24th May 2022
- Suicide is a leading cause of death worldwide, and many people at risk for suicide do not respond to existing antidepressant treatment.
- Ketamine has been shown to have a fast-acting affect, reducing suicide ideation within hours.
- Psychedelic ETFs offer an opportunity to invest in groundbreaking interventions for depression and suicide ideation while mitigating risk.
Suicide is the 10th leading cause of death in the United States—47,511 people died of suicide in the U.S. in 2019 alone1. It is also the second leading cause of death among 10- to 34 year-olds2, even more prevalent than cancer. According to the World Health Organization, more than 700,000 people worldwide die of suicide every year3. The root cause of those staggering statistics is depression—most people who attempt or commit suicide suffer from depression.
Despite significant advancements in antidepressant treatments, modern medicine has yet to find a solution for approximately 30% of patients who suffer from a condition called treatment-resistant depression, or TRD, who do not respond to standard antidepressants4. Due to the inability to impact their depression, people with TRD are at extremely high risk for suicide, even if they are receiving treatment and have an active support system.
Suicide isn’t usually a spontaneous act—weeks or even months of ideation and planning almost always precede an actual suicide attempt, creating a window for intervention. However, standard treatment protocols that combine drugs like Prozac and Zoloft with talk therapy, can take up to two months to have an effect—too long to help someone who is acutely suicidal. For many people suffering from TRD, the interventions do not work at all5. Caregivers and family members are often left helpless, lacking the tools to save a loved one from suicide, even if they are aware that he or she is at risk.
Potential treatment horizons for TRD
Given the scope and severity of the suicide problem, it is clear that new solutions are desperately needed. One drug that has shown great promise as a potential treatment for TRD is ketamine. In high doses, ketamine is an effective anesthetic. But it can also be given in lower, sub-anesthetic doses to treat a variety of psychiatric conditions, including TRD.
Ketamine is an NMDA receptor antagonist, part of a class of drugs that inhibit the action of the N-Methyl-D-aspartate receptor (NMDA). Since it is soluble in lipids and in water, sub-anesthetic doses of ketamine can be delivered in many ways including through lozenges, nasal sprays, intramuscular shots, and IV infusions.
Ketamine appears to facilitate communication across specific areas of the brain, and produce a dissociative state, a ‘high’, making it a popular recreational drug. However, it can also be extremely effective in treating some cases of TRD. Scientists are not exactly sure why ketamine impacts depression. What is known is that ketamine binds to NMDA receptors in the brain which increases the amount of a neurotransmitter called glutamate in the space between neurons. Glutamate activates a receptor called the AMPA and causes it to release molecules that help neurons communicate along new pathways. This process—called synaptogenesis—can affect thought patterns, including ones that lead to depression and suicide ideation.
Ketamine has been proven to cause a moderate to significant reduction in suicidal thoughts in patients with TRD, and has the potential to become a fast-acting, efficient treatment for people experiencing suicidal ideation. In a recent study of patients at very high suicidal risk, 63.0% of patients who received two ketamine infusions reached full remission of suicide ideation within three days6. In clinical trials, the improvement began as early as four hours after ketamine treatment and lasted on average three days, and up to a week.
The improvement in suicide ideation with ketamine may be related to more than a reduction of depression. In fact, a study at Columbia University found that cognitive improvements can also lead to a decline in suicidal ideation and protect suicidal patients, at least in the short term. In the Columbia study, a rapid improvement of suicidal thoughts following the administration of a standard dose of intravenous ketamine was correlated with an improvement in problem-solving and thinking more clearly. The improvement in neurocognition and suicidal ideation was present even in some individuals who did not demonstrate comparable improvement in depressive symptoms .7
FDA approval for ketamine treatment for TRD
The only ketamine treatment that the FDA has approved as a medication for depression to date is a nasal spray called esketamine (Spravato). Studies have shown that esketamine can lead to significant improvement in depression using the Montgomery-Åsberg Depression Rating Scale (MADRS)8. It is usually recommended for adult patients for whom antidepressant pills haven’t been helpful, or who are suicidal. According to the treatment protocol, the esketamine has to be given at a doctor’s office or in a clinic under medical supervision.
However, researchers have only begun to scratch the surface of ketamine’s potential. For example, ketamine infusions have been proven to be extremely effective, but are still not approved by the FDA9. Yet physicians can and do prescribe them off-label to patients, including those suffering from TRD, and they have shown promising results. Many leading researchers believe that various types of ketamine treatments including infusions, shots, and lozenges, as well as psychedelic drugs like psybicilin, may have the potential to revolutionize the world of psychiatry, and save thousands, or even hundreds of thousands of lives lost to suicide every year.
Investing in alternative psychiatry treatments–should you buy psychedelic stock?
Despite the enormous potential of ketamine and other emerging therapies for TRD, the pharmaceutical world is famously uncertain. Clinical drug trials take years, and only a small percentage of drugs tested in initial phases are eventually approved by the FDA or CE in Europe. Currently, there is still not enough long-term data on the effects of ketamine in its various forms and modes of delivery. Furthermore, the potential of abuse of the drug poses a significant risk and may slow its widespread approval as a treatment for people with TRD or patients at risk of suicide.
Therefore, many investors may find themselves wondering whether or not it makes sense to invest in companies that are developing ketamine treatments or other types of psychedelic drug related stocks. While there is no clear-cut answer to that question, the uncertainty alone should not necessarily deter investors, especially given the positive performance of similar fields in the past. The challenge is knowing where to invest.
Consider the world of marijuana stocks or cannabis stocks—who would have been able to guess which would have been the best growth marijuana stocks to invest in ten, or even five years ago, before medical marijuana had been legalized in most states? Psychedelic stocks, in some aspects, appear to be in a similar place today. While it is impossible to predict the best performing psychedelic stocks at such an early stage, or which ones will grow and which will not, they do offer an interesting and potentially lucrative investment opportunity. In a few years’ time it may be completely normal to buy psilocybin or buy ‘shrooms (aka magic mushrooms) to treat your depression, and investing in shroom stocks may seem as natural as investing in top cannabis stocks is today.
If you’re looking to invest in the field, but don’t want to put all of your eggs in one basket, one option to consider is a psychedelic stock ETF (Exchange Traded Fund) such as Defiance’s PSY. Instead of trying to decipher what you hope will be the best performing psychedelic stocks, trying to guess a shrooms price, or betting on the results of a specific clinical trial, a psychedelics ETF enables you to invest in several different companies that are working on groundbreaking treatments for diseases like TRD. The net asset value of an investment in PSY is linked to the value of its composite stocks, mitigating risk while still offering investors a way to connect to what may become a transformative wave in psychiatry.
For current performance and holdings, please visit defianceetfs.com/PSY
3 “Suicide”, June 17, 2021, https://www.who.int/news-room/fact-sheets/detail/suicide
4 “Pharmacological approaches to the treatment of treatment-resistant depression”, June 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518696/
5 “Major Depressive Disorder and Treatment-Resistant Depression: Targeting Suicidal Ideation”, September 2020, https://www.psychiatryadvisor.com/howtotreat/major-depressive-disorder-and-treatment-resistant-depression-targeting-suicidal-ideation/
8 “Rapid Onset of Intranasal Esketamine in Patients with Treatment Resistant Depression and Major Depression with Suicide Ideation: A Meta-Analysis”, May 31, 2021, https://www.cpn.or.kr/journal/view.html?uid=1248&vmd=Full