New study on psilocybin for smoking cessation
If you follow the scientific literature on smoking cessation, you usually see the same pattern recurring. There are aids that do help, but long-term success often remains limited. Precisely for this reason, this new pilot study on psilocybin for nicotine addiction is so interesting. In this study, a single high dose of psilocybin, combined with a structured cognitive behavioural therapy programme, worked clearly better than nicotine patches with the exact same behavioural therapy programme. That is important, because here the comparison was not just with a placebo, but with an existing and accepted treatment.
In this study, psilocybin worked better than nicotine patches
The study was conducted at Johns Hopkins Bayview Medical Center in Baltimore and was published in JAMA Network Open on 10 March 2026. It was a pilot randomised clinical trial. The participants were psychiatrically healthy adult smokers. A total of 82 people took part. The average age was 47.6 years, they smoked an average of 15.7 cigarettes per day, and the median history was six previous quit attempts. The participants were randomised into two groups: 42 people went into the psilocybin group and 40 people into the nicotine patch group.
Both groups received not only a treatment, but also a comprehensive 13-week, manually developed CBT smoking cessation programme. That makes this study stronger, because the effect of psilocybin was not investigated in isolation from guidance, but rather within a therapeutic trajectory. On the target quit date in week 5, the psilocybin group received a single high dose of psilocybin of 30 mg per 70 kg of body weight. On that same quit day, the nicotine patch group started an FDA-approved nicotine patch schedule of 8 to 10 weeks. People who smoked more than 10 cigarettes a day started with 21 mg per day for six weeks, followed by 14 mg per day for two weeks, and then 7 mg per day for two weeks. Lighter smokers received a lower schedule.
The study mainly looked at biochemically verified prolonged abstinence after six months. That is important, because people were not simply taken at their word. Researchers verified abstinence using, among other things, exhaled carbon monoxide en urinary cotinine, a nicotine breakdown product. For the primary outcome, a two-week grace period after the quit date. After that, continued smoking was counted as a relapse. The analysis was moreover a intention-to-treat analysis, meaning that participants who dropped out or were no longer reachable were counted as non-abstinent. That makes the results less inflated and therefore more reliable.
After six months, 40.5 per cent of the psilocybin group were biochemically confirmed to be long-term smoke-free, compared with 10.0 per cent in the nicotine patch group. For the second key measure, namely 7-day point prevalence abstinence, this was 52.4 per cent versus 25.0 per cent. Statistically translated, this meant that the psilocybin group had more than six times higher odds of long-term abstinence than the nicotine patch group, with an odds ratio of 6.12. For 7-day abstinence, the odds ratio was 3.30. The psilocybin group also scored better when looking at daily cigarette use between the quit date and six months later. The model estimated an average of 1.69 cigarettes per day for the psilocybin group compared with 3.64 cigarettes per day for the nicotine patch group, which is approximately 53.7 per cent fewer.
The result was remarkably strong
Even just after the quit day, a difference could already be seen. On the day after the target quit date, [they/it] reported 90.5 per cent of the psilocybin group that they had not smoked for at least 24 hours, compared to 80 per cent in the nicotine patch group.
That in itself doesn't yet say everything about the long term, but it does show that the start of the quitting process in the psilocybin group was powerful.Â
See also the image.
What makes this study extra interesting is that the nicotine patch group did not perform poorly compared with the literature. In the discussion, the authors refer to a recent meta-analysis in which standalone nicotine replacement therapy yielded approximately 8 per cent long-term abstinence and roughly 20 per cent 7-day point prevalence abstinence after six months. In this study, the nicotine patch group achieved 10 per cent and 25 per cent, which indicates that the control group was credible. This makes psilocybine's advantage more serious.
Why this study impresses, but is not yet the final word
This research is strong because it makes a direct comparison with an existing standard treatment, because both groups received CBT, because abstinence was biochemically verified, and because dropouts were not swept under the rug in the analysis. At the same time, one must also be honest about the limitations. It was a pilot study, so it was still relatively small. The study was not blinded, which is practically almost unavoidable with psychedelics. Moreover, the participants were psychiatrically healthy, predominantly white, and relatively often highly educated, and 64.6 per cent had previously used classical psychedelics. That limits the generalisability.
There is another important point. The psilocybin group also received more contact time during the course of the treatment. Across the entire study, participants in the psilocybin group spent a median of 29.6 hours in treatment contact, compared to 16.8 hours in the nicotine patch group. The authors explain that this difference was mainly due to the 8 to 9-hour psilocybin day and the debriefing the following day. This means that part of the benefit may not come solely from the substance itself, but from the combination of the intensive experience, extra therapeutic attention, and meaning-making. That is precisely what is also of interest to us, as it fits the idea that the session is not separate from preparation and integration, but interwoven with it.
What this study means for the Triptherapie vision
This smoking cessation study aligns remarkably well with how we at Triptherapie have long viewed addiction. In our previous explanation about psilocybin and nicotine addiction, it is explained that psilocybin, after conversion into psilocin, acts on 5-HT2 receptors, and that stimulation of 5-HT2A receptors is associated with increased BDNF, more new connections and new choices. In addition, especially with addictions, we focus on how preparation for the session is much more important than people often think, because that preparation influences the psyche, neurochemistry, the body and ultimately the outcome of the session. That is precisely the kind of model that this JAMA study, although not identical, now lends extra credibility to.
The question then becomes not only whether psilocybin works, but also how best to prepare someone for such a change. That is where the supportive factors come into the picture. Not as a replacement for psilocybin, and not with the same level of evidence, but as potential enhancers of calm, resilience, stress regulation and sustainability.
What extra can you do?
At Triptherapie we believe in the synergy of psychedelics with lifestyle coaching, talk therapy, supplements and good preparation plus integration. In this article, we are therefore happy to provide a theoretical foundation for various supplements that can support quitting smoking. This is a selection of the possibilities within our holistic protocols.
GABA as an inhibitory counterpart to restlessness and craving
GABA is a neurotransmitter with an inhibitory function on the nervous system. That page states that in cases of overactivity, GABA can provide calm, reduce stress and anxiety responses, and also plays a role in relaxation and falling asleep. This makes GABA relevant for smokers who smoke not only for nicotine, but also to dampen inner tension.
The neurobiology of nicotine also points in that direction. Nicotine affects not only dopamine, but also glutamate and GABA in the mesocorticolimbic circuits. In the VTA, nicotine stimulates both glutamatergic and GABAergic terminals, but due to rapid desensitisation of certain nicotinic receptors on GABA neurons, the balance ultimately shifts relatively towards dopamine release. Reviews therefore describe that greater GABA transmission or less glutamate transmission can reduce the rewarding effect of nicotine and cue-induced nicotine seeking.
That does not mean that a GABA supplement by itself is a proven smoking cessation treatment. It does mean that the GABA pathway makes sense as a supportive layer. Furthermore, there are also ways to make GABA work better, such as nutrition, supplements, walking in nature, meditation, cuddling, music and dance. Before experimenting with GABA yourself, you should be careful with benzodiazepines, barbiturates, antidepressants or alcohol. This can cause problems, so good advice is important here.
Vitamin B6 as a potential supplement for greater anxiety reduction
Vitamin B6 is interesting because it is involved in the synthesis of GABA. In a double-blind, placebo-controlled study in young adults, participants were given 100 mg of vitamin B6 or a placebo daily for 30 to 35 days. The study included 478 young adults, with 265 participants available for anxiety measurements. B6 reduced self-reported anxiety, increased visual surround suppression, and the authors conclude that their results suggest that high-dose vitamin B6 increases inhibitory GABAergic neural influence.
Source: High-dose Vitamin B6 supplementation reduces anxiety
This is not direct proof for nicotine addiction, because this was not a smoking cessation study. However, in terms of content, it is relevant. Part of smoking behaviour is driven by anxiety or tension. If B6 can slightly strengthen the inhibitory side of the system, it is biologically plausible that this could reduce the need for nicotine as a sedative. The step from less anxiety to reduced urge to smoke It remains a hypothesis, not a proven causal link.
Arginine as a potential GABA enhancer
Arginine comes into the picture via an animal study from 2002. In that study, rats were looked at to see whether L-arginine via nitric oxide could increase the permeability of the blood-brain barrier to GABA. GABA alone increased brain GABA, L-arginine alone did so too, and the combination of GABA plus L-arginine produced a much greater increase. When beforehand a ACE inhibitor was administered, that effect largely disappeared. The authors concluded that high NO concentrations following L-arginine can increase the passage of peripheral GABA into the brain.
Source: Nitric oxide production increases gamma-amino butyric acid permeability of blood-brain barrierÂ
That is not direct proof either that arginine helps smokers to quit, but it is an interesting mechanistic argument for including arginine in a hypothesis regarding inhibition, rest and tension regulation. In addition, there is also human research in which a combination of L-lysine and L-arginine, both 2.64 grams per day for one week, in a randomised, double-blind, placebo-controlled study in 108 healthy adults reduced both trait anxiety and stress-induced state anxiety. In men, basal cortisol and chromogranine A also decreased. This was not about smoking and not about arginine alone, but it does support the idea that this pathway can affect stress sensitivity and potentially help with stress-related smoking addictions.
For us, arginine therefore fits primarily as a potential support in the preliminary stage, rather than as a primary treatment. Particularly for people who smoke out of nervousness, alertness, or a hyperactive system, this could be substantively interesting, but the level of evidence is clearly lower than with psilocybin.
DHEA as a factor in stress, negative affect and relapse
DHEA and DHEAS are substances in the body that are probably mainly concerned with how well someone deals with stress, how someone feels and how great the likelihood of relapse is. Therefore, they are of interest in addiction, even though they are not the sole explanation for everything.
In smokers, researchers observe that higher DHEAS levels often coincide with fewer gloomy or tense feelings and less craving for nicotine. There are also studies showing that the ratio of DHEA to cortisol during smoking cessation can say something about relapse. If this ratio changes unfavourably during the first days without a cigarette, the chance of someone starting to smoke again in the following week appears to be greater. At the same time, it is not as simple as DHEA alone determining whether someone relapses. It rather appears to be part of a bigger picture of stress, mood and recovery.
Sources: Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers | Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users
The strongest evidence that DHEA might help comes from research in people with multiple addictions at the same time. In that study, participants were given 100 mg of DHEA or a placebo every day for a month. The DHEA group felt less negative during the treatment and also used addictive substances less often in the months that followed. That study was not specifically about smoking, but it does show that DHEA might help with a smoking addiction, particularly regarding stress, mood and relapse
Combine everything with lifestyle changes
At Triptherapie, therefore, you are also helped with your lifestyle. This goes beyond just some general tips. It also involves balancing neurochemistry with nutrition, supplements and practical advice that suits your situation. Think about supporting neurotransmitters such as GABA, serotonin, dopamine and acetylcholine, so that the nervous system can become calmer and more stable. Precisely that more stable foundation can ensure that you are less likely to reach for nicotine in moments of stress, restlessness or fatigue.
The aim of that is not to replace smoking with lifestyle alone, but to reduce the underlying vulnerabilities. If you sleep better, have fewer energy fluctuations, experience more peace of mind and are better able to recover emotionally, it becomes easier to let go of old patterns. Lifestyle coaching thus forms a strong foundation for the entire process. Not only to enter a session better prepared, but also to better maintain the change afterwards.
Conclusion
Psilocybin currently provides the strongest scientific signal regarding smoking addiction. In this comparative study, psilocybin even worked better than nicotine patches. That is striking and deserves serious attention. At the same time, this subject also shows that good preparation can make a big difference. GABA is particularly suited to greater calmness and less restlessness. Vitamin B6 may possibly help to support that calming GABA effect. Arginine is interesting because it might influence stress and the way GABA works. DHEA appears to be especially important in cases of low mood, tension and the risk of relapse. Lifestyle coaching helps to make the body and brain stronger and more stable, so that change is easier to sustain.
Therefore, the fairest conclusion is not that all these components together are already proven to form a single fixed treatment. What we can say is that these factors together form a logical and strong whole, and that in practice we see a lot of progress when combining these elements. Individually, the separate components focus on more calm, less stress, a better neurochemical balance, and breaking old patterns. Within that, psilocybin is currently the component with the strongest directly proven effectiveness, and yet we believe in a better holistic approach. Precisely for this reason, an approach involving preparation, lifestyle, guidance, and integration fits so well with smoking cessation.
Make use of our protocol
At Triptherapie, therefore, we do not work with just a standalone session, but with a protocol in which multiple elements come together. We look at safety, intake, lifestyle, neurochemical balance, intention, guidance during the session, and subsequent integration. That makes the approach suitable for people who do not just want to stop temporarily, but want to understand why the addiction arose and how they can maintain a new direction.
If you would like to use the Triptherapie protocol for addiction or smoking addiction yourself, you can sign up for an intake and work out together which form of guidance suits you best. This will help assess whether a programme involving lifestyle coaching, preparation and a guided psychedelic session is a suitable step for you.
Reviews about addiction
Anyone who wants to quit smoking or break another addiction often benefits more from relatable real-life stories than from theory alone. That is why below you will also find nine previous experiences of people for whom addiction, dependency or stubborn habitual patterns played a significant role. In those stories you can read how preparation, lifestyle, guidance during the session and integration together can make all the difference. It is precisely this combination that often ensures that an insight does not just remain a fleeting moment, but can truly resonate in daily life.