By Tom Insel, MD, and Matthew Hirschtritt, MD, MPH

In today’s edition, we bring you research about marijuana, psychedelics and Amsterdam – and those are each different studies. With marijuana now legal for recreational use in more than a third of American states, what’s the impact on traffic safety? Research from British Columbia and San Diego explore the risks. It’s become a truism during this pandemic that if you’re not anxious or depressed you’re not paying attention. But for people with serious mental illness who depend on treatment, the disruption to their care caused by the pandemic has been a cause of major concern. A new study quantifies the extent of that disruption. What happens to teenagers getting mental health treatment when co-pays increase for their families? A study from the Netherlands explores that issue. And finally, who wants psilocybin without hallucinations? Perhaps a lot of people, if it eases symptoms of depression – and now laboratory research suggests that may be on its way.

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Driving Under the Influence

Recreational cannabis is now legal in 17 states, Washington, DC, and Canada. The widespread use of cannabis and the development of more potent forms of the drug have introduced questions about the risks for mental health. Now two new reports have raised questions about the risk cannabis poses for traffic safety.

Jeffrey R. Brubacher and colleagues report on THC levels from moderately injured drivers who were treated in trauma centers in British Columbia before and after marijuana was legalized there in October 2018. The team found that during the 17 months after legalization, the percentage of injured drivers with high THC levels doubled compared with the years before.  The increase in THC use among injured drivers was especially higher in males over age 50. Across these same years, they found no increase in the number of trauma center patients with high blood alcohol levels. While more injured drivers tested positive for cannabis after it became legal, this study did not demonstrate a change in the number of accidents or a causal role for cannabis.

But a causal role for cannabis in potentially causing auto crashes does come from a new study by Thomas D. Marcotte and colleagues from University of California San Diego. They tested regular cannabis users in a driving simulator to measure the drug’s effect on performance and found that THC impaired driving performance for up to 3.5 hours after smoking. Here’s the big worry: While participants reported that they were OK to drive about 1.5 hours after smoking –their performance continued to be impaired for another 2 hours. This gap between a person’s ability to perform and their assessment of their own ability creates concern for traffic safety.

The legalization of cannabis has led to increased use and there is a growing public sense that this drug is safe. But as these new papers remind us, there are significant risks to be managed.

Cannabis Legalization and Detection of Tetrahydrocannabinol in Injured Drivers NEJM Jan 13, 2022

Driving Performance and Cannabis Users’ Perception of Safety: A Randomized Clinical Trial JAMA Psychiatry, Jan 26, 2022

–Tom Insel

Care for People with Serious Mental Illness Was Interrupted by the Pandemic

While the COVID-19 pandemic has negatively impacted just about everyone, people with serious mental illness – like schizophrenia, bipolar disorder, and major depression – have fared especially poorly. It’s no surprise that people with serious mental illness were more likely than others to experience severe anxiety, concentration difficulties and concerns about paying for medical care and accessing food during the first year of the pandemic. Now a study using Medicare claims data shows that the use of mental health treatment decreased significantly during the early phase of the pandemic among people with serious mental illness.

Alisa Busch of McLean Hospital and Harvard Medical School and colleagues examined claims data among two groups of adults with diagnoses of schizophrenia or bipolar disorder who were receiving Medicare. One group got treatment between January and September 2019, the other during the same months in 2020. There were about 700,000 patients in each group.

Among those treated in 2020, the use of services dropped steeply in the early months of the pandemic before later leveling off somewhat as time went by. How steep were the drop-offs? In the first four weeks of the pandemic lockdown, starting in mid-March of 2020, compared with the same period the previous year:

•use of outpatient mental health services fell 20%

•visits to the emergency room dropped 28%

•use of inpatient hospital services fell 28%

•the filling of prescriptions for antipsychotics or mood stabilizers dropped 20%.

Through September 2020, the decline in use of outpatient services was especially high among people who received disability income, Black patients (compared with whites), and those who also received Medicaid benefits.

By August 2020, the use of services rebounded but remained lower than in August the year before. The use of telemedicine – both phone and video – skyrocketed from just 2% of visits in January 2020 to 65% of visits by late March 2020. Six months later, in September, more than half of all outpatient mental health visits were still being conducted via telehealth.

People with serious mental illness are already badly underserved and face many obstacles to getting the treatment they need. The pandemic has further disrupted their ability to get care, especially for patients of color and those who are disabled or have the lowest incomes, highlighting the need to make mental health services more equitable and accessible. The one silver lining here: The major increase in the use of telemedicine use may provide an enduring way to improve access, but it will also take work on other fronts.

Disruptions in Care for Medicare Beneficiaries with Severe Mental Illness During the COVID-19 Pandemic  JAMA Network Open, January 28, 2022

– Matthew Hirschtritt

When Out-of-Pocket Costs Rise, Dutch Teens Get Less Mental Health Care

Medical care comes with a steep price tag, and who pays the bill is a source of perennial debate. In the U.S., patients are often subject to cost-sharing, which can take the form of high deductibles and co-pays. Even small increases in cost-sharing can deter people – especially those with lower incomes – to avoid needed medical care. Unlike the U.S., the Netherlands blends private and public financing to ensure universal coverage for all residents. But like their American counterparts, Dutch residents may also have to pick up some costs, depending on their insurance plan.

Francisca Vargas Lopes of Erasmus University in Rotterdam and colleagues measured the effects of increased deductibles on mental health care among adolescents living in the Netherlands. Using administrative data for over 1.5 million youth between 17 and 19, the research team studied the effects of a 180 euro (about $200 USD) increase in deductibles between 2009 and 2014. They found that this increase in costs was associated with a 13.6% decrease in mental health service use among females and a 5.3% decrease among males. Further, the drop in usage of mental health care was even starker among lower-income females, a group that saw a 20% decline.

The transition to adulthood is a particularly sensitive period as adolescents become more independent and face new pressures. This study suggests that even modest increases in costs can make people – or parents – less willing or able to contribute to costs of mental health services for transition-age youth. It also raises other questions: Are parents less willing to pay for needed help for their daughters? And as these teens age into adulthood, will they be less protected from future mental health problems?

Patient cost-sharing, mental health care and inequalities: A population-based natural experiment at the transition to adulthood  Social Science & Medicine, January 29, 2022.

Matthew Hirschtritt

Psychedelics Without Hallucinations as Antidepressants

Psychedelics are enjoying a renaissance as potential medications for mental illness. Science magazine even honored the psychiatric use of psychedelics as one of the breakthroughs of 2021 – along with Covid treatments and the landing on Mars. One of the most active areas of research is the use of psilocybin for depression, which a paper last year in the New England Journal of Medicine described as equivalent to the commonly prescribed antidepressant escitalopram (brand name: Lexapro). Most scientists believe the hallucinogenic experience is vital for the antidepressant effect, but a new report suggests that non-hallucinogenic psychedelics with antidepressant properties should be possible to develop.

To understand this finding, you need to appreciate how far pharmacological science has progressed with new molecular tools. The basic science is simple: When drugs bind to receptors on the surface of cells, receptors activate second messengers that alter cell function. Scientists can now map precisely where a drug is binding to a receptor. Then, using crystals of the receptor complex, they can see how the structure of the receptor changes when the drug is attached and design new drugs that push or pull specific binding sites to influence how the receptor activates those second messengers.

That’s how a team led by Dongmei Cao and Jing Yu from the Shanghai Institute of Biochemistry and Cell Biology approached the study of psychedelics. They knew that psychedelics bind to a specific serotonin receptor (5HT2a) in the human brain and that this binding was crucial for the hallucinogenic experience. What they discovered is that psychedelics bind to two different pockets within the 5HT2a receptor. These pockets activate different second messengers – one that works in a pathway that triggers hallucinations, and another that influences a pathway that may trigger an antidepressant effect.

If this were true, it should be possible to develop drugs that are antidepressant but not hallucinogenic. The Cao and Yu group designed psychedelic analogs specifically to test this idea. Given to mice, these non-hallucinogenic psychedelics induced behaviors typically found with classic antidepressants, with no hint of the head twitches that mice display after being given hallucinogens.

It would be ironic indeed if research on psychedelics delivers a set of drugs that are non-hallucinogenic. Rather than the psychedelic renaissance bringing back the Summer of Love, we might simply have new antidepressants that will be easier to administer than psilocybin. Some may prefer the hallucinations, but a new family of safe, effective antidepressants would be welcome as well.

Structure-based discovery of nonhallucinogenic psychedelic analogs  Science, Jan 28, 2022

–Tom Insel

Tom Insel, MD, is a psychiatrist, neuroscientist, and former director of the National Institute of Mental Health (NIMH). He is a donor to MindSite News and chair of its Editorial Advisory Board. Dr. Insel’s financial conflict of interest statement, which includes equity and advisory roles in several early-stage mental health technology companies, can be found here.

Matthew Hirschtritt, MD, MPH, is a clinical psychiatrist with the Permanente Medical Group, Inc., a mental health services researcher with the Division of Research, Kaiser Permanente Northern California, and assistant program director of the Kaiser Permanente Oakland Adult Psychiatry Training Program. His current research focuses on identification and treatment of patients with first-episode psychosis, as well as implementation of a telehealth-based mental health evaluation and referral program.

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