Addictive Behaviors 38 (2013) 24332436

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Addictive Behaviors

Short Communication

Cannabidiol reduces cigarette consumption in tobacco smokers:

Preliminary ndings
Celia J.A. Morgan , Ravi K. Das, Alyssa Joye, H. Valerie Curran, Sunjeev K. Kamboj
Clinical Psychopharmacology Unit, University College London, London, UK

H I G H L I G H T S
We examined whether cannabidiol could impact on cigarette consumption.
Ad hoc use of CBD but not placebo reduced cigarette consumption over a week.
Drugs that alter the endocannabinoid system may be effective treatments for nicotine addiction.

a r t i c l e
Keywords:
Nicotine
Smoking cessation
Addiction
Cannabidiol
Endocannabinoids

i n f o

a b s t r a c t
The role of the endocannabinoid system in nicotine addiction is being increasingly acknowledged. We conducted
a pilot, randomised double blind placebo controlled study set out to assess the impact of the ad-hoc use of
cannabidiol (CBD) in smokers who wished to stop smoking. 24 smokers were randomised to receive an inhaler
of CBD (n = 12) or placebo (n = 12) for one week, they were instructed to use the inhaler when they felt the
urge to smoke. Over the treatment week, placebo treated smokers showed no differences in number of cigarettes
smoked. In contrast, those treated with CBD signicantly reduced the number of cigarettes smoked by ~40% during treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, combined with the strong preclinical rationale for use of this compound, suggest CBD to be a potential treatment for
nicotine addiction that warrants further exploration.
2013 Elsevier Ltd. All rights reserved.

1. Introduction
Cannabidiol (CBD) is a non-psychoactive component of the cannabis
plant. CBD has a complex action at a number of receptors including antagonistic action at the cannabinoid 1 and 2 (CB1 and CB2) receptors
and inhibition of the uptake and enzymatic hydrolysis of the endogenous cannabinoid ligand, anandamide. CBD has recently attracted interest for its anxiolytic (Crippa et al., 2011) and antipsychotic (Leweke et
al., 2012) properties. The endocannabinoid system is now thought to
be intrinsic to reward and reinforcement (Serrano & Parsons, 2011)
and several lines of evidence suggest that CBD may also be a useful
treatment in nicotine dependence.
A variety of sources have shown that CB1 receptors modulate the
rewarding effects of nicotine and other drugs. Conditioned place preference (CPP) is absent in both CB1-knockout mice (Cossu et al., 2001) and
rats treated with a systemic dose of the CB1 antagonist rimonabant
(Le Foll & Goldberg, 2004). Pretreatment with rimonabant also reduced
Corresponding author at: Clinical Psychopharmacology Unit, Clinical Health Psychology,
UCL, Gower Street, London, WC1E 6BT, UK. Tel.: +44 20 7679 1932; fax: +44 20 7916
1989.
E-mail address: c.morgan@ucl.ac.uk (C.J.A. Morgan).
0306-4603/$ see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.addbeh.2013.03.011

nicotine, ethanol, methamphetamine, and morphine self-administration

in rodents (Arnone et al., 1997; Cohen, Perrault, Voltz, Steinberg, &
Soubrie, 2002; Navarro et al., 2001; Vinklerova, Novakova, & Sulcova,
2002). Rimonabant blocks reinstatement of drug seeking following withdrawal from nicotine (Cohen, Perrault, Griebel, & Soubrie, 2005). Perhaps
most signicantly however a Cochrane review that included 3 clinical trials of rimonabant for smoking cessation concluded that 20 mg may
increase the chances of quitting (nicotine) approximately 1.5-fold
(Cahill & Ussher, 2007, pp. 3). These effects were attributed to its capacity
to regulate the endocannabinoid system which has been suggested
in turn to regulate dopamine (Rodriguez De Fonseca et al., 2001).
Rimonabant has, however, been withdrawn from clinical use in humans
due to increased depression and suicide in some patients. But CBD, unlike rimonabant, has an excellent safety prole (Bergamaschi, Queiroz,
Zuardi, & Crippa, 2011), and is an alternative strategy for normalising
the endocannabinoid system as recent research has shown that regular
dosing with CBD raises depleted levels of anandamide: the main neurotransmitter of the endocannabinoid system (Leweke et al., 2012).
Although no research has been conducted specically in cigarette
smokers addiction, other sources of evidence suggest that CBD may be
an effective treatment in addiction. In heroin-addicted rats, CBD reduces cue-related drug seeking, and this effect was still evident

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C.J.A. Morgan et al. / Addictive Behaviors 38 (2013) 24332436

14 days after a single CBD injection (Ren, Whittard, Higuera-Matas,

Morris, & Hurd, 2009). Parker, Burton, Sorge, Yakiwchuk, and
Mechoulam (2004) found that systemic administration of CBD prior
to exposure to a previously cocaine- or amphetamine-paired environment facilitated extinction of cocaine and amphetamine CPP.
Naturalistic studies in humans have shown that CBD reduces the salience of THC stimuli in cannabis dependent humans. Those smoking
cannabis low in CBD showed a marked bias towards drug and
food-related images which was absent, or reversed, in those smoking
high CBD cannabis (Morgan, Freeman, Schafer, & Curran, 2010). CBD
is also a potentially excellent treatment of addiction due to its anxiolytic
properties, as anxiety is a key symptom often observed in withdrawal
from nicotine and other drugs (Hughes, Higgins, & Bickel, 1994). No research as yet has examined the effects of directly administered CBD in
addiction in humans.
The current study set out to assess the impact of ad-hoc use of low
dose CBD in an inhaler form on nicotine addiction in tobacco smokers
who wished to stop smoking. We hypothesised that the use of CBD,
via mediation of the endocannabinoid system, would reduce cigarette
smoking.
2. Methods and materials
2.1. Design and participants
In a double-blind placebo controlled study, 24 smokers were
recruited from the community and were randomised to receive an
inhaler of CBD (n = 12; 6 females) or placebo (n = 12; 6 females).
Inclusion criteria were that participants smoked > 10 cigarettes per
day, and expressed an intention to quit smoking using a brief screen
(Taking Steps to Quit: Etter, Laszlo, Zellweger, Perrot, & Perneger,
2002); were aged 1835 years old; had no history of psychiatric,
substance misuse or physical health problems; and were not pregnant.
The study was approved by the institutional ethics committee (UCL
Graduate School) and was conducted in accordance with the Declaration of Helsinki. All participants gave written, witnessed, and informed
consent.

2.3. Drug administration

CBD (STI Pharmaceuticals: Brentwood, UK) or placebo was administered via a pressurised Metered Dose Inhaler (pMDI). Each depress
of the solution aerosol in the inhaler administered a dose of 400 g
CBD dissolved in absolute ethanol 5%; or placebo (ethanol alone).
Initial studies suggest a bioavailability of CBD following administration through this delivery device of > 65% (Davies, STI pharmaceuticals, personal communication).

2.4. Assessments
2.4.1. Baseline measures
Dependence was assessed with the 4 item severity of dependence
scale (SDS). Trait anxiety and depressive symptoms were assessed using
the Spielberger Trait Anxiety Inventory (STAI:Spielberger & Gorusch,
1970) and Beck Depression Inventory (BDI:Beck, Ward, Mendelson,
Mock, & Erbaugh, 1961), respectively. Trait impulsivity was assessed
using the Behaviour Impulsivity Scale (BIS: Gest, 1997).

2.4.2. Interim measures

In the days between testing participants were required to text the
number of uses of inhaler each day, and the number of cigarettes
consumed. They also responded to the question on a scale of 1100,
at this moment in time, how much do you want a cigarette?. The
VAS craving measure assesses momentary subjective craving.

2.4.3. Repeated measures on Day 1 and Day 7

Recorded number of cigarettes smoked was the key outcome variable. Exhaled carbon monoxide levels were taken on both testing days
as an indicator of smoking status. Craving was assessed using the Tiffany
Craving Questionnaire {TCQ: 11}. The 16-item Mood Rating Scale
(MRS: Bond and Lader, 1974) was used to assess key side effects (preand 1 hour post-placebo/DCS). Principle component analysis of this
measure yields factors for sedation, depression and anxiety.

2.2. Procedure
2.5. Statistical analysis
Participants were screened prior to randomisation. They responded
to an SMS with their daily cigarette use for the week prior to their rst
visit to the study centre. Participants attended the study centre on two
days separated by one week. On the rst testing session (pre-testing),
demographic data, premorbid IQ (Wechsler Test of Adult Reading:
WTAR) and exhaled carbon monoxide levels were recorded following
1 hour abstinence, participants also completed the baseline measures
detailed below and were given brief counselling on smoking reduction.
This consisted of around ten minutes of simple psychoeducational information on relapse prevention focused around urge surng (Bowen
& Marlatt, 2009). Participants were then given the inhaler and trained
in how to use it to maximise inhalation of the drug. They were
instructed to use the inhaler whenever they felt like smoking in the intervening week and given a diary in which to record their daily cigarette
and inhaler use. During the week between the two testing days (pre- and
post-testing) participants were reminded via daily text message at the
same time each day, which was agreed with the participant. They were
reminded 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 number of times they had used the
inhaler. On the post-testing day at the study centre they returned, and
repeat measures of mood and craving were conducted (see below). Participants kept a daily diary for the two weeks following the second testing session and were telephoned at the end of this period to assess their
cigarette use over this period.

Data were analysed using PASW Statistics (v.18.0). t-Tests or where

data were non-parametric Mann-Whitney U tests were used to analyse
baseline characteristics and a series of repeated measures ANOVA to analyse smoking, craving and mood and anxiety data. Pearson's correlation was used to examine the relationship between inhaler and
cigarette use.

Table 1
Baseline and pre- and post-treatment data following CBD and placebo.

Age
IQ-WTAR
Cigarettes smoked
per day
Years smoked
cigarettes
Fagerstrom score
Depression: BDI
Dependence: SDS
Trait Anxiety: STAI
Impulsivity: BIS
MRS-Sedation
MRS-Depression
MRS-Anxiety

Day 0 CBD

Day 0 placebo Day 7 CBD

28.00 (4.29)
43.93 (4.46)
18.20 (3.42)

28.08 (6.17)
44.33 (3.42)
16.54 (2.67)

14.25 (5.95)

11.33 (4.23)

5.0 (1.53)
9.42 (5.98)
7.58 (3.61)
35.67 (8.98)
66.17 (6.95)
38.35 (17.01)
30.58 (14.57)
39.08 (23.50)

5.17
10.08
9.58
33.58
67.25
29.19
34.62
34.14

(1.11)
(2.94)
(1.62)
(8.10)
(12.89)
(14.19)
(12.01)
(15.96)

TCQ: Tiffany Craving Scale; MRS: Mood Rating Scale.

Day 7 placebo

41.68 (16.43) 39.85 (15.00)

34.67 (11.12) 31.43 (13.05)
25.79 (16.58) 31.96 (14.34)

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2435

3.4. Anxiety and mood (Table 2)

2 2 repeated measures ANOVA were 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] reecting greater
sedation in both groups on the second testing day, but no main effect of
Treatment or interaction. Analysis of depression scores revealed no
main effects of Time or Treatment or interaction. There was a main effect of Time on anxiety [F(1,22) = 4.79, p = 0.04], reecting lower
scores in both groups at Time 2, however there was no interaction or
main effect of Treatment.

4. Discussion

Fig. 1. CBD treatment reduces cigarette consumption in smokers.

3. Results
3.1. Participants
Participants were well-matched demographically, groups were balanced for gender with no differences in age, IQ on the WTAR, baseline
smoking variables of cigarettes per day, years of cigarette smoking
and Fagerstrom scale of nicotine dependence score and there were no
signicant group differences in BDI score, BIS score, SDS score or STAI
score (Table 1).

3.2. Number of cigarettes smoked (see Fig. 1)

A 2 3 repeated measures ANOVA with a within subjects factor of
Time (Pre, Post and Follow-up) and between subjects factor of Treatment (CBD, placebo) found a borderline signicant Time Treatment
interaction [F(2,42) = 3.12, p = 0.054; p2 = 0.13]. Planned comparisons revealed this to be attributable to a signicant reduction in
number of cigarettes smoked across the treatment week in the CBD
group (p = 0.002) but no difference in the placebo group, and a trend,
following Bonferroni correction, for a maintenance of this effect in the
2 weeks following the study (p = 0.034). Total cigarettes smoked over
treatment week were correlated with the total inhaler users in the CBD
group however no signicant correlation emerged.

3.3. Nicotine craving (Table 2)

Craving assessed by the TCQ on Day 1 and Day 7 and at Follow-up
(Day 21) was subjected to a repeated measures ANOVA that found a
main effect of Time [F(2,42) = 3.26, p = 0.048; p2 = 0.13] but no
main effect of Treatment or interaction. Planned comparisons revealed a
signicant reduction in craving in both groups Day 1Day 7 (p b 0.001)
but no difference between Day 1 and Follow-up. A 7 2 repeated measures ANOVA of the mean craving reported on SMS across the 7 days of
inhaler use also revealed no signicant main effects of Time, Treatment
or interactions.

Table 2
Pre- and post-treatment data following CBD and placebo.

TCQ
MRS-Sedation
MRS-Depression
MRS-Anxiety

Day 0 CBD

Day 0 placebo

Day 7 CBD

Day 7 placebo

43.83
38.35
30.58
39.08

51.25
29.19
34.62
34.14

37.08
41.68
34.67
25.79

38.75
39.85
31.43
31.96

(15.50)
(17.01)
(14.57)
(23.50)

(10.65)
(14.19)
(12.01)
(15.96)

TCQ: Tiffany Craving Scale; MRS: Mood Rating Scale.

(12.36)
(16.43)
(11.12)
(16.58)

(12.68)
(15.00)
(13.05)
(14.34)

This preliminary study set out to assess the impact of the ad-hoc
use of an inhaler of the naturally occurring cannabinoid CBD on cigarette smoking in tobacco smokers who wanted to quit. The main nding of this study was a dramatic reduction in the number of cigarettes
smoked across a 7 day period in the individuals using the CBD inhaler,
compared to no reduction in the placebo group. However, this reduction
occurred in the absence of a change in cigarette craving reported daily
across the week. There was a reduction in craving in both groups between
Day 1 and Day 7 but this reduction was not maintained at follow-up. Both
the CBD and placebo groups in this study showed reduced anxiety across
the 7 days.
This is the rst study, as far as we are aware, to demonstrate the
impact of CBD on cigarette smoking. The reduction in smoking observed
in this study was striking and occurred in the absence of other specic effects, notably on craving. Given the pivotal role of craving in relapse, this
is a potentially very encouraging nding, in that participants using the
CBD inhaler reduced the number of cigarettes they smoked without
increased craving for nicotine. The decrease in smoking observed here
may plausibly relate to the action of CBD at the CB1 receptor, given
previous literature on similar reductions following treatment with
rimonabant. Neurochemically, another putative mechanism suggested
by recent research has shown that the reinforcing and neurochemical effects of nicotine in rats are reduced by fatty acid amide hydrolase (FAAH)
inhibition (Gonzalez et al., 2002), as it has been proposed that some of the
behavioural effects of CBD are related to its properties as an
FAAH-inhibitor (Leweke et al., 2012).
Psychologically, the reduction in smoking may occur via a modulation of the salience of smoking cues by CBD, consistent with preclinical
studies (Ren et al., 2009) and a naturalistic study that found CBD to reduce the attentional bias of dependent cannabis users to cannabis stimuli (Morgan et al., 2010). CBD may have acted to weaken the attentional
bias of smokers to smoking stimuli. Attentional bias is thought to play a
fundamental role in maintaining the cycle of craving and relapse in addiction and therefore a reduction in salience of smoking cues would be
predicted to have a powerful effect on substance use, as is seen in this
study. CBD has also been recently found to disrupt reconsolidation
(Stern et al., 2012), a memory process by which memories are
destabilised which has been suggested to have a therapeutic role in addiction (Taylor et al., 2009). Such a disruption with inhaler use on a
daily basis might also explain these ndings.
This was a preliminary study requiring replication, especially in light
of the absence of any other biochemical assays (e.g. cotinine levels). The
results reported here are solely based on self-report which is a clear limitation, as is that we only assessed craving once per day which could have
been contaminated by recent cigarette use. At the doses used in this
study, CBD did not produce changes in self-rated anxiety or increase sedation, both previous noted effects of the drug (Scherma et al., 2008).
CBD produced no increase in depression unlike selective CB1 antagonists
such as rimonabant, which is encouraging for the use of CBD as a treatment for nicotine addiction should future, larger-scale studies, reinforce
the suggestions of this pilot study.

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C.J.A. Morgan et al. / Addictive Behaviors 38 (2013) 24332436

In conclusion, the preliminary data presented here suggest that

CBD may be effective in reducing cigarette use in tobacco smokers,
however larger scale studies, with longer follow-up are warranted to
gauge the implications of these ndings. These ndings add to a growing literature that highlights the importance of the endocannabinoid
system in nicotine addiction.
Role of funding sources
This research was supported by a grant awarded to SKK, CJAM and HVC by the
Medical Research Council, UK.
Author contributions
CJAM and SJK designed research, CJAM analysed data and wrote manuscript, and AJ
and RD performed research.
Conict of interest
None.
Acknowledgements
The authors would like to thank Andrew Davies and STI Pharmaceuticals, Brentwood,
Essex, UK for providing the CBD and inhalers.

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