An article with the above title appeared in the Friday, December 6, 2019 Wall Street Journal. The article is written by the Jewish psychoanalyst Erica Komisar of New York City. She draws her conclusions from her reading of the scientific literature, her experience treating anxious and depressed children, and her Jewish faith and community. Her advice transcends any particular faith. I recommend her article to you.
Ms. Komisar cites a 2018 study in the American Journal of Epidemiology that looked at how being raised in a household with religious or spiritual beliefs affects mental health compared to an equal size non- religious control group. The children that attended a religious service one a week or more scored more highly on tests of mental wellbeing and a lower risk of mental illness. These children also had a lower probability of drug use and early sexual behavior. The children also had a higher rate of volunteering, a greater sense of mission, and a greater ability to forgive. From a purely secular point of view, these attributes alone might be worth “faking it to you make it”.
Ms. Komisar then goes on to address what she sees at the root of much of the increased anxiety and depression in today’s children, existential nihilism. When there is no meaning to a life beyond the here and now day to day survival, no ultimate meaning and purpose beyond our existence, then a person is ripe for not only depression and anxiety but also despair. This has been addressed by numerous authors including, most notably, Dr. Fiktor Frankl. Therefore, I ask almost all my patients, “what is your reason for getting out of bed each morning, what is your meaning and purpose in life, what is the hope that keeps you going?”
Having this transcendent anchor point external to ourselves, but with personal meaning to the induvial believer as well as the community of believers, allows us to answer the big questions common to all children and to provide solace in their time of anxious questioning. This hopeful belief system allows us to talk frankly to our children about death. I will quote directly from Ms. Komisar’s article: “The idea that you simply die and turn to dust may work for some adults, but it doesn’t help children. Belief in heaven helps them grapple with this tremendous and incomprehensible loss. In an age of broken families, distracted parents, school violence and nightmarish global-warming predictions, imagination plays a big part in children’s ability to cope.”
Ms. Komisar states she is often asked by parents how they can instill gratitude and empathy in their children. These are virtues found in all religious traditions, even those without a deity or belief in an afterlife such as Zen Buddhism. Ms. Komisar states in her article: “It’s rare to find a faith that doesn’t encourage gratitude as an antidote to entitlement or empathy for anyone who needs nurturing. These are the building blocks of strong character. They are also protective against depression and anxiety.”
Finally, Ms. Komisar points out that religion provides a natural community. Ms. Komisar expresses this beautifully in the following passage: “The idea that hundreds of people can gather together and sing joyful prayers as a collective is a buffer against the emptiness of modern culture. It’s more necessary than ever in a world where teens can have hundreds of virtual friends and few real ones, where parents are often too distracted physically or emotionally to soothe their children’s distress.”
I will leave you with the final paragraph of Ms. Komisar’s article: “Today the U.S. is a competitive, scary and stressful place that idealizes perfectionism, materialism, selfishness and virtual rather than real human connection. Religion is the best bulwark against that kind of society. Spiritual belief and practice reinforce collective kindness, empathy, gratitude and real
connection. Whether children choose to continue to practice as adults is something parents cannot control. But that spiritual or religious center will benefit them their entire lives.”
Currently available antidepressants, at least in their initial action, exert their antidepressant effect by influencing monoamine levels in the brain. Despite increasing the monoamine levels within the first day, the clinical manifestation of the antidepressant effect may be delayed by days to weeks. Approximately one third of major depressed patients will have a 50% or more reduction in symptoms with the first agent prescribed. Although the total number of patients responding increases with subsequent medication trials, the proportionate response to each new drug is much less than to the original drug. This series of trials may take months to years. This scenario has led to the search for a medication that rapidly reduces depressive symptoms. Esketamine seems to fulfill those criteria.
The brain’s response to any medication is much more complex than increasing as certain neurotransmitter. Esketamine does not raise monoamine neurotransmitters. Instead, esketamine binds to the post-synaptic NMDA glutamate receptor blocking glutamate neurotransmission. There are a few other biochemical happenings at the receptor level that are necessary for this to effectively occur, but that is a bit in the weeds for this article. Another result of this binding is the activation of the mTOR pathway. This is a pathway that eventually leads to increased BDNF and increased synapse formation. Pay no attention to the acronyms, just know it’s a good thing to happen. Wikipedia can give you a fuller explanation. This is amazing in two ways. First, that protein formation (needed for the building of synapses) can be elicited and seen occurring within 2 hours of administration is remarkable. This occurs with typical antidepressants but may take weeks. Second, the BDNF increase and the onset of new synapse formation correlates with a decrease in depressive symptoms and suicidal ideations. A medication that can be administered intranasally in a psychiatrist’s office and reduce suicidal ideations and decrease depression within 2 hours is a large leap forward in psychiatric treatment.
Serendipity and Urine Drug Screens
A not unusual occurrence in medicine is that while looking for one thing we find another. This happens all the time at the drug discovery level with many of our drugs being developed for one disease while looking for a cure for another disease. A classic example is the development of the tricyclic antidepressants. All the antidepressants can trace their lineage in one way or another back to isoniazid. Isoniazid was being developed as a treatment for tuberculosis. When this drug was given to severely depressed patients at state hospitals, many of the patients had a remission of their depression. As is often said, the rest is history.
With the urine drug screens we have seen another bit of medical serendipity, although not nearly to the level of importance as the above example. About one year ago the state board of medical licensure mandated point of service urine drug testing when a physician writes a prescription for benzodiazepines (Xanax, Ativan, Valium, Klonopin, etc.), opiates (oxycodone, Norco, Hydrocodone, etc.), or stimulants (Adderall, Ritalin, etc.). The reasoning that led to this decision seems to be that people that are prescribed one addictive substance such as an opiate are often prescribed another addictive substance by the same or different physician (the VA study). These patients have an increased risk of fatal drug interactions leading to respiratory depression and death. In addition, patients who are addicted to heroin or other opiates obtained either legally or illegally are often using other drugs, particularly benzodiazepines, that increases the risk of a fatal overdose.
At the time of the promulgation of these regulations, I argued strongly to the medical board that the routine urine drug testing of patients prescribed benzodiazepines was unlikely to discover patients using opiates not already noted in the PMP (a computerized data base of all controlled substances prescribed to a patient nationwide). The physician is mandated to check the PMP each time a controlled substance is prescribed. Now, about one year into this experiment some clear patterns have emerged. The first is that my reasoning regarding opiates and benzodiazepines has been confirmed. However, a totally unexpected pattern and area of concern has been manifest.
Since the institution of the above regulations, the federal government has passed the Farm Bill. In this bill was the legalization of the production of industrial hemp. In addition, proliferation of states with legalized “medical” marijuana has exploded, making marijuana products, even in states without such laws, more readily available. What we have discovered at my clinic over the past year is that the number of urine drug screens positive for opiates who had a negative PMP has been very low. However, patients positive for THC, the psychoactive component of marijuana, has been large. In addition, over the past two or three months, we have seen a dramatic rise in the number of THC positive urines who claim to have only used CBD products. Why is this clinically relevant? Please read the next blog post.
CBD and the Medical Patient
Medical marijuana and recreational marijuana are derived from Cannabis Indica or Cannabis Sativa. The important ingredient is the resin produced by the flower. CBD products are derived from the flower of a Cannabis Sativa strain with a different genetic profile than the marijuana Cannabis Sativa. In the following paragraphs I will illustrate why I am concerned about the rise in CBD and THC usage, especially in patients with a psychiatric condition.
First, a major caveat: No one under the age of 25 or a patient with schizophrenia and possibly bipolar disorder should use compounds that contain THC.
There are two CB (cannabinoid) receptors in human tissues. These are found throughout the body including the brain (CNS or central nervous system). These receptors are CB1 and CB2. In the brain CB receptors are instrumental in neuronal maturation and especially in the expansion and pruning process that occurs starting at about age twelve years and culminating at around age 25 years. Use of marijuana in this age group has been associated with an early onset of schizophrenia. Despite the speculation that CBD may be beneficial in schizophrenia and other conditions, there are virtually no medical studies (especially, double blind, placebo-controlled studies, the gold standard) of any cannabis product on any medical condition.
Cannabis products contain approximately 108 cannabinoids and 420 other compounds. CBD preparations are notable for their relative lack of THC (the content is supposed to be about 0.5%). However, this is not a guarantee of any type of purity. Commercially available CBD is still a mixture of a vast number of CBDs and other compounds. Although marketed as CBD or cannabidiol the preparation is far from pure cannabidiol. The reason that this is possible is because the FDA does not regulate the content, purity, safety, or investigate any clinical claim of CBD effectiveness. CBD does not even have to pass the over the counter drug review at the FDA. The over the counter drug review is much less stringent than the review of a prescription medication.
From a purely pharmacologic standpoint and for the sake of our conversation at the level of the brain, the major difference
Andrew Bishop, MD FAPA