Antidepressants don’t work so let’s try psychedelics instead... on kids
Is the choice of drug the problem, or the failure to address the real causes of 'mental illness'?
Almost half of teens feel ‘sad and hopeless’
Multiple articles and clinical studies open with a depiction of a “mental health crisis” among the nation’s youth. The statistics certainly confirm that something is very wrong: In 2021, suicide was the third leading cause of death in adolescents between the ages of 14 and 18, with almost 2,000 deaths that year, a rate of 9 per 100,000, up from around 5 percent in 2007.
The most recent CDC Youth Risk Behavior Survey results, from 2023, found that 40 percent of high-school students experienced “persistent feelings of sadness and hopelessness.”
Overall, 39.7% of students experienced persistent feelings of sadness and hopelessness, 28.5% experienced poor mental health, 20.4% seriously considered attempting suicide, and 9.5% had attempted suicide.
According to a new study in the Journal of Child and Adolescent Psychopharmacology (JCAP) what this means in practice is that around 1 in 10 adolescents are functionally impaired due to mental health issues — mostly “major depressive episodes” but also PTSD (post-traumatic stress disorder) and GAD (generalized anxiety disorder).
The United States is in the midst of a youth mental health crisis, with psychiatric illnesses as the leading cause of death and disability in children and adolescents.
Therefore, they conclude, there is an “imminent need for novel treatments in adolescent mental health.”
This need for novel treatments is based on the simple fact that standard treatment protocols often don’t work. Almost half of teenagers using antidepressants or other psychiatric drugs to treat depression report no improvement in their symptoms. So, what is to be done? The study, which is titled, “Psychedelic Treatments in Adolescent Psychopharmacology: Considering Safety, Ethics, and Scientific Rigor,” suggests that drugs such as LSD, mushrooms, and MDMA may be the answer.
Approximately 40% of teens with major depressive disorder find their symptoms persist even after receiving first-line, evidence-based treatment. This underscores the need for not only increased access to care but also the exploration of more effective psychotherapeutic and pharmacologic treatments.
One promising emerging treatment modality is psychedelic therapy, particularly the use of psilocybin for depression, lysergic acid diethylamide (LSD) for GAD, and 3,4-methylenedioxymethamphetamine (MDMA) for PTSD.
Meanwhile, psychiatric drug use soars; psychedelic use is dropping
Experimenting on children with psychoactive substances has been controversial, to say the least, for decades. The authors of the JCAP study (from the Mayo Clinic and the University of Vermont) suggest a controversial justification for viewing such experiments without so much trepidation: kids are using drugs anyway:
... adolescents may still experiment with these substances for both recreational and therapeutic purposes as accessibility continues to increase. This raises significant concerns, as adolescents are a vulnerable population requiring heightened caution and safety measures. Therefore, we advocate for structured, safe, and well-controlled exploration of psychedelic therapies in adolescents.
In fact, the number of teens using hallucinogens and MDMA in recent years is lower than it’s been in a long time. According to the Monitoring the Future database, less than 4 percent of high-school students use hallucinogens and use of MDMA is close to zero, with use in both categories having dropped off significantly over the past few decades from a high of around 10 percent in the 1990s and early 2000s.
Even ketamine use is on a downward trend. Meanwhile, these drugs are being shamelessly promoted by a variety of private clinics as virtually a cure-all for mental illness. Why “shameless”? Because research has shown that around half of these clinics make fraudulent claims (such as describing ketamine as “FDA-approved” without clarifying that this refers to using the drug as an anesthetic) and omit any reference to adverse events, even though they are extremely common.
FDA as psychedelic cheerleader
Nonetheless, many researchers are very much in favor of advancing research on psychedelic use in the under-18 population, and they commonly cite as supporting evidence trials which supposedly show significant rates of success in using psychedelics in adults. Thus, the FDA has granted “breakthrough therapy” designation for MDMA for PTSD, LSD for GAD, and psilocybin for treatment-resistant depression and major depressive disorder. Such a designation gives companies investigating these treatments significant advantages including FDA assistance in conducting the trials as well as fast-tracking of the approval process.
The study being described here, which supports expanding research to the adolescent population, is rather economical with its description of these ongoing trials, downplaying the unresolved question of how to conduct a double-blinded placebo trial on psychedelic drugs when the drug being tested has such a marked effect on trial participants that pretty much everyone in the trial knows whether they are getting the drug or the placebo.
For example, niacin (vitamin B3) is commonly used as a placebo in LSD trials because the symptoms it elicits — flushing, slight rise in heart rate, mild dizziness — are vaguely similar to those caused by a psychedelic drug. But is it realistic to suppose that people won’t detect the difference? Many believe it is not.
Are psychedelics safe and effective? Not quite…
There are also other problems with psychedelics and MDMA such as the potential for abuse by those administering the drugs. This was precisely what the FDA discovered from accounts by participants in MDMA trials who described intimate physical contact by the therapists to which they had given no prior consent. The JCAP study downplays these concerns too, merely noting in passing that,
Despite these promising results [of efficacy], the FDA recently rejected the new drug application for MDMA, citing insufficient data on safety and efficacy.
And as for efficacy, the jury is very much out on whether psychedelics reliably ease mental illness symptoms. One analysis of around 16,000 adolescents in Sweden found that while psychedelics may be linked to lower rates of psychosis, they also appear to be linked to higher rates of mania. Furthermore, the authors of the JCAP study admit that what they call “activation” side-effects of psychedelic treatment are more commonly experienced by youths than adults:
... side effects of “activation” (symptoms such as hyperactivity, insomnia, restlessness, and irritability) have been shown to be more common in children than adolescents, and more common in both children and adolescents than in adults.
“Restlessness and irritability” are often innocuous ways of describing an adverse event common to many psychoactive drugs, both legal (such as antipsychotics) and illegal — and this is akathisia, a disorder characterized by an intense, uncontrollable feeling of inner restlessness, often accompanied by an irresistible compulsion to move, which has driven people to suicide in numerous documented cases. While there is no conclusive evidence linking psychedelic drugs and akathisia, a link is plausible given that both psychedelics and antipsychotics act on similar parts of the brain (the 5-HT2A receptor especially) and can cause serotonin and dopamine dysregulation.
With regard to suicide, arguably the most critical factor, an article in Nature notes:
MDMA/ecstasy and classic psychedelics represent two areas for exploration, as use of these substances has been associated with both increased and lowered odds of STBs [suicidal thoughts and behaviors].
Ketamine can help — or kill
Ketamine-assisted therapy is already legal for teenagers. An article in MedCentral describes why the treatment can appear so enticing:
The teen was so severely depressed that they dropped out of high school. Previous treatments – including hospitalization and residential treatment – had not been effective. When the teen’s family heard about a study in Minnesota using intravenous ketamine, an off-label and somewhat controversial treatment, they decided the associated travel to participate was worth it.
As noted above, failed treatment is very common: over 40 percent of adolescents experience this. The parents of this teen thus enrolled him in the trial. Kathryn Cullen, MD, head of the child and adolescent mental health division and associate professor of psychiatry and behavioral sciences at the University of Minnesota, Minneapolis, who led the study, described their immense relief when the treatment succeeded:
I remember the mother saying, “Why couldn’t we try this earlier? This should have been first-line.”
But Cullen was not at all reticent in admitting that this success was actually the less likely outcome. Her study was tiny (just 13 teenagers were enrolled), making the results less conclusive; furthermore, of the 13, only 5 teens improved significantly and 2 of them relapsed within a fortnight of stopping the ketamine.
Sometimes it didn’t work. There were cases when they didn’t get better. People came to the study thinking this is going to be the thing [that works]. And unfortunately, that was not always the situation.
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Furthermore, ketamine is not always as safe as people believe, even when its administration is closely monitored, as was the case in a trial conducted in France in 2022. In this study, no one in the placebo group committed suicide but one person did die by suicide in the ketamine group:
In the ketamine arm, one patient died from suicide (determined by the oversight committee to be unrelated to the intervention).
Other researchers believe that psychedelics may be just the thing needed to keep a person from committing suicide until the effect of traditional psychiatric medication “kicks in.” There is evidence that this can be the case, as Dr. Walkup, professor and chair of psychiatry at the Children’s Hospital of Chicago notes:
[If a patient admitted to a psychiatric hospital could get ketamine] on their way to the psych unit, you might do something dramatic ... that brief mood alteration can be just enough to take away someone’s acute risk [of suicide].
However, quite the opposite can also happen, as the French study showed: several participants described an onset of suicidal feelings due to use of the drug; the person who actually took his life had not previously been suicidal.
(Who is) making brains more malleable ?
The unpredictability of psychedelic treatment in general may prove even more of an issue in adolescents, many stress, due to the difference between adult and adolescent brains. While the human brain is constantly in flux, this is far more pronounced in adolescents, as the JCAP study notes:
Adolescence marks a significant neuroplastic period of brain maturation, often referred to as a “critical period,” where teens undergo significant development of higher-order cognitive abilities through structural and functional changes that facilitate the transition to a mature brain.
They therefore caution that one must consider the potential impact of meddling with these processes, especially given that cannabis is known to negatively impact brain function:
Due to this critical period in development, it is prudent to fully consider the potential impact of any substance (therapeutic or nontherapeutic) on the development of the mature brain. Emerging research on the impacts of cannabis on the developing brain has raised concerns regarding potential disruptions in synaptic plasticity, functional connectivity, and structural morphology.
But there appears to be a critical difference between the effect of cannabis and that of psychedelics. Whereas cannabis has been shown to cause “maladaptive changes to plasticity,”
Research suggests psychedelics may induce beneficial plasticity [which is both] rapid and sustaining ... Studies have suggested this could be the mechanism by which they produce a positive therapeutic effect.
That is to say, psychedelics (quite unsurprisingly) make brains more malleable, which may make it easier for psychotherapists using such drugs to help their clients resolve trauma:
Maladaptive and inflexible changes in brain circuitry (which can be induced by adverse childhood experiences) are strongly associated with a heightened risk of depression and other mental disorders ... psychedelic therapeutic agents may hold promise in restoring adolescent brains to a developmentally beneficial level of plasticity.
Drugging distress in new bright packaging
And so, this July, a new trial is to be launched at UCLA, titled, “MDMA-Assisted Psychotherapy for Treatment Resistant PTSD in Adolescents: A study on Post-Traumatic Stress Disorder, Psychotherapy, MDMA, and Stress.”
The plan is to recruit adolescents aged 16 and 17 in an open-label study (i.e., without a placebo group). The trial is set to last three months during which participants will undergo 13 psychotherapy sessions including 2 MDMA experimental sessions. Follow-up will be just 6 months post-treatment.
In an attempt to limit the risks, the trial will not be open to any teen who is deemed to be at “imminent risk for trauma and victimization,” nor will anyone with a personal or first-degree family history of a psychotic or bipolar disorder be allowed to participate.
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If psychedelics are conclusively shown to ease symptoms of mental illness, many people who would otherwise end up taking antidepressants or antipsychotics may benefit, as the adverse event profile of most psychedelics is far more limited than that of many psychiatric drugs, and withdrawal from psychedelics, while complex, may be less challenging.
However, the underlying paradigm, where “mental illness” is blamed for distress and vulnerable adolescents are treated with drugs instead of having the true causes of their symptoms addressed, will remain. As Dr. Walkup notes,
It’s crucial to differentiate between adolescents who are severely unhappy and whose lives are very bad, from those adolescents who truly have treatment-resistant depression.
Thank you for the informed update on "research" into psychiatric treatments for minors. It is discouraging that our culture and the medical community seems unwilling to look for the underlying causes of anxiety and depression in our youth. The great experiment of children entering daycare at six weeks of age rolls on without investigation.
How useful and reliable is the "CDC Youth Risk Behavior Survey" for accurate data? Its results are presented as the gold standard (no pun intended) for understanding the behaviors and well-being of young people. Self-reporting by teenagers while sitting in a high school classroom with their peers doesn't seem to be clinically rigorous.