Psychedelic drugs, psilocybin, and transcendent experiences as antidepressants | Charles Raison
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The mammalian brain seems drawn to substances that induce altered states of consciousness. For example, cats crave catnip, elks seek out a hallucinogenic moss, and humans around the world have used psychedelic substances. Researchers studying the psychedelic compound psilocybin and its potential effects on depression observed that a single exposure in humans induced a powerful anti-depressive response that persisted for six months or longer. Investigators speculate that the anti-depressive effect may result from the subjects having a mystical experience rather than the psychedelic agent itself. Dampening of the default mode network in the brain may also play a role in the anti-depressive effect. The default mode network is involved in rumination, a significant component of depression that some studies have linked to inflammation. In this clip, Dr. Charles Raison discusses how psychedelic substances like psilocybin, which induce transcendent trance-like states, may be useful in the treatment of depression.
- Charles: So humans, you know, I think many of these ancient practices that induce heightened states of awareness, evolved out of strategies, unique human strategies for survival and reproduction. But then they become fascinating on their own. Exercise is one of them. Another one that I’m particularly interested and involved with is psychedelics. If you say, “What’s another thing that humans all around the world did repeatedly and for extended periods to alter consciousness?” It’s psychedelics. It’s much older than just humans. You know, mammals have a tropism, a craving for drugs that make them hallucinate and go crazy. You can make a list. Many mammal species have their psychedelics: cats have catnip, elks have a certain kind of moss. So there’s something about mammalian brains that are drawn to substances that induce the sort of altered states of consciousness, and widespread use of psychedelic medicines, psychedelic substances around the world. You know, you say, “Well, what do these things do?” Well, they tap into this interesting human evolved capacity for transcendent states. You know, they can be induced in all sort of other ways. One of the most species typical human behaviors is trying to put yourself in a whacked state, you know, a trance state. Dancing, I mean, there’s a whole list of these things. The urgency with which these were pursued in indigenous groups is really highlighted nicely by people that were indigenous in my part of the world, which is up about 200 miles from here. I grew up in Fresno, in central California. Prior to them all being wiped out, the Yokuts, that were the indigenous groups in Central California, they were one of the world’s great shamanistic cultures. But they didn’t have good psychedelic substances and so they felt so strongly about the need to induce these types of experiences at puberty, that they would have their young people at puberty, you know, strip naked and lay on these ant hills. Their bodies would be completely covered with ants and bitten, bitten, bitten, bitten. And the ants, I don’t know whether formic acid, I’m not sure what it was, but there’s a substance that if you get, you know, just hideously bitten, it will induce a psychedelic experience. I mean that’s the length...
- Rhonda: That’s crazy.
- Charles: Yeah, that’s the length people would go to induce these experiences, because they were so integrated into certain societies.
- Rhonda: Why puberty? Was it like a coming of age?
- Charles: Yeah. Well, in cultures that have a strong shamanistic emphasis, there’s a very powerful feeling that you want to identify a spirit guide for a lifetime. So, you know, psychedelic experiences, or transcendent trance-like experiences, on a repeated basis, were usually just the province of a very small group of specialists, shamans that had very complex relationships with the rest of the population. Very ambivalent. It’s fascinating stuff. But most of these cultures, everybody would at least have one experience, and if that happened, it would be at puberty. And yeah, I think basically, that’s the time where you sort of have a transcendent experience that points you to the spirit world so that you can have, you know, you’re not going to have the same potency of the spirit guide help that you would have if you’re constantly moving into the spirit realm like a shaman would, but it was sort of... people would, you know, everybody sort of wants one of these in those sort of cultures. So I think that’s why they were used there. Now there’s some evidence that “The Eleusinian Mysteries” of ancient Greece, which we know very little about because they were all kind of hush-hush. But there’s some suggestion now, I think in the last 20-30 years, some researchers suggest that they may have also ingested psychedelic substances, that was sort of at the core. Because these were really the core of spirituality, especially esoteric spirituality in a Greco-Roman world, you know. And we know so little about because it was so secret, but they were very widespread. Another example of these things being used, not just at puberty, but for these sort of transformational purposes, and I know you would, off camera you told me you interviewed my colleague, Roland Griffiths.
- Rhonda: Yeah.
- Charles: And so a number of us are now involved in this work of looking really rigorously at psychedelic substances as treatment for depression, because Roland and Steve Ross at NYU, Roland at Hopkins, showed that, you know, a single exposure to something like psilocybin, which is a psychedelic substance in magic mushrooms, you know, tends to induce you to very unusual states of mind, that often have a kind of mystical characteristic to them. A single exposure in a couple of studies induce these powerful anti-depressive responses that last for like six months, longer. I mean, I know from Steve, you know, that he’s followed up on people, these are depressed, anxious people with cancer, that those who are still alive two years, later many of them, most of them are still un-depressed and not taking...
- Rhonda: After one experience?
- Charles: Profoundly life transforming.
- Rhonda: That is phenomenal.
- Charles: Oh, it’s fascinating.
- Rhonda: Yeah, I mean...
- Charles: It’s one of the most fascinating things going in our world right now.
- Rhonda: I know with my discussion with Dr. Griffiths, he was mentioning, again, he did say that this mystical experience seemed to be important for the antidepressant effect. Of course, he doesn’t really know the mechanism why, but parallel to that, there are also some studies looking at a part of the brain that’s involved in like rumination, forgot what it was called.
- Charles: The default mode.
- Rhonda: Yeah, the default mode network. And how that was changed also.
- Charles: Oh, absolutely, yes.
- Rhonda: Of course rumination, that’s a big part of depression.
- Charles: Huge, huge part. And it’s interesting to link back, there are studies linking rumination particularly to inflammation.
- Rhonda: Oh, really?
- Charles: Yeah. So inflammation probably, preferentially drives rumination. We know from interferon studies that one of the places that inflammatory molecules most change in the brain is the rumination center in the anterior, dorsal anterior cingulate, right? So there’s a beautiful sort of story there. Now why you should ruminate, when you’re...? That’s an interesting question that I don’t think we know the answer to, why should inflammation make you ruminate? But it does. And yes, rumination is a big problem.
- Rhonda: Yeah. And that also sort of leads to this, you know, you’re talking about these transformative experiences which also are brought about by meditation. And I know you’ve, you know, there seems to be, at least Roland was talking about some overlap between meditative state and there is something that’s happening with this mystical experience. You know, there are sort of mystical experiences that are like calming to nerves.
- Charles: Absolutely. It’s very much like sauna versus my $50,000 fancy machine, right? It’s not the machine, it’s the heat.
- Rhonda: Uh, huh. Right.
- Charles: I am utterly convinced it’s not the psychedelic. We know it’s not psychedelic, it’s the experience. Because we know, every study pretty much that’s looked this shows that the more intensely you have one of these sort of mystical type experiences, depending how you define mystical, there’s other ways. Spiritual is almost the better word, because people also have these very difficult personal experiences but that it makes them feel like their life, they see their life in a different way that produces a transformation. You know, that realm of response, it’s just been repeatedly associated with antidepressant and anti-anxiety effects. And not just that, but also these agents seem to have anti-smoking effect, they help people quit smoking. You see the same thing there, right? So we think that exactly, there’s nothing special about the psychedelics other than the fact that they can take a wide, wide range of people and on cue, induce these sorts of experiences. You know, just like if you wanna study inflammation, it’s great to have interferon because I can just wait around until you get inflamed, you know, God forbid, but I’m going to wait. I’m going to wait, you know. Or I can just give you interferon shot and away you go, right? So in the same way, I could wait around for you to have mystical experience. There was a wonderful study done a number of years ago, that I unfortunately, wasn’t smart enough to put in my file. I just read about it. Where they did this huge sort of, you know, anonymous survey of Americans. And I don’t know, some crazy percent, 15%, 20% of people said, “I’ve had a powerful mystical experience that changed my life, I just never talk about it. I was at the kitchen sink, you know, and I boom, the world looked like it was interconnected in ways I had never mentioned.” So it happens, but it doesn’t happen predictably. Whereas believe me, if it wasn’t illegal and unethical, I could give you a big old dose of psilocybin right now, put you on the couch over there, and it would be very likely you’d have a profound mystical experience, right?
A group of interacting brain regions implicated in self-related thinking, rumination, and depression. The default mode network is typically active when a person is not focused on the outside world and the brain is at wakeful rest, such as during daydreaming and mind-wandering. Functions include autobiographical information, self-reference, emotions of one's self and others, theory of mind, moral reasoning, social evaluations, social categories, remembering past, imagining future, and story comprehension.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
The annual rites performed by the ancient Greeks at the village of Eleusis near Athens in honor of Demeter and Persephone. They've been referred to as "the most famous of the secret religious rites of ancient Greece" by the Encyclopedia Britannica. The rites, ceremonies, and beliefs were kept secret and consistently preserved from antiquity.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
A group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and tumor cells. Interferons are named for their ability to interfere with viral replication and are critical components of the body's innate immune response to viruses. SARS-CoV-2, the virus that causes COVID-19, impairs the body's interferon response.
A naturally occurring psychedelic compound produced by more than 200 species of mushrooms. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects including euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.
A class of hallucinogenic substances whose primary action is to alter cognition and perception, typically as serotonin receptor agonists, causing thought and visual/auditory changes, and "heightened state of consciousness." Major psychedelic drugs include mescaline, LSD, psilocybin, and DMT. Psychedelics have a long history of traditional use in medicine and religion, for their perceived ability to promote physical and mental healing.
The practice of dwelling on external stressors to excess. Rumination can set in motion a cascade of hormonal and physiological responses that harm mental and physical health. A key player in the body’s response to rumination is a biological pathway that starts in the brain’s hypothalamus with the release of corticotrophin-releasing hormone and has a direct effect on many parts of the body including the brain, gut, and DNA. Meditation has been shown to reduce rumination and its negative effects.
The Yokuts (previously known as Mariposas) are an ethnic group of Native Americans native to central California. Before European contact, the Yokuts consisted of up to 60 tribes speaking the same language. "Yokuts" means "People."
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