For instance: I did not know that Bill W., founder of Alcoholics Anonymous, not only did a series of supervised LSD trips in the late 1950s, he was so impressed by the results that he wanted to include it in AA programs.
Turns out he credited his own sobriety to a mystical experience he had on belladonna in 1934. His entire concept of a spiritual awakening and surrendering to a higher power was based on his drug experience. If more people knew that, they might not be so resistant to the program!
Now, this is interesting to me because I had a spontaneous transcendental experience in 1999. At the time, I talked about it with a friend who was in AA, and he said, “That sounds just like what William James wrote about in The Varieties of Religious Experience.” James is considered the founder of modern psychology. (You can read what he has to day about mystical experiences here if you’re interested.)
I’d never heard about it and was shocked to discover it was not exactly common, but not unknown, either. The thing is, my experience was completely spontaneous and had nothing to do with drugs.
I began to cautiously approach the subject with people. I remember this one Southern co-worker (former college quarterback) who told me the same thing happened with him. “I just don’t talk about it because I don’t want to be lumped in with all those right-wing Christians saying they’re born again,” he said. (Good point.)
Anyway, I’d love to feel that way again. It’s been so long now, all I have left are the intellectual remnants, and not the rush of overwhelming compassion and tranquility that lingered for years.
It seems that psychedelics do more than simply alter perception. According to the latest research from my colleagues and me, they change the structures of neurons themselves.
My research group has been studying the effects of psychedelics on neuronal structure and function, and we found that these compounds cause neurons to grow. A lot. Many of these compounds are well-known and include lysergic acid diethylamide (LSD), psilocin (from magic mushrooms), N,N-dimethyltryptamine (DMT, from ayahuasca) and 3,4-methylenedioxymethamphetamine (MDMA, aka ecstasy).
These are among the most powerful drugs known to affect brain function, and our research shows that they can alter the structure of the brain as well. Changes in neuronal structure are important because they can impact how the brain is wired, and consequently, how we feel, think and behave.
Prior to our study, there were relatively few compounds known to have such drastic and rapid effects on neuronal structure. One of those compounds was ketamine – a dissociative anesthetic and quite possibly the best fast-acting antidepressant that we have available to us at the moment.
If you think of a neuron like a tree, then its dendrites would be the large branches, and its dendritic spines – which receive signals from other neurons – would be the small branches. Some of these small branches might have leaves, or synapses in the case of a neuron. In fact, neuroscientists often use terms like “arbor” and “pruning” much like a horticulturist would. When we grew neurons in a dish – which is not unlike growing a plant in a pot – and fed them psychedelic compounds, the neurons sprouted more dendritic branches, grew more dendritic spines, and formed more connections with neighboring neurons.
The rainbow-colored neuron was treated with LSD, while the purple neuron was the control. LSD altered the structure of the neuron, allowing it to grow more branches and develop a more complex structure. Calvin Ly and Joanne Ly, CC BY-ND
One of the hallmarks of depression is the atrophy of neurons in the prefrontal cortex – a region of the brain that controls anxiety and regulates mood among other things. Basically, these branches and spines shrivel up, disconnecting from other neurons in the brain. One hypothesis for why ketamine is so effective is because it can rapidly regrow the arbors and spines of these critical neurons.
Strictly speaking, a psychedelic is a “mind-manifesting” drug – a definition that’s open to interpretation. They tend to produce perceptual distortions or hallucinations by activating 5-HT2A receptors. Our research group has found that compounds typically regarded as psychedelics, like LSD and DMT, as well as those that are sometimes called psychedelics, like MDMA, and those that are not usually called psychedelics, like ketamine, are all capable of profoundly impacting neuronal structure.
Our group has coined the term “psychoplastogen” to refer to such compounds, and we believe that these molecules may hold the key to treating a wide variety of brain diseases.
Our studies on neurons grown in dishes, as well as experiments performed using fruit flies and rodents, have demonstrated that several psychoplastogens, including psychedelics and ketamine, encourage neurons to grow more branches and spines. It seems that all of these compounds work by activating mTOR – a key protein involved in cell growth.
The biochemical machinery that regulates mTOR activity is intricate. As we tease apart how psychedelics and other psychoplastogens turn on mTOR signaling, we might be able to engineer compounds that only produce the therapeutic effects on neuronal growth while bypassing pathways that lead to undesired hallucinations.
This figure shows the effects of three psychedelics and one control (VEH) on cortical neurons. These neurons were treated for 24 hours before being visualized using super-resolution microscopy. The colors represent proteins found in specific locations of the neuron. Orange protrusions from the purple dendrite indicate dendritic spines. Ly et al., CC BY-ND
The field has known for some time now that psychedelics can produce lasting positive effects on brain function, and it’s possible that these long-lasting changes result from the psychoplastogenic effects of these drugs. If true, this would suggest that psychoplastogens might be used to repair circuits that are damaged in mood and anxiety disorders.
Panacea or poison?
Many diseases, such as depression and anxiety disorders, are characterized by atrophy of dendritic branches and spines. Therefore, compounds capable of rapidly promoting dendritic growth, like psychedelics, have broad therapeutic potential. The number of papers demonstrating that psychedelics can produce therapeutic effects continues to grow every year.
However, we should temper our enthusiasm because we do not yet know all of the risks associated with using these drugs. For example, it’s possible that promoting neuronal growth during development could have negative consequences by interfering with the normal processes by which neural circuits are refined. We just don’t know, yet.
Similarly, it is unclear what effects psychoplastogens will have on the aging brain. It’s important to keep in mind that excessive mTOR activation is also associated with a number of diseases including autism spectrum disorder (ASD) and Alzheimer’s disease.
To me, it’s obvious that we need to understand how these powerful compounds affect the brain, in both positive and negative ways, if we hope to fully comprehend the fundamental laws governing how the nervous system works and how to fix it when it doesn’t.
To me, it’s obvious that we need to understand how these powerful compounds affect the brain, in both positive and negative ways, if we hope to fully comprehend the fundamental laws governing how the nervous system works and how to fix it when it doesn’t.