Cannabis-based medicines and medical cannabis for patients with neuropathic pain and other pain disorders: Nationwide register-based pharmacoepidemiologic comparison with propensity score matched controls.

BACKGROUND: Neuropathic pain and other pain disorders have received attention as potential indications for use of cannabis-based medicines or medical cannabis (CBM/MC). Evidence regarding the efficacy and safety of CBM/MC for pain disorders is, however, insufficient. Denmark introduced a pilot programme of medical cannabis in January 2018. We aimed to evaluate efficacy, safety, and non-specific effects of CBM/MC used under the pilot programme compared with controls. METHODS: We conducted a nationwide register-based cohort study in Denmark, identifying all individuals redeeming at least one prescription for CBM/MC for either neuropathic pain (n = 1817) or other and unspecified pain disorders (n = 924), and to match one control to each case using propensity score matching. RESULTS: Among both patient groups, users of THC used more opioids during follow-up than controls. Among patients with neuropathic pain, however, users of either CBD, THC, or combined CBD + THC used less gabapentin than controls. Users of all three classes of CBM/MC were hospitalized fewer days than controls among neuropathic-pain patients but not among patients with other or unspecified pain disorders. CONCLUSIONS: CBM/MC were generally safe and even displayed some positive effects among patients with neuropathic pain. We conclude that CBM/MC are safe and possibly efficacious for patients with neuropathic pain but not patients with other pain disorders. SIGNIFICANCE: Patients with neuropathic pain may benefit from treatment with cannabis-based medicines or medical cannabis (CBM/MC), particularly in terms of reduced use of gabapentin and fewer days admitted to hospitals, compared with propensity score matched controls. CBM/MC did not, however, reduce the use of opioids. We did not find evidence that CBM/MC were effective for patients with other pain disorders.

Medical cannabis and cannabis-based medicine show both potential efficacy and potential harms: Cross-sectional comparison with controls on self-rated and interviewer-rated outcomes within the Danish pilot program on medical cannabis.

BACKGROUND AND PURPOSE: Denmark launched a pilot program of medical cannabis in January 2018. The aim was to establish whether medical cannabis and cannabis-based medicine (MC/CBM) were superior and safe compared to conventional treatment, regardless of the indications for which people received such medication. MATERIALS AND METHODS: People (cases) were identified who had redeemed at least one prescription of MC/CBM according to the nationwide, unselected Danish registers. These were propensity-score matched to controls with the same indications who had not used MC/CBM. Potential participants were contacted electronically, and if willing to participate filled in various survey instruments online. Participants were also interviewed in person in order to investigate symptoms of depression, anxiety, and to assess cognitive levels. Different sets of analyses were conducted, handling potential confounders in different ways. RESULTS: In the primary analyses, cases were more satisfied with their treatment than were controls (mean (SD) 29.2 (4.8) versus 26.5 (4.5) on the CSQ, p = 0.006), and scored lower on depression (3.3 (3.0) versus 4.6 (2.9), p = 0.03). Cases reported higher levels of pain than controls when measured on the SF-36 bodily-pain subdomain (36.3 (23.0) versus 48.7 (30.1), p = 0.01). There were indications of worse symptoms of multiple sclerosis in cases compared to controls. Reported side-effects were generally mild. CONCLUSION: Both potential effects and harms of MC/CBM were observed. Randomized trials are required to establish if these are true effects and harms, or due to confounding by indication.

Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark.

Importance: Cannabis use and potency of cannabis have increased during the past 2 decades. If the association between cannabis use and schizophrenia is causal, this should be reflected in an increase in the proportion of cases of schizophrenia being attributable to cannabis, the population-attributable risk fraction (PARF). Objective: To determine whether the PARF for cannabis use disorder in schizophrenia has increased over time. Design, Setting, and Participants: This nationwide, register-based historical prospective cohort study included all people in Denmark born before December 31, 2000, who were alive and 16 years or older at some point from January 1, 1972, to December 31, 2016. Data analysis was performed from August 2020 to April 2021. Exposure: Diagnosis of cannabis use disorder. Main Outcomes and Measures: Diagnosis of schizophrenia, with estimated PARF of cannabis use disorder in schizophrenia from 1972 to 2016. Results: A total of 7 186 834 individuals were included in the analysis, including 3 595 910 women (50.0%) and 3 590 924 men (50.0%). The adjusted hazard ratio for schizophrenia fluctuated at approximately 4 (with 95% CIs ranging from approximately 3 to 6) throughout most of the study period when people diagnosed with cannabis use disorder were compared with those without cannabis use disorder. The PARF of cannabis use disorder in schizophrenia also fluctuated, but with clear evidence of an increase from 1995 (when the PARF was relatively stable around 2.0%, with a 95% CI of approximately 0.3% to either side) until reaching some stability around 6.0% to 8.0% (with a 95% CI of approximately 0.5% to either side) since 2010. Conclusions and Relevance: The results from these longitudinal analyses show the proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which is expected given previously described increases in the use and potency of cannabis. This finding has important ramifications regarding legalization and control of use of cannabis.

The Danish OPUS Early Intervention Services for First-Episode Psychosis: A Phase 4 Prospective Cohort Study With Comparison of Randomized Trial and Real-World Data.

OBJECTIVE: The Danish OPUS trial showed significant efficacy of early intervention services for first-episode schizophrenia spectrum disorders compared with standard treatment, leading to implementation of the OPUS intervention in clinical practice. The authors sought to determine whether the effectiveness of OPUS treatment in real-world clinical practice is comparable to the efficacy seen in the trial. METHODS: The study compared patients who received OPUS treatment as part of the original randomized trial to those who received standard treatment in the trial (the control group) and those who received OPUS treatment after it was implemented in Denmark. The authors investigated whether the three groups differed on register-based outcomes, such as use of secondary health care, functional outcomes, and death. Analyses were adjusted for relevant confounders. RESULTS: Compared with trial study participants, patients who received OPUS treatment after implementation (N=3,328) had a tendency toward lower mortality (hazard ratio=0.60, 95% CI=0.33, 1.09), fewer and shorter psychiatric admissions, and possibly fewer filled prescriptions of antipsychotics and other psycholeptics after 4 or 5 years. While at first less likely to be working or studying, patients who received postimplementation OPUS treatment eventually had higher odds of working than did those in the OPUS trial (after 5 years, odds ratio=1.49, 95% CI=1.07, 2.09). The odds of being in a couple relationship were also higher among patients in the postimplementation group than those in the trial. Other outcomes showed less clear associations with treatment group. Generally, the control group in the trial fared worse than both of the OPUS treatment groups. CONCLUSIONS: Not only did OPUS treatment maintain its efficacy after it was implemented as a standard treatment, it paralleled or surpassed many of the effects observed when the OPUS intervention was delivered in a randomized trial. The study results provide further evidence in support of implementation and funding of early intervention services worldwide.

Cannabis use disorders may protect against certain disorders of the digestive organs in people with schizophrenia but not in healthy controls.

BACKGROUND: Previous studies have shown a potential for cannabis in disorders of the digestive organs. We aimed to investigate whether cannabis use disorders (CUD) would decrease the risk of incident disorders of the digestive organs, in people with schizophrenia and population controls. METHODS: We combined nationwide Danish registers to identify 21 066 cases with schizophrenia and 176 935 sex-and-age-matched controls. Two models were analyzed for the associations between CUD and digestive disorders in time-varying Cox regressions: one adjusted for sex, year of birth, and calendar year; and one further adjusted for alcohol and other substance use disorders and parental education. RESULTS: CUD was associated with a decreased risk of developing disorders of gut-brain interaction (e.g. irritable bowel syndrome, dyspepsia, etc.) among cases with schizophrenia (HR = 0.84, 95% CI 0.74-0.94, p = 0.003). CUD was associated with decreased risk of inflammatory bowel disease (HR = 0.70, 95% CI 0.49-0.99, p = 0.045) in the basically adjusted model, dropping just below statistical significance in the fully adjusted model (HR = 0.71, 95% CI 0.48-1.03, p = 0.07). CUD displayed a tendency toward a decreased risk of serious disorders of the digestive organs among cases with schizophrenia (HR = 0.89, 95% CI 0.77-1.02, p = 0.09) in the fully adjusted model. No associations were observed among controls. CONCLUSIONS: In people with schizophrenia, but not in controls, CUD is associated with decreased risk of disorders of gut-brain interaction and inflammatory bowel disease, and possibly other serious disorders of the digestive organs. Our findings could lead to new targets for treatment and prevention of disorders of the digestive organs.