Saturday, February 4, 2023

Many People with Bipolar Disorder Use Cannabis. It May Sometimes Help

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Many people with bipolar disorder have a strong attraction to marijuana. A 2019 review of 53 studies found that almost a quarter of a combined sample of 51,756 individuals with the condition used cannabis or had a problematic pattern of consumption (cannabis use disorder), compared with 2 to 7 percent in the general population—and an earlier study placed usage estimates still higher.

Cannabis and bipolar disorder do not go particularly well together. Consumption may increase manic and psychotic symptoms, and there may be a greater risk of suicide. But can the allure of cannabis be explained as a mere form of substance misuse? Why are people with bipolar disorder so attracted to marijuana? Could they be getting any possible benefit from it?

Alannah Miranda of the University of California, San Diego, is a postdoctoral scholar working with U.C.S.D. psychiatry professors William Perry and Arpi Minassian to explore these questions. Miranda presented her and her colleagues’ unpublished work at this year’s giant Society for Neuroscience conference, which attracted more than 24,000 people earlier this month. She talked to Scientific American about what she discovered in this continuing study, which has been funded by the National Institute on Drug Abuse.

[An edited transcript of the interview follows.]

Tell me about what you’re studying.

I’m researching the effects of cannabis on cognition in people with bipolar disorder. People with bipolar disorder report that it’s helping alleviate some of their symptoms in terms of issues related to memory, attention, focus and anxiety.

What did the preliminary study that you’re presenting at this conference show?

Our study had four different comparison groups: healthy participants who do not use cannabis, healthy participants that do use cannabis, people with bipolar disorder that do not use cannabis and people with bipolar disorder that do use cannabis.

We tested them on a number of their goal-directed behaviors, including risky decision-making and what we call effortful motivation, meaning their willingness to continue to engage in a task despite the fact that the potential for reward continues to decrease over time. And what we found was that people with bipolar who use cannabis actually made fewer risky decisions and had a decreased tendency to pursue trivial tasks for an excessive amount of time. Those studied without bipolar disorder who ingested marijuana had higher risk-taking and effortful motivation levels.

How many people were in the study?

There have been about 60 total participants so far. The study is continuing, and we’re aiming for about 100 in total. And we’ll finish it in less than a year.

There have been previous studies on the effects of cannabis on people with bipolar disorder. How does your study differ?

A lot of the focus in cannabis use for bipolar disorder has classically been on whether the drug affects mood symptoms of the disorder, perhaps making mania and psychosis worse. But impaired cognition such as decision-making is something that tends to be overlooked. So we’re looking at these cognitive functions that are really impacting people’s everyday functioning.

Are you also doing animal studies?

Yes, I’ve been collaborating with Jared Young at U.C.S.D. on his animal work. So I think what sets our study apart from a lot of previous studies on cannabis and bipolar is that we are looking at this in humans, but we are also looking at this in animals. The paradigm is to test cognitive functions in humans, but we have very similar tasks that we’re using in mice. And we can do some genetic manipulations in mice or administer specific levels of drugs in the animals that we can’t do in humans. We can look at the specific mechanisms of bipolar disorder that we hypothesize exist, such as a dysregulation of the signaling molecule dopamine. It’s much more difficult to look at specific proteins in humans, but we can certainly do that in our animal research.

Do you have hypotheses about what might be going on with cannabis and how it’s affecting the brain?

Currently, we think that cannabis may be affecting the reward and motivation processing system. Dopamine regulates behavior and functions we use toward achieving certain goals. People with bipolar disorder might have too much of the chemical dopamine activity in their system, and that is what we hypothesize is leading to greater cognitive impairment

So we think that cannabis may be reducing the excess dopamine in people with bipolar disorder that’s leading to cognitive impairment.

Could you talk about your work’s implications for possible treatments?

Clinically, there would be a concern with cannabis about making the mania and psychotic symptoms of bipolar disorder worse. So I wouldn’t go so far as to say people with bipolar disorder should use cannabis. But our research could lead to an understanding of the mechanisms of the effects of cannabis that could possibly lead to drug treatments.

What about your work going forward?

Right now, with our ongoing study, we’re looking at acute effects of THC (tetrahydrocannabinol) versus CBD (cannabidiol). I think that’s probably one of the more promising directions that we’re taking this research. THC can actually have opposing effects to CBD, and we want to disentangle that. We want to see whether we can maximize any therapeutic benefits of cannabis but minimize any of those harmful effects to produce a lower negative side effect profile. CBD doesn’t have the same kind of psychoactive effects that THC has, generally speaking, so you don’t get a high from it. It’s a possibility that CBD might be a better candidate for a therapy, but there are very little data on it so far.

And we’re extending this to other populations as well. That includes HIV patients, who have similar neurocognitive impairments. We are also hoping to study the effects of cannabis on aging populations, who are also at risk for cognitive decline. With the increasing legalization of cannabis, more older people are turning to cannabis as a medical treatment, but we don’t know how cannabis effects the aging brain. I think this is a really important branch off from this current research.

ABOUT THE AUTHOR(S)

Gary Stix is a senior editor at Scientific American. Follow Gary Stix on Twitter Credit: Nick Higgins

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