It’s long been accepted that mental health conditions are greatly underserved by current medications and treatments. And none more so than bipolar disorder (BD), a debilitating condition in which patients’ moods swing uncontrollably between manic episodes and deep depression. For many, simply existing becomes intolerable, with between 25-60% attempting suicide at some point in their lives.1
Most BD patients are prescribed a cocktail of drugs that include mood stabilizers like lithium, antidepressants, antipsychotics, anti-anxiety medication, anticonvulsants, and sleeping tablets, often leaving them so medicated they’re unable to function. Eighty-nine percent of BD sufferers report experiencing serious impairment due to their condition (and undoubtedly their medication), more so than any other mental health disorder.2
As such, self-medication with cannabis and/or alcohol is common, although universally discouraged by health professionals.3 Indeed, of the clinicians who regularly prescribe cannabis for other health conditions such as anxiety and depression, most give the cannabis plant a wide berth when it comes to bipolar disorder, citing the risk of worsening manic episodes and its link with increasing the risk of psychosis.4
And yet, anecdotal evidence both from patients and the few pioneering doctors are reporting some life changing benefits from CBD-rich cannabis, including mood stabilization, the holy grail in bipolar disorder symptom management.
What Is Bipolar Disorder?
Bipolar disorder, formerly called manic depression, often manifests in adolescence, although it can come on at any time, and affects almost 3% of the US population.
On average, it can take 8 years to get an official diagnosis5 after a first episode, with younger patients sometimes misdiagnosed with ADHD.6 However, when the diagnosis eventually comes it’s usually classified as either bipolar I disorder, where one manic episode is preceded or followed by hypomanic or major depressive episodes, including in some cases, psychosis; or bipolar II disorder when patients have had one major depressive episode and at least one hypomanic episode, but never a full-on manic episode.
Because of bipolar disorder’s complex nature, patients are prescribed multiple pharmaceuticals, some of which can actually make certain symptoms worse and leave them feeling like zombies.
Bipolar Disorder, Dopamine, & the Endocannabinoid System
Why BD develops is not completely understood. However, one commonly held theory suggests an imbalance in the dopaminergic system may play a role,7 with excessive dopamine transmission contributing to the manic phase and increased dopamine transporter levels leading to reduced dopaminergic function and depression. Dopamine is a class of neurotransmitter that plays a role in pleasure, motivation, and learning.
It’s commonly accepted among scientists that the endocannabinoid system acts as a master regulator, maintaining homeostasis in neurological activity and throughout the body. This includes acting as an ‘important filter’ to incoming inputs acting locally in the midbrain and shaping how information is passed onto dopamine neurons.8
While it’s not clear whether some kind dysregulation within the endocannabinoid system has a causal relationship with BD, authors of the paper, “Endocannabinoid Modulation of Dopamine Neurotransmission” suggest “endocannabinoid-based therapies as valuable treatments for disorders associated with aberrant DA function.” As an aside, CBD is a partial agonist [activator] of the dopamine D2 receptors, which researchers suggest may partly account for its antipsychotic effect.9
A further line of study, outlined in the 2019 paper ‘Bipolar Disorder and the Endocannabinoid System’,10 is based on the premise that inflammation plays a role in many mood disorders including BD, and suggests CB2 cannabinoid receptors, considered to have an immunomodulating effect,11 may be a therapeutic target for managing BD symptoms.
Studies show elevated levels of certain inflammatory pro-cytokines are present in the manic phase and depressive phases of BD and normalise when patients have returned back to a neutral phase.12
Thus, the researchers posit that reducing inflammation by targeting the CB2 receptors and using selective CB1 receptor antagonists, “may lead to remarkable advances pertaining to pharmacotherapy of BD based on modulation of the ECS, and this approach offers a brand-new treatment strategy to broaden the arsenal available to pharmacologically mange BD.”
A Patient’s Story
Diane Green, 62, from Rocklin, California, first started showing symptoms of bipolar disorder when she was 15. However, it would take over twenty years until she eventually got an accurate diagnosis.
Most of what Diane has held dear in life has been destroyed by BD; her education, her relationship with her family, her marriages, and her career as a nurse.
“The one thing that I know is being bipolar and being on meds,” she shares. “It touches every part of life… it takes everything away.”
Before she got her diagnosis at 38, Diane self-medicated with alcohol and occasionally cannabis to calm her agitation. However, her violent outbursts, agitation, and depression continued unabated, leaving Diane desperate for help.
“Once I called the cops,” she recalls. “They came over and I’m begging him, ‘Please take me to the mental institution.’ He asked me if I was drinking, and I said yes. And he said, ‘Well, they won’t take you, and I remember I went and got in his car anyway.”
While finally getting a bipolar disorder diagnosis was a relief in many ways, it heralded a new phase of her life: coping with the side effects of the various pharmaceuticals she was prescribed.
“The medication is its own nightmare of a journey,” says Diane, “the side effects were shockingly terrible. The fog I was in, it was horrible.”
In fact, according to Diane, rather than improving her depressive episodes, the medication actually made them worse.
“Once they put me on meds is when the depression got to where I could hardly get out of bed at all,” she remembers. “It never stopped the episodes… But it helped take the edge off. So, I still had to go through the cycles, manic depression and rapid cycling.”
CBD to the Rescue
It was in one of her desperate lows that Diane decided to try CBD oil.
“About 45 minutes later, I just noticed I’m calmer,” says Diane. “I’m more relaxed. Something felt better I think because I wasn’t depressed.”
Delighted with the results, Diane started taking CBD everyday, eventually over time carefully coming off her meds (a process best undertaken with the guidance of a health professional). Free from their debilitating side effects, Diane could finally begin to enjoy her life again.
“I just remember the amazement of the mornings with a clear mind and going for walks and just feeling the air and looking at nature,” she recalls fondly. “And that just became so precious to me having a clear mind… I feel like it just balances it out, so that I really don’t have symptoms. Sometimes I forget I’m bipolar.”
It’s taken a bit of experimentation with different CBD products for Diane to find her therapeutic sweet spot. But interestingly, for her at least, rather than whole plant CBD-rich cannabis, it’s actually been 33 mg of CBD isolate taken twice a day that has worked best at managing her symptoms.
After a life dominated by her bipolar disorder, Diane wishes she’d found CBD earlier.
“I think about those hopes and dreams because I wanted a career, I was excited about life in college and getting married someday and having the perfect kids in the perfect house… And all that just gets taken away slowly. It just does… I don’t think with CBD I would have ever had to have gone on disability.”
A Clinician’s Experience
Holistic physician Deborah Malka MD has seen a number of patients with bipolar disorder over the years. Indeed, she is one of only a few clinicians worldwide willing to recommend medicinal cannabis to help manage bipolar disorder symptoms.
In her book ‘Medicinal Cannabis: Pearls for Clinical Practice,’ Malka shares a number of case studies of bipolar patients who have responded favorably to CBD-rich cannabis, and in a conversation with Project CBD she reveals why treating bipolar disorder with cannabis isn’t just about alternating between CBD and THC to manage the manic and depressive cycling.
“I had about 10 patients with bipolar disorder,” says Malka, “and what I found is that most of them responded best to being on some kind of CBD as an ongoing mood stabiliser, to actually prevent the ups and downs.
According to Dr. Malka, because CBD has proven anticonvulsant effects, and anticonvulsants are commonly prescribed for bipolar disorder to complement drugs like Lithium, it’s not so shocking that CBD has mood stabilizing effects.
“I believe that [CBD’s] anticonvulsant properties are actually inherently affecting the lability of probably the serotonin, probably of dopamine, and actually smoothing out the bipolar disorder patients into a more moderate range.”
But for Malka, CBD isn’t the end of the story. She feels it’s important to highlight how compounds within the cannabis plant hold multiple therapeutic keys for the complex bipolar symptoms that a multitude of pharmaceutical drugs fail to manage – without the horrendous side effects.
In Malka’s experience, terpenes play a key role in managing cycling episodes and she favors myrcene to promote calmness and improve sleep during manic phases and alpha pinene and/or limonene for invigorating patients when they fall into depression.
Caution With THC
She will turn to THC chemovars containing myrcene to regulate sleep, which is often disrupted in bipolar disorder, but does not recommend THC when patients are manic or experiencing suicidal ideations.
“If somebody uses too much stimulating THC-rich cannabis because that’s what you’d want to use if you’re suicidal and in a very low mood,” explains Malka, “it alters your perception to a place where you skip reasoning and you just get disoriented, especially if you’re not used to cannabis. Too much THC can actually induce a psychotic experience. So, we don’t want that.”
To avoid any worsening of symptoms, Malka recommends bipolar patients seek professional help from an experienced physician before trying cannabis to manage their mood fluctuations.
“It’s really not safe if you’re a naive patient,” she stresses. “Too much THC is not safe, especially when you have a mood disorder. Please don’t do that. Get professional help.”
Preliminary Clinical Studies
With the buzz surrounding the therapeutic application of CBD in a number of mood disorders, including as an antipsychotic treatment in schizophrenia,13 it’s not a surprise that a preliminary clinical trial is examining whether the compound could also be effective in bipolar disorder. This despite some earlier reviews14 finding only weak evidence that CBD was effective for BD.15
So far, unfortunately, there are no definitive results to report. One small Brazilian study,16 which was terminated prematurely due to COVID, gave 36 bipolar patients 150-300 mg of CBD or a placebo over twelve weeks, to assess whether their depression and anxiety symptoms improved, as well as measuring inflammatory biomarkers. However, despite ending the study early, the researchers have been able to submit the results to a journal, which is awaiting review and hopefully a future publication.
Another clinical trial17 currently recruiting in San Diego, will compare the administration of a one-time 600mg dose of Epidiolex (pharmaceutical CBD) with 5mg of dronabinol (synthetic THC) and a placebo on 144 bipolar participants in order to assess their effects on “cognitive domains relevant to bipolar disorder, e.g., arousal, decision making, cognitive control, inhibition, and temporal perception (sense of timing),” as well as measuring anandamide, an endocannabinoid and homovanillic acid, a marker of dopamine activity in the brain.
However, the study’s objective appears to be less about cannabinoids as potential treatment for bipolar disorder and more geared towards understanding why many patients with BD also suffer from substance abuse.
It appears then that the stigma against cannabis and bipolar disorder among health professionals remains ingrained, and more clinical trials are needed before prescribing CBD-rich cannabis or just plain old CBD will be readily accepted by mental health clinicians and psychiatrists.
Mary Biles, a UK-based journalist, educator, and Project CBD contributing writer, is the author of The CBD Book (Harper Collins, UK). © Copyright, Project CBD. May not be reprinted without permission.
- Danielle M Novick et al. Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord. 2010 Feb; 12(1): 1–9.
- National Institute of Mental Health. Bipolar Disorder.
- Glenn E Hunt et al. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: Systematic review and meta-analysis. J Affect Disord 2016 Dec;206:331-349.
- Deepak Cyril D’Souza et al. Cannabinoids and Psychosis. Curr Pharm Des 2016;22(42):6380-6391.
- Boseok Cha et al. Polarity of the First Episode and Time to Diagnosis of Bipolar I Disorder. Psychiatry Investig. 2009 Jun; 6(2): 96–101.
- Jagan K Chilakamarri et al. Misdiagnosis of bipolar disorder in children and adolescents: a comparison with ADHD and major depressive disorder. Ann Clin Psychiatry 2011 Feb;23(1):25-9
- A H Ashok, et al. The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment. Mol Psychiatry. 2017 May; 22(5): 666–679.
- Dan Covey et al. Endocannabinoid modulation of dopamine neurotransmission. Neuropharmacology. 2017 Sep 15; 124: 52–61.
- P Seeman. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry v.6(10); 2016 Oct.
- Shokouh Arjmand et al. Bipolar disorder and the endocannabinoid system. Acta Neuropsychiatrica, 31(4), 193-201. doi:10.1017/neu.2019.21
- Slava Rom et al. Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation. J Neuroimmune Pharmacol 2013 Jun;8(3):608-20. doi: 10.1007/s11481-013-9445-9. Epub 2013 Mar 8.
- Sinead M O’Brien et al. Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. J Affect Disord 2006 Feb;90(2-3):263-7. doi: 10.1016
- Cathy Davies et al. Cannabidiol as a potential treatment for psychosis. Ther Adv Psychopharmacol. 2019; 9: 2045125319881916.
- Rabia Khan et al. The therapeutic role of Cannabidiol in mental health: a systematic review. J Cannabis Res 2020 Jan 2;2(1):2.
- Julia Machado Khoury et al. Is there a role for cannabidiol in psychiatry? World J Biol Psychiatry 2019 Feb;20(2):101-116.
- Cannabidiol as an Adjunctive Treatment for Bipolar Depression (CBDBD). ClinicalTrials.gov
- Effects of Cannabis on Cognition and Endocannabinoid Levels in Bipolar Disorder Patients and Healthy Volunteers. ClinicalTrials.gov
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