What does that missing piece of the puzzle that we think that it is providing and is worth pursuing?

It depends a little bit on the psychedelic, but what we generally think is that the psychedelic allows us to tap in or allows the brain to have more connectivity than it does otherwise on its own. So, if you look at an fMRI of someone on like LSD or psilocybin magic mushrooms, you can see that their brain is totally lit up across all of these different cross functional networks that don’t exist when someone’s not on that. So, it literally allows for connections to be built and made and for people to see things in a different way. We can sit in talk therapy for like ten years with someone and never get them there because their brain just physically won’t do that without the drug. So, it allows like kind of a shortcut or a catalyst in some conditions.

What fits under the psychedelic-assisted therapy umbrella and what doesn’t?

When we talk about classical psychedelics, we’re usually talking about the ones that that have affinity for serotonin receptors. Although ibogaine is considered a psychedelic and it is an opioid receptor antagonist. Most people will throw things like ketamine in there, ketamine is not a psychedelic.  Something a lot of people argue about is whether MDMA should be considered. It is not a classic psychedelic. People have hallucinogenic or kind of out-of-body experiences on it, but it is not the same thing and doesn’t work in the same way as like LSD, PCP, mushrooms and ibogaine.

Was LSD listed as a tool for therapy?

LSD was first developed so therapists could know what their psychotic patients were experiencing. Shulgin, who also developed MDMA, passed out MDMA to all of his therapist friends and was like, “Hey, you should use this when you’re doing therapy. It’s amazing.” But if you throw just a little substance at people, they do so much better together.

What is the unifying thread across these different drugs, is it sensory perceptions?

It’s hard because throughout the literature and the research it’s an ongoing debate about what gets couched where.  Sensory perceptions is just a really fancy term for what’s an hallucination. A hallucination is mis wired, misinterpreted sensory information, whether it is seen, heard, or tactile. So something is going on, on those planes, those dimensions.

How does the therapy piece fit in?

Think about the drug or the substance as a catalyst rather than a cure, it’s sort of more like you do some work, maybe you do a substance and that allows for greater expansion of the work you could do after. So, it’s really like that 24 to 48 hour window post trip. You’ve got some really awesome neuroplasticity. We know that the brain is forming new connections. Things can really be changed at a neurophysiological level and so that can help, kind of like a booster. It’s like a therapy booster almost. You can move into a really different place with it, but you have to do the integration afterwards, which includes like behavioral changes. the people who like walk into my office and they’re like, I want to do mushrooms and then I’m going to be all better, “No, you’re going to do mushrooms, and then you’re going to realize just how much you have to do.” Like, welcome to the start.

Some of the some of the arguments for the psychedelics seem very much piggybacked on the medicinal benefits of marijuana. Would you say that those are reasonable analogies? Do we know far more about medicinal marijuana?

By and large, once marijuana got legalized, people stopped doing research on it, so we actually know less. There is a real fight within the psychedelic community to not have psychedelics get rolled out in the way that marijuana has been, which is where you start to see a lot of the schisms within this field around people who feel like decriminalization and full legalization are the only ways to go versus folks who believe we need to be careful about this and do the research. I think cannabis is one of our maps for like, oh, that that maybe didn’t go the way we had hoped. Ketamine is another example of it not going the way we hoped. 

What about therapeutic Ketamine?

It was never intended to be used as its off label use right now. It was an anesthetic that had a great safety profile. They found it while trying to find something else to provide soldiers in the battlefield. They found ketamine while they were actually producing PCP. PCP creates like such a strong response. They kept looking for a different molecule and found ketamine and ketamine has a great safety profile. It’ll knock people out during surgery. Safer to use on kids, not a lot of the problems that you get from other anesthetics. So it’s been used a lot.  I think around the eighties it started to be seen in the streets and then got really big in the rave scene. So, then it was scheduled to be managed well.

How are these drugs are scheduled and what’s the respective tiers.

Schedule 1 has a propensity for addiction, but has little benefit, which includes cannabis and MDMA. And so this all came out of the 1970s Controlled Substances Act. And there’s five categories.

The DEA is federal. So even though Colorado has passed this measure, the federal government has not.  Technically, all these states right now that have marijuana legal, they’re actually in violation of federal law. Just federal prosecutors aren’t prosecuting them.There’s federal law which supersedes state.

There are different studies going on right now, such as which substances seem to hold promise. Is it a case that one works for all mental health isues or is it problem dependent?

I would say the latter and it depends on the indication. I can’t legally do preparation therapy, as its illegal in Colorado. But hypothetically, when people call a provider and they say I want to do a psychedelic, I don’t know which one to do, the provider can ask them, “Well, where do you want to go? Because those are very different.

Do you need to be in your head and, like, figure something out? Or do you need to be in your body and reprocess experience. Do you need to get a better sense of your connection to the world in the universe and what’s true then? That’s DMT.” They all go to different places.

Then either theoretically or practically, what would you say are some positive prognostic indicators that somebody might be a good fit for this type of intervention, that this this might be a good medicine, so to speak?

Most candidates have done talk therapy for a while, but it really is folks who have done some work prior who do not have any sort of major mental illness like bipolar or psychosis. We’re also unsure about personality disorders at this time. Those are rule outs as well. And no first degree relatives who have psychosis or bipolar. We don’t know what it could do for those folks. Those have always been excluded from trials. So I think it’s really important that people know that people who have room and space to kind of do the work on the other side of it. Ketamine is actually great for suicidal depression, so if you’re acutely suicidal, ketamine will really help with that. But if it’s more like a long term, need to sort of figure some things out or get to the root of depression that doesn’t respond to an antidepressant. Psilocybin seems to be really good for that. Kind of depends on the person, but primarily like you want to get those ruled-out, No cardiac conditions.

When we’re talking about predisposition, what we’re saying is, there is a family history of severe mental illness, schizophrenia, bipolar. And that’s kind of the line nowadays with the THC that gets produced. If you have a family member who’s schizophrenic, you might carry a vulnerability that high THC low CBD might cause a psychotic break, and unfortunately for the rest of one’s days have to monitor against that.

Read blog 2 in this series next week where we uncover risks, how this treatment can affect youths, and organizations that implementing this well.

Dr. Tippett has been trained primarily in Harm Reduction to address addiction, and teaches from that theoretical framework. As the director of the Substance Use Disorder specialty program, Dr. Tippett is passionate about training graduate students to be responsible and informed clinicians.