🫠 Psychonaut POV

Welcome to Tricycle Day. We’re the psychedelics newsletter that hit the jackpot the day you subscribed. 🫶  

Rayyan Zafar knows what happens in Vegas doesn’t always stay in Vegas. For people with gambling addiction, it shows up on an MRI. (Fun souvenir, huh?) He’s leading a world-first trial at Imperial College London to see if psilocybin can help.

We asked Rayyan what gambling addiction does to the brain, how psilocybin might let people take back control, and what makes money such a dangerous drug. 

We probably sound like a broken record, but this still needs to be said.

Integration is essential.

It’s the step that makes a psychedelic experience count for something. It's also, of course, the part people tend to skip.

So once a month, Althea hosts a free, 90-minute integration circle for anyone who's processing a journey. (Doesn’t even have to be recent.)

The circle is led by a pro with 15 years of experience in somatics and ceremonial facilitation. You’ll do a little practice, share in small groups, and feel something… not just be lectured at.

The next one’s on Tuesday.

When I was 12, I had anorexia nervosa. It was my first experience of mental illness, and of feeling driven to do something I knew was harming me. It felt as though I’d lost control. I wanted to understand how that happens, and what could help people regain a sense of agency.

Then while I was in high school, David Nutt came to speak and showed us some of the first brain imaging scans of people on LSD from his work at Imperial. That’s how I discovered neuropsychopharmacology. At the time, I planned to become a psychiatrist. But later, when I studied biomedical science at university, I realized I was more interested in the mechanism behind disorders and treatments. 

After my master’s in clinical neuropsychiatry, I applied to Imperial for a PhD fellowship on psychedelics and addiction. I’d known a lot of people who had recovered from addiction, and I felt there was an enormous unmet need. But stigma and a lack of funding made that work difficult to pursue. So I spent four years studying addiction neurobiology, comparing the brains of people with gambling addiction to healthy controls.

Eventually, David Erritzoe and I secured funding for a clinical study of psilocybin in gambling addiction. It’s taken roughly 18 years to get from those first questions to this research. I never knew whether I’d get to do it, and I feel very lucky.

Gambling gives us a way to study addiction without some of the complicating effects of repeated exposure to neurotoxic drugs or alcohol. We’re looking at how a behavior can come to dominate the systems involved in reward, motivation, and salience—what the brain treats as important.

Those systems matter far beyond addiction. They help us seek food, safety, and connection. To study addiction is, in a sense, to study why we do anything at all.

Part of the process involves learning. When an experience feels rewarding, the brain learns to associate it with the things surrounding it. Eventually, a cue—a betting app, for example—can trigger anticipation and craving before someone has placed a bet. We call that cue reactivity.

David Erritzoe designed a scanner task to measure that response in gamblers. Usually you’d compare gambling cues to something neutral, like a washing machine. But with a future psilocybin trial in mind, we also added natural rewards like food, socializing, and nature, because people often report feeling more connected to others and to nature after psychedelic therapy. 

We haven’t published yet, but the task worked. Gamblers showed hyperactivation to gambling cues and, in some individuals, hypoactivation to natural rewards. Their ability to perceive anything in their world as more engaging than gambling is severely limited. 

We also saw structural differences, with greater volume in parts of the default mode network and less volume in reward circuits and the cortex. You’d expect that with alcohol, which destroys neurons, but not necessarily with gambling. Connectivity within the limbic system seemed reduced too. We only have one snapshot in time, so we don’t know whether those differences predispose someone to addiction or come from it.

Our working hypothesis is that addiction narrows what feels important or rewarding, and that psilocybin, alongside therapy, might help broaden that again. We call this “re-broadening of salience under psychedelics,” or RESUP.

It draws on ideas including Robin Carhart-Harris’s REBUS model and Ralph Metzner’s idea that addiction is a contraction of consciousness. The question is whether treatment can help people reconnect with parts of life that gambling has crowded out.

We’re also interested in control. Craving starts in the limbic system, which tells the body to go seek a reward. In most people, the frontal cortex steps in and says maybe not today. In people with addiction, that ability to shush the limbic system is reduced. We want those networks to sync up again, either in how they fire together or in the white matter that physically connects them. Psilocybin may help with the latter. There’s evidence that one high dose can change those white matter tracts. 

Control is a funny one, though. It works like a U-shaped curve. With too little control or too much, you won’t like who you are or what you do. The psychological sweet spot sits in the middle. Psychedelics might take someone from total rigidity all the way to complete surrender during the trip, and the hope is that they settle back into harmony afterward.

But flexibility alone isn’t the same as resilience. The hope is that therapy helps people turn a period of increased flexibility into lasting changes in daily life. That’s why we’re studying psilocybin alongside therapy.

Universities often do the early research in a new treatment area, supported by grants or philanthropy. That work can provide the foundation for pharmaceutical companies to fund larger trials, which is what happened with Imperial’s depression research and Compass Pathways.

But our team has rare expertise across both gambling addiction and psilocybin therapy delivery, so we wanted to co-develop the therapy and its pathway into NHS services, if the evidence supports it. 

Keeping the work closer to academia protects it from premature commercial exploitation and lets us shape how the treatment could reach patients. That said, we’re open to working with pharmaceutical partners, because taking a treatment through larger trials requires substantial resources. We’re working with Imperial’s technology transfer team to explore the route forward.

Our main commercial focus is a biomarker platform that could help predict who is likely to benefit from treatment. We’re collecting brain imaging, microbiome and blood data, metabolic profiles, neurocognitive test results, and speech samples for language analysis. We don’t yet know which measures, or combination of measures, will prove useful. That’s what we’re trying to establish.

At least half of people treated with psilocybin therapy don’t respond, going by Compass’ recent durability data. If you’re a patient, why go through that process if it might not work? We also need to understand what happens when someone doesn’t respond. Would a different kind or amount of therapy help? Would another treatment be more appropriate? Understanding non-response is just as important as understanding success.

They raise important questions about how we recognise gambling-related harm. Prediction markets and day trading are different activities, but I’m interested in where their features overlap with gambling: putting money at risk, anticipating an uncertain outcome, and repeatedly returning for another opportunity.

Calling an activity trading or investing doesn’t tell us whether someone’s relationship with it has become harmful. Clinically, I’d want to know whether they can stop, whether they’re chasing losses, and what effect it’s having on their finances, relationships, and daily life.

Money needs to be treated completely differently from other drugs. You don’t need to smoke or drink to survive, but you do need money. That’s what makes gambling addiction one of the most ferocious addictions I’ve ever seen. Many patients have been ravaged financially, and they have to recalibrate their relationship with the very thing that caused their downfall.

There’s a broader question here about technology and attention, too. So many digital products encourage us to keep checking and responding. I’d go as far as to say we’re all becoming somewhat addicted to our phones. I certainly am. It’s like a rampant evil in my pocket, waiting for me to respond.

I’d love to scan people while they doomscroll, give them a short-acting psychedelic like DMT, then scan them again to see if it works as a circuit breaker. Maybe some people just need a neural reset.

Learn about Imperial’s PsiloGambling study, now recruiting participants in the UK.

That’s all for today, Cyclists! Whenever you’re ready, here’s how we can help.

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DISCLAIMER: This newsletter is for educational and informational purposes only and is not intended as a substitute for professional medical advice. The use, possession, and distribution of psychedelic drugs are illegal in most countries and may result in criminal prosecution.