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Dronabinol-induced hypomania: A case report and literature review

Case Report
Mental Health and Addiction Research
Ment Health Addict Res, 2019 doi: 10.15761/MHAR.1000174 Volum 4: 1-2
ISSN: 2398-5380
Dronabinol-induced hypomania: A case report and
literature review
Shirshendu Sinha1, Audrey Umbreit2*and Charles Sieberg3
1Department of Psychiatry and Psychology, Mayo Clinic Health System, Southwest Minnesota region, Mankato, MN, USA
2Department of Pharmacy, Mayo Clinic Health System, Southwest Minnesota region, Mankato, MN, USA
3College of Pharmacy Postgraduate Residency Program, University of Minnesota, New Ulm, MN, USA
*Correspondence to: Audrey Umbreit, PharmD, Mayo Clinic Health System
Eastridge Clinic, 101 Martin Luther King Jr Drive, Mankato, MN, 56001, USA,
Received: January 16, 2019; Accepted: January 30, 2019; Published: February
04, 2019
Dronabinol is a synthetic derivative of cannabis that is commonly
prescribed for chemotherapy-induced nausea and vomiting or cachexia
due to HIV/AIDS. Dronabinol and the cannabinoids found in medical
marijuana have complex eects on the central nervous system that can
lead to both positive and negative patient outcomes. Here we present
a case of dronabinol-induced hypomania in a 55-year-old male with
a history of bipolar disorder and substance use disorder. is case
emphasizes the need to thoroughly evaluate mental health conditions
before prescribing medical marijuana or synthetic cannabis derivatives
such as dronabinol.
Medical cannabis is used for a variety of conditions including
chemotherapy induced nausea and vomiting, appetite stimulation
in HIV/AIDs, chronic pain, and spasticity [1]. e safety of medical
cannabis as well as FDA-approved cannabinoids, dronabinol and
nabilone, in those with bipolar disorder warrants further investigation
as previous studies suggest that the use of cannabis may be associated
with exacerbation of manic symptoms [2]. Medical cannabis is available
in several formulations that contain varying amounts of psychoactive
delta-9-tetrahydrocannabinol (THC) and non-psychoactive
cannabidiol (CBD) [3]. e risk of developing manic symptoms in
patients with bipolar disorder who use dronabinol, a synthetic version
of THC administered orally, is largely unknown.
Clinical Case
Our patient is a 55-year-old Caucasian male who has been following
with psychiatry since July of 2016 for substance use disorder and the
following mental health conditions: bipolar I disorder, generalized
anxiety disorder, PTSD, and intermittent sleep disturbances with no
history of sleep apnea but recent reports of restless legs syndrome.
Other relevant medical conditions include HIV and a history of primary
restrictive eating disorder. He has no history of inpatient psychiatric
hospitalizations or of suicide attempts. In terms of substance use he has
a history of alcohol, cocaine, and cannabis use disorder but has been
abstinent from alcohol, tobacco, and illicit substances for more than a
year. e patient’s relevant medication list includes: bupropion XL 150
mg daily, quetiapine 300 mg daily at bedtime, and trazodone 50-100
mg at bedtime.
As a result of his HIV our patient was struggling with wasting
syndrome and signicant weight loss for which he was prescribed
dronabinol 2.5 mg twice daily on 5/19/17. At his visit with his
psychiatrist on 7/10/17, his bipolar disorder was noted to be stable. His
dose of dronabinol was later increased on 7/21/17 to 5mg twice daily.
At his psychiatrist visit on 8/1/2017, the patient was found to be in
a state of hypomania, presenting with symptoms including: increased
interest in sex, insomnia and increased animation. His judgment and
impulse control were also noted to be slightly impaired at this visit.
Excluding the dronabinol dose increase, no other medication changes
had taken place and the patient was not using any alcohol or other
To treat the patient’s hypomania, quetiapine was discontinued and
olanzapine 10 mg at bedtime was started to also help with insomnia
and promote weight gain. Bupropion was discontinued, his trazodone
was tapered o, and dronabinol was also discontinued under suspicion
for causing the hypomania. Upon follow up within a month, our
patient’s hypomania symptoms had mostly resolved. He had also begun
gaining weight with the olanzapine and reported improved sleep. He
acknowledged having a feeling of “buzz” while he had been taking the
dronabinol. He was continued on olanzapine 10 mg at bedtime and
continued o the trazodone, bupropion and dronabinol. He continues
to remain abstinent from alcohol and illicit drugs.
e underlying mechanism of dronabinol induced manic
symptoms in those with bipolar disorder remains unclear but may
involve dopamine. Sensitization of the dopaminergic system by THC
is thought to be associated with the development of manic symptoms
in those that use cannabis [2]. THC is associated with increased
dopaminergic cell ring, dopamine synthesis, and dopamine release
when used acutely [4].
Other medications have been associated with causing manic
symptoms, including bupropion and trazodone, as relevant to our
case [5,6]. However, our patient had previously been stable on these
medications prior to the addition of dronabinol. us, it is reasonable
to conclude that the dronabinol likely caused our patient’s hypomania
Sinha S (2019) Dronabinol-induced hypomania: A case report and literature review
Ment Health Addict Res, 2019 doi: 10.15761/MHAR.1000174 Volume 4: 2-2
In recent years the regulatory status of marijuana for medical and
recreational use has changed in several states [7]. is has led to a
growing population of patients who are using cannabinoids and as our
case report has shown, those with underlying mental health conditions
may be at risk of developing serious adverse eects. A thorough
evaluation of mental health conditions and substance use disorders is
necessary to identify patients for whom the use of medical cannabis or
dronabinol is appropriate.
Dr. Sinha has received grant funding from UCare. Drs. Umbreit
and Sieberg have no disclosures.
No funding received for this case report.
1. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, et al. (2015) Cannabinoids for
Medical Use: A Systematic Review and Meta-analysis. JAMA 313: 2456-2473. [Crossref]
2. Gibbs M, Winsper C, Marwaha S, Gilbert E, Broome M, et al. (2015) Cannabis use and
mania symptoms: a systematic review and meta-analysis. J Affect Disord 171: 39-47.
3. Lim K, See YM, Lee J (2017) A Systematic Review of the Effectiveness of Medical
Cannabis for Psychiatric, Movement and Neurodegenerative Disorders. Clin
Psychopharmacol Neurosci 15: 301-312. [Crossref]
4. Bloomeld MA, Ashok AH, Volkow ND, Howes OD (2016) The effects of Δ9-
tetrahydrocannabinol on the dopamine system. Nature 539: 369-377. [Crossref]
5. Goren JL, Levin GM (2000) Mania with bupropion: a dose-related phenomenon? Ann
Pharmacother 34: 619-621. [Crossref]
6. Warren M, Bick PA (1984) Two case reports of trazodone-induced mania. Am J
Psychiatry 141: 1103-1104. [Crossref]
Copyright: ©2019 Sinha S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
ResearchGate has not been able to resolve any citations for this publication.
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The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials). A total of 24 reports that evaluated the use of medical cannabis for Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis and Tourette syndrome were included in this review. Trial quality was assessed with the Cochrane risk of bias tool. There is a lack of evidence on the therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and dystonia. Although trials with positive findings were identified for anorexia nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in Parkinson's disease, definitive conclusion on its efficacy could not be drawn. Evaluation of these low-quality trials, as rated on the Cochrane risk of bias tools, was challenged by methodological issues such as inadequate description of allocation concealment, blinding and underpowered sample size. More adequately powered controlled trials that examine the long and short term efficacy, safety and tolerability of cannabis for medical use, and the mechanisms underpinning the therapeutic potential are warranted.
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The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid–dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system. Acute THC administration causes increased dopamine release and neuron activity, whereas long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of THC.
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Background Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. Methods A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Results Six articles met inclusion criteria. These sampled 2,391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80 to 4.90) increased risk for the new onset of manic symptoms. Limitations We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. Conclusions Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time.
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To report a case in which bipolar depression was resistant to usual therapies, requiring dosages of bupropion >450 mg/d and to review the literature on mania associated with bupropion and propose a potential theory of a dose-related threshold associated with bupropion and mania. A 44-year-old white man with a 25-year history of bipolar affective disorder presented with depression resistant to usual therapies. Bupropion therapy was initiated and the dosage was titrated to 600 mg/d. After exceeding the maximum recommended daily dose (450 mg/d), he experienced a manic episode attributed to high-dose bupropion. Due to increased risk of seizures, current prescribing guidelines state that the total daily dose of bupropion is not to exceed 450 mg/d. Since bupropion is the agent least likely to cause a manic switch in bipolar disorder, this agent seemed a logical choice to treat the patient's depression. Due to a lack of response, the bupropion dosage was titrated to a maximum of 600 mg/d. Since the patient did not switch into mania until the dosage exceeded 450 mg/d, we speculate that this adverse reaction is a dose-related phenomenon. Scientific literature supports this theory. A switch into mania is a potential risk associated with antidepressant drug use in bipolar affective disorder. Bupropion is believed to be associated with a decreased risk compared with other antidepressant therapies. However, our case report as well as others support the theory that this decreased risk may be due to dosages not exceeding the recommended daily dose (450 mg/d). Doses of bupropion >450 mg/d should be used with caution in depressed patients with bipolar affective disorder.
Two unipolar depressed patients developed manic symptoms when treated with trazodone. The symptoms resolved when the drug was discontinued. The authors believe these to be the first two cases of such a reaction reported in the literature.