This is exciting research just published looking at changes in neural activity in response to psychedelic therapy using psilocybin to treat alcohol use disorder. We have good evidence that this...
This is exciting research just published looking at changes in neural activity in response to psychedelic therapy using psilocybin to treat alcohol use disorder. We have good evidence that this form of therapy is effective at reducing alcohol consumption for people that have an addiction to it, and the question now is how does it work?
The data from this study is preliminary - it's identifying correlates of activity changes to the intervention of psilocybin, but it's promising! I was just as surprised by the lead author that motivation/reward systems didn't seem to be as heavily influenced. I think their hypothesis about recruiting other brain mechanisms makes sense, especially considering that structures in the frontal cortex seem to have been affected.
One thing that stood out to me is that the study only recruited participants that had never used hallucinogens before. I understand from a scientific perspective why you wouldn't want that confound influencing any results, but it makes me wonder if psychedelic therapy is as effective for someone that has used hallucinogens.
This is, unfortunately, super common in studies on psychedelic substances. It's a common practice with any medication going through human trials, especially during phase 2. The goal is to control...
One thing that stood out to me is that the study only recruited participants that had never used hallucinogens before. I understand from a scientific perspective why you wouldn't want that confound influencing any results, but it makes me wonder if psychedelic therapy is as effective for someone that has used hallucinogens.
This is, unfortunately, super common in studies on psychedelic substances. It's a common practice with any medication going through human trials, especially during phase 2. The goal is to control for external variables as much as is possible, to be sure that you understand as best as you can how the drugs interacts with a very small set of humans. Phase 3 is where diversity of patients becomes a factor and members which do not resemble your phase 2 patients are actively recruited. This idea, specifically attempting to recruit a diverse set of patients is a rather new one, pushed onto the FDA in recent history, due to longstanding issues with healthcare development in the US and in the world primarily recruiting college aged white men and some of the issues that's lead to.
Some of these hallucinogens are already entering phase 3 trials and are seeing a much more diverse recruitment of individuals and I expect we'll start seeing more papers published with non-naive hallucinogen participants within the next few years. Of particular note with respect to substance use disorders, a study on ibogaine was recently published. If you're unfamiliar with ibogaine, it's been used in plant, naturopathic, and alternative medicine for quite some time specifically for substance abuse. It's basically never been studied in medicine, however, because of it's unusual propensity to cause atrial fibrillation (a heart attack) in a small number of individuals. The very real risk of death makes it a substance of last resort for most individuals, but this innovative study ended up co-administering ibogaine with magnesium as a way to offset the risk of afib (theorized with respect to the mechanism of action). I'm hoping that we'll see a lot more headway into theorized mechanisms of action for certain hallucinogens (notably mushrooms, LSD, and ibogaine) and their effect on substance use disorders as anecdotally these have been used to reframe the brain with regards to substance abuse for quite some time in alternative medicine communities.
Yeah I totally get it. We want homogeny of participant backgrounds to make mechanisms easy to isolate. As you point out though, too much homogeny can be a bad thing when we want to generalize to...
Yeah I totally get it. We want homogeny of participant backgrounds to make mechanisms easy to isolate. As you point out though, too much homogeny can be a bad thing when we want to generalize to the population at large.
I had not heard of ibogaine. The abstract of the paper you linked sounds awesome! I'm supposed to do some experiments here soon, but hey reading articles is part of the work right?
“A recent Phase II clinical trial in patients with alcohol use disorder (AUD) found that psilocybin-assisted therapy significantly improved drinking outcomes for up to 8 months relative to an active placebo. The positive effects of this treatment were observed rapidly (as early as the day after treatment), large in magnitude, and sustained after only one to two applications,” said study author Broc Pagni, a cognitive neuroscientist and postdoctoral fellow in the Center for Psychedelic Medicine at NYU Grossman School of Medicine.
“These are especially promising findings, as currently available treatments for AUD, and psychiatric disorders more generally, do not have these combined properties. However, it is unclear how psilocybin therapy works on the brains of patients with AUD. Thus, this was a perfect opportunity to begin studying what brain mechanisms are responsible for these encouraging clinical outcomes.”
The core of the methodology involved functional magnetic resonance imaging (fMRI) scans conducted three days before and two days after the treatment. These scans allowed researchers to observe changes in brain activity as participants were exposed to images of alcoholic beverages and pictures designed to evoke positive, negative, and neutral emotional responses.
The researchers observed notable changes in brain activity patterns in response to alcohol-related and emotionally charged cues. These changes were indicative of altered neural processing in areas of the brain associated with craving, emotional regulation, and decision-making.
Specifically, psilocybin treatment led to increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate — regions implicated in higher-order cognitive functions such as goal-directed behavior, decision-making, and emotional regulation.
Additionally, a decrease in activity was noted in the insula, motor, temporal, parietal, and occipital cortices, as well as the cerebellum. These areas are often associated with craving, automatic behavior patterns, and sensory processing, indicating that psilocybin may diminish the salience of alcohol cues.
The study also revealed unique responses to different types of emotional cues. For negative cues, psilocybin increased activity in the supramarginal gyrus, a region involved in empathy and emotional processing. For positive cues, there was an increase in right hippocampus activity and a decrease in left hippocampus activity, which may reflect changes in how positive emotional experiences are processed and integrated.
Contrary to their expectations, the researchers did not observe changes in several regions involved in the brain’s reward system.
“We anticipated to see changes in the reward circuitry of the brain, which is excessively active in AUD patients, when viewing images of alcohol,” Pagni explained. “Surprisingly, we did not see changes in the nucleus accumbens, a core reward region of the brain, and we saw increased activity in other parts of the reward pathway, including the caudate and medial prefrontal cortex.
“These increases in activation were in the opposite direction that we would have hypothesized. If these findings are replicated in larger studies, it could be that psilocybin is recruiting compensatory brain mechanisms, rather than normalizing brain responses to resemble those without AUD.”
“It is also unclear how these changes in the brain relate to the clinical outcomes that have been observed in AUD. Although inferences are commonly made in neuroimaging studies about the types of cognitive and psychological processes that underlie functional changes in specific brain regions, these processes must be verified by using specific tasks that tap into these constructs.”
“For this reason, we cannot say that changes in activity mean anything,” Pagni explained. “We can only say that the involvement of these brain regions might mean that the cognitive and psychological functions associated with them are involved. To this end, future research may base decisions to include relevant tasks to test these ideas directly.”
This is exciting research just published looking at changes in neural activity in response to psychedelic therapy using psilocybin to treat alcohol use disorder. We have good evidence that this form of therapy is effective at reducing alcohol consumption for people that have an addiction to it, and the question now is how does it work?
The data from this study is preliminary - it's identifying correlates of activity changes to the intervention of psilocybin, but it's promising! I was just as surprised by the lead author that motivation/reward systems didn't seem to be as heavily influenced. I think their hypothesis about recruiting other brain mechanisms makes sense, especially considering that structures in the frontal cortex seem to have been affected.
One thing that stood out to me is that the study only recruited participants that had never used hallucinogens before. I understand from a scientific perspective why you wouldn't want that confound influencing any results, but it makes me wonder if psychedelic therapy is as effective for someone that has used hallucinogens.
This is, unfortunately, super common in studies on psychedelic substances. It's a common practice with any medication going through human trials, especially during phase 2. The goal is to control for external variables as much as is possible, to be sure that you understand as best as you can how the drugs interacts with a very small set of humans. Phase 3 is where diversity of patients becomes a factor and members which do not resemble your phase 2 patients are actively recruited. This idea, specifically attempting to recruit a diverse set of patients is a rather new one, pushed onto the FDA in recent history, due to longstanding issues with healthcare development in the US and in the world primarily recruiting college aged white men and some of the issues that's lead to.
Some of these hallucinogens are already entering phase 3 trials and are seeing a much more diverse recruitment of individuals and I expect we'll start seeing more papers published with non-naive hallucinogen participants within the next few years. Of particular note with respect to substance use disorders, a study on ibogaine was recently published. If you're unfamiliar with ibogaine, it's been used in plant, naturopathic, and alternative medicine for quite some time specifically for substance abuse. It's basically never been studied in medicine, however, because of it's unusual propensity to cause atrial fibrillation (a heart attack) in a small number of individuals. The very real risk of death makes it a substance of last resort for most individuals, but this innovative study ended up co-administering ibogaine with magnesium as a way to offset the risk of afib (theorized with respect to the mechanism of action). I'm hoping that we'll see a lot more headway into theorized mechanisms of action for certain hallucinogens (notably mushrooms, LSD, and ibogaine) and their effect on substance use disorders as anecdotally these have been used to reframe the brain with regards to substance abuse for quite some time in alternative medicine communities.
Yeah I totally get it. We want homogeny of participant backgrounds to make mechanisms easy to isolate. As you point out though, too much homogeny can be a bad thing when we want to generalize to the population at large.
I had not heard of ibogaine. The abstract of the paper you linked sounds awesome! I'm supposed to do some experiments here soon, but hey reading articles is part of the work right?
Key bits from the article: