Blood pressure management, risks and benefits of cannabis use and psilocybin treatment for MDD

Staying informed about the latest developments in health care is a crucial aspect of a career in medicine. Given the wealth of medical journals, research and studies available, staying up to date can be a challenge. The DO has reviewed recently published research pieces and has compiled three new studies that are pertinent to the work of DOs. See below for summaries and links to original research.

“Intensive vs Conventional Blood Pressure Lowering After Endovascular Thrombectomy in Acute Ischemic Stroke,” JAMA Network, Sept. 5, 2023

Researchers set out to determine whether intensive blood pressure management during the first 24 hours following a successful reperfusion leads to better clinical outcomes compared to conventional blood pressure management in patients who had acute ischemic strokes and underwent endovascular thrombectomy (EVT).

A multicenter, randomized, open-label trial was conducted across 19 stroke centers in South Korea. From June 2020 to November 2022, 306 patients with large vessel occlusion acute ischemic stroke were treated with EVT, along with a modified thrombolysis in cerebral infarction score of 2b or greater (partial or complete reperfusion). Each participant was randomly assigned to receive either intensive blood pressure management (systolic blood pressure target <140 mm Hg; n=155) or conventional management (systolic blood pressure target 140-180 mm Hg; n=150) for 24 hours after being enrolled.

Among the 306 randomized patients, 305 were determined to be eligible and 302 (99.0%) completed the trial. The average age of participants was 73 and 122 women participated, equating to 40.4% of participants. Unfortunately, the trial was terminated early due to safety concerns.

The trial determined that the intensive management group had a lower number of patients achieving functional independence (39.4%) compared to the conventional management group (54.4%). It was also found that there was a significant risk difference. The rate of symptomatic intracerebral hemorrhage was 9.0% in the intensive group and 8.1% in the conventional group. Deaths within three months that were linked to the index stroke occurred in 7.7% of the intensive group and 5.4% of the conventional group.

The study concluded that intensive blood pressure management led to a lower likelihood of functional independence at three months when compared to conventional blood pressure management. This conclusion suggests that intensive blood pressure management should be avoided following a successful EVT in acute ischemic stroke.

“Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies,” The BMJ, Aug. 30, 2023

Researchers set out to assess the credibility of associations between cannabis, cannabinoids and cannabis-based medicines and human health by examining observational studies and randomized controlled trials (RCTs). Credibility was rated using GRADE, or the grading of recommendations, assessment, development and evaluations, as well as a scale consisting of “convincing,” “highly suggestive,” “suggestive,” “weak” or “not significant” (observational evidence). Additionally, reviews with meta-analyses of observational studies and RCTs that reported on the efficacy and safety of cannabis, cannabinoids or cannabis-based medicines were also included.

Over 100 meta-analyses were included. Based on RCTs that were supported by high to moderate certainty, cannabis-based medicines heightened adverse events related to the central nervous system, psychological effects and vision in people with mixed conditions. These medicines improved nausea/vomiting, pain and spasticity, but also increased psychiatric and gastrointestinal adverse events, along with somnolence among others.

Furthermore, it was found that cannabidiol reduced seizures and seizure events. However, cannabidiols increased pneumonia and gastrointestinal adverse events and somnolence. In terms of chronic pain, cannabis-based medicines and cannabinoids reduced pain by 30% across a variety of conditions but also increased psychological distress.

Those with epilepsy experienced an increased risk of diarrhea caused by cannabidiol. It was also found that cannabidiol had no effect on sleep disruption and reduced seizures, while also improving quality of life. Cannabidiols also increased the risk of somnolence in patients with epilepsy.

The general population was found to have experienced worsened positive psychotic symptoms due to cannabis, along with negative psychotic symptoms and cognition. Cannabinoids improved the pain threshold for healthy people. For individuals who suffer from inflammatory bowel disease, multiple sclerosis and cancer, cannabinoids were found to mostly have positive effects, but did render some negative events such as dizziness or nausea.

Harmful effects were also noted for neonatal outcomes, outcomes related to car crashes and outcomes in the general population that include psychotic symptoms, suicide attempts, depression and mania, along with impaired cognition in cannabis users (all had suggestive to highly suggestive results). Researchers concluded that individuals who are in adolescence or early adulthood, people prone to or already suffering with mental health disorders and pregnant people should avoid cannabis. Additionally, cannabis use should be avoided before and while driving.

It was also found that cannabidiol is effective for people with epilepsy, while cannabis-based medicines are effective for those suffering from multiple sclerosis and inflammatory bowel disease, as well as in palliative medicine, but some adverse events should be noted.

“Single-Dose Psilocybin Treatment for Major Depressive Disorder,” JAMA Network, Aug. 31, 2023

In this study, researchers set out to determine the efficacy and safety of psilocybin in patients with major depressive disorder (MDD). They used a randomized, placebo-controlled trial of 104 adults over the course of six weeks. Participants were administered a 25 mg dose of psilocybin and received psychological support. The trial was conducted between Dec. 2019 and June 2022 in 11 research sites in the United States.

Participants ranged in age from 21 to 65 years old with a “Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition” (DSM-5) diagnosis of MDD for at least 60 days with moderate or greater symptom severity. Participants who were found to suffer from psychosis, mania, active substance use disorder, or active suicidal ideation with intent were excluded. Outcomes were assessed at baseline and at two, eight, 15, 29 and 43 days after dosing.

Of the 104 total participants, the average age was 41.1 years and 52 (50%) were women. The participants were randomized, with 51 being assigned to the psilocybin group and 53 to placebo niacin group. It was found that psilocybin treatment was associated with significantly reduced Montgomery-Asberg Depression Rating Scale (MADRS) scores when compared to those who were given the niacin. Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores, and more participants receiving psilocybin had sustained response than those receiving niacin.

While there were no serious treatment-emergent adverse events (AEs), psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Researchers concluded that psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability without serious adverse effects. These conclusions add to increasing evidence that psilocybin (when administered with psychological support) may be a promising intervention for MDD.

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