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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
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.
abstractarticle info
Smoking cessation
The role of the endocannabinoid system in nicotine addiction is being increasinglyacknowledged. 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. Overthe treatment week, placebo treated smokers showed no differences in numberof cigarettes
smoked. In contrast, those treated with CBD signicantly reduced the numberof cigarettes smoked by ~40% dur-
ing treatment. Results also indicated some maintenance of this effect at follow-up. These preliminary data, com-
bined with the strong preclinical rationalefor 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 an-
tagonistic action at the cannabinoid 1 and 2 (CB1 and CB2) receptors
and inhibition of the uptake and enzymatic hydrolysis of the endoge-
nous cannabinoid ligand, anandamide. CBD has recently attracted inter-
est 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 prefer-
ence (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
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 with-
drawal from nicotine (Cohen, Perrault, Griebel, & Soubrie, 2005). Perhaps
most signicantly however a Cochrane review that included 3 clinical tri-
als 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, un-
like 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: themain neuro-
transmitter 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 re-
duces cue-related drug seeking, and this effect was still evident
Addictive Behaviors 38 (2013) 24332436
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
E-mail address: (C.J.A. Morgan).
0306-4603/$ see front matter © 2013 Elsevier Ltd. All rights reserved.
Contents lists available at SciVerse ScienceDirect
Addictive Behaviors
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 envi-
ronment facilitated extinction of cocaine and amphetamine CPP.
Naturalistic studies in humans have shown that CBD reduces the sa-
lience 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 re-
search 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
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 Declara-
tion of Helsinki. All participants gave written, witnessed, and informed
2.2. Procedure
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 in-
formation 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 in-
tervening 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). Par-
ticipants kept a daily diary for the two weeks following the second test-
ing session and were telephoned at the end of this period to assess their
cigarette use over this period.
2.3. Drug administration
CBD (STI Pharmaceuticals: Brentwood, UK) or placebo was admin-
istered via a pressurised Metered Dose Inhaler (pMDI). Each depress
of the solution aerosol in the inhaler administered a dose of 400 μg
CBD dissolved in absolute ethanol 5%; or placebo (ethanol alone).
Initial studies suggest a bioavailability of CBD following administra-
tion through this delivery device of >65% (Davies, STI pharmaceuti-
cals, 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 vari-
able. 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 (pre-
and 1 hour post-placebo/DCS). Principle component analysis of this
measure yields factors for sedation, depression and anxiety.
2.5. Statistical analysis
Data were analysed using PASW Statistics (v.18.0). t-Tests or where
data were non-parametric Mann-Whitney Utests were usedto analyse
baseline characteristics and a series of repeated measures ANOVA to an-
alyse smoking, craving and mood and anxiety data. Pearson's correla-
tion was used to examine the relationship between inhaler and
cigarette use.
Table 1
Baseline and pre- and post-treatment data following CBD and placebo.
Day 0 CBD Day 0 placebo Day 7 CBD Day 7 placebo
Age 28.00 (4.29) 28.08 (6.17)
IQ-WTAR 43.93 (4.46) 44.33 (3.42)
Cigarettes smoked
per day
18.20 (3.42) 16.54 (2.67)
Years smoked
14.25 (5.95) 11.33 (4.23)
Fagerstrom score 5.0 (1.53) 5.17 (1.11)
Depression: BDI 9.42 (5.98) 10.08 (2.94)
Dependence: SDS 7.58 (3.61) 9.58 (1.62)
Trait Anxiety: STAI 35.67 (8.98) 33.58 (8.10)
Impulsivity: BIS 66.17 (6.95) 67.25 (12.89)
MRS-Sedation 38.35 (17.01) 29.19 (14.19) 41.68 (16.43) 39.85 (15.00)
MRS-Depression 30.58 (14.57) 34.62 (12.01) 34.67 (11.12) 31.43 (13.05)
MRS-Anxiety 39.08 (23.50) 34.14 (15.96) 25.79 (16.58) 31.96 (14.34)
TCQ: Tiffany Craving Scale; MRS: Mood Rating Scale.
2434 C.J.A. Morgan et al. / Addictive Behaviors 38 (2013) 24332436
3. Results
3.1. Participants
Participants were well-matched demographically, groups were bal-
anced 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 Treat-
ment (CBD, placebo) found a borderline signicant Time × Treatment
interaction [F(2,42) = 3.12, p = 0.054; η
= 0.13]. Planned compar-
isons 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; η
= 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 b0.001)
but no difference between Day 1 and Follow-up. A 7 × 2 repeated mea-
sures 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.
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 ef-
fect 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
This preliminary study set out to assess the impact of the ad-hoc
use of an inhaler of the naturally occurring cannabinoid CBD on ciga-
rette smoking in tobacco smokers who wanted to quit. The main nd-
ing 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 specicef-
fects, 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 ef-
fects 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 modula-
tion of the salience of smoking cues by CBD, consistent with preclinical
studies (Ren et al., 2009) and a naturalistic study that found CBD to re-
duce the attentional bias of dependent cannabisusers to cannabis stim-
uli (Morgan et al., 2010). CBD may have acted to weaken the attentional
bias of smokers to smoking stimuli. Attentional bias is thought toplay a
fundamental role in maintaining the cycle of craving and relapse in ad-
diction 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 ad-
diction (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 lim-
itation, 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 se-
dation, 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 treat-
ment for nicotine addiction should future, larger-scale studies, reinforce
the suggestions of this pilot study.
Fig. 1. CBD treatment reduces cigarette consumption in smokers.
Table 2
Pre- and post-treatment data following CBD and placebo.
Day 0 CBD Day 0 placebo Day 7 CBD Day 7 placebo
TCQ 43.83 (15.50) 51.25 (10.65) 37.08 (12.36) 38.75 (12.68)
MRS-Sedation 38.35 (17.01) 29.19 (14.19) 41.68 (16.43) 39.85 (15.00)
MRS-Depression 30.58 (14.57) 34.62 (12.01) 34.67 (11.12) 31.43 (13.05)
MRS-Anxiety 39.08 (23.50) 34.14 (15.96) 25.79 (16.58) 31.96 (14.34)
TCQ: Tiffany Craving Scale; MRS: Mood Rating Scale.
2435C.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 grow-
ing 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
The authorswould like to thank Andrew Daviesand STI Pharmaceuticals, Brentwood,
Essex, UK for providing the CBD and inhalers.
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... Eight studies (14%) investigated the effects of CBD on substance use, which included cannabis [50,52,67], alcohol [81], crack-cocaine [86], opioids [74], tobacco [57], and recreational polysubstance use [100]. As for cannabis, a secondary analysis of a clinical trial [71] focused on the abuse liability of a range of oral CBD doses alone and in combination with smoked marijuana (5.3-5.8% of THC); this study found that CBD did not display any abuse-related subjective effects (i.e., feeling high, feeling mellow, cravings) unlike active marijuana [67]. ...
... Cannabidiol might not be an ideal treatment for crack-cocaine withdrawal [86]. However, CBD could be a potential treatment for opioid abuse [74], reduce tobacco smoking consumption [57], and has a low abuse potential among polydrug users [100]. ...
... Some studies suggested that CBD may be an effective treatment for some substance use problems, but not others. For example, one study determined that both 400 mg and 800 mg of CBD were safe and effective for cannabis use disorder treatment [50], while other studies found CBD may be a potential treatment for opioid abuse [74] and could reduce tobacco cravings [57]. However, another study found that CBD was not effective for the treatment of crack-cocaine craving [86]. ...
Background: Legislative changes have fueled the global availability of cannabis and cannabis-derived compounds, such as cannabidiol. Little is known about the effectiveness and safety of cannabidiol for treating health conditions other than seizure disorders. Objective: A systematic review of the literature was performed to investigate other health conditions, characteristics of the studied populations, and the effectiveness of cannabidiol in randomized clinical trials. Methods: Seven publication databases were searched from February to March 2021. The inclusion criteria for studies were: (1) utilized a randomized clinical trial design; (2) published in a peer-reviewed journal or thesis/dissertation; (3) published in English; (4) investigated either prescription (i.e., Epidiolex) or non-prescription CBD that was derived from the Cannabis sativa plant with < 3% ∆9-tetrahydrocannabinol; and (5) reported at least one outcome. This review excluded seizure-related disorders as several previous reviews have been done on this topic; it also excluded published protocols, other systematic reviews, or meta-analyses of randomized clinical trials that investigated cannabidiol. Independent reviewing, risk of bias assessment, and data abstraction were performed by two authors. Results: Fifty-eight studies from eight countries were included in this review. Twenty-seven studies (47%) were conducted in healthy populations, 14% were restricted to male individuals (n = 8), and 72% had sample sizes of fewer than 40 participants. Doses of cannabidiol used in these studies ranged from 400 µg to 6000 mg. The effect of cannabidiol on mental health was the most studied topic (53%), which focused mainly on anxiety, psychosis, schizophrenia, and substance use disorders. The remaining studies investigated neurological conditions (19%) and a myriad of other health conditions or outcomes. While cannabidiol appears to be anxiolytic, its effectiveness for other conditions was highly variable. Conclusions: This review highlights the inconsistencies of cannabidiol as a treatment for non-seizure-related health conditions or outcomes. Studies incorporating larger sample sizes in more diverse populations are encouraged. While cannabidiol was generally safe and well tolerated even in high doses among the included studies, clearer dosing guidelines and increased regulation of cannabidiol products are also needed.
... Symptoms of depression caused by diverse medical conditions were evaluated with dronabinol in seven RCTs versus placebo [12,23,45,75,92,102,117] and in one study versus prochlorperazine [86]; with nabilone, three studies comparing placebo [118,125,151] and two comparing an active drug [121,123] were carried out; placebo was compared with CBD in 6 RCTs [15,19,22,24,153,154] and with nabiximols in 7 RCTs [48,49,53,[61][62][63][64]. ...
... The overall analysis (Fig. 9) indicates that cannabinoids have a beneficial effect in the treatment of drug dependence (SMD − 0.41, 95% CI − 0.63 to − 0.19; P = 0.0003), an effect seen in all subgroup analyses except for CBD [19,20,22,24,[30][31][32]. Although dronabinol [92,110,111] Further meta-regression analysis indicated that the differences in the effect sizes were not related to the cannabinoid type (Additional file 5). ...
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Background Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events. Methods We systematically reviewed (registered at PROSPERO: CRD42021229932) eight databases for randomized controlled trials (RCTs) of dronabinol, nabilone, cannabidiol and nabiximols for chronic pain, spasticity, nausea /vomiting, appetite, ALS, irritable bowel syndrome, MS, Chorea Huntington, epilepsy, dystonia, Parkinsonism, glaucoma, ADHD, anorexia nervosa, anxiety, dementia, depression, schizophrenia, PTSD, sleeping disorders, SUD and Tourette. Main outcomes and measures included patient-relevant/disease-specific outcomes, retention and adverse events. Data were calculated as standardized mean difference (SMD) and ORs with confidence intervals (CI) via random effects. Evidence quality was assessed by the Cochrane Risk of Bias and GRADE tools. Results In total, 152 RCTs (12,123 participants) were analysed according to the type of the cannabinoid, outcome and comparator used, resulting in 84 comparisons. Significant therapeutic effects of medical cannabinoids show a large variability in the grade of evidence that depends on the type of cannabinoid. CBD has a significant therapeutic effect for epilepsy (SMD − 0.5[CI − 0.62, − 0.38] high grade) and Parkinsonism (− 0.41[CI − 0.75, − 0.08] moderate grade). There is moderate evidence for dronabinol for chronic pain (− 0.31[CI − 0.46, − 0.15]), appetite (− 0.51[CI − 0.87, − 0.15]) and Tourette (− 1.01[CI − 1.58, − 0.44]) and moderate evidence for nabiximols on chronic pain (− 0.25[− 0.37, − 0.14]), spasticity (− 0.36[CI − 0.54, − 0.19]), sleep (− 0.24[CI − 0.35, − 0.14]) and SUDs (− 0.48[CI − 0.92, − 0.04]). All other significant therapeutic effects have either low, very low, or even no grade of evidence. Cannabinoids produce different adverse events, and there is low to moderate grade of evidence for this conclusion depending on the type of cannabinoid. Conclusions Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.
... Substance Use Disorders: Limited research suggests that CBD may have potential in treating substance use disorders including those involving tobacco, cannabis, and opiates. In a 2013 study [99], a group of 24 individuals with tobacco smoking were randomized to receive an inhaler of CBD or placebo for one week. They were instructed to use the inhaler whenever they felt a craving to smoke. ...
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Purpose of review There have been many debates, discussions, and published writings about the therapeutic value of cannabis plant and the hundreds of cannabinoids it contains. Many states and countries have attempted, are attempting, or have already passed bills to allow legal use of cannabinoids, especially cannabidiol (CBD), as medicines to treat a wide range of clinical conditions without having been approved by a regulatory body. Therefore, by using PubMed and Google Scholar databases, we have reviewed published papers during the past 30 years on cannabinoids as medicines and comment on whether there is sufficient clinical evidence from well-designed clinical studies and trials to support the use of CBD or any other cannabinoids as medicines. Recent findings Current research shows that CBD and other cannabinoids currently are not ready for formal indications as medicines to treat a wide range of clinical conditions as promoted except for several exceptions including limited use of CBD for treating two rare forms of epilepsy in young children and CBD in combination with THC for treating multiple-sclerosis-associated spasticity. Summary Research indicates that CBD and several other cannabinoids have potential to treat multiple clinical conditions, but more preclinical, and clinical studies and clinical trials, which follow regulatory guidelines, are needed to formally recommend CBD and other cannabinoids as medicines.
... Additionally, psychedelic substances have diverse pharmacology and heterogeneous mechanisms of action [258] and are mostly considered as such by its ability to promote altered states of perception and thoughts, although the terms 'classic psychedelics' or 'serotonergic psychedelics' are being employed to elucidate these particularities [ 19 , 259 ]. Nonetheless, organizations such as the Beckley Foundation and the Multidisciplinary Association for Psychedelic Sciences hold important publications and ongoing research investigating therapeutic effects of cannabis and cannabinoids [260][261][262] . This session attempted to gather studies investigating how the psychedelic component in cannabis, THC, could act as therapeutic agent for continuous drug consumption or SUD. ...
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Substance use disorder (SUD) is a global public health concern that affects millions of people worldwide. Considering current research, addiction has been noted as the last stage of a chronic disease that may impair brain reward circuit responses and affects personal and social life. Treatments for SUD face challenges including availability and limited pharmacological response, often resulting in low retention of patients. A growing number of studies from the 'psychedelic renaissance' have highlighted the therapeutic potential of psychedelics for several psychiatric disorders, including SUD. In this non-systematic review we discuss past and current clinical and observational studies with classic (LSD, DMT, psilocybin and mescaline) and non-classic (ibogaine, ketamine, MDMA, salvinorin A and THC) psychedelics for the treatment of SUD published until December 2021. Although results are still inconclusive for LSD, DMT, mescaline, MDMA and Salvinorin A, in general, the literature presents moderate evidence on the controlled use of psilocybin and ketamine for Alcohol Use Disorder, ketamine for management of opiate and alcohol withdrawal, and THC preparations for reducing withdrawal symptoms in Cannabis and possibly in Opioid Use Disorder. Importantly, studies suggest that psychedelics should be more effective when employed as an adjunct therapy. Extensive research is warranted to further elucidate the role of psychedelics in the treatment of SUD.
Cannabidiol’s (CBD) safety profile and broad action has made it a popular treatment option for anxiety and co-occurring sleep disturbance. However, its efficacy in healthy and clinical populations, treatment duration, formulation and doses for optimal therapeutic benefits remains unclear. Selected databases were examined from inception to October 2022. Study selection, data extraction and Cochrane Risk of Bias assessments were conducted according to PRISMA guidelines and registered on the PROSPERO database (CRD42021247476) with 58 full-text studies meeting the eligibility criteria and administered CBD only or with Δ-9-tetrahydrocannabinol (THC) across healthy and clinical populations. In healthy populations and certain non-cannabis using clinical populations, CBD had greater anxiolytic effects without prominent effects on sleep. An inverted U-shaped dose relationship, and CBD ratio to THC in combined treatments likely moderated these effects. Mechanistically, observed CBD effects occurred via primary modulation of the endocannabinoid system and secondary regulation of neuroendocrine function. Additional research is needed to understand CBD mechanisms of action across diverse groups.
Endocannabinoid signalling plays an important role in affect, anxiety, and reward, and thus targeting this system could potentially be used to treat mental health and substance use disorders. This chapter discusses the current state of the clinical evidence evaluating the potential of various cannabinoid drugs as mental health and addiction pharmacotherapy, with a focus on randomized controlled trials. A few small clinical trials have found preliminary evidence for different cannabinoids in mental health disorders, including cannabidiol (CBD) for anxiety disorders, and Δ9-tetrahydrocannabinol (THC) for post-traumatic stress disorder (PTSD) and Tourette syndrome. The evidence for cannabinoids in other mental health conditions (e.g., psychotic disorders) is mixed. The clinical evidence also suggests that a combination of CBD and THC may be useful in reducing cannabis craving and/or withdrawal in patients with cannabis use disorder (CUD), with possible longer-term effects on reducing cannabis use and promoting abstinence. CBD alone may have the potential to reduce cannabis use, promote tobacco smoking cessation, and attenuate opioid craving, though these findings need replication. Finally, the cannabinoid type-1 (CB1) receptor antagonist rimonabant showed promise as a smoking cessation pharmacotherapy, yet this drug was withdrawn from the market due to serious psychiatric adverse effects. The current evidence demonstrates the potential for cannabinoid drugs in the treatment of mental health and substance use disorders, yet this evidence is clearly in its early stages. Future directions for the field are discussed.
There are global concerns about the proliferation and misuse of club drugs and novel psychoactive substances, yet we know little about their harms and research on clinical management and treatment remains limited. This book fills the knowledge gap by providing a detailed overview of the research evidence available to date. The book provides a framework that allows readers to understand this large number of new drugs, using classifications based on primary psychoactive effect. Within this framework, the book provides detailed reviews of the more commonly used drugs. Each chapter explores pharmacology, patterns and mode of use, acute and chronic harms, and clinical interventions supported by research evidence. An invaluable resource for clinical staff, this book will support clinicians working in the emergency department, substance misuse and addiction services, mental health services, primary care, sexual health services and more. It will also be of interest to academics and those developing drug policy.
Nowadays, the light hemp is promoted by different stakeholders and the customer’s preference due to the different use of crop products. The aim of this chapter was to discuss the Italian perspectives concerning the utilization of light hemp connected to customer’s preferences. It is discussed the sustainability of hemp crop to produce wellness products in Italy. It is applied as a cost model based on empirical data from hemp farmers. Customers’ preferences on light cannabis wellness products are analyzed through an online survey in Italy and other six European countries. A general misunderstanding about the differences between psychoactive hemp and nonpsychoactive hemp (light cannabis) makes the demand unstable. Light hemp business in Italy is new and there are a few studies that help entrepreneurs in assessing the attractiveness of certain investment analyzing the demand for such a product. Demand for CBD-based products indicates interest, but customers’ confusion highlights a lack of regulation and transparency about CBD-cannabis.
Therapeutic Use of Cannabidiol in Adult Psychiatry: State of Play Cannabidiol (CBD) is a major component of Cannabis sativa L. Compared to the psychotomimetic delta-9-tetrahydrocannabinol (Δ-9-THC), CBD exerts a different psychoactive action. CBD has been suggested to possess a range of possible therapeutic effects. In psychiatric context, it is claimed to exert antipsychotic, antidepressant, anxiolytic, anticraving and procognitive effects. This literature review attempts to provide an up-to-date overview of the therapeutic applications of CBD in the context of adult psychiatry. The clinical studies conducted are compiled, with an emphasis on psychotic disorders, substance use disorders, anxiety disorders, mood disorders, and trauma and stress related disorders. In addition, the side effect, safety, and interaction profile of CBD are reviewed. Despite some favorable preliminary results, it can be broadly stated that there is insufficient evidence yet to make recommendations around use of CBD in clinical practice in psychiatric disorder. It is essential to provide the (psychiatric) patient using CBD with psychoeducation about the (unknown) efficacy and the safety profile with possible side effects and interactions. Future qualitative and placebo-controlled research is necessary to obtain more evidence on the clinical effectiveness, applicability, and dosage of CBD in adult psychiatry. Subsequently, longitudinal research is necessary to understand the effects of long-term CBD treatment, as well as to gain more insight into potential side effects and interactions.
Legalization of cannabis in the US and other countries highlight the need to understand the health consequences of this substance use. Research indicates that some cannabis ingredients may play beneficial role in treating various medical conditions while other ingredients may pose health risks. This review is focused on the brain and mental health effects of cannabis use. The rationale for examining cannabis use in behavioral and neural conditions is that these conditions are highly widespread in the US and account for high level of medical healthcare and associated cost. The purpose of this review is to provide an overview of the known medicinal benefits of selected cannabis cannabinoids in conditions like pediatric epilepsy, attention deficit hyperactivity disorder, autism spectrum disorder, and the known side effects or contraindications in conditions such as addiction, cognition, and psychosis. Several recommendations are made as to studies that will help further understanding the increasing role of cannabis in neuropsychiatric health and disease.
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Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
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The search for reconsolidation blockers may uncover clinically relevant drugs for disrupting memories of significant stressful life experiences, such as those underlying the posttraumatic stress disorder. Considering the safety of systemically administered cannabidiol (CBD), the major non-psychotomimetic component of Cannabis sativa, to animals and humans, the present study sought to investigate whether and how this phytocannabinoid (3-30 mg/kg intraperitoneally; i.p.) could mitigate an established memory, by blockade of its reconsolidation, evaluated in a contextual fear-conditioning paradigm in rats. We report that CBD is able to disrupt 1- and 7-days-old memories when administered immediately, but not 6 h, after their retrieval for 3 min, with the dose of 10 mg/kg being the most effective. This effect persists in either case for at least 1 week, but is prevented when memory reactivation was omitted, or when the cannabinoid type-1 receptors were antagonized selectively with AM251 (1.0 mg/kg). Pretreatment with the serotonin type-1A receptor antagonist WAY100635, however, failed to block CBD effects. These results highlight that recent and older fear memories are equally vulnerable to disruption induced by CBD through reconsolidation blockade, with a consequent long-lasting relief in contextual fear-induced freezing. Importantly, this CBD effect is dependent on memory reactivation, restricted to time window of <6 h, and is possibly dependent on cannabinoid type-1 receptor-mediated signaling mechanisms. We also observed that the fear memories disrupted by CBD treatment do not show reinstatement or spontaneous recovery over 22 days. These findings support the view that reconsolidation blockade, rather than facilitated extinction, accounts for the aforementioned CBD results in our experimental conditions.
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Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.
The difficulties inherent in obtaining consistent and adequate diagnoses for the purposes of research and therapy have been pointed out by a number of authors. Pasamanick12 in a recent article viewed the low interclinician agreement on diagnosis as an indictment of the present state of psychiatry and called for "the development of objective, measurable and verifiable criteria of classification based not on personal or parochial considerations, but on behavioral and other objectively measurable manifestations."Attempts by other investigators to subject clinical observations and judgments to objective measurement have resulted in a wide variety of psychiatric rating scales.4,15 These have been well summarized in a review article by Lorr11 on "Rating Scales and Check Lists for the Evaluation of Psychopathology." In the area of psychological testing, a variety of paper-and-pencil tests have been devised for the purpose of measuring specific
Many of the symptoms of nicotine withdrawal are similar to those of other drug withdrawal syndromes: anxiety, awakening during sleep, depression, difficulty concentrating, impatience, irritability/anger and restlessness. Slowing of the heart rate and weight gain are distinguishing features of tobacco withdrawal. Although nicotine withdrawal may not produce medical consequences, it lasts for several weeks and can be severe in some smokers. Like most other drug withdrawals, nicotine withdrawal is time-limited, occurs in non-humans, is influenced by instructions/expectancy and abates with replacement therapy and gradual reduction. Unlike some other drug withdrawal syndromes, protracted, neonatal or precipitated withdrawal does not occur. Whether nicotine withdrawal is associated with tolerance, acute physical dependence, greater duration and intensity of use, rapid reinstatement, symptom stages, cross-dependence with other nicotine ligands, reduction by non-pharmacological interventions and genetic influences is unclear. Whether nicotine withdrawal plays a major role in relapse to smoking has not been established but this is also true for other drug withdrawal syndromes.
The endogenous cannabinoid system is a new signaling system composed by the central (CB1) and the peripheral (CB2) receptors, and several lipid transmitters including anandamide and 2-arachidonylg-lycerol. This system is the target of natural cannabinoids, the psychoactive constituents ofCannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with subjective feelings of pleasure and relaxation, but also to the onset of psychiatric syndromes, a decrease of the efficacy of neuroleptics and alterations in the extrapyramidal system regulation of motor activity. These actions points to a tight association of the cannabinoid system with the brain dopaminergic circuits involved in addiction, the clinical manifestation of positive symptoms of schizophrenia and Parkinson’s disease. The present work discuss anatomical, biochemical and pharmacological evidences supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid CB1 receptors are present in dopamine projecting brain areas. In primates and certain rat strains it is also located in dopamine cells of the A8, A9 and A10 mesencephalic cell groups, as well as in hypothalamic dopaminergic neurons controlling prolactin secretion. CB1 receptors co-localize with dopamine D1/D2 receptors in dopamine projecting fields. Manipulation of dopaminergic transmission is able of altere the synthesis and release of anandamide as well as the expression of CB1 receptors. Additionally, CB1receptors can switch its transduction mechanism to oppose to the ongoing dopamine signaling. Acute blockade of CB1 receptor potentiates the facilitatory role of dopamine D2 receptor agonists on movement. CB1 stimulation results in sensitization to the motor effects of indirect dopaminergic agonists. The dynamics of these changes indicate that the cannabinoid system is an activity-dependent modulator of dopaminergic transmission, an hypothesis relevant for the design of new therapeutic strategies for dopamine-related diseases such as the psychosis and Parkinson’s disease.
Administered 16 visual analog scales to 8 normal Ss to test the validity of the scales in measuring drug effects; Ss received 150 mg of butobarbitone sodium, 15 and 30 mg of flurazepam, and a placebo. Results indicate that (a) there were no significant effects on Factor 1 (Alertness), but there was a tendency for Ss to rate themselves as more alert after placebo; (b) there was a significant Drug * Times interaction effect on Factor 2 (Contentedness); and (c) Factor 3 (Calmness) also showed a significant Drug * Times interaction effect which was caused by the anti-anxiety effect of flurazepam. (15 ref) (PsycINFO Database Record (c) 2004 APA, all rights reserved)