Psychedelics Q&A: Fact Vs. Fiction With Dr. Meghan Hibicke

May 25, 2023

Meghan Hibicke, Ph.D. from LSU Health Sciences Center talks about what is known about psychedelic compounds, like psilocybin, and how they work.

Video Transcript

Q1: What is a Psychoactive Drug?

Answer: "A psychoactive drug is one that affects the nervous system, the central nervous system. It changes a person's perception, mood cognition or behavior. Which includes psychedelics, but also all recreational drugs, all drugs of abuse, medicines, like SSRI’s and Ritalin and gabapentin, and common use items, like nicotine and caffeine."

Q2: How is a Psychoactive Drug Different From a Psychedelic?

Answer: "Classical psychedelics are LSD and psilocybin and DMT. They're all 5HT-2A receptor agonists. They interact with the serotonin system and do strange things to our brain by activating the 5HT-2A serotonin receptor."

Q3: What is Psilocybin?

Answer: "Psilocybin is grown in mushrooms and not just the Psilocybe cubensis, but also a few others. It's a 5HT-2A and 5HT-1A serotonin receptor agonist. Like LSD, it interacts with a whole lot of different receptors. It's what pharmacologists call promiscuous or dirty.

Psilocybin’s a pro drug, which means that it actually has very low bioactivity on its own. Once it's absorbed into the circulatory system, it is almost immediately de-phosphorylated and turned into psilocin, which is the actual active form. The psilocin is the one that actually interacts with the 5HT-2A receptor."

Q4: What is the Difference Between Clinical-Grade and Home-Made Psychedelic Drugs?

Answer: "Homemade medicines are stuff that's extracted. Anything that's not regulated by some kind of oversight like the FDA is going to have the same kind of issues, which are purity and potency. The Psylocibe mushrooms, if you grow them at your house or someone else grows them, they might have a parasitic fungus on them that could make you sick.

Aside from the purity there's always potency issues. The amounts of drug in homemade stuff can vary wildly from batch to batch. When you're using pharmaceutical grade drugs that are meeting FDA chemical purity standards, they’re going to have a set amount of drug per dose. FDA decides how much is required for each specific kind of drug. There won't be any kind of contaminants in there. Consistent purity and potency from badge to batch without residual compounds."

Q5: What are the Effects of Psychedelics on Neuroplasticity?  

Answer: "The current understanding is the psychedelics precipitate a temporary window of neuronal plasticity, where the neurons grow, and new connections are made to other neurons, and they strengthen existing connections between the neurons.

Whatever you do during that time—that window of plasticity—you can learn new things, or you can get better at what you're already doing. Then when the growth period is done—in, we believe, maybe a week or 2—these unused connections are allowed to atrophy.  

It doesn't look right now like there's any kind of permanent neural growth. But there's temporary neural growth. The neurons that are used during that time become much more efficient and have higher function."

Q6: What is Known About the Effects of Psychedelics on Depression?

Answer: "Psychedelics, especially psilocybin and to some extent Ayahuasca, which means DMT, have been shown to have pretty long-lasting antidepressant effects. Also they've shown similar effects in animal models. Certain behaviors, like passive coping, are very comparable to human behaviors who are experiencing depression.

If we do a forced swim test, which is where we take a rat and we throw it in a bucket of water, and the rat just floats and waits to either drown or be saved, that's a passive coping strategy, an inescapable stressor. An active coping strategy would be for the rat to try and get out even if it knows it can't, to just keep trying. Psychedelics like LSD and DMT and psilocybin have been shown to increase active coping strategies in animal models." 

Q7: What is Known About the Effects of Psychedelics on Bipolar Disorder?

Answer: "Not a whole lot is actively known about the effects of psychedelics on bipolar disorder. People with bipolar disorder who are on lithium are at a much higher risk of having seizures if they take psychedelics." 

Q8: What is Known About the Effects of Psychedelics on Borderline Personality Disorder?

Answer: "The effects of psychedelics on borderline personality disorder are iffy also. There are case studies of psychedelic-assisted therapy relieving major depressive episodes in people with borderline personality disorder. There's no publications in which psychedelics were used to treat the original disorder.

It's highly conflated with complex PTSD, so it's kind of hard to say what exactly is going on there and how psychedelics might help. Psychedelics probably will help PTSD though, so there's a chance that these anecdotes about people with borderline personality disorder who got helped by psychedelics might actually just had severe PTSD and were not actually born with this vulnerability to stressors that people with BPD have."

Q9: What is Known About the Effects of Psychedelics on Psychosis?

Answer: "Psychedelics and psychosis, they get a bad rap. For a long time, they were considered psychomimetics. They were mimicking psychosis. But if you actually look at what a psychotic episode is like and compare it to what a psychedelic episode is like, they are vastly different; they are not at all alike.

Psychedelics are not stand-ins for psychosis at all. Psychotic breaks can be caused by a number of different things like manic episodes, extended psychostimulant usage and subsequent sleep deprivation, age-related dementias, traumatic brain injury, schizophrenia. There's no evidence that classical psychedelics cause psychotic breaks in people who are not already at risk of psychosis for some other reason."

Q10: What are Some of the Challenges in Doing Human Clinical Trials for Psychedelics?

Answer: "One of the other issues with clinical trials is that they're supposed to be double-blind, which is where neither the clinicians nor the subjects participating in the study are aware of whether the subject is getting the control drug or placebo or the experimental drug. However, it's very easy for someone who's having a psychedelic experience to know which option they got, and it's called unmasking.

The problem with unmasking is one of expectation. This introduces credibility issues because the power of expectation, often called “the placebo effect,” can make you feel better. If you think you took medicine that'll make you better, you are a lot more likely to report that you feel better. Of course if you actually study the physiology of it, there's no difference. But you feel better and vice versa. If you think you did not get medicine that helped you, you will not feel better.

This is really important for the animal research because the animals do not have any expectation of their psychedelic experience. When they have parallel behaviors to the humans in the clinical results, we can say, 'yes this is definitely valid physiological neurological process,' and not because these people felt like they needed to meet these expectations by saying they were less depressed." 

Q11: Is the Psychedelic Experience Necessary for the Effects of Psychedelic Drugs?

Answer: "Whether or not the psychedelic experience is necessary to get the effects of psychedelic drugs, or at least the cognitive mental health benefits, that is the question of the ages for psychedelic researchers right now.
The cognitive benefits don't seem to be coming from the psychedelic experience itself. Rather the psychedelic experience is an indicator that sufficient dosage has been given to initiate the neurological process that's responsible for the mental health benefits.

If we could find a drug that you could give a lot to and have the same kind of neurological response, but without the neurological response that causes the psychedelic trip, then yes you could have a non-psychedelic psychedelic."
Read more about the history of psilocybin, the psychoactive compound in “magic mushrooms,” and its potential for clinical use in this next article, "Psilocybin and Mental Health: the Magic in the Mushrooms."


Author: Geoff Hunt, Ph.D.

Geoff Hunt, Ph.D.
Geoff Hunt earned his Ph.D. in molecular biology from Princeton University.