“Psychedelics and Neural Plasticity” – A keynote address at the international symposium “psychosurges and neural plasticity”
The symposium called “psychosurges and Neural Plasticity” had about 1000 brain scientists squeezed into an auditorium.
The fact that psychedelics were featured at the world’s largest meeting of brain scientists suggests the drugs are poised to enter the scientific mainstream. That was a recent development.
Dendrites form connections through small protrusions known as dendritic spines. And in mice that got psilocybin, the size and number of these spines increased by about 10%, which allowed cells to form new connections.
“It can be months or years,” says Dr. Gitte Knudsen a neurologist from University of Copenhagen in Denmark who spoke at the psychedelics session. “It’s a stunning effect.”
These long-term effects have been shown with drugs including psilocybin, LSD and DMT (ayahuasca), Knudsen says. In contrast, most existing psychiatric drugs need to be taken every day.
Tales From The Synapse: Neuropsychopharmacological Applications of Cannabis and Pseudogrenics on Brain and Behaviour
It can be very overwhelming to people. Preparing them for that and also being with them while they are in the experience are two things that need to be done.
“When people have been through a psychedelic experience in my lab, they say, ‘Wow this was amazing, this was just a fantastic experience,'” she says. You want them to come back next week? They say, ‘Thank you, but no thank you.’ “
Two studies published by prominent researchers caught the attention of everyone in 2016, says Joshua Gordon, who directs the National Institute of Mental Health.
The effects on the individual have been less dramatic than in the smaller studies. Also, he says, some companies hoping to market psychedelics have overstated their benefits.
Hello and welcome to Tales From The Synapse, a podcast brought to you by Nature’s careers section, in partnership with Nature Neuroscience. I am Jean Mary Zarate, the senior editor at the journal Nature Neuroscience, and in this series, we speak to brain scientists from all over the world about their life, their research, their collaborations, and the impact of their work.
My name is Natasha Mason. I am an assistant professor in the department of psychopharmacology at Maastricht University. So this is a yeah, a small pretty town in the south of the Netherlands.
And yeah, and I have been living here for for eight years doing research and studying the effects of cannabis, and also psychedelic drugs on brain and behaviour.
This is similar but maybe has a focus on how drug effects work in the brain and how they affect behavior.
As well as that, it is more of a fundamental level. There is also a high need, of course, for effective pharmacological treatments for mental health disorders.
I’m interested in both sides of the story. So both the therapeutic effects, and the potential negative effects. And when it comes to negative effects, it is how we can mitigate them.
So cannabis, the most widely used illicit drug in the world. And also psychedelic drugs, which are, yeah, they have a long history, but their use and interest in them is is also growing. I have different interests in these two drugs. I think in regards to cannabis, I am interested in the behavioural effects of these substances.
And I find this really interesting because I think that this can have both positive and negative outcomes. Recreational users use cannabis for the relaxing effect.
So here tolerance can be seen as kind of a maladaptive thing, and that you have to use more of the drug to get the high that you want. This is the place where addiction dependence can come in.
So here this would be seen as a positive effect. So I am very interested in understanding the brain mechanisms underlying this occurrence of tolerance.
Behavioural Tolerance and Dosing of Cannabis for a Brain Study of Subjective High Feelings and Behavioral Impairedness
So for example, if you are prescribed cannabis daily, you have to consistently use a drug for your indication, but you also have to perform day to day operations, right, like driving to work or the store.
And currently, what happens is legal individuals may take a blood sample and say, “Okay, you have cannabis in your blood, you were driving under the influence.”
So finding a way to measure behavioural tolerance. Who was able to use the drug at that point and who did not? Blood or a breathalyzer are sufficent, but they’re not enough because it doesn’t consider other factors.
If you give cannabis to someone with a condition such as pain, or anxiety, you can see what’s changing in the brain. And if this relates to symptom outcome would teach us a lot about how this drug can be used clinically.
Through this we are able to see how certain changes in the brain relate to subjective high feelings. Also, behavioural impairment. So focus, impairments and attention.
So future research could study at what dose of cannabis and use frequency is necessary to produce this biomarker, to produce tolerance. And this can be used to, again find a correct dosing regimen for people who do not want to experience the high or the impairment.
So if you can prescribe the dose of cannabis to people that induces a therapeutic effect, but doesn’t surpass this threshold to induce the high or the behavioural effect, you know, then they can go about day-to-day after operations without having these kinds of side effects in that regards.
And what we see is that individuals had developed tolerance. They were not experiencing the subjective high of the drug and they weren’t experiencing the impairment of the drug.
When recreational users start developing tolerance it can get a bit risky which is why it’s useful for more clinical uses. They begin using more of the drug.
So I’ve always been interested in how drugs affect the brain and behaviour. And in America, when you say that, they said, “Okay, you should be a pharmacist.” So I thought, “Okay, I will be a pharmacist.”
I went and studied pharmacy, and also worked at various drugstores to gain experience. Also here, as well as being a little bit bored with the job. I was also confronted with the fact that the patients coming in, a lot of the conversations were revolving around complaints about their drugs actually not working.
Another class of drug that stuck out was opiates. Not complaining that the drug wasn’t working, but you could kind of see a deterioration in some people that, you know, becoming more dependent on the drug.
I didn’t like the career choice so I didn’t want to go to school. All of these drugs that actually were not effective, were not good options for people.
And after graduation, I just knew I wanted to pursue research into you know, alternative drugs, psychedelic drugs for in order to try to understand more their therapeutic potential, and how the mechanisms of this therapeutic potential.
One administration of a drug can result in a long term reduction in symptoms. That was fascinating to me. I had never heard about that in my pharmacy classes. I felt like I had gotten to the point where I was trying to like this substance, which was a potential substance that could be used to fix the problem instead of the substances we had today, which were just reducing symptoms, but not addressing the underlying problem.
Internship at the Thermonuclear College of Ostr”om, Schleswig-Holt, Germany
This is quite common in the US, I think, unpaid interns or research assistants or something. I was running out of time. I wouldn’t have done it because it was not allowed in the Netherlands.
I did the Master’s so that I could do the internship. During my internship, I did work on cannabis. So that was an ongoing project at the time, which turned into a PhD and some psychedelic work as well.
And that is an assistant professor position. I am sticking around as long as possible. It is a very nice group to work with. We are able to do some really interesting studies.
The CANNABINOS receptors of THC, a widely used illicit drug in the world, and the implications on how we can mitigate the consequences of that use
In the case of THC, these are called cannabinoid receptors, which are receptors that are part of the endocannabinoid system in the body. And the endocannabinoid system is always there, right? It works if you do not consume cannabis. Our body has naturally occurring neurotransmitters.
The densities of these receptors are so high in certain areas that it is like a kind of reward. This is the area where you get the high.
So yeah, people notice when you smoke cannabis, you really experience a wide range of effects. The body has these Receptors located throughout it and they are implicated in many processes.
So the system is involved in, in many processes. From my perspective, we are just beginning to understand how the system works and interacting, and I think appetite, pain, mood, memory, and some inflammatory processes are just some of the things you can expect from that.
So because of it’s involvement in a wide range of processes, it can potentially correct the processes when there’s a paraments. I think it’s there. I’m not sure how explored it is currently.
So as I said that this drug is one of the most widely used illicit drugs in the world. I think it is important to understand the consequences of this use.
So we know that developmental age when you start using cannabis, depending on the age you start using cannabis, one can assume that this would have alter the impact of that.
And if there are, you know, potentially negative consequences of this, how we can mitigate these consequences since people are going to continue to use cannabis? We can’t stop that. I’m not saying we shouldn’t. Research should be done into understanding how to use the drug in a way that does not harm others.