In the present study we report on the results of an exploratory survey on OTC CBD products. Beyond their use for promoting overall wellbeing, CBD products were commonly employed in the treatment of various medical conditions. This is consistent with other studies (Fortin et al., 2021; Moltke and Hindocha, 2021; Corroon and Phillips, 2018). The consumed CBD products were predominantly distributed through general retail channels and online markets. Unlike pharmaceutical CBD preparations, these OTC products are characterized by unclear composition and variability in their cannabinoid content (Liebling et al., 2022; Lindekamp et al., 2024). Moreover, the evidence base for their effectiveness and appropriate use remains limited, as few high-quality, well-controlled studies have been conducted in this area (Engeli et al., 2025). While many studies in cell cultures and pre-clinical animal models have demonstrated a range of promising effects of CBD, including anti-inflammatory and anxiolytic properties (Engeli et al., 2025; Atalay et al., 2019), these findings cannot be directly extrapolated to humans due to differences in pharmacokinetics, dosing, and the complexity of human diseases and behavior (Schwark and Wakshlag, 2023; Iffland and Grotenhermen, 2017). This creates a considerable knowledge gap, leaving both consumers and healthcare professionals with limited resources to guide informed decision-making regarding expected outcomes, dosage, or administration. As a result, it remains uncertain which effects, at what dosages, may arise from CBD itself, or from other bioactive compounds in the product. A meta-analysis of observational clinical studies in treatment-resistant epilepsy reported, for example that CBD-rich extracts were associated with better therapeutic outcomes and fewer adverse effects compared to purified CBD formulations (Pamplona et al., 2018).

A critical and still unresolved question is whether the doses commonly consumed in OTC CBD products are sufficient to produce genuine pharmacological effects, as current evidence does not provide a clear answer. Although our survey did not capture precise data on the amounts of CBD consumed, the study by McGregor et al. (2020) provides an indicative estimate of typical consumption levels among OTC CBD users. This study identified the highest-strength CBD products as 50 mg capsules and oils with 270 mg/mL CBD, resulting in likely daily CBD intakes of less than 150 mg. However, if one considers informal dosage guidelines frequently cited online - based on the classification by Leinow and Birnbaum (2019) - CBD doses between 0.5 mg/day up to 1500 mg/day are recommended, depending on the severity of symptoms (see also [10]). So far, clinical studies suggest that therapeutic benefits of oral CBD become apparent at doses of approximately 300 mg per day (Arnold et al., 2023), although further robust trials are needed to clarify effects at lower doses. Observational data from a cross-sectional study of 387 CBD users reported possible symptom improvements in anxiety and sleep disturbances at daily doses below 100 mg (Moltke and Hindocha, 2021). Similarly, a case series including 47 patients with anxiety and 25 with sleep disorders described improvements at doses as low as 25 mg/day when CBD was administered as adjunctive therapy (Shannon et al., 2019). In an open-label study sublingual treatment of N = 14 patients suffering from moderate-to-severe anxiety with a full-spectrum CBD product significantly improved the symptoms at a dose of around 35 mg/day CBD and 1 mg/day THC, while only minor adverse effects like sleepiness/fatigue, increased energy, and dry mouth were reported (Dahlgren et al., 2022). However, given the absence of placebo controls in these “low-dose effect” studies, the relative contribution of pharmacological effects versus expectation-driven placebo responses remains uncertain.

Placebo effects are well-documented across conditions involving subjective, brain-mediated symptoms such as pain, anxiety, stress, and sleep disturbances—all of which were reasons for CBD use in our study, but also in the studies reported from France (Fortin et al., 2021), United Kingdom (Moltke and Hindocha, 2021), and United States (Corroon and Phillips, 2018). Meta-analyses have consistently demonstrated substantial placebo responses in these domains. For instance, a meta-analysis by Peerdeman et al. (2016) demonstrated robust placebo effects in both acute and chronic pain, largely driven by expectation mechanisms. Likewise, placebo responses in anxiety and depression treatments have been estimated to account for up to 40% of the total treatment effect in clinical trials (Furukawa et al., 2016; Motta et al., 2023). Supporting this, a recent placebo-controlled study demonstrated that expectancy alone—the belief of having ingested CBD—was sufficient to increase sedation and attenuate stress responses during an acute stressor (Zhekova et al., 2024). Furthermore, reports of adverse effects such as dry mouth and tiredness, observed both in our study and in other surveys (Moltke and Hindocha, 2021; Corroon and Phillips, 2018), do not necessarily indicate pharmacological activity, as such symptoms are also commonly reported in placebo groups due to nocebo effects (Häuser et al., 2012; Zhekova et al., 2024). Given the widespread public association between CBD and such adverse effects, it is plausible that consumer expectations shaped both perceived benefits and adverse experiences.

For many endpoints investigated in our survey, about 40% of the participants reported an effect after the first CBD intake. While this could correspond to the known pharmacokinetics of CBD, including its half-life and T_max (Millar et al., 2018), it is also plausible that expectancy contributed to the rapid onset of perceived benefits, as placebo responses can manifest quickly, particularly in subjective symptoms such as stress, anxiety, or pain (Benedetti et al., 2011; Benedetti et al., 2022).

Importantly, CBD pharmacology and placebo mechanisms may converge at the neurobiological level. CBD interacts with the endocannabinoid system, which itself is involved in placebo-induced analgesia and stress reduction. Placebo responses in pain modulation have been associated with increased endogenous cannabinoid signaling, including elevated anandamide levels (Benedetti et al., 2011). Since CBD can enhance anandamide availability via fatty-acid amide hydrolase 1 (FAAH) inhibition (Mangiatordi et al., 2023), it is conceivable that both pharmacological effects of CBD and expectation-driven placebo mechanisms converge on the same neurobiological pathways (Pamplona et al., 2018). This overlap could help explain the perceived symptom improvements reported by participants at low CBD doses, where pharmacological activity might be limited, but expectancy effects are pronounced. Gertsch (2018) provides an insightful commentary on this, highlighting that the placebo effect plays a significant role in the perceived efficacy of medical cannabis and cannabinoids, as patient expectations can modulate outcomes via the endocannabinoid system (Gertsch, 2018).

It is important to note that a large majority of the survey participants claimed to be convinced of the health benefits of dietary supplements and expressed a strong belief in the positive effects of CBD. This could indeed indicate that consumer expectations may play a relevant role in the perceived benefits of these products, potentially amplifying placebo responses. The reported belief in the positive effects of CBD could have been a result of perceived positive effects or the belief itself contributed to the perception of effectiveness, again potentially reflecting a placebo response.

Most participants reported taking CBD independently of meals, which suggests that timing of intake has not been a primary consideration for consumers, or that they were unaware of the impact of food intake on CBD absorption. This is surprising since previous pharmacokinetic studies have shown that concomitant food intake, particularly high-fat meals, can significantly enhance systemic CBD exposure (Taylor et al., 2018). In line with this, participants more frequently reported CBD as ineffective when it was consumed more than 2 hours after meals or one to 2 hours before meals. While sublingual administration of CBD is intended to allow absorption through the oral mucosa, recent studies indicate that in practice, much of the CBD may be swallowed before significant mucosal absorption occurs (Johnson et al., 2024). This means that gastrointestinal absorption indeed becomes the predominant route, making factors like food intake relevant to CBD bioavailability. Many consumers used CBD products without professional guidance and relied far more on scientific literature as well as brochures than on consultations with healthcare professionals. In an environment saturated with promotional claims and low-quality studies, it remains uncertain whether lay consumers are able to reliably distinguish between high-quality scientific evidence and less robust information. However, it is also questionable whether healthcare professionals could have provided competent advice on these products, given the variability in product composition and the limited clinical data available for OTC CBD formulations. Future research should investigate the sources consumers consider credible and the criteria they apply to assess scientific validity. This could help to better understand the effect of information (e.g., impact of positive or exaggerated claims about CBD) on perceived CBD effects.

Interestingly, regardless of their level of background knowledge, most participants in our survey expressed no doubt about the safety of the CBD products. This observation concurs with the results from Geppert et al., where survey participants associated CBD consumption with low risk (Geppert et al., 2023). However, this stands in contrast to current scientific and regulatory evaluations, such as the recent review by Engeli et al. (2025), and the joint position paper by the EFSA and United Kingdom authorities (Advisory committee on novel foods and processes and its CBD subcommittee, 2023), both of which highlight substantial uncertainties and potential health risks associated with CBD, particularly concerning liver toxicity and insufficient data on long-term safety. Considering that a high proportion of our survey participants were chronic CBD users and used it at least once a day, this gap between public perception and scientific assessment highlights the importance of evidence-based information strategies to support informed consumer choices.