Psychedelics' Plastic Potential

 

In recent years, the image surrounding psychedelic drugs has morphed into a somewhat positive one. Conversations surrounding drugs in general have seemed to become more complex, medicine and the general public considering each drug’s unique affects on the human nervous system and chemical properties—properties that might lend to possible therapeutic applications. Psychedelics are a class of drug that seem to be highlighted in this conversation, their potential healing ability implicated particularly in psychiatric disorders like Generalized Anxiety Disorder, Bipolar Disorder, and even schizophrenia.

            Grieco et al (2022) explores the potential therapeutic implications of psychedelics, hinting at their facility to drive neural plasticity in some areas of the brain. They discuss certain unmet clinical needs and the current state of translation to the clinic for psychedelics. Psilocybin, LSD, and ketamine function as “psychoplastogens”—compounds that induce long-lasting neural plasticity after just one or a few doses. This mirrors the circuit-level changes described in the Puranik study, where manipulating glutamatergic inputs from the laterodorsal tegmental nucleus (LDTg) to the ventral tegmental area (VTA) blocked cocaine-induced behavioral and dopamine responses. Both studies underscore the significance of glutamatergic signaling in reshaping neural pathways linked to reward and addiction. These compounds primarily act through serotonin 2A receptors (5-HT2ARs) and influence downstream pathways such as BDNF (brain-derived neurotrophic factor) signaling and glutamate release, both of which are critical for synaptic remodeling.

Psychedelics can also increase dendritic spine density, and enhance synaptic strength, especially in brain regions like the prefrontal cortex. The question of whether these changes underlie improvements in mood, personality traits (like openness), and behavior following psychedelic therapy is considered in this study.

In Puranik et al (2022) a maladaptive plasticity is seen in cocaine sensitization, as described, where repeated drug exposure leads to hyperactivity in circuits like the LDTg-VTA pathway. Since sensitization involves lasting changes in these circuits, psychedelics may help reverse or rewire these maladaptive changes by reintroducing a more adaptive form of neuroplasticity, potentially offering a method to desensitize overactive reward pathways and mitigate addiction-related behaviors.

It is interesting to note the ways the current culture’s attitude towards psychedelics has altered, still, it is important to consult the vast literature on systems neuroscience to evaluate the true value of this possible healing ability.

References:

Grieco, S. F., Castrén, E., Knudsen, G. M., Kwan, A. C., Olson, D. E., Zuo, Y., Holmes, T. C., & Xu, X. (2022). Psychedelics and Neural Plasticity: Therapeutic Implications. The Journal of Neuroscience, 42(45), 8439–8449. https://doi.org/10.1523/jneurosci.1121-22.2022

Puranik, A., Buie, N., Arizanovska, D., Vezina, P., & Steidl, S. (2022). Glutamate inputs from the laterodorsal tegmental nucleus to the ventral tegmental area are essential for the induction of cocaine sensitization in male mice. Psychopharmacology, 239(10), 3263–3276. https://doi.org/10.1007/s00213-022-06209-2