One of my chronically depressed patients recently discovered a psychotropic medication that works for him after decades of searching. He took psilocybin from his friend and miraculously he felt his mood improved. “It was like taking off dark sunglasses,” he told me in a therapy session. “Everything suddenly seemed brighter.” He said the trip gave him new insight into his difficult relationships with his grown children, and even made him feel connected to strangers.
I have no doubt that the patient will improve. His anxiety, world-weariness, and self-doubt seemed to disappear within hours of taking psilocybin, and the effects lasted for at least three months for him. However, I am not convinced that his brief ocean experience was the source of the magic. In fact, some neuroscientists now believe that this transcendent reality-warping trip is just a side effect of psychedelics, and is not sufficient or necessary to produce the mental health benefits that psychedelic drugs are thought to provide. I believe there is no.
Researchers have known for several years that the hallucinogenic effects of psychedelics are theoretically distinguishable from other effects that drugs have on our mental state and brain structure. However, until recently, it has not been possible to design psychedelic drugs that reliably produce only neurocognitive effects and not hallucinogenic effects. That may change soon. A new generation of non-hallucinogenic psychedelics, at least one currently being tested in humans, aims to provide all the mental health benefits of LSD, psilocybin, or ecstasy without the travel. Trip-free psychedelics would be a huge therapeutic boon, and the number of people able to experience the benefits of these drugs would increase dramatically. It may also shed new light on how well psychedelics can reduce mental suffering and why they do so in the first place.
Research over the past five years has demonstrated that psilocybin has powerful antidepressant effects and that MDMA (also known as ecstasy) can reduce symptoms of PTSD when used in conjunction with psychotherapy.Surprisingly, just a bit either dose psilocybin Alternatively, MDMA provides rapid and lasting improvement in symptoms of depression and anxiety. This means that your symptoms will be reduced within minutes or hours and can last up to 12 weeks. (MDMA is what psychiatrists call an “atypical psychedelic,” a combination of psychedelic-like and amphetamine-like effects that produces a sensation of bliss rather than a transcendental or mystical state.) widely expected Approving MDMA for supervised use in 2024 would be an unusual turning point for a drug that has long been criticized for its potential to cause serious (albeit rare) harm.
From a clinical perspective, this psychedelic revolution is potentially miraculous.Estimation 23 percent of Americans suffer from a mental illness, and a significant number, like my patient, do not receive adequate relief from treatment or existing medications. Medications like psilocybin, ayahuasca, and LSD may help many of these patients, but some cannot tolerate travel. (“Trip” refers to a variety of altered mental states caused by psychedelic drugs, such as the transcendence and mystical experiences of LSD and psilocybin, and the blissful and social freedom of MDMA.) Drug-induced hallucinations is known to cause symptoms such as: Certain people, such as those with psychotic disorders or severe personality disorders, can experience extreme anxiety or even have psychotic breaks. That’s why clinical trials of psychedelic drugs usually exclude these patients.
I do not mean to downplay the joy and power of transcendental visions. Many people who have tried psychedelics say the experience was one of the most rewarding of their lives.and some the study When administering psilocybin for depression, the intensity of the trip correlates with the magnitude of the therapeutic effect. Travel is a special and consciousness-expanding experience that provides travelers with new insights into their lives and emotions. That feels pretty good too. But that’s not the only effect drugs have on the human brain.
While traveling, psychedelics are quietly doing something even more remarkable than warping reality. Psychedelics are rapidly inducing a state of neuroplasticity that allows the brain to more easily reorganize its structure and function. (Microdosing enthusiasts who take subtherapeutic doses of drugs such as psilocybin claim that they experience increased creativity. They may be affected by neuroplasticity without traveling, but their There is still little scientific evidence to support the idea.) The ability to react and adapt to our environment, and it may be possible center About the therapeutic effects of psychedelics.in depressionFor example, the prefrontal cortex (the brain’s best reasoner) loses some executive control over the limbic system (the brain’s emotional center). Drugs that increase neuroplasticity allow the formation of new connections between regions, reset Repair relationships and restore your prefrontal cortex to emotional control.
Like MDMA, ketamine (an animal tranquilizer, surgical anesthetic, and dissociative party drug, also approved as a fast-acting antidepressant in 2019) does not typically cause hallucinations. However, it is known to induce a dissociative mental state and cause neurons to sprout new spines within hours of administration, a structural change associated with a reduction in depression-related behaviors in animals. In humans, ketamine has been shown to increase mood, even when administered while the patient is unconscious. Several the study Patients given ketamine during surgery have been shown to be more awake than before the surgery. This suggests that it is not necessary to consciously experience the dissociative effects of antidepressants to have an effect.
Scientists are definitely trying to figure it out.first time, Researchers have intentionally developed a psychedelic drug that appears to have neuroplastic effects without causing trips. These drugs stimulate the same serotonin receptor, 5-HT2A, as traditional hallucinogens. When this is triggered, it causes the brain to produce more of a compound called BDNF, a type of brain fertilizer that promotes neuron growth and connections. However, the non-hallucinogenic version activates 5-HT2A without leading to trips. (Receptor binding and activation is not an all-or-nothing phenomenon; different drugs can bind to the same receptor in different ways and produce very different effects.)
Some of these trip-free psychedelics are new inventions.For example, last year, scientists synthesized A new non-hallucinogenic psychedelic that mimics lisuride, an analogue of LSD. (An analogue is a chemical that is structurally very similar to the original compound, but has been modified to have a different function.) It doesn’t have a name yet (only serial number IHCH-7113) is being researched. animal.
Other trip-free psychedelics have been around for decades, even if they are not recognized as such. 2-Br-LSDanother non-hallucinogenic analog of LSD was first used. synthesized It was developed by the same chemist who developed LSD in 1957. (It was intended to treat migraines.) Recent experiments have shown that 2-Br-LSD, like LSD, reduces depressive behavior in mice. But unlike LSD, it doesn’t cause mice’s heads to twitch, a sign that the substance causes hallucinations or other psychotic symptoms in humans. More than 60 years after his invention of 2-Br-LSD, Canadian company BetterLife Pharma plans to: study Used as a treatment for major depression and anxiety.
LSD is not the only counterfeit drug that provides psychedelic stimulation. Derix Therapeutics, a Boston-based biotechnology company, is using animal models to study tabernantalog, an analog of the active psychedelic substance found in ibogaine. Tavernantalog has acute antidepressant and neurogenic effects in animal models and does not cause head twitches like 2-Br-LSD. Derix is also testing a drug called DLX-1. david olsonOne of Derix’s co-founders told me that it was the first non-psychedelic psychedelic to be tested on humans. He said the Phase 1 study is nearly complete. Olson, who is also director of the Psychedelic and Neurotherapeutic Research Institute at the University of California, Davis, calls the drugs he studies “psychoplastogens” because of their ability to rapidly induce neuroplasticity. He said other non-hallucinogenic psychoplastogens the company is working on are “closer to clinical trials,” but it’s unclear how quickly they will be brought to market.
So far, the federal government has provided little funding for nonpsychedelic psychedelic research. Derix and other manufacturers of these new psychedelic drugs must submit applications to the FDA to have their drugs approved, and their new drugs typically outperform placebo controls in two randomized clinical trials. Desired. While this may be a time-consuming process, the FDA can speed it up by designating the drug as a “breakthrough therapy,” which is exactly what it did with psilocybin in 2018. It is.
In clinical trials, non-trip psychedelics have at least one major advantage over similar drugs that induce trips. That means it’s easier to do a placebo trial. Research on classical psychedelics has been plagued by the simple fact that it is virtually impossible not to know that you are taking a classical psychedelic. In fact, in clinical trials of MDMA and psilocybin, over 90% of treated subjects correctly guessed that the drug they were given was real. Participants given the real drug would expect to feel better, which defeats the purpose of placebo testing these types of psychedelics altogether. However, new non-trip psychedelics do not induce the transcendental state of mind that tends to “unblind” those studied. More typical drug side effects may occur, such as dry mouth and sedation, but they are far from a mystical experience.
Non-trip psychedelics may also be easier to regulate. If they don’t get you high or create a transcendental state, they have little appeal as recreational drugs. The Drug Enforcement Administration classifies LSD and psilocybin as Schedule I drugs, making them difficult for researchers to study and doctors to prescribe. Even ketamine is Schedule III and must be administered in a medical setting, which can be inconvenient for patients. Perhaps the DEA will be more kind to psychedelic drugs that don’t trip. This would make it easier to access for both patients and researchers. Additionally, non-hallucinogenic psychedelics do not require the time and expense of a guide to monitor the experience. That said, non-trip psychedelics may end up becoming a more popular and better-researched option than traditional psychedelics.
If the FDA does indeed approve MDMA next year, psychiatrists will have plenty of reason to celebrate. However, I suspect that the future of psychedelic medicine will lean away from transcendence and towards the wonder of the possibilities of pure neuroplasticity. Psychedelic travel will probably never disappear from society. First, they are considered essential to some religious and cultural rituals. But perhaps they will be seen less as therapy and more as good old-fashioned fun.