“Background: The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others.

Methods: We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24-49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology).

Results: In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (β_w = 0.11, p = 1.3 × 10^-3), and had fewer AUD symptoms (β_w = -0.11, p = 6.7 × 10^-3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome.

Conclusions: Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.”

https://pubmed.ncbi.nlm.nih.gov/36601811/

https://www.cambridge.org/core/journals/psychological-medicine/article/abs/recreational-cannabis-legalization-has-had-limited-effects-on-a-wide-range-of-adult-psychiatric-and-psychosocial-outcomes/D4AB5EB78D588473A054877E05D45F16

“Maternal stress can result in changes in the hypothalamic-pituitary-adrenal (HPA) axis and lead to stress-related behaviours in offspring. Under physiological conditions, delta-9 tetrahydrocannabinol (THC) appears to be detrimental for fertility. However, cannabis is also commonly used for stress-relief. THC acts on the endocannabinoid receptors in granulosa cells (GCs), which affects oocyte competency. The objective of this study was to evaluate the effects of THC on in vitro bovine granulosa cell viability, apoptosis, and stress response pathway. GCs were cultured in vitro in the presence of clinically relevant therapeutic and recreational plasma doses of THC. Cortisol doses reflecting normal and elevated plasma levels were used to evaluate the effects of THC under induced stress in vitro. No effect of THC was observed on cell viability or apoptosis. High and low cortisol concentrations caused significant increases in 11β-HSD1 mRNA expression (n = 6, p < 0.0001). Interestingly, when combined with high [THC], there was a significant decrease in 11β-HSD1 expression compared to high and low cortisol treatments alone (p < 0.001, p < 0.05). GR expression was unaffected by cortisol treatments, and low [THC] treatment maintained increased expression in the presence of high and low cortisol treatments (n = 6, p < 0.01, p < 0.0001). Our findings represent a foundation to obtain useful data for evaluating THC potential therapeutic benefit.”

https://pubmed.ncbi.nlm.nih.gov/36596389/

“THC treatment does not affect granulosa cell viability or apoptosis.•

Cortisol treatments increase 11β-HSD1 gene expression.•

11β-HSD1 gene expression is reduced by THC treatment in combination with cortisol.•

Glucocorticoid receptor gene expression is increased in response to THC.”

https://www.sciencedirect.com/science/article/abs/pii/S0887233322002478?via%3Dihub

“Introduction: Smoking and general categorizations of substance use are linked with increased postoperative complications following total knee arthroplasty (TKA) and total hip arthroplasty (THA). There is a lack of similar evidence on how cannabis use may affect outcomes after arthroplasty. The present study aims to compare postoperative outcomes in cannabis users versus non-cannabis users who underwent THA/TKA. We hypothesize that cannabis users will have no difference in primarily the complication rate, revision rate, and secondarily post-operative Patient-Reported Outcomes Information System (PROMIS) scores, hospital stay, or pain compared to matched controls.

Methods: Billing codes were used to generate lists of hip/knee arthroplasty patients from 2013 to 2019 at our institution. In the case group, cannabis use was confirmed via chart review. Cannabis-using patients were matched appropriately with non-users by (1) the same arthroplasty procedure; (2) BMI ± 3.5; (3) age ± 3 years; (4) sex. Data on postoperative outcomes were collected from charts and compared between groups using either a Chi-square test for qualitative variables or a paired t-test for quantitative variables.

Results: A total of 24 patients with an average age of 57.1 and a BMI of 30.6 were confirmed to have isolated cannabis use. They were matched to 24 patients with an average age of 57.6 and a BMI of 31.4. There were no significant differences in the complication rate (4.2% vs 4.2%, p=1.00), the revision rate (0% vs 4.2%, p=0.31), days of hospital stay (2.7 vs 3.3, p=0.22), or postoperative pain (4.7 vs 4.9, p=0.86). Similarly, there were no significant differences in all PROMIS score measures.

Discussion/conclusions: Current research shows that cannabis use may lead to increased revision arthroplasty and decreased mortality, with mixed findings regarding post-surgical complications. The present study suggests that cannabis-using patients have no difference in postoperative complication rate, revision rate, PROMIS scores, hospital stay, or pain compared to matched controls.”

https://pubmed.ncbi.nlm.nih.gov/36582568/

https://www.cureus.com/articles/126590-cannabis-use-among-lower-extremity-arthroplasty-patients-does-not-lead-to-worse-postoperative-outcomes

“Objective: To investigate the safety and effectiveness of medical cannabis (MC) in the real-world clinical practice setting. 

Design: A 4-year prospective noncomparative registry of adult patients who initiated MC for a variety of indications. This paper reports on patients followed for up to 12 months, with interim visits at 3, 6, and 9 months after enrollment. 

Setting: Public or private outpatient clinics certified to authorize MC in the province of Quebec, Canada. 

Participants: Overall, 2991 adult (age ≥18 years) patients (mean age 51 years; 50.2% women) were enrolled between May 2015 and October 2018, with the last follow-up ending in May 2019. 

Interventions/Exposures: Cannabis products (dried, oil, or other) purchased from a Canadian licensed cannabis producer as authorized by physicians. 

Main Outcome Measures: The primary outcomes were self-reported pain severity, interference and relief (Brief Pain Inventory [BPI]), symptoms using the Revised Edmonton Symptom Assessment System (ESAS-r) and health-related quality of life dimensions (EQ-5D-5L) at baseline and each follow-up visit. The secondary outcomes were self-reported adverse events (AEs) and characteristics of cannabis treatment. 

Results: All patient-reported outcomes (BPI, ESAS-r, and EQ-5D-5L) showed a statistically significant improvement at 3 months (all p<0.01), which was maintained or further improved (for pain interference, tiredness, and well-being) over the remainder of the 12-month follow-up. Results also revealed clinically significant improvements in pain interference and tiredness, anxiety, and well-being from baseline. There were 79 AE reports (77 patients), 16 met the regulatory definition of seriousness, in which only 8 AEs were certainly or probably related to MC. 

Conclusions: MC directed by physicians appears to be safe and effective within 3 months of initiation for a variety of medical indications.”

https://pubmed.ncbi.nlm.nih.gov/36579921/

https://www.liebertpub.com/doi/10.1089/can.2022.0041