A Conversation with Ziva Cooper

The public relations push for Alex Berenson’s book Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence has certainly slowed, but its aftershocks are still rumbling.

Take, for example, the full-throated correction posted on Mother Jones’ original story about Berenson’s book, one of many that shared Berenson’s interpretation of data related to cannabis.

The article, the correction read, “overstated the connection between the increasing number of pot users and the number of people over 30 coming into the ER with psychosis; the researchers in that case ‘did not directly examine whether marijuana had led to any psychotic diagnoses.’”

Those of us on the cannabis beat took notice when Ziva Cooper, Research Director of UCLA’s Cannabis Research Initiative, took to Twitter to respond to Berenson’s interpretation of the watershed 2017 National Academies of Sciences, Engineering, and Medicine’s comprehensive review on cannabis research. Cooper, one of the authors of the report, told me that Berenson’s view that the NASEM report found that “cannabis causes schizophrenia” is wrong, and in fact “a gross misinterpretation of our conclusions in the text. And and to make that claim is quite dangerous and it’s misinformed.”

I talked to Cooper about Berenson’s work, but much more interestingly, what she’s working on next (research at the intersection of opioids and cannabis, and a study that will shine light on how men and women react differently to cannabinoids).

This interview has been edited for clarity and space.

Alyson Martin, Cannabis Wire: Let’s narrow the conversation for now down to the New York Times op-ed written by Alex Berenson, because that’s what prompted you to take to Twitter. What were your first thoughts?

Ziva Cooper: Mr. Berenson was trying to convey the risks associated with cannabis. But he did so in a biased manner where he only presented data to support his arguments, even though there is very strong data on the other side to disprove his arguments. And so for instance he was talking about how cannabis use leads to greater opioid consumption, but there is evidence pointing to the contrary that he failed to raise. So, in that respect it was biased. And then with respect to his misinterpretation of the conclusions of the National Academy of Sciences report stating that cannabis causes schizophrenia, that was a gross misinterpretation of our conclusions in the text. And to make that claim is quite dangerous and it’s misinformed.

Martin: Why did you respond to Berenson on Twitter?

Cooper: Well, he was misrepresenting our conclusions. He was spreading this idea that cannabis causes schizophrenia. He actually stated that that we concluded that cannabis causes schizophrenia, which we didn’t. So I was prompted to speak up, because I don’t have time to write a New York Times editorial in response, and Twitter seems like the fastest way to get my message out. And none of the other committee members are on social media or haven’t been active on social media. And so it was brought to my attention by colleagues that Alex Berenson was pointing to the National Academy of Sciences report to help support his argument. But in fact he was misrepresenting our findings.

I have yet to see scientists strongly support his claims, so that speaks volumes. To misrepresent the scientific findings delegitimizes the actual research related to the risks that are known to be related to cannabis, such as cannabis use disorder and impaired driving. He’s immediately striking fear in the readers’ minds rather than portraying the data that we have a great deal of information on.

My fear is that people really aren’t going to look at our report as a primary source. They’re going to look at his interpretation of our findings.

Martin: Alex has said that you’re disassociating yourself from NASEM. Is that true?

Cooper: He’s delegitimizing the NASEM conclusion by saying that I am disassociating myself from the committee. I’m the only one who’s spoken up about this. So, therefore I am not a representation of what the committee concluded. Therefore he is able to twist what the report says to support his argument that cannabis causes schizophrenia.

Martin: Walk me through the NASEM conclusion for our readers.

Cooper: With regard to our consensus report and how we synthesize and evaluated available research we all work hard to come to an agreement as to what the conclusions are. What does the data support? Conclusions were that there is substantial evidence to support that cannabis use is associated with developing schizophrenia and other psychotic disorders. Associated. Not causation, but association.

And if you look at the report, we also have a conclusion that says that cannabis use history is associated with improved cognitive function in people that have psychotic disorders. So, again there’s an example of bias here. He chose the first conclusion, which says that there’s an association between cannabis use and schizophrenia, but not the second one that shows that there’s clearly a very complex relationship between cannabis use and schizophrenia.

Martin: Now, for me, the fun, and much more interesting part of the conversation: what are you working on now?

Cooper:  In order to determine the actual impact of cannabis on opioids, one avenue that I’ve taken is to determine if people who use cannabis, can they actually use lower doses of opioids and achieve pain relief? So this idea comes from the animal literature, which shows that THC, the primary psychoactive component of cannabis, when it’s combined with an opioid you need very small doses of opioids to achieve pain relief. So there’s a synergistic effect. And so I decided to look at this in humans, and that’s the first double-blind placebo-controlled study looking at combinations of cannabis and its ability to increase the pain relieving effects of the opioid, such that you need a lower dose of opioids. And the idea is that if you need a lower dose of the opioid you’ll have fewer adverse effects associated with the opioids.

So we published this study in February 2018. And that did show that when you combine the two, only need a very small dose of an opioid that isn’t usually effective on its own, but when it’s combined with cannabis, you get robust pain relief.

Martin: That’s fascinating. Are you following up with any additional research?

Cooper: We didn’t study pain patients, so we have to look at these effects in a pain population. We want to make sure that while we are increasing its pain relieving effects we weren’t also increasing other adverse effects related to the opioid. And one of the primary adverse effects related to opioids is this idea of abuse liability. It’s the chance that they might want to take it, if given the opportunity. So, I have a follow up study going on with colleagues at Columbia that was just funded by the NIH that looks at cannabis in combination with opioids to see if we could again get this robust pain reliever in effect with a very low dose of an opioid.

But, the interesting thing here with this study is that we’re looking at cannabis that has THC in it. We’re also looking at cannabis that has cannabidiol in it, the other cannabinoid that people are very interested in, that people think has pain-relieving properties. So we’re going to look at cannabidiol’s effects alone, and in combination with THC. That is scheduled to start within the next week or two.

Martin: I’ve been very eager to ask you about your work related to how men and women experience cannabinoids differently. What can you share?

Cooper: What’s interesting is that up until very recently men outnumbered women with regard to cannabis use two to one. But what we’re seeing now is that with the legislation passing related to medical cannabis laws is that there is increased numbers of women who are seeking medical cannabis specifically to alleviate pain. So now the ratio is about 1 to 1. If you look in the animal literature female animals are a lot more sensitive to the pain relieving effects of THC, that primary psychoactive component of cannabis. It might indicate that women might also be a lot more sensitive than men to the pain relieving effects of cannabis.

And so I started a line of research actually looking at these sex differences between men and women, not only for the pain relieving effects, but also for adverse effects. Because if they are more sensitive to the pain relieving effects of cannabis, are they also more sensitive to the adverse effects of cannabis? And this is really important to help inform patients who are turning to medical cannabis to help alleviate their pain.

I published a paper actually looking at sex differences between men and women using these cold pressure tests. And what I found was really surprising. Women actually did not show a pain relief with cannabis, whereas men showed robust pain relief with cannabis. And it was surprising, given the animal literature which showed that female animals were a lot more sensitive. But then I thought about it and I looked at my population, I looked at the participants that were involved in the study, and they were really heavy cannabis smokers. They were smoking every single day, more than five times a day.

When I was trying to figure out the data, a paper came out from an animal researcher and she showed that when you just give one dose of THC, females are much more sensitive to the pain relieving effects of THC. If you give it to them on what we call a chronic basis, females develop this tolerance to the pain relieving effects of THC at a much faster rate than the males. Meaning that although females start off a lot more sensitive to the pain relieving effects of the THC, they develop tolerance much faster, so a week later you don’t see the same pain relieving effects.

And so because our participants were really heavy smokers, this is probably what we saw. We probably saw that females become a lot more tolerant to the pain relieving effects of cannabis, relative to males. That’s one hypothesis. And it’s the hypothesis that we’re working on right now in this study that I hope to run in a grant that was recently submitted. I’m going to actually compare the pain relieving effects of cannabis in people that don’t really smoke that much cannabis.

Martin: I have one last question for you: Are you seeing an increased interest in cannabis? And has it gotten easier at all to deal with the federal research hurdles?

Cooper: Research has not gotten easier to conduct. There’s a need now for the research and so we are starting to see increased attention to research related to cannabis and cannabinoids.

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Cannabis is rich territory for serious journalism. Legalization raises urgent questions about regulation and law, technology and taxation, science and business, criminal justice and individual liberties. It stands at the intersection of a booming billion-dollar industry and promising advances in medicine, all while remaining federally illegal.

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