Could ‘psychedelics’ without hallucinations be the future of antidepressants?

  • Depression is one of the most common mental health problems people face, and sometimes doctors treat the symptoms with medication.
  • One pharmaceutical route being studied by scientists is to use psychedelics such as LSD and psilocin to treat depression.
  • However, psychedelics can cause hallucinations, which can be problematic because they can contribute to psychosis or put someone in a dangerous situation.
  • In a new study from Finland, researchers have found that the mechanism behind the benefits of antidepressants is separate from the mechanism behind the hallucinations.

Although there are many antidepressant medications that doctors prescribe to treat clinical depression, not everyone responds to them.

Finding the right medication and the right dose can be difficult, and sometimes people just don’t respond well to commonly prescribed antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin reuptake inhibitors. norepinephrine (SNRI).

This problem has led researchers to look for other ways to treat depression, and one of the avenues researchers have explored is psychedelics. Some psychedelics may be able to relieve symptoms of depression, but they can also cause hallucinations.

In a study by researchers at the University of Helsinki in Finland, scientists explored a way to benefit from psychedelics without hallucinations. The study is published in Natural neuroscience.

Current research shows that psychedelics can be effective in treating depression, especially depression that is otherwise treatment resistant.

The caveat, however, is that psychedelics such as LSD and magic mushrooms can cause hallucinations, which is not ideal as it can potentially trigger psychosis and dangerous behaviors.

This prompted the researchers in the current study to look at the mechanisms that give psychedelics their antidepressant and hallucinogenic effects to see if the latter could be blocked.

According to the authors, they learned through a preliminary study that the antidepressants fluoxetine and ketamine “act by binding TrkBthe receiver of brain-derived neurotrophic factor (BDNF). »

This contributes to neuroplasticity and response to antidepressants, and National Institutes of Health note that neuroplasticity “is a process that involves adaptive structural and functional changes in the brain”.

“(BDNF) and its receptor TrkB (neurotrophic tyrosine kinase receptor, Ntrk2) are central mediators of plasticity and the therapeutic action of antidepressants,” the authors write.

To see if the mechanisms that contribute to an antidepressant effect and hallucinations are distinct, the researchers’ first step was to conduct experiments by injecting cells into dishes to determine how and where psychedelics bind.

The scientists learned not only the location of the binding site, but that the binding of psychedelics to TrkB receptors in human, rat, and mouse cells was stronger than that of other antidepressants.

Additionally, the researchers learned that a different mechanism is responsible for the antidepressant and hallucinogenic effects. The next step was to see if it was possible to block the hallucinogenic effect.

The next phase of the research project was to see how the mice reacted to LSD and if it could block hallucinations in mice.

The researchers did this by conditioning the mice to fear foot shocks – they used this approach to measure symptoms of depression. After conditioning the mice, the scientists divided the mice into control and treatment groups.

The study authors said they gave the treatment group LSD with a serotonin 2A blocker – to potentially block the hallucinogenic effects – and then tried to get the mice conditioned to not fear shocks to the feet.

The scientists learned two things from this experiment: first, that the mice on LSD were more successful than the control group in overcoming the fear response. Second, the hallucinogenic effect pathway is distinct from the antidepressant effect.

This study shows that psychedelics promote neuroplasticity and that it is possible to achieve this effect without hallucinations.

Since researchers learned that the mechanisms that help depression and induce hallucinations are distinct, they have opened up a new avenue to work on creating a psychedelic-based antidepressant without the side effects.

Additionally, since psychedelics have been shown to be far more potent than the antidepressants tested, psychedelics may one day be the future of treatment for antidepressant-resistant depression.

“Lysergic acid diethylamide (LSD) and psilocin bind directly to TrkB with 1,000 times greater affinities than other antidepressants,” the authors note.

Dr. Abid Nazeerpsychiatrist and founder of Advanced Psych Solutions based in Oak Brook, IL, not involved in the research, spoke about the study with Medical News Today.

Although Dr. Nazeer emphasized that research into the use of psychedelics as antidepressants is not new, he believes the study sets the stage for further research.

“I think this is a very landmark study in terms of how it’s going to open up a lot more research that will be done with this study as a base,” Dr. Nazeer commented. “And more studies will now start to dig deeper into this concept of getting antidepressant responses without altering someone’s state of mind.”

Dr. Nazeer also pointed out that the scientists tested on mice, so we should take the results with a grain of salt.

“I would say a weakness is that it’s an animal model. When you study it in mice, it doesn’t necessarily mean that the human brain will have the same reaction,” Dr. Nazeer noted.

Dr. Daniel F. Kellya board-certified neurosurgeon and founder and director of the Pacific Neuroscience Institute in Santa Monica, California, not involved in the study, also spoke with DTM on its takeaway meals.

“This excellent study by Moliner and colleagues challenges the long-held assumption of many that the therapeutic effects of classic psychedelics like LSD and psilocybin depend on the individual having the psychedelic or hallucinogenic experience,” said the Dr Kelly.

Dr Kelly cited the “careful design and controls” as strengths of the study and looks forward to what the future holds for the use of psychedelics in the treatment of depression.

“We are just beginning to unravel the complex mechanisms and pathways underlying the psychotherapeutic effects of psychedelic drugs. It also raises the possibility that new psychedelic compounds are being developed without hallucinogenic effects that provide safe and long-lasting antidepressant effects or other positive psychological benefits.

– Dr. Daniel F. Kelly

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