Pleasant Odors for Craving

(OdorCrave Trial)

Overseen By Michael A Sayette, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Psychoactive drugs

Disqualifiers: Neurological, Psychotic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study uses fMRI and behavioral measures in and outside the laboratory to investigate the neurobehavioral mechanisms underlying the impact of pleasant olfactory cues (OCs) on cigarette craving. The investigators plan to randomize 278 participants to a pleasant OC condition or an odor blank (neutral) condition and due to anticipated drop out expect to run 250 adult (half female) smokers, including both daily and nondaily smokers through the protocol. This study involves three visits. In the first visit, participants will complete a baseline breath carbon monoxide reading, a brief odor threshold test, and complete a series of self-report measures. In the next session, participants who are 8-hrs deprived of nicotine will undergo a 60-minute fMRI scan that will include structural, resting state, and task-based data collection. The fMRI task involves completing a series of tasks designed to index responses linked to key neural networks found to relate to addiction (e.g., reward processing, working memory). Participants will also be exposed to smoking cues to heighten craving and then depending on their condition (randomly assigned) will either receive a pleasant or neutral (odor blank) OC. In the third session, behavioral data will be collected to test the impact of either a pleasant or neutral OC on cigarette craving using self-reported urge and behavioral measures linked to craving. Finally, for pilot purposes designed to offer data for a subsequent clinical study (beyond this study), participants will additionally complete a 7-day ecological momentary assessment (EMA) protocol in which they will monitor cigarette craving and initial data will be collected outside the laboratory to evaluate the impact of OCs on naturally occurring craving. It is hypothesized that pleasant OCs will disrupt craving brain states and attenuate craving (as compared to neutral olfactory cues). Further, it is hypothesized that individual variation in neural responses to cognitive and affective tasks will reveal variation in mechanisms underlying pleasant OC craving reduction and that individual differences will moderate pleasant OC-induced craving relief. Finally, it is also expected that emotional responses to pleasant OCs will mediate the impact of OCs on craving and smoking-related processes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those with current psychoactive drug use and drug dependence outside of nicotine or caffeine.

What data supports the effectiveness of the treatment Pleasant Odors for Craving?

Research shows that pleasant smells can help reduce cravings, such as cigarette cravings, by providing a positive sensory experience that distracts from the urge. In one study, smokers who smelled pleasant odors reported less craving compared to those exposed to neutral or tobacco-related smells. ^{1 2 3 4 5}

Is it safe to use pleasant odors for reducing cravings?

The research does not provide specific safety data on using pleasant odors for reducing cravings, but studies on pleasant odors generally suggest they can improve mood and reduce hunger without reported adverse effects. ^{4 6 7 8 9}

How does the Pleasant Odor treatment differ from other treatments for cravings?

The Pleasant Odor treatment is unique because it uses pleasant smells to reduce food cravings by engaging the brain's limited-capacity resources, which is different from traditional methods that might involve medication or dietary changes. This approach leverages the brain's response to pleasant scents to curb cravings, offering a non-invasive and sensory-based alternative. ^{9 10 11 12 13}

Research Team

Marc N Coutanche, PhD

Principal Investigator

The University of Pittsburgh

Michael A Sayette, PhD

Principal Investigator

The University of Pittsburgh

Eligibility Criteria

This trial is for right-handed, English-speaking adults aged 18-49 who smoke cigarettes daily (10-30 per day) or nondaily. They must weigh less than 250lbs to fit in an MRI machine safely, have a working smartphone, and an intact sense of smell. Smokers with extreme habits or other drug dependencies besides nicotine or caffeine are excluded.

Inclusion Criteria

Fluent in English

No drug dependence outside of nicotine or caffeine

I weigh 250lbs or less and can safely undergo an MRI.

Exclusion Criteria

Individuals will also be excluded if they report any allergies to the odors used in our study

Baseline CO readings will need to be consistent with our criteria for daily and nondaily smokers for participants to be considered eligible. Specifically, we plan to rule out extremely heavy smokers (nondeprived CO > 55, for whom the smoking abstinence requirement may be too extreme to allow a sensitive test of our OC manipulation) and daily smokers with a nondeprived CO reading <10 PPM as this would raise concerns that they do smoke enough to be classified as a daily smoker.

I have a current neurological or psychotic disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants complete a baseline breath carbon monoxide reading, odor threshold test, and self-report measures

1 hour

1 visit (in-person)

fMRI Session

Participants undergo a 60-minute fMRI scan including structural, resting state, and task-based data collection

1 week after screening

1 visit (in-person)

Behavioral Session

Participants complete behavioral tasks to assess the impact of olfactory cues on cigarette craving

1 week after fMRI session

1 visit (in-person)

Ecological Momentary Assessment (EMA)

Participants monitor cigarette cravings over a 7-day period to evaluate the impact of olfactory cues on naturally occurring craving

7 days

Follow-up

Participants are monitored for safety and effectiveness after the main study procedures

4 weeks

Treatment Details

Interventions

• Odor Blank
• Pleasant Odor

Trial Overview The study tests if pleasant smells can reduce cigarette cravings more effectively than neutral odors. It involves three visits: baseline assessments, fMRI scans while exposed to smoking cues and either pleasant/neutral smells, and behavioral tests on craving responses. Participants will also track their cravings for a week using their smartphones.

Participant Groups

Group I: Pleasant Odor Experimental Treatment 1 Intervention

Participants in this condition will sniff the olfactory cue they rate as both pleasant (\>5 on the 1-9 scale) and the most intense following cigarette cue exposure. If this odor is the same as their self-reported preferred e-cigarette flavor, we will choose the next most intense odor out of the odors rated as pleasant.

Group II: Odor Blank Experimental Treatment 1 Intervention

Participants in this condition will sniff a neutral olfactory cue (odor blank) following cigarette cue exposure.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

Olfactory priming can reactivate a preference for chocolate in sated mice, suggesting that smells can trigger cravings even after a period of abstinence from palatable foods.

This study highlights the importance of olfactory cues in the relapse of maladaptive eating habits, indicating that addressing smell-related triggers could be crucial in treating eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory priming reinstates extinguished chocolate-induced conditioned place preference. La Mela, I., Latagliata, EC., Patrono, E., et al.[2019]

In a study involving 232 abstinent smokers, pleasant olfactory cues (OCs) were found to significantly reduce cigarette cravings compared to neutral or tobacco-related odors, with the effect lasting for at least 5 minutes.

Participants with stronger autobiographical memory systems responded better to the craving-reducing effects of pleasant OCs, suggesting that these cues could be a promising tool for smoking cessation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pleasant olfactory cues can reduce cigarette craving. Sayette, MA., Marchetti, MA., Herz, RS., et al.[2021]

Exposure to both pleasant and unpleasant odors significantly reduced the urge to smoke in nicotine-deprived smokers compared to a control odor (water), suggesting that olfactory stimuli can be a useful tool for craving reduction.

Odors that did not elicit negative facial expressions were more effective in reducing the urge to smoke, indicating that the emotional response to the odor may play a role in its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of olfactory stimuli on urge reduction in smokers. Sayette, MA., Parrott, DJ.[2019]

In a study with 29 healthy-weight females, smelling food odours that matched the taste (sweet or savoury) significantly increased appetite for similar-tasting foods compared to different-tasting or neutral foods.

The effect of food odours also extended to energy density, where odours signaling high or low energy density increased appetite for congruent food products, regardless of the participants' hunger state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food Odours Direct Specific Appetite. Zoon, HF., de Graaf, C., Boesveldt, S.[2022]

The study involving 19 healthy participants found that a congruent visual context enhances the perception of pleasant odors, specifically increasing the perceived flowery note of a floral scent, which could have implications for olfactory therapy in patients with smell disorders.

In contrast, unpleasant odors were not influenced by visual context, and incongruent visual cues disrupted odor sampling behavior, suggesting a protective mechanism against unexpected aversive stimuli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual Priming Influences Olfactomotor Response and Perceptual Experience of Smells. Manesse, C., Fournel, A., Bensafi, M., et al.[2021]

A study comparing acetone-exposed workers and naive controls revealed significant differences in how they perceived irritation from acetone, highlighting the influence of exposure history on irritancy judgments.

The perceived intensity of acetone's odor and individual response bias were key factors affecting reported irritancy, suggesting that both factors should be considered in evaluating chemical irritancy in workplace and experimental settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceived odor, irritation, and health symptoms following short-term exposure to acetone. Dalton, P., Wysocki, CJ., Brody, MJ., et al.[2019]

A field study near six odor-emitting plants revealed that the pleasantness of odors significantly affects community annoyance, with pleasant odors causing little to no annoyance, while neutral and unpleasant odors do lead to higher levels of annoyance.

The study established that the frequency of reported health symptoms was directly linked to odor annoyance, leading to modifications in existing guidelines for managing odor exposure in communities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odor frequency and odor annoyance Part II: dose-response associations and their modification by hedonic tone. Sucker, K., Both, R., Bischoff, M., et al.[2021]

The study found that the perception of food odors changes based on whether a person is hungry or satiated, with both fatty and non-fat food odors being rated as less pleasant and appetent when subjects were full.

The decrease in desire (appetence) for fatty food odors was more pronounced than for non-fat food odors, indicating that alliesthesia is more sensitive to the type of food odor, and that measuring appetence is a better way to understand how internal states affect reward perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alliesthesia is greater for odors of fatty foods than of non-fat foods. Plailly, J., Luangraj, N., Nicklaus, S., et al.[2016]

In a study with 90 participants aged 18 to 35, exposure to pleasant scents like baby powder and chocolate led to longer viewing times of images, improved mood, and reduced hunger ratings compared to no scent.

Specific odors influenced different outcomes: chocolate scent heightened arousal, while baby powder scent was associated with fewer reported health symptoms, indicating that pleasant odors can have both general and specific effects on mood and perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pleasant odors and congruency: effects on approach behavior. Knasko, SC.[2019]

A brief exposure to a neutral unfamiliar odor can significantly reduce cravings for highly desired foods, as shown in a study comparing olfactory tasks to auditory tasks and control conditions.

Specifically, the study found that smelling an odor reduced cravings for chocolate, suggesting that olfactory stimulation could be a useful strategy for managing unwanted food cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory stimulation curbs food cravings. Kemps, E., Tiggemann, M.[2020]

In a study with 24 healthy female participants, it was found that being satiated (full) significantly lowered the detection threshold for the food-related odor isoamyl acetate, meaning they could smell it better when full compared to when hungry.

While satiety decreased the pleasantness of the food odor, it did not affect the detection threshold for a non-food odor (n-butanol), suggesting that the state of satiety influences how we perceive food-related smells, which may play a role in controlling food intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety. Albrecht, J., Schreder, T., Kleemann, AM., et al.[2013]

In a study involving 21 women, exposure to palatable food odors for 20 minutes significantly increased both general appetite and sensory-specific appetite (SSA) without becoming satiating over time.

Food odors enhanced the desire for congruent foods (e.g., savory odors increased appetite for savory foods) while decreasing the appetite for incongruent foods, suggesting that the body prepares for specific types of food based on the odors present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odors: appetizing or satiating? Development of appetite during odor exposure over time. Ramaekers, MG., Boesveldt, S., Lakemond, CM., et al.[2021]

About 35% of neurons in the orbitofrontal cortex are involved in associating odors with tastes, indicating that our brain learns to connect what we smell with what we taste over time.

Neurons in this area also show decreased responses to foods we've eaten to satiety, which helps explain why we may lose interest in certain foods after eating them, while still responding to the smells of other foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rules of formation of the olfactory representations found in the orbitofrontal cortex olfactory areas in primates. Rolls, ET.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Olfactory priming reinstates extinguished chocolate-induced conditioned place preference. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Pleasant olfactory cues can reduce cigarette craving. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of olfactory stimuli on urge reduction in smokers. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Food Odours Direct Specific Appetite. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Visual Priming Influences Olfactomotor Response and Perceptual Experience of Smells. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Perceived odor, irritation, and health symptoms following short-term exposure to acetone. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Odor frequency and odor annoyance Part II: dose-response associations and their modification by hedonic tone. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Alliesthesia is greater for odors of fatty foods than of non-fat foods. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Pleasant odors and congruency: effects on approach behavior. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Olfactory stimulation curbs food cravings. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety. [2013]

12. England pubmed.ncbi.nlm.nih.gov

Odors: appetizing or satiating? Development of appetite during odor exposure over time. [2021]

13. England pubmed.ncbi.nlm.nih.gov

The rules of formation of the olfactory representations found in the orbitofrontal cortex olfactory areas in primates. [2019]