RINPAS Journal Supplement

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Impact of Co-Morbid Cannabis Dependence on Symptom
Presentation in Acute Mania
Santosh Kumar, Vidhata Dixit, S. Chaudhury
Abstract

Background: Cannabis is among common substances used by bipolar patients. The relationships between
cannabis use and bipolar disorders are complex and remain incompletely described. The aim of this study
was to evaluate the impact of co-morbid cannabis dependence (CDS) on symptom presentation of acute
bipolar mania. Methods: The impact of co-morbid cannabis dependence on symptom presentation of
acute mania was examined by comparing subjects with ‘acute bipolar mania with psychotic symptoms
with co-morbid cannabis dependence (n=30) and with subjects with ‘acute bipolar mania with psychotic
symptoms but without co-morbid cannabis dependence (n=30)’. Results: Though the total scores on
MSRS and BPRS were comparable in two groups, significantly higher scores on three items of BPRS-
Anxiety (Mann Whitney-U=279.5; p<.01), Conceptual Disorganization (Mann Whitney-U=297; p<.05), and
Unusual Thought Content (Mann Whitney-U=286.5; p<.01) were found in patients of acute mania with
CDS in comparison to those without CDS. A statistically significant positive correlation was found between
MSRS total score and BPRS total score in patients of acute mania with CDS (rs=.504; p<.01; n=30) as well
as in those without CDS (rs=.491; p<.01; n=30). Conclusion: Overall there is no significant difference in
manic or psychotic symptoms in patients of acute bipolar mania either with or without co-morbid cannabis
dependence. Symptom domains of BPRS like anxiety, unusual thought content, and conceptual
disorganization are more severe in such patients with co-morbid cannabis dependence in comparison to
those without co-morbid cannabis dependence. There is a positive relationship in severity of psychotic
and manic symptoms in acute mania.
Key Words: Symptom presentation, acute mania, co-morbid cannabis dependence

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People with bipolar disorder frequently struggle with
substance abuse and dependence (Regier et al.,
1990; Strakowski et al., 1996; Strakowski et al.,
2000a; Cassidy et al., 2001; Baethge et al., 2005).
Apart from tobacco, alcohol and cannabis are two
substances commonly abused by bipolar patients
(Regier et al., 1990). There has always been an
underestimation of the users and uses of cannabis
in comparison to alcohol or tobacco (Hall and
Degenhardt, 2005). The reasons explaining the
intake of cannabis are often relaxation, well-being,
curiosity but also the desire to have fun, sociability,
group conformity, and complicity with others.
Cannabis and its different forms can be found easily
and at lower prices. In some studies (Regier et al.,
1990; Strakowski et al., 1998b; Strakowski et al.,
2000b; Strakowski et al., 2005) of bipolar disorder,
particularly those with younger patients, the rates
of cannabis use disorders equal or exceed those of
alcohol abuse or dependence. There are several
studies (Salloum et al., 2002; Winokur et al., 1995;
Strakowski et al., 2005) which investigated effect
of co-morbid alcohol abuse/dependence on
symptoms presentation of acute mania. In contrast,
the effects of cannabis have been less studied.
Salloum et al. (2002) concluded that acute bipolar
mania complicated by concurrent alcohol misuse
was differentiated from acute bipolar mania without
alcohol misuse by the presence of higher numbers
of manic symptoms and increased high risk
behavior such as mood lability, impulsivity, and
violence.
The relationships between cannabis use and
bipolar disorders are complex and remain
incompletely described (Strakowski et al., 2000a).
Some investigators (Grinspoon et al 1998; Ashton
et al., 2005) have implied that cannabis may actually
be mood stabilizing in patients with bipolar
disorder, although this suggestion lacks research
support. In previous studies (Strakowski et al.,
1998a; Strakowski et al., 2000b), it has been found
that almost any temporal relationship occurs
between cannabis use and affective symptoms in
bipolar samples. Few systematic studies published
suggest that cannabis abuse is associated with
poor treatment adherence (Strakowski et al.,
1998a), increased duration or severity of mania

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(Strakowski et al., 2000; Baethge et al., 2005), and
negative outcome in bipolar disorder (Cassidy et
al., 2001; Baethge et al., 2005). Prospective studies
by Regeer et al. (2006) and Henquet et al. (2006)
suggest that cannabis use may affect population
expression of manic symptoms (and subsequent
risk to develop bipolar disorder) and that these
findings may not be due to the emergence of
psychotic symptoms or the effects of self-
medication. However, this relationship is not well
studied in clinical samples. In a very recent study
(Katz et al., 2010), no significant difference in
general manic symptoms between cannabis
abusers and nonusers was observed among
psychiatric inpatients admitted with various
diagnoses like schizophrenia, major affective and
anxiety disorders, organic psychotic and affective
disorders etc. However, cannabis users were less
depressive and with more severe thought/language
disturbances and poorer insight than nonusers
(Katz et al., 2010).
Systematic studies are not available from India
assessing the co-morbidity of cannabis abuse/
dependence in mania. In India, Kumar and Raju
(1998) found that the substance abuse in mania
led to significantly more dysphoric and irritatable
mood states and grandiose and persecutory
delusions.
Patients with acute mania often require
hospitalization, as their symptoms (grandiosity,
impulsiveness, agitation, psychosis etc.) may have
substantial legal, civil, work-related and social
repercussions. It would be of interest to see that
how co-morbidity of cannabis dependence in bipolar
patients affects the symptom-presentation of acute
mania. This could be of great importance in
developing effective treatment strategies for manic
patients with this co-morbidity. In India, where
cannabis abuse is prevalent and frequently
associated with patients of mania, the idea becomes
much more pertinent.
MATERIALS AND METHODS
Study Design
It was a hospital based cross sectional comparative
study between patients of two groups:
a)Patients with “acute bipolar mania with psychotic
symptoms with co-morbid cannabis dependence
syndrome” and
b)Patients with “acute bipolar mania with psychotic
symptoms but without co-morbid cannabis
dependence syndrome”.
Sample
The sample included 30 patients of each group. It
was selected from the outpatient department (OPD)
of Ranchi Institute of Neuropsychiatry & Allied
Sciences (RINPAS), Ranchi (India), through
consecutive sampling technique.
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Inclusion and Exclusion Criteria
The patients of both the groups were male in age
range of 18-45 years and they were free from oral
psychotropic medication for at least four weeks and
for injectable (depot) psychotropic medication for
at least six weeks before appearance of symptoms.
It was ensured that the psychiatric symptoms were
not due to acute medical illness or acute drug
withdrawal. There was no history of mental
retardation, manic stupor or catatonia, or any other
psychiatric co-morbidity. Harmful use or
dependence of any substance other than nicotine,
caffeine was ruled out in both the groups. A
diagnosis of ‘Acute Mania’ in patients of both groups
was labeled as “bipolar affective disorder, current
episode manic with psychotic symptoms (F31.2)”
as per ICD-10, DCR (W.H.O., 1993).
The patients with co-morbid cannabis dependence
had additional diagnosis of “mental and behavioral
disorders due to use of cannabinoids; dependence
syndrome, currently using the substance [active
dependence] (F12.24)” as per ICD-10, DCR (W.H.O.,
1993). It was must for the patients with co-morbid
cannabis dependence to score at least 8 on the
CUDIT (Cannabis Use Disorder Identification Test).
The patients of both the groups gave informed
consent.
Tools for Assessment
·Socio-demographic and clinical data sheet [self
prepared]
This was a self prepared semi structured performa
especially designed for this study. It was used for
recording socio-demographic details like age,
religion, marital status, education, occupation,
residence, state, socioeconomic status, and family
type as well as clinical details such as age of onset,
duration of illness, episodes, previous
hospitalizations, treatment details etc.
·Cannabis Use Disorders Identification Test (CUDIT;
Adamson and Sellman, 2003)
The CUDlT is a 10-question, self-report screening
instrument employing a 5-point Likert Scale. It is
a modification of the AUDIT (Alcohol Use Disorders
Identification Test). The instrument was recently
developed and its ability to accurately assess
cannabis abuse or dependence was tested. The first
2 questions ask about current use while the other
8 refer to the past 6 months. The maximum score
possible is 40 with a cut-off of 8 demonstrating a
positive predictive value of 81.8% and sensitivity
of 73.3 %.
· Manic State Rating Scale(MSRS) (Beigel et al.,
1971)
The MSRS (also referred to as the Beigel scale) is a
26-item clinician-administered scale developed to
assess severity of symptoms of mania. Relying upon
observation of the patient rather than patient report,
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the MSRS is useful in situations where conducting
an interview is difficult. The scale can be followed
over time to monitor the patient’s state and
response to interventions. Items are rated on a
frequency (0–5 scale, range 0–130) and intensity
scale (1–5 scale, range 26–130). Score for each
behavior is the product of the points for frequency
and intensity. Thus minimum score for each
observation is 0 and maximum score for each
observation is 25. The scores on MSRS vary from
0-625. The higher the score, the more marked the
manic state. The items best characterizing a
change in manic severity are 3, 5, 9, 15, 18 and 26.
Brief Psychiatric Rating Scale (BPRS; Overall and
Gorham, 1962)
The Brief Psychiatric Rating Scale (BPRS) is a
clinician-rated tool designed to assess symptoms
that are common in patients with psychotic
disorders, including schizophrenia and other
psychotic disorders, as well as those found in
patients with severe mood disorders, especially
those with psychotic features. The scale originally
published in 1962 contained only the first 16 items;
2 additional items (excitement and disorientation)
were added in 1972. The 18-item BPRS is the most
commonly used version. The 18 items of BPRS
RESULTS
Table 1: Comparison of Socio-demographic Variables between Two Groups
include somatic concern, anxiety, emotional
withdrawal, conceptual disorganization, guilt
feelings, tension, mannerisms and posturing,
grandiosity, depressive mood, hostility,
suspiciousness, hallucinatory behaviors, motor
retardation, uncooperativeness, unusual thought
content, blunted affect, excitement, and
disorientation. The scale is a reliable and valid
instrument to assess the broad range of psychotic
symptoms, but it is not designed to
comprehensively measure theoretical domains of
psychopathology.
Procedure
After taking the informed consent, socio-
demographic & clinical details of patients of both
the groups were collected. The patients with co-
morbid cannabis dependence were screened on the
CUDIT. The patients of both the groups were
assessed for manic symptoms with the Manic State
Rating Scale (MSRS; Beigel et al., 1971) and for
psychotic symptoms with the Brief Psychiatric
Rating Scale (BPRS; Overall and Gorham, 1962).
Analysis of Data
The data obtained was analyzed using the
Statistical Package for Social Sciences version 16.0
(SPSS -16.0) with parametric and nonparametric

Acute Mania Acute Mania p /

Socio-demographic Variables with CDS without CDS t/χ2 df Fisher’s
(N = 30) (N = 30) exact p
Mean ± SD Mean ± SD
Age (in years) 29.37 ± 7.98 31.57 ± 7.60 -1.09 58 .279
Education (in years) 7.13 ± 4.36 8.13 ± 4.20 -.905 58 .369
n (%) n (%)
Religion Hindu 26 (86.7) 25 (83.3)
Non-Hindu 4 (13.3) 5 (16.7) .131 1 .718
Marital Married 11 (36.7) 11 (36.7) .000 1 1.00
status Unmarried 19 (63.3) 19 (63.3)
Occupation Unemployed 4 (13.3) 7 (23.3)
Employed 26 (86.7) 24 (80) .480 1 .488
Residence Rural 20 (66.7) 24 (80)
Urban 10 (33.3) 6 (20) 1.364 1 .415
State Jharkhand 12 (40) 19 (63.3) 3.27 1 .071
Bihar 18 (60) 11 (36.7)
SES Low 14(46.7) 17 (56.7) .601 1 .438
Middle 16 (53.3) 13 (43.3)
Family Nuclear 4 (13.3) 6 (20) .48 1 .488
Extended 26 (86.7) 24 (80)
Legend: CDS: Cannabis Dependence Syndrome; SES: Socioeconomic status

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Table 1 shows comparison of socio-demographic details of patients of acute mania with and without
cannabis dependence syndrome. Statistically no significant difference was observed in two groups in
terms of age, education, marital status, religion, and other socio-demographic details. The majorities of
the patients of two groups were Hindu, unmarried, employed, and belonged to extended family and rural
background.
Table 2A and 2B show comparison of clinical details of patients of acute mania with and without co-
morbid cannabis dependence syndrome.
Table 2A: Comparison of Clinical Variables between Two Groups

Acute Acute Mania p /

Clinical Variables Mania with without CDS t/χ2 df Fisher’s
CDS (N=30) exact p
(N=30)
Mean ± SD Mean ± SD
Age of onset of bipolar illness (in years) 21.23 ± 20.63 ± 4.47 .507 58 .614
4.70
Duration of bipolar illness (in years) 7.93 ± 5.54 10.86 ± 6.78 -1.84 58 .072
No. of past affective episodes 3.37 ± 1.99 3.70 ± 2.10 -0.630 58 .531
No. of past psychiatric hospitalizations 1.27 ± 1.67 1.13 ± 1.22 .354 58 .725
Duration of current manic episode 1.07 ± .47 1.05 ± .50 .15 58 .880
(in months)
n (%) n (%)
Family history Absent 11 (36.7) 8 (26.7) .693 1 .405
(affective illness) Present 19 (63.3) 22 (73.3)
Mode of onset Abrupt 2 (6.7) 4 (13.3)
(current m anic episode) Acute 12 (40) 17 (56.7) - - .182
Insidious 16 (53.3) 9 (30)
Precipitating factor Absent 7 (23.3) 10 (33.3) .739 1 .567
(current manic episode) Present 23 (76.7) 20 (66.7)

Legend: CDS: Cannabis Dependence Syndrome.

Statistically no significant difference was found between two groups in terms of age of onset & duration of
bipolar illnesses, number of past affective episodes & past psychiatric hospitalizations, and family history
of affective illnesses. Also, there was no significant difference in two groups regarding duration, mode of
onset & occurrence of precipitating factor(s) of current manic episode.
Table 2B: Comparison of Clinical Variables between Two Groups

Acute Mania with Acute Mania

Clinical Variables CDS (N=30) without CDS (N=30) U p
Mean ± SD Mean ± SD
MSRS Total Score 258.17 ± 82.19 260.13 ± 79.70 327.5 .069
BPRS Total Score 45.47 ± 5.94 42.33 ± 7.55 426.5 .728
Anxiety 2.13 ± 1.14 1.43 ± .81 279.5** .005
Conceptual Disorganization 3.23 ± 1.65 2.26 ± 1.20 297* .020
Unusual Thought Content 3.37 ± 1.88 2.43 ± 1.76 286.5* .013

Legend: CDS: Cannabis Dependence Syndrome; MSRS: Manic State Rating Scale; BPRS: Brief Psychiatric
Rating Scale; U: Mann Whitney-U; *significant at p<.05; **significant at p<.01.

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Table 3: Correlation of MSRS Total Score & BPRS Total Score in patients of Acute Mania with (N=30)
and without (N=30) CDS
Acute Mania with CDS
Correlation (N=30)
rs
MSRS Total Score
& .504**
BPRS Total Score
tests being used as applicable.
Although there was no significant different between
the patients of both groups in terms of the total
scores on MSRS (Manic State Rating Scale) and
BPRS (Brief Psychiatric Rating Scale), a significantly
higher score of three items of BPRS- Anxiety (Mann
Whitney-U=279.5; p<.01), Conceptual
Disorganization (Mann Whitney-U=297; p<.05), and
Unusual Thought Content (Mann Whitney-U=286.5;
p<.01) was found in patients of acute mania with
co-morbid cannabis dependence syndrome in
comparison to those without co-morbid cannabis
dependence syndrome. The scores of remaining
items of BPRS and all the items of MSRS were
comparable statistically in two groups.
A statistically significant positive correlation was
found between the MSRS total score and BPRS total
score in both the patients of acute mania with
cannabis dependence syndrome (rs=.504; p<.01;
n=30) as well as in patients of acute mania without
cannabis dependence syndrome (rs=.491; p<.01;
n=30).
No significant correlation was found between the
age, age of onset of affective illness, total duration
of affective illness, duration of current manic
episode, or number of previous hospitalizations
with either MSRS Total Score or BPRS Total Score
in patients of either group. Also, there was no
significant correlation between total CUDIT score
and total scores on MSRS or BPRS.
DISCUSSION
The finding of comparable total scores of MSRS and
BPRS in patients of both the groups indicates that
there was no significant difference in presentation
of the manic and psychotic symptoms in general of
acute mania either with or without co-morbid
cannabis dependence. However, three symptom
domains namely ‘anxiety’, ‘unusual thought
content’, and ‘conceptual disorganization’ of the
BPRS were significantly more severe in patients of
acute mania with co-morbid cannabis dependence.
To some extent these findings are supported by a
recent study of Katz et al. (2010). They too found
no significant difference in general manic symptoms
between cannabis abusers and nonusers observed
among psychiatric inpatients admitted with various
S178 RINPAS Journal 3 (Supplement) : September 2011
Acute Mania without CDS
(N=30)
p rs p
.005 .491** .006
diagnoses like schizophrenia, major affective and
anxiety disorders, organic psychotic and affective
disorders etc. However, cannabis users were less
depressive and with more severe thought/language
disturbances and poorer insight than nonusers
(Katz et al., 2010). Also, Katz et al. (2010) have
suggested some anxiolytic effect of cannabis on
psychotic and affective symptoms inpatients.
In literature, the effect of co-morbid cannabis
abuse/dependence on manic symptoms in patients
of bipolar disorder is not as clear as that on
psychotic symptoms of patients of psychotic
disorders like schizophrenia. Since the 1970’s, the
diagnosis of ‘Cannabis-modified mania’ has been
used (Knight, 1976), though Goldberg et al. (1996)
found cannabis use to be more related to mixed
mania than pure mania. The issue of cannabis
influence on appearance of manic symptoms in both
the general population and psychiatric patients is
controversial. Although, some case studies
(Strakowski and DelBello, 2000; Grinspoon and
Bakalar, 1998) have claimed cannabis to be the
substance that patients tried to use as self-
treatment of mania, a large-scale prospective study
(Henquet et al., 2006) suggested that cannabis may
be connected to development of mania.
The findings of the present study cannot be
compared directly with that of an Indian study by
Kumar and Raju (1998) who found that substance
abuse, in general, in mania led to significantly more
dysphoric and irritatable mood states and grandiose
and persecutory delusions.
Increased severity of the item ‘anxiety’ in patients
of mania with co-morbid cannabis dependence
indicated increased apprehension, tension, fear,
panic or worry reported by the cannabis dependent
patients. Findings of various studies support this
as cannabis use may be associated with long-
lasting anxious symptomatology. In a study of
persons who regularly used cannabis for at least
10 years, Reilly et al. (1998) found that 21% of these
subjects had high levels of state anxiety, and
several case reports have described cannabis-
induced agoraphobia (Moran, 1986) and panic
disorder (Deas et al., 2000; Langs et al., 1997).
Further, it has been found that panic attacks
constitute the most frequent acute anxiety

syndrome associated with cannabis use (Hall and
Solowij, 1998) and 20–30% of consumers present
with acute and brief anxiety reactions after smoking
cannabis (Thomas, 1996). However, it is currently
unclear if anxiety is best conceptualized as a
consequence of cannabis use in vulnerable
subjects, or conversely, if anxiety disorders may
favour cannabis use. Degenhardt et al. (2001) have
reported that among individuals with cannabis
dependence, 17% had at least one anxiety disorder
compared to 5% of non-users. An additional
possibility is that both cannabis use and anxiety
disorders may be independently induced by a shared
risk factor, such as specific pre-existing personality
traits. Though, in our study, we ruled out co-
morbidity of other psychiatric disorders including
anxiety disorders, there is need for further studies
which should take into account of pre-existing
personality traits.
A significant positive correlation of scores of MSRS
and BPRS indicates that the severity of psychotic
symptoms has bearing on severity of manic
symptoms in patient s of acute mania.
CONCLUSION
Overall there is no significant difference in manic
or psychotic symptoms in patients of acute bipolar
mania either with or without co-morbid cannabis
dependence. Symptom domains of BPRS like
anxiety, unusual thought content, and conceptual
disorganization are more severe in such patients
with co-morbid cannabis dependence in comparison
to those without co-morbid cannabis dependence.
There is positive relationship in severity of
psychotic and manic symptoms in acute mania.
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