesthesia or pain (7.9%). LIMITATION: Missing data (for example, from California), descriptive analysis, lack of information on individual use patterns, and changing evidence base. CONCLUSION: Enrollment in medical cannabis programs increased overall but generally decreased in jurisdictions with nonmedical adult-use laws. Use for conditions or symptoms without a strong evidence basis continues to increase. Given these trends, more research is needed to better understand the risks and benefits of medical cannabis. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse of the National Institutes of Health.

Mice that are resistant to diet-induced weight loss have greater food anticipatory activity and altered melanocortin-3 receptor (MC3R) and dopamine receptor 2 (D2) gene expression.

Diet-induced weight loss varies considerably between individuals, but the mechanisms driving these individual differences remain largely unknown. Here we investigated whether key neuropeptides involved in the regulation of energy balance or reward systems were differentially expressed in mice that were prone or resistant to caloric restriction (CR) induced weight loss. Mice (n=30 males and n=34 females) were fed 70% of their own baseline ad libitum intake for 25days, after which their brains were collected and expression of various neuropeptides were investigated and compared between the 10 male and 10 female mice that showed the greatest (high weight loss, HWL) or lowest weight loss (LWL) (n=40 in total). HWL mice showed a differential neuropeptide profile to LWL in both sexes, characterised by increased expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), leptin receptor (ObRb), and melanocortin 3 receptor (MC3R) in the arcuate nucleus. No changes in the expression of fat mass and obesity related gene (FTO) or suppressor of cytokine signalling 3 (Socs3) were observed. Levels of dopamine D2 receptor were decreased in the nucleus accumbens in HWL compared to LWL mice. HWL mice showed a stronger increase in food anticipatory activity (FAA) in response to CR than LWL mice. These results indicate that the mice prone to diet-induced weight loss experienced greater hunger, potentially driving their elevated FAA.

Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet-induced obese mice.

OBJECTIVE: The melanin-concentrating hormone (MCH) is a centrally acting peptide implicated in the regulation of energy homeostasis and body weight, although its role in glucose homeostasis is uncertain. Our objective was to determine effects of MCHR1 antagonism on energy budgets and glucose homeostasis in mice. METHODS: Effects of chronic oral administration of a specific MCHR1 antagonist (GW803430) on energy budgets and glucose homeostasis in diet-induced obese (DIO) C57BL/6J mice were examined. RESULTS: Oral administration of GW803430 for 30 days reduced food intake, body weight, and body fat. Circulating leptin and triglycerides were reduced but insulin and nonesterified fatty acids were unaffected. Despite weight loss there was no improvement in glucose homeostasis (insulin levels and intraperitoneal glucose tolerance tests). On day 4-6, mice receiving MCHR1 antagonist exhibited decreased metabolisable energy intake and increased daily energy expenditure. However these effects had disappeared by day 22-24. Physical activity during the dark phase was increased by MCHR1 antagonist treatment throughout the 30-day treatment. CONCLUSIONS: GW803430 produced a persistent anti-obesity effect due to both a decrease in energy intake and an increase in energy expenditure via physical activity but did not improve glucose homeostasis.

Limits to sustained energy intake. XIV. Heritability of reproductive performance in mice.

Limits to sustained energy intake (SusEI) are important because they constrain many aspects of animal performance. Individual variability in SusEI may be imposed by genetic factors that are inherited from parents to offspring. Here, we investigated heritability of reproductive performance in MF1 mice. Food intake, milk energy output (MEO) and litter mass were measured in mothers (F0) and daughters (F1) that were raising litters of 10 pups. Cross-fostering was designed so that half of each litter consisted of biological offspring and the rest came from one unrelated female (i.e. fostered pups). Food intake increased linearly during early lactation and reached a plateau during late lactation (day 9-13, called the asymptotic food intake, FIAS, equivalent to SusEI). Parent-offspring regression showed that FIAS, MEO and litter mass were all positively and significantly related between mothers and their biological daughters, but no significant relationships were found between the same traits for mothers and fostered daughters. FIAS at peak lactation was significantly correlated to adult food intake and body mass when the mice were 6 months old and not lactating. In conclusion, a large part of the variation in FIAS could be explained by genetic variation or maternal effects in pregnancy whereas non-genetic maternal effects in lactation were negligible. As a consequence, biological daughters of mothers with high reproductive performance (i.e. high milk production and hence higher litter mass at weaning) had a better reproductive performance themselves, independent of the mother that raised them during lactation.

Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice.

The endocannabinoids have been recognized as an important system involved in the regulation of energy balance. Rimonabant (SR141716), a selective inverse agonist of cannabinoid receptor 1 (CB1), has been shown to cause weight loss. However, its suppressive impact on food intake is transient, indicating a likely additional effect on energy expenditure. To examine the effects of rimonabant on components of energy balance, we administered rimonabant or its vehicle to diet-induced obese (DIO) C57BL/6 mice once daily for 30 days, by oral gavage. Rimonabant induced a persistent weight reduction and a significant decrease in body fatness across all depots. In addition to transiently reduced food intake, rimonabant-treated mice exhibited decreased apparent energy absorption efficiency (AEAE), reduced metabolizable energy intake (MEI), and increased daily energy expenditure (DEE) on days 4-6 of treatment. However, these effects on the energy budget had disappeared by days 22-24 of treatment. No chronic group differences in resting metabolic rate (RMR) or respiratory quotient (RQ) (P > 0.05) were detected. Rimonabant treatment significantly increased daily physical activity (PA) levels both acutely and chronically. The increase in PA was attributed to elevated activity during the light phase but not during the dark phase. Taken together, these data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. In the short term, the effect included both reduced intake and elevated PA but the chronic effect was only on increased PA expenditure.