Debra Borchardt
Can psychedelic drugs provide the same kind of neurological results if the hallucinogenic effects are removed? A new study published in Nature Neuroscience said the answer might be yes – a development that could expand the number of people willing to explore psychedelics as a therapy.
The study was published on June 5 and written by several authors. The authors noted that recent clinical studies suggest that psychedelics produce rapid and long-lasting antidepressant effects and have received tremendous attention.
Psychedelic trips are often described as “mystical experiences” in scientific jargon, and while many believe this is part of the journey of taking psychedelic drugs, the study authors also believe that this effect limits widespread use of the drugs. These experiences require clinical settings and intensive monitoring.
They also noted that concerns exist that psychedelics may trigger hallucinogen-persisting perception disorder (HPPD) or irreversible episodes of psychosis in susceptible populations, which has already led to the exclusion of patients with a family history of bipolar disorder or schizophrenia from psychedelic clinical trials for depression.
By exploring the binding traits of these chemicals, the researchers found they were able to separate the hallucinogenic properties: “Overall, our results suggest that the TrkB-dependent effects of psychedelics on plasticity can be detached from their hallucinogenic-like effects mediated by 5-HT2A.”
The report stated that psychedelics readily penetrate into the brain after a single dose and bind to TrkB with much higher affinities than antidepressants in current clinical use. “This may contribute to the fast and potent induction of neuroplasticity and more persistent behavioral effects produced by psychedelics when compared with other antidepressants,” said the researchers.
The researchers recently reported that diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for brain-derived neurotrophic factor. BDNF is important in the development and maintenance of the vertebrate nervous system. It promotes the survival of neuronal populations located either in the central nervous system or directly connected to it.
The study showed that LSD and psilocin directly bind to TrkB with affinities 1,000-fold higher than those for other antidepressants and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers.
The researchers wrote, “The effects of psychedelics on neurotrophic signaling, plasticity and antidepressant-like behavior in mice depend on TrkB binding and promotion of endogenous BDNF signaling but are independent of serotonin 2A receptor (5-HT2A) activation, whereas LSD-induced head twitching is dependent on 5-HT2A and independent of TrkB binding. Our data confirm TrkB as a common primary target for antidepressants and suggest that high-affinity TrkB positive allosteric modulators lacking 5-HT2A activity may retain the antidepressant potential of psychedelics without hallucinogenic effects.”
The study was performed on mice and used ketamine, psilocybin, and LSD as the tested drugs. The study was funded by the University of Helsinki including Helsinki University Central Hospital.
