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Q&A: Understanding Your Risk Factors

photo of Sylver Quevedo

Sylvestre (Sylver) Quevedo

Sylvestre (Sylver) Quevedo has been a physician for over forty years, specializing in internal medicine, nephrology, and integrative medicine. He’s currently one of the principal investigators of the Phase 3 MDMA study at the San Francisco Insight and Integration Center and co-therapist at the Phase 3 site at UCSF. He’s a professor at UCSF and Stanford and a co-founder of the Polaris Insight Center, which offers ketamine-assisted therapy.


BCSP

Can psychedelics exacerbate pre-existing physical or psychological conditions?

Sylvestre (Sylver) Quevedo

“The short answer to the question is yes. That’s true for all drugs, even aspirin. The important question to ask is: What conditions are particularly high-risk for the use of psychedelics? 

Who should not use psychedelics casually, or without looking into this? Anybody with a history of mania, bipolar disorder, psychosis, or suicidal ideation. It’s not to say that psychedelic agents aren’t effective in depression—they are. But these are areas where we carefully assess people for risk. Anybody that has anything suggesting psychotic ideation or ongoing psychosis should not be doing psychedelics. 

There’s a soft contraindication of hyperthyroidism for psychedelics, because hyperthyroid states are stimulant states, and adding to that could put somebody into a clinical situation called hyperthyroid toxicosis.

There may be cardiovascular risk with psychedelics, too. In general, psychedelics raise cardiac output about 20 to 30 percent. I’m talking about a person who is at risk for heart failure or who couldn’t do moderate exercise for a half hour: people with cardiac arrhythmias, congestive heart failure, high blood pressure that’s not controlled. These would be relative contraindications, as opposed to more absolute complications from the situations I mentioned earlier.

Anyone who is at risk for cerebrovascular events, like strokes or aneurysms, is at an elevated risk because of the increased cardiac output and increased pulse. If someone elderly is reporting that they have vascular headaches associated with stroke symptoms, there’s definitely a question mark about whether they’d want to use psychedelics.”


BCSP

“How do psychedelics interact with other medications?”

Sylvestre (Sylver) Quevedo

“The big category to be concerned about is monoamine oxidase inhibitors, or MAO inhibitors, which are used as antidepressants in psychiatry. (Some common MAO inhibitors are Nardil, Emsam, Parnate, and Marplan.) They put people at risk for serotonin syndrome, a clinical syndrome characterized by a flooding of the nervous system with serotonin. It occurs with certain drug interactions and in anesthesia. It’s life-threatening and has been reported with psychedelics, although it’s probably very rare. But it is a real thing, and it can happen to people who are on drugs that increase serotonin levels and change with serotonin metabolism, such as MAO inhibitors and SSRIs. People can have seizures, anxiety, hypertension, and stroke, and they can die from it. 

Similarly, the major tranquilizers that are used for depression, the antipsychotics, and all of the major psychiatric drugs are probably not a good idea to have with psychedelics.”

“There’s a lot of information that suggests that the classic psychedelics are virtually not addictive, which is rather remarkable.”


BCSP

“Should someone stop taking selective serotonin reuptake inhibitors (SSRIs) before doing psychedelics?”

Sylvestre (Sylver) Quevedo

“Just stopping these drugs without medical supervision is risky, because people are on them for a reason. And if you self-taper, it can be problematic. For example, depression can get worse. Generally speaking, it takes at least a couple of weeks to taper off of SSRIs, and some of them have very long half lives.”


BCSP

“Can users become physically addicted to psychedelics?”

Sylvestre (Sylver) Quevedo

“There’s a lot of information that suggests that the classic psychedelics are virtually not addictive, which is rather remarkable. In terms of whether or not a specific psychedelic is addictive, I like to think about a few different categories. 

First is the tryptamines: LSD, psilocybin, and anything else with the tryptamine nucleus. Unlike traditionally habit-forming substances like nicotine, cocaine, and caffeine, which trigger dopamine receptors, tryptamines work directly on serotonin receptors. Although it’s possible to develop a tolerance for tryptamines, it’s unlikely for people to become physically dependent on them, because they don’t deliver the dopamine rush triggered by other chemicals.

Then there’s the phenethylamines: MDMA, mescaline, peyote. These drugs have a lot of different names in pharmacology, but they’re often referred to as attenuated amphetamines. They do work on dopamine receptors, although they do so more slowly. They raise cardiac output, heart rate, and blood pressure, and if the dosing is wrong, they can have the effect of amphetamines. We really don’t know if they’re addictive. I’ve been suspicious about MDMA because it’s an amphetamine and we absolutely know from methamphetamine that amphetamines can be addictive. I wonder about MDMA, although most of the reports are that it’s not addictive.

The third category is the ones that are atypical, like ketamine. It does have psychedelic properties and antidepressant properties, but it’s different. Ketamine does have a well-defined abuse pattern and use disorder. People get into bad relationships with it. Ironically, ketamine has also been studied for addiction, and it does seem to help. It can be used in addictive disorders, very similarly to the way that things like suboxone or other agents are used.”


BCSP

“Can users become psychologically dependent on psychedelics?”

Sylvestre (Sylver) Quevedo

“In the addiction world, that dichotomy is debated a lot. What can seem like a ‘physical addiction’ has psychological underpinnings or a psychological component. The short answer is that we don’t function as a mind or a body separately. They’re quite integrated—physical problems typically have a psychological component and vice versa. I have heard of people that are absolutely addicted to doing too much psilocybin or too much LSD, because they’re really addicted to the peak experience.”


BCSP

“What about treating addictions with psychedelics?”

Sylvestre (Sylver) Quevedo

“Psychedelics and addiction really need to be approached with special caution. Addiction is such a serious, difficult problem that even if people have an improvement short-term with psychedelics, it doesn’t necessarily mean that they’re in recovery. I usually tell people that in order to treat addiction, they have to actively become involved in a recovery program and be substance-free for at least some time — at least a month or more. To me, those things are best done in a structured or semi-structured program. You need psychosocial support, social connections, and therapy.”

This interview was edited for length and clarity.

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