Is there any literature to support the use of cannabidiol (CBD) for smoking cessation?

Comment by InpharmD Researcher

There are limited data examining the use of cannabidiol (CBD) for tobacco smoking cessation. Cannabidiol is not currently recommended in practice guidelines. Studies exploring the potential of CBD in smoking cessation are generally focused on marijuana smoking cessation. Studies examining tobacco cessation are limited to pilot studies or single-dose studies. At this time there is not enough evidence to routinely recommend CBD for tobacco smoking patients attempting to reduce the number of cigarettes or abstain from smoking.
Background

The World Health Organization, U.S. Centers for Disease Control and Prevention, and the American Cancer Society each recommend nicotine replacement therapy (NRT) as first line therapy for tobacco cessation. In addition, they note vaping is not a suitable substitution for cigarette smoke as it also has carcinogenic effects. [1,2,3] Current smoking cessation clinical guidelines and recommendations do not mention cannabidiol (CBD) as a therapeutic option. However, the National Institute on Drug Abuse does stress that marijuana products, those containing tetrahydrocannabinol (THC), should not be utilized. [4]

A 2021 review of available evidence in the use of cannabidiol in substance use found 3 studies (see tables 1 and 2) of CBD in tobacco smoking cessation or current tobacco smokers. However, these studies did not meet the review’s inclusion criteria as they either lacked direct comparison with control group, and/or utilized surrogate markers as the only measured outcomes. [5] The third study identified in the review used a single dose of CBD and did not find any change in verbal or spatial working memory, or impulsivity during tobacco abstinence. [6]

References:

[1] World Health Organization. WHO report on the global tobacco epidemic 2019: offer help to quit tobacco use. https://www.who.int/publications/i/item/9789241516204 Updated July 27, 2019. Accessed October 11, 2021.
[2] Centers for Disease Control and Prevention. Cessation Materials for State Tobacco Control Programs. https://www-cdc-gov.libpublic3.library.isu.edu/tobacco/quit_smoking/cessation/index.htm Updated September 20, 2020. Accessed October 11, 2021.
[3] American Cancer Society. Nicotine Replacement Therapy to Help You Quit Tobacco. https://www.cancer.org/healthy/stay-away-from-tobacco/guide-quitting-smoking/nicotine-replacement-therapy.html Accessed October 11, 2021.
[4] National Institute on Drug Abuse. Tobacco/Nicotine and Vaping. https://www.drugabuse.gov/drug-topics/tobacconicotine-vaping. Accessed October 11, 2021.
[5] Morel A, Lebard P, Dereux A, et al. Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers. Front Psychiatry. 2021;12:565617. doi:10.3389/fpsyt.2021.565617
[6] Hindocha C, Freeman TP, Grabski M, et al. The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers. Sci Rep. 2018;8(1):7568. Published 2018 May 15. doi:10.1038/s41598-018-25846-2

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is there any literature to support the use of cannabidiol (CBD) for smoking cessation?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


 

Cannabidiol Reduces Cigarette Consumption In Tobacco Smokers: Preliminary Findings

Design

Randomized, double-blind, placebo-controlled, pilot study

N= 24

Objective

To assess the impact of ad-hoc use of low dose cannabidiol (CBD) in an inhaler form on nicotine addiction in tobacco smokers who wished to stop smoking

Study Groups

CBD inhaler (n= 12)

Placebo (n= 12)

Inclusion Criteria

Patients aged 18-35, who smoked at least 10 cigarettes per day, and expressed an intention to quit smoking using the "Taking Steps To Quit" brief screen, no history of psychiatric, substance misuse, or physical health problems, and not pregnant

Exclusion Criteria

N/A

Methods

Participants were screened prior to randomization and responded to a text message with their daily cigarette use for the week before their first visit to the study center. Participants also attended the study center on two days separated by a week.

On the first of these days, demographics and baseline carbon monoxide levels were measured (at least one hour after attempting to quit). They were also briefly counseled for ten minutes on smoking cessation. Participants were also instructed on how to use the inhaler and when to use it. Participants' dependence was measured using the Spielberg Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). Trait impulsivity was measured using the Behavior Impulsivity Scale (BIS). Participants were tracked daily via text messaging and were reminded to detail inhaler use and cigarette smoking in a diary.

During the week between the two testing days, patients were reminded daily via text message to enter details of cigarette and inhaler use in their diary and required to respond via text message with the number of cigarettes, level of craving for cigarettes, and the number of times they had used the inhaler. On the second day of testing, participants repeated measurements of mood and craving similar to what was done on the first day. Participants also kept a daily diary for the two weeks following the second day of testing and were then telephoned one final time. During the two-week, in-between period, participants also responded to a 1-100 scale of momentary subjective craving as another data point.  

CBD or placebo was administered via pressurized metered-dose inhaler as 400 mcg of cannabidiol or placebo. 

Duration

One-week treatment period, two week follow-up period. 

Outcome Measures

Primary Outcome: number of cigarettes smoked

Secondary Outcome: nicotine craving, anxiety and mood

Baseline Characteristics

 

CBD

Placebo

 

Age, years

28.00 ± 4.29 28.08 ± 6.17  

Female

6 (50%) 6 (50%)  

Mean cigarettes smoked per day

18.20 ± 3.42 16.54 ± 2.67  

Mean years smoked cigarettes 

14.25 ± 5.95 11.33 ± 4.23  

Both groups were balanced for gender with no differences in age, IQ, baseline smoking variables of cigarettes per day, years of cigarette smoking, and Fagerstrom scale of nicotine dependence score and there were no significant group differences in BDI score, BIS score, SDS score or STAI score. 

Results

Endpoint

CBD

Placebo

p-Value

Number of cigarettes smoked 

During Treatment Week: Decrease in CBD group (p = 0.002 CBD pre versus CBD post) but no difference in the placebo group. (Raw data not presented; figure only.)

At 2 week follow up: Significant decrease in CBD group (0.034)

Not available Not available 

 

NS; (0.054 treatment week) 

Nicotine Craving

ANOVA measures found no main effect of treatment or interaction. Planned comparisons also revealed a significant reduction in craving in both groups Day 1–Day 7 (p < 0.001) but no difference between Day 1 and Follow-up.

Not available Not available NS

Anxiety and Mood 

Comprised of 2 × 2 repeated measures ANOVA of MRS (Sedation, Depression, and Anxiety) scores

For sedation scores on the MRS there was a trend for a main effect of Time [F(1,22) = 3.88, p = 0.084] reflecting more sedation in both groups on the second testing day, but no main effect of treatment or interaction on this day. Analysis of depression scores revealed no specific main effects of time or treatment or interaction.

Adverse Events

Not reported

Study Author Conclusions

Over the treatment week, placebo-treated smokers showed no differences in number of cigarettes smoked. In contrast, those treated with CBD significantly reduced the number of cigarettes smoked by ~40% during treatment. Results also indicated some maintenance of this effect at follow-up.

InpharmD Researcher Critique

As this study was published as a short communication, minimal quantitative data were recorded and/or shared. While a significant decrease occurred in number of cigarettes smoked during the treatment week (CBD pre versus post), the results were not significant compared to placebo. This study demonstrates potential interest for further study, but at this time it does not provide support for routinely recommend CBD as an option for smoking cessation. 



References:

Morgan CJA, Das RK, Joye A, Curran HV, Kamboj SK. Cannabidiol reduces cigarette consumption in tobacco smokers: Preliminary findings. Addictive Behaviors. 2013;38(9):2433-2436.

 

Cannabidiol Reverses Attentional Bias to Cigarette Cues in a Human Experimental Model of Tobacco Withdrawal

Design

Randomized, double‐blind, cross‐over study

N= 30

Objective

To investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette‐related stimuli and increased craving and withdrawal; and (2) cannabidiol (CBD) in comparison to placebo, would attenuate AB, pleasantness of cigarette‐related stimuli, craving and withdrawal and not produce any side effects

Study Groups

CBD (n= 15)

Placebo (n= 15)

Inclusion Criteria

Age 18-50 years, smoke ≥ 10 cigarettes/day for at least the last year, Fagerström Test for Nicotine Dependence (FTND) score ≥ 4 (indicating moderate dependence), smoking the first cigarette within an hour of waking, negative drug urine screen for all major drugs of abuse at baseline. Participants were cigarette dependent but non treatment seeking. 

Exclusion Criteria

Use of nicotine replacement therapy/cessation pharmacotherapy, self‐reported recent use of cannabis or other illicit drugs, recent (past 4 weeks) or ongoing use of e‐cigarettes, current mental or physical health issues or learning impairments, pregnancy or breastfeeding, allergies to CBD, gelatine, lactose, microcrystalline cellulose or chocolate

Methods

Patients smoked as normal prior to the first session. Following this, they attended two sessions after overnight (approximately 12 hours) abstinence. Patients were administered one dose of oral 800 mg CBD [pure synthetic (−) CBD, STI Pharmaceuticals, Brentwood, UK] or placebo. Treatment order was randomized. The minimum washout period between sessions was one week. Various assessments were performed. Visual probe task was used to measure attentional bias via images of smoking versus composition matched neutral images. Pleasantness rating task utilized a cigarette or natural cue to assess patients' ratings of pleasantness of each image on a scale of -3 (very unpleasant) to 3 (very pleasant). Withdrawal was assessed with the Mood and Physical Symptoms Scale (MPSS). Craving was assessed with Questionnaire of Smoking Urges–Brief (QSU‐B). Nicotine dependence was assessed using FTND. State–Trait Anxiety Inventory (STAI) was used to assess anxiety, and the Beck Depression Inventory (BDI) was used for depression. 

Duration

Three sessions, mean of 7.85 ± 2.77 days between sessions

Outcome Measures

Tobacco abstinence, pleasantness of cigarette images, craving, withdrawal, systolic blood pressure

Baseline Characteristics

 

All participants (N= 30)

 

 

Age, years

28.07 ± 8.66     

Female

14 (46%)    

FTND score

5.56 ± 1.13    

Cigarettes per day

13.5 ± 2.39    

Time to first cigarette (min)

25.5 ± 15.87    

Years smoked

9.55 ± 7.36    

Years smoking ≥ 10 cigarettes/day

8.17 ± 7.08    

Life‐time quit attempts

3.2 ± 3.91    

Most successful quit attempt (days)

100.48 ± 163.47    

Results

Endpoint

CBD

Placebo

p-Value

Tobacco abstinence 

36.47 ms 45.15 ms 0.001

Pleasantness of cigarette images

- 0.51 -- 0.011

Systolic blood pressure

-- +3.40 mmHg NS (95% CI = 0.72–6.08)

Craving and withdrawal values were not significant and unaffected by CBD. 

Adverse Events

Common Adverse Events: headache (n=1)

Serious Adverse Events: none

Percentage that Discontinued due to Adverse Events: none

Study Author Conclusions

After overnight tobacco abstinence, cigarette smokers administered 800 mg CBD, in comparison to placebo, show a reduced salience and pleasantness of cigarette cues, in the absence of any reductions in withdrawal or craving. This study highlights the potential utility of CBD as a treatment for specific neurocognitive components of tobacco use disorder, and suggests that one potential mechanism by which CBD may exert its effects on addiction is via a reduction in the salience of drug cues. These results support the growing literature regarding CBD in the treatment of addictive disorders.

InpharmD Researcher Critique

This was a very short study, with only one dose of CBD given in participants who were non-treatment seeking. It is unclear whether the magnitude of change between statistically significant results have any clinical relevance. The results of this study cannot be extrapolated to the long-term efficacy of CBD for smoking cessation or to patients who have demonstrated a willingness to quit smoking. 



References:

Hindocha C, Freeman TP, Grabski M, et al. Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal [published online ahead of print, 2018 May 1]. Addiction. 2018;113(9):1696-1705. doi:10.1111/add.14243