Tag: 6/6/22

Categories : Mental HealthTags :

LSD Microdosing Trips up in Randomised Controlled Study

On By ModernMedia
Photo by Bruce Christianson on Unsplash

A randomised controlled study of LSD microdosing in healthy adults found no evidence of improvements to mood or cognition, which are some of its purported benefits. Other benefits were found to steadily decrease with time. The research has been published in the journal Addiction Biology.

‘Microdosing’ involves taking small amounts of a psychedelic drug at regular intervals. Preliminary research has indicated that microdosing is associated with a range of psychological benefits, such as increased productivity and reduced stress, but the gold standard for proving causation – randomised placebo-controlled studies – had not yet been done.

“I saw how widespread the practice of microdosing is, and yet there are few well-controlled studies to document its apparent benefits,” said study author Harriet de Wit, a professor of psychiatry and behavioral neuroscience at the University of Chicago. “My human psychopharmacology laboratory is well suited to test effects of drugs under double-blind conditions.”

In the study, four low doses of LSD (13 or 26 μg) or placebo were administered to 56 healthy adults at 3–4 day intervals. The participants were aged 18–35 and they all reported having used a psychedelic drug at least once in their lifetime, but were not experienced with microdosing. The doses were administered under double-blind conditions, meaning that neither the participants nor the researchers knew who was receiving an active dose and who was receiving an inactive placebo.

“We removed any expectations that this was a psychedelic drug,” Prof de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”

After ingesting their dose, the participants completed cardiovascular assessments and hourly mood questionnaires. During the first and last sessions, the participants also completed cognitive and behavioral tasks related to emotional processing, working memory, simulated social rejection, and general cognitive performance.

Participants received their dose during five-hour laboratory sessions. They remained in a comfortable room and were given access to movies and reading materials when no activities were scheduled.

The researchers found that the higher dose of LSD (26 μg) produced a small decrease in false alarm rates for recognising fearful emotions and a small decrease in feelings of social rejection. The higher dose of LSD also produced heightened feelings of vigor and some participants who received the higher dose reported feeling a modest “high” during the drug sessions.

But neither the lower or higher doses of LSD had a significant effect on other aspects of emotional processing, mood, working memory, or general cognitive performance. “Under these limited conditions, the effects did not differ from placebo. But, future studies are needed to assess the effects of repeated doses under different conditions,” de Wit told PsyPost.

The participants also appeared to build a tolerance to LSD over the course of the study, with the strongest “high” reported at the first session, and the perception of a drug effect diminishing at each subsequent session.

“We can’t say necessarily that microdosing doesn’t work,” Prof de Wit said in a news release. “All we can say is that, under these controlled circumstances, with this kind of participant, these doses, and these intervals, we didn’t see a robust effect.”

There are more questions to explore in future research “Does microdosing have more pronounced effects in individuals with anxiety or depression, or pressing psychological problems?” Prof de Wit said. “Would the effects be detected if different outcome measures were used, or if dosing continued for more than 2 weeks?”

Source: PsyPost

Categories : CancerTags :

New KRAS-mutated Lung Cancer Treatment Effective in 43% of Cases

On By ModernMedia
MRI or CT machine
Photo by Mart Production on Pexels

Nearly 43% of patients with non-small cell lung cancer (NSCLC) that had a specific KRAS mutation responded to the experimental drug adagrasib, which also showed activity against metastases, according to results of a study published in the New England Journal of Medicine.

Mutations in the potent oncogene known as KRAS occur in about one in four patients with NSCLC, and approximately 13% of NSCLC patients’ tumours are driven by a specific KRAS mutation called G12C. KRAS mutations have long been considered nearly impossible to attack with targeted drugs after many years of research attempts. However, in 2021 a targeted drug, sotorasib, became the first drug approved by the Food and Drug Administration for NSCLC patients with the G12C mutation, based on a clinical trial showing a 36% response rate in those patients after having initially received treatment with chemotherapy and a PD-1 immune checkpoint inhibitor.

Reporting the results of a new phase 2 trial, investigators led by Pasi Jänne, MD, PhD, director of the Lowe Center for Thoracic Oncology at Dana-Farber, showed that treatment with a different KRASG12C mutant inhibitor, adagrasib, yielded a 42.9% objective response rate and a median overall survival rate of 12.6 months in a cohort of 112 patients who had previously received both chemotherapy and immunotherapy with a PD-1 immune checkpoint blocker. Notably, adagrasib treatment also achieved a 33.3% response rate in 33 patients who had stable metastatic lesions in the brain and central nervous system that had spread from the lung tumours.

“These data highlight that inhibiting KRASG12C can lead to clinically meaningful benefits to NSCLC patients with this form of lung cancer,” said Dr Jänne. “Brain metastases are challenging to treat and having a pharmacologic agent that shows activity in this setting is an advancement and movement in the right direction.”

Patients with KRASG12C have had few options after initial chemotherapy and immunotherapy stopped working. In the new clinical trial of adagrasib, taking the oral drug twice daily resulted in a median progression-free survival (the time patients lived before the cancer began to worsen again) was 6.5 months and the median response duration was 8.5 months.

Because the KRASG12C tumor cells typically continue to proliferate, researchers believe sustained inhibition with drugs may be necessary. Thus, adagrasib was optimised for favourable properties including a long half-life of 23 hours and the ability to penetrate the central nervous system. Clinical activity with adagrasib has been shown in patients with other KRASG12C tumors, including colorectal, pancreatic, biliary tract, and other cancers.

Source: Dana-Farber Cancer Institute

Categories : Cancer Surgeries & ProceduresTags :

Bariatric Surgery Reduces Cancer Risks with Obesity

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Obesity
Image source: Pixabay CC0

A study published in JAMA shows that weight loss through bariatric surgery for adults with obesity was associated with a 32% lower risk of developing cancer and a 48% lower risk of cancer-related death compared with those who did not have the surgery.

Rising obesity numbers are being seen all over the world. The International Agency for Research on Cancer describes 13 types of cancer as obesity-associated cancers such as endometrial cancer, postmenopausal breast cancer, and cancers of the colon, liver, pancreas, ovary and thyroid.

Lead author of the study, Ali Aminian, MD, at Cleveland Clinic, said that bariatric surgery is currently the most effective treatment for obesity. “Patients can lose 20 to 40% of their body weight after surgery, and weight loss can be sustained over decades. The striking findings of this study indicate that the greater the weight loss, the lower the risk of cancer,” said Dr Aminian.

From 2004 and 2017, the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) study matched a group of 5053 adult patients with obesity who had bariatric surgery 1:5 to a control group of 25 265 patients with obesity who did not undergo the surgery.

After 10 years, 2.9% of patients in the bariatric surgery group and 4.9% of patients in the non-surgical group developed an obesity-associated cancer.

After 10 years, 0.8% of patients in the surgery group and 1.4% of patients in the non-surgical group died from cancer, indicating that bariatric surgery is associated with a 48% lower cancer mortality risk.

Researchers noted that the benefits of bariatric surgery were seen in a wide range of study participants in terms of age, sex and race. In addition, benefits were similarly observed after both gastric bypass and gastric sleeve operations.

“According to the American Cancer Society, obesity is second only to tobacco as a preventable cause of cancer in the United States,” said the study’s senior author, Steven Nissen, MD, Chief Academic Officer of the Heart, Vascular and Thoracic Institute. “This study provides the best possible evidence on the value of intentional weight loss to reduce cancer risk and mortality.”

Numerous studies have shown the health benefits of bariatric or weight-loss surgery in patients with obesity. The Cleveland Clinic-led STAMPEDE study showed that following bariatric surgery, significant weight loss and control of type 2 diabetes last over time. The SPLENDOR study showed that in patients with fatty liver, bariatric surgery decreases the risk of the progression of liver disease and serious heart complications.

The SPLENDID study adds important findings to the literature focused on the link between obesity and cancer. Given the growing epidemic of obesity worldwide, these findings have considerable public health implications.

“Based on the magnitude of benefit shown in our study, weight loss surgery can be considered in addition to other interventions that can help prevent cancer and reduce mortality,” said Jame Abraham, M.D., chairman of the Hematology and Medical Oncology Department at Cleveland Clinic. “Further research needs to be done to understand the underlying mechanisms responsible for reduced cancer risk following bariatric surgery.”

Source: Cleveland Clinic