Drug

Hair-loss drug finasteride repeatedly linked to depression and suicidal thoughts. https://doi.org/10.4088/JCP.25nr15862

Drug Hormones

Finasteride is one of the most popular prescription drugs for male hair loss, but questions about its psychiatric safety have lingered for over two decades. A new review analyzed postmarketing data to determine whether the drug contributes to depression, anxiety, or suicidality, and to examine why these risks took so long to be recognized.

The analysis brought together eight independent human studies conducted over the last decade. Four used adverse event reporting systems from agencies such as the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO), and four used national health records from Canada, Sweden, France, and Israel. The studies involved men taking finasteride for androgenetic alopecia, commonly called male pattern baldness, usually at the standard 1-milligram dose.

The results were strikingly consistent across all studies:

Every study reported higher rates of depression, anxiety, self-harm, or suicide among finasteride users compared with controls
FDA reports showed roughly three to five times more suicidal thoughts and up to nine times more completed suicides among users relative to the combined background reporting for all other medications in the database.
Global data from the WHO's VigiBase found similar patterns, with about a fourfold increase in reports of suicidal thinking or psychological distress.
National health-record studies found roughly doubled risks of depression and self-harm, with the highest suicide risk in people who already had mood disorders before taking the drug.
Despite these signals, underreporting was severe. In a population of about 4.6 million finasteride users, the FDA received only 18 suicide reports by 2011 and 320 by 2024, compared with tens of thousands that would be expected based on general population rates.

The author points to a biological explanation: finasteride blocks an enzyme called 5-alpha-reductase, which is needed to produce neurosteroids such as allopregnanolone that help regulate mood and stress. Reduced levels of these brain chemicals can alter nerve growth, inflammation, and gene activity, leading to long-lasting depression and anxiety, even after the drug is stopped.

These findings reflect both a genuine safety signal and a systemic failure of drug oversight. Neither the manufacturer nor regulators conducted the necessary analyses when early warning signs appeared in the early 2000s. Depression was added to finasteride's safety label only in 2011, and suicide risk was formally acknowledged by U.S. regulators in 2022 and by the European Medicines Agency in 2025.

The paper concludes that finasteride can cause serious and sometimes persistent psychiatric effects, urging stricter postmarketing surveillance, public reporting of medication histories in suicide cases, and a reassessment of the risk-benefit balance for a drug used mainly for cosmetic purposes. Discover other approaches to reverse hair loss and graying in Aliquot #112.

Semaglutide use reduces biological age by 3.1 years on average, with a 9% slower pace of aging as measured by DNA methylation. www.medrxiv.org

Aging Drug Epigenetics

The biology of aging is increasingly seen as treatable, and drugs like semaglutide—once solely used for diabetes and weight loss—may be part of the solution. A recent study found that people with HIV who took semaglutide for 32 weeks experienced up to a 4.9-year reduction in biological age, as measured by changes in DNA methylation.

The study involved 84 adults with HIV-associated lipohypertrophy—a condition marked by excess abdominal fat and faster biological aging. Participants received weekly semaglutide injections or a placebo for 32 weeks. Researchers collected blood samples at the beginning and end of the study and analyzed DNA methylation, a type of molecular tag that shifts predictably with age.

Compared to those on placebo, participants taking semaglutide showed consistent reductions across several established epigenetic clocks, which estimate biological age from DNA patterns. One clock showed an average drop of 3.1 years, while another suggested a 9% slower pace of aging. Aging signals linked to inflammation, brain health, and heart function also declined in the semaglutide group, though measures of overall physical capacity remained unchanged.

These findings suggest that semaglutide influences more than metabolism—it may also target the molecular hallmarks of aging. Learn more about drugs like semaglutide in Aliquot #128: The Expanding Role of Weight Loss Drugs

Regular cannabis use during adolescence may be linked to long-term insomnia risk. doi.org

Development Drug Sleep Circadian Rhythm

Adolescence is a critical window for brain development, and choices made during this time can shape long-term health. A twin study examined whether beginning regular cannabis use during the teenage years is connected to sleep problems in young adulthood.

Researchers examined 1,882 twins with an average age of 23, and grouped them by cannabis use history: early regular users who started at 17 or younger, later regular users who started after 17, and never-regular users. Sleep outcomes included clinically defined insomnia and a more severe pattern combining insomnia with short weekday sleep (under six hours). By comparing identical twins, who share nearly all their genes, with fraternal twins, who share about half, the team could estimate how much of the link between cannabis use and sleep was due to genetic influences.

Key findings from the study:

About 29 percent of early users reported insomnia, compared with 21 percent of later users and 19 percent of never-users. For the more severe type of insomnia, the rates were 9.9 percent in early users, 7.9 percent in later users, and 5.5 percent in never-users.
Early regular users were more likely to report both forms of insomnia, even after taking mental health and other factors into account.
Both the age at cannabis use onset and insomnia outcomes were strongly shaped by inherited factors. The same genetic influences contributed to both traits, indicating shared genetic liability rather than environmental overlap.

Several pathways could link early cannabis use with later insomnia. One involves circadian and genetic factors, as cannabis may interact with the biological clock systems and genes that regulate circadian timing. Another concerns neurodevelopmental effects: during adolescence, brain regions involved in regulating arousal and sleep-wake patterns are still maturing, and exposure to cannabis may interfere with their normal neurodevelopment. Lastly, cannabis acts directly on the endocannabinoid system, which plays a role in both sleep and circadian regulation.

Conclusion:

The results suggest that starting cannabis use before age 18 is linked to a higher likelihood of insomnia in young adulthood. There was substantial genetic influence on cannabis use, sleep problems, and their association. Because adolescence is a sensitive period, early cannabis exposure could heighten long-term insomnia risk by disrupting ongoing brain and biological development. Since the study relied on self-reports, retrospective cannabis histories, and lacked information on other substances at the time sleep was measured, more prospective research is needed to clarify the long-term effects. Learn more about how cannabis, alcohol, and other factors affect sleep in this clip featuring Dr. Matthew Walker.

Antidiabetes drugs semaglutide and tirzepatide potentially lower dementia and stroke risk by up to 37% in patients with type 2 diabetes and obesity. jamanetwork.com

Dementia Diabetes Drug Obesity

Type 2 diabetes and obesity increase a person's risk of developing dementia and other forms of neurodegeneration, particularly when the two conditions occur together. However, newer antidiabetes drugs may mitigate this risk. A recent study found that people taking the antidiabetes drugs semaglutide or tirzepatide were 37% less likely to develop dementia than those taking other diabetes medications.

Researchers analyzed electronic health records from more than 60,000 adults in the United States who had both type 2 diabetes and obesity. All participants began treatment with semaglutide, tirzepatide, or another type of antidiabetic medication between late 2017 and mid-2024. The researchers matched participants in the different treatment groups by age, sex, and health status and tracked their health for up to seven years.

People who took semaglutide or tirzepatide had a 37% lower risk of dementia, a 19% lower risk of stroke, and a 30% lower likelihood of dying during the study period than those on other antidiabetic drugs. These benefits were even greater among people over age 60, women, and those with a body mass index between 30 and 40. However, the risk of Parkinson's disease and brain bleeds did not differ between the groups.

These findings suggest that antidiabetes drugs like semaglutide and tirzepatide offer protection against cognitive decline and stroke, possibly extending life expectancy in people with type 2 diabetes and obesity. Semaglutide and tirzepatide are GLP-1RA drugs. Learn more about this class of medication in Aliquot #128: The Expanding Role of Weight Loss Drugs

Chronic cannabis use, whether smoked or ingested, impairs arterial function—an early red flag for cardiovascular disease. jamanetwork.com

Cardiovascular Drug

Although often perceived as benign, cannabis—particularly when smoked—may pose underrecognized risks to vascular health. Like tobacco smoke, cannabis smoke contains numerous toxic compounds and fine particles known to impair cardiovascular function. A recent study found that regular cannabis users had roughly 40% lower arterial function than nonusers, raising concerns about the long-term vascular consequences of chronic use.

In this cross-sectional study, researchers categorized 55 healthy adults aged 18 to 50 as chronic marijuana smokers, regular users of edible tetrahydrocannabinol (THC) products, and nonusers. They assessed vascular health using two established measures: arterial flow-mediated dilation (the ability of blood vessels to widen in response to increased blood flow) and carotid-femoral pulse wave velocity (a measure of arterial stiffness). They also assessed how each participant's blood serum affected nitric oxide production in cultured human endothelial cells.

Marijuana smokers and edible THC users both showed impaired vascular function. On average, marijuana smokers had 6% arterial dilation, while edible users averaged 4.6%—substantially lower than the 10.4% observed in nonusers. In cell culture experiments, serum from cannabis smokers markedly reduced nitric oxide production, whereas serum from edible users had no such effect. Higher frequency of smoking and greater THC consumption were both linked to worse vascular outcomes.

These findings suggest that chronic cannabis use—whether smoked or ingested—may promote compromised endothelial function, a known early marker of cardiovascular disease. Compounds in cannabis can also pass into breast milk, potentially harming infants. Learn more in this clip featuring Dr. Rhonda Patrick.

Depression symptoms dropped markedly after one 25-milligram psilocybin dose in a study of people with severe treatment-resistant depression. psychiatryonline.org

Depression Mental Health Drug Psychedelic

People with severe treatment-resistant depression—those who don’t respond to five or more treatments—often struggle for years, cycling through medications and therapies that fail to provide relief. Standard treatments, including neuromodulation techniques like deep brain stimulation, have limited success and carry considerable risks. A recent study found that a single dose of psilocybin, a psychedelic compound found in certain mushrooms, provided rapid and lasting relief for people with treatment-resistant depression.

Researchers conducted a 12-week, open-label trial involving 12 adults with severe treatment-resistant depression. Participants received a single 25-milligram dose of synthetic psilocybin and met with therapists before, during, and after the dosing session to help process their experiences. Using a standard depression symptom scale, researchers assessed changes in depression severity at three weeks, with additional assessments up to 12 weeks.

By week three, the participants' depressive symptoms had dropped markedly, with an average reduction in severity of nearly 16 points on a standard scale. These improvements persisted through week 12. However, participants with post-traumatic stress disorder experienced less benefit, indicating that having more than one neuropsychiatric condition may influence treatment response.

This was a small study, but the findings suggest that psilocybin, combined with psychological support, could be a powerful tool for people with severe treatment-resistant depression. Larger studies may yield more conclusive results. Learn more about psilocybin in this episode featuring the late Dr. Roland Griffiths.

GLP-1 receptor agonists may lower risks for major illnesses like dementia and seizures. www.nature.com

Diabetes Drug Dementia Weight Loss Cardiovascular

Ozempic, Wegovy, and other glucagon-like peptide-1 (GLP-1) drugs have catapulted into the mainstream of diabetes care, with more than 15 million people in the U.S. currently taking one. Evidence suggests GLP-1 drugs have many off-target effects—both good and bad—but healthcare providers don’t currently know the full extent of the drugs' effects. However, a recent analysis found that GLP-1s may reduce the risk of dementia, seizures, respiratory illnesses, cardiometabolic disorders, and certain infections more effectively than other diabetes drugs and typical care.

Using the U.S. Department of Veterans Affairs healthcare databases, researchers identified roughly two million people with diabetes who were using a GLP-1 drug, one of three common anti-diabetes drugs (sulfonylureas, DPP4 inhibitors, or SGLT2 inhibitors), or continuing their usual care without adding new therapies. They tracked the participants' health for about 3.6 years.

They found that GLP-1 use was associated with a reduced risk of dementia (8%), seizures (10%), respiratory illnesses (10% to 25%), cardiometabolic disorders (7% to 22%), and certain infections (12% to 25%). However, the drugs were associated with an increased risk of gastrointestinal issues (5% to 20%), low blood pressure (10%), kidney problems (10% to 15%), arthritic disorders (10% to 16%), and pancreatitis (15% to 20%).

These findings suggest that GLP-1 receptor agonists offer promising benefits for people with diabetes while highlighting potential risks. Further research will illuminate the full range of the drugs' effects. Learn more about GLP-1 drugs in this clip featuring Dr. Rhonda Patrick.

Adolescent attention deficits are linked to higher cannabis use in young adulthood due to weaker connectivity in attention-related brain networks. elifesciences.org

Brain Drug Development

Cannabis use during adolescence has profound effects on critical cognitive functions, particularly sustained attention—the ability to focus on a task over time. A recent study found that problems with sustained attention in early adolescence may predict increased cannabis use later in life.

The study involved more than 1,000 participants, starting at age 14 and continuing until age 23. Researchers measured the participants' attention performance and brain connectivity throughout the study. They also monitored their substance use over time to uncover long-term patterns.

They found that poor sustained attention at age 14, in conjunction with weaker connectivity in attention-related brain networks, predicted higher cannabis use in young adulthood. Differences in these brain networks were stable over time, and the findings were consistent when tested in an external group of participants.

These findings suggest that sustained attention and its underlying brain networks serve as reliable early markers of susceptibility to cannabis use. Cannabis use may disrupt the delicate balance of brain chemicals like dopamine, a neurotransmitter critical for attention and motivation. Learn how to improve attention by leveraging the effects of dopamine in this episode featuring Dr. Andrew Huberman.

Long-term use of rapamycin in humans may not outweigh potential drawbacks, including side effects such as infections, impaired metabolism, and increased heart rate–and may even accelerate aging markers. x.com

Epigenetics Aging Drug

Rapamycin, a compound initially discovered as an antifungal agent, has garnered considerable interest in longevity research due to its ability to inhibit mTOR, a protein that plays a critical role in cellular growth and aging. Studies in animal models have demonstrated rapamycin’s potential to extend lifespan and improve healthspan. However, translating these findings into human applications has proven complex, as substantial risks often accompany the benefits.

Bryan Johnson is an internet personality who has made a name for himself by talking about his sometimes extravagant n=1 biohacking attempts to reverse aging. Recently, Johnson announced a reversal on his position on rapamycin: He thinks it might be making him age worse.

Johnson tested various rapamycin dosing protocols to explore its anti-aging potential while minimizing adverse effects. These protocols included weekly doses of 5, 6, and 10 milligrams, biweekly doses of 13 milligrams, and an alternating weekly schedule of 6 and 13 milligrams.

Although data from preclinical trials were promising, Johnson concluded that the long-term use of rapamycin in humans does not outweigh its drawbacks. Side effects, including intermittent skin and soft tissue infections, impaired lipid metabolism, elevated glucose levels, and increased resting heart rate, persisted regardless of dosage adjustments. After ruling out other potential causes, he attributed these issues to rapamycin and ultimately decided to discontinue its use.

Other research supports his observations, demonstrating that chronic rapamycin use can impair lipid profiles, induce insulin resistance, and contribute to glucose intolerance and pancreatic beta-cell toxicity. While anecdotal evidence suggests that rapamycin may slow tumor growth, its suppression of natural killer cells raises concerns about impaired immune surveillance and potentially increased cancer risk over time.

Further complicating the picture, a recent pre-print study presented new findings about rapamycin’s effects on aging. The study assessed the effects of rapamycin across 16 epigenetic aging clocks and found that it accelerated aging markers in humans. This analysis is noteworthy because most assessments have relied on only one or two aging clocks, raising concerns about the reliability of the findings.

As Johnson notes, longevity research is a rapidly evolving field that requires continuous scrutiny of emerging studies and biomarkers. For now, his experience underscores the importance of balancing potential benefits against risks when exploring experimental compounds like rapamycin. Learn more about rapamycin in our overview article.

Early cannabis exposure disrupts brain development, reducing dendritic branching and neural spine complexity in areas critical for learning and emotional regulation. www.jneurosci.org

Brain Memory Drug Cannabinoid Development

Cannabis use is prevalent among teens, whose brains are undergoing massive developmental changes. Evidence suggests that THC (tetrahydrocannabinol), the primary psychoactive ingredient in cannabis, has profound effects on the brain, impairing neurodevelopment. A recent study in mice found that adolescent cannabis use influences gene expression and neural connections, potentially altering the brain’s structure.

Researchers exposed adolescent male mice to THC and then analyzed changes in gene expression and brain cell structure within the cerebral cortex—a brain region responsible for memory, thinking, learning, reasoning, problem-solving, emotions, consciousness, and sensory functions. They also scanned the brains of more than 450 adolescent human males to compare the cerebral cortex thickness of those who tried cannabis before age 16 to those who did not.

They found that adolescent mice exposed to THC exhibited less dendritic branching and fewer neural spines, indicating a loss of complexity in brain cells. Similarly, human teens who used cannabis had thinner cortex regions. Further analysis linked these structural changes to genes involved in brain development, including processes like learning and memory.

These findings suggest that early cannabis exposure interferes with the normal development of brain structure, especially in areas critical for learning and emotional regulation. This interference likely occurs through effects on specific genes and brain cells responsible for building neural connections during adolescence.

Teens aren’t the only ones at risk for the harmful developmental effects of THC exposure—the compound can pass into breast milk, influencing an infant’s neurodevelopment. Learn more in this clip featuring Dr. Rhonda Patrick.

Low medication use may promote longevity, according to a study in centenarians. link.springer.com

Exercise Diet Aging Alcohol Drug Genetics Tobacco Salt

Genes play critical roles in determining how long a person lives, but a new study suggests that the secret to longevity may be as simple as “food as medicine.” Centenarians—people who live 100 years or more—typically eat healthy, balanced diets and require fewer medications than their shorter-lived peers.

Researchers analyzed studies examining the lifestyles, medication use, and overall health of centenarians and near-centenarians aged 95 to 118. Their analysis included 34 studies and involved more than 59,000 participants.

They identified several healthy lifestyle habits of long-lived adults: Engaging in regular physical activity Avoiding alcohol and tobacco Adhering to a diverse, macronutrient-balanced diet Preferring less salty foods Using few medications—with just over four taken daily, primarily blood pressure medicines or other cardiovascular drugs

Multiple drug use—known as polypharmacy—is common in older adults. Defined as taking more than five medications daily, polypharmacy is linked with many adverse health effects, especially among older adults, who are at risk of a “prescription cascade”—where the side effects of drugs can be misdiagnosed as symptoms of another disease, creating a vicious cycle of more drug use.

This analysis suggests that using food as medicine—through healthy, balanced diets—combined with lower drug use contributes to healthy aging and longevity. Learn how other healthy lifestyle behaviors like exercise and dietary supplementation also promote longevity in this episode featuring Dr. Rhonda Patrick.

Cannabidiol restores the gut microbiome in cocaine users, weakening memory of the drug's reward, according to a study on mice. www.psypost.org

Gut Microbiome Drug Cannabinoid

Cocaine affects nearly every organ system in the body, including the gastrointestinal system, drastically altering the gut microbiome. It also increases dopamine levels in the brain, creating a memory of the dopamine reward and strengthening the association between the drug and the pleasurable feelings it produces. A recent study in mice found that cannabidiol, a non-psychoactive compound in marijuana, restores the gut microbiome in cocaine users, reversing memory-associated cocaine addiction.

Researchers gave adult mice either cocaine + placebo or cocaine + cannabidiol. They collected fecal samples before and after the drug treatments to analyze changes in the gut microbiome.

They found that the mice that received cocaine + placebo developed a strong preference for environments where they received the drug that lasted even after its cessation, indicating they had a memory of the reward. These mice also experienced long-lasting reductions in their gut microbial diversity. However, the mice that received cocaine + cannabidiol showed a reduced preference for the cocaine-associated environment after drug cessation and exhibited greater gut microbial diversity, with more beneficial microbes and fewer harmful ones.

These findings suggest that cannabidiol reverses changes in the gut microbiome caused by cocaine and helps reduce the memory of cocaine’s rewarding effects. Beneficial activities like exercise and hard work also boost dopamine levels but without the massive peaks associated with cocaine use. Learn more in this clip featuring Dr. Andrew Huberman.

Read full publication.

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.

Adding omega-3s to statin therapy significantly reduces the residual risk of major cardiovascular events. www.sciencedirect.com

Heart Disease Cholesterol Omega-3 Drug Mortality Cardiovascular

Statins are among the most widely prescribed drugs in the U.S., with more than 92 million users reported in 2018. Although the drugs are generally effective, nearly 22 percent of statin users with cardiovascular disease will experience a major adverse cardiovascular event within five years of drug initiation – a phenomenon known as “residual risk.” Findings from a recent meta-analysis indicate that combined statin-omega-3 therapy markedly reduces the risk of major adverse cardiovascular events and improves lipid and inflammatory markers.

Researchers analyzed the findings of 14 randomized controlled trials involving more than 40,000 participants. The trials investigated links between statin use, omega-3s, and the risk of cardiovascular disease and related death. Omega-3 doses varied, ranging from 930 milligrams to 4,000 milligrams daily. However, most studies provided a dose of 1,800 milligrams daily.

They found that combined statin-omega-3 therapy reduced the residual risk of experiencing myocardial infarction (heart attack) by 28 percent, a major adverse cardiovascular event by 15 percent, angina (chest pain) by 25 percent, and hospitalization for angina by 25 percent. Those receiving the combined treatment also experienced decreased cholesterol, triglycerides, and hsCRP (a marker of inflammation). However, the combined therapy did not reduce the residual risk of fatal and non-fatal stroke, coronary revascularization, and cardiovascular disease-related death.

These findings suggest that combined statin-omega-3 therapy reduces the residual cardiovascular risks associated with statin therapy alone. Learn more about statins in this episode featuring Dr. Peter Attia.

High-dose statin impairs mitochondrial energy output by more than 30 percent in adults with overweight. pubmed.ncbi.nlm.nih.gov

Cholesterol Mitochondria Drug Muscle Cardiovascular

Statins comprise a large class of drugs that lower blood cholesterol levels by blocking the production of an enzyme involved in cholesterol synthesis. Although statins are generally well tolerated, as many as 10 to 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems. A recent study found that atorvastatin, a commonly prescribed statin, reduces muscle cells' energy production.

The study involved eight inactive but otherwise healthy adults with overweight who took a high dose of atorvastatin (80 milligrams) daily for 56 days. Researchers collected muscle samples from the participants before they took the statin and then again after 14, 28, and 56 days to assess their muscle cells' capacity for energy production.

They found that over the 56 days, the muscle cells' ability to produce energy via oxidative phosphorylation diminished by more than 30 percent. Additionally, the muscle’s capacity to use oxygen, a key indicator of cardiorespiratory fitness, dropped by as much as 45 percent. The study investigators attributed this decline to the statin’s inhibition of specific components (complexes III and IV) within the mitochondria that are vital for energy production.

The findings from this very small study shed light on how high-dose atorvastatin therapy can significantly reduce the energy production in muscle cells, driving a decrease in muscle and aerobic fitness. They also underscore the importance of further research in larger groups to balance the health benefits of statins with their potential effects on muscle function. Learn more about statins in this deep-dive discussion with Dr. Peter Attia.

Meta-analysis: Psilocybin therapy yields a threefold likelihood of remission of depression symptoms. www.sciencedirect.com

Depression Drug Psychedelic

Nearly 25 million adults living in the United States take antidepressant medications. Unfortunately, 10 to 30 percent of those taking antidepressants are resistant to the drugs' effects. A recent systematic review and meta-analysis found that patients with depression who took psilocybin were more than three times more likely to experience remission than those who didn’t.

Researchers evaluated the findings of randomized clinical trials and open-label trials that evaluated depression symptoms among patients diagnosed with life-threatening illnesses or major depressive disorder after receiving psilocybin therapy. They included nine studies involving nearly 600 patients in their final analysis.

They found that participants taking psilocybin were more than twice as likely to have a positive response to therapy than those not taking the drug. They were also more than three times more likely to experience symptom remission.

These findings suggest that psilocybin exerts potent antidepressant effects when used with psychotherapy. Several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating the symptoms of depression, including exercise, dietary modification, meditation, sauna use, and light therapy. Learn more about these approaches in our overview article on depression.

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.

Medications induce gray hair re-pigmentation, pointing to potential future therapies. www.ncbi.nlm.nih.gov

Nutrition Aging Inflammation Drug

Graying hair is a cardinal sign of aging, typically beginning in a person’s fourth or fifth decade. Nutritional deficiencies, including low intake of protein, vitamin B12, iron, and copper, can contribute to premature graying. However, a recent review found that some medications may promote gray hair re-pigmentation.

Researchers reviewed 27 studies and case reports of medication-induced gray hair re-pigmentation, totaling 133 patients. They categorized the various drugs as anti-inflammatories, stimulators of melanogenesis (the production of melanin, the pigment responsible for hair, skin, and eye color), vitamins, medications that accumulate in tissues, and those with an undetermined mechanism. Then, they ranked the quality of the evidence for each study or report.

They found that medications that reduce inflammation or stimulate melanogenesis can promote diffuse re-pigmentation of gray hair. They also found that vitamin B complex supplementation may contribute to the darkening of gray hair, but they cautioned that evidence supporting this finding was weak.

These findings suggest that certain medications induce gray hair re-pigmentation. Although these drugs aren’t presently recommended for treating gray hair, their mechanisms provide insights into potential targets for future medications aimed at hair re-pigmentation.

Antidepressants can affect testosterone and estrogen levels. (2021) www.sciencedirect.com

Hormones Depression Drug Testosterone Estrogen

From the publication:

Firstly, according to the reviewed data from preclinical studies, SSRIs affect to a greater extent, both testosterone and estrogen serum levels compared to the rest of drug classes (Tables 1 and 3). In particular, more than 50% of the reviewed publications report changes in testosterone and estrogen levels after SSRI administration. The same conclusion cannot be drawn from the comparatively fewer studies that investigated other classes of monoaminergic antidepressants. Secondly, data indicated differences between acute and sub-chronic or chronic drug administration on testosterone and estrogen levels. On the one hand, acute antidepressant treatment either decreases or does not affect testosterone and estrogen levels. On the other hand, data from sub-chronic and chronic antidepressant treatment are conflicted, probably due to variable treatment duration and differences in the time and method of sampling. Furthermore, from our reviewed data it appears that testosterone levels are more frequently affected by antidepressants in comparison to estrogen. More specifically, the majority of studies found no changes in estrogen levels following drug administration, whereas the rest of the studies reported either increased or decreased levels of testosterone in both males and females (Tables 1 and 3). Unfortunately, inconsistencies in methods, i.e., inclusion of both sexes, doses, age, duration, and strain, as well as the technical difficulties in measuring low and variable estrogen levels account for the conflicting data and impede any firm conclusions.

Study suggests a link between aspirin use and lower brain aneurysm growth rate. (2019) www.sciencedaily.com

Drug Blood Pressure Aneurysm

From the article:

According to the univariate analysis, significant predictors of aneurysm growth included a patient’s history of ruptured aneurysm, drug abuse, hypertension, and polycystic kidney disease. There was an association between both aspirin use and one type of treatment, stent-assisted coil embolization, and a lower rate of aneurysm growth. In the multivariate analysis, the independent factors associated with aneurysm growth were again patient’s history of ruptured aneurysm, drug abuse, hypertension, and polycystic kidney disease. Only aspirin use proved to be associated with a significant decreased rate of aneurysm growth.

On the basis of the statistical analyses, use of aspirin appears to exert a protective effect against aneurysm growth and very likely against future rupture.

The authors point out that their findings are observational and that future, interventional studies should be conducted.

View full publication

The contraceptive pill and hormone replacement therapy may protect against brain aneurysm. (2011) www.eurekalert.org

Hormones Drug Aneurysm

From the article:

Oestrogen helps maintain the structure of blood vessel walls by promoting the division of endothelial cells within the vessel walls, which is important for repair if the vessels become damaged. However, oestrogen levels drop significantly at the menopause.

Women have been shown to be more likely to develop a cerebral aneurysms after the age of 40 years, and aneurysms are most likely to rupture between the ages of 50 and 59 years.

The authors asked 60 women with cerebral aneurysms about their use of the oral contraceptive pill and hormone replacement therapy, and this was compared with usage in 4,682 other women drawn from the general public.

Women with cerebral aneurysms were found to have been significantly less likely to have taken oral contraceptives or hormone replacement therapy. Women with cerebral aneurysms also had an earlier average age of menopause.

Previous studies have shown that use of the oral contraceptive pill protects against haemorrhagic stroke in later life, while women who start their periods early and/or do not have children are at greater risk.

View full publication

A new drug treatment may extend the lifespan of people with cystic fibrosis. www.washingtonpost.com

Drug

Cystic fibrosis is a progressive, genetic disease that causes persistent lung infections and limits a person’s ability to breathe over time. The average life expectancy of a person with cystic fibrosis is approximately 37 years. Findings from a recent clinical trial indicate that a new drug may help manage the symptoms of the disease and extend their lifespan.

The phase 3, randomized, double-blind, placebo-controlled trial involved more than 400 people aged 12 years and older who have cystic fibrosis. Participants were randomized to receive either the new drug, commonly known as Trikafta, or a placebo for 24 weeks.

At the end of the 24-week period, the participants' lung capacity was measured. Those who received the Trikafta scored 14.3 points higher on lung function tests, were 63 percent less likely to have worsening of symptoms, and had better quality of life compared to those given a placebo. Trikafta was considered safe and elicited few, mild side effects.

The drug works by targeting the underlying genetic mutation that causes the most common form of the disease.

Link to the study abstract.

Drug combo removes senescent cells, restores cell growth in obese mouse model www.nia.nih.gov

Aging Drug

The senolytic drug combination of dasatinib and quercetin cleared senescent cells from obese mice in a study by researchers at the Mayo Clinic in Rochester, Minnesota funded by NIA. When the senescent cells were removed, cell growth resumed in the brain regions involved in that process, also known as neurogenesis, and obesity-related anxiety behavior decreased.

Abstract cellsOver time, accumulation of senescent cells may slow or stop cell regeneration and tissue maintenance, thus contributing to tissue aging.

Clearing senescent cells from the brain and other tissues can delay, prevent, or alleviate multiple age-related disorders.

The combination of dasatinib and quercetin was recently shown to prevent cell damage, delay physical dysfunction, and, when used in naturally aging mice, extend their life span.

The researchers sought to determine whether anxiety-like behavior in obesity can be caused by increased senescent cell burden.

When the senescent cells had been eliminated from the mice brains, anxious behavior decreased and new nerve cell growth in the brain was detected.

The scientists note that the data show that senescent cells play a role in causing impaired cell growth due to obesity.

Eating out at restaurants and fast food chains may increase our exposure to phthalates, a chemical in plastics thought to disrupt hormones. www.theguardian.com

Exercise Hormones Drug Heat Stress Dairy

Phthalates were 35% higher in participants who had eaten out the previous day compared with those who ate at home.

Phthalates are ubiquitous in plastic products yet I have not phthalates listed on consumer product labels. Unfortunately, I’m not sure if it is required to be listed.

In 2013, a randomized trial with five families that involved dietary replacement with organic foods that lacked plastic packaging found that phthalates increased 2000% during the trial because the chemical was found in organic imported spices and dairy products.

Other studies have found that phthalates are excreted through sweat suggesting that forced perspiration such as from exercise and/or using a sauna or other types of heat stress may be a good way to eliminate these potentially harmful compounds.

Link to 2013 phthalate trial: https://www.nature.com/articles/jes20139

One excretion study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504417/

Impact of non-antibiotic drugs on the microbiome www.nature.com

Microbiome Drug

[Abstract]

A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug–microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.

Inflammation Meditation Pregnancy Controversial Drug Rhonda Curcumin Vitamin A Dairy

Hi Rhonda, my wife takes pain medication pretty regularly (at least a 2 in a day a couple of times a week) for headaches and in Joe Rogan’s podcast i heard you mention the negative effects of ibuprofen… Strokes etc…

I was wondering what you would recommend as a substitute to this issue? I was figuring curcumin could be a possibility. Also, i had an thought about the regular use of pain medication for something like a headache and whether or not regular use could increase the likelihood of headaches. If there is any basis in fact for my thoughts i’d be interested to know as i haven’t really done any research on this.

Some things to note: She takes contraceptive pills and skips the sugar pills as to not get her period - I feel this is a terrible idea but she won’t listen to me. If you have insight on this, either relating to the original question or as a side note i’d be interested to know your take on it

Her nutrition is decent. She eats a lot of fruit, nuts, fish and vegetables and takes daily vitamin supplements (fish oil, D3, multi’s, glucosamine, and a few others).

Cheers Rhonda :)

Taking common non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen for only a week may increase heart attack risk by as much as 50%. www.telegraph.co.uk

Heart Disease Drug NSAID Mortality Nitric Oxide

Multiple studies have now linked chronic use of these painkillers with an increased risk of heart attack and stroke. They mechanisms appear to be mediated through the inhibition of an enzyme known as Cox 2. There have been a couple of mechanisms investigated in animal studies. First, NSAIDs have been shown to inhibit the production of a molecule called prostacyclin that relaxes blood vessels and “unglues” platelets. Second, they have been shown to inhibit the production of nitric oxide (which cox 2 also regulates to some degree).

Other studies have shown that people taking 2 grams of phytosomal curcumin (called Meriva) had pain reduction equivalent to 800 mg of ibuprofen.

To hear a longer discuss surounding NSAIDS and heart attack risk, as well as the relevance of curcumin in pain-relief make sure to check out JRE#773 or, more recently, Tim Ferriss Show #237 where both topics are discussed.

Almost one-third of drugs cleared by the FDA have safety risks that are identified only after their approval. www.sciencedaily.com

Drug

Safety risks are defined as those that lead to withdrawal from the market due to safety concerns, a boxed warning, or FDA issuance of a safety communication. The median time for an FDA action to pose new safety risks or withdraw a drug after the drug already hit the market was 4.2 years after approval. The problem is that many clinical trials used for FDA approval involve fewer than 1,000 participants with follow-up of 6 months or less! Long-term side effects often crop up years later after drugs have been used by much larger numbers of people. Another part of the problem is that clinical trials often cherry-pick participants likely to produce the best results, which is not representative of the entire population. One out of three drugs posing safety concerns after they have been deemed safe is alarming. It seems as though the process of approving drugs needs to be revised including more comprehensive clinical trials with a longer follow-up and more participants. Since it takes the FDA about 4 years to identify safety concerns after a drug has been on the market, perhaps a clinical trial investigating a new drug needs a follow-up of 4 years to determine how safe it is in the first place.

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