Month: July 2022

Ketamine is an unusual type of psychedelic drug — called a dissociative — that is undergoing a resurgence in popularity. Originally derived from PCP, or “angel dust,” ketamine has been used in hospitals and veterinary clinics as an anesthetic for decades, and has been cited as a drug of misuse under the moniker “special K.”

It is the effects that ketamine reliably produces that underlie both its medical and recreational uses: pain control, forgetfulness, intoxication, disassociation, and euphoria. Recently, it has been used more widely due to its approval for treatment-resistant depression (TRD) — that is, severe depression that has not improved via other therapies, including people who are experiencing suicidal thoughts.

Evidence of the benefit of ketamine

A prescription version of ketamine called esketamine (Spravato), given through a nasal spray, was approved in 2019 by the FDA for TRD; however, according to the guidelines, it is only to be used “under the supervision of a health care provider in a certified doctor’s office or clinic.” That means medical professionals need to watch you use it, and then follow you after you’ve taken your dose, checking your vital signs and how you are doing clinically.

The effectiveness of ketamine for TRD was first demonstrated for short-term treatment in research that resulted in clinically and statistically significant decreases in depression scores for ketamine versus placebo (In both groups in this study, the patients continued with their regular antidepressants because of concern of not treating TRD in the placebo arm.) Nasal ketamine was shown to have longer-term efficacy, in a study where ketamine (plus the regular antidepressant) helped people stay in stable remission 16 weeks into treatment.

Relief from TRD with ketamine happens rapidly. Instead of waiting for an SSRI to hopefully provide some relief over the course of weeks, people who are suffering under the crushing weight of depression can start to feel the benefits of ketamine within about 40 minutes.

Is ketamine the right treatment for you?

This is a discussion that should include your primary care doctor, your mental health provider, and any other health care professionals who care for you. It’s important to remember that ketamine isn’t a first-option treatment for depression, and it is generally used only when other, more longstanding treatments haven’t been effective. It is not thought to be curative; rather, it improves symptoms for a certain amount of time. It is easier to say who isn’t appropriate for ketamine treatment, based on the side effects.

Should you go to a ketamine clinic for treatment?

Independent, outpatient ketamine clinics are popping up all over the place. It is estimated that there are currently hundreds to thousands of these clinics — almost all of which were established in 2019 when ketamine was approved for TRD. Typically, these clinics are for-profit enterprises that are staffed by some combination of either a psychiatrist or an anesthesiologist (who can administer the infusion), a nurse, a social worker, and (of course) the businesspeople who make it all work.

In writing this piece, I called several ketamine clinics, posing as a patient, to investigate what would be involved in receiving ketamine therapy. Most of them seemed as if they would provide ketamine for me without any major hurdles, after an introductory medical interview by a nurse or a social worker. A few clinics required communication or a diagnosis from my psychiatrist — and this seemed quite sensible.

The clinics operate on a fee-for-service arrangement, so you would pay out of pocket, as insurance rarely covers this treatment. In the Boston area where I live, the ketamine infusions cost about $600 each, and a course of six infusions and a clinical re-evaluation are typically recommended. (I should note that the ketamine clinics affiliated with medical academic institutions seem to have more safeguards in place, and they may also be enrolling people in clinical trials.)

Are ketamine clinics safe?

These ketamine clinics raise many questions — namely, what does one look for in a reputable and safe ketamine clinic? Currently, we don’t yet have definitive answers to that question. One wonders if a ketamine infusion, which can cause a profound dissociation from reality, would be better controlled in a hospital setting, where there are protocols for safety in case anything goes wrong. It was unclear (in part because I didn’t actually go through with the therapy) how much communication, if any, there would be between the ketamine clinic staff and your health care providers, and typically the treatments you receive would not be included in your primary electronic medical record.

What are the side effects?

Ketamine is generally considered safe, including for those who are experiencing suicidal ideation (thoughts or plans for suicide). The main side effects are dissociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, nausea, and vomiting. Ketamine is avoided or used with extreme caution in the following groups:

• people with a history of psychosis or schizophrenia, as there is concern that the dissociation ketamine produces can make psychotic disorders worse
• people with a history of substance use disorder, because ketamine can cause euphoria (likely by triggering the opioid receptors) and some people can become addicted to it (which is called ketamine use disorder)
• teenagers, as there are some concerns about the long-term effects of ketamine on the still-developing adolescent brain
• people who are pregnant or breastfeeding
• older adults who have symptoms of dementia.

More detailed research needs to be done on the longer-term benefits and side effects of ketamine treatment, and on its safety and effectiveness for teens and older adults, as well as for the emerging indications of ketamine therapy for PTSD, OCD, alcohol use disorder, and other mental health conditions.

Finally, there is some concern that, with repeated dosing, ketamine can start to lose its effectiveness and require larger doses to produce the same effect, which is not sustainable.

Ketamine could provide hope for people with serious depression

Serious, treatment-resistant depression can rob people of hope for the future and hope that they will ever feel better. Ketamine can provide help and hope to patients who have not found relief with any other treatments. Given its efficacy in people considering suicide, it is plausible that ketamine may be lifesaving.

As we learn more from research on ketamine and from people’s experiences in newer clinics, we will be better able to answer the questions of ketamine’s longer-term effectiveness and what safeguards are needed for treatment. We may also learn who is most likely to safely benefit from ketamine therapies, and the best method of administration: intravenous infusion, a nasal spray, or a pill.

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

Hot flashes and sleep or mood changes are well-known, troublesome symptoms that may occur during perimenopause and menopause. Now, one survey suggests nearly 80% of midlife women use cannabis to ease certain symptoms, such as mood issues and trouble sleeping.

Mounting numbers of US states have legalized marijuana for medical or recreational use in recent years. This wave of acceptance runs alongside skepticism in some quarters concerning FDA-approved menopause treatment options, including hormone therapy. But a lack of long-term research data surrounding cannabis use has led one Harvard expert to question how safe it may be, even while acknowledging its likely effectiveness for certain menopause woes.

“More and more patients tell me every year that they’ve tried cannabis or CBD (cannabidiol, an active ingredient in cannabis), particularly for sleep or anxiety,” says Dr. Heather Hirsch, head of the Menopause and Midlife Clinic at Harvard-affiliated Brigham and Women’s Hospital. “Adding to its appeal is that cannabis is now legal in so many places and works acutely for a couple of hours. You don’t need a doctor’s prescription. Socially, it may be easier to justify than using a medication. But why is there a movement toward saying okay to something that has unknown long-term effects, more than something that’s been studied and proven safe?” she asks.

Survey reports on who uses cannabis, why, and how

The new Harvard-led survey, published in the journal Menopause, looked at patterns of cannabis use in 131 women in perimenopause — the often years-long stretch before periods cease — along with 127 women who had passed through menopause. Participants were recruited through online postings on social media sites and an online recruitment platform. Nearly all survey respondents were white and most were middle-class, according to income reporting.

The vast majority (86%) were current cannabis users. Participants were split on whether they used cannabis for medical reasons, recreational purposes, or both. Nearly 79% endorsed it to alleviate menopause-related symptoms. Of those, 67% said cannabis helps with sleep disturbance, while 46% reported it helps improve mood and anxiety.

Perimenopausal women reported worse menopausal symptoms than their postmenopausal peers, as well as greater cannabis use to address their symptoms. More than 84% of participants reported smoking cannabis, while 78% consumed marijuana edibles, and nearly 53% used vaping oils.

One glaring limitation of the analysis is its self-selected group of participants, which lacked diversity and might skew results. But Dr. Hirsch wasn’t surprised by the high proportion reporting regular cannabis use. “I wouldn’t be surprised if those numbers reflect the broader population,” she says.

How might cannabis help menopause symptoms?

It makes sense that midlife women reported cannabis improves anxiety, mood, and sleep, Dr. Hirsch says. The drug likely helps all of these symptoms by “dimming the prefrontal cortex, the decision-making part of our brain.”

For many women, anxiety spikes during perimenopause, she notes. Common stressors during that time, such as aging parents or an emptying nest, add to the effects of dipping hormones. “It’s that feeling of, ‘I can’t turn my brain off.’ It’s really disturbing because they get in bed and can’t fall asleep, so they’re more tired, moody, and cranky the next day,” she explains. Dimming the prefrontal cortex enables people to calm down.

Hot flashes, often cited as the most common menopause symptom, did not improve as much from cannabis use, according to survey respondents. That too makes sense, Dr. Hirsch says, because the hypothalamus — the brain region considered the body’s thermostat — isn’t believed to be significantly affected by the drug.

No research yet on long-term effects

Given a lack of clinical trials objectively testing the effectiveness and safety of cannabis to manage menopause symptoms, more research is clearly needed.

“If people are finding relief from cannabis, great. But is it safe? We think so, but we don’t know,” she says. “There are no studies of middle-aged women using cannabis for 10 years, for as long as menopause symptoms often last. Are there going to be long-term effects on memory? On lung function? We don’t know.”

About the Author

Maureen Salamon, Executive Editor, Harvard Women's Health Watch

Maureen Salamon is executive editor of Harvard Women’s Health Watch. She began her career as a newspaper reporter and later covered health and medicine for a wide variety of websites, magazines, and hospitals. Her work has … See Full Bio View all posts by Maureen Salamon

A simple word we all hear often — exercise — makes many people cringe. Unhappy childhood memories of school sports or gym classes, flat-out physical discomfort, guilty reluctance, or trouble finding time or pleasurable activities may help explain this. Additionally, for some people with obesity, fear of falling or injury is a high barrier to activity, recent research suggests.

That finding has important implications for health and well-being. So, how can we make movement safe and joyful for people of all weights?

Why be active?

As you may know, being physically active helps combat anxiety and depression. It prevents bone from thinning and tones muscle, helps you sleep better, lowers your blood pressure and blood sugar, and improves your cholesterol levels. It would take numerous medications to do all that routine physical activity can do for you.

Weight loss programs often incorporate exercise. Research shows that exercise helps with weight maintenance and may help with weight loss. Beyond burning calories, regular exercise also builds muscle mass. This matters because muscles are metabolically active, releasing proteins that play a role in decreasing appetite and food intake.

What does this study tell us?

The study found that many people with obesity fear injury and falling, which interferes with willingness to exercise. It followed 292 participants enrolled in an eight-week medical weight loss program in Sydney, Australia. All met criteria for obesity or severe obesity. The average age was 49; one-third of participants were male and two-thirds were female.

At the beginning of the study, participants filled out a 12-question injury perception survey. The majority reported fear of injury or falling, and believed their weight made injury more likely to occur. One-third said that their fear stopped them from exercising. The researchers also recorded weight, height, and waist circumference, and administered strength tests during the first, fourth, and last sessions.

When the study ended, the researchers found that the participants most concerned about getting injured hadn’t lost as much weight as those who did not express this fear. Those who hadn't lost as much weight also tended to have the highest scores of depression, anxiety, and sleepiness.

Fear of injury fuels a dangerous cycle

As noted, exercise is healthy at every weight: it protects your heart, lowers your blood sugar, boosts your mood, and tamps down anxiety. It also builds balance. Weight-bearing exercise such as walking prevents bone thinning.

If worries about injury or falls cause people to avoid exercise, they miss out on the balance-building, muscle-and-bone-strengthening, and mood-enhancing benefits of regular activity. They may be more likely to fall — and possibly more likely to experience fractures if they do.

Find a blend of activities that will work for you

Everyone, at every weight, needs to find ways to exercise safely, confidently, and joyfully.

• Start low and go slow. If you’re not currently active, start by simply sitting less and standing more. Try walking for two minutes every half hour. If you’re afraid of falling, try walking in place or alongside a friend or loved one who can provide security and comfort.
• Ask for guidance. Consider joining a YMCA where you can engage in supervised activities, or ask your doctor for a prescription to physical therapy to help you improve your balance and build your confidence.
• Try different activities to see what works for you. Walking is a simple, healthful activity, but it’s not the only form of activity you can try. You might enjoy swimming or water aerobics. Try pedaling a seated bike or an arm bike (upper body ergometer) that allows you to stay seated while you propel pedals with your arms instead of your feet. Adaptive activities and sports designed for people with physical limitations and disabilities are an option, too. Depending on your fitness level and interests, you might also consider dancing, biking, or anything else that gets you moving more often.

Lastly, keep in mind that many people suffer from anxiety, and a fear of falling is not insurmountable. If you’re really struggling, talk to your doctor or a mental health professional.

About the Author

Elizabeth Pegg Frates, MD, FACLM, DipABLM,

Contributor

Dr. Beth Frates is a trained physiatrist and a health and wellness coach, with expertise in lifestyle medicine. She is an award-winning teacher at Harvard Medical School, where she is an assistant clinical professor. Dr. Frates … See Full Bio View all posts by Elizabeth Pegg Frates, MD, FACLM, DipABLM