The Effects of Certain Psychedelics on the Brain

Steve Jobs consumed copious amounts of LSD. "The Beatles" may have named a song for it (guess which). Let's learn about what kinds of drugs these "geniuses" were taking and what they do.


Figure 1: Steve Jobs (predecessor to current Apple CEO Tim Apple)

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Psychedelic substances have shown promise, in a variety of studies conducted internationally, in treating mental maladies. A drug known as Esketamine with a chemical formula nearly identical to Ketamine (a schedule 1, psychedelic substance) was recently approved by the FDA as antidepressant medication. According to Cristina L. Magalhaes, Ph.D., of Alliant International University Los Angeles “Some psychedelic substances like MDMA, psilocybin and ayahuasca may improve symptoms of anxiety, depression, and post-traumatic stress disorder”.

These substances are illegal in the US. Today, I am going to try to help you understand what some of these substances are and how they can affect your brain. As a necessary disclaimer: this post is not meant to advocate for the legalization of psychedelic substances, nor is it meant to encourage the consumption of them (I highly recommend refraining from consuming any foreign substances), this merely intended to provide information on how they can affect people's brains.

For the sake of simplicity, I am only going to write about the effects of two psychedelic substances: ketamine, and MDMA.



Some ketamine; in particular a ketamine prescription.

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One of the many forms of MDMA. The most common form is pills or tablets. Funnily enough this picture comes from a news source specializing in news related to EDM.

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Ketamine (you probably know it as an often-abused club drug or horse tranquilizer) came to prevalence in the Vietnam War, when it was used as an anesthesia medication. It’s chemical formula is C13H16ClNO. It can be more properly labelled a dissociative anesthetic (meaning it blocks sensory perception). As a dissociative drug, it distorts sights, sounds, colors, sense of self and environment, it can also inhibit memory, which makes it particularly dangerous.

Getting to the brain science stuff, ketamine is a “dirty drug." This doesn’t mean it's literally grimy, but instead it doesn’t just target one system in the brain, it targets dozens. Ketamine has weak effects on the opioid and dopamine systems. Most significantly, it affects the glutamate system.



 The Chemical Formula of Glutamate

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Glutamate is an excitatory neurotransmitter released by nerve cells in the brain, it sends signals between nerve cells, and plays a role in learning and memory. Glutamate is the dominant neurotransmitter neural circuit communication. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. The NMDA receptor is one of three ionotropic receptors (membrane-bound receptor proteins that respond to ligand binding by opening an ion channel and allowing ions to flow into the cell) which glutamate binds to, allowing electrical signals to be sent between various parts of the brain. Ketamine allosterically inhibits the receptor, causing it to lose function.








Ketamine at work. It is blocking the ion channel that the glutamine would normally be opening.


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Some of the side effects of the depressed NMDA receptor function are hallucinogenic, there are also concerns that there is a correlation between reduced NMDA receptor function and schizophrenia, paranoid delusions, and memory deficits. Despite the negatives, largely for unknown reasons, Ketamine usage may result in the creation of new synapses between neurons. The creation of new synapses is why it may be an effective antidepressant, because depression is correlated with a decrease in synapses. Because Ketamine is a dirty drug, and can affect so many different receptors, it is difficult to determine how it could affect all receptors in different people, this makes it difficult to prescribe.

MDMA (3,4-methylenedioxy-methamphetamine) is a synthetic drug. Chemically, it's similar to stimulants and hallucinogens. It’s commonly known as ecstasy and molly. MDMA increases the activity of three chemicals in our brains: dopamine, serotonin, and norepinephrine. Dopamine is a neurotransmitter that interacts with parts of our brain responsible for feelings of pleasure and reward. When dopamine activity is increased, our sense of pleasure and reward is as well. The increased levels of dopamine while on the drug make your brain crave similar levels, over time this prevents you from feeling the same level of pleasure and reward a smaller dose of dopamine would have caused. Additionally, while MDMA hasn’t been studied thoroughly enough, other dopamine-increasing drugs are often addictive, leading to speculation that MDMA is. Serotonin is another neurotransmitter and is associated with mood, appetite, and sleep. can cause the release of various hormones affecting arousal (of a sexual nature) and trust. The increased release of serotonin is why some users report higher levels of empathy. Norepinephrine increases heart rate and blood pressure. Only about half of users “trip” while on MDMA, and it's largely dependent on the make-up of the individual's brain. While there is not incredibly substantial evidence to back this theory up, there is speculation that the increased norepinephrine activity is largely responsible for the psychedelic effects which include blurry or cartoon-like vision, color changes, people appearing as if they are wearing hats or glasses when they aren’t, false shadows, and more). Before you think: wow! Increased empathy and cartoon vision!, there are some negatives. In the week after using MDMA there are often certain effects including increased aggression, depression, irritability, and memory problems. So yeah, it's not perfect.

Now a bit of an explanation and post-drug-analysis-analysis is warranted. I was not able to explain exactly how these drugs cause the hallucinogenic effects that they are so widely known for. This harkens back to the beginning of this blog entry: they are illegal for most uses resulting in a lack of evidence, particularly for MDMA. There was more information available for ketamine because it's been around longer and is legal for certain uses.

I hope you learned something about drugs. For a less cautious perspective on psychedelics check out this podcast.