by Eugene Rubin MD, PhD, and Charles Zorumski, MD

In an article published recently in the journal Cell Reports, David Olson, Calvin Ly, and colleagues investigate the biologic actions of a class of drugs that they have named psychoplastogens. The authors provide the following description of drugs that fall into this new class: “To classify the growing number of compounds capable of rapidly promoting induced plasticity, we introduce the term ‘psychoplastogen’ from the Greek roots psych- (mind), -plast (molded), and -gen (producing).” These drugs cause nerve cells in the brain to form new neurites, i.e., projections that extend out from the cell body and have the potential to become axons and dendrites. In addition, these agents enhance the ability of nerve cells to interact with other nerve cells by increasing the number of synapses — the regions where nerve cells connect with one another.

appears to be an example of one such drug. Ketamine has been shown to have rapid and anti- properties. Ketamine-like drugs are likely to be approved by the Food and Drug Administration (FDA) for the treatment of in the future. Ketamine works by influencing brain receptor systems that respond to the neurotransmitter glutamate. The glutamatergic system then stimulates a variety of chemical pathways in nerve cells that control cell growth and cell connections.

Ly, Olson, and colleagues elegantly demonstrate that another group of drugs are as powerful, or even more powerful, than ketamine in causing cellular changes in brain cells. Whereas ketamine exerts its effect through glutamate-related systems, these other drugs work through serotonergic systems. Although they involve different neurotransmitters, the effects of both groups of drugs lead to similar influences on the chemical systems inside neurons that are involved in growth and development.

The group of serotonergic drugs that the authors studied include psilocybin ( ), , ayahuasca, and ecstasy. They note that there is preliminary clinical evidence that these drugs may be helpful in treating several conditions, including depression, states, and possibly addictive states. These drugs are currently undergoing formal clinical trials.

The authors note that while ketamine can be addictive, these non-ketamine drugs are not. However, they have psychedelic properties and have long been known to be abused for their mind-altering effects, including perceptual changes that some people find enjoyable and other people find terrifying. Thus, the continued development of these drugs as therapeutic agents will have to consider risks, potential benefits, and methods of administration carefully in well-designed clinical trials. Olson and colleagues are hopeful that new medications can be derived from the existing drugs that retain the psychoplastogen properties while eliminating the psychedelic effects.

The next decade will be a very interesting time with respect to the development of truly unique pharmacologic approaches for the treatment of psychiatric disorders such as depression, anxiety, and — disorders that are among the most impairing of all illnesses.