She watched herself from the corner. She saw herself pull a pack of cigarettes from the pocket of her favorite red coat. As she lit the cigarette, she watched as the smoking silhouette broke like shattered glass. She saw a thousand versions of herself staring back at her, inhaling and exhaling cigarette smoke. In that moment, she realized that smoking just one cigarette was committing to smoking a thousand more. When the psilocybin-induced trip subsided, she vowed to never smoke again.

This is just one experience amongst participants in a clinical study at Johns Hopkins University. Researchers conducting the study planned to determine if psilocybin, a substance that induces hallucinations, could help smokers break the habit (1). 

Long before they turned their sights to addiction, the research team wondered if psilocybin could provide meaningful, spiritual experiences. In 2006, the team published that under expert supervision, psilocybin-induced mystical experiences could have long-term positive effects. Eighty percent of participants reported increased well-being two months after the study completed (2). 

“I think [that psilocybin] has an ability to change behavior in the long-term and allow people to see things through a new lens,” said Matthew Johnson, a psychiatric researcher at the Center for Psychedelic and Consciousness Research at Johns Hopkins University. “It seems that the models that people have used to define how they behave in the world can be changed.”

Studies from the 1950s and 1960s indicated that psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin were promising candidates for addiction treatment, but further study was halted in the United States when the Controlled Substances Act was passed in 1970. The act classified psychedelic substances as schedule one substances, meaning that they were considered high risk for abuse and lacked any accepted medical applications. But after the Johns Hopkins study in 2006, psychedelics research entered a renaissance. 

In 2009, Johnson and his colleagues recruited fifteen smokers to participate in a fifteen-week trial to test if psilocybin could help smokers quit (1). Participants went through a month of preparation, where a psychiatric researcher developed a strong working relationship with the participant so that they became comfortable sharing formative and difficult life experiences. They employed cognitive behavioral therapy (CBT) to get a sense of the relationship between a participant and their smoking habit, why they want to stop, and any roadblocks preventing them from quitting. 

“They also keep a smoking diary, which is used as a tool to start contemplating the situations that prompt their smoking and the effect it has on them. It raises their awareness around the role that smoking plays in their life, and we can work out methods to replace smoking with alternate activities,” said Johnson.

After the initial CBT sessions, participants had three, seven-hour, medically supervised psilocybin-induced experiences spaced out over several weeks. The participants continued CBT every week before and after their experiences with psilocybin. More than 60% of the participants were non-smokers a year later (3).

Johnson and his team later reviewed the psilocybin-induced experiences the patients had to look for any commonalities (4). While the CBT employed beforehand seemed to influence their hallucinations to center around smoking, others had more general mystical experiences like those observed in the initial 2006 study conducted at Johns Hopkins University. Whether or not the hallucinations directly addressed the participant’s smoking habit, however, did not impact smoking cessation.

“We’ve had a lot of experiences where people have spiritual or unitive type qualitative features in their experiences,” said Albert Garcia-Romeu, a psychiatric researcher at the Center for Psychedelic and Consciousness Research at Johns Hopkins University, who also contributed to this study. “Those people are also having very positive effects, even in the absence of any kind of narrative, image, or memory related to smoking. That’s consistent with biological changes we’re seeing in the brain and the way that the brain is working, not only when people are under the influence of the drug.”

Alex Kwan, a neuroscientist from Yale University who was not involved in the smoking trials, recently reported that psilocybin “rewired” neurons in mouse brains within 24 hours of taking the drug, and these changes persisted for a month (5). Researchers previously hypothesized that psilocybin’s effects are mediated by serotonin, a hormone that regulates mood. Serotonin helps send messages between neurons through spine like extensions called synapses. 

Kwan found significantly increased growth in dendritic spines, which receive messages from synapses, after exposure to psylocibin. Researchers imaged the mouse brains every day for a month, and found that spine density and length increased by about 5% in just 24 hours, and capped out at about 10% increase over the course of two weeks. This increased growth persisted 34 days after the initial treatment with psilocybin.

“In addition to the immediate effect on the brain, maybe [psilocybin] changes the plasticity in the brain, which means it can change the brain’s architecture and function in a way that then sustains and mediates prolonged changes in behavior,” said Kwan. “This is strong evidence that this drug can promote plasticity in the brain.”

Psilocybin isn’t the only psychedelic shown to change neuroplasticity. 3,4-methylenedioxymethamphetamine (MDMA), commonly known as ecstasy, also enhances synaptic growth. The pharmaceutical company Awakn is using MDMA and derivatives they are developing in house to treat addictions to alcohol, opioids, and tobacco. 

David Nutt, chief research officer of Awakn, said that since MDMA doesn’t have the same intense, hallucinatory effect that psilocybin does, psychotherapy can be conducted while the person experiences the drug’s effect.

“That’s what makes MDMA rather different and interesting because when the brain is more malleable and most receptive, you can actually begin to get the person to engage in and think differently,” said Nutt. “It could be that MDMA turns out to be better than [psilocybin] in therapy because it actually allows you better engage with the therapist.”

Overall, Nutt thinks that psychedelics have the potential to treat the true cause of addiction: thinking patterns.

“Addiction has many different roots, but a single trunk. Cutting off one root isn't going to cure the problem. You've got to cut the tree down. This approach of disrupting the kind of core phenomenology is not only novel, but it might also be better,” said Nutt.

References

1. Johnson, M.W. et al. Pilot study of the 5HT2AR agonist psilocybin in the treatment of tobacco addiction. J. Psychopharmacol., 28, 983-982 (2014).
2. Griffiths, R.R. et al. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology (2006).
3. Johnson, M.W. et al. Long-term follow-up of psilocybin-facilitated smoking cessation. Am. J. Drug Alcohol Abuse, 43, 55-60 (2017).
4. Noorani, N. et al, Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts. J. Psychopharmacol., 32, 756-769 (2018).  
5. Shao, L-X. et al. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. 109, 2535-2544 (2021).