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Cannabis use and related clinical variables in
patients with obsessive-compulsive disorder
Beatrice Benatti
1,2
, Matteo Vismara
1,2
*, Lorenzo Casati
1
, Simone Vanzetto
1
,
Dario Conti
1
, Giovanna Cirnigliaro
1
, Alberto Varinelli
1
, Martina Di Bartolomeo
3
,
Claudio D’addario
3,4
, Micheal Van Ameringen
5
and Bernardo Dell’Osso
1,2,6,7
1
Department of Mental Health, Department of Biomedical and Clinical Sciences “Luigi Sacco”, University of Milan,
Milan, Italy,
2
Department of Health Sciences, “Aldo Ravelli”Center for Neurotechnology and Brain Therapeutic,
University of Milan, Milan, Italy,
3
Faculty of Bioscience and Technology for Food, Agriculture and Environment,
Teramo, Italy,
4
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden,
5
Department of
Psychiatry and Behavioural Neuroscience, McMaster University-MacAnxiety Research Centre, Hamilton, ON, Canada,
6
Department of Psychiatry and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, Stanford, CA, USA
and
7
“Centro per lo studio dei meccanismi molecolari alla base delle patologie neuro-psico-geriatriche”, University
of Milan, Milan, Italy
Abstract
Objective. Limited studies have investigated cannabis use in patients with obsessive-compulsive
disorder (OCD), despite its widespread use by patients with psychiatric illnesses. The aim of this
study was to assess the frequency, correlates, and clinical impact of cannabis use in an Italian
sample of patients with OCD.
Methods. Seventy consecutive outpatients with OCD were recruited from a tertiary specialized
clinic. To assess cannabis-related variables, patients completed a questionnaire developed for
the purpose of this study, investigating cannabis use-related habits and the influence of cannabis
use on OCD symptoms and treatments. A set of clinician and self-reported questionnaires was
administered to measure disease severity. The sample was then divided into three subgroups
according to the pattern of cannabis use: “current users”(CUs), “past-users”(PUs), and “non-
users”(NUs).
Results. Approximately 42.8% of patients reported lifetime cannabis use and 14.3% reported
current use. Approximately 10% of cannabis users reported an improvement in OCD symptoms
secondary to cannabis use, while 23.3% reported an exacerbation of anxiety symptoms. CUs
showed specific unfavorable clinical variables compared to PUs and NUs: a significant higher
rate of lifetime use of tobacco, alcohol, and other substances, and a higher rate of pre-OCD onset
comorbidities. Conversely, the three subgroups showed a similar severity of illness.
Conclusion. A considerable subgroup of patients with OCD showed a predisposition towards
cannabis use and was associated with some specific clinical characteristics, suggesting the need
for targeted consideration and interventions in this population.
1. Introduction
Obsessive-compulsive disorder (OCD) is a prevalent and highly disabling psychiatric illness
responsible for a substantial reduction in quality of life and a significant functional impairment
for patients and their caregivers.
1–3
Available treatments for OCD are at times only partially successful and treatment resistance
might be a reason for patients’drop-outs with conventional medications.
4
In some circum-
stances, patients might use alternative substances to self-medicate or to cope with OCD
symptoms. Among these, cannabis is the most widely used substance of abuse in the United
States among youths and adolescents, due to its easy availability and affordable price. In a general
population survey conducted in the USA, 1-year prevalence of cannabis use amounted to 34.5%
of adults between 18 and 25 years old.
5
In a cross-national study, the prevalence of cannabis use
disorder in Italian adolescents reached 2.77%, with a slightly higher rate in males than females
(3.49% vs 2.09%).
6
Considering patients with OCD typically manifest the first symptoms during
the school age,
7
these data might suggest an overlap of OCD and cannabis use in terms of age
distribution, with young subjects being the most affected in both disorders.
Conventionally, impulsivity is the most important dimension involved in substance use
disorders.
8
However, compulsivity has been recently proposed as a determinant of addiction,
9
being a common feature of OCD, as suggested by neurological and neuropsychological mech-
anisms coexisting in these disorders.
10,11
On the other hand, several studies exploring brain
models of addiction and risk-oriented behaviors underlined the presence of high impulsivity in
patients with OCD.
12–14
This characteristic is somehow opposite to personality traits
CNS Spectrums
www.cambridge.org/cns
Original Research
Cite this article: Benatti B, Vismara M, Casati
L, Vanzetto S, Conti D, Cirnigliaro G, Varinelli
A, Di Bartolomeo M, D’addario C, Van
Ameringen M, and Dell’Osso B (2022).
Cannabis use and related clinical variables in
patients with obsessive-compulsive disorder.
CNS Spectrums
https://doi.org/10.1017/S1092852922001006
Received: 02 March 2022
Accepted: 12 September 2022
Key words:
Obsessive compulsive disorder; cannabis;
substance use; prevalence; addiction
Author for correspondence:
*Matteo Vismara
Email: matteo.vismara@unimi.it
© The Author(s), 2022. Published by Cambridge
University Press. This is an Open Access article,
distributed under the terms of the Creative
Commons Attribution licence (http://
creativecommons.org/licenses/by/4.0), which
permits unrestricted re-use, distribution and
reproduction, provided the original article is
properly cited.
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
characterized by harm-avoidance typically expressed by patients
with OCD
15–17
which, in turn, might discourage patients with OCD
from involving themselves in potentially dangerous and unsafe
situations often connected to substance use. Overall, substance
use in OCD might be considered a result of a complex overlay
and interplay of compulsivity, impulsivity, personality traits, and
likely other dimensions whose roles need to be further investigated.
Previous investigations sought to describe the correlation
between cannabis use and OCD. First, evidence from both animal
and human studies suggests that the endocannabinoid system may
play a role in OCD and related disorders.
18
A recent study, based on
data from an online survey, assessed patterns of cannabis use in a
large sample of individuals with a diagnosis of OCD (N=601,
based on a self-reported prior diagnosis by a healthcare profession
or well-established cutoff on the OCI-R).
19
42% of participants
with OCD met cannabis use disorder criteria and nearly 70% for
problematic cannabis use. Among negative factors associated with
cannabis use, most participants were not currently receiving
evidence-based OCD treatment, and the likelihood of this treat-
ment decreased as cannabis use frequency increased.
Deepening the correlation between cannabis and OCD, some
investigations reported cannabis use as a potential harmful factor
for OCD. One study that primarily investigated prevalence, corre-
lates, and predictors of OCD in a large (N =390) birth cohort
showed that a history of substance use disorder (cannabis/alcohol)
was a prospective risk factor for OCD.
20
Challenging this finding, a
prospective study in an adult population, recruited through a
national survey, showed that cannabis use at baseline was unrelated
to an increased risk of OCD diagnosis within 3 years of follow-up.
21
On the other hand, some investigations collecting cannabis users
reported how OC symptoms severity predicted more frequent
cannabis use.
22,23
Furthermore, the effect of cannabis on OC symptoms has been
investigated in some studies. Thus far, there have been only
two small cannabinoid trials in individuals with OCD. With the
limitation of a small sample (12 patients with OCD), a placebo-
controlled investigation of different concentrations of tetrahydro-
cannabinol and cannabidiol suggested that smoked cannabis has a
little acute impact on OC symptoms, compared to placebo.
24
In the
second trial, 11 patients received nabilone over 4 weeks showing
little effect on OC symptoms.
25
Conversely, the recent online
survey from Kayser and colleagues
19
reported a relevant amount
of participants (68.3%) experienced cannabis typically improved
their obsessions to varying degrees, while a subset reported that
cannabis worsened obsessions (17.3%) or compulsions (13.8%).
Another study including 87 individuals self-identifying with OCD,
measured (as tracked with a mobile app) a 60% reduction in
compulsions and a 49% reduction in intrusions from before to
after inhaling medical cannabis.
26
Other evidence of the effect of
cannabis on OC symptoms is based on case reports, which showed
a variable degree of improving after receiving dronabinol, a syn-
thetic oral form of THC
27,28
or medicinal cannabis treatment.
29
Although the results of this sparse literature suggest a possible
link between OCD and cannabis use, to the best of our knowledge
only limited studies have primarily investigated cannabis use in
patients with OCD. In addition, the favoring role of specific socio-
demographic or clinical features in cannabis users has not been
investigated. Therefore, the primary aim of this study was to
describe, in an Italian sample of patients with OCD, the frequency,
correlates, and predictors of cannabis use and its impact on OC
symptoms and on prescribed medications. Additionally, we wanted
to stratify the sample according to the degree of cannabis use. We
hypothesized that patients with sustained cannabis use would
manifest more unfavorable sociodemographic and clinical charac-
teristics compared with patients with discontinuous use or who
never use this substance. This work is part of an international
multicenter study in collaboration with the Department of Psychi-
atry and Behavioral Neuroscience at McMaster University in
Canada and the present report illustrates the preliminary results
of the Italian sample.
2. Methods
2.1. Participants
This retrospective and observational study was conducted at “Luigi
Sacco”University Hospital in Milan, Italy. Patients with OCD were
recruited from a tertiary psychiatric service dedicated to the diag-
nosis and treatment of outpatients with OCD. Recruitment took
place between May 2019 and September 2021.
Inclusion criteria were: adult subjects (over age 18 years) with a
diagnosis of OCD confirmed by trained psychiatrists through the
administration of the Structured Clinical Interviews for DSM-5
(SCID), clinical version.
30
In case of psychiatric comorbidities,
OCD had to be considered the primary disorder and directly
responsible for OC symptoms. Exclusion criteria included brain
diseases, intellectual disability, and psychiatric disorders secondary
to a medical condition.
The study was conducted in accordance with the declaration of
Helsinki.
31
Patients provided their written informed consent to
participate in this study and to use their anonymized data for
research purposes.
2.2. Measures
All patients were screened using a specific questionnaire developed
for the purpose of the study, which was edited by the McMaster
University Anxiety Working Group (through a collaboration of the
International College of Obsessive-Compulsive Spectrum Disor-
ders (ICOCS)). This questionnaire specifically investigated the
frequency and related features of cannabis use in a clinical popu-
lation of patients with OCD (see Supplementary material for the
extended version). The questionnaire comprises 34 questions
administered at baseline by specifically trained research investiga-
tors. The first part of the questionnaire collected sociodemographic
variables, including gender, age relationship status, ethnicity, living
situation, highest level of education achieved, and occupational
status. The second section focused on current and previous treat-
ments for OCD (including psychotropic medications and psycho-
therapeutic approaches) assessing the perceived effectiveness and
the reasons for discontinuation of previous treatments. The third
section of the questionnaire investigated current and past use of any
substance of abuse. Additional questions focused on cannabis use-
related habits. In particular, the following information was col-
lected: type of cannabis used (dried leaves or flowers, oils, edible,
tinctures), frequency of use in the past week, average amount of
cannabis consumed during a typical use and amount of cannabis
consumed daily. Additionally, patients were asked to report if they
were prescribed cannabis to treat OCD symptoms or another
medical condition. The last questions focused on the influence of
cannabis use on OCD symptoms (eg, improving or worsening
OCD symptomatology after cannabis use) and on OCD treatments
(eg, use of cannabis to treat OCD symptoms instead of a prescribed
medication/psychotherapy).
2 B. Benatti et al.
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
Additionally, to assess patients’clinical picture at study entry,
the questionnaire comprises three validated self-reported question-
naires: the Obsessive-Compulsive Inventory-Revised to measure
obsessive-compulsive traits (OCI-R),
32
the 9-item Patient Health
Questionnaire to measure depressive symptoms (PHQ-9),
33
and
the Generalized Anxiety Disorder-7 scale to assess symptoms of
general anxiety (GAD-7).
34
Patients’medical records were analyzed to integrate additional
clinical variables, in particular age at illness onset (AAO), age at
first treatment, duration of untreated illness (DUI, defined as
the time interval—in months—elapsing between the onset of the
disorder and the administration of the first adequate psycho-
pharmacological treatment), psychiatric comorbidities (pre-
existing or occurring after the onset of OCD), and family history
of psychiatric disorders. OCD symptoms severity was assessed at
study entry by trained clinicians also through the administration of
the Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS).
35
2.3. Statistical analysis
Descriptive analyses of socio-demographic and clinical variables
were performed for the whole sample. Additionally, descriptive
analyses of habits related to cannabis use were performed in the
subgroup of patients who reported current or lifetime cannabis use.
To stratify the sample accordingto the degree of cannabis use, we
adopted the following criteria, which were previously adopted in an
ICOCS study investigating cigarette smoking in patients with
OCD
36
:“current users”(CUs), ie, patients who used cannabis within
6 months prior to study entry; “past users”(PUs), ie, patients who
used cannabis in their lifetime but discontinued at least 6 months
before receiving the questionnaire; and “non-users”(NUs), ie,
patients who had never used cannabis in their lifetime. This distri-
bution ideally reflected different severitiesof cannabis use in terms of
frequency and duration, where CUs were patients with a more
sustained and severe form of substance use, compared with PUs
that used cannabis in their past, and, lastly, compared with NUs who
ideally did not share risk factors for cannabis use.
Nonparametric Kruskal–Wallis and chi-squared tests were used
to compare the three subgroups with respect to continuous and
categorical variables considering the non-normal distribution of
these data. Statistical significance was set at P< .05. Statistical
analyses were performed using Statistical Package for the Social
Sciences (SPSS) version 26 software (IBM Corp.; Armonk, NY,
USA).
3. Results
3.1. Sample description
Seventy consecutive patients were included in the study (females:
57%, mean age: 37.1 13.4 years). Nearly all patients were iden-
tified as Caucasian (98%). Table 1 outlines the main socio-
demographic and clinical features of participants.
3.2. Habits related to cannabis and other substances use
With respect to cannabis use, 40 subjects had never used cannabis
in their life (NUs, 57.1%), while 30 patients (42.9%) had. Among
those who had used cannabis, 20 subjects had not used cannabis
6 months prior to study entry (PUs, 28.6% of the total sample),
while 10 patients (CUs, 14.3% of the total sample) were still using it.
With respect to other substances, 50% of patients reported a
lifetime use of tobacco, 67.7% reported a lifetime use of alcohol,
40.8% a combination of cannabis and alcohol use, and 7.2% used
other substances. Moreover, 19.9% of patients reported having
used, in their lifetime, prescription medications (ie, painkillers,
anxiolytics, sleep aids/sedatives, stimulants outside the therapeutic
regimen, on higher doses or frequency). In the last 6 months, 37.1%
of patients reported tobacco use, 58.5% alcohol, 12.8% a combina-
tion of cannabis and alcohol, and 10% prescription medications.
Focusing on the effect of substances use on OC symptoms, 30%
the total sample reported to have consumed a substance with the
purpose to treat or help managing OC symptoms. In particular,
cannabis was used for this purpose in 10% of patients, alcohol in
15.7%, tobacco in 7.1%, and prescription psychotropic drugs in
8.5%. Among cannabis users, a minority (10%) reported that this
substance had helped reducing OC symptoms, with an average
satisfaction score of 1.4 2.9 on a scale from 0 (not at all effective)
to 10 (extremely effective). Further details on the impact of canna-
bis on OC symptoms revealed that one patient (3.3%) reported a
reduction in the number of intrusive thoughts, one (3.3%) a ces-
sation of obsessions, and one (3.3%) a decrease in general anxiety.
On the other hand, 23.3% of cannabis users reported a worsening of
OC symptoms because of their cannabis use, associated with an
increase in general anxiety.
No patient reported to have used cannabis instead of their
prescribed treatment for OCD. Additionally, no patient reported
to have reduced their prescribed OCD medications dose because of
cannabis use or went off of OCD treatment or chose to use only
cannabis to treat their OC symptoms. Only one patient (1.4%)
reported using a cannabis prescription for a different medical
condition (ie, chronic pain) than OCD.
3.2.1. Comparison between current cannabis users, previous
users, and non-users
Figures 1 and 2outline significant differences between the three
subgroups.
PUs and CUs showed a lower age (31 10.6 and
31.4 11.3 years, respectively) compared to NUs (41.4 14.5,
P=.01). No significantly differences emerged between the three
subgroups with respect to gender, living situation, highest level of
education achieved, employment, or relationship status.
Considering clinical variables, age at first treatment was signif-
icantly earlier for PUs and CUs (20.9 5.2 years and
22.4 5.3 years, respectively) compared to NUs (29.2 12.2 years,
P=.033).
With respect to comorbidities, a pre-OCD onset comorbidity
was significantly more common in CUs (90%) compared to NUs
(55%) and PUs (60%, P=.033). In detail, pre-OCD onset bipolar
disorder II was significantly more frequent in CUs (20%) compared
to PUs (0%) and NUs (2.5%, P=.027). The prevalence of post-
OCD onset comorbid major depression emerged to be higher
among NUs (32.5%) versus the other subgroups (PUs: 0% and
CUs: 20%, P=.015). Considering current medications, NUs were
treated more frequently with more than two psychotropic drugs
(25%) compared to PUs and CUs (5% and 0%, respectively,
P=.045).
Additionally, compared with NUs, PUs and CUs showed a more
frequent use of substances other than cannabis. In particular,
lifetime alcohol use emerged to be significantly more frequent in
PUs (100%) and CUs (90%) than NUs (45%, P< .001) and this
difference was confirmed when the question referred to the past
CNS Spectrums 3
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
Table 1. Sociodemographic and Clinical Variables of the Whole Sample and in the Three Subgroups
Variables All patients NUs PUs CUs
Number (%) 70 (100) 40 (57.1) 20 (28.6) 10 (14.3)
Age (years, mean SD) 37.01 13.8 41.4 14.5 31 10.6 31.4 11.3
Female gender (%) 57.1 55 55 83.3
Education (%)
Secondary school 14.3 7.5 25 20
High school 54.3 55 55 50
University 31.4 37.5 20 30
Employment (%)
Unemployed 24.5 27.5 20 20
Employed 55.7 55 65 40
Student 20 17.5 15 40
Co-habitation (%)
Alone 15.7 17.5 15 10
Family 42.9 40 50 40
Family of origin 40 42.5 35 50
In a stable relationship (%) 52.9 45 65 60
Age of onset (years) 21.1 10.6 24.1 12.2 17.7 5.8 16.3 7.9
<18 years (%) 42.9 37.5 40 70
Age at first treatment (years) 25.7 10.4 29.2 12.2 20.9 5.2 22.4 5.3
DUI (months) 58.8 81.4 61.9 89.7 43.8 75.6 77.3 57
Y-BOCS 21.5 9.5 17.6 10.1 19.9 8 24.3 7.3
OCI-R 23.8 12.6 22.6 11.7 27.3 15.1 21.2 9.9
PHQ-9 11 6 10.6 6.5 11.2 5 12.2 6.2
GAD-7 9.7 5.4 8.9 5.8 11.2 4.9 10.1 3.9
Family history of psychiatric disorder (%) 64.3 57.5 75 70
Psychiatric comorbidities (%)
Pre-onset (any) 65.7 55 60 90
Bipolar disorder II 4.3 2.5 0 20
Post-onset (any) 65.7 70 55 70
Major depression 21.4 32.5 0 20
Tourette syndrome 8.6 2.5 15 20
Current medication (%)
Antidepressants 90 90 95 80
Antipsychotics 28.5 37.5 15 20
Mood stabilizers 7.1 7.5 5 10
Psychotherapy 17.1 12.5 25 20
Polytherapy (> 2 drugs) 15.7 25 5 0
Substance use lifetime (%)
Cannabis 42.9 0 100 100
Tobacco 50 32.5 75 70
Alcohol 67.1 45 100 90
Other substances 82.8 70 100 100
Non-prescription medications 19.9 22.5 10 30
4 B. Benatti et al.
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
6 months, although not at a significant level (PUs: 75.0%, CUs:
90%, NUs: 67.5%). Moreover, PUs (35%) and CUs (50%) reported
to have consumed more frequently more than one alcoholic drink
daily compared to NUs in the past 6 months (10%, P=.034).
Considering the use of alcohol as a coping strategy for OC symp-
toms, PUs and CUs (25% and 40%, respectively) reported the use of
alcohol as self-medication more frequently than NUs (5%, P=.01).
With respect to tobacco use, similar results emerged. Lifetime
tobacco use was significantly more frequent in PUs (75%) and
CUs (70%) than NUs (32.5%, P=.003); the same difference
emerged also for the previous 6 months (CUs: 70% vs PUs: 50%
vs NUs: 22.5%, P< .001). Lifetime use of at least one other sub-
stances of abuse (ie, cocaine, amphetamine/methamphetamine,
inhalants, hallucinogens, or heroin) was significantly higher in
CUs (100.0%) and PUs (100%) compared to NUs (70%, P=.004).
4. Discussion
In the present sample, 42.8% of patients with OCD reported lifetime
cannabis use (PUs plus CUs). This percentage is understandably
higher compared to a previous general population survey that
indicated1-year cannabis use in 34.5% ofyoung adults,
5
being likely
related to the different periods of time that were investigated (life-
time vs 1 year, respectively). Among patients who had used cannabis,
14.2% reported cannabis use in the 6 months prior to study entry
(CUs), reflecting more sustained and habitual use. Our results seem
to underestimate the use of cannabis in patients with OCD if
comparing to the recent study from Kayser and colleagues,
19
where
nearly 90% of participants reported using cannabis at least 1 day over
the previous month and nearly 60% reported using cannabis at least
daily. This latter study was conducted in the USA which shows an
increasing access to cannabis both for recreational and therapeutic
uses compared to European countries, and, additionally, the data
could have been biased since only participants with at least one
lifetime use of cannabis were recruited in the survey.
Table 1. Continued
Variables All patients NUs PUs CUs
Substance use past 6 months (%)
Cannabis 14.2 0 0 100
Tobacco 37.1 22.5 50 70
Alcohol 51 67.5 75 90
> 1 alcoholic drink daily (%) 22.8 10 35 50
Substance use to cope with OC symptoms (%)
Cannabis 14.2 0 0 100
Alcohol 15.7 52540
Note: Values for categorical and continuous variables are expressed in percentages and mean standard deviation (SD), respectively. Bold indicates a statistically significant difference.
Abbreviations: CUs: current cannabis users; NUs: non-cannabis users, PUs: past cannabis users; DUI: duration of untreated illness; GAD-7: General Anxiety Disorders Scale; OCI-R: Obsessive-
Compulsive Inventory-Revised; PHQ-9: Patient Health Questionnaire; Y-BOCS: Yale-Brown Obsessive-Compulsive Scale.
0
20
Pre-OCD
onset
comorbidity
Pre-onset
comorbidity
with Bipolar
Disorder II
Post-onset
comorbidity
with Major
Depression
More than
two
psychotropic
drugs
Lifetime
tobacoo use
Lifetime
alcohol use
Lifetime use
of other
substances
Use of
tobacco past
6 months
Use of
alcohol for
coping
motives
More than
one
alcoholic
drink daily
past 6
months
40
60
80
100
120
*
*
**
*
** *
*
**
Non Users Previous Users Current Users
Figure 1. Statistically significant categorical variables in the comparison between non-users, previous users, and current users of cannabis. Values for categorical variables are
expressed as %. OCD: obsessive-compulsive disorder; statistics: *: P< .05; **: P< .001.
Figure 2. Statistically significant continuous variables in the comparison between
non-users, previous users, and current users of cannabis. Values for continuous vari-
ables are expressed as mean standard deviation; statistics: *: P< .05.
CNS Spectrums 5
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
With respect to other substances, a considerable number of
patients investigated in the present study reported lifetime use of
tobacco and alcohol (50% and 67.1%, respectively). Comparing our
findings with previous studies (reporting rates ranging between 7%
and 22.4%
37,38
), we found an overall higher rate of smoking habits
(50%). Cigarette smoking in outpatients with OCD has been studied
in a previous report from the ICOCS, showing a cross-sectional
prevalence of 24.4% in the sample, and tobacco smokers were more
frequentlyassociated with comorbidity with Tourette’syndrome and
tic disorder and with a higher number of suicide attempts.
36
Arecent
systematic review, aimed at assessing the therapeutic use of nicotine
on OC symptoms, showed some efficacy in treatment-refractory
patients with OCD.
39
Therefore, tobacco might be potentially used
by more severe patients as a self-medication strategy. The prevalence
of alcohol use disorder in OCD differs among recent studies (rates
ranging from 7.5% to 20%)
40–42
and has been associated with
compulsivity trait,
43
male gender, and an increased risk of suicide.
41
Additionally, in our sample around two out of 10 patients reported
lifetime use of other non-prescription medications (19.9%) and
other substances of abuse (7.2%). These data seem to support a
certain predisposition towards substance use in patients with
OCD. This phenomenon has been investigated and debated in the
literature, with controversies about its reasons and frequency.
44
On
one hand, OCD is phenomenologically characterized by compulsiv-
ity and impulsivity
12
that would drive affected individuals to use
substances while, on the other hand, patients with OCD often show a
harm-avoidance phenotype, which would elicit the opposite effect.
The prevalence of a full-blown substance use disorder varied exten-
sively in previous literature investigations, from 1% (in an interna-
tional multicenter study carried out on community samples of
patients with OCD
45
) to 11% (in a large Danish population study
46
).
These differences are probably related to different sampling pro-
cedures. In a cross-sectional population survey conducted in the
Netherlands, the life-time and 12-month odds of being diagnosed
with a substance use disorder in subjects with OCD was significantly
higher than theodds for people without a psychiatric disorderand, in
men, the co-occurrence of substance dependence and OCD was
significantly higher than the co-occurrence of substance dependence
and any other psychiatric disorders.
47
On the contrary, the hypoth-
esis that OCD and substance use are not related emerged in some
studies showing that both alcohol and drug misuse disorders were
not significantly associated with OCD.
48
In another report, more-
over, substance use disorder was half as common in patients with
OCD than in the general population.
49
These mixed results under-
line the need to further investigate the reasons behind substance use
in OCD which may be related to different comorbidity profiles and
trajectories of OCD course.
In this light, the present study showed that 30% of patients with
OCD used a substance of potential abuse during their lifetime to
treat or to help manage their symptoms. In particular, alcohol was
the most used substance for this purpose (15.7%), followed by
cannabis (10%), other prescription medications (8.5%), and
tobacco (7.1%). A minority of cannabis users (10%) reported that
this substance has helped treat OCD symptoms (in reducing the
number of obsessions or levels of general anxiety), even if they
considered this effect minimal (average level of satisfaction around
2 on a scale from 0 to 10). Interestingly, no improvements in
compulsions were reported. On the other hand, 23.3% of cannabis
users reported a worsening of OCD symptoms because of cannabis
use (ie, increase of general anxiety). Even though the limited sample
size did not allow us to discover if an effect was more frequent than
the other, we could state these effects were not univocal among
patients. In the Italian culture, cannabis is often used as an illicit
substance outside of government authority’s control, although the
recent legalization of medical cannabis has not, so far, lead to
cannabis being indicated as a treatment for anxiety disorders.
Consequently, it is not surprising that the effects of cannabis use
were different, presumably also reflecting the variability of concen-
tration of phytocannabinoids, the different administrations, the
amount of substance consumed on one occasion, and the frequency
and total period of use.
50
Indeed, patients with OCD might decide
to experiment with cannabis due to the partial efficacy of conven-
tional medications (in our sample treatment satisfaction was
around 6.5 on a scale from 1 to 10). However, we observed that
no patient used cannabis to reduce or stop the therapy already
prescribed by their treating psychiatrist. Nonetheless, the social
perception related to the effect of cannabis might have led to the
cannabis use as a coping strategy to handle anxiety or OC symp-
toms. Relaxation and tension reduction were the most commonly
reported effects of cannabis use in previous investigations that
demonstrated a positive effect of cannabis use for anxiety
51,52
and other psychopathological dimensions (ie, to cope).
53–55
Considering the second aim of the present study, our hypothesis
that patients who used cannabis were clinically more severe was
supported by the higher frequency of more severe clinical variables
in cannabis users. First, CUs and PUs showed a younger mean age
and an earlier mean age of first treatment than NUs. As reported in
the literature, younger subjects are the ones more frequently using
cannabis and presumably, CUs and PUs received earlier clinical
attention or showed an earlier full-blown expression of the disease
due to a higher illness severity.
Another variable associated with a higher disease severity was
the presence of psychiatric comorbidities. CUs showed an addi-
tional psychiatric comorbidity before and after the onset of OCD,
although only pre-onset comorbidity rate was significantly higher
in this subgroup compared to PUs and Nus. Additionally, CUs
showed a significantly higher rate of pre-OCD onset comorbidity
with bipolar disorder II, compared with NUs and PUs.
The comorbidity between OCD and bipolar disorder has been
extensively investigated. In a recent meta-analysis, 13.5% of
patients with OCD had a comorbid bipolar disorder, with more
severe OCD symptoms during depressive episodes and decreased
severity during manic or hypomanic episodes.
56
An international
multicenter study conducted by the ICOCS reported that a higher
number of hospitalizations, more frequent add-on therapy, and a
higher severity of OCD symptoms were observed in the cases of
comorbidity with bipolar disorder.
57
This is likely the case of the
CUs subgroup investigated in the present study, reflecting a higher
severity of the disease.
Conversely, a significantly higher rate of comorbidity with
major depression disorder emerged in NUs compared to CUs
and PUs. This result is quite unusual, considering that the co-
occurrence of depression and cannabis use has strong evidence in
the literature.
58
Indeed, given the high frequency of depression as a
comorbidity, cannabis use may not be necessary to induce a
depressive episode. Interestingly, PUs showed no history of major
depression, but we believe that this could be a consequence of the
limited sample size of this subgroup, and a large sample seems
necessary to better understand the impact of this comorbidity.
Other clinical variables that have been consistently associated
with greater disease severity in different psychiatric disorders
including OCD
7
emerged to be more frequent in CUs compared
to the other subgroups. In detail, CUs showed a longer DUI and an
earlier AAO compared to the other subgroups. Despite the earlier
6 B. Benatti et al.
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
age of first treatment, CUs showed a longer DUI (more than 6 years)
compared with NUs (5 years) and PUs (less than 4 years). Con-
sidering available literature on OCD, the DUI is high (up to around
10 years in adults) and a longer DUI has been correlated with poor
treatment response and with considerable suffering for the indi-
vidual and their families.
59–61
The reasons why patients who use
cannabis have a longer DUI have not been investigated in patients
with OCD thus far. Previous studies reported how cannabis use
62,63
and substance use disorder
64
were responsible for a longer duration
of untreated psychosis. In the present sample, we might cautiously
suggest that the same effects took place in the context of DUI in
patients with OCD. Moreover, CUs showed an average AAO
younger than 18 years (AAO around 16.3 years), and this has been
identified by some authors as the “early onset”OCD phenotype,
previously associated with male gender, a longer DUI,
65
a more
frequent family history for OCD, as well as comorbidity with tic
disorders.
66
Similarly, psychometric questionnaires revealed a greater
degree of OC, depressive, and general anxiety symptoms in CUs
and PUs, compared to NUs. All these differences presumably
reflect a higher disease burden in patients with cannabis use,
although not reaching a statistically significant difference; a wider
sample size might increase the statistical significance.
Outside cannabis use, CUs and PUs showed a higher tendency
to other substances consumption, as highlighted by a significantly
more frequent lifetime use of alcohol, cigarette smoking, and
illicit substances compared with NUs. This association was main-
tained even in the closest temporal range, with alcohol and
tobacco (the latter at a statistically significant level) more fre-
quently used in PUs and CUs than NUs in the 6 months prior to
study entry. The higher use of alcohol, cigarettes, and other sub-
stances might be a consequence of a substance-use diathesis
manifested by cannabis users. On the other hand, it might reflect
another effort to cope with OC symptoms (ie, alcohol use to
reduce anxiety derived from obsessive thoughts) not adequately
treated with conventional medications. Indeed, NUs showed to be
more frequently on polypharmacotherapy, compared to CUs and
PUs, which might reflect a better care of these patients, with
consequently better response to their OC symptoms and therefore
a lower tendency to reach for other substances to manage their OC
symptoms.
Some limitations should be considered in the interpretation of
the results. First, the limited sample size of the sample, in particular
when divided in three subgroups, did not allow us to perform
additional subgroups analyses that would have better described
the impact of specific variables and might have reduced the power
of the study and increased the margin of error. Moreover, another
limitation of the study is represented by the possibility of type I
error since no adjustment for multiple comparisons were per-
formed. Our data showed cannabis users being the ones associated
with more severe markers of illness with respect to OCD; however,
this relationship might have been influenced by other variables (eg,
a greater number of comorbid conditions), not being primar-
ily related to cannabis use. Considering that cannabis is perceived
as an illegal substance in Italy, patients might have been fearful of
disclosing their use of cannabis to study investigators or have
minimized how much of this substance that they used. Moreover,
the cross-sectional/retrospective collection of data may have influ-
enced the results, with longitudinal data being likely more infor-
mative. Additionally, lifetime/current cannabis or other substances
use were the only variables related to substance use that have been
collected. Indeed, other characteristics related to substance use
disorders (ie, impaired control, social impairment, risky use, and
pharmacological implications derived from substances) were not
investigated and deserve further study. Lastly, the limited sample
size did not allow us to perform additional subgroup analyses that
would have better described the impact of specific variables.
5. Conclusion
Overall, the specific pattern of substance use might contribute to
the identification of a specific subgroup of patients with OCD that
manifest a low level of harm-avoidance trait and more consistent
impulsivity traits (although not measured in this study). Further
specific investigations targeted to explore the impact of neuropsy-
chological traits will need to be evaluated in future studies. Addi-
tionally, considering that these features might be associated with
more severe clinical variables, clinicians should pay specific atten-
tion to substance use during the assessment to correctly identify
and address these patients using specific therapeutic approaches.
Considering the young age and the brain susceptibility of these
patients, we believe additional attention must be raised at clinical
and at societal levels. Lastly, potential interference of cannabis with
pharmacokinetics of OCD medications is another area of potential
concern that requires further evaluation.
Acknowledgments. All authors were involved in drafting the manuscript and
agreed to its publication. All authors read and approved the final version of the
manuscript.
Ethics Statement. The study was conducted in accordance with the declara-
tion of Helsinki. The patients provided their written informed consent to
participate in this study and for the use of their anonymised data for research
purposes.
Financial Support. This research did not receive any specific grant from
funding agencies in the public, commercial, or not-for-profit sectors.
Author Contributions. Conceptualization: B.D.-O., B.B., M.V.A., C.D.,
M.D.B., M.V.; Investigation: B.D.-O., B.B., M.V.A., D.C., G.C., L.C., S.V.,
M.V.; Methodology: B.D.-O., B.B., M.V.A., A.V., D.C., G.C., L.C., M.V.; Project
administration: B.D.-O., B.B., M.V.A., M.V.; Supervision: B.D.-O., B.B., M.V.A.;
Validation: B.D.-O., B.B., M.V.A.; Visualization: B.D.-O., B.B., M.V.A., C.D.,
M.D.B., M.V.; Writing—original draft: B.D.-O., B.B., M.V.A., A.V., C.D., D.C.,
G.C., L.C., M.D.B., S.V., M.V.; Writing—review and editing: B.D.-O., B.B.,
M.V.A., C.D., L.C., M.D.B., M.V.; Data curation: B.B., A.V., L.C., M.V.;
Resources: B.B., L.C., S.V., M.V.; Formal analysis: A.V.
Disclosures. Drs Benatti, Vismara, Casati, Varinelli, Vanzetto, Conti, Cirni-
gliaro, Di Bartolomeo, and D’addario report no financial conflict of competing
interests.
Prof. Dell’Osso has received Grant/Research Support from LivaNova, Inc.,
Angelini and Lundbeck and Lecture Honoraria from Angelini, FB Health and
Lundbeck.
Dr. Van Ameringen reports personal fees from Allergan, personal fees from
Almatica, personal fees from Brainsway, personal fees from Lundbeck, personal
fees from Myriad Neuroscience, personal fees from Otsuka, grants, and
personal fees from Purdue Pharma (Canada), other from Janssen-Ortho Inc.,
personal fees from Pfizer, grants from Hamilton Academic Health Sciences
Organization, Innovation Grant, outside the submitted work.
Data Availability Statement. The data that support the findings of this study
are available from the corresponding author, [MV], upon reasonable request.
CNS Spectrums 7
https://doi.org/10.1017/S1092852922001006 Published online by Cambridge University Press
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