Many people with bipolar disorder have a strong attraction to marijuana. A 2019 review of 53 studies found that nearly a quarter of a combined sample of 51,756 people with the condition used cannabis or had a problematic use pattern (cannabis use disorder), compared with 2 to 7 percent in the general population — and the earlier study put the usage estimates even higher.
Cannabis and bipolar disorder don’t mix well. Use can increase manic and psychotic symptoms and increase the risk of suicide. But can the appeal of cannabis be explained as a mere form of substance abuse? Why are people with bipolar disorder so attracted to marijuana? Could they derive any potential benefit from it?
Alannah Miranda of the University of California, San Diego, is a postdoctoral fellow working with UCSD psychiatry professors William Perry and Arpi Minassian to explore these questions. Miranda presented her and her colleagues’ unpublished work at this year’s major Society for Neuroscience conference, which drew more than 24,000 people earlier this month. She spoke to Scientific American about what she discovered in this ongoing study funded by the National Institute on Drug Abuse.
[An edited transcript of the interview follows.]
Tell me what you study.
I am researching the effects of cannabis on cognition in people with bipolar disorder. People with bipolar disorder report that it helps relieve some of their symptoms related to problems related to memory, attention, concentration, and anxiety.
What did the preliminary study you are presenting at this conference show?
Our study had four distinct comparison groups: healthy participants who did not use cannabis, healthy participants who used cannabis, people with bipolar disorder who did not use cannabis, and people with bipolar disorder who used cannabis.
We tested them on a range of their goal-directed behaviors, including risky decision-making and what we call effort motivation, which is their willingness to keep engaging in a task even though the potential for a reward continues to diminish over time. And we found that people with bipolar disorder who used cannabis actually made fewer risky decisions and had less of a tendency to engage in trivial tasks for excessively long periods of time. Those screened without bipolar disorder who used marijuana had higher risk-taking and higher levels of motivation.
How many people were in the study?
A total of around 60 participants have taken part so far. The study is ongoing and we are aiming for around 100 in total. And we will finish it in less than a year.
There have been previous studies on the effects of cannabis on people with bipolar disorder. How is your course different?
Many focus on cannabis use Bipolar disorder has classically referred to whether the drug works Mood symptoms of the disorder that may aggravate mania and psychosis. But impaired cognition like decision making is something that tends to be overlooked. So we’re looking at these cognitive functions that really impact how people function on a day-to-day basis.
Do you also do animal experiments?
Yes, I worked with Jared Young at UCSD on his animal work. So I think what makes our study different from a lot of previous studies on cannabis and bipolar disorder is that we’re looking at this in humans, but we’re also looking at this in animals. The paradigm is to test cognitive functions in humans, but we have very similar tasks that we use in mice. And we can do some genetic manipulations in mice or give animals specific amounts of drugs that we can’t do in humans. We can look at the specific mechanisms of bipolar disorder that we suspect exist, such as dysregulation of the signaling molecule dopamine. It’s a lot harder to look at specific proteins in humans, but we can certainly do that in our animal research.
Do you have any hypotheses about what might be going on with cannabis and how it affects the brain?
Currently we believe that cannabis may affect the reward and motivation processing system. Dopamine regulates the behavior and functions we use to achieve specific goals. People with bipolar disorder may have too much dopamine chemical activity in their system, and we suspect this leads to greater cognitive impairment
So we think cannabis can reduce the excess dopamine that leads to cognitive impairment in people with bipolar disorder.
Could you talk about the implications of your work for potential treatments?
Clinically, there would be concerns about cannabis exacerbating the mania and psychotic symptoms of bipolar disorder. So I wouldn’t go so far as to say that people with bipolar disorder should use cannabis. But our research could lead to an understanding of cannabis’ mechanisms of action, which could potentially lead to drug treatments.
How does your work look in the future?
At the moment we are investigating the acute effects of THC (tetrahydrocannabinol) versus CBD (cannabidiol) in our ongoing study. I think that’s probably one of the more promising directions that we’re taking this research. THC can actually have opposite effects to CBD, and we want to unravel that. We want to see if we can maximize the therapeutic benefits of cannabis, but minimize all of these harmful effects to produce a lower negative side effect profile. CBD generally doesn’t have the same psychoactive effects as THC, so you won’t get a high from it. There is a possibility that CBD is a better candidate for therapy, but so far there is very little data on it.
And we are extending this to other population groups as well. This includes HIV patients who have similar neurocognitive impairments. We also hope to study the effects of cannabis on aging populations who are also at risk of cognitive decline. With the growing legalization of cannabis, more and more older people are turning to cannabis as a medical treatment, but we don’t know how cannabis affects the aging brain. I think that’s a really important branch of this current research.