Month: September 2022

There is no definitive evidence yet that microdosing with psychedelics is either effective or safe.

Psychedelic drugs have been capturing the attention of doctors and patients alike, for their increasingly proven potential to effect long-lasting improvements in the mental health of people who are suffering from conditions such as treatment-resistant depression. Microdosing of psychedelic substances such as LSD or psilocybin involves taking a fraction of a regular dose (a subperceptual dose) that is much lower than one would take if one wanted to “trip” or hallucinate on these substances.

Many people share the idea that microdosing with psychedelics enhances one’s mood, creativity, concentration, productivity, and ability to empathize with others. Or could the benefits be an “expectancy effect”? This means that most people who take a daily pill that they fervently expect will help them feel happier and smarter will feel like they are happier and smarter — just from taking the pill, regardless of what’s in it.

What is microdosing?

There isn’t a single, clearly recognized definition of microdosing for any psychedelic drug, and this complicates attempts to perform consistent research. One definition is approximately 1/5 to 1/20 of a recreational dose. (From anecdotal experience this is accurate, as a medium-strength dose of psilocybin is 2 to 3 grams of dried mushrooms, and a microdose is typically around 0.3 grams.) One obstacle is that the potency of mushrooms can vary greatly, as they are not regulated outside of clinical trials, so this isn’t an exact science. Likewise, LSD is an invisible, tasteless, odorless substance that usually comes either in liquid form or embedded into a piece of paper to be slipped under the tongue.

Given its current illegality and lack of regulation, there is no good way to know what dosage you are taking unless you have an extraordinarily reliable supplier. LSD is an extremely powerful and long-acting drug, and you don’t want to take more of it than intended. Further, psychedelics such as psilocybin and LSD can produce physiological tolerance, which might suggest that, even if microdosing does help, there could be diminishing returns if one stays at the same dosage.

Is microdosing safe?

We don’t know as much about safety as we might have learned if not for the War on Drugs, which curtailed much of the research into psychedelics starting in the late 1960s. This research has been renewed over the last five to 10 years, and many medical centers are conducting research on psychedelics. Psilocybin is generally thought to be safe in low dosages and has been used for centuries by indigenous peoples. However, if one takes too large a dose it can result in a terrifying — even traumatic — experience.

Psilocybin is a compound produced by almost 200 species of fungi (mushrooms), and the mushrooms must come from a trusted source. It is very easy to poison oneself with the wrong type of mushroom, as there are many types of mushrooms in nature that can look quite similar to each other, but some are poisonous and can harm your liver, causing severe illness or even death.

Could psychedelics become safer if legalized?

It is anticipated by experts in the field that some psychedelics may become fully legalized — for medical usage, under supervision — within the next few years, specifically psilocybin and MDMA (ecstasy). Some policy makers and public health experts believe that the safety of these psychedelics would be enhanced if they were decriminalized, and if their cultivation and production were monitored and regulated. At least one state (Oregon), and many cities around the country, have decriminalized psychedelics at the local level.

Some advocates of decriminalization are looking forward to a safer product, and wider access that could include not having to see a medical professional to get a prescription or be under medical supervision when using psychedelics. Skeptics are worried that uncontrolled access to these drugs might affect patients with mental illness, or might even precipitate mental illness such as psychosis in people that are vulnerable.

It is important to mention that the use of all psychedelic drugs should be undertaken with utmost caution — if they should be used at all — in patients with major mental illness such as schizophrenia or bipolar disorder. For safety reasons, these patients are typically excluded from studies involving psychedelic drugs.

Evidence for microdosing of psychedelics is mixed

Does microdosing work? In short, the jury is still out. Some studies indicate a very real and significant benefit from microdosing, whereas others are much less convincing and show little to no benefit. One recent study used a naturalistic, observational design to study 953 psilocybin microdosers compared with 180 nondosing participants for 30 days, and found “small to medium-sized improvements in mood and mental health that were generally consistent across gender, age, and presence of mental health concerns.” This study and others like it appear to confirm many anecdotal reports of people who swear by the benefits they have experienced from microdosing.

Other studies on microdosing are far less impressive. In one example the researchers conducted a randomized controlled study, which represents the strongest type of evidence because it weeds out the placebo effect. The researchers took 34 patients and randomized half of them to receive psilocybin and half to placebo. While there were some intriguing subjective effects (people felt happier and more creative), and even some changes in brain waves recorded on an EEG machine, they concluded that low-dose psilocybin mushrooms did not show objective evidence of improvements in creativity, well-being, and cognitive function. Studies such as this one support the hypothesis that the effect people receive from psychedelics at these subperceptual doses is mostly an expectancy effect, and that one needs to consume a higher dosage to receive a therapeutic benefit.

To microdose or not to microdose?

While any medical or lifestyle decision is an individual’s choice (assuming that they aren’t harming others), I would highly recommend that you speak with your doctor to explore your decision to take psychedelics, and see if there are any medical reasons why you should be cautious or avoid these drugs. It is critical to pay attention to the legality and the quality of your product — you likely can’t afford to get into legal jeopardy, and certainly can’t afford to poison yourself.

Finally, it is important to understand that there isn’t yet definitive proof that microdosing is at all helpful, or even that it is safe in the long term. With these points in mind, it is fair to say that psychedelic drugs are becoming better understood, and are undergoing a resurgence of research and a more widely accepted use.

About the Author

Peter Grinspoon, MD, Contributor

Dr. Peter Grinspoon is a primary care physician, educator, and cannabis specialist at Massachusetts General Hospital; an instructor at Harvard Medical School; and a certified health and wellness coach. He is the author of the forthcoming book Seeing … See Full Bio View all posts by Peter Grinspoon, MD

It used to be that doctors would automatically recommend treating all men with prostate cancer, even if their initial biopsies suggested the disease would grow slowly (or at all). But during the last several decades, the pendulum on treatment has swung the other way.

Doctors are now likely to advise active surveillance for low- to intermediate-risk cancers that may never turn deadly over the course of a man’s life. Active surveillance involves routine PSA checks, follow-up biopsies, and more recently, magnetic resonance imaging of a patient’s tumor. Treatment is initiated only when — or if — the disease shows signs of progression.

Recent evidence from Johns Hopkins University shows that the long-term risks of metastasis and death from low-grade prostate cancer among men on active surveillance averages just 0.1%. But doctors who care for such men also face a nagging question: which of their patients might have more aggressive cancer that should require closer monitoring? New findings published by the Johns Hopkins team in January provide useful insights.

The researchers’ approach

The researchers in this case zeroed in on the prognostic value of so-called perineural invasion, or PNI, on tumor biopsy samples. PNI simply means that cancer cells are moving into the perineural space between nerves in the prostate and their surrounding tissues. A finding of PNI raises red flags because the perineural space “provides a conduit by which tumor cells can potentially escape the prostate and grow elsewhere in the body,” says Dr. Christian Pavlovich, a urologic oncologist at Johns Hopkins who led the research.

Dr. Pavlovich’s team wanted to know if PNI detected on initial or follow-up biopsies would be associated with higher risks for cancer progression. So they analyzed long-term follow-up data from 1,969 men who had enrolled in an active surveillance research protocol at Johns Hopkins between 1995 and 2021. All the men were diagnosed initially with Grade Group 1 prostate cancer (the least risky form of the disease) and had undergone at least one follow-up biopsy since then.

What did the results show?

Among the 198 men with PNI, 44% of them (87 men in all) eventually progressed to Grade Group 2 prostate cancer, which is a more advanced form of the disease with an intermediate risk of further spread. Conversely, just 26% of the remaining 1,771 men without PNI (461 men) had progressed to Grade Group 2.

Pavlovich emphasizes that despite the new findings, PNI “does not make patients ineligible for active surveillance.” Importantly, the research showed that PNI was not associated with high-risk features, such as cancer in the lymph nodes of patients who wound up having surgery, or post-surgical elevations in PSA that show cancer still lurks in the body.

“What we’ve really shown here is that PNI puts men at a slightly higher risk of extraprostatic extension (cancer cells located just beyond the confines of the prostate),” Pavlovich says. “This is not necessarily a new finding. But PNI only occurs in about 10% of Grade Group 1 patients, and this is the boldest statement yet from the largest study conducted so far.” Pavlovich and his colleagues concluded that PNI provides an inexpensive and readily available indicator for identifying which men on active surveillance will benefit from more intensive monitoring protocols, including MRI and genetic tests.

Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, agrees, while pointing out that PNI evaluations aren’t performed often enough. A PNI analysis of pathology specimens, he says, “along with emerging and sophisticated genetic testing of the tissue samples, may lead to more certainty in our recommendations to patients.”

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. In addition to writing for Harvard Health Publishing, Charlie has written for Science magazine, the Journal of the National Cancer Institute, Environmental Health Perspectives, … See Full Bio View all posts by Charlie Schmidt

About the Reviewer

Marc B. Garnick, MD,

Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases

Dr. Marc B. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical … See Full Bio View all posts by Marc B. Garnick, MD

The wait is finally over: after 40 weeks of medical appointments, nursery planning, and anticipation, your baby has finally arrived. She is perfect in your eyes, healthy and adorable. Yet over the next few weeks, your initial joy is replaced by all-consuming worries: Is she feeding enough? Why is she crying so often? Is something medically wrong with her? These worries are constant during the day and keep you up at night. You feel tense and irritable, your heart races, and you feel panicky. Your family members start to express their concern —not just about the baby, but about you. You wonder whether your anxiety is normal.

Baby blues, postpartum depression, or postpartum anxiety?

Chances are, you have heard about the baby blues or postpartum depression. You may have even filled out questionnaires about your mood during your postpartum doctor’s visit. The baby blues are a very common reaction to decreasing hormone levels after delivery, and may leave you feeling sad, weepy, and overwhelmed. However, these symptoms are mild and only last for a couple of weeks. When the symptoms persist and become debilitating, something else could be going on.

Many symptoms overlap between postpartum depression and postpartum anxiety (such as poor sleep, trouble relaxing, and irritability). Mothers experiencing postpartum depression commonly experience symptoms of anxiety, although not all mothers suffering from anxiety are depressed. Establishing the correct diagnosis is important, as women with postpartum anxiety may not respond as well to certain treatments for depression, such as interpersonal psychotherapy or medications such as bupropion (Wellbutrin).

Similar to postpartum depression, postpartum anxiety may spike due to hormonal changes in the postpartum period. It may also increase as a response to real stressors — whether it’s the health of the baby, finances, or in response to navigating new roles in your relationships. A history of pregnancy loss (miscarriage or stillbirth) also increases your risk for developing postpartum anxiety. If you have a history of anxiety before or during pregnancy, postpartum anxiety symptoms may also return after delivery. Anxiety and sadness may also appear after weaning from breastfeeding due to hormonal changes.

Some women experience panic attacks or symptoms of obsessive-compulsive disorder (OCD) in the postpartum period. Panic attacks are distinct episodes of intense anxiety accompanied by physical symptoms including a rapidly beating heart, feelings of doom, shortness of breath, and dizziness. Obsessions are intrusive, unwanted thoughts and may be accompanied by compulsions, or purposeful behaviors to relieve distress. These symptoms may be frightening to a new mother, especially when these thoughts involve harming the baby. Fortunately, when obsessions are due to an anxiety disorder, mothers are extremely unlikely to harm their babies.

What are the treatments for postpartum anxiety?

In general, postpartum anxiety is less studied than its cousin postpartum depression; however, it is estimated that at least one in five women has postpartum anxiety. We do know that therapies such as cognitive behavioral therapy (CBT) are excellent treatments for anxiety disorders, including OCD. For some women, medications can be helpful and are more effective when combined with therapy. Selective serotonin reuptake inhibitors (SSRIs) are generally the first-line medications (and the best studied medication class) for anxiety disorders, whereas benzodiazepines are rapidly acting anti-anxiety medications that are often used while waiting for an SSRI to take effect.

Should you take medications when breastfeeding?

Breastfeeding provides many benefits to the baby: it’s the perfect nutrition, it helps build a baby’s immune system, it may help prevent adulthood obesity, and it provides comfort and security. Breastfeeding also provides benefits for the mother: it releases prolactin and oxytocin (the love and cuddle hormones), which help a mother bond with her baby and provide a sense of relaxation. When considering whether to start a medication, it is important to be aware that all psychiatric medications are excreted into the breast milk. Your doctor can help you think through the risks and benefits of medications based on the severity of your illness, medication preference, and previous response, as well as factors unique to your baby, such as medical illness or prematurity.

What non-medication strategies are helpful in decreasing postpartum anxiety?

• Cuddle your baby (a lot). This releases oxytocin, which can lower anxiety levels.
• Try to maximize sleep. Although the baby may wake you every three hours (or 45 minutes) to feed, your partner should not. Sleeping in separate rooms or taking shifts caring for the baby may be necessary during the first few months. Aim for at least one uninterrupted four-hour stretch of sleep, and be mindful about caffeine intake.
• Spend time with other mothers. Although you may feel like you don’t have the time, connecting with other mothers (even online) can do wonders in lowering your fears and validating your emotions. Chances are you are not the only one worrying up a storm.
• Increase your physical activity. In spite of the physical toll that pregnancy, delivery, and milk production take on your body, physical activity is one of the most powerful anti-anxiety strategies. Activities that incorporate breathing exercises, such as yoga, may be particularly helpful.
• Wean gradually. If you are breastfeeding and make the decision to wean, try to do so gently (when possible) to minimize sudden hormonal changes.
• Ask for help. Caring for a baby often requires a village. If you are feeding the baby, ask someone else to help with household chores. There is an old saying “sleep when the baby sleeps.” You may prefer “do laundry when the baby does laundry.”

And finally, give yourself a break — after all, you just had a baby. Postpartum anxiety is common, and in many cases, it will pass with time.

About the Author

Stephanie Collier, MD, MPH, Contributor

Dr. Stephanie Collier is the director of education in the division of geriatric psychiatry at McLean Hospital; consulting psychiatrist for the population health management team at Newton-Wellesley Hospital; and instructor in psychiatry at Harvard Medical School. … See Full Bio View all posts by Stephanie Collier, MD, MPH

A positive outlook has been linked to better heart health and a longer life. But is that true for Black Americans, whose average lifespan is about 72 years, compared with an average lifespan of 77 years for all Americans?

Recent findings from the nation’s largest and longest-running study of cardiovascular risk factors in Black Americans, the Jackson Heart Study, suggest that the answer is a qualified yes. Cardiovascular diseases, which give rise to heart attack and stroke, are the leading cause of death and disability worldwide. Perhaps not surprisingly, the association between optimism and longevity in Black Americans appears to be strongest among people with higher education or income levels, and those ages 55 and younger. It also proved stronger among men than among women.

Is optimism the only key to longevity in this study?

Probably not. There’s another possible explanation for the findings, says Dr. Rishi Wadhera, a cardiologist at Harvard-affiliated Beth Israel Deaconess Medical Center (BIDMC).

“Instead of optimism leading to better health, it’s possible that healthier individuals are simply more optimistic, or less healthy individuals are less optimistic,” he says. This so-called reverse causality — when cause and effect are the opposite of what one assumes — is always a possibility in observational studies, even when scientists take pains to control for possible confounding factors such as health conditions and behaviors, as they did in this study.

“Nonetheless, these findings contribute to a body of evidence that suggests that psychosocial resources, mood, and mental health are all associated with health,” says Dr. Wadhera, who is section head of health policy and equity research at the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at BIDMC.

Measuring optimism in the study

Led by researchers at the Harvard T.H. Chan School of Public Health, the study included 2,652 women and 1,444 men who were part of the Jackson Heart Study. Researchers measured optimism using the Life Orientation Test-Revised, which includes questions such as “In uncertain times, I usually expect the best.” Responses are scored on a scale of 0 (strongly disagree) to 4 (strongly agree). The researchers administered this test and others between 2000 and 2004, and tracked mortality among the study participants until 2018.

Optimism — the general belief that good things will happen — may be partly inherited, although genetic factors are thought to explain only about 20% to 30% of this trait. Some research suggests that people can enhance their feelings of optimism either through cognitive behavioral therapy or writing exercises that focus on imagining their “best possible future self.”

Looking forward

Still, optimism is but one of many intertwined social factors that influence how long people live. A better understanding of biological pathways that could potentially explain the outcomes observed in this study may help, says Dr. Wadhera.

“But to meaningfully address the alarming and ubiquitous health inequities that exist in our country, we need to tackle the unacceptable gaps in care and resources that exist between different racial and ethnic groups,” he adds. This includes disparities in health insurance coverage, access to health care, neighborhood factors such as access to green space and healthy foods, and environmental stressors such as pollution exposure. “Doing so may help people and communities from all backgrounds live happier and longer lives,” Dr. Wadhera says.

 

About the Author

Julie Corliss, Executive Editor, Harvard Heart Letter

Julie Corliss is the executive editor of the Harvard Heart Letter. Before working at Harvard, she was a medical writer and editor at HealthNews, a consumer newsletter affiliated with The New England Journal of Medicine. She … See Full Bio View all posts by Julie Corliss