A new study from Spain, titled Future Treatments for Tobacco Dependence (Jimenez-Ruiz, 2026), takes a look at various advances that might help people quit smoking over the next few years. The literature review contains a few of the usual suspects, some novel approaches, and a glaring exclusion of the best-supported way to quit cigarettes.
The paper
While the paper falls short in some ways, it’s still very interesting. Here is a quick summary of what it’s about.
It’s a narrative review that brings together earlier trials, observational studies, systematic reviews and biological research to identify useful next steps. The authors suggest they looked at data from the last 10 years, but didn’t have predefined inclusion criteria or a formal quality-appraisal process. As such, there is an element of selectivity about which papers made the cut.
They suggest that the established treatment framework combines psychological counselling with one of the following:
Nicotine replacement therapy, or NRT.
Varenicline.
Cytisinicline.
Bupropion.
From there, they look at the data to find out which dose, duration, formulation and combination works best for individual smokers, before asking whether additional interventions can improve the result.
Various treatments
Here is a quick rundown of what the selected literature says about the various treatments.
Psychological counselling
The authors suggest psychological counselling plus medication is the core clinical approach. The thinking here is that counselling addresses behavioural aspects, while the medication treats the biological components.
Cytisinicline
Cytisinicline is a partial agonist at nicotinic acetylcholine receptors. In simple terms, it stimulates receptors involved in nicotine dependence sufficiently to help reduce withdrawal and support quitting.
The paper cites studies that suggest one in six smokers receiving 12 weeks of cytisinicline remained abstinent at six-month follow-up. However, other studies are far less effective.
Varenicline
Varenicline works similarly to cytisinicline. The paper cites a couple of studies that compare the two, and cytisinicline scores 11.7% and 12.1% six-month abstinence rates, while varenicline is successful 13.3% and 7.9% of the time.
NRT
Some of the available nicotine replacement therapies (NRTs) include patches, gum, lozenges, nasal spray, oral spray, and inhalers.
Unfortunately, the paper doesn’t provide a six-month quit rate comparison for these products to go head-to-head with cytisinicline or varenicline. However, it does quote numerous trials that compare NRT with placebo, and the aggregate scores place oral/mouth spray as the highest at 148% more effective, with gum the lowest at 48%.
Cochrane’s comparative estimates suggest that single-product nicotine replacement therapy helps roughly eight or nine people in every 100 quit for six months or longer.
Bupropion
Bupropion features in the literature, but evidence is limited. However, the researchers earmark it for future trials, especially for people who want to quit vaping or heated tobacco products (HTPs).
Novel formulations of existing drugs
The paper also mentions a few novel ideas under pharmaceutical innovation, including:
Cytisinicline oral solution
New formulations of cytisinicline or varenicline.
A dry-powder formulation containing tryptophan and tyrosine, which are precursors of serotonin and dopamine.
It’s important to remember that these novel variants don’t have clinical data, but may be promising or more effective than current solutions in the future.
Vaping and heated-tobacco cessation medicines
As vaping and HRT have eaten some of smoking’s marketshare, there is increased interest in ways to give up these lower-risk products. Again, solid research is thin on the ground, but some studies cited in the paper include:
Nicotine mouth spray that reduced vape-related cravings.
Varenicline trials that outperformed placebo quit rates at three-months (2.67) and six-months (2.52).
A cytisinicline for vaping trial using 3 mg every eight hours for 12 weeks that had limited success.
Totally novel approaches
Then, things get more interesting, as the paper highlights some fairly out of the box solutions that are being considered or developed.
Some standout ideas include:
Non-surgery stimulation of brain networks involving the insula and dorsolateral prefrontal cortex. These regions contribute to craving and dependence-related behaviour.
Using nicotine metabolite ratio testing to see how quickly someone metabolises nicotine. It could help a doctor match a smoker to the treatment most likely to work, rather than choosing a medicine and seeing what happens.
The use of GLP-1 receptor agonists to modulate two interacting systems: one involved in nicotine reward and another involved in aversion to nicotine.
Again, these ideas are in early stages, but it does give a taste of what the future of smoking cessation could look like.
A glaring absence
The fact that vaping is almost lumped into the same category as smoking should give you a clue about the ideological stance of the authors. Indeed, they are not really considered as a method to help smokers quit combustible cigarettes, which is a shame, because there is a lot of research that suggests they are the best supported way to quit.
Some studies work reading include:
E-cigarettes compared with nicotine replacement therapy within the UK Stop Smoking Services: the TEC RCT (Hajek, 2019)
Vaping produced an 18% one-year quit rate compared to 9.9% for NRT.
Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses (Lindson, 2023)
In a 2023 Cochrane review, vaping (2.37) had a higher odd ratio than Cytisine (2.21) and Varenicline (2.33). The difference is modest yet still interesting.
Electronic cigarettes for smoking cessation (Lindson, 2026)
Another Cochrane review that looked at 11 trials and found vaping had a 61% higher relative likelihood of quitting when compared to NRT.
Final thoughts
I really liked the paper because it understands that personalisation is at the heart of lowering smoking prevalence. Matching treatments to each smoker and exploring different pathways that could work for them makes sense.
However, while the paper focuses on NRT and medicines, there is a proven, effective, and theoretically low-cost option on the market in vaping. If health bodies are serious about lowering smoking rates, vaping should be part of this personalisation, too.
