•There are many patients with psychiatric disorders who may benefit
from CBD therapy
✓Deemed to be a relatively safe compound
✓Good candidate for future clinical use in humans as it lacks
psychomimetic and other psychotropic effects
✓Controlled clinical trials are needed to determine efficacy for
✓Past studies have been limited to small patient populations,
which suggests that further studies still need to be executed on a
larger scale to prove therapeutic benefits
•Pharmacokinetics (PK) and Pharmacodynamics (PD)
✓Animal studies show that CBD has a narrow therapeutic dose
✓Research on a larger scale with human subjects is needed to
more clearly define the PK and PD of CBD
✓Its narrow therapeutic index (NTI) and insufficient PK data,
warrants further research to elucidate appropriate dosing
✓Further research is needed to examine wider dose ranges of CBD
•Mechanisms of Action
✓Determined that multiple mechanisms are involved that differ
from each other
✓Further research is needed to discover the exact mechanisms
responsible for its unique properties
The Future of CBD Oil as a Possible Pharmacologic Treatment Option in
Psychiatry: The Current State of the Literature
Authors and Affiliates: Ileana Arce, PharmD candidate 2020 ; Nisha Bhavsar, PharmD candidate 2021 ; Emily Casey, PharmD candidate 2021 ; Justine
Gabion, PharmD candidate 2020 ; Young Kim, PharmD candidate 2020 ; Soorim Yoo, PharmD candidate 2020 ; Megan E. Maroney, PharmD, BCPP [1,2].
1. Ernest Mario School of Pharmacy at Rutgers, the State University of New Jersey, 2. Monmouth Medical Center-RWJ Barnabas Health, Long Branch, NJ.
Cannabidiol (CBD) is a natural constituent of Cannabis sativa which has been
used medically throughout history.
•CBD does not elicit psychoactive effects unlike tetrahydrocannabinol (THC)
•Mediated through G-protein coupled receptors, cannabinoid type 1 (CB1) (in
the hippocampus, CNS), CB2 (in the immune system)
✓CB1 stimulation inhibits synaptic transmission of voltage-gated calcium
and potassium channels which prevents excessive neuronal activity to
reduce pain, anxiety, and inflammation
✓CB2 stimulation is limited in the central nervous system; CBD does not
✓CBD is highly lipophilic and readily crosses to intracellular sites of action
exerting effects of calcium homeostasis. This potentially provides
✓CBD has a multifold mechanism of action:
oDecreases GPCR activity
oIndirectly inhibits glutamate release
at CB1 receptors
oMildly mediates release of cytokines
by stimulation of CB2 to reduce
inflammation and pain
oTargets transient receptor potential (TRP) channels which
modulate intracellular calcium
oMay activate adenosine receptors for anti-inflammatory effects
•Past studies have shown benefits in the administration of CBD oil in patients
who have experienced a wide variety of disorders including anxiety and post
traumatic stress disorder.
•Epidiolex (cannabidiol) (CBD) was approved by the FDA on June 25, 2018 for
the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) or
Dravet Syndrome (DS) in patients >2 years of age.
•Sativex (tetrahydrocannabinol and cannabidiol) has not yet been approved by
the FDA but has been approved internationally for the adjunctive treatment
of multiple sclerosis in adults that experience neuropathic pain or spasticity
and who are unresponsive to other therapies; for the adjunctive treatment of
moderate-to-severe pain in adults with advanced cancer at the highest
tolerated dose of strong opioid therapy
1. Health Canada. Information for Healthcare Professionals: Cannabis (marihuana, marijuana) and the cannabinoids (October 2018)
2. Campos AC, Moreira F, Gomes F, et al. Multiple Mechanisms Involved in the Large-Spectrum Therapeutic Potential of Cannabidiol
in Psychiatric Disorders. Philos Trans R Soc Lond B Biol Sci. 2012;376(1607):3364-3378.
3. Karl T, Garner B, Cheng D. The therapeutic potential of the phytocannabinoid cannabidiol for Alzheimer’s disease. Behav
4. Lee JLC, Bertoglio LJ, Guimaraes FS, et al. Cannabidiol regulation of emotion and emotional memory processing: relevance for
treating anxiety-related and substance abuse disorders. BR J Pharmacol. 2017;174(19):3242-3256.
5. Bitencourt RM, Takahashi RN. Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to
Confirmation in Human Trials. Front Neurosci. 2018;12(502):1-10.
6. Zuardi AW, Crippa J, Hallak JEC, et al. Cannabidiol for the Treatment of Psychosis in Parkinson’s Disease. J Psychopharmacol.
7. Álverez BG, Izquierdo AY et al. The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene
and responds well to cannabidiol treatment. Seizure - European Journal of Epilepsy. August 2018;60:68-70.
8. Boggs DL, Surti T, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic
schizophrenia a randomized placebo controlled trial. Psychopharmacol. 2018;235(7):1923-1932.
9. Shannon S and Opila-Lehman J. Effectiveness of Cannabidiol One il for Pediatric Anxiety and Insomnia as Part of Posttraumatic
Stress Disorder: A Case Report. Perm J. 2016;20(4):108-111.
10. Russo M, Dattola V, Logiudice AL, et al. The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rational,
study design, and methodology. Medicine. 2018;96(46):1-5.
11. Hazekamp A. The Trouble with CBD Oil. Med Cannabis Cannabinoids. 2018;1:65-72.
12. Beardsley PM, Brands B, Ekwere IT, et al. Cannabidiol (CBD). Critical Review Report presented at WHO ECDD Fortieth Meeting.
Geneva, Switzerland. 2018 June.
•A literature search was completed using OVID to compile articles related to
the current place in pharmacotherapy of CBD and its potential for treating
•Search terms utilized: “Cannabinoids” “Cannabidiol” “Pharmacotherapy” and
•The search was further limited to include articles that met the following
✓Published between January 1st, 2016 and July 31st, 2018
(Articles published earlier were added if deemed)
✓Reviewing at least one of the following: Anxiety, Schizophrenia, Post-
traumatic Stress Disorder (PTSD), Alzheimer’s Disease (AD), Parkinson’s
Disease, and/or Multiple Sclerosis (MS)
•Relevant case reports, pre-clinical trials, as well as clinical trials were also
included in the search
•A total of 8 articles were identified and included in the literature review
•Anxiety/Substance Abuse: Human/preclinical trials supports anxiolytic effects
of CBD in disruption of fear memory reconsolidation and extinction of fear.
Possible mechanism has been shown to be via activation of one of the key
neurotransmitters, serotonin (5HT-1A). Author supports further investigation
of CBD as a common treatment for the disorder, especially its effects on
serotonin. Effects on processing of addictive memory as well as other possible
pharmacological mechanisms still need to be researched. A higher ratio of
CBD:THC may be more favorable.
✓Post-Traumatic Stress Disorder (PTSD): Both human/preclinical studies
on this subtype of anxiety disorder have shown significant
improvements in symptoms of the disease. Author suggests further
investigation of how the cannabinoid system and serotonergic
neurotransmission are involved in aversive memory processing.
✓Case report of a 10 year old female patient with PTSD secondary to
sexual abuse has shown that CBD oil can be effective in reducing
symptoms of anxiety and insomnia secondary to PTSD.
•Chronic Schizophrenia: Parallel-group, 6-week randomized placebo controlled
trial looking at a fixed tablet dosage form of CBD oil in stable patients treated
with antipsychotics; found that although well-tolerated, CBD was not
associated with improvements in cognitive and symptom evaluation scales.
•Alzheimer’s Disease (AD): Only done in-vitro; multiple methods of
administration used; author suggests looking specifically more into how the
CB2 receptors are related to an immunologic response that ultimately leads to
inflammatory neurodegeneration in AD; higher (10 fold or greater) ratio of
CBD:THC may be needed for efficacy.
•Psychosis in Parkinson’s Disease: Pilot study with 6 patients with psychosis
symptoms were evaluated; powder form of CBD was used for evaluation,
which was found to be effective and well-tolerated. Author suggests a
randomized double-blind clinical trial to further confirm such observations,
possibly investigating the effects of CBD on dopamine, one of the key
neurotransmitters involved in psychosis and Parkinson's disease.
•Explore the use of CBD oil in behavioral psychiatric disorders and illnesses
•Review past human trials or articles related to place in therapy of CBD oil, and
legal issues which have arisen in the past regarding the use of CBD oil
•Find out how the efficacy/safety of CBD may be affected by different routes given
AKNOWLEDGEMENTS & AFFILIATIONS
•Dr. Megan E. Maroney is a member of the Otsuka EXCEL Speaker’s Bureau and consultant for Novus Medical Education. She has
received educational honoraria from PlatformQ and Pharmacy Times.
•We would like to sincerely recognize the contributions of Dr. Megan E. Maroney. Thank you for your help and guidance throughout
the development of this project.
•A special thank you to Rutgers University for providing us with library resources as well as the Ernest Mario School of Pharmacy for
their encouragement of our participation in this project.
•This research received no outside donations. The authors of this literature review have no conflicts of interest or affiliations with any
of the manufacturers or distributors of the pharmaceutical agents discussed.
Analgesic, nonopioid; Cannabinoid; Skeletal muscle relaxant
Unknown antiepileptic action
Does not involve its effect on
Stimulates cannabinoid receptors CB1 and CB2 in CNS and dorsal root
induced analgesia; Stimulation of CB2 receptors
modulates immune function through cytokine release
Oral liquid; Increased absorption with
-fat or high-calorie meals
Buccal spray only; Do not inhale, spray into nose or towards throat; Do
not spray to sore or inflamed mucosa
Hypersensitivity to cannabidiol or any
component of the formulation
Hypersensitivity to cannabinoids, propylene glycol, ethanol,
peppermint oil, or any other component of the formulation; Serious
cardiovascular disease, history of schizophrenia or any other psychotic
disorder; Women of child
-bearing potential who are not using a
reliable form of contraception; Males intending to start a family;
-feeding; Children <18 years old
CNS depression, increased AST/ALT,
hypersensitivity reactions, suicidal
ideation, withdrawal from abrupt
Buccal mucosa irritation, cardiovascular effects, CNS effects,
genitourinary effects, substance abuse