The therapeutic role of Cannabidiol in mental health: a systematic review
The therapeutic application of cannabidiol (CBD) is gaining interest due to expanding evidence for its use.
To summarize the clinical outcomes, study designs and limitations for the use of CBD and nabiximols (whole plant extract from Cannabis sativa L. that has been purified into 1:1 ratio of CBD and delta-9-tetrahydrocannabinol) in the treatment of psychiatric disorders.
Materials and method
A systematic review was conducted including case reports, case series, open-label trials, non-randomized and randomized controlled trials (RCTs). The search resulted in 23 relevant studies on CBD and nabiximols in the treatment of a wide range of psychiatric disorders. The quality of evidence was judged by using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence that ranges from Level 1 to Level 5 based on the quality and study design. These levels of evidence help in grading the recommendations, including Grade A (strong), Grade B (moderate), Grade C (weak), and Grade D (weakest).
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating psychotic symptoms and cognitive impairment in patients with a variety of conditions, and several studies provided evidence of effectiveness in the treatment of cannabis withdrawal and moderate to severe cannabis use disorder with Grade B recommendation. There is Grade B recommendation supporting the use of CBD for the treatment of schizophrenia, social anxiety disorder and autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Grade C recommendation exists for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. These recommendations should be considered in the context of limited number of available studies.
CBD and CBD-containing compounds such as nabiximols were helpful in alleviating symptoms of cannabis-related disorders, schizophrenia, social anxiety disorder, and comorbidities of ASD, and ADHD with moderate recommendation. However, there is weaker evidence for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. The evidence for the use of CBD and CBD-containing compounds for psychiatric disorders needs to be explored in future studies, especially large-scale and well-designed RCTs.
Cannabis sativa, a species of cannabis plant, is well known to humankind, with its earliest use in ancient Chinese culture dating as far back as 2700 B.C. (Zuardi, 2006). The use of medical cannabis in China was reported in the world’s oldest pharmacopoeia (Martin et al., 1999). However, interest in the role of cannabis flourished in the late twentieth century after the recognition of an endogenous cannabinoid system in the brain (Zuardi, 2006; Martin et al., 1999). More recently, research has centered on the description and cloning of specific receptors and the therapeutic effects of medical cannabis, and different cannabinoids in the cannabis plant have gained interest (Martin et al., 1999). Recent studies have focused on the therapeutic role of medical cannabis in different disorders. As a result, there is a growing need to summarize and review the evidence for its therapeutic and adverse effects as an aid to public health policy development, and to provide direction and impetus to pharmaceutical research in this field.
The cannabis plant has more than 140 cannabinoid compounds, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) attracting significant interest (Citti et al., 2018). Δ9-THC is the primary psychoactive ingredient, and CBD is a non-intoxicating ingredient (Zuardi, 2006; Citti et al., 2018). Evidence from preclinical studies suggested that CBD had potential therapeutic benefits ranging from antiinflammatory to neuroprotective, antipsychotic, analgesic, anticonvulsant, antiemetic, antioxidant, antiarthritic, and antineoplastic properties; for a review, see (Pertwee, 2006). CBD has several receptors and molecular targets. This compound antagonizes the action of CB1 and CB2 receptor agonist (Blessing et al., 2015; Peres et al., 2018). The CB1 and CB2 receptors are coupled negatively through G-proteins to adenylate cyclase and positively to mitogen-activated protein kinase (Pertwee, 2006). In addition to CB1 and CB2 receptor activity, CBD is an agonist of vanilloid receptor TRPV1. It also acts as an agonist of serotonin receptor 5-hydroxytryptamine (5-HT1A), an antagonist of G-protein-coupled receptor GPR55, and an inverse agonist of GPR3, GPR6, and GPR12 (Peres et al., 2018). Data from single-photon emission computed tomography showed CBD to exert anxiolytic effects by acting on paralimbic and limbic pathways (Crippa et al., 2011). The agonist effect of CBD on 5-HT1A also supports its anxiolytic and antidepressant properties (Russo et al., 2005). CBD inhibits enzymatic hydrolysis and anandamide uptake through its agonist action on CB1, CB2, and TRPV1 receptors (Peres et al., 2018). In addition, CBD indirectly enhances endogenous anandamide signaling by inhibiting the intercellular degradation of anandamide (Leweke et al., 2012). This endogenous neurotransmitter exerts antipsychotic effects in patients with schizophrenia (Leweke et al., 2012).
The pharmacokinetic profile of CBD has been extensively explored in the existing literature. A recently published systematic review of the pharmacokinetics of CBD found that the area under curve (AUC0 − t) and maximum serum concentration (Cmax) occurs between 1 and 4 h (Millar et al., 2018). The AUC0 − t and Cmax reach maximum values faster after smoking or inhalation compared to oral or oromucosal routes. Bioavailability was 31% after smoking, but no other studies reported the absolute bioavailability of CBD after other routes in humans. The half-life of CBD ranges between 1.4 and 10.9 h after oromucosal spray and 2–5 days after chronic oral administration (Millar et al., 2018). Fed states and lipid formulations increase Cmax (Millar et al., 2018). The bioavailability of oral CBD ranges between 11 and 13%, compared to 11 to 45% (mean 31%) via inhalation (Scuderi et al., 2009). CBD is well-tolerated, yet despite a relatively lower risk of drug–drug interactions, it should be used cautiously in combination with drugs metabolized by the CYP3A4 and CYP2C19 pathways, and the substrates of UDP-glucuronosyltransferases UGT1A9 and UGT2B7 (Millar et al., 2018). The clinical relevance of these interactions needs to be explored in future studies (Brown & Winterstein, 2019).
Dronabinol and nabilone are synthetic in origin, whereas nabiximols is plant-based (Papaseit et al., 2018). The percentage of THC and its ratio to CBD (THC/CBD ratio) defines the potency and psychoactive effects of a given formulation (Papaseit et al., 2018). Those with higher CBD/Δ9-THC ratios have euphoric, anxiolytic, and relaxing effects, whereas lower CBD/Δ9-THC ratios have sedative properties (Papaseit et al., 2018). Nabiximols, a CBD-containing compound, contains Δ9-THC and CBD at a 1:1 ratio (Papaseit et al., 2018). The Food and Drug Administration has approved Epidiolex® (an oral formulation of CBD) for two forms of childhood seizures (Lennox–Gastaut syndrome and Dravet syndrome) in children 2 years of age and older (Papaseit et al., 2018).
Previous efforts to synthesize the evidence for medical cannabis use in patients with psychiatric disorders have been published (Hoch et al., 2019; Lowe et al., 2019). For example, Hoch et al. conducted an excellent systematic review that summarized four systematic reviews and 14 randomized controlled trials (RCTs), but did not consider non-clinical trial evidence (case reports and case series) (Hoch et al., 2019). A review by Mandolini et al. recently summarized the clinical findings from 14 studies of psychiatric disorders, but these authors did not provide information about nabiximols (Mandolini et al., 2018). In contrast to the review articles noted above, the present article aims to provide a more comprehensive review of the use of CBD and CBD-containing compounds such as nabiximols to treat psychiatric disorders. The present review included studies focused on schizophrenia, cannabis-related disorders, attention deficit hyperactivity disorder (ADHD), comorbidities in autism spectrum disorder (ASD), social anxiety disorder (SAD), other anxiety disorders, insomnia, bipolar disorder, post-traumatic stress disorder (PTSD), psychosis in Parkinson’s disease, and Tourette syndrome. This article broadly reviews the efficacy, safety, and psychiatric benefits of CBD and CBD-containing compounds (nabiximols). We distinguish clearly here between the clinical findings for CBD and nabiximols, as the latter also contains THC.
The main inclusion criterion was studies of the psychiatric use of CBD and CBD-containing compounds such as nabiximols. Only case reports, case series, retrospective chart reviews, open-label trials, and RCTs were considered. All books, conference papers, theses, editorials, review articles, metaanalyses, in-vitro studies, laboratory studies, animal studies, studies of participants without psychiatric disorders, and abstract-only articles were excluded. No restrictions on language, country, publication year, or patients’ age, gender, or ethnicity were applied.
Eight electronic databases were searched on October 28th, 2018: PubMed, Scopus, Web of Science, POPLINE, New York Academy of Medicine Grey Literature Report, PsycINFO, Psycarticles, and CINAHL. The following search strategy was used in all cases: (CBD OR Cannabi* OR nabiximols) AND (psychiat* OR Depress* OR Anxiety OR Psycho* OR schizo* OR Bipolar OR Substance OR ADHD OR Attention OR Autism) AND (treatment). The manual search of references of included studies was performed by four independent reviewers.
The search results from the eight databases were imported to Endnote v. 7 (Thompson Reuters, CA, USA) to remove any duplicates. Four independent reviewers (RK, NM, AF, MAF) screened the titles and abstracts (when available), followed by full-text screening of each included article with the predetermined eligibility criteria. All articles included after full-text screening were then searched manually. Discrepancies were resolved by consensus through discussion among reviewers, or with guidance from a third reviewer (SN).
Data extraction and grading
The data were extracted independently by the authors, and were cross-checked by discussion among the four reviewers (RK, NM, AF, MAF), with guidance from the senior author (SN) in case of discrepancy. The data were categorized as pertaining to target diagnosis, study design, sample size, duration of the trial, age range, dose ranges, measurement scales, clinical outcomes, study limitations, and common side effects.
The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence was used to grade the quality of evidence (OCEBM, 2019). Level 1 evidence is for systematic review of RCTs or individual RCT of narrow confidence interval, Level 2 for cohort studies or systematic review of cohort studies, Level 3 for case-control studies or systematic review of case-control studies, and Level 4 for case-series for studies focused on therapy, prevention, etiology and harm (OCEBM, 2019). These levels of evidence are used to generate Grades of Recommendation. Grade A is for consistent level 1 studies, Grade B for consistent level 2 or 3 studies or extrapolations from level 1 studies, and Grade C for level 4 studies or extrapolations from level 2 or 3 studies. Grade D is ranked for level 5 evidence or inconsistent or inclusive studies of any level (OCEBM, 2019).
Results & discussion
The search of eight electronic databases and our manual screening method generated 511 results. After the removal of duplicates, titles and abstracts were screened, resulting in the exclusion of 459 articles. Full-text screening of 52 articles was performed, and 23 articles meeting the inclusion criteria were analyzed. Figure 1 summarizes the screening process.
PRISMA Flow Diagram
Of the 23 articles, there were eight RCTs, one clinical trial, four open-label trials, one retrospective chart review, seven case reports, and two case series, comprising a total patient population of 526. The studies focused on CBD and nabiximols use in the treatment of schizophrenia, cannabis-related disorders, ADHD, ASD and comorbidities, anxiety, insomnia, SAD, bipolar disorder, PTSD, psychosis in Parkinson’s disease, and Tourette syndrome. No studies of substance use disorders other than cannabis use were identified. In this review article, the authors have used DSM-5 terminologies for most of the disorders except for DSM-IV-Text Revised terminology of substance dependence. A comparable DSM-5 terminology of moderate-severe substance use disorder was used in this case.
Qualitative synthesis of eligible studies
Schizophrenia and psychosis in Parkinson’s disease
There were three RCTs (164 patients), one clinical trial (27 patients), one case series (three patients), one case report for schizophrenia, and one open-label trial (six patients) for psychosis in Parkinson’s disease (Table 1) (Leweke et al., 2012; Hallak et al., 2010; Boggs et al., 2018; McGuire et al., 2018; Zuardi et al., 2006; Zuardi et al., 1995; Zuardi et al., 2009). Of the seven studies, level 2 evidence was found in three RCTs, level 3 evidence in two clinical trial, and level 4 evidence in one case report and one case series (OCEBM, 2019). Since most of the studies were from level 2 and level 3 evidence, there is Grade B recommendation for schizophrenia. The dose of CBD in these studies ranged from 200 to 1500 mg daily. The highest dose was titrated to 1500 mg daily as reported by Zuardi and colleagues (Zuardi et al., 1995). Irrespective of the study design, three studies reported that CBD alleviated psychotic symptoms and cognitive impairment in patients with chronic cannabis use and Parkinson’s disease (Leweke et al., 2012; Zuardi et al., 1995; Zuardi et al., 2009), while only two RCTs and one clinical trial provided evidence for the effectiveness of CBD among patients with schizophrenia, albeit with mixed results (Leweke et al., 2012; McGuire et al., 2018; Zuardi et al., 2009).
Table 1 Studies of CBD use in the treatment of schizophrenia and psychosis in Parkinson’s disease and levels of evidence (1 to 5)*
In a clinical trial, Hallak and colleagues suggested an improvement in schizophrenia-associated cognitive impairment with a CBD dose of 300 mg/day, while no significant improvement was seen at a CBD dose of 600 mg/day (Hallak et al., 2010). In another RCT, McGuire and colleagues found that CBD (1000 mg/day) improved positive psychotic symptoms, but failed to improve negative symptoms and general psychopathology associated with this illness (McGuire et al., 2018). In another RCT, Boggs and colleagues found that CBD (600 mg/day) failed to improve outcomes pertaining to reasoning and problem-solving domains (Boggs et al., 2018).
In a comparison of CBD with amisulpride, Leweke and colleagues reported similar improvements in patients taking CBD 800 mg/day and those taking amisulpride (Leweke et al., 2012). This study also indicated an increase in intrinsic anandamide signaling, an effect that explained the antipsychotic properties of CBD (Leweke et al., 2012). Moreover, CBD treatment was associated with a lower risk of extrapyramidal symptoms, less weight gain, and a lower increase in prolactin, which is a predictor of galactorrhea and sexual dysfunction (Leweke et al., 2012). An open-label study of CBD to treat psychosis in Parkinson’s disease also suggested promising results at a dose of 400 mg daily; however, there was a strong risk of bias because of inadequate blinding of participants, personnel and outcome assessors (Zuardi et al., 2009).
The remaining evidence comprised two minimal quality case reports and case series. Zuardi and colleagues were the first to report favorable findings for CBD in patients with schizophrenia (Zuardi et al., 1995). The dose of CBD ranged from 600 to 1500 mg daily in schizophrenia studies. A case series of three patients with treatment-resistant schizophrenia found improvement in only one patient (Zuardi et al., 2006). In the first case, there was an improvement in psychotic symptoms with CBD at 1280 mg/day; however, the symptoms worsened after CBD was discontinued. In second case, CBD was ineffective for the symptoms. Patient had an improvement in symptoms with clozapine. In the third case, no improvement with CBD and partial improvement with olanzapine were observed, although clozapine was subsequently required. In case 3, mild improvement was reported with CBD in a patient who had previously failed to respond to olanzapine, clozapine, or haloperidol decanoate. These results suggest a limited role of CBD in treatment-resistant schizophrenia (Zuardi et al., 2006). The dose were not individually mentioned for case 1 and 2.
Four of the included studies did not report any adverse effects of CBD among patients with psychosis. CBD was well-tolerated in these patients except for mild transient sedation, hyperlipidemia, and gastrointestinal distress. Patients with schizophrenia had fewer instances of extrapyramidal symptoms, less weight gain, and a lower increase in prolactin levels.
CBD is postulated to improve cognitive performance in psychosis through the mediation of CB1 and CB2 receptor agonism at lower concentrations (Hallak et al., 2010; Solowij et al., 2018; Manseau & Goff, 2015). This cognitive improvement has been hypothesized due to the higher concentration of cannabinoid receptors in the hypothalamus, suggesting a role in superior cognitive functioning (Hallak et al., 2010). Naturalistic studies of CBD report better cognitive performance including memory, increased grey matter in the hippocampus, and fewer psychotic symptoms in patients given higher doses of CBD (Solowij et al., 2018).
The therapeutic benefits for psychosis is hypothesized due to the inhibition of anandamide re-uptake and degradation, resulting in increased anandamide levels in the brain (Manseau & Goff, 2015). Increased anandamide levels and improvements in the symptoms of psychosis were reported in another 4-week-long RCT comparing the efficacy of CBD to amisulpride for the treatment of schizophrenia (Leweke et al., 2012). Interestingly, anandamide levels were elevated in patients with acute schizophrenia compared to chronic schizophrenia, indicating a compensatory increase in an acute state (Giuffrida et al., 2004).
The present review included three RCTs (107 patients), two open-label trials (28 patients), one case series of four patients, and two case reports for cannabis-related disorders as summarized in Table 2 (Solowij et al., 2018; Crippa et al., 2013; Trigo et al., 2016a; Trigo et al., 2018; Trigo et al., 2016b; Allsop et al., 2014; Pokorski et al., 2017; Shannon & Opila-Lehman, 2015). Of the eight studies, level 2 evidence was found in three RCTs, level 3 evidence in two clinical trial, and level 4 evidence in two case reports and one case series (OCEBM, 2019). For cannabis-related disorders, there is Grade B recommendation based on majority of studies ranked at the level 2 and level 3 of evidence.
Table 2 Studies of the use of CBD and CBD-containing compounds such as nabiximols in the treatment of cannabis-related disorders and levels of evidence (1–5)
Four of these studies evaluated the efficacy of nabiximols, and four others reported the use of CBD. The doses tested ranged from 20 mg CBD to a maximum of 1200 mg/day. Nabiximols was used in spray form at doses ranging from an average of 28.9 sprays/day (equivalent to 77.5 mg THC or 71.7 mg CBD) to 40 sprays/day (equivalent to 108 mg THC or 100 mg CBD). In CBD-only studies the dose of CBD ranged from 200 to 600 mg/day in divided doses. All three RCTs in this section provided evidence for the use of nabiximols for moderate to severe cannabis use disorder. These trials tested different doses of nabiximols ranging from 21.6 mg THC and 20 mg CBD (twice a day) to 113.4 mg THC or 105 mg CBD per day. All trials reported lower withdrawal rates, better tolerance, and retention rates in the experimental group. Moreover, no serious adverse effects were reported in any of these studies. In one RCT, nabiximols (total dose of 21.6 mg THC and 20 mg CBD at 4 and 10 in evening and night, respectively) was associated with marked improvement in cannabis withdrawal symptoms, leading to shorter withdrawal times and higher retention rates (Allsop et al., 2014). In a second RCT, a fixed dose of nabiximols produced more positive results compared to self-titrated administration (Trigo et al., 2016a). Patients in the fixed-dose group had four sprays of medications every hour compared to four sprays as needed every hour in self-titrated dose group. The maximum dose was 40 sprays/day in the self-titrated dose group. Medication intake was higher with fixed doses, which were associated with fewer withdrawal symptoms compared to the self-titrated regimen (Trigo et al., 2016a). In another RCT, the efficacy and safety of nabiximols were compared to a placebo while all participants also received weekly motivational enhancement therapy (MET) and cognitive–behavioral therapy (CBT) (Trigo et al., 2018). The dose range of 4.1 to 12.8 sprays/day was reported among nabiximols group. The withdrawal scores in this study were similar in both groups (Trigo et al., 2018). Only one of the studies reported decreased appetite, while the number and severity of adverse effects were not reported or observed in the other two RCTs.
Two open-label studies testing the effectiveness of two different concentrations of CBD (200 mg/day and 600–1200 mg/day) obtained positive outcomes with doses as low as 600 mg/day (Hallak et al., 2010; Pokorski et al., 2017). These studies had a small sample size of eight (Solowij et al., 2018) and 20 (Pokorski et al., 2017) participants, respectively. In the former open-label trial with eight participants, a dose of 600 mg/day was tested, and two out of five participants completed the 7-day inpatient treatment. These two participants reported abstinence at follow-up (day 28), and the remaining three participants reported decreased use of cannabis, confirmed by blood and urine analysis. In the second group, participants took 600 mg twice a day. Two out of three participants reported abstinence and in the remaining one, cannabis use had decreased, as confirmed by blood and urine analysis. All participants showed a decrease in Cannabis Withdrawal Scale scores. The second open-label trial tested the effectiveness of 200 mg CBD in divided doses in improving cognition and depressive symptomatology among patients with chronic cannabis use, and found improvement in severity of depression, verbal learning, and memory performance, and decreased frequency of positive psychotic-like symptoms and level of distress from baseline to endpoint (Solowij et al., 2018). State anxiety increased with no change in trait anxiety, functional impairment, or accuracy on cognitive tests (Solowij et al., 2018).
The remaining studies were either case series or case reports; all found positive outcomes in withdrawal and cannabis-dependence symptoms (Crippa et al., 2013; Trigo et al., 2016b; Shannon & Opila-Lehman, 2015). Mean age in the case series was 35 years, although the first participant was 19 years old and the second was 27 years old. The case series used self-titrated nabiximols at a dose of 77.5–113.4 mg THC and 71.5–105.0 mg CBD (Trigo et al., 2016b). Moreover, all participants reported a significant reduction in craving (Crippa et al., 2013; Trigo et al., 2016b; Shannon & Opila-Lehman, 2015), quicker relief (Crippa et al., 2013), lower anxiety, and an improved sleep schedule (Shannon & Opila-Lehman, 2015). However, the case series reported increased craving scores during the first 2 weeks with a subsequent reduction in craving at week 9. CBD was well-tolerated in this patient population, except for decreased appetite reported in one study (Trigo et al., 2016b). For patients receiving nabiximols or CBD, treatment should be augmented with psychotherapeutic modalities considering the positive evidence for an effect on cravings.
The effectiveness and tolerability of CBD and nabiximols for moderate to severe cannabis use disorder was reported in several studies. The efficacy may also be due to the synergetic or additive benefits of Δ9-THC and CBD rather than CBD alone. The Δ9-THC component of nabiximols decreases the severity of withdrawal symptoms, lowering the risk of relapse (Trigo et al., 2016a). However, there is mixed evidence for the role of nabiximols in cannabis-related craving (Trigo et al., 2016a; Trigo et al., 2018; Trigo et al., 2016b). Studies that included combined motivation enhancement and behavioral response prevention strategies suggested a reduction in craving (Trigo et al., 2016a; Trigo et al., 2018). CBD is thought to modulate the euphoric, anxiogenic, psychological, and physiological effects of Δ9-THC (Crippa et al., 2013). However, these benefits of CBD alone and in combination with THC need to be explored in head-to-head studies.
The present review included two RCTs (54 patients), one open-label trial (53 patients), one retrospective chart review (72 patients), and four case reports for CBD and nabiximols use in the treatment of other psychiatric disorders. Specifically, this review looked at ADHD (one RCT), comorbidities in ASD (one open-label trial), anxiety and sleep problems (one retrospective chart review), SAD (one clinical trial), bipolar disorder (one case report), PTSD (one case report), and Tourette syndrome (two case reports), as summarized in Table 3 (Cooper et al., 2017; Barchel et al., 2018; Bergamaschi et al., 2011; Shannon et al., 2019; Zuardi et al., 2010; Shannon & Opila-Lehman, 2016; Trainor et al., 2016; Pichler et al., 2019). Of the nine studies, level 2 evidence was found in two RCTs, level 3 evidence in one clinical trial, and level 4 evidence in one retrospective chart review, four case reports (OCEBM, 2019). There is Grade B recommendation for comorbidities in patients with ASD, anxiety disorders including SAD and sleep problems, and ADHD where as bipolar disorder, PTSD and Tourette Syndrome has Grade C recommendation. However, this should be considered in the context of fewer studies of each these diagnoses.
Table 3 Studies of the use of CBD and CBD-containing compounds such as nabiximols in the treatment of other psychiatric disorders and levels of evidence (1–5)*
The oromucosal nabiximols spray was tested to evaluate its effects on cognitive performance, hyperactivity, inattention, and emotional lability in 15 participants in a placebo-controlled RCT (Cooper et al., 2017). The mean dose of nabiximols was 4.7 sprays per day (2.7 mg Δ9-THC and 2.5 mg CBD). Although an improvement in these symptoms was observed in the intervention group, it failed to reach statistical significance (Cooper et al., 2017). However, this result may not be valid or reliable due to the low power of the study.
One case report on the use of CBD by two patients with bipolar disorder showed limited to no improvement with doses of 600–1200 mg for bipolar mania in one of the patients (Shannon et al., 2019). The second patient was prescribed CBD 600 mg (5–9 days) and olanzapine (10–15 mg), followed by CBD 900–1200 mg (20–33 days), and showed improvement on the Brief Psychiatric Rating Scale (37% reduction) and Young Mania Rating Scale (33% reduction) with CBD and olanzapine, but no additional improvement with CBD monotherapy (Shannon et al., 2019). This effect was consistent with results from animal studies that modeled acute mania with dextroamphetamine (Shannon et al., 2019). The lack of effectiveness can be attributed to the shorter duration of treatment in both cases. This evidence from studies of bipolar mania should be considered in the context of different pharmacological agents responding differently to certain episodes of bipolar disorder. In animal studies, CBD induced a rapid, persistent antidepressant response by increasing brain-derived neurotrophic factor in the prefrontal cortex (Shannon et al., 2019). Given its possible antidepressant benefits, the role of CBD should be explored in unipolar and bipolar depression.
In an open-label trial involving children with ASD, Barchel and colleagues reported that a solution of CBD and Δ9-THC (1,20 ratio) was effective for hyperactivity, insomnia, self-injurious behaviors, and anxiety (Barchel et al., 2018). The median dose was 90 mg with an interquartile range (IQR) of 45–143 mg for CBD whereas The medical dose was 7 mg with IQR of 4–11 mg. In this cohort of 53 patients, 74.5% showed improvement in their comorbid symptoms, 68.4% in hyperactivity, 67.6% in self-injurious behaviors, 71.4% in sleep problems, and 47.1% in anxiety symptoms. This treatment regimen lasted for a median of 66 days. However, Salgado and Castellanos suggested guiding principles for the use of CBD in this population, including a better clinical understanding of CBD, open discussion with parents and patients, addressing their perceptions, promoting informed consent, and exercising caution in the use of CBD (Salgado & Castellanos, 2018). Patients with ASD make up a heterogeneous group of individuals with different comorbidities that should be considered.
The efficacy of CBD for SAD and PTSD was explored in three studies including one RCT, one case report, and one chart review. The RCT reported the results of a simulated public speaking test among 12 healthy control participants and 24 patients with SAD who received a single dose of CBD 600 mg or a placebo before the test. This study reported that pretreatment with CBD resulted in less anxiety, cognitive impairment, and discomfort during their speaking performance. It also resulted in a significant reduction in alertness in their anticipatory speech compared to the placebo group (Bergamaschi et al., 2011).
In a 10-year-old patient, 5 months of treatment with CBD oil (25 mg) and liquid CBD (6–12 mg) in a sublingual spray as needed was associated with less anxiety and better sleep quality, with no adverse effects (Shannon & Opila-Lehman, 2016). These results were replicated for anxiety in a recently published chart review of 72 adult patients with insomnia and anxiety (Shannon et al., 2019). Most patients in this group were given 25 mg CBD/day, while a few patients were given 50 or 75 mg/day, and one patient with schizoaffective disorder and trauma was given up to 175 mg/day. All patients showed less anxiety and improved sleep, with reductions of 65–80% in the Hamilton Anxiety Rating Scale and Pittsburgh Sleep Quality Index scores.
Nabiximols produced improvements in patients with Tourette syndrome at a much lower dose than what was used for cannabis-related disorders (Trainor et al., 2016; Pichler et al., 2019). These case reports tested two oromucosal nabiximols sprays used twice a day (total dose 10.8 mg Δ9-THC and 10 mg CBD per day) (Trainor et al., 2016), and the second also tested cannabis tincture (34 drops three times a day (Pichler et al., 2019). Both case reports found improvements in tic frequency (Trainor et al., 2016; Pichler et al., 2019), severity (Trainor et al., 2016; Pichler et al., 2019), quality of life, and social activity (Trainor et al., 2016). These treatments regimens were used for 4 weeks with the oromucosal spray form (Trainor et al., 2016) and 8 weeks for cannabis tincture (Pichler et al., 2019). The therapeutic benefits can be attributed to the anxiolytic and sleep-inducing properties of CBD (Trainor et al., 2016). It is difficult to ascertain whether these improvements were due to due to CBD, Δ9-THC, additive, or synergetic effects. The anxiolytic properties of CBD explain the attenuation of anxiety associated with the onset of tics, and the improvement in tics with a combination of Δ9-THC and CBD (Trainor et al., 2016; Pichler et al., 2019).
Adverse effects were reported in four of the studies, and included muscular seizures and spasms (Cooper et al., 2017), somnolence and changes in appetite (Barchel et al., 2018), fatigue, and sexually inappropriate behavior in a patient with developmental disorder (Shannon et al., 2019), mild sedation (Zuardi et al., 2010), and mild xerostomia (Pichler et al., 2019).
Summary of evidence
The present article provides a comprehensive review of the evidence supporting the use of CBD and CBD-containing compounds such as nabiximols to treat psychiatric disorders. CBD and nabiximols were effective in cannabis use-related disorders, and preliminary evidence was found in support of their use for other psychiatric disorders. Of the 23 studies reviewed here, level 2 evidence was found in eight RCTs, level 3 evidence in four open-label trials and one clinical trial, and level 4 evidence in one retrospective chart review, seven case reports, and two case series, according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (OCEBM, 2019). This review covers the evidence for different routes of administration, e.g. oral, inhalation spray, and sublingual. The bioavailability of these routes (11–13% for oral vs. 11–43% for inhalation) varies significantly – a factor that can impact the efficacy of different formulations.
Their antipsychotic, neuroprotective, anxiolytic, and sedating properties suggest a potential therapeutic role of CBD and nabiximols to treat various psychiatric disorders. The use of CBD at higher doses (above 1200 mg per day) showed promising results in case studies of schizophrenia and psychosis in patients with Parkinson’s disease, except in treatment-resistant cases. Regarding the use of CBD to treat anxiety disorders, its anxiolytic effect can help patients with PTSD-related and social performance-related anxiety, and nabiximols can reduce the anxiety associated with the onset of tics. There is also favorable evidence in patients with ASD for reducing hyperactivity, self-injurious behaviors, anxiety, and insomnia. Nabiximols showed no credible effect in the treatment of ADHD, while CBD was also found to be ineffective for bipolar disorder. Of all the cases examined, the strongest evidence was found for the treatment of cannabis-related disorders. The use of nabiximols yielded positive results in multiple studies of moderate to severe cannabis use disorder; however, the use of CBD alone has not been adequately documented outside a few cases and case series. Notably, CBD compounds were helpful in alleviating psychotic symptoms and improving cognitive impairment in patients across a variety of conditions.
Recommendations for future research
This review found low-level evidence for the use of cannabis and nabiximols in a variety of disorders. Despite our comprehensive literature search, only a few RCTs related to the disorders of interest were found. These RCTs were marred by a number of limitations, most importantly failure to blind the outcome assessor, participants, and research personnel (in the open-label trials). In addition, most RCTs had a small sample size, critically reducing the power of the study to draw robust conclusions. The findings of the RCTs reviewed here need to be validated via a series of larger, well planned, randomized, double-blinded, and placebo-controlled studies. The present report can be used to design and plan further studies; however, at present the use of CBD and nabiximols in clinical practice cannot be recommended with confidence due to the drawbacks noted above.
The evidence from studies included in this review can guide future trials by providing information pertaining to the dosages, formulations and routes of administration of CBD and nabiximols. Moreover, future studies should investigate different routes of administration in light of the differences in bioavailability. In view of the (albeit limited) evidence for treatment-resistant schizophrenia, the role of CBD should be explored in the early stages of psychosis or as an adjunct medication. Although CBD was ineffective for bipolar mania, its possible efficacy as an antidepressant should be assessed in studies focused on bipolar depression. Nabiximols has been helpful in cannabis-related disorder and Tourette syndrome, owing to the synergetic benefits of CBD and THC. Future studies designed to explore the comparative benefits of these treatments can shed further light on their clinical potential. Future RCTs should also consider adding first-line treatment agents as comparison arms, to ascertain the comparative efficacy of CBD in different mental disorders. Although fewer side effects were reported overall by patients in the studies reviewed here, the vulnerability to addiction to cannabinoids should not be ignored.
Limitations of the review
This review article has several limitations that should be considered. This review article provides evidence for CBD and CBD-containing nabiximols are two different pharmacological agents. Nabiximols has two active compounds and included studies do not consider the separate effects of THC VS CBD. There is need for future analyses to carefully consider their benefits individually. Only one-third of studies (8/23) in this review article are RCTs and most of these RCTs had a small sample size decreasing the power of the study to draw robust conclusions.
The evidence reviewed here favors CBD use for patients with schizophrenia and psychosis in Parkinson’s disease in four out of seven studies, except in treatment-resistant cases. There is a Grade B recommendation this diagnosis based on the levels of evidence. Nabiximols and CBD were beneficial in cannabis-related disorders in almost all studies with Grade B recommendation, resulting in a decreased risk of withdrawal symptoms and dependence among participants. The effect on cannabis-related craving was pronounced, with an additive benefit from the use of psychotherapeutic options such as MET or CBT. One open-label trial suggested favorable evidence for the use of cannabinoids CBD and Δ9-THC for hyperactivity, self-injurious behaviors, and anxiety symptoms in patients with ASD with Grade B recommendation. CBD was helpful in patients with anxiety and insomnia related to SAD and PTSD in one chart review. Nabiximols was found to be effective in reducing the frequency and severity of tics and improving the quality of life in patients with Tourette syndrome according to case reports. There was no firm evidence to support CBD to treat bipolar mania (one case report) or nabiximols (one RCT) to treat ADHD. There is Grade B (moderate) recommendation for attention deficit hyperactivity disorder. Grade C recommendation (weaker) exists for insomnia, anxiety, bipolar disorder, posttraumatic stress disorder, and Tourette syndrome. These recommendations should be considered in the context of limited number of available studies. The authors recommend well-planned randomized controlled trials to further study the benefits of CBD and CBD-containing options such as nabiximols in patients with psychiatric disorders. It is also important to assess the individual pharmacodynamic and pharmacokinetic effects of CBD and Δ9-THC in different treatments.
CBD for Bipolar Disorder: Potential Treatment and Benefits
Communication between the neurotransmitters in your brain is a key player in mood stabilization. These chemical messengers help regulate your thoughts, feelings, mood, and behavior. But in order to function properly, they need to be balanced; otherwise, our brain will become either hyperactive or hypoactive. The frequent fluctuation between the activity of neurotransmitters may lead to a range of mood disorders, including bipolar disorder.
The driving force behind the functioning of neurotransmitters and their matching receptors is called the endocannabinoid system (ECS). The discovery of the ECS has given researchers new insight into the interaction between different chemicals in your body; what happens when the communication system fails; and how to potentially restore the neurochemical homeostasis.
Today we’ll cover the role of the endocannabinoid system in the development of the bipolar disorder, a pesky condition whose symptoms can negatively impact your daily life as well as people around you.
We’ll also explain how cannabidiol – CBD may contribute to healthy communication between neurotransmitters, thus reducing the severity of bipolar disorder.
Let’s jump right into this without further ado.
Bipolar Disorder and CBD
A 2010 study published in the journal Psychological Medicine suggested that cannabis can improve cognitive functioning in people with mental disorders. Interestingly, the study tested low doses of high-THC cannabis strains (marijuana) (1). And while people with bipolar disorders may benefit from small amounts of THC, using intoxicants — even in moderate amounts — is a controversial approach among the sufferers and medical professionals.
However, THC is only one of the 115 identified cannabinoids in the cannabis plant. The second major compound, CBD, is non-intoxicating and can actually counteract the psychoactive effects of THC. According to a 2015 study published in the Journal of Psychopharmacology, using CBD has the same antipsychotic and anticonvulsant properties as conventional bipolar disorder medications (2). Considering the lack of intoxicating effects, hemp-derived CBD oil will be a decent pick for bipolar sufferers.
CBD products sourced from hemp are more accessible due to the recent legal changes in hemp cultivation and sales. The US federal government legalized hemp under the 2018 Farm Bill, which was de-scheduled from the Controlled Substances Act. Hemp is now an agricultural commodity that can be grown for a variety of purposes. Hemp-derived CBD is widely available without a prescription; you can find it in local organic stores, dispensaries, vape shops, and online.
Here’s how CBD can help manage the symptoms of bipolar disorder.
CBD as a Mood Stabilizer
CBD is touted for its ability to reduce stress and anxiety. Numerous studies have mentioned the anxiolytic and antidepressant-like properties of CBD oil. People use CBD to manage different types of mental disorders, including panic disorder, general anxiety disorder, social anxiety, post-traumatic stress disorder (PTSD), schizophrenia, and more.
Below we share an explanation of the mechanisms behind CBD’s therapeutic effects.
CBD May Alleviate Manic Episode
People with bipolar disorder often show intense symptoms of mania, during which they feel highly motivated and filled with energy. In a 1998 study published in the Journal of Psychoactive Drugs, the authors concluded that cannabis users responded better to their herbal treatment than those given conventional medications. The study mentioned CBD as a promising treatment for bipolar disorder, although the results came from only one type of the condition — hypomania (3).
CBD Acts as a Natural Antidepressant
A 2007 study from the Journal of Neural Transmission correlated the depressive period of bipolar disorder with a low density of CB1 cannabinoid receptors in the brain. CBD may help restore these receptors through the endocannabinoid system signaling, which would explain its positive effects on bipolar disorder (4).
CBD also interacts with the serotonin receptors that regulate mood and emotional processing. CBD oil can enhance mood by helping the body use serotonin more effectively. With sufficient levels of serotonin in the circulatory system, and with CBD oil helping prevent anxiety and regulate sleep, bipolar patients may prevent depressive disorders.
CBD Improves Stress Response
Most anxiety-related disorders derive from stress, and CBD oil appears to be one of the most effective natural stress relievers known to mankind. Stressed people with a history of mental disorders in their families will only increase their risk of bipolar disorder if proper stress management is ignored.
Taking CBD oil daily for bipolar disorder can effectively support the endocannabinoid system, which is responsible for regulating stress responses among many other physiological functions.
People Don’t Get Addicted to CBD
Traditional bipolar medications, such as Symbiax, lithoid, and benzodiazepines like Xanax, Valium, and Klonopin are typically prescribed for bipolar disorder. However, they have a long list of possible adverse reactions, not to mention the negative consequences of their long-term use. In this clash, cannabis compounds have a much better safety profile.
Some of the common side effects of pharmaceutical medications include their addictive potential, difficulty sleeping, manic depression, weight gain, and suicidal ideation.
The only side effects of CBD oil you might experience are dry mouth, changes in appetite, drowsiness, fatigue, and diarrhea. However, in normal doses, these effects are almost non-existent. Studies on the side effects of CBD oil have concluded that the compound is safe in regular use. Unlike traditional medications, CBD is not addictive and can’t lead to a fatal overdose. In fact, CBD has been shown by recent research to relieve withdrawal symptoms and prevent relapse in those who have gone cold turkey (5).
The Role of Cannabinoid Neurotransmitters in Mood Stability
Your body produces the neurotransmitters called endocannabinoids — anandamide and 2-AG. These molecules interact with the endocannabinoid system, and their concentrations increase whenever the communication between the chemical messengers in your body gets disturbed. Your body also interacts with exogenous cannabinoids found in cannabis plants, such as hemp and marijuana. Both plants have their unique benefits, but marijuana has high levels of THC, which is an intoxicating compound. Hemp, on the other hand, comes with only 0.3% THC per dry mass, so using hemp-derived products like CBD oil won’t get you high.
Cannabinoids & Our Health
Plant-based cannabinoids mimic the effects of your endogenous cannabinoids, communicating with receptors in the ECS. The ECS is responsible for managing nearly every process and function in your body, including:
- Cardiovascular function
- Metabolism and energy
- Mood and emotional processing
- Neuroprotection and muscle movement
- Pain perception and inflammation
The endocannabinoids in your body are produced for a short duration and your body doesn’t store them. The exogenous cannabinoids are more potent, longer-lasting, and they can also signal the production of the endocannabinoids — allowing them to circulate longer in the bloodstream.
Long story short, cannabinoids from the cannabis plant help keep our master regulatory network in good shape in order to maintain well-being.
When this network falls out of whack, it may give rise to a range of health concerns. There’s even a medical term, the endocannabinoid deficiency, where the efficacy of ECS is compromised to the point it becomes deficient in its natural cannabinoids.
Research suggests that CBD has the potential to reduce pain, lower inflammation, bolster the immune system, improve sleep, and alleviate the symptoms of anxiety and depressive disorders, such as bipolar affective disorder. Studies of the endocannabinoid system are relatively new, but the results are promising.
Let’s make sure you’ve got a good understanding of bipolar disorder before we continue with the benefits of CBD for mental health.
Bipolar Disorder 101: Causes, Symptoms & Treatment Options
Bipolar disorder affects around 1.6 million Americans. It causes changes in a person’s mood, emotions, energy levels, behavior, and function. People with bipolar disorder experience extreme emotional states known as mood episodes. The complexity of the condition makes it easy to misdiagnose as depression.
The above episodes are broken down into manic, hypomanic, and depressive.
What Causes Bipolar Disorder?
Researchers have yet to find the underlying cause of the bipolar disorder, although the most likely explanation involves imbalances between specific neurotransmitters in the brain. As mentioned earlier, bipolar disorder is difficult to treat. People usually go through trial and error, most often trying one medication and waiting to see if it improves the symptoms. If not, another drug is prescribed until the symptoms become manageable.
Some of the causes of bipolar disorders include:
- Chronic depression
- Severe mental stress
- Hereditary factors (family history of bipolar disorder)
- Hormone imbalances
- Imbalances in neurotransmitters
- Post-traumatic stress disorder (PTSD)
Types of Bipolar Disorder & Their Symptoms
- Manic Episodes – a manic episode occurs when the receptors in the brain are overstimulated by the neurotransmitters. During a manic event, those with bipolar disorders experience a surge of energy, showing signs of being euphoric and highly motivated. The overexcitation may lead to a short attention span, recklessness, anxiety, and insomnia. Manic episodes may also cause paranoia, delusions, and psychosis.
- Hypomanic Episodes –During a hypomanic episode, a person goes through a less severe version of the manic episode, often being put between mania and depression. Those under the influence of a hypomanic episode struggle with anxiety and distractor, although they’re usually able to complete their daily tasks.
- Major Depressive Episodes – a major depressive episode involves the opposite symptoms of mania. It results in low motivation, feelings of sluggishness, low energy levels, and depression. This type of bipolar disorder is also accompanied by social isolation and suicidal thoughts.
How Is Bipolar Disorder Typically Treated?
Treating bipolar disorder is difficult because it is a multifaceted problem. The best approach to the problem is a combination of counseling and psychiatric care. Psychotherapy helps patients determine behavioral problems, such as high mental stress or a history of substance abuse. Other contributors, such as hormonal imbalances, should also be analyzed and treated pharmacologically.
Doctors usually prescribe the following medications for bipolar disorder:
- Mood stabilizers (carbamazepine, lithium, valproic acid)
- Antipsychotics (Abilify, Latuda, Zyprexa)
- Antidepressants (Sertraline)
- Antidepressant-antipsychotics (Symbyax)
- Anticonvulsants (Depakote, Tegretol)
However, these medications often have dangerous side effects. For this reason, people have started seeking help in complementary treatments, such as sensory deprivation, elimination of mental stresses, nutritional adjustments, support groups, herbal medicine, and CBD supplementation.
Below we share the current scientific findings regarding the use of CBD for bipolar disorder.
Pros & Cons of Using CBD Oil for Bipolar Disorder
- In vitro studies show that CBD is a neuroprotectant, including reduction of oxidative stress and free radical damage. These factors are believed to contribute to the development of the bipolar disorder (6).
- CBD promotes healthy stress responses. It can also alleviate both acute and chronic anxiety.
- CBD is an anti-inflammatory. Chronic inflammation may damage neurons in the brain, leading to imbalances in neurotransmitters. The anti-inflammatory effects of CBD have been found in both animal and human studies.
- CBD is non-intoxicating, so it won’t get you high. This is a particularly valuable trait, as intoxicants are known for increasing the risk of aggravating the symptoms of bipolar disorder.
- You can’t get addicted to CBD.
- CBD doesn’t have the serious side effects associated with commonly prescribed antipsychotics.
- The CBD market is largely unregulated, so there’s a risk of buying a mislabeled product that contains significant amounts of THC, even if the label states otherwise.
- Much of the evidence supporting the benefits of CBD for bipolar disorder comes from animal studies and preclinical human trials. More clinical studies are needed to determine whether the effects of CBD are consistent on large groups of the population.
How to Use CBD for Bipolar Disorder?
- CBD Oil – CBD oil is the most common form of cannabidiol due to its ease of use and dosage precision. CBD oil contains hemp extract and food-grade inert oil. The infusion in the carrier oil boosts the bioavailability of CBD, allowing lower doses to remain effective. Such a product is easier to apply and dose. CBD oil is taken under the tongue, where the user holds it for up to a minute before swallowing.
- CBD Capsules – Capsules are a good choice if you dislike the natural taste of CBD oil. They also take away the guesswork associated with dosing CBD in the liquid form because each capsule contains a premeasured dose. All you need to do is take as many capsules as you need to match your dosage and swallow them down with water. Since capsules need to pass through the digestive system, they have a delayed onset, usually kicking in after 40–90 minutes.
- CBD Edibles – Edibles like gummies and honey sticks provide a fun way to supplement CBD. The only concern when it comes to CBD edibles is the lower potency of the final dose. Similar to capsules, edibles need to be processed in your gut before they can be released into the bloodstream, so dosing is often inconsistent and unreliable.
- CBD Vape Pens – if you’re looking for the most efficient of all consumption methods in terms of dosing, then CBD vape pens will be your best bet. Vaporized CBD shows the highest bioavailability because it enters the bloodstream through the lungs. As a result, the CBD acts within minutes after inhalation. Vaping is a good choice for people with bipolar disorder because it provides consistent dosage and fast symptom relief.
How Often Should You Take CBD for Bipolar?
Consistency is an essential component of successful bipolar disorder treatment. Only by being consistent can you manage the symptoms of the condition and level the endocannabinoid deficiencies in your system, which is one of the probable causes of bipolar disorder.
For the best results, you should take CBD a few times a day depending on the route of administration. CBD oils provide relatively long-lasting effects, up to 6 hours, allowing the user to split the dosage into two servings. For products like CBD hemp flowers or CBD vapes, you’ll probably need to use them more often, as vaporized CBD has a shorter duration, usually between 3–4 hours.
How Much CBD to Take for Bipolar Disorder?
Finding the optimal dosage range for your situation will require some experimenting. Everybody is different, so a dose that works for your friend may not necessarily be enough to relieve your symptoms. Self-testing is an inevitable part of that process, but the goal is to minimize the number of errors.
Most experts recommend starting with a low dose and gradually increasing it until you find the desired relief from your bipolar disorder. Many bipolar patients experience benefits upon reaching a medium- or high-strength dose. The amount of CBD oil you’ll need to notice the positive change depends on the severity of your symptoms and your overall health. The only way to determine your effective dosage range is to try it out.
You can start by taking 10 mg twice a day — in the morning and in the evening — and observe the effects for one week. It’s good to keep a dosage journal where you will keep notes of how you feel after each dose, and whether or not it alleviates your symptoms. If you find no change after that time, add another 10 mg to your routine and continue the trial. Once you’ve reached the sweet spot, you can lock in at that dosage.
Is CBD Safe?
Taking CBD for bipolar disorder doesn’t carry a risk of life-threatening side effects. In fact, CBD has been mentioned by several studies as a safe and well tolerable compound. In humans, examined dosages ranged between 300–1,500 mg of CBD daily. However, there are a few mild reactions you should keep in mind when using CBD oil for bipolar disorder. Since most people with the condition benefit from medium- to high-strength doses, you may experience the following side effects:
- Dry mouth
- Changes in appetite
CBD-drug interactions are also possible, so we encourage you to visit a doctor knowledgeable about CBD and cannabis to avoid these interactions. A qualified professional will also help you establish the right dosage regime to maximize the benefits of your treatment.
CBD vs Lithium: Which is Better for Bipolar Treatment?
CBD is praised for its ability to stabilize mood and alleviate anxiety. Anecdotal reports, as well as clinical evidence, indicate that CBD produces the same effects as some other bipolar medication and antidepressants.
Like we said, CBD has remarkable antioxidant properties and neuroprotective effects which may help patients with bipolar disorder without causing dangerous adverse effects. There are also studies suggesting that CBD acts similarly to atypical and antipsychotic drugs, thereby producing mood-stabilizing and anticonvulsant effects.
Lithium is prescribed for treating certain types of depression, especially bipolar one. It’s effective and has been used for decades by psychiatrists. Despite its mood-stabilizing properties, scientists aren’t sure how these effects are exactly produced. Nevertheless, studies have proven that lithium-based medications can reduce the frequency of suicidal thoughts during manic episodes. These properties have been attributed to lithium’s interaction with a certain nervous system, increasing the number of neurotransmitters that help balance mood. Lithium also strengthens nerve connections, translating into a better regulation of emotions.
However, lithium also has dangerous side effects. Approximately 70% of bipolar patients treated with lithium experience negative reactions. Although most of them are minor, common side effects of taking lithium include acne, diarrhea, poor memory, and weight gain. High doses of lithium are associated with ringing ears, poor muscle control, and blurry vision. Hypothyroidism is another potential side effect of long-term lithium treatment. It can also give rise to rare but severe kidney illnesses. None of these side effects were observed during the studies examining the safety and efficacy of CBD.
Summarizing the use of CBD for Bipolar Disorder
Bipolar disorder can negatively impact your daily life. The condition is not only challenging to diagnose but also difficult to treat, often involving a series of trial-and-error with different pharmaceutical medications. Some of these drugs are simply ineffective, while others pose a threat to one’s health with long-term use.
People are now turning to natural remedies for bipolar disorder, one of them being CBD oil. Some studies suggest CBD can be a safe and effective alternative to conventional treatments. CBD indirectly affects different neurotransmitters and hormones, balancing their activity, and thus helping the body maintain its homeostasis, especially in the central nervous system. Researchers are wondering if CBD can address the probable underlying cause of bipolar disorder — the clinical endocannabinoid deficiency (CECD). Studies on animal models, as well as preclinical human trials, have shown promising results in this regard.
If you’re considering adding CBD oil as a complementary treatment for bipolar disorder, make sure to consult the idea with your doctor. You should also do your research on your potential vendors, as no two CBD oils are the same. The CBD market lacks regulation when it comes to manufacturing and labeling standards, and some brands are very liberal when it comes to health claims and the cannabinoid content of their products.
Did you try CBD oil for bipolar disorders? Share your thoughts in the comments!
- Ringen, P A et al. “Opposite relationships between cannabis use and neurocognitive functioning in bipolar disorder and schizophrenia.” Psychological medicine vol. 40,8 (2010): 1337-47. doi:10.1017/S0033291709991620
- Blessing, Esther M et al. “Cannabidiol as a Potential Treatment for Anxiety Disorders.” Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics vol. 12,4 (2015): 825-36. doi:10.1007/s13311-015-0387-1
- Grinspoon, L, and J B Bakalar. “The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research.” Journal of psychoactive drugs vol. 30,2 (1998): 171-7. doi:10.1080/02791072.1998.10399687
- Koethe, D et al. “Expression of CB1 cannabinoid receptor in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression.” Journal of neural transmission (Vienna, Austria : 1996) vol. 114,8 (2007): 1055-63. doi:10.1007/s00702-007-0660-5
- Prud’homme, Mélissa et al. “Cannabidiol as an Intervention for Addictive Behaviors: A Systematic Review of the Evidence.” Substance abuse: research and treatment vol. 9 33-8. 21 May. 2015, doi:10.4137/SART.S25081
- Machado-Vieira, Rodrigo et al. “Oxidative stress parameters in unmedicated and treated bipolar subjects during an initial manic episode: a possible role for lithium antioxidant effects.” Neuroscience letters vol. 421,1 (2007): 33-6. doi:10.1016/j.neulet.2007.05.016
Livvy is a registered nurse (RN) and board-certified nurse midwife (CNM) in the state of New Jersey. After giving birth to her newborn daughter, Livvy stepped down from her full-time position at the Children’s Hospital of New Jersey. This gave her the opportunity to spend more time writing articles on all topics related to pregnancy and prenatal care.
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CBD Oil for Bipolar Disorder: Does It Help, Dosage, & How to Use
Bipolar disorder is a condition involving unusual shifts in mood, focus, and energy.
There’s some evidence that CBD can help, but there are a few cautions to be aware of too.
Bipolar disorder affects between 0.4% and 1.6% of the world’s population, according to recent reports. This means roughly 70 million people around the planet suffer from bipolar disorder to some degree.
There are treatment options available — however, they often come with a myriad of negative side-effects, and often don’t work at all.
Cannabidiol (CBD), has been shown to protect the brain from damage and support healthy neurotransmitter function. Through these effects, it’s believed to reduce the severity of the bipolar disorder and help those affected to maintain a more stable mood throughout the day.
Here, we’ll explore the role CBD plays in maintaining mood, how to use CBD for bipolar disorder, and when to avoid it.
Let’s get started.
MEDICALLY REVIEWED BY
Updated on October 20, 2021
Table of Contents
$49 – $229
Royal CBD Oil 30 mL
5 / 5
|Total CBD:||500 – 2500 mg|
|Potency:||16.6 – 83.3 mg/mL|
|Cost per mg CBD:||$0.12 – $0.18|
The Benefits of CBD Oil For Bipolar Disorder
Using CBD for bipolar disorder isn’t a new concept, and there’s currently one phase II clinical trial underway comparing the long-term effects of CBD with the effects of a placebo in patients diagnosed with bipolar disorder.
In order to get to this stage of research, CBD needed to pass similar tests with flying colors. If it failed any of the studies prior to this phase II clinical trial, it wouldn’t have been approved for use in the study.
Previous studies found that CBD offers a clear benefit to mood disorders with little to no side-effects.
The benefits of CBD for bipolar disorder include:
- Relieves common side effects such as anxiety or insomnia
- Helps stabilize mood & alleviates depression
- Regulates the endocannabinoid system (involved with the cause of bipolar disorder)
Although there are clear benefits to using CBD with bipolar disorder, there are some important cautions to be aware of before deciding if it’s right for you or not.
Best CBD Products For Bipolar Disorder
Caution #1: The Type of CBD Product You Use Matters
Some cannabinoids in the cannabis plant, including THC, can actually make bipolar disorder significantly worse. Therefore, it’s critical that the CBD product you purchase contains low levels of THC to avoid this.
For bipolar disorder, it’s recommended that only a high-grade, full-spectrum extract with third-party lab testing to confirm the cannabinoid profiles of the product is used.
The other option is to use a CBD isolate — which contains nothing but active CBD.
Caution #2. Other Medications Need to Be Considered
Bipolar disorder is usually treated with powerful antipsychotic drugs. These medications alter neurotransmitters in the brain. Users need to be cautious when taking other supplements, including herbs and nutritional supplements such as CBD oil because it can be difficult to predict how they interact with prescription medications.
Always consult your doctor before trying CBD for bipolar symptoms to check for drug-herb interactions.
What is Bipolar Disorder?
Bipolar disorder is characterized by dramatic changes in mood, behavior, and energy levels.
The root of the condition is the balance of neurotransmitters in the brain. Neurotransmitters such as serotonin, dopamine, GABA, glutamate, and others all fluctuate and interact throughout the day to regulate our moods.
Everybody’s mood fluctuates to some extent — we have periods of feeling joy and periods of discomfort and irritability. This is normal — however, in bipolar patients, these fluctuations are far more severe, often making it difficult to perform daily activities such as complete work or socially interact.
The specific neurotransmitters responsible for bipolar symptoms can vary, and in many cases, the exact cause is never truly identified.
This makes the condition hard to treat, and much of the treatment in a hospital is done through trial and error — patients try a drug and wait to see if it produces results. If not, they try the next one in line until they find something that relieves their symptoms.
Bipolar disorder causes episodes of extreme emotion that can last anywhere from a few minutes to a few weeks at a time. Episodes can range from mild to extreme.
There are three primary types of episodes experienced by those with bipolar disorder.
1. Manic Episodes
The brain is in a state of hyperactivation, which can make people seem intense or overly happy. During manic episodes, those affected tend to have a lot of energy. They can seem highly motivated and euphoric and tend to develop side-effects such as anxiety and insomnia.
Manic episodes can become dangerous as they can make people reckless and may bring negative side-effects such as paranoia, psychosis, or delusions.
2. Hypomanic Episodes
A hypomanic episode is similar to a manic episode — but tends to be less extreme. It’s often considered a halfway point between mania and depression.
People experiencing hypomania are often able to continue their normal responsibilities, but find it more challenging to avoid distraction or bursts of anxiety.
3. Major Depressive Episodes
Major depressive episodes are the opposite of manic episodes. It causes those affected to have low motivation. They may feel tired and sluggish and can feel severely depressed. They often go through periods of social isolation, and some experience thoughts of suicide or death.
The Causes of Bipolar Disorder
There’s no single cause of bipolar disorder. It’s a combination of many factors ranging from genetic inheritance to environmental and social influences.
Some of the Known Causes of Bipolar Disorder Include:
Are There Any Treatment Options For Bipolar Disorder?
Treating bipolar disorder is difficult because the cause is hard to determine.
The best treatment for the condition comes in the form of psychiatric therapy to determine potential triggers and underlying causes such as a history of abuse or mental stresses.
Other causes, such as hormone imbalances, should also be tested for and treated as necessary.
In terms of symptomatic support, there are a few pharmaceutical medications effective for treating bipolar disorder.
Medications Used to Control Bipolar Symptoms
- Mood stabilizers (lithium, valproic acid, carbamazepine)
- Antipsychotics (Abilify, Zyprexa, Latuda)
- Antidepressants (Sertraline)
- Antidepressant-antipsychotics (Symbyax)
- Anticonvulsants (Depakote, Tegretol)
Other Treatments for Bipolar Disorder
- Hospitalization during extreme episodes of mania or depression
- Nutritional support
- CBD supplementation
- Herbal medicine
- Removal of mental stresses
- Sensory deprivation
- Support groups
How to Use CBD for Bipolar Disorder Safely
CBD alleviates many of the common symptoms of bipolar disorder. However, there are also reports of people who had their symptoms magnified due to cannabis use. This is mainly due to the THC content in marijuana, which is neuro-stimulating and can aggravate symptoms.
For this reason, it’s not safe for people with bipolar disorder to consume marijuana that has a high THC content.
To use this supplement safely, it’s important to find CBD oils, capsules, or edibles confirmed to be low in THC and high in therapeutic CBD.
It’s also crucial that you speak with your doctor before taking CBD for bipolar disorder to make sure the compound won’t interact negatively with the medications you’re taking.
Once your doctor has approved you to start taking CBD to alleviate symptoms of bipolar disorder, you need to find the right product to use and determine the best dose of CBD.
There are many different ways you can take CBD. Here, we’ll discuss the most common options in detail and how they can be used alongside a bipolar diagnosis.
1. CBD Oils & Tinctures
CBD oils and tinctures are the most common forms of CBD supplementation because it allows for simple and precise dosing.
They’re made by mixing a CBD extract with oil. CBD oils easier to consume because pure CBD or cannabis resin comes as tiny crystals or a sticky, oily, resin — both of which make it difficult to measure the dose accurately.
As an oil, the dose is measured by counting the number of drops using the provided dropper.
CBD oils and tinctures come in a variety of potencies. It’s recommended that you choose a potency that best matches the dose you aim to take. Use our CBD oil dosage calculator to find your approximate dosage.
2. CBD Capsules
CBD capsules provide another popular method of consuming CBD. They take away a lot of the guesswork when it comes to dosing and make it easy to take your CBD on the go.
CBD capsules also come in both low-potency and high-potency options.
Many people who take a variety of capsules throughout the day with their other medications or supplements find this form the easiest to integrate into their daily routines.
3. CBD Edibles
CBD edibles are a great option for people who don’t like the taste of the oils or tinctures and want to avoid swallowing capsules.
They come in all different forms — from CBD-infused honey to CBD chocolates.
The only downside to edibles is that the amount of CBD they contain is often unreliable, making dosing inconsistent.
For a condition such as bipolar disorder, it’s important to be consistent with your CBD use — something that edibles aren’t always able to provide.
4. CBD E-Liquids & Vape Oils
CBD vape pens & vape oils provide the most efficient form of dosing because bioavailability through the lungs is much higher than it is through the digestive tract.
Vaping is a good option for people with bipolar disorder because it offers fast relief from symptoms. It’s also one of the most portable methods of taking CBD.
What’s The Dose of CBD Oil For Bipolar Disorder?
Deciding on the right dose of CBD can take some trial and error. Everybody responds to this compound differently, so a little bit of self-testing is needed to find the right dose. This is also the case with most of the pharmaceutical bipolar medications used.
It’s best to start with a low dosage and build up gradually over time until you find relief from your symptoms.
In most cases, people with bipolar disorder won’t start to experience benefits until they reach the medium- or high-strength doses. Some people even require doses outside the listed range. The only way to find out your optimal dose is to test it.
With that said, you can use our dosage calculator below to find the approximate dose based on your weight and desired strength.
General Dosage Ranges for Psychological Disorders
|Low-Strength CBD||Medium-Strength CBD||High-Strength CBD|
|• Mild depression or anxiety
• Periods of higher-than-average stress
• Daily maintenance dose for asymptomatic bipolar disorder
|• Moderate bipolar symptoms
• High stress
|• Severe bipolar symptoms
• Severe insomnia
Most bipolar patients take a medium- or high-strength dose of CBD — however, this can vary from one person to the next.