New research provides evidence that LSD alters the effects of brain stimulation and produces different and potentially larger changes in brain activity. The preliminary findings suggest that psychedelic drugs and brain stimulation may have a synergistic effect that could be used in innovative ways for treating various conditions. The proof-of-concept study has been published in the journal Psychedelic Medicine.
Psychedelic-assisted psychotherapy has shown promising potential as a therapeutic approach for various mental health conditions. This treatment combines the use of psychedelic substances, such as psilocybin or LSD, with psychotherapy sessions to enhance the therapeutic process.
The psychedelic substances used in this type of therapy are known to induce altered states of consciousness, leading to profound experiences that can have therapeutic benefits. These substances are thought to work by affecting brain receptors, particularly the serotonin 2A receptor, which influences perception, mood, and cognition.
These drugs have also been found to enhance neural plasticity, which refers to the brain’s ability to reorganize and form new connections. This may contribute to their long-term therapeutic effects. It is believed that combining psychedelic drugs with therapies like psychotherapy or brain stimulation could help direct these neuroplastic changes and lead to lasting behavioral changes.
“Current treatments like transcranial magnetic stimulation (TMS) have a large potential to help people with a variety of psychiatry disorders, however, these neuromodulatory treatments tend to have relatively short-lived effects,” explained study author Lucas Dwiel, a postdoctoral fellow at The Doucette Lab at the Geisel School of Medicine at Dartmouth. “So if we could prolong the effects of these treatments by first using drugs like LSD to make the brain more malleable or susceptible to change, we could help a large number of patients achieve their therapeutic goals.”
The researchers conducted experiments using rats to eliminate the biases inherent in human studies. The study focused on the effects of LSD and involved two main components: measuring brain activity changes after LSD administration and assessing the effects of brain stimulation combined with LSD.
To measure brain activity, the researchers implanted custom electrode arrays in specific brain regions of the rats. They recorded local field potentials (LFPs) and analyzed features such as power and coherence in different frequency ranges. This allowed them to describe the brain states of the rats and examine the effects of LSD and brain stimulation.
In the first part of the study, the researchers administered LSD or an inert saline solution to the rats and recorded their brain activity before and after the drug administration. In the second part, the researchers focused on brain stimulation. They delivered electrical stimulation to the rat infralimbic cortex (IL), either after administering LSD or saline 24 hours earlier.
The researchers found that a single dose of LSD induced changes in brain activity that returned to normal after 24 hours. However, applying brain stimulation after this 24-hour window produced distinct shifts in brain state compared to brain stimulation applied after saline treatment. This suggests that the LSD-induced neuroplastic changes created a different brain state that responded differently to external interventions.
“This study is the first step in developing psychedelic-assisted neuromodulation; we were able to show that pretreatment with LSD 24 hours before brain stimulation allowed for larger and different changes in brain activity than brain stimulation alone,” Dwiel told PsyPost.
“Interestingly, there was no difference in brain activity before brain stimulation between the two groups (those given LSD or saline 24 hours previously), suggesting that LSD is leading to latent changes in the brain that can then be revealed with brain stimulation.”
The study provides new insights into the potential interaction between psychedelic drugs, brain stimulation, and enhanced neural plasticity. But Dwiel noted that “like almost all studies, our work has limitations.”
“We have not yet shown that pairing LSD pretreatment with brain stimulation leads to longer lasting changes in brain activity or, perhaps more importantly, behavior,” the researcher explained.
“There are many avenues for future studies we are interested in pursuing, for example, what is the dose-dependency of this effect (i.e., can the same effect be seen with smaller doses), do other psychedelic drugs promote the same effects, what is the optimal timing between giving the drug and the brain stimulation, and are these effects mediated by the enhanced metaplasticity induced by psychedelics?”
Psychedelic-assisted psychotherapy is still an area of ongoing research and is not yet widely available or regulated. However, the promising results from early studies have sparked renewed interest and support for further exploration of this therapeutic approach.
“This is an exciting time for studying the neuroscience of psychedelics and I am hopeful for the potential for these medicines in helping people either on their own or as adjuvants in treatments like psychedelic-assisted neuromodulation and psychedelic-assisted psychotherapy,” Dwiel said.
The study, “Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents“, was authored by Lucas Dwiel, Angela Henricks, Elise Bragg, Jeff Nicol, Jiang Gui, and Wilder Doucette.
