Psilocybin reduces symptoms of depression, especially among people with secondary depression. www.bmj.com

Depression Mushroom Drug Psychedelic

Antidepressant use is increasing worldwide, especially in high-income countries. However, roughly 30 percent of people taking the drugs are resistant to their effects. A recent systematic review and meta-analysis found that people with depressive symptoms who took psilocybin were two times more likely to respond to treatment than those not taking the drug.

Researchers analyzed the findings of randomized clinical trials that evaluated the effects of psilocybin therapy on depressive symptoms. They included nine studies involving 436 patients in their analysis.

They found that participants taking psilocybin were two times more likely to respond to treatment than those not taking the drug, especially among those with secondary depression, which can arise due to another medical or psychological issue. Participants experienced few adverse effects, and most were mild and transient. Interestingly, those who had used psychedelics before experienced greater symptom relief, possibly due to “expectancy bias” – a phenomenon where a person’s previous experience makes them expect positive results.

These findings suggest that psilocybin exerts potent antidepressant effects. Although the treatment response was high, the review’s authors graded the quality of the evidence as “low” due to heterogeneity among the studies, including dose and concomitant psychotherapy.

Psilocybin is a psychedelic compound present in mushrooms. Learn more about the effects of psilocybin and other psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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Psilocybin, the active ingredient of "magic mushrooms," triggers rapid and lasting growth of new connections in the brain.

Brain Mushroom Psychedelic LSD
Psilocybin is a bioactive psychedelic compound present in certain varieties of mushrooms, commonly referred to as “magic” mushrooms. With clinical trials finding psilocybin treatment to be effective at reducing symptoms of treatment-resistant depression and obsessive compulsive disorder, increasingly more attention is being drawn to the potential mental health benefits of the compound. Findings from a recent study indicate that a single dose of psilocybin triggers a tangible and lasting proliferation of new neuronal connections in the mouse brain, improving brain plasticity.

In the first phase of their study, the researchers set out to identify a dose of psilocybin that was sufficient to trigger behavioral indicators of mice having a psychedelic-like experience. This involved injecting 82 mice with five doses of psilocybin or a saline solution (of 0, 0.25, 0.5, 1, and 2 milligrams per kilogram of bodyweight) and pinpointing the minimal dose of the drug that reliably caused the animals to twitch their heads. Then, after providing the animals a “psychedelic” dose of one milligram per kilogram of bodyweight, the researchers examined whether psilocybin had an influence on the neurons of the rodents’ frontal cortex – an area of the mammalian brain heavily involved in higher-level cognition, imagination, and decision-making. Their focus fell primarily on the neurons’ dendritic spines: tiny mushroom-like protrusions of membrane that act as neuronal connections by receiving signals and passing them on as electrical impulses.

To track these miniscule anatomical structures using a microscope, the researchers used genetically modified mice whose frontal cortex neurons (spines included) produced a glowing green fluorescent protein known as GFP. All mice began with receiving two microscopy sessions during which the researchers quantified baseline densities of dendritic spines in a tiny section of their frontal cortex. The animals were then randomly allocated to receive either a single dose of psilocybin or a control saline injection, after which the researchers quantified their spine densities on five more occasions (days 1, 3, 5, 7, and 34), blinded to whether the mice had received the active compound or saline.

Tracking spine densities this way revealed that a single dose of psilocybin reliably induced a significant increase in the formation of new spines, which peaked at a 12 percent increase one week after exposure. A proportion of these new connections persisted 34 days after drug exposure. Interestingly, the effect was more pronounced in female animals, although whether this has any therapeutic implications remains to be seen.

This study provides anatomical evidence that psilocybin is capable of stimulating new and lasting connections in the brain – an occurrence that may contribute to the drug’s ability to change mental state both in the short and longer terms. As recent studies report that psychedelic compounds promote mTOR signaling and protein synthesis to stimulate and support the production of new cellular machinery (e.g., dendritic spines), scientists are on the cusp of understanding the biological mechanisms and therapeutic potential of these compounds.
- Link to full report.
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Mushroom consumption is associated with a reduced risk of cognitive impairment in older adults with dementia. www.sciencedaily.com

Brain Mushroom Dementia
Mild cognitive impairment is an intermediary stage between normal cognitive functioning and dementia and may be treatable with diet and lifestyle interventions. Mushrooms contain a number of bioactive compounds, such as hericenones and erinacines, that increase nerve growth factor production and ergothione, an antioxidant and cytoprotective compound. One group of researchers examined the relationship between mushroom consumption and mild cognitive impairment in older adults.

Previous research has shown that mushroom intake improved cognitive performance among Norwegian participants (ages 70 to 74 years). Another epidemiological study in Japanese participants (ages 65 years and older) found that mushroom consumption of at least three times per week or more was associated with a 19 percent reduced risk of dementia. However, the effect of mushroom consumption on the risk of mild cognitive impairment is unknown.

The authors reviewed data from over 600 participants without dementia (ages 60 years and older) from a study in Singapore aiming to identify dietary factors that are associated with healthy aging. Participants provided data regarding demographics, lifestyle, diet, health history, cognitive function, and psychological well being, among others. The researchers interviewed participants to assess their mushroom intake and measured participants’ cognitive function using a standardized questionnaire.

Participants who consumed greater than two servings of mushrooms per week (1.5 cups of cooked mushrooms, about 300 grams) were 43 percent less likely to have mild cognitive impairment than those who consumed mushrooms less than once per week. This association was independent of age, sex, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities. Participants with mild cognitive impairment were more likely to have hypertension and diabetes and were less active in social activities.

The results of this cross-sectional study support the potential of mushroom consumption in delaying the development of cognitive decline. The authors noted that a strength of their study was their accounting of lifestyle and health factors.
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Mushroom consumption reduces the risk of breast and all cancers. www.sciencedaily.com

Cancer Mushroom
Cancer is the second leading cause of death following cardiovascular disease. For many cancers, the risk may be reduced by consumption of a healthy diet rich in plant-based foods because many plants contain anticancer compounds. One team of researchers aimed to determine the role of mushroom consumption in reducing cancer risk.

Mushrooms are rich in bioactive compounds, including phytochemicals (plant chemicals such as flavonoids and carotenoids), fiber, selenium, vitamins, and antioxidants, such as ergothioneine and glutathione, which may help prevent cancer. While laboratory studies have shown the ability of mushroom compounds to inhibit cancer growth, epidemiological evidence is mixed, with some studies reporting a link between mushroom consumption and decreased cancer risk and others reporting no link.

The current report is a systematic review and meta-analysis, meaning the authors searched the existing literature on mushroom consumption and cancer risk, selected studies based on a set of criteria meant to select for relevant studies of high quality, and combined the risk data from each trial to calculate a new set of risk estimates. They selected observational studies of mushroom intake and cancer incidence that included at least two doses of mushroom intake and were published between January 1966 and October 2020.

The authors identified 17 studies that met their selection criteria. Pooled data from these studies showed that higher mushroom consumption was associated with lower risk of total cancer, with participants in the highest consumption group having a 66 percent lower risk of all cancers than participants in the lowest consumption group. Higher mushroom consumption was associated with an 80 percent lower risk for non-breast cancers and a 65 percent lower risk of breast cancer specifically. When the authors calculated risk for specific cancers (lung, breast, prostate, colon, etc.), only breast cancer was significantly associated with mushroom consumption, but they noted this could be due to the small number of studies conducted with non-breast cancers. Finally, the data revealed a significant dose-response association between mushroom consumption and the risk of total cancer with a 45 percent lower risk at high intake (about a quarter cup of sliced mushrooms per day) compared to the lowest intake of zero grams per day.

The results show a significant benefit of mushroom consumption in preventing breast and non-breast cancers. The authors noted that there are limitations to their study including variation in study design among trials.
- Link to full study.
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