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Article ; Online: Panicolytic-like effects of environment enrichment on male mice threatened by Bothrops jararaca lancehead pit vipers.

de Paula Rodrigues, Bruno Mangili / Falconi-Sobrinho, Luiz Luciano / de Campos, Alline Cristina / Kanashiro, Alexandre / Coimbra, Norberto Cysne

Journal of neuroscience research

2024 Volume 102, Issue 2, Page(s) e25300

Abstract: Environment enrichment (EE) is a well-known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas ...

Abstract	Environment enrichment (EE) is a well-known eustress model showing beneficial effects in different psychiatric diseases, but its positive properties in panic disorders are not yet established. The confrontation between prey and predator in complex arenas has been validated as a putative panic attack model. The principal aim of this work was to investigate the role of the EE on panic-like defensive responses elicited by mice threatened by venomous snakes. After 6 weeks of exposure either to an enriched or standard environments, 36 male mice were habituated in a complex polygonal arena for snakes containing an artificial burrow and elevated platforms for escape. The animals were confronted by Bothrops jararaca for 5 min, and the following antipredatory responses were recorded: defensive attention, stretched attend posture, flat back approach, prey versus predator interaction, oriented escape behavior, time spent in a safe place, and number of crossings. Mice threatened by snakes displayed several antipredatory reactions as compared to the exploratory behavior of those animals submitted to a nonthreatening situation (toy snake) in the same environment. Notably, EE causes anxiolytic- and panicolytic-like effects significantly decreasing the defensive attention and time spent in safe places and significantly increasing both prey versus predator interaction and exploratory behavior. In conclusion, our data demonstrate that EE can alter the processing of fear modulation regarding both anxiety- and panic-like responses in a dangerous condition, significantly modifying the decision-making defensive strategy.
MeSH term(s)	Mice ; Male ; Animals ; Bothrops jararaca ; Crotalinae ; Panic Disorder ; Fear ; Panic/physiology
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.25300
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Zs.A 1232: Show issues

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Article ; Online: Environmental Enrichment Facilitates Anxiety in Conflict-Based Tests but Inhibits Predator Threat-Induced Defensive Behaviour in Male Mice.

Dos Anjos-Garcia, Tayllon / Kanashiro, Alexandre / de Campos, Alline Cristina / Coimbra, Norberto Cysne

Neuropsychobiology

2022 Volume 81, Issue 3, Page(s) 225–236

Abstract: Introduction: Environmental enrichment (EE) is a useful and sophisticated tool that improves rodents' well-being by stimulating social behaviour and cognitive, motor, and sensory functions. Exposure to EE induces neuroplasticity in different brain areas, ...

Abstract	Introduction: Environmental enrichment (EE) is a useful and sophisticated tool that improves rodents' well-being by stimulating social behaviour and cognitive, motor, and sensory functions. Exposure to EE induces neuroplasticity in different brain areas, including the limbic system, which has been implicated in the control of anxiety and fear. However, the effects of EE on ethologically relevant naturalistic behaviours, such as those displayed by prey in the presence of predators, remain largely unexplored. Material and methods: In the present study, we investigated anxiety- and panic attack-like behaviours in a predator (cat)-prey confrontation paradigm and compared them with those in classical assays, such as the elevated plus-maze (EPM), marble-burying, and open field tests (OFTs), using C57BL/6J male mice housed in enriched or standard environments for 6 weeks. Results: We observed that EE exposure caused enhancement of the levels of anxiety-like behaviours in the EPM and OFTs, increasing risk assessment (an anxiety-related response), and decreasing escape (a panic attack-like response) behaviours during exposure to the predator versus prey confrontation paradigm. Conclusion: Taken together, our findings suggest that enriched external environments can modify the processing of fear- and anxiety-related stimuli in dangerous situations, changing the decision-making defensive strategy.
MeSH term(s)	Animals ; Anxiety ; Anxiety Disorders/psychology ; Behavior, Animal/physiology ; Fear/physiology ; Fear/psychology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Panic Disorder
Language	English
Publishing date	2022-01-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	442239-9
ISSN	1423-0224 ; 0302-282X
ISSN (online)	1423-0224
ISSN	0302-282X
DOI	10.1159/000521184
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Article ; Online: Sex and estrous cycle-linked differences in the effect of cannabidiol on panic-like responding in rats and mice.

Hernandes, Paloma Molina / Batistela, Matheus Fitipaldi / Nascimento-Silva, Jefferson Manoel / Frias, Alana Tercino / Matthiesen, Melina / Campos, Alline Cristina / Lovick, Thelma Anderson / Zangrossi, Helio

Behavioural brain research

2023 Volume 455, Page(s) 114663

Abstract: Clinical and preclinical studies point towards anxiolytic actions of cannabidiol (CBD), but its effect in panic disorder has been less explored and few studies consider effects in females. We here compared the effect of CBD on the response of male and ... ...

Abstract	Clinical and preclinical studies point towards anxiolytic actions of cannabidiol (CBD), but its effect in panic disorder has been less explored and few studies consider effects in females. We here compared the effect of CBD on the response of male and female rats and mice to a panicogenic challenge; exposure to low O
Language	English
Publishing date	2023-09-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2023.114663
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Zs.A 1599: Show issues

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Article ; Online: Neonatal maternal deprivation facilitates the expression of a panic-like escape behavior in adult rats.

Rosa, Daiane Santos / Frias, Alana Tercino / Vilela-Costa, Heloísa Helena / Spiacci, Ailton / Sant'Ana, Ana Beatriz / Fusse, Eduardo Junji / Suchecki, Deborah / Campos, Alline Cristina / Lovick, Thelma Anderson / Zangrossi, Hélio

Behavioural brain research

2022 Volume 434, Page(s) 114031

Abstract: A wealth of evidence associates disruptions of the parent-infant relationship (e.g. childhood parental loss or parental neglect) with the later appearance of panic disorder. In rodents, neonatal maternal separation and maternal deprivation (MD) are ... ...

Abstract	A wealth of evidence associates disruptions of the parent-infant relationship (e.g. childhood parental loss or parental neglect) with the later appearance of panic disorder. In rodents, neonatal maternal separation and maternal deprivation (MD) are reported to increase the expression of anxiety-related defensive responses in adult animals. However, little is known about the long-term consequences of these early-life stressors in animal models of panic. We here investigated the effects of a single 24 h-episode of MD on post-natal day 11 (PND 11) in adult male Wistar rats submitted to two animal models that associate escape expression with panic attacks: the elevated T-maze and exposure to severe hypoxia (7% O
MeSH term(s)	Animals ; Animals, Newborn ; Escape Reaction ; Fenclonine ; Hypoxia ; Male ; Maternal Deprivation ; Panic ; Periaqueductal Gray ; Rats ; Rats, Wistar ; Serotonin
Chemical Substances	Serotonin (333DO1RDJY) ; Fenclonine (R5J7E3L9SP)
Language	English
Publishing date	2022-07-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2022.114031
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Zs.A 1599: Show issues

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Article ; Online: Neuroprotection and gliosis attenuation by intravenous application of human mesenchymal stem cells (hMSC) following ventral root crush in mice.

Cartarozzi, Luciana Politti / Perez, Matheus / Fernandes, Gabriel Gripp / Chiarotto, Gabriela Bortolança / Luzo, Ângela Cristina Malgeiros / Campos, Alline Cristina / Kirchhoff, Frank / de Oliveira, Alexandre Leite Rodrigues

Molecular and cellular neurosciences

2021 Volume 118, Page(s) 103694

Abstract: Rupture and stretching of spinal roots are common incidents that take place in high-energy accidents. The proximal axotomy of motoneurons by crushing of ventral roots is directly related to the degeneration of half of the lesioned population within the ... ...

Abstract	Rupture and stretching of spinal roots are common incidents that take place in high-energy accidents. The proximal axotomy of motoneurons by crushing of ventral roots is directly related to the degeneration of half of the lesioned population within the first two weeks. Moreover, only a small percentage of surviving motoneurons can successfully achieve regeneration after such a proximal lesion, and new treatments are necessary to improve this scenario. In this sense, mesenchymal stem cells (MSC) are of great interest once they secrete a broad spectrum of bioactive molecules that are immunomodulatory and can restore the environment after a lesion. The present work aimed at studying the effects of human mesenchymal stem cells (hMSC) therapy after ventral root crush (VRC) in mice. We evaluated motoneuron survival, glial reaction, and synapse preservation at the ventral horn. For this purpose, C57BL/6 J were submitted to a crush procedure of L4 to L6 ventral roots and treated with a single intravenous injection of adipose-derived hMSC. Evaluation of the results was carried out at 7, 14, and 28 days after injury. Analysis of motoneuron survival and astrogliosis showed that hMSC treatment resulted in higher motoneuron preservation (motoneuron survival ipsi/contralateral ratio: VRC group = 53%, VRC + hMSC group = 66%; p < 0.01), combined with reduction of astrogliosis (ipsi/contralateral GFAP immunolabeling: VRC group = 470%, VRC + hMSC group = 250%; p < 0.001). The morphological classification and Sholl analysis of microglial activation revealed that hMSC treatment reduced type V and increased type II profiles, indicating an enhancement of surveying over activated microglial cells. The glial reactivity modulation directly influenced synaptic inputs in apposition to axotomized motoneurons. In the hMSC-treated group, synaptic maintenance was increased (ipsi/contralateral synaptophysin immunolabeling: VRC group = 53%, VRC + hMSC group = 64%; p < 0.05). Overall, the present data show that intravenous injection of hMSC has neuroprotective and anti-inflammatory effects, decreasing reactive astrogliosis, and microglial reaction. Also, such cell therapy results in motoneuron preservation, combined with significant maintenance of spinal cord circuits, in particular those related to the ventral horn.
MeSH term(s)	Animals ; Gliosis/therapy ; Humans ; Mesenchymal Stem Cells ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Spinal Cord ; Spinal Nerve Roots/injuries ; Spinal Nerve Roots/pathology
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1046640-x
ISSN	1095-9327 ; 1044-7431
ISSN (online)	1095-9327
ISSN	1044-7431
DOI	10.1016/j.mcn.2021.103694
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Zs.A 3035: Show issues

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Article ; Online: Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity.

Meyer, Erika / Bonato, Jéssica Mendes / Mori, Marco Aurélio / Mattos, Bianca Andretto / Guimarães, Francisco Silveira / Milani, Humberto / de Campos, Alline Cristina / de Oliveira, Rúbia Maria Weffort

Molecular neurobiology

2021 Volume 58, Issue 10, Page(s) 5338–5355

Abstract: Evidence for the clinical use of neuroprotective drugs for the treatment of cerebral ischemia (CI) is still greatly limited. Spatial/temporal disorientation and cognitive dysfunction are among the most prominent long-term sequelae of CI. Cannabidiol (CBD) ...

Abstract	Evidence for the clinical use of neuroprotective drugs for the treatment of cerebral ischemia (CI) is still greatly limited. Spatial/temporal disorientation and cognitive dysfunction are among the most prominent long-term sequelae of CI. Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa that exerts neuroprotective effects against experimental CI. The present study investigated possible neuroprotective mechanisms of action of CBD on spatial memory impairments that are caused by transient global cerebral ischemia (TGCI) in rats. Hippocampal synaptic plasticity is a fundamental mechanism of learning and memory. Thus, we also evaluated the impact of CBD on neuroplastic changes in the hippocampus after TGCI. Wistar rats were trained to learn an eight-arm aversive radial maze (AvRM) task and underwent either sham or TGCI surgery. The animals received vehicle or 10 mg/kg CBD (i.p.) 30 min before surgery, 3 h after surgery, and then once daily for 14 days. On days 7 and 14, we performed a retention memory test. Another group of rats that received the same pharmacological treatment was tested in the object location test (OLT). Brains were removed and processed to assess neuronal degeneration, synaptic protein levels, and dendritic remodeling in the hippocampus. Cannabidiol treatment attenuated ischemia-induced memory deficits. In rats that were subjected to TGCI, CBD attenuated hippocampal CA1 neurodegeneration and increased brain-derived neurotrophic factor levels. Additionally, CBD protected neurons against the deleterious effects of TGCI on dendritic spine number and the length of dendritic arborization. These results suggest that the neuroprotective effects of CBD against TGCI-induced memory impairments involve changes in synaptic plasticity in the hippocampus.
MeSH term(s)	Animals ; Cannabidiol/pharmacology ; Cannabidiol/therapeutic use ; Disease Models, Animal ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/pathology ; Ischemic Attack, Transient/metabolism ; Ischemic Attack, Transient/pathology ; Ischemic Attack, Transient/prevention & control ; Male ; Neuronal Plasticity/drug effects ; Neuronal Plasticity/physiology ; Neuroprotection/drug effects ; Neuroprotection/physiology ; Organ Culture Techniques ; Rats ; Rats, Wistar ; Spatial Memory/drug effects ; Spatial Memory/physiology ; Synapses/drug effects ; Synapses/metabolism ; Synapses/pathology
Chemical Substances	Cannabidiol (19GBJ60SN5)
Language	English
Publishing date	2021-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-021-02479-7
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Zs.A 2411: Show issues

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Article ; Online: Evidence for a potential role for TRPV1 receptors in the dorsolateral periaqueductal gray in the attenuation of the anxiolytic effects of cannabinoids.

Campos, Alline Cristina / Guimarães, Francisco Silveira

Progress in neuro-psychopharmacology & biological psychiatry

2009 Volume 33, Issue 8, Page(s) 1517–1521

Abstract: Several studies have shown anxiolytic effects of cannabinoids after systemic or central injections. The periaqueductal gray matter is a midbrain structure involved in the control of anxiety states. Intra-cerebral administration of cannabidiol, a ... ...

Abstract	Several studies have shown anxiolytic effects of cannabinoids after systemic or central injections. The periaqueductal gray matter is a midbrain structure involved in the control of anxiety states. Intra-cerebral administration of cannabidiol, a phytocannabinoid, or anandamide, an endocannabinoid, into the dorsolateral portion of periaqueductal gray (dlPAG) promotes anxiolytic-like effects in several animal models of anxiety with bell-shaped dose-response curves. The reasons for these curves are still unclear, but since these drugs can also activate TRPV1 receptors and increase glutamate release, we hypothesized that, at high doses, cannabidiol and WIN 55,212-2, a CB1 receptor agonist, could activate TRPV1 receptors, facilitating glutamate neurotransmission and anxiety responses. To test this hypothesis male Wistar rats with cannulae aimed toward the dlPAG were submitted to the following intra-dlPAG treatments: Experiment 1. Vehicle (0.2 microL) or WIN 55,212-2 (3-30 pmol); Experiment 2. Capsazepine (CPZ, 10 nmol, a TRPV1 receptor antagonist) or vehicle followed, 5 min later, by vehicle or WIN 55, 212-2 (10 or 30 pmol); Experiment 3. CPZ (10 nmol) or vehicle followed, 5 min later, by cannabidiol (30 or 60 nmol). Ten minutes after the last injection the animals were tested in the elevated plus maze (EPM). WIN 55,212-2 and cannabidiol induced anxiolytic effects at lower doses that disappeared at the higher dose. Although CPZ+WIN 10 or CPZ+WIN 30 pmol groups were not different from control (CPZ+V), capsazepine prevented the decrease in open arm exploration caused by the higher of dose of WIN 55,212-2 (30 nmol) relative to the lower dose of WIN 55,212-2 (10 nmol) and, in the case of cannabidiol (60 nmol), increased open arm exploration (V+CBD 60 group versus CPZ+CBD 60 group). These results suggest that TRPV1 receptors in the dlPAG modulate anxiety and that activation of these receptors by high doses of cannabinoids could be involved in the bell-shaped dose-response curves observed with these compounds.
MeSH term(s)	Analgesics/administration & dosage ; Analysis of Variance ; Animals ; Anxiety/drug therapy ; Anxiety/pathology ; Arachidonic Acids/therapeutic use ; Benzoxazines/administration & dosage ; Cannabinoid Receptor Modulators/agonists ; Cannabinoid Receptor Modulators/antagonists & inhibitors ; Cannabinoid Receptor Modulators/therapeutic use ; Capsaicin/administration & dosage ; Capsaicin/analogs & derivatives ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Endocannabinoids ; Male ; Microinjections/methods ; Morpholines/administration & dosage ; Naphthalenes/administration & dosage ; Periaqueductal Gray/drug effects ; Polyunsaturated Alkamides/therapeutic use ; Rats ; Rats, Wistar ; TRPV Cation Channels/physiology ; Time Factors
Chemical Substances	Analgesics ; Arachidonic Acids ; Benzoxazines ; Cannabinoid Receptor Modulators ; Endocannabinoids ; Morpholines ; Naphthalenes ; Polyunsaturated Alkamides ; TRPV Cation Channels ; Trpv1 protein, rat ; (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone (5H31GI9502) ; capsazepine (LFW48MY844) ; Capsaicin (S07O44R1ZM) ; anandamide (UR5G69TJKH)
Language	English
Publishing date	2009-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	781181-0
ISSN	1878-4216 ; 0278-5846
ISSN (online)	1878-4216
ISSN	0278-5846
DOI	10.1016/j.pnpbp.2009.08.017
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Zs.A 1342: Show issues

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Article ; Online: Effects of Ayahuasca on the Recognition of Facial Expressions of Emotions in Naive Healthy Volunteers: A Pilot, Proof-of-Concept, Randomized Controlled Trial.

Rocha, Juliana Mendes / Rossi, Giordano Novak / de Lima Osório, Flávia / Bouso, José Carlos / de Oliveira Silveira, Gabriela / Yonamine, Mauricio / Campos, Alline Cristina / Bertozi, Giuliana / Cecílio Hallak, Jaime E / Dos Santos, Rafael G

Journal of clinical psychopharmacology

2021 Volume 41, Issue 3, Page(s) 267–274

Abstract: Background: The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of ... ...

Abstract	Background: The recognition of emotions in facial expressions (REFE) is a core aspect of social cognition. Previous studies with the serotonergic hallucinogens lysergic acid diethylamide and psilocybin showed that these drugs reduced the recognition of negative (fear) faces in healthy volunteers. This trial assessed the acute and prolonged effects of a single dose of ayahuasca on the REFE. Methods: Twenty-two healthy volunteers participated in a pilot, proof-of-concept, randomized trial. Study variables included a REFE task performed before and 4 hours after drug intake, subjective effects (self-reports/observer impressions), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. The REFE task was applied again 1, 7, 14, and 21 days and 3 months after drug intake. Stability of ayahuasca alkaloids during the study was also assessed (room temperature, 18 months). Findings: Compared with placebo, ayahuasca did not modify the REFE. No significant effects were observed on cardiovascular measures and brain-derived neurotrophic factor levels. Volunteers reported visual effects, tranquility/relaxation, and well-being, with few reports of transient anxiety/confusion. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting. A significant time-dependent deterioration of alkaloids was observed, especially for dimethyltryptamine. Conclusions: Absence of significant effects on the REFE task could be due to lack of effects of ayahuasca (at the doses used), alkaloid degradation, learning effects, and the high educational level of the sample. Further trials with different samples are needed to better understand the effects of ayahuasca and other serotonergic hallucinogens on the REFE. Future trials should improve methods to guarantee the stability of ayahuasca alkaloids.
MeSH term(s)	Adult ; Banisteriopsis/chemistry ; Double-Blind Method ; Facial Recognition/drug effects ; Female ; Hallucinogens/pharmacology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Plant Preparations/pharmacology ; Proof of Concept Study ; Time Factors ; Young Adult
Chemical Substances	Hallucinogens ; Plant Preparations
Language	English
Publishing date	2021-04-12
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	604631-9
ISSN	1533-712X ; 0271-0749
ISSN (online)	1533-712X
ISSN	0271-0749
DOI	10.1097/JCP.0000000000001396
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Zs.A 1664: Show issues

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Article ; Online: Role of 5-HT

Vilela-Costa, Heloisa H / Maraschin, Jhonatan Christian / Casarotto, Plinio C / Sant'Ana, Ana Beatriz / de Bortoli, Valquiria C / Vicente, Maria Adrielle / Campos, Alline Cristina / Guimarães, Francisco S / Zangrossi, Helio

Behavioural brain research

2021 Volume 404, Page(s) 113159

Abstract: Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5- ... ...

Abstract	Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5-HT
MeSH term(s)	Aminopyridines/pharmacology ; Animals ; Antidepressive Agents/pharmacology ; Anxiety/drug therapy ; Blotting, Western ; Elevated Plus Maze Test ; Fluoxetine/pharmacology ; Imipramine/pharmacology ; Indoles/pharmacology ; Male ; Open Field Test/drug effects ; Panic/drug effects ; Periaqueductal Gray/drug effects ; Periaqueductal Gray/metabolism ; Periaqueductal Gray/physiology ; Piperazines/pharmacology ; Pyridines/pharmacology ; Rats ; Rats, Wistar ; Receptor, Serotonin, 5-HT1A/drug effects ; Receptor, Serotonin, 5-HT1A/metabolism ; Receptor, Serotonin, 5-HT1A/physiology ; Receptor, Serotonin, 5-HT2C/drug effects ; Receptor, Serotonin, 5-HT2C/metabolism ; Receptor, Serotonin, 5-HT2C/physiology ; Serotonin 5-HT1 Receptor Antagonists/pharmacology
Chemical Substances	6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline ; Aminopyridines ; Antidepressive Agents ; Indoles ; Piperazines ; Pyridines ; Receptor, Serotonin, 5-HT2C ; Serotonin 5-HT1 Receptor Antagonists ; Fluoxetine (01K63SUP8D) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (71IH826FEG) ; Imipramine (OGG85SX4E4)
Language	English
Publishing date	2021-02-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2021.113159
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Article ; Online: Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le cannabidiol comme traitement d'appoint de la dépression bipolaire aiguë : une étude pilote.

Pinto, Jairo Vinícius / Crippa, José Alexandre S / Ceresér, Keila Maria / Vianna-Sulzbach, Miréia Fortes / Silveira Júnior, Érico de Moura / Santana da Rosa, Gabriel / Testa da Silva, Manoella Guatimuzim / Hizo, Gabriel Henrique / Simão Medeiros, Leonardo / Santana de Oliveira, Carlos Eduardo / Bristot, Giovana / Campos, Alline Cristina / Guimarães, Francisco Silveira / Hallak, Jaime E C / Zuardi, Antonio W / Yatham, Lakshmi N / Kapczinski, Flávio / Kauer-Sant'Anna, Márcia

Canadian journal of psychiatry. Revue canadienne de psychiatrie

2023 Volume 69, Issue 4, Page(s) 242–251

Abstract: Objective: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the ...

Abstract	Objective: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. Method: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. Results: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. Conclusion: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.
MeSH term(s)	Humans ; Bipolar Disorder/drug therapy ; Cannabidiol/pharmacology ; Cannabidiol/therapeutic use ; Pilot Projects ; Depression ; Psychotic Disorders/drug therapy ; Double-Blind Method ; Treatment Outcome
Chemical Substances	Cannabidiol (19GBJ60SN5)
Language	English
Publishing date	2023-11-03
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304227-3
ISSN	1497-0015 ; 0008-4824 ; 0706-7437
ISSN (online)	1497-0015
ISSN	0008-4824 ; 0706-7437
DOI	10.1177/07067437231209650
Database	MEDical Literature Analysis and Retrieval System OnLINE

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